@article {pmid40588585, year = {2025}, author = {Mondo, SJ and Grigoriev, IV}, title = {A genomic perspective on fungal diversity and evolution.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, pmid = {40588585}, issn = {1740-1534}, abstract = {Originating from aquatic unicellular ancestors, over the course of ~1 billion years, the fungi have evolved to occupy nearly all aerobic environments on the planet, diversified into millions of different 'species' and have developed complex multicellular structures. Their relatively small, simple genomes have facilitated massive-scale sequencing and allowed us to explore genome evolution across an ancient eukaryotic kingdom. With thousands of genomes from diverse lineages now available, this Review will discuss insights into fungal biology and evolution gleaned with genomics and other multi-omics approaches. Using published genomes available through GenBank and the Joint Genome Institute's MycoCosm platform, we generated kingdom-wide phylogenies and used them to highlight how fungal genomes have changed over time. With this phylogeny as a guide, we also discuss major evolutionary transitions that occurred across the fungal kingdom. Although progress has been made, these efforts are hampered by biases in genome representation and limited characterization of gene functions. Here, we discuss these challenges and possible future directions to address them, including initiatives to characterize conserved genes of unknown function and scale up sequencing towards 10,000 annotated fungal genomes.}, } @article {pmid40555192, year = {2025}, author = {Parker, J and Pennell, M}, title = {The cellular substrate of evolutionary novelty.}, journal = {Current biology : CB}, volume = {35}, number = {12}, pages = {R626-R637}, doi = {10.1016/j.cub.2025.04.014}, pmid = {40555192}, issn = {1879-0445}, mesh = {*Biological Evolution ; Animals ; Phenotype ; *Gene Expression ; }, abstract = {A major challenge in biology is comprehending how complex multicellular novelties evolve. Central to this problem is explaining how qualitatively new phenotypic traits - typically the focus of comparative developmental and macroevolutionary studies above the species level - can become established through population genetic processes. Here, we suggest that a resolution may be found by acknowledging the fundamental entities from which functional organismal phenotypes are constructed. We argue that these are not genes, proteins or cell types, but rather gene expression programs (GEPs): sets of co-expressed transcripts that collectively encode cellular subfunctions. We advance that, because GEPs are the smallest, elemental functional units underlying phenotypes, it follows that they represent the substrate upon which population genetic processes must act to explain the origin of evolutionary novelty at the cellular level and above. Novelty arises through the evolution of novel GEPs, through novel synergisms between GEPs that become co-expressed within the same cell or through interactions between different GEPs juxtaposed in cooperating cells within organs. The revolution in single cell biology offers the chance to trace evolution at the resolution of GEPs in populations and across clades, potentially unifying our view of multicellular phenotypic evolution.}, } @article {pmid40540574, year = {2025}, author = {Narayanasamy, N and Bingham, E and Fadero, T and Bozdag, GO and Ratcliff, WC and Yunker, P and Thutupalli, S}, title = {Metabolically driven flows enable exponential growth in macroscopic multicellular yeast.}, journal = {Science advances}, volume = {11}, number = {25}, pages = {eadr6399}, pmid = {40540574}, issn = {2375-2548}, mesh = {*Saccharomyces cerevisiae/growth & development/metabolism ; Models, Biological ; }, abstract = {The ecological and evolutionary success of multicellular lineages stems substantially from their increased size relative to unicellular ancestors. However, large size poses biophysical challenges, especially regarding nutrient transport: These constraints are typically overcome through multicellular innovations. Here, we show that an emergent biophysical mechanism-spontaneous fluid flows arising from metabolically generated density gradients-can alleviate constraints on nutrient transport, enabling exponential growth in nascent multicellular clusters of yeast lacking any multicellular adaptations for nutrient transport or fluid flow. Beyond a threshold size, the metabolic activity of experimentally evolved snowflake yeast clusters drives large-scale fluid flows that transport nutrients throughout the cluster at speeds comparable to those generated by ciliary actuation in extant multicellular organisms. These flows support exponential growth at macroscopic sizes that theory predicts should be diffusion limited. This demonstrates how simple physical mechanisms can act as a "biophysical scaffold" to support the evolution of multicellularity by opening up phenotypic possibilities before genetically encoded innovations.}, } @article {pmid40532703, year = {2025}, author = {Glotzer, M}, title = {A key role for centralspindlin and Ect2 in the development of multicellularity and the emergence of Metazoa.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2025.05.052}, pmid = {40532703}, issn = {1879-0445}, abstract = {Obligate multicellularity evolved at least five times in eukaryotes, including at the origin of Metazoa, 650-850 million years ago.[1][,][2][,][3][,][4] While obligate multicellularity could result from cell-cell adhesion, aggregation-based mechanisms for multicellularity are susceptible to mixing with genetically unrelated cells.[5] Alternatively, or in addition, multicellularity can emerge from a series of mitotic divisions followed by incomplete cytokinesis, resulting in a cluster of cells connected by intercellular bridges.[6][,][7][,][8][,][9][,][10] In addition to being multicellular, all five clades of extant Metazoa are diploid organisms that reproduce via eggs and sperm (anisogamy).[7][,][11][,][12][,][13] Thus, by inference, the last common ancestor (LCA) of Metazoa could produce sperm and eggs and could cleave fertilized eggs into smaller cells that self-organize into fertile organisms[14]-processes that directly involve the cytokinetic machinery. Here, I present an integrated analysis into the emergence of three regulators of cytokinesis. Phylogenetic analysis and structural modeling indicate that Kif23, Cyk4, and Ect2 are highly conserved across all metazoans. These proteins cooperate to link the plane of cell division with the position of the spindle during anaphase and subsequently nucleate the assembly of stable intercellular bridges,[15][,][16][,][17][,][18] structures prevalent in metazoan germ lines.[7] The closest relatives of Metazoa, Choanoflagellata, encode orthologs of Kif23 and Ect2. Choanoflagellate species variably encode proteins homologous to Cyk4, a subset of which are predicted to interact with Kif23. These findings, in light of prior knowledge, suggest that the evolutionary refinement of these three cytokinetic regulators was a proximal prerequisite for the evolution of defining features of Metazoa.}, } @article {pmid40530903, year = {2025}, author = {Fotedar, R and Zalar, P and Al Malaki, A and Al Zeyara, A and Kaul, R and Kolecka, A and Fell, JW and Boekhout, T and Gunde-Cimerman, N}, title = {Euryhaline Black Yeasts From the Arabian Gulf: Descriptions of Salinomyces qatarensis sp. nov. and Hortaea werneckii Genotypic Variations.}, journal = {IUBMB life}, volume = {77}, number = {6}, pages = {e70026}, doi = {10.1002/iub.70026}, pmid = {40530903}, issn = {1521-6551}, support = {NPRP 6-647-1-127//Qatar Foundation/ ; MRIC UL I0-0022//Slovenian Research and Innovation Agency: Infrastructural Centre Mycosmo:/ ; P1-0198,P4-0432//Slovenian Research and Innovation Agency: Infrastructural Centre Mycosmo:/ ; }, mesh = {Phylogeny ; *Ascomycota/genetics/classification/isolation & purification ; Genotype ; Genetic Variation ; Seawater/microbiology ; Salinity ; DNA, Fungal/genetics ; RNA Polymerase II/genetics ; }, abstract = {The Arabian Gulf surrounding Qatar is an oligotrophic marine environment characterized by extreme conditions, such as increased water temperatures and high salinity compared to other semi-enclosed seas, such as the Mediterranean Sea. Thirty-six black yeast-like isolates were obtained from marine waters surrounding Qatar, representing 4% of all isolated yeasts. DNA sequence analysis of the internal transcribed spacers (ITS1, ITS2), the 5.8S rRNA gene, and the D1/D2 domains of the LSU rDNA identified 20 isolates as Hortaea werneckii, and 15 (75%) of them represent previously unknown genotypes with a wide NaCl tolerance at 37°C. In addition, 16 meristematic black yeast-like cultures were isolated that grew as multi-cellular bodies and reproduced by endoconidiation. Phylogenetic analysis based on the D1/D2 domains of LSU rDNA, partial sequences of the second largest subunit of RNA polymerase II (RPB2) and translation elongation factor 1-alpha (TEF) of selected representative strains of Dothideomycetes and of morphologically similar taxa, Pseudotaeniolina globosa and Trimmatostroma salinum, supported the proposal of meristematic black yeast-like cultures as a new species, Salinomyces qatarensis sp. nov., within Teratosphaeriaceae, Mycosphaerellales. The holotype is designated as CBS 150510, with ex-type strains EXF-15246 and QCC/Y38/18, and the species is registered in Mycobank as MB#848869. In addition, based on the above molecular analysis, a new combination was proposed for an euryhaline fungus from Mediterranean salterns, Trimmatostroma salinum, into the genus Verrucocladosporium as V. salinum, MB#856063. This study increases our knowledge of the distribution and genetic diversity of Hortaea werneckii, the etiological agent of tinea nigra. In addition, the description of S. qatarensis and the combination of euryhaline T. salinum to Verrucocladosporium provides support for halotolerance as one of the traits in Dothideomycetes.}, } @article {pmid40523936, year = {2025}, author = {Muthukumar, G and Weissman, JS}, title = {Shaping the composition of the mitochondrial outer membrane.}, journal = {Nature cell biology}, volume = {}, number = {}, pages = {}, pmid = {40523936}, issn = {1476-4679}, support = {T32GM007287//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, abstract = {Mitochondria are critical double-membraned organelles that act as biosynthetic and bioenergetic cellular factories, with the outer membrane providing an interface with the rest of the cell. Mitochondrial outer membrane proteins regulate a variety of processes, including metabolism, innate immunity and apoptosis. Although the biophysical and functional diversity of these proteins is highly documented, the mechanisms of their biogenesis and the integration of that into cellular homeostasis are just starting to take shape. Here, focusing on α-helical outer membrane proteins, we review recent insights into the mechanisms of synthesis and cytosolic chaperoning, insertion and assembly in the lipid bilayer, and quality control of unassembled or mislocalized transmembrane domains. We further discuss the role convergent evolution played in this process, comparing key biogenesis players from lower eukaryotes, including yeast and trypanosomes, with multicellular metazoan systems, and draw comparisons with the endoplasmic reticulum biogenesis system, in which membrane proteins face similar challenges.}, } @article {pmid40523311, year = {2025}, author = {Chen, Z and Zhang, X and Deng, M and Li, C and Nguyen, TT and Liu, M and Dou, K and Ishibashi, T and Wang, J and Yan, Y}, title = {Epigenetic reprogramming induced by key metabolite depletion is an evolutionarily ancient path to tumorigenesis.}, journal = {Disease models & mechanisms}, volume = {18}, number = {6}, pages = {}, doi = {10.1242/dmm.052313}, pmid = {40523311}, issn = {1754-8411}, support = {GRF16103620//University Grants Committee/ ; T13-602/21N//University Grants Committee/ ; GRF16104324//University Grants Committee/ ; JCYJ20200109140201722//Science, Technology and Innovation Commission of Shenzhen Municipality/ ; Z0428//Hong Kong University of Science and Technology/ ; 32170548//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Carcinogenesis/genetics/pathology/metabolism ; Humans ; *Epigenesis, Genetic ; DNA Methylation/genetics ; *Drosophila melanogaster/genetics/metabolism ; Histones/metabolism ; Methionine/metabolism ; Acetylation ; Acetyl Coenzyme A/metabolism ; Mutation/genetics ; S-Adenosylmethionine/metabolism ; *Cellular Reprogramming/genetics ; Neoplasms/genetics/pathology/metabolism ; *Biological Evolution ; *Evolution, Molecular ; }, abstract = {Tumor growth is a challenge for multicellular life forms. Contrary to human tumors, which take years to form, tumors in short-living species can arise within days without accumulating multiple mutations, raising the question whether the paths to tumorigenesis in diverse species have any commonalities. In a fly tumor model caused by loss of cell polarity genes, we identified two key metabolic changes: first, systemic depletion of acetyl-CoA leading to a reduction in histone acetylation levels and stochastic silencing of actively transcribed genes; and second, defects in the methionine cycle causing systemic depletion of S-adenosyl methionine, which further reduces histone methylation levels and causes stochastic activation of transposons. Perturbation of the methionine metabolic process inhibits tumor growth. To understand the evolutionary origin of tumorigenesis, we performed comparative studies of fly and human tumors and found that human tumors with metabolic signatures similar to those of fly tumors have a lower mutational load, younger patient age and lower DNA methylation levels. This study indicates that depletion of key metabolites is an evolutionarily ancient driving force for tumorigenesis.}, } @article {pmid40517085, year = {2025}, author = {Schoenle, A and Francis, O and Archibald, JM and Burki, F and de Vries, J and Dumack, K and Eme, L and Florent, I and Hehenberger, E and Hoffmeyer, TT and Irisarri, I and Lara, E and Leger, MM and Lukeš, J and Massana, R and Mathur, V and Nitsche, F and Strassert, JFH and Worden, AZ and Yurchenko, V and Del Campo, J and Waldvogel, AM}, title = {Protist genomics: key to understanding eukaryotic evolution.}, journal = {Trends in genetics : TIG}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tig.2025.05.004}, pmid = {40517085}, issn = {0168-9525}, abstract = {All eukaryotes other than animals, plants, and fungi are protists. Protists are highly diverse and found in nearly all environments, with key roles in planetary health and biogeochemical cycles. They represent the majority of eukaryotic diversity, making them essential for understanding eukaryotic evolution. However, these mainly unicellular, microscopic organisms are understudied and the generation of protist genomes lags far behind most multicellular lineages. Current genomic methods, which are primarily designed for animals and plants, are poorly suited for protists. Advancing protist genome research requires reevaluating plant- and animal-centric genomic standards. Future efforts must leverage emerging technologies and bioinformatics tools, ultimately enhancing our understanding of eukaryotic molecular and cell biology, ecology, and evolution.}, } @article {pmid40056574, year = {2025}, author = {Klompstra, TM and Yoon, KJ and Koo, BK}, title = {Evolution of organoid genetics.}, journal = {European journal of cell biology}, volume = {104}, number = {2}, pages = {151481}, doi = {10.1016/j.ejcb.2025.151481}, pmid = {40056574}, issn = {1618-1298}, mesh = {*Organoids/metabolism/cytology ; Humans ; Animals ; CRISPR-Cas Systems/genetics ; Gene Editing ; Pluripotent Stem Cells/cytology ; }, abstract = {Organoids have revolutionized in vitro research by offering three-dimensional, multicellular systems that recapitulate the structure, function, and genetics of human tissues. Initially developed from both pluripotent stem cells (PSCs) and adult stem cells (AdSCs), organoids have expanded to model nearly every major human organ, significantly advancing developmental biology, disease modeling, and therapeutic screening. This review highlights the progression of organoid technologies, emphasizing the integration of genetic tools, including CRISPR-Cas9, prime editing, and lineage tracing. These advancements have facilitated precise modeling of human-specific pathologies and drug responses, often surpassing traditional 2D cultures and animal models in accuracy. Emerging technologies, such as organoid fusion, xenografting, and optogenetics, are expected to further enhance our understanding of cellular interactions and microenvironmental dynamics. As organoid complexity and genetic engineering methods continue to evolve, they will become increasingly indispensable for personalized medicine and translational research, bridging gaps between in vitro and in vivo systems.}, } @article {pmid40499887, year = {2025}, author = {Just, BB and Farias, ST}, title = {Major Transitions in the Physiological Machinery of Cognition.}, journal = {Bio Systems}, volume = {}, number = {}, pages = {105517}, doi = {10.1016/j.biosystems.2025.105517}, pmid = {40499887}, issn = {1872-8324}, abstract = {Cognition refers to the processes organisms use to interact with and understand their world, a fundamental biological function present in all cellular life. As with any biological process, cognitive capacity and its underlying mechanisms vary widely across species. Evolution has shaped cognition, leading to increasingly complex forms in certain lineages. The concept of evolutionary transitions, introduced by Maynard-Smith and Szathmary, describes major shifts in biological organization. In 2021, Ginsburg & Jablonka, and in 2023, Barron and collaborators explored cognitive transitions within neural systems, the evolution of cognition in aneural organisms remains understudied. Building on prior frameworks, we analyze cognitive transitions in the aneural realm, focusing on the physiological machinery responsible for cognition. The first transition is the emergence of cognitive machinery in prokaryotic cells (cellular cognition), followed by its complexification in eukaryotes (complex cellular cognition). The third transition marks cognition based on multiple cells (multicellular-based cognition). The fourth is the development of neurons and a diffuse nervous system (decentralized neural cognition), followed by its centralization (brain cognition). The sixth transition involves advanced brain architectures enabling complex cognition (complex brain cognition). The final transition is the emergence of human cognition, supported by symbols and culture (cultural-linguistic cognition). This hierarchical framework captures the increasing complexity of cognitive machinery across evolutionary transitions. By incorporating aneural cognition, we provide a more comprehensive view of the diversity of cognitive systems in nature.}, } @article {pmid40489295, year = {2025}, author = {Piccinini, G and Valdrè, U and Milani, L}, title = {The Early Evolution of Tudor Genes in Holozoa and How Their Distribution Was Influenced by Life History Traits in Metazoa.}, journal = {Genome biology and evolution}, volume = {17}, number = {6}, pages = {}, doi = {10.1093/gbe/evaf051}, pmid = {40489295}, issn = {1759-6653}, support = {//Ricerca Fondamentale Orientata/ ; //University of Bologna/ ; }, mesh = {Animals ; *Evolution, Molecular ; Phylogeny ; *Life History Traits ; Multigene Family ; RNA, Small Interfering/genetics ; }, abstract = {Early metazoan evolution was characterized by the expansion of multiple gene families, such as the Tudor family, involved in novel multicellularity-related functions. In eukaryotes, Tudor genes (i.e. genes including at least one Tudor domain) are numerous, heterogeneous, and mostly associated with gene expression regulation. However, they underwent an animal-specific expansion, with novel elements almost exclusively involved in retrotransposon regulation through Piwi-interacting RNAs, as spatiotemporal regulators of the key-element Piwi, another previously considered animal-specific gene. Here, we used online-available proteomes covering 25 major taxonomic groups to characterize the Tudor gene family at a holozoan-wide level, confirming the apomorphic metazoan expansion of Piwi-interacting RNA-related Tudor genes. However, we also annotated elements of the Piwi-interacting RNA pathway (Tudor and Piwi genes) in Ichthyosporea species, suggesting that elements of the Piwi-interacting RNA pathway were already present in the holozoan common ancestors. We observed an outstanding variability (34-fold) of Tudor gene number between and within metazoan phyla that could be associated with convergent genomic and phenotypic evolutions: expansions were usually sided by whole-genome duplications and/or life history traits such as parthenogenesis; reductions were mostly associated to overall phenotypic and genomic simplifications, like in almost all considered endoparasites. Lastly, we phylogenetically tested, and mostly (but not completely) confirmed, a previously proposed model for the evolution of the Tudor domain secondary structures.}, } @article {pmid40467258, year = {2025}, author = {Li, Y and Liu, Y and Zheng, B and Zhang, C and Cai, Y and Cheng, Y and Wang, J}, title = {Multicellular behavior and genomic characterization of Salmonella Typhimurium in animal-derived food chains in Xinjiang, China: Phenotypic resistance, biofilm formation, and sequence types.}, journal = {Food research international (Ottawa, Ont.)}, volume = {214}, number = {}, pages = {116698}, doi = {10.1016/j.foodres.2025.116698}, pmid = {40467258}, issn = {1873-7145}, mesh = {*Biofilms/growth & development ; Animals ; China ; *Salmonella typhimurium/genetics/drug effects/isolation & purification/physiology/classification ; *Food Microbiology ; Drug Resistance, Multiple, Bacterial/genetics ; Phenotype ; Anti-Bacterial Agents/pharmacology ; Sheep ; Cattle ; Whole Genome Sequencing ; Genome, Bacterial ; }, abstract = {Salmonella Typhimurium Is a globally significant foodborne pathogen that causes diseases in livestock and poultry, which can lead to human infections and fatalities through contaminated food. In this study, we investigated the prevalence of Salmonella Typhimurium in the animal-derived food chain in Xinjiang, China. Among 5075 samples, the detection rate of Salmonella was 8.26 % (419/5075). Of these isolates, 27.21 % (114/419) were identified as Salmonella Typhimurium. Phenotypic analysis revealed significant antibiotic resistance: 82.46 % (94/114) of the strains exhibited multidrug resistance (MDR), with high resistance rates to amoxicillin / clavulanic acid, ampicillin, and tetracycline. Congo red plate assays demonstrated that 62.28 % (71/114) of the strains exhibited multicellular behavior (RDAR morphotype). Biofilm formation assays indicated that 96.49 % (110/114) of the strains possessed biofilm-forming capabilities, with 18.18 % (20/110) showing strong biofilm formation. Notably, strains displaying multicellular behavior exhibited enhanced biofilm formation, and biofilm capability was positively correlated with antibiotic resistance phenotypes. Whole-genome sequencing of 40 representative strains identified four sequence types (ST19, ST34, ST99, ST128), with ST34 being the most predominant. Distinct host preferences were observed: ST34 strains originated exclusively from cattle and sheep, while ST19, ST99, and ST128 strains were isolated from geese and pigeons. Resistance gene profiling revealed that strains harboring resistance genes exhibited stronger resistance phenotypes, while ST99 and ST128 strains lacked detectable resistance genes. Plasmids R64, R478, and pKPC_CAV1321 were identified in cattle- and sheep-derived strains, whereas pSLT-BT and pSPCV plasmids were predicted in strains from geese and pigeons. Pan-genome analysis and phylogenetic reconstruction demonstrated distinct genetic clustering among ST types, with ST19 and ST128 showing closer evolutionary relationships. This study provides comprehensive insights into the prevalence, phenotypic characteristics, and genomic diversity of Salmonella Typhimurium in the animal-derived food chain in Xinjiang. Our findings contribute to region-specific pathogen control strategies, enhancing public health safety and consumer protection.}, } @article {pmid40412365, year = {2025}, author = {Zheng, J and Wu, Y and Zhang, L and Yang, L and Jin, J and Li, C and Tong, S and Yu, J}, title = {Overexpression of NtMYB306c reduces the glandular trichomes density in tobacco.}, journal = {Biochemical and biophysical research communications}, volume = {772}, number = {}, pages = {152061}, doi = {10.1016/j.bbrc.2025.152061}, pmid = {40412365}, issn = {1090-2104}, mesh = {*Nicotiana/genetics/metabolism ; *Trichomes/genetics/metabolism ; *Transcription Factors/genetics/metabolism ; *Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant ; Plant Leaves/genetics/metabolism ; Plants, Genetically Modified/genetics ; Phylogeny ; }, abstract = {Trichomes, as multicellular structures with diverse functions, play a crucial role in protecting plants against various stresses. Nicotiana tabacum (tobacco) leaves are characterized by numerous glandular trichomes, which are responsible for the production of substantial quantities of secondary metabolites and are critical determinants of tobacco quality. Although their importance is well established, the molecular regulatory mechanisms governing the development of tobacco glandular trichomes remain poorly characterized. Through comparative transcriptome analysis of trichome and trichome-free leaves, we identified NtMYB306c, an R2R3-MYB transcription factor that is phylogenetically distinct from its paralog NtMYB306a (designated as NtMYB306e in this study) and shows highly expressed in trichomes. Functional characterization revealed that overexpression of NtMYB306c significantly suppresses glandular trichome density and markedly alters the expression of three key regulatory genes, NtJAZ3, NtCycB2 and NtHD9 and the key gene LOX1 in JA biosynthesis. Protein-protein interaction screening identified NtMYB308, another member of the R2R3-MYB family. Bioinformatic analysis predicted that its Arabidopsis thaliana homolog interacts with GL3, EGL3, and TTG1, core components of the MBW complex that regulates Arabidopsis glandular trichome development. Yeast two-hybrid (Y2H) and co-immunoprecipitation (Co-IP) assays confirmed the physical interaction between NtMYB306c and NtMYB308, while bioinformatic analysis identified MYB binding sites in the promoter region of NtJAZ3. Collectively, our study demonstrates that NtMYB306c regulates the density of tobacco glandular trichomes via its interaction with NtMYB308.}, } @article {pmid40380887, year = {2025}, author = {Chen, ICK and Khatri, S and Herron, MD and Rosenzweig, F}, title = {Genetic Predisposition Toward Multicellularity in Chlamydomonas reinhardtii.}, journal = {Genome biology and evolution}, volume = {17}, number = {6}, pages = {}, doi = {10.1093/gbe/evaf090}, pmid = {40380887}, issn = {1759-6653}, support = {NNA17BB05A//NASA Astrobiology Institute Award/ ; 80NSSC20K0621//NASA Exobiology/ ; 80NSSC23K1357//NASA ICAR/ ; }, mesh = {*Chlamydomonas reinhardtii/genetics/cytology ; *Biological Evolution ; Selection, Genetic ; Genotype ; Evolution, Molecular ; }, abstract = {The evolution from unicellular to multicellular organisms facilitates further phenotypic innovations, notably cellular differentiation. Multiple research groups have shown that, in the laboratory, simple, obligate multicellularity can evolve from a unicellular ancestor under appropriate selection. However, little is known about the extent to which deterministic factors such as ancestral genotype and environmental context influence the likelihood of this evolutionary transition. To test whether certain genotypes are predisposed to evolve multicellularity in different environments, we carried out a set of 24 evolution experiments, each founded by a population consisting of 10 different strains of the unicellular green alga Chlamydomonas reinhardtii, all in equal proportions. Twelve of the initially identical replicate populations were subjected to predation by the protist Paramecium tetraurelia, while the other 12 were subjected to settling selection by slow centrifugation. Population subsamples were transferred to fresh media on a weekly basis for a total of 40 transfers (∼600 generations). Heritable multicellular structures arose in 4 of 12 predation-selected populations (6 multicellular isolates in total), but never in the settling selection populations. By comparing whole genome sequences of the founder and evolved strains, we discovered that every multicellular isolate arose from one of two founders. Cell cluster size varied not only among evolved strains derived from different ancestors but also among strains derived from the same ancestor. These findings show that both deterministic and stochastic factors influence whether initially unicellular populations can evolve simple multicellular structures.}, } @article {pmid40220996, year = {2025}, author = {Page-McCaw, PS and Pokidysheva, EN and Darris, CE and Chetyrkin, S and Fidler, AL and Gallup, J and , and Murawala, P and Hudson, JK and Boudko, SP and Hudson, BG}, title = {Collagen IV of basement membranes: I. Origin and diversification of COL4 genes enabling metazoan multicellularity, evolution, and adaptation.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {5}, pages = {108496}, doi = {10.1016/j.jbc.2025.108496}, pmid = {40220996}, issn = {1083-351X}, mesh = {*Collagen Type IV/genetics/metabolism/chemistry ; Animals ; Humans ; *Evolution, Molecular ; Phylogeny ; *Basement Membrane/metabolism ; Nephritis, Hereditary/genetics/metabolism ; }, abstract = {Collagen IV (Col-IV) is a major component of basement membranes, a specialized form of extracellular matrix that enabled the assembly of multicellular epithelial tissues. In mammals, Col-IV assembles from a family of six α-chains (α1-α6), forming three supramolecular scaffolds: Col-IV[α121], Col-IV[α345], and Col-IV[α121-α556]. The α-chains are encoded by six genes (COL4A1-6) that occur in pairs in a head-to-head arrangement. In Alport syndrome, variants in COL4A3, 4, or 5 genes, encoding Col-IV[α345] scaffold in glomerular basement membrane (GBM), the kidney ultrafilter, cause progressive renal failure in millions of people worldwide. The molecular mechanisms of how variants cause dysfunction remain obscure. Here, we gained insights into Col-IV[α345] function by determining its evolutionary lineage, as revealed from phylogenetic analyses and tissue expression of COL4 gene pairs. We found that the COL4A⟨1|2⟩ gene pair emerged in basal Ctenophores and Cnidaria phyla and is highly conserved across metazoans. The COL4A⟨1|2⟩ duplicated and arose as the progenitor to the COL4A⟨3|4⟩ gene pair in cyclostomes, coinciding with emergence of kidney GBM, and expressed and conserved in jawed vertebrates, except for amphibians, and a second duplication as the progenitor to the COL4A⟨5|6⟩ gene pair and conserved in jawed vertebrates. These findings revealed that Col-IV[α121] is the progenitor scaffold, expressed ubiquitously in metazoan basement membranes, and which evolved into vertebrate Col-IV[α345] and expressed in GBM. The Col-IV[α345] scaffold, in comparison, has an increased number of cysteine residues, varying in number with osmolarity of the environment. Cysteines mediate disulfide crosslinks between protomers, an adaptation enabling a compact GBM that withstands the high hydrostatic pressure associated with glomerular ultrafiltration.}, } @article {pmid40174588, year = {2025}, author = {Wang, K and Lu, Z and Yao, Z and He, X and Hu, Z and Zhou, D}, title = {Single-cell phylodynamic inference of stem cell differentiation and tumor evolution.}, journal = {Cell systems}, volume = {16}, number = {5}, pages = {101244}, doi = {10.1016/j.cels.2025.101244}, pmid = {40174588}, issn = {2405-4720}, mesh = {Humans ; *Cell Differentiation/genetics/physiology ; *Single-Cell Analysis/methods ; Phylogeny ; Animals ; *Stem Cells/cytology ; Cell Lineage ; *Neoplasms/pathology/genetics ; Computer Simulation ; }, abstract = {Phylodynamic inference (PI) quantifies population dynamics and evolutionary trajectories using phylogenetic trees. Single-cell lineage tracing enables phylogenetic tree reconstruction for thousands of cells in multicellular organisms, facilitating PI at the cellular level. However, cell differentiation and somatic evolution challenge the direct application of existing PI frameworks to somatic tissues. We introduce scPhyloX, a computational framework modeling structured cell populations by leveraging single-cell phylogenetic trees to infer tissue development and tumor evolution dynamics. A key advancement is its ability to infer time-varying parameters, capturing dynamic biological processes. Simulations demonstrate scPhyloX's accuracy in scenarios including tissue development, disease treatment, and tumor growth. Application to three real datasets reveals insights into somatic dynamics: cycling stem cell overshoot in fly organ development, clonal expansion of multipotent hematopoietic progenitors during human aging, and pronounced subclonal selection in early colorectal tumorigenesis. scPhyloX thus provides a computational approach for investigating somatic tissue development and evolution.}, } @article {pmid40399443, year = {2025}, author = {Gatenby, RA and Teer, JK and Tsai, KY and Brown, JS}, title = {Parallel and convergent dynamics in the evolution of primary breast and lung adenocarcinomas.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {775}, pmid = {40399443}, issn = {2399-3642}, mesh = {Humans ; *Breast Neoplasms/genetics/pathology ; *Lung Neoplasms/genetics/pathology ; Female ; *Adenocarcinoma of Lung/genetics/pathology ; Mutation ; *Evolution, Molecular ; Gene Expression Regulation, Neoplastic ; }, abstract = {Cancer development requires an evolutionary transformation from mammalian cells fully regulated by and integrated into multicellular tissue to cancer cells that, as single cell protists, are individually subject to Darwinian selection. Through genetic and epigenetic mechanisms of inheritance, the evolving cancer phenotype must acquire independence from host controls, downregulate differentiated functions that benefit the host but not individual cells, and generate phenotypic traits that increase fitness in the context of the selection forces within the local microenvironment. Here, we investigate this evolutionary transition in breast (BRCA) and lung (LUAD, without EGFR, KRAS or BRAF driver mutations) adenocarcinomas using bulk mutation and expression data from the TCGA database. We define evolution selection for genes and molecular pathways based on 1) changes in gene expression compared to normal tissue, and 2) significantly larger or smaller observed mutation rates compared to those expected based on the gene size. We find BRCA and LUAD disable different genes and gene pathways associated with tissue-specific signaling and differentiated functions but promote common molecular pathways associated with cell cycle, cell-cell interactions, cytoskeleton, voltage gated ion channels, and microenvironmental niche construction. Thus, tissue-specific parallel evolution in early cancer development is followed by convergence to a common cancer phenotype.}, } @article {pmid40392851, year = {2025}, author = {Zhu, L and Beichman, A and Harris, K}, title = {Population size interacts with reproductive longevity to shape the germline mutation rate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {21}, pages = {e2423311122}, doi = {10.1073/pnas.2423311122}, pmid = {40392851}, issn = {1091-6490}, support = {R35GM133428//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32 AG066574/AG/NIA NIH HHS/United States ; Pew Scholarship//Pew Charitable Trusts (PEW)/ ; Career Award at the Scientific Interface//Burroughs Wellcome Fund (BWF)/ ; Discovery Center for Cell Lineage Tracing//Allen Foundation (The Allen Foundation)/ ; }, mesh = {*Mutation Rate ; *Germ-Line Mutation/genetics ; Animals ; Population Density ; Male ; *Reproduction/genetics ; Female ; *Longevity/genetics ; DNA Repair ; Germ Cells ; Spermatogonia ; DNA Damage ; }, abstract = {Mutation rates vary across the tree of life by many orders of magnitude, with fewer mutations occurring each generation in species that reproduce quickly and maintain large effective population sizes. A compelling explanation is that large effective population sizes facilitate selection against weakly deleterious "mutator alleles" such as variants that modulate cell division or interfere with the molecular efficacy of DNA repair. However, while the fidelity of a single cell division largely determines microorganisms' mutation rates, the relationship of the mutation rate to the molecular determinants of DNA damage and repair is more complex in multicellular species with long generation times. Since long generations leave more time for mutations to accrue each generation, we posit that a long generation time likely amplifies the fitness consequences of any damage agent or DNA repair defect that creates extra mutations in the spermatogonia or oocytes. This leads to the counterintuitive prediction that the species with the highest germline mutation rates per generation are also the species with most effective mechanisms for avoiding and repairing mutations in their reproductive cells. Consistent with this, we show that mutation rates in the reproductive cells are inversely correlated with generation time; in contrast, the number of germline mutations that occur during prepuberty development trends weakly upward as generation time increases. Our results parallel recent findings that the longest-lived species have the lowest mutation rates in adult somatic tissues, potentially due to selection to keep the lifetime mutation load below a harmful threshold.}, } @article {pmid40245677, year = {2025}, author = {Tsubota, KI and Horikoshi, S and Hiraiwa, T and Okuda, S}, title = {Strain softening and hysteresis arising from 3D multicellular dynamics during long-term large deformation.}, journal = {Journal of the mechanical behavior of biomedical materials}, volume = {168}, number = {}, pages = {107001}, doi = {10.1016/j.jmbbm.2025.107001}, pmid = {40245677}, issn = {1878-0180}, mesh = {*Stress, Mechanical ; Biomechanical Phenomena ; Viscosity ; Elasticity ; Animals ; Humans ; }, abstract = {Living tissues exhibit complex mechanical properties, including viscoelastic and elastoplastic responses, that are crucial for regulating cell behaviors and tissue deformations. Despite their significance, the intricate properties of three-dimensional (3D) cell constructs are not well understood and are inadequately implemented in biomaterial engineering. To address this gap, we developed a numerical method to analyze the dynamic properties of cell constructs using a 3D vertex model framework. By focusing on 3D tissues composed of confluent homogeneous cells, we characterized their properties in response to various deformation magnitudes and time scales. Stress relaxation tests revealed that large deformations initially induced relaxation in the shapes of individual cells. This process is amplified by subsequent transient cell rearrangements, homogenizing cell shapes and leading to tissue fluidization. Additionally, dynamic viscoelastic analyses showed that tissues exhibited strain softening and hysteresis during large deformations. Interestingly, this strain softening originates from multicellular structures independent of cell rearrangement, while hysteresis arises from cell rearrangement. Moreover, tissues exhibit elastoplastic responses over the long term, which are well represented by the Ramberg-Osgood model. These findings highlight the characteristic properties of cell constructs emerging from their structures and rearrangements, especially during long-term large deformations. The developed method offers a new approach to uncover the dynamic nature of 3D tissue mechanics and could serve as a technical foundation for exploring tissue mechanics and advancing biomaterial engineering.}, } @article {pmid40168695, year = {2025}, author = {Wang, Q and Chen, C and Zhao, H and Jiao, Y and Chen, H and Wang, P and Song, T}, title = {Magnetotactic bacteria-mediated integrated magnetic targeted hyperthermia for in-situ deep-seated tumor.}, journal = {Colloids and surfaces. B, Biointerfaces}, volume = {252}, number = {}, pages = {114658}, doi = {10.1016/j.colsurfb.2025.114658}, pmid = {40168695}, issn = {1873-4367}, mesh = {Animals ; *Hyperthermia, Induced/methods ; Mice ; Mice, Inbred BALB C ; Humans ; *Liver Neoplasms/therapy/pathology ; Magnetic Fields ; *Magnetospirillum ; Cell Line, Tumor ; }, abstract = {Unlike hyperthermia after intratumoral injection, the method of integrated magnetic targeted hyperthermia (iMTH) guides magnetic medium to the target site and then directly performs in-situ heating, showing great potential for effective treatment of deep-seated tumors in the body. Magnetotactic bacteria (MTB), having chain-like arranged magnetic nanoparticles within its body and active movement along an external magnetic field, are considered as a very fitted material for iMTH. However, the amount of MTB concentrated on the deep-seated tumor posed a significant challenge for the successful implementation of iMTH. Herein, we aim to validate the strategy of integrating magnetic targeting and hyperthermia. An in-situ liver tumor model in mouse was developed as deep-seated tumors. After administering the polar MTB MO-1 intravenously via the tail vein, a focusing magnetic field navigated these bacteria to effectively accumulate at the deep-seated tumor site. Immediately afterwards, this targeted aggregation of MO-1 cells triggered a localized magnetic hyperthermia directly at the cancer site under an applied alternating magnetic field. Our findings demonstrated that this hyperthermia induced by the bacteria led to the death of liver cancer cells, thereby effectively curbing the progression and growth of the cancer. These promising results suggested that an iMTH approach was developed, harnessing the power of MTB. This method stands as an exciting and potential therapeutic strategy for the treatment of deep-seated tumors, offering new hope in the fight against cancer.}, } @article {pmid40226989, year = {2025}, author = {Lv, CL and Li, B}, title = {Interface morphodynamics in living tissues.}, journal = {Soft matter}, volume = {21}, number = {19}, pages = {3670-3687}, doi = {10.1039/d5sm00145e}, pmid = {40226989}, issn = {1744-6848}, mesh = {Humans ; Extracellular Matrix/metabolism ; Animals ; *Morphogenesis ; Models, Biological ; Cell Adhesion ; }, abstract = {Interfaces between distinct tissues or between tissues and environments are common in multicellular organisms. The evolution and stability of these interfaces are essential for tissue development, and their dysfunction can lead to diseases such as cancer. Mounting efforts, either theoretical or experimental, have been devoted to uncovering the morphodynamics of tissue interfaces. Here, we review the recent progress of studies on interface morphodynamics. The regulatory mechanisms governing interface evolution are dissected, with a focus on adhesion, cortical tension, cell activity, extracellular matrix, and microenvironment. We examine the methodologies used to study morphodynamics, emphasizing the characteristics of experimental techniques and theoretical models. Finally, we explore the broader implications of interface morphodynamics in tissue morphogenesis and diseases, offering a comprehensive perspective on this rapidly developing field.}, } @article {pmid39894974, year = {2025}, author = {Voronkina, A and Cárdenas, P and Adam, J and Meissner, H and Nowacki, K and Joseph, Y and Tabachnick, KR and Ehrlich, H}, title = {Biosilica 3D Micromorphology of Geodiidae Sponge Spicules Is Patterned by F-Actin.}, journal = {Microscopy research and technique}, volume = {88}, number = {6}, pages = {1701-1711}, doi = {10.1002/jemt.24798}, pmid = {39894974}, issn = {1097-0029}, support = {2020/38/A/ST5/00151//National Science Centre/ ; }, mesh = {Animals ; *Porifera/ultrastructure/anatomy & histology/chemistry ; *Actins/analysis ; *Silicon Dioxide/chemistry ; }, abstract = {Demosponges (phylum Porifera) are among the first multicellular organisms on the planet and represent a unique archive of biosilica-based skeletal structures with species-specific microstructures called spicules. With more than 80 morphotypes, this class of sponges is recognized as a unique source of amorphous silica with superficial ornamentation patterned by organic phases. In this study, we investigated spicules of selected representatives of the family Geodiidae (order Tetractinellida), to identify F-actin-containing axial filaments within these 3D skeletal microconstructs defined as oxyspherasters and sterrasters. Their desilicification using 10% HF leads to isolation of multifilamentous, radially oriented organic matrices, which resemble the shape and size of the original spicules. Our data show that highly specific indicators of F-actin such as iFluorTM 594-Phalloidin, iFluorTM 488-Phalloidin, as well as iFluorTM 350-Phalloidin unambiguously confirm its localization within demineralized oxyspherasters and sterrasters of 11 diverse demosponges species belonging to the subfamily Geodiinae (genera Geodia, Rhabdastrella) and the subfamily Erylinae (genera Caminella, Caminus, Erylus, Pachymatisma). Well-defined periodicity in Geodia cydonium sterrasters actin filaments has been observed using atomic force microscopy (AFM) for the first time. The findings of F-actin as a possible pattern driver in spicules of geodiids brings additional light to our knowledge of spiculogenesis in this group. However, no specific actin structures were found between the geodiid subfamilies or genera thereby suggesting a common actin process, present already at the emergence of the family (~170 million years ago).}, } @article {pmid40345196, year = {2025}, author = {Petroll, R and West, JA and Ogden, M and McGinley, O and Craig, RJ and Coelho, SM and Borg, M}, title = {The expanded Bostrychia moritziana genome unveils evolution in the most diverse and complex order of red algae.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2025.04.044}, pmid = {40345196}, issn = {1879-0445}, abstract = {Red algae are an ancient eukaryotic lineage that were among the first to evolve multicellularity. Although they share a common origin with modern-day plants and display complex multicellular development, comprehensive genome data from the most highly evolved red algal groups remain scarce. Here, we present a chromosome-level genome assembly of Bostrychia moritziana, a complex red seaweed in the Rhodomelaceae family of the Ceramiales-the largest and most diverse order of red algae. Contrary to the view that red algal genomes are typically small, we report significant genome size expansion in Bostrychia and other Ceramiales, which represents one of at least three independent expansion events in red algal evolution. Our analyses suggest that these expansions do not involve polyploidy or ancient whole-genome duplications, but in Bostrychia rather stem from the proliferation of a single lineage of giant Plavaka DNA transposons. Consistent with its enlarged genome, Bostrychia has an increased gene content shaped by de novo gene emergence and amplified gene families in common with other Ceramiales, providing insight into the genetic adaptations underpinning this successful and species-rich order. Finally, our sex-specific assemblies resolve the UV sex chromosomes in Bostrychia, which feature expanded gene-rich sex-linked regions. Notably, each sex chromosome harbors a three amino acid loop extension homeodomain (TALE-HD) transcription factor orthologous to ancient regulators of haploid-diploid transitions in other multicellular lineages. Together, our findings offer a unique perspective of the genomic adaptations driving red algal diversity and demonstrate how this red seaweed lineage can provide insight into the evolutionary origins and universal principles underpinning complex multicellularity.}, } @article {pmid40333983, year = {2025}, author = {Jinno, C and Fujisaki, K and Yotsui, I and Ouchi, M and Singh, P and Naramoto, S and Takezawa, D and Sakata, Y and Fujita, T}, title = {Abscisic acid signaling regulates primary plasmodesmata density for plant cell-to-cell communication.}, journal = {Science advances}, volume = {11}, number = {19}, pages = {eadr8298}, pmid = {40333983}, issn = {2375-2548}, mesh = {*Abscisic Acid/metabolism/pharmacology ; *Plasmodesmata/metabolism ; *Cell Communication ; *Signal Transduction ; *Bryopsida/metabolism/genetics ; Gene Expression Regulation, Plant ; *Plant Cells/metabolism ; Plant Proteins/metabolism/genetics ; Plant Growth Regulators/metabolism ; }, abstract = {Cell-to-cell communication is essential for multicellular organisms. Plasmodesmata (PD) are plant-specific nanopore structures pivotal for cell-to-cell communication and plant survival. However, how PD form and their structure, regulation, and evolution remain largely unknown. Here, we demonstrate that the exogenous supply of abscisic acid (ABA), a well-conserved phytohormone in land plants, reduces primary PD density in the moss Physcomitrium patens. This regulation requires all core components of the ABA signaling pathway. Furthermore, we reveal that ABA-INSENSITIVE 5, a well-conserved transcription factor in the ABA signaling pathway of land plants, plays a pivotal role in PD density regulation, whereas ABA-INSENSITIVE 3 does not. Our findings show that the ABA-induced reduction in primary PD density is mediated by these ABA-responsive factors in P. patens. Considering previous reports on ABA-dependent PD regulation in both moss and angiosperms, we propose that the ABA-mediated control of PD biogenesis and permeability represents a conserved mechanism in land plants, with critical implications for cell-to-cell communication and stress adaptation.}, } @article {pmid40331617, year = {2025}, author = {Cheng, XH and Yu, WJ and Wang, DX and Jiang, LY and Hu, LH}, title = {[Enriching plasma exosomes for proteomic analysis using a phosphatidylserine-imprinted polymer].}, journal = {Se pu = Chinese journal of chromatography}, volume = {43}, number = {5}, pages = {539-546}, pmid = {40331617}, issn = {1872-2059}, mesh = {*Exosomes/chemistry ; Humans ; *Phosphatidylserines/chemistry ; *Proteomics/methods ; *Polymers/chemistry ; *Molecular Imprinting/methods ; }, abstract = {Exosomes are 40-160 nm vesicular nano-bodies secreted by most cells that carry large amounts of biologically active substances originating from the parent cell. Proteins in exosomes are protected by phospholipid bilayer membranes that protect them from degradation by enzymes within body fluids. Along with nucleic acid, proteins and metabolites, exosomes are biomolecules that are considered to be among the most important for discovering tumor markers. Plasma is among the most commonly used body fluids in clinical settings; it is highly complex and contains many proteins and metabolites that interfere with exosome isolation. Consequently, the development of methods for effectively isolating exosomes is a key challenge prior to their use in clinical research. In this study, we used a phosphatidylserine molecularly imprinted polymer (PS-MIP) to enrich plasma exosomes. Subsequent immunoblotting analyses for the CD9, TSG101, and CD81 exosome marker proteins showed that signals can be detected using only 5 μL of plasma, thereby demonstrating the efficiency and specificity of the enrichment protocol. Transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA) data revealed that the enriched vesicles are 30-100 nm in size with elliptical or cup-shaped structures, consistent with the morphology and particle-size-distribution characteristics of the exosomes, suggesting that PS-MIP is capable of successfully isolating exosomes. Nanoflow cytometry revealed that 75.4% of the multi-angle laser scattering (MALS) signal is derived from the PS-MIP-enriched exosomes, which indicates that these enriched exosomes are highly pure and free of interference from impurities, such as aggregated protein particles that are similar in size to the exosomes themselves. This method was used to analyze the proteomes and potential exosomal protein markers of clinical plasma samples from three pancreatic-cancer patients and three healthy volunteers. A total of 1052 proteins and 4545 peptides were identified in the plasma exosomes of healthy volunteers, with a total of 972 proteins and 4096 peptides identified in the plasma exosomes of the pancreatic-cancer patients. Further bioinformatics analyses revealed that the Vesiclepedia database covered 84% of the proteins identified in the plasma exosomes isolated using the PS-MIP method; these proteins comprise 77 of the 100 most frequently identified exosomal proteins in the ExoCarta database. The identified proteins from the cellular components were subjected to gene ontology (GO) analysis, which revealed that they are mainly derived from the exosomes, thereby demonstrating the high selectivity of the PS-MIP method for enriching plasma exosomes and providing specificity for subsequent tumor-marker screening. Label-free quantitative analysis showed that 11 proteins were upregulated and 24 proteins were downregulated in the plasma exosomes of patients with pancreatic cancer compared to those of healthy volunteers. The highly expressed and lowly expressed proteins in the plasma exosomes of patients with pancreatic cancer were subjected to GO, which showed that highly expressed proteins related to the positive regulation of metabolic and biological processes were found in the plasma exosomes of patients with pancreatic cancer compared to those of healthy volunteers, whereas the most significantly under-expressed proteins are related immune-system processes, followed by stimulus-responsive, multicellular bioprocesses, bioregulatory, and interspecies-interacting biological-process-related proteins. The top three proteins, which are relatively highly correlated through protein-protein interaction networks (PPI) analysis, were determined to be complement factor D (CFD), complement component 3 (C3), and von Willebrand factor (VWF). Among the upregulated proteins in the exosomes of patients with pancreatic cancer, exostosin-like glycosyltransferase 2 (EXTL2), α-2-macroglobulin like 1 (A2ML1), and Parkinson's disease protein 7 (PARK7) were the most significantly overexpressed. Hence, these proteins are potential biomarkers for the diagnostic and prognostic assessment of pancreatic cancer and may provide support for further clinical studies into pancreatic cancer.}, } @article {pmid40324073, year = {2025}, author = {Hoffman, PF}, title = {Ecosystem relocation on Snowball Earth: Polar-alpine ancestry of the extant surface biosphere?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {20}, pages = {e2414059122}, doi = {10.1073/pnas.2414059122}, pmid = {40324073}, issn = {1091-6490}, support = {EAR-0417422//NSF (NSF)/ ; }, mesh = {*Ecosystem ; Earth, Planet ; Oceans and Seas ; Ice Cover ; Fossils ; Biological Evolution ; }, abstract = {Geological observations informed by climate dynamics imply that the oceans were 99.9% covered by light-blocking ice shelves during two discrete, self-reversing Snowball Earth epochs spanning a combined 60 to 70 Myr of the Cryogenian Period (720 to 635 Ma). The timescale for initial ice advances across the tropical oceans is ~300 y in an ice-atmosphere-ocean general circulation model in Cryogenian paleogeography. Areas of optically thin oceanic ice are usually invoked to account for fossil marine phototrophs, including macroscopic multicellular eukaryotes, before and after each Snowball, but different taxa. Ecosystem relocation is a scenario that does not require thin marine ice. Assume that long before Cryogenian Snowballs, diverse supra- and periglacial biomes were established in polar-alpine regions. When the Snowball onsets occurred, those biomes migrated in step with their ice margins to the equatorial zone of net sublimation. There, they prospered and evolved, their habitat areas expanded, and the cruelty of winter reduced. Nutrients were supplied by dust (loess) derived from cozonal ablative lands where surface winds were strong. When each Snowball finally ended, those biomes were mostly inundated by the meltwater-dominated and rapidly warming lid of a nutrient-rich but depauperate ocean. Some taxa returned to the mountaintops while others restocked the oceans. This ecosystem relocation scenario makes testable predictions. The lineages required for post-Cryogenian biotic radiations should be present in modern polar-alpine biomes. Legacies of polar-alpine ancestry should be found in the genomes of living organisms. Examples of such tests are highlighted herein.}, } @article {pmid40320517, year = {2025}, author = {Khan, I and Guo, J and Karamat, U and Li, G and Fu, M}, title = {Identification and expression profiles of tubby‑like proteins coding genes in Brassica rapa (B. rapa) in response to hormone and drought stress.}, journal = {BMC plant biology}, volume = {25}, number = {1}, pages = {584}, pmid = {40320517}, issn = {1471-2229}, mesh = {*Brassica rapa/genetics/physiology/metabolism/drug effects ; *Droughts ; *Plant Proteins/genetics/metabolism ; *Plant Growth Regulators/metabolism/pharmacology ; Gene Expression Regulation, Plant/drug effects ; Stress, Physiological/genetics ; Abscisic Acid/pharmacology ; Gene Expression Profiling ; Ethylenes/pharmacology/metabolism ; Multigene Family ; Phylogeny ; Genes, Plant ; }, abstract = {BACKGROUND: Tubby-like proteins (TLPs) are a widespread multigene family found in single-celled to multicellular eukaryotes. Despite their significance, no reports of TLPs in B. rapa have been made up to this point.

RESULTS: Herein, we identified 14 TLPs in the B. rapa genome and renamed them BrTUB1-BrTUB14 based on their chromosomal location. The bulk of BrTUB proteins contain two characteristic domains: the F-box and Tubby domains. Subcellular localization prediction confirmed that BrTUBs are localized in the nucleus. Expression profiling showed that many BrTUB reacts to a variety of stressors, including drought stress and hormonal treatments (ABA and ethylene). In particular, the BrTUB1 displayed elevated expression to ABA and the drought stress treatment.

CONCLUSION: This study is the first thorough identification of the BrTUB family, providing critical insights into its function and regulation, and laying the groundwork for future functional analyses, particularly concerning drought tolerance of B. rapa.}, } @article {pmid40320413, year = {2025}, author = {Liu, J and Costello, JH and Kanso, E}, title = {Flow physics of nutrient transport drives functional design of ciliates.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {4154}, pmid = {40320413}, issn = {2041-1723}, support = {RAISE IOS-2034043//National Science Foundation (NSF)/ ; CBET-210020//National Science Foundation (NSF)/ ; R01-HL153622//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; N00014-19-1-2035//United States Department of Defense | United States Navy | ONR | Office of Naval Research Global (ONR Global)/ ; }, mesh = {*Cilia/physiology/metabolism ; *Ciliophora/physiology/metabolism ; *Nutrients/metabolism ; Biological Transport ; Models, Biological ; Animals ; Phagocytosis/physiology ; }, abstract = {Phagotrophy, the ability of cells to ingest organic particles, marked a pivotal milestone in evolution, enabling the emergence of single-celled eukaryotes that consume other organisms and leading to multicellular life. However, reliance on food particles also created a mechanical challenge-how to coordinate the transfer of particles from the exterior environment to the cell interior? Here, we investigate this important link using mechanistic models of ciliates, a clade of single-celled eukaryotes that either swim or attach and generate feeding currents to capture prey. We demonstrate that ciliates optimize their feeding efficiency by designating a specific portion of the cell surface as a 'mouth,' and optimal cilia coverage varies by life strategy: for sessile ciliates, prey encounter is most efficient when cilia are arranged in bands around oral structures while ciliates that swim display diverse ciliary arrangements that meet the cell's nutritional needs. Importantly, beyond a threshold of doubling nutrient uptake, further increases in feeding flux do not seem to be a dominant selective force in cell design.}, } @article {pmid40263484, year = {2025}, author = {Pai, VP and Pio-Lopez, L and Sperry, MM and Erickson, P and Tayyebi, P and Levin, M}, title = {Basal Xenobot transcriptomics reveals changes and novel control modality in cells freed from organismal influence.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {646}, pmid = {40263484}, issn = {2399-3642}, support = {S10 OD032203/OD/NIH HHS/United States ; 62212//John Templeton Foundation (JTF)/ ; }, mesh = {Animals ; *Transcriptome ; *Xenopus laevis/genetics/embryology ; Embryo, Nonmammalian/metabolism ; *Gene Expression Regulation, Developmental ; Gene Expression Profiling ; Ectoderm/metabolism/cytology ; }, abstract = {Would transcriptomes change if cell collectives acquired a novel morphogenetic and behavioral phenotype in the absence of genomic editing, transgenes, heterologous materials, or drugs? We investigate the effects of morphology and nascent emergent life history on gene expression in the basal (no engineering, no sculpting) form of Xenobots -autonomously motile constructs derived from Xenopus embryo ectodermal cell explants. To investigate gene expression differences between cells in the context of an embryo with those that have been freed from instructive signals and acquired novel lived experiences, we compare transcriptomes of these basal Xenobots with age-matched Xenopus embryos. Basal Xenobots show significantly larger inter-individual gene variability than age-matched embryos, suggesting increased exploration of the transcriptional space. We identify at least 537 (non-epidermal) transcripts uniquely upregulated in these Xenobots. Phylostratigraphy shows a majority of transcriptomic shifts in the basal Xenobots towards evolutionarily ancient transcripts. Pathway analyses indicate transcriptomic shifts in the categories of motility machinery, multicellularity, stress and immune response, metabolism, thanatotranscriptome, and sensory perception of sound and mechanical stimuli. We experimentally confirm that basal Xenobots respond to acoustic stimuli via changes in behavior. Together, these data may have implications for evolution, biomedicine, and synthetic morphoengineering.}, } @article {pmid40262731, year = {2025}, author = {Kong, Z and Zhu, L and Liu, Y and Liu, Y and Chen, G and Wang, H}, title = {Effects of different stages, dosages and courses of prenatal dexamethasone exposure on testicular development in mice.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {201}, number = {}, pages = {115468}, doi = {10.1016/j.fct.2025.115468}, pmid = {40262731}, issn = {1873-6351}, mesh = {Animals ; *Dexamethasone/administration & dosage/toxicity/adverse effects ; Male ; *Testis/drug effects/growth & development/embryology ; Female ; Pregnancy ; Mice ; *Prenatal Exposure Delayed Effects ; Testosterone/blood ; Dose-Response Relationship, Drug ; Leydig Cells/drug effects ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Sertoli Cells/drug effects ; }, abstract = {PURPOSE: Observe the effects of prenatal dexamethasone exposure (PDE) at different stages, dosages, and courses on testicular morphology and multicellular function in offspring mice.

METHODS: Pregnant Kunming mice were subjected to subcutaneous injections of dexamethasone at different stages [GD (gestational day) 14-15 and 16-17], dosages (0.2, 0.4, and 0.8 mg/kg·d), and courses (GD 14-15 and 14-17). Pregnant mice were euthanized on GD 18, and fetal serum and testicular samples were collected to assess serum testosterone level, testicular morphology, cellular proliferation/apoptosis function, expression of multicellular marker/functional gene, and the expression of developmental regulatory signalling pathways such as Notch and Wnt.

RESULTS: PDE could lead to widening of the interstitial area and reduction of seminiferous tubules in fetal testicular tissue, accompanied by significant impairment of Sertoli cell function, particularly evident during late gestation, at high doses, and with multiple courses. However, changes in Leydig cells and spermatogonia function of PDE are not significant. Furthermore, we discovered that PDE could activate the Notch signalling pathway in Sertoli cells while inhibiting the Wnt signalling pathway.

CONCLUSION: PDE could affect fetal testicular development, especially for Sertoli cells during late gestation, at high doses and multiple courses. This study confirms the effects of PDE on testicular tissue morphology and multicellular function, providing a comprehensive understanding of the testicular developmental toxicity of dexamethasone and evidence for guiding rational medication during pregnancy.}, } @article {pmid40254399, year = {2025}, author = {Durymanov, M}, title = {Tumor Spheroids, Tumor Organoids, Tumor Explants, and Tumoroids: What Are the Differences between Them?.}, journal = {Biochemistry. Biokhimiia}, volume = {90}, number = {2}, pages = {200-213}, doi = {10.1134/S0006297924604234}, pmid = {40254399}, issn = {1608-3040}, mesh = {Humans ; *Organoids/pathology/metabolism ; *Spheroids, Cellular/pathology/metabolism ; *Neoplasms/pathology/metabolism ; Tumor Microenvironment ; Animals ; Cell Culture Techniques, Three Dimensional ; }, abstract = {Three-dimensional (3D) cell cultures that mimic tumor microenvironment have become an essential tool in cancer research and drug response analysis, significantly enhancing our understanding of tumor biology and advancing personalized medicine. Currently, the most widely mentioned 3D multicellular culture models include spheroids, organoids, tumor explants, and tumoroids. These 3D structures, exploited for various applications, are generated from cancer and non-cancer cells of different origin using multiple techniques. However, despite extensive research and numerous studies, consistent definitions of these 3D culture models are not clearly established. The manuscript provides a comprehensive overview of these models, detailing brief history of their research, unique biological characteristics, advantages, limitations, and specific applications.}, } @article {pmid40231984, year = {2025}, author = {Chen, C and Zhao, H and Yuan, W and Chen, H and Wang, P and Wang, Q and Chen, C and Song, T}, title = {Tumoral Nanovesicles-Loaded Magnetotactic Bacteria for Tumor-Targeted Therapy under a Swing Magnetic Field.}, journal = {ACS applied materials & interfaces}, volume = {17}, number = {17}, pages = {25048-25058}, doi = {10.1021/acsami.5c02422}, pmid = {40231984}, issn = {1944-8252}, mesh = {Humans ; Magnetic Fields ; Mice ; Animals ; Reactive Oxygen Species/metabolism ; *Neoplasms/drug therapy/pathology ; Cell Line, Tumor ; *Magnetospirillum/chemistry ; *Antineoplastic Agents/chemistry/pharmacology ; Cell Survival/drug effects ; Mice, Inbred BALB C ; }, abstract = {Tumor heterogeneity poses numerous challenges for targeted drug therapy. Although tumor cell-derived nanovesicles (NVs) have emerged as an intriguing method for tumor targeting, how to exert the antitumor effect after targeting remains a key concern. Magnetotactic bacteria (MTB) synthesize chain-like magnetite (Fe3O4) crystals with inherent magnetic moments, which could generate significant torque under a desired magnetic field and move along the magnetic field using their own flagella. Herein, a composite of MTB AMB-1 and NVs was fabricated via electrostatic adsorption where AMB-1 could transport NVs to the tumor site by a guiding magnetic field, while NVs also assist AMB-1 in binding to tumor cells. Subsequently, under the influence of a swing magnetic field (sMF), MTB exert physical stimuli on the cells, inducing the changes of mitochondrial membrane potential and cellular reactive oxygen species (ROS). Finally, it is revealed that the NVs-loaded AMB-1 induced a decrease in cellular viability and significantly inhibited the growth of tumors in vivo under the sMF. Therefore, by remote control of the guidance and stimuli production, the NVs-loaded AMB-1 was highly promising to advance the development of targeted therapeutic strategies for tumors under the context of tumor heterogeneity.}, } @article {pmid40228789, year = {2025}, author = {McFarland, A and Fenton, M and Madsen, JJ and Ye, L}, title = {Unraveling a Receptor-Mediated Bioluminescence Signaling Pathway in Red Tide Algae.}, journal = {Journal of molecular biology}, volume = {437}, number = {13}, pages = {169153}, doi = {10.1016/j.jmb.2025.169153}, pmid = {40228789}, issn = {1089-8638}, mesh = {*Receptors, G-Protein-Coupled/metabolism/genetics ; *Signal Transduction ; *Dinoflagellida/metabolism/genetics ; *Harmful Algal Bloom ; Luminescence ; Humans ; }, abstract = {G protein-coupled receptors (GPCRs) are ubiquitous transmembrane proteins in multicellular life. Human vision, taste, and neuron activity are all mediated by GPCRs, and a large percentage of currently approved drugs target GPCRs. However, our understanding of GPCRs in single-celled eukaryotes is incomplete, and many of the components of GPCR signal transduction are underrepresented in protists. Previous works studying bioluminescent dinoflagellates-single-celled algae involved in coral reef endosymbiosis and toxic red tide blooms-implicate GPCRs in a signaling pathway for bioluminescence but have not elucidated the individual components comprising the pathway. Herein, we identified a novel GPCR in dinoflagellates-Bioluminescence-Inducing Receptor 1 (BIR1)-which plays a significant role in the signaling pathway for bioluminescence in red tide blooms in response to wave turbulence. Additionally, we identified a full endogenous G-protein complex and downstream effectors that are integral to known calcium signaling networks. Based on these identifications, we used knockdown and knockout techniques to demonstrate the integral role of BIR1 in bioluminescence and highlight its role in predator response and shear force-elicited GPCR signaling in red tide blooms. This advance opens avenues for red tide control and supports the existence of similar GPCR pathways involved in bloom toxicity dynamics.}, } @article {pmid40198726, year = {2025}, author = {Liu, X and Pitchford, JW and Constable, GWA}, title = {Cell size and selection for stress-induced cell fusion in unicellular eukaryotes.}, journal = {PLoS computational biology}, volume = {21}, number = {4}, pages = {e1012418}, pmid = {40198726}, issn = {1553-7358}, mesh = {*Cell Fusion ; *Models, Biological ; *Cell Size ; Biological Evolution ; *Stress, Physiological/physiology ; *Eukaryota/physiology/cytology ; *Eukaryotic Cells/physiology/cytology ; Selection, Genetic ; }, abstract = {In unicellular organisms, sexual reproduction typically begins with the fusion of two cells (plasmogamy) followed by the fusion of their two haploid nuclei (karyogamy) and finally meiosis. Most work on the evolution of sexual reproduction focuses on the benefits of the genetic recombination that takes place during meiosis. However, the selection pressures that may have driven the early evolution of binary cell fusion, which sets the stage for the evolution of karyogamy by bringing nuclei together in the same cell, have seen less attention. In this paper we develop a model for the coevolution of cell size and binary cell fusion rate. The model assumes that larger cells experience a survival advantage from their larger cytoplasmic volume. We find that under favourable environmental conditions, populations can evolve to produce larger cells that undergo obligate binary cell fission. However, under challenging environmental conditions, populations can evolve to subsequently produce smaller cells under binary cell fission that nevertheless retain a survival advantage by fusing with other cells. The model thus parsimoniously recaptures the empirical observation that sexual reproduction is typically triggered by adverse environmental conditions in many unicellular eukaryotes and draws conceptual links to the literature on the evolution of multicellularity.}, } @article {pmid40188154, year = {2025}, author = {Nguyen, AQ and Huang, J and Bi, D}, title = {Origin of yield stress and mechanical plasticity in model biological tissues.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3260}, pmid = {40188154}, issn = {2041-1723}, support = {DMR-2046683//National Science Foundation (NSF)/ ; PHY-2019745//National Science Foundation (NSF)/ ; RGP0007/2022//Human Frontier Science Program (HFSP)/ ; }, mesh = {*Stress, Mechanical ; *Models, Biological ; Biomechanical Phenomena ; Animals ; Humans ; }, abstract = {During development and under normal physiological conditions, biological tissues are continuously subjected to substantial mechanical stresses. In response to large deformations, cells in a tissue must undergo multicellular rearrangements to maintain integrity and robustness. However, how these events are connected in time and space remains unknown. Here, using theoretical modeling, we study the mechanical plasticity of cell monolayers under large deformations. Our results suggest that the jamming-unjamming (solid-fluid) transition can vary significantly depending on the degree of deformation, implying that tissues are highly unconventional materials. We elucidate the origins of this behavior. We also demonstrate how large deformations are accommodated through a series of cellular rearrangements, similar to avalanches in non-living materials. We find that these 'tissue avalanches' are governed by stress redistribution and the spatial distribution of "soft" or vulnerable spots, which are more prone to undergo rearrangements. Finally, we propose a simple and experimentally accessible framework to infer tissue-level stress and predict avalanches based on static images.}, } @article {pmid40183649, year = {2025}, author = {Zielenkiewicz, U and Kaushal, V and Kaczanowski, S}, title = {On the origins and evolution of apoptosis: the predator‒mitochondrial prey hypothesis.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jeb/voaf039}, pmid = {40183649}, issn = {1420-9101}, abstract = {Different types of programmed cell death have been described both in unicellular and multicellular organisms. The fundamental mode of eukaryotic cell death is programmed cell death initiated by mitochondria, which is frequently referred to as apoptosis (or mitochondrial apoptosis). It is initiated by mitochondria through mitochondrial permeability transition and the release of apoptotic factors. It is widely thought that mitochondrial apoptosis evolved concurrently with mitochondrial domestication. Programmed cell death initiated by mitochondria is observed in various multicellular and unicellular eukaryotes. We discuss key hypotheses-namely, the "pleiotropy", "addiction", "immunological", and our "predator-mitochondrial prey" hypotheses-to explain the mechanisms of mitochondrial domestication that lead to apoptosis. In this perspective paper, we present evidence from various phylogenetic and experimental studies that strongly indicates our hypothesis is the most plausible. For the first time, we also present evidence that challenges the assumptions underlying all other hypotheses.}, } @article {pmid40181506, year = {2025}, author = {Lewis, EM and Becker, O and Symons, AN and LaCoss, C and Baclig, AJ and Guzman, A and Sanders, C and Gonzalez, L and Warner, LR and Lewis, KA}, title = {The LARP6 La module from Tetrabaena socialis reveals structural and functional differences from plant and animal LARP6 homologues.}, journal = {RNA biology}, volume = {22}, number = {1}, pages = {1-9}, pmid = {40181506}, issn = {1555-8584}, support = {T34 GM136483/GM/NIGMS NIH HHS/United States ; R15 GM141770/GM/NIGMS NIH HHS/United States ; P20 GM103408/GM/NIGMS NIH HHS/United States ; P20 GM109095/GM/NIGMS NIH HHS/United States ; R15 GM119096/GM/NIGMS NIH HHS/United States ; }, mesh = {*Ribonucleoproteins/chemistry/metabolism/genetics ; Animals ; *Autoantigens/chemistry/metabolism/genetics ; SS-B Antigen ; Models, Molecular ; Protein Binding ; Amino Acid Sequence ; *RNA-Binding Proteins/metabolism/chemistry/genetics ; Nucleic Acid Conformation ; *Chlorophyta/genetics/metabolism ; }, abstract = {This study identified the LARP6 La Module from Tetrabaena socialis (T. socialis), a four-celled green algae, in an effort to better understand the evolution of LARP6 structure and RNA-binding activity in multicellular eukaryotes. Using a combination of sequence alignments, domain boundary screens, and structural modelling, we recombinantly expressed and isolated the TsLARP6 La Module to > 98% purity for in vitro biochemical characterization. The La Module is stably folded and exerts minimal RNA binding activity against single-stranded homopolymeric RNAs. Surprisingly, it exhibits low micromolar binding affinity for the vertebrate LARP6 cognate ligand, a bulged-stem loop found in the 5'UTR of collagen type I mRNA, but does not bind double-stranded RNAs of similar size. These result suggests that the TsLARP6 La Module may prefer structured RNA ligands. In contrast, however, the TsLARP6 La Module does not exhibit the RNA chaperone activity that is observed in vertebrate homologs. Therefore, we conclude that protist LARP6 may have both distinct RNA ligands and binding mechanisms from the previously characterized LARP6 proteins of animals and vascular plants, thus establishing a distinct third class of the LARP6 protein family.}, } @article {pmid40179183, year = {2025}, author = {Rados, T and Leland, OS and Escudeiro, P and Mallon, J and Andre, K and Caspy, I and von Kügelgen, A and Stolovicki, E and Nguyen, S and Patop, IL and Rangel, LT and Kadener, S and Renner, LD and Thiel, V and Soen, Y and Bharat, TAM and Alva, V and Bisson, A}, title = {Tissue-like multicellular development triggered by mechanical compression in archaea.}, journal = {Science (New York, N.Y.)}, volume = {388}, number = {6742}, pages = {109-115}, doi = {10.1126/science.adu0047}, pmid = {40179183}, issn = {1095-9203}, support = {S10 OD034223/OD/NIH HHS/United States ; T32 GM139798/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/metabolism ; Archaeal Proteins/metabolism ; Glycosylation ; Elasticity ; Biological Evolution ; Biomechanical Phenomena ; Stress, Mechanical ; }, abstract = {The advent of clonal multicellularity is a critical evolutionary milestone, seen often in eukaryotes, rarely in bacteria, and only once in archaea. We show that uniaxial compression induces clonal multicellularity in haloarchaea, forming tissue-like structures. These archaeal tissues are mechanically and molecularly distinct from their unicellular lifestyle, mimicking several eukaryotic features. Archaeal tissues undergo a multinucleate stage followed by tubulin-independent cellularization, orchestrated by active membrane tension at a critical cell size. After cellularization, tissue junction elasticity becomes akin to that of animal tissues, giving rise to two cell types-peripheral (Per) and central scutoid (Scu) cells-with distinct actin and protein glycosylation polarity patterns. Our findings highlight the potential convergent evolution of a biophysical mechanism in the emergence of multicellular systems across domains of life.}, } @article {pmid40153489, year = {2025}, author = {Kumagai, S and Momoi, Y and Nishikawa, H}, title = {Immunogenomic cancer evolution: A framework to understand cancer immunosuppression.}, journal = {Science immunology}, volume = {10}, number = {105}, pages = {eabo5570}, doi = {10.1126/sciimmunol.abo5570}, pmid = {40153489}, issn = {2470-9468}, mesh = {Humans ; *Neoplasms/immunology/genetics/therapy ; *Tumor Microenvironment/immunology/genetics ; Animals ; Immunotherapy/methods ; Immune Tolerance/immunology/genetics ; Precision Medicine ; Tumor Escape/immunology/genetics ; Genomics ; }, abstract = {The process of tumor development involves tumor cells eluding detection and suppression of immune responses, which can cause decreased tumor cell antigenicity, expression of immunosuppressive molecules, and immunosuppressive cell recruitment to the tumor microenvironment (TME). Immunologically and genomically integrated analysis (immunogenomic analysis) of patient specimens has revealed that oncogenic aberrant signaling is involved in both carcinogenesis and immune evasion. In noninflamed cancers such as epidermal growth factor receptor (EGFR)-mutated lung cancers, genetic abnormalities in cancer cells contribute to the formation of an immunosuppressive TME by recruiting immunosuppressive cells, which cannot be fully explained by the cancer immunoediting hypothesis. This review summarizes the latest findings regarding the links between cancer genetic abnormalities and immunosuppression causing clinical resistance to immunotherapy. We propose the concepts of immunogenomic cancer evolution, in which cancer cell genomic evolution shapes the immunosuppressive TME, and immunogenomic precision medicine, in which cancer immunotherapy can be combined with molecularly targeted reagents that modulate the immunosuppressive TME.}, } @article {pmid40146859, year = {2025}, author = {Muro, EM and Ballesteros, FJ and Luque, B and Bascompte, J}, title = {The emergence of eukaryotes as an evolutionary algorithmic phase transition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {13}, pages = {e2422968122}, pmid = {40146859}, issn = {1091-6490}, support = {310030_197201/SNSF_/Swiss National Science Foundation/Switzerland ; PID2019-109592GBI00//Ministerio de Ciencia, Innovación y Universidades (MICIU)/ ; Excellence Prometeo/2020/085//Conselleria d'Educacio, Universitats i Ocupacio de la Generalitat Valenciana/ ; ASFAE/2022/025//European Union NextGenerationEU 922 and Generalitat Valenciana/ ; PID2020-113737GB-I00//Ministerio de Ciencia, Innovación y Universidades (MICIU)/ ; }, mesh = {*Algorithms ; *Eukaryota/genetics/metabolism ; Evolution, Molecular ; Biological Evolution ; Eukaryotic Cells/metabolism ; Proteins/genetics/metabolism ; Phylogeny ; Models, Genetic ; }, abstract = {The origin of eukaryotes represents one of the most significant events in evolution since it allowed the posterior emergence of multicellular organisms. Yet, it remains unclear how existing regulatory mechanisms of gene activity were transformed to allow this increase in complexity. Here, we address this question by analyzing the length distribution of proteins and their corresponding genes for 6,519 species across the tree of life. We find a scale-invariant relationship between gene mean length and variance maintained across the entire evolutionary history. Using a simple model, we show that this scale-invariant relationship naturally originates through a simple multiplicative process of gene growth. During the first phase of this process, corresponding to prokaryotes, protein length follows gene growth. At the onset of the eukaryotic cell, however, mean protein length stabilizes around 500 amino acids. While genes continued growing at the same rate as before, this growth primarily involved noncoding sequences that complemented proteins in regulating gene activity. Our analysis indicates that this shift at the origin of the eukaryotic cell was due to an algorithmic phase transition equivalent to that of certain search algorithms triggered by the constraints in finding increasingly larger proteins.}, } @article {pmid40127687, year = {2025}, author = {Petroll, R and Papareddy, RK and Krela, R and Laigle, A and Rivière, Q and Bišova, K and Mozgová, I and Borg, M}, title = {The Expansion and Diversification of Epigenetic Regulatory Networks Underpins Major Transitions in the Evolution of Land Plants.}, journal = {Molecular biology and evolution}, volume = {42}, number = {4}, pages = {}, pmid = {40127687}, issn = {1537-1719}, support = {101090308//European Research Executive Agency/ ; ERC200961901//Czech Academy of Sciences/ ; }, mesh = {*Epigenesis, Genetic ; *Embryophyta/genetics ; *Evolution, Molecular ; *Gene Regulatory Networks ; *Biological Evolution ; Histones/metabolism ; DNA Methylation ; }, abstract = {Epigenetic silencing is essential for regulating gene expression and cellular diversity in eukaryotes. While DNA and H3K9 methylation silence transposable elements (TEs), H3K27me3 marks deposited by the Polycomb repressive complex 2 (PRC2) silence varying proportions of TEs and genes across different lineages. Despite the major development role epigenetic silencing plays in multicellular eukaryotes, little is known about how epigenetic regulatory networks were shaped over evolutionary time. Here, we analyze epigenomes from diverse species across the green lineage to infer the chronological epigenetic recruitment of genes during land plant evolution. We first reveal the nature of plant heterochromatin in the unicellular chlorophyte microalga Chlorella sorokiniana and identify several genes marked with H3K27me3, highlighting the deep origin of PRC2-regulated genes in the green lineage. By incorporating genomic phylostratigraphy, we show how genes of differing evolutionary age occupy distinct epigenetic states in plants. While young genes tend to be silenced by H3K9 methylation, genes that emerged in land plants are preferentially marked with H3K27me3, some of which form part of a common network of PRC2-repressed genes across distantly related species. Finally, we analyze the potential recruitment of PRC2 to plant H3K27me3 domains and identify conserved DNA-binding sites of ancient transcription factor families known to interact with PRC2. Our findings shed light on the conservation and potential origin of epigenetic regulatory networks in the green lineage, while also providing insight into the evolutionary dynamics and molecular triggers that underlie the adaptation and elaboration of epigenetic regulation, laying the groundwork for its future consideration in other eukaryotic lineages.}, } @article {pmid40121259, year = {2025}, author = {Chow, PCK and Bentley, PJ}, title = {Development necessitates evolutionarily conserved factors.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {9910}, pmid = {40121259}, issn = {2045-2322}, mesh = {*Biological Evolution ; Animals ; Transcription Factors/metabolism/genetics ; Morphogenesis/genetics ; Models, Biological ; Evolution, Molecular ; }, abstract = {Early-stage generalised transcription factors in biological development are often evolutionarily conserved across species. Here, we find for the first time that similar factors functionally emerge in an alternative medium of development. Through comprehensively analysing a Neural Cellular Automata (NCA) model of morphogenesis, we find multiple properties of the hidden units that are functionally analogous to early factors in biological development. We test the generalisation abilities of our model through transfer learning of other morphologies and find that developmental strategies learnt by the model are reused to grow new body forms by conserving its early generalised factors. Our paper therefore provides evidence that nature did not become locked into one arbitrary method of developing multicellular organisms: the use of early generalised factors as fundamental control mechanisms and the resulting necessity for evolutionary conservation of those factors may be fundamental to development, regardless of the details of how development is implemented.}, } @article {pmid40112176, year = {2025}, author = {Matthews, S and Nikoonejad Fard, V and Tollis, M and Seoighe, C}, title = {Variable Gene Copy Number in Cancer-Related Pathways Is Associated With Cancer Prevalence Across Mammals.}, journal = {Molecular biology and evolution}, volume = {42}, number = {3}, pages = {}, pmid = {40112176}, issn = {1537-1719}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Neoplasms/genetics ; *Mammals/genetics ; Gene Dosage ; Longevity/genetics ; DNA Copy Number Variations ; Body Size/genetics ; Phylogeny ; Prevalence ; }, abstract = {Cancer is a disease of multicellularity, observed across the tree of life. In principle, animals with larger body sizes and longer lifespans should be at increased risk of developing cancer. However, there is no strong relationship between these traits and cancer across mammals. Previous studies have proposed that increased copy number of cancer-related genes may enhance the robustness of cancer suppression pathways in long-lived mammals, but these studies have not extended beyond known cancer-related genes. In this study, we conducted a phylogenetic generalized least squares analysis to test for associations between copy number of all protein-coding genes and longevity, body size, and cancer prevalence across 94 species of mammals. In addition to investigating the copy number of individual genes, we tested sets of related genes for a relationship between the aggregated gene copy number of the set and these traits. We did not find strong evidence to support the hypothesis that adaptive changes in gene copy number contribute to the lack of correlation between cancer prevalence and body size or lifespan. However, we found several biological processes where aggregate copy number was associated with malignancy rate. The strongest association was for the gene set relating to transforming growth factor beta, a cytokine that plays a role in cancer progression. Overall, this study provides a comprehensive evaluation of the role of gene copy number in adaptation to body size and lifespan and sheds light on the contribution of gene copy number to variation in cancer prevalence across mammals.}, } @article {pmid40109106, year = {2025}, author = {Korb, J}, title = {Changes of division of labour along the eusociality spectrum in termites, with comparisons to multicellularity.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {380}, number = {1922}, pages = {20230268}, pmid = {40109106}, issn = {1471-2970}, mesh = {*Isoptera/physiology ; Animals ; *Social Behavior ; Reproduction/physiology ; }, abstract = {Eusocial insects are characterized by reproductive division of labour, with one (or a few) individuals specialized in reproduction (queen and in termites, also a king) and the other individuals performing all other tasks (workers). Among workers, further division of labour can occur. Termites have three main castes: reproductives, comprising a queen and king; morphologically differentiated sterile soldiers; and workers. Task division among workers varies greatly depending on lifestyle and degree of workers' reproductive potential, which varies from totipotency to reproduce up to sterility. In wood-dwelling species, which do not forage outside the nest, all tasks are performed by totipotent workers, comprising multiple-instars with less further division of labour. Foraging species with pluripotent workers also have a multi-instar worker caste, but some division of labour between brood care versus foraging and defence exists. The first task seems mainly to be done by smaller-and potentially younger-instars, while the latter two tasks are performed by larger-and potentially older-workers. The highest degree of division of labour occurs in foraging species with sterile workers. Here, morphological worker castes with defined tasks and age polyethism occur. Comparisons with Metazoa reveal striking similarities with termites concerning gradients in germline/soma differentiation and cell totipotency.This article is part of the theme issue 'Division of labour as key driver of social evolution'.}, } @article {pmid40106424, year = {2025}, author = {Wright, BA and Osigus, HJ and Schmidt, MJ and Ratcliffe, J and Kamm, K and Martinez-Ortiz, GC and Rehn, M and Kvansakul, M and Schierwater, B and Humbert, PO}, title = {Tolerance of Placozoa for temperate climates: Evidence for known and new placozoan clades in the southern waters of Australia.}, journal = {PloS one}, volume = {20}, number = {3}, pages = {e0317878}, pmid = {40106424}, issn = {1932-6203}, mesh = {Animals ; *Placozoa/genetics/classification ; Haplotypes ; Phylogeny ; Australia ; Climate ; Genetic Variation ; }, abstract = {Placozoans are small multicellular sea-dwelling animals that are typically found in shallow, warm ocean waters and have been reported in various marine environments worldwide. Their unique morphology makes them a powerful new model organism to study the evolutionary cell biology in early metazoans. Yet, knowledge on their biodiversity and ecological distribution is severely limited. Here, we report the isolation of placozoans in the temperate waters of Victoria, Australia, their most southern location known to date. Using light, electron, and confocal microscopy, we describe their morphology and behaviour. In addition to the known haplotypes H2 and H17, we have identified a new haplotype, here designated as H20, which defines a new placozoan clade. This study provides novel insights into the distribution, ecological niche separation and genetic diversity of placozoans, and reports the first morphological and ultrastructural characterisation of placozoan clades isolated from the southern waters of Victoria, Australia.}, } @article {pmid40086443, year = {2025}, author = {Weiss, B and Rohkin Shalom, S and Dolgova, A and Teh, LS and Kaltenpoth, M and Dale, C and Chiel, E}, title = {Maternal symbiont transmission via envenomation in the parasitoid wasp Spalangia cameroni.}, journal = {Current biology : CB}, volume = {35}, number = {8}, pages = {1693-1705.e4}, doi = {10.1016/j.cub.2025.02.035}, pmid = {40086443}, issn = {1879-0445}, mesh = {Animals ; *Wasps/microbiology/physiology ; *Symbiosis ; Female ; Male ; Larva/microbiology/physiology ; *Wasp Venoms/metabolism ; *Enterobacteriaceae/physiology ; }, abstract = {Microbial symbionts of multicellular hosts originate from free-living ancestors and often persist through vertical transmission, but their mechanisms of establishment are not well understood. Here, we studied acquisition and transmission routes in a nascent symbiosis involving the bacterium Sodalis praecaptivus subsp. spalangiae (Sodalis SC) and the parasitoid wasp Spalangia cameroni. Using fluorescence in situ hybridization, transmission electron microscopy, and experimental infections, we found that oocytes are devoid of Sodalis SC, but the female venom gland is densely colonized. Sodalis SC is injected with the venom into the fly host, subsequently acquired by larval progeny during feeding, invades through the larval gut epithelium into multiple host organs, and eventually localizes in the venom gland. Adult wasps can also acquire Sodalis SC by artificial feeding, but, in this case, the bacterium is not transmitted vertically. Additionally, Sodalis SC is localized in the testes of some males, transmitted paternally at low frequency, and females that inherit Sodalis SC paternally can subsequently transmit it via the venom. To assess the specificity of the symbiosis, we performed experiments with the closely related free-living species Sodalis praecaptivus subsp. praecaptivus (Sodalis PP), known to initiate symbiosis with other insects. Sodalis PP is readily acquired when supplied artificially to wasp larvae but not transmitted to wasp progeny, because it fails to proliferate in the parasitized host. Our results indicate that non-ovarian transmission routes of intracellular symbionts may be more common than currently appreciated and provide a scenario for the early steps in establishing persistent symbiotic associations in insects.}, } @article {pmid40081461, year = {2025}, author = {Marijuán, PC and Navarro, J}, title = {Human cognitive limitations and emotions: The emergence of social complexity.}, journal = {Bio Systems}, volume = {251}, number = {}, pages = {105454}, doi = {10.1016/j.biosystems.2025.105454}, pmid = {40081461}, issn = {1872-8324}, mesh = {Animals ; Humans ; *Biological Evolution ; Brain/physiology ; *Cognition/physiology ; *Emotions/physiology ; *Social Behavior ; *Social Evolution ; }, abstract = {An evolutionary approach to human cognition and social complexity, acknowledging the essential role of social emotions, is attempted. From the start, every kind of cognition, either artificial or natural, is limited. In living beings, it is the life cycle, life course, or life history what determines the extension, intensity, and limitations of the cognitive tools evolved to adapt to the own niche: from bacteria to multicellulars, animals, mammals, anthropoids, etc. Herein we will briefly survey some of those instances. In the human case, the essential niche becomes an extended social group with a rich diversity of cognitive links or 'bonds' in continuous interaction. Evolutionarily, the adaptation process to this social niche has involved a series of brain size increases, allowing, above all, the cognitive wonders inherent in language. But it has also involved a restructuring of the cognitive 'shortcuts' - essentially, emotions - that help individuals to navigate their own life in the natural environment and, especially, within the highly complex social milieu. Ultimately, this social adaptation process made possible the emergence of human 'ultrasociality' -the crux of Anthropogenesis-- and the most conspicuous behavioral traits still observable in contemporary societies, the effects of which also reverberate in the practice of science itself.}, } @article {pmid40052705, year = {2025}, author = {Kataki, AD and Gupta, PG and Cheema, U and Nisbet, A and Wang, Y and Kocher, HM and Pérez-Mancera, PA and Velliou, EG}, title = {Mapping Tumor-Stroma-ECM Interactions in Spatially Advanced 3D Models of Pancreatic Cancer.}, journal = {ACS applied materials & interfaces}, volume = {17}, number = {11}, pages = {16708-16724}, pmid = {40052705}, issn = {1944-8252}, mesh = {Humans ; *Pancreatic Neoplasms/pathology/metabolism ; *Extracellular Matrix/metabolism/pathology ; Tumor Microenvironment ; Tissue Scaffolds/chemistry ; Cell Line, Tumor ; *Carcinoma, Pancreatic Ductal/pathology/metabolism ; Stromal Cells/metabolism/pathology ; Polyurethanes/chemistry ; Extracellular Matrix Proteins/metabolism ; }, abstract = {Bioengineering-based in vitro tumor models are increasingly important as tools for studying disease progression and therapy response for many cancers, including the deadly pancreatic ductal adenocarcinoma (PDAC) that exhibits a tumor/tissue microenvironment of high cellular/biochemical complexity. Therefore, it is crucial for in vitro models to capture that complexity and to enable investigation of the interplay between cancer cells and factors such as extracellular matrix (ECM) proteins or stroma cells. Using polyurethane (PU) scaffolds, we performed a systematic study on how different ECM protein scaffold coatings impact the long-term cell evolution in scaffolds containing only cancer or only stroma cells (activated stellate and endothelial cells). To investigate potential further changes in those biomarkers due to cancer-stroma interactions, we mapped their expression in dual/zonal scaffolds consisting of a cancer core and a stroma periphery, spatially mimicking the fibrotic/desmoplastic reaction in PDAC. In our single scaffolds, we observed that the protein coating affected the cancer cell spatial aggregation, matrix deposition, and biomarker upregulation in a cell-line-dependent manner. In single stroma scaffolds, different levels of fibrosis/desmoplasia in terms of ECM composition/quantity were generated depending on the ECM coating. When studying the evolution of cancer and stroma cells in our dual/zonal model, biomarkers linked to cell aggressiveness/invasiveness were further upregulated by both cancer and stroma cells as compared to single scaffold models. Collectively, our study advances the understanding of how different ECM proteins impact the long-term cell evolution in PU scaffolds. Our findings show that within our bioengineered models, we can stimulate the cells of the PDAC microenvironment to develop different levels of aggressiveness/invasiveness, as well as different levels of fibrosis. Furthermore, we highlight the importance of considering spatial complexity to map cell invasion. Our work contributes to the design of in vitro models with variable, yet biomimetic, tissue-like properties for studying the tumor microenvironment's role in cancer progression.}, } @article {pmid40044858, year = {2025}, author = {Tong, K and Datta, S and Cheng, V and Haas, DJ and Gourisetti, S and Yopp, HL and Day, TC and Lac, DT and Khalil, AS and Conlin, PL and Bozdag, GO and Ratcliff, WC}, title = {Genome duplication in a long-term multicellularity evolution experiment.}, journal = {Nature}, volume = {639}, number = {8055}, pages = {691-699}, pmid = {40044858}, issn = {1476-4687}, support = {R01 AI171100/AI/NIAID NIH HHS/United States ; }, mesh = {*Saccharomyces cerevisiae/genetics/cytology ; *Genome, Fungal/genetics ; *Tetraploidy ; Diploidy ; Aneuploidy ; *Gene Duplication/genetics ; Time Factors ; Selection, Genetic ; *Evolution, Molecular ; Genetic Fitness/genetics ; *Biological Evolution ; Cell Size ; }, abstract = {Whole-genome duplication (WGD) is widespread across eukaryotes and can promote adaptive evolution[1-4]. However, given the instability of newly formed polyploid genomes[5-7], understanding how WGDs arise in a population, persist, and underpin adaptations remains a challenge. Here, using our ongoing Multicellularity Long Term Evolution Experiment (MuLTEE)[8], we show that diploid snowflake yeast (Saccharomyces cerevisiae) under selection for larger multicellular size rapidly evolve to be tetraploid. From their origin within the first 50 days of the experiment, tetraploids persisted for the next 950 days (nearly 5,000 generations, the current leading edge of our experiment) in 10 replicate populations, despite being genomically unstable. Using synthetic reconstruction, biophysical modelling and counter-selection, we found that tetraploidy evolved because it confers immediate fitness benefits under this selection, by producing larger, longer cells that yield larger clusters. The same selective benefit also maintained tetraploidy over long evolutionary timescales, inhibiting the reversion to diploidy that is typically seen in laboratory evolution experiments. Once established, tetraploidy facilitated novel genetic routes for adaptation, having a key role in the evolution of macroscopic multicellular size via the origin of evolutionarily conserved aneuploidy. These results provide unique empirical insights into the evolutionary dynamics and impacts of WGD, showing how it can initially arise due to its immediate adaptive benefits, be maintained by selection and fuel long-term innovations by creating additional dimensions of heritable genetic variation.}, } @article {pmid40044726, year = {2025}, author = {Gao, Y and Pichugin, Y and Traulsen, A and Zapién-Campos, R}, title = {Evolution of irreversible differentiation under stage-dependent cell differentiation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {7786}, pmid = {40044726}, issn = {2045-2322}, support = {12401644//National Natural Science Foundation of China/ ; 2024JC-YBQN-0005//Natural Science Basic Research Program of Shaanxi Province/ ; }, mesh = {*Cell Differentiation ; *Biological Evolution ; *Models, Biological ; Germ Cells/cytology ; Animals ; Cell Division ; }, abstract = {The specialization of cells is a hallmark of complex multicellularity. Cell differentiation enables the emergence of specialized cell types that carry out separate functions previously executed by a multifunctional ancestor cell. One view about the origin of cell differentiation is that it first occurred randomly in genetically identical cells exposed to the same life history environment. Under these conditions, differentiation trajectories producing more offspring could be favored by natural selection; yet, how dynamic variation in differentiation probabilities can affect the evolution of differentiation patterns is unclear. We develop a theoretical model to investigate the effect of dynamic-stage-dependent-cell differentiation on the evolution of optimal differentiation patterns. Concretely, we model trajectories in which cells can randomly differentiate into germ or soma cell types at each cell division. After comparing many of these trajectories, we found that irreversible differentiation, where cells gradually lose their ability to produce the other cell type, is more favored in small organisms under dynamic than under constant (stage-independent) cell differentiation. Furthermore, we found that the irreversible differentiation of germ cells, where germ cells gradually lose their ability to produce soma cells, is prominent among irreversible patterns. Only large variations in the differentiation probabilities prohibit irreversible trajectories from being the optimal pattern.}, } @article {pmid40042639, year = {2025}, author = {Zhu, T and Ning, P and Liu, Y and Liu, M and Yang, J and Wang, Z and Li, M}, title = {Knowledge of microalgal Rubiscos helps to improve photosynthetic efficiency of crops.}, journal = {Planta}, volume = {261}, number = {4}, pages = {78}, pmid = {40042639}, issn = {1432-2048}, support = {6651121004//"First class grass land science discipline" program in Shandong Province, the Talents of High Level Scientific Research Foundation of Qingdao Agricultural University/ ; 6651120032//"First class grass land science discipline" program in Shandong Province, the Talents of High Level Scientific Research Foundation of Qingdao Agricultural University/ ; 22278233//National Natural Science Foundation of China/ ; ZR2022QB143//Natural Science Foundation of Shandong Province/ ; ZR2020QC069//Natural Science Foundation of Shandong Province/ ; M2023-05//State Key Laboratory of Microbial Resources, Chinese Academy of Sciences/ ; M2022-07//State Key Laboratory of Microbial Technology Open Projects Fund/ ; }, mesh = {*Photosynthesis/physiology ; *Microalgae/enzymology/genetics ; *Ribulose-Bisphosphate Carboxylase/metabolism/genetics/chemistry ; *Crops, Agricultural/physiology/enzymology/metabolism/genetics ; }, abstract = {A comprehensive understanding of microalgal Rubiscos offers opportunities to enhance photosynthetic efficiency of crops. As food production fails to meet the needs of the expanding population, there is increasing concern about Ribulose-1, 5-diphosphate (RuBP) carboxylase/oxygenase (Rubisco), the enzyme that catalyzes CO2 fixation in photosynthesis. There have been many attempts to optimize Rubisco in crops, but the complex multicellular structure of higher plants makes optimization more difficult. Microalgae have the characteristics of rapid growth, simple structure and easy molecular modification, and the function and properties of their Rubiscos are basically the same as those of higher plants. Research on microalgal Rubiscos helps to broaden the understanding of Rubiscos of higher plants. Also, transferring all or part of better microalgal Rubiscos into crop cells or giving crop Rubiscos the advantages of microalgal Rubiscos can help improve the photosynthesis of crops. In this review, the distribution, origin, evolution, molecular structure, folding, assembly, activation and kinetic properties of microalgal Rubiscos are summarized. Moreover, the development of some effective methods to improve the properties and application of Rubiscos in microalgae are also described.}, } @article {pmid40008892, year = {2025}, author = {Leon, F and Espinoza-Esparza, JM and Deng, V and Coyle, MC and Espinoza, S and Booth, DS}, title = {Cell differentiation controls iron assimilation in the choanoflagellate Salpingoeca rosetta.}, journal = {mSphere}, volume = {10}, number = {3}, pages = {e0091724}, pmid = {40008892}, issn = {2379-5042}, support = {R35 GM147404/GM/NIGMS NIH HHS/United States ; T32GM139786//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R35GM147404//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32 GM139786/GM/NIGMS NIH HHS/United States ; S10 OD018174/OD/NIH HHS/United States ; //David and Lucile Packard Foundation (PF)/ ; //NSF | National Science Foundation Graduate Research Fellowship Program (GRFP)/ ; }, mesh = {*Iron/metabolism ; *Choanoflagellata/metabolism/genetics/cytology ; *Cell Differentiation ; FMN Reductase/genetics/metabolism ; }, abstract = {UNLABELLED: Marine microeukaryotes have evolved diverse cellular features that link their life histories to surrounding environments. How those dynamic life histories intersect with the ecological functions of microeukaryotes remains a frontier to understanding their roles in critical biogeochemical cycles. Choanoflagellates, phagotrophs that cycle nutrients through filter feeding, provide models to explore this intersection, for many choanoflagellate species transition between life history stages by differentiating into distinct cell types. Here, we report that cell differentiation in the marine choanoflagellate Salpingoeca rosetta endows one of its cell types with the ability to utilize insoluble ferric colloids. These colloids are a predominant form of iron in marine environments and are largely inaccessible to cell-walled microbes. Therefore, choanoflagellates and other phagotrophic eukaryotes may serve critical ecological roles by cycling this essential nutrient through iron utilization pathways. We found that S. rosetta can utilize these ferric colloids via the expression of a cytochrome b561 iron reductase (cytb561a). This gene and its mammalian ortholog, the duodenal cytochrome b561 (DCYTB) that reduces ferric cations for uptake in gut epithelia, belong to a subgroup of cytochrome b561 proteins with distinct biochemical features that contribute to iron reduction activity. Overall, our findings provide insight into the ecological roles choanoflagellates perform and inform reconstructions of early animal evolution where functionally distinct cell types became an integrated whole at the origin of animal multicellularity.

IMPORTANCE: This study examines how cell differentiation in a choanoflagellate enables the uptake of iron, an essential nutrient. Choanoflagellates are widespread, aquatic microeukaryotes that are the closest living relatives of animals. Similar to their animal relatives, we found that the model choanoflagellate, S. rosetta, divides metabolic functions between distinct cell types. One cell type uses an iron reductase to acquire ferric colloids, a key source of iron in the ocean. We also observed that S. rosetta has three variants of this reductase, each with distinct biochemical properties that likely lead to differences in how they reduce iron. These reductases are variably distributed across ocean regions, suggesting a role for choanoflagellates in cycling iron in marine environments.}, } @article {pmid40001581, year = {2025}, author = {Liu, Z and Fan, X and Wu, Y and Zhang, W and Zhang, X and Xu, D and Wang, Y and Sun, K and Wang, W and Ye, N}, title = {Comparative Genomics of Bryopsis hypnoides: Structural Conservation and Gene Transfer Between Chloroplast and Mitochondrial Genomes.}, journal = {Biomolecules}, volume = {15}, number = {2}, pages = {}, pmid = {40001581}, issn = {2218-273X}, mesh = {*Genome, Chloroplast ; *Genome, Mitochondrial ; Phylogeny ; *Genomics/methods ; RNA, Transfer/genetics ; Codon Usage ; Chloroplasts/genetics ; Evolution, Molecular ; *Chlorophyta/genetics ; Gene Transfer, Horizontal ; }, abstract = {Bryopsis hypnoides, a unicellular multinucleate green alga in the genus Bryopsis, plays vital ecological roles and represents a key evolutionary link between unicellular and multicellular algae. However, its weak genetic baseline data have constrained the progress of evolutionary research. In this study, we successfully assembled and annotated the complete circular chloroplast and mitochondrial genomes of B. hypnoides. The chloroplast genome has a total length of 139,745 bp and contains 59 protein-coding genes, 2 rRNA genes, and 11 tRNA genes, with 31 genes associated with photosynthesis. The mitochondrial genome has a total length of 408,555 bp and contains 41 protein-coding genes, 3 rRNA genes, and 18 tRNA genes, with 18 genes involved in oxidative phosphorylation. Based on the data, we conducted a genetic comparison involving repeat sequences, phylogenetic relationships, codon usage preferences, and gene transfer between the two organellar genomes. The major results highlighted that (1) the chloroplast genome favors A/T repeats, whereas the mitochondrial genome prefers C/G repeats; (2) codon usage preference analysis indicated that both organellar genomes prefer codons ending in A/T, with a stronger bias observed in the chloroplast genome; and (3) sixteen fragments with high sequence identity were identified between the two organellar genomes, indicating potential gene transfer. These findings provide critical insights into the organellar genome characteristics and evolution of B. hypnoides.}, } @article {pmid39999802, year = {2025}, author = {Saier, MH}, title = {Cooperation and Competition Were Primary Driving Forces for Biological Evolution.}, journal = {Microbial physiology}, volume = {35}, number = {1}, pages = {13-29}, pmid = {39999802}, issn = {2673-1673}, support = {R01 GM077402/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Humans ; Symbiosis ; Animals ; Cooperative Behavior ; }, abstract = {BACKGROUND: For many years, scientists have accepted Darwin's conclusion that "Survival of the Fittest" involves successful competition with other organisms for life-endowing molecules and conditions.

SUMMARY: Newly discovered "partial" organisms with minimal genomes that require symbiotic or parasitic relationships for growth and reproduction suggest that cooperation in addition to competition was and still is a primary driving force for survival. These two phenomena are not mutually exclusive, and both can confer a competitive advantage for survival. In fact, cooperation may have been more important in the early evolution of life on earth before autonomous organisms developed, becoming large genome organisms.

KEY MESSAGES: This suggestion has tremendous consequences with respect to our conception of the early evolution of life on earth as well as the appearance of intercellular interactions, multicellularity and the nature of interactions between humans and their societies (e.g., social Darwinism).}, } @article {pmid39999174, year = {2025}, author = {Matte, A and LeBoeuf, AC}, title = {Innovation in ant larval feeding facilitated queen-worker divergence and social complexity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {9}, pages = {e2413742122}, pmid = {39999174}, issn = {1091-6490}, support = {PR00P3_179776//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)/ ; }, mesh = {Animals ; *Ants/physiology/classification ; Larva/physiology ; *Feeding Behavior/physiology ; Phylogeny ; Biological Evolution ; *Social Behavior ; Female ; }, abstract = {Building differences between genetically equivalent units is a fundamental challenge for all multicellular organisms and superorganisms. In ants, reproductive or worker fate is typically determined during the larval stage, through feeding regimes managed by adult caretakers. However, the feeding care provided to larvae varies significantly across ants, as does phenotypic divergence between queen and worker castes. Here, we employed comparative phylogenetic methods and causal inference to investigate the relationships between larval feeding care, caste size dimorphism, and social complexity across ant diversity. We digitized the life's work of George and Jeanette Wheeler, cataloging the larval morphology of over 700 species, and we compiled data on species diets and larval feeding behaviors from the literature and our own observations. We measured queen-worker size dimorphism in 392 species and gathered data for colony size, worker polymorphism, and worker reproduction. Our analyses revealed that ancestral active-feeding larvae evolved passive morphologies when adults began feeding them individually, typically with processed material and often following a shift to nonpredatory diets. Greater queen-worker size dimorphism coevolved with larval passiveness, alongside traits indicative of increased social complexity, including larger colony sizes, worker subcastes, and a reduction in workers' reproductive potential. Likelihood comparisons of causal phylogenetic models support that extended alloparental care facilitated stronger caste dimorphism, which, in turn and along with increased colony sizes, promoted higher social complexity. Our results suggest that enhanced adult control over larval development enabled greater phenotypic specialization within colonies, with profound implications for social evolution.}, } @article {pmid39998200, year = {2025}, author = {Hu, P}, title = {mSphere of Influence: Rapid evolution of pathogenesis and drug resistance in human pathogenic fungi.}, journal = {mSphere}, volume = {10}, number = {3}, pages = {e0057024}, pmid = {39998200}, issn = {2379-5042}, mesh = {Humans ; *Drug Resistance, Fungal/genetics ; *Evolution, Molecular ; Virulence ; *Fungi/pathogenicity/genetics/drug effects ; *Cryptococcus/genetics/pathogenicity/drug effects ; DNA Transposable Elements ; Antifungal Agents/pharmacology ; Mycoses/microbiology ; }, abstract = {Pengjie Hu works in the field of fungal pathogenesis, drug resistance, and evolution. In this mSphere of Influence article, he reflects on how three works, "Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro" and "Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans" by Gusa et al. and "Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection" by Bing et al. have impacted his work on the evolution of virulence, resistance, and adaptation in human fungal pathogens.}, } @article {pmid39981820, year = {2025}, author = {Du, Y and Wang, C and Zhang, Y and Liu, H}, title = {Evolutionary Origins and Adaptive Significance of A-to-I RNA Editing in Animals and Fungi.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {47}, number = {5}, pages = {e202400220}, doi = {10.1002/bies.202400220}, pmid = {39981820}, issn = {1521-1878}, support = {32170200//National Natural Science Foundation of China/ ; 31872918//National Natural Science Foundation of China/ ; }, mesh = {*RNA Editing/genetics ; Animals ; *Fungi/genetics ; *Adenosine/genetics/metabolism ; *Inosine/genetics/metabolism ; *Evolution, Molecular ; *Biological Evolution ; Adaptation, Physiological/genetics ; }, abstract = {Adenosine-to-inosine (A-to-I) RNA editing, capable of protein recoding, has evolved independently in animals and fungi. This study proposes adaptive hypotheses regarding its origins and phenotypic significance, suggesting that A-to-I editing enhances adaptability by alleviating genetic trade-offs. In metazoans, its emergence may have been driven by a development-defense trade-off associated with transposable element activation during the evolution of multicellularity. Late Devonian cooling and End-Permian warming are hypothesized to have driven the emergence of extensive A-to-I recoding in coleoid nervous systems and Sordariomycete sexual fruiting bodies, respectively. These adaptations may have influenced key evolutionary innovations, including the evolution of metazoan nervous systems, coleoid intelligence, and shell loss, and fungal sexual reproductive structures. Additionally, extensive A-to-I recoding is proposed to facilitate accelerated development and specific life-history strategies in both animals and fungi. This paper provides new perspectives on the evolutionary forces shaping A-to-I RNA editing and its role in phenotypic diversity across taxa.}, } @article {pmid39981724, year = {2025}, author = {Siemons, C and Jonkers, S and Vlieg, RC and Corral-Martínez, P and van Noort, J and Boutilier, K}, title = {Establishment and maintenance of embryogenic cell fate during microspore embryogenesis.}, journal = {The Plant journal : for cell and molecular biology}, volume = {121}, number = {4}, pages = {e17243}, pmid = {39981724}, issn = {1365-313X}, support = {656579//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; 435005024/ZONMW_/ZonMw/Netherlands ; 737.016.013//NWO Building Blocks of Life/ ; }, mesh = {*Brassica napus/embryology/genetics/cytology ; *Pollen/embryology/cytology/genetics ; *Seeds/cytology/genetics/embryology ; Gene Expression Regulation, Plant ; Plant Proteins/genetics/metabolism ; Cell Differentiation ; Indoleacetic Acids/metabolism ; Time-Lapse Imaging ; }, abstract = {Microspore embryogenesis is a type of in vitro totipotency in which the immature male gametophyte (pollen) develops into a haploid embryo after an abiotic stress treatment. In Brassica napus, heat-stress treatment of male gametophytes induces the development of different types of multicellular embryogenic structures, each with different cellular characteristics and the capacity to form a differentiated embryo. The origin and early development of these different embryogenic structures have not been determined. We used two-photon excitation fluorescence microscopy and time-lapse imaging of cells expressing either a LEAFY COTYLEDON1 (LEC1) embryo identity reporter or a DR5v2 auxin response reporter to follow the development of embryogenic structures starting at the single- to few-cell stage. We show for the first time that the developmental fate of embryogenic structures is defined by the symmetry of the first embryogenic division and that the division plane also predicts the timing of subsequent pollen wall (exine) rupture: suspensorless embryos develop after a symmetric division and undergo late exine rupture, while suspensor-bearing embryos and embryogenic callus develop after an asymmetric division and undergo early exine rupture. Live imaging also captured previously unknown dynamic LEC1 and DR5v2 expression patterns that are associated with changes in exine integrity. This study highlights the developmental plasticity of cultured pollen and uncovers new roles for the first embryogenic cell division plane and the exine in defining and maintaining cell fate during microspore embryogenesis.}, } @article {pmid39979449, year = {2025}, author = {Thibault, B and Thole, A and D'Angelo, R and Basset, C and Guillermet-Guibert, J}, title = {PI3Kα-specific inhibitor BYL-719 synergizes with cisplatin in vitro in PIK3CA-mutated ovarian cancer cells.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6265}, pmid = {39979449}, issn = {2045-2322}, support = {ARCPGA2022120005630_6362//Foundation for Cancer Research (ARC)/ ; TOUCAN//ANR/ ; }, mesh = {Humans ; Female ; *Cisplatin/pharmacology ; *Class I Phosphatidylinositol 3-Kinases/genetics/antagonists & inhibitors/metabolism ; *Ovarian Neoplasms/genetics/drug therapy/pathology ; Cell Line, Tumor ; Drug Synergism ; *Mutation ; Signal Transduction/drug effects ; Antineoplastic Agents/pharmacology ; *Thiazoles/pharmacology ; *Phosphoinositide-3 Kinase Inhibitors ; Proto-Oncogene Proteins c-akt/metabolism ; Drug Resistance, Neoplasm/drug effects ; }, abstract = {Peritoneal carcinomatosis in ovarian cancer is often associated with ascites where cancer cells grow as aggregates. Given the emerging evidence that multicellular growth enhances resistance to conventional therapies, and that patients frequently develop resistance to platinum salts, we investigated the efficiency of PI3K/Akt signalling pathway targeting in multicellular growth and its importance as a potential therapeutic target in cells resistant to platinum salts. Due to its importance in many cancers and to the frequent mutations of its encoding gene PIK3CA, we focused on targeting PI3Kα using BYL-719 (Alpelisib), an isoform-specific inhibitor already used in clinics. We used a panel of 3 ovarian cancer cell lines, SKOV-3, EFO-21 and OVCAR-3, which come from different histological origins and bear different mutations. PI3K targeting drugs inhibit the activity of the PI3K/Akt pathway in all tested ovarian cancer cell lines with a drastic reduction of the phosphorylation of Akt on the serine 473, regardless the histology or the mutational profile. We showed that when cultured in 3D aggregates, ovarian cancer cells are more resistant to the PI3Kα-specific inhibitor BYL-719 and cisplatin compared to 2D monolayers. BYL-719 synergizes with cisplatin in 3D cultures only in PIK3CA-mutated SKOV-3 cells. This drug combination leads to a major cytotoxicity in 3D aggregates of this cell line. Finally, BYL-719 in combination with cisplatin remains active in 3D aggregates of SKOV-3 cells co-cultured with mesenchymal stem cells. We have identified a signalling pathway of interest for the treatment of advanced ovarian cancer in vitro, which could limit the progression of this disease. These data pave the road to investigate whether PI3Kα-specific inhibitor BYL-719 should be proposed in combination with cisplatin, in priority in patients bearing a PIK3CA mutation.}, } @article {pmid39970120, year = {2024}, author = {Finoshin, AD and Kravchuk, OI and Mikhailov, KV and Ziganshin, RH and Adameyko, KI and Mikhailov, VS and Lyupina, YV}, title = {[Structure and Function of the Transglutaminase Cluster in the Basal Metazoan Halisarca dujardinii (Sponge)].}, journal = {Molekuliarnaia biologiia}, volume = {58}, number = {5}, pages = {797-810}, pmid = {39970120}, issn = {0026-8984}, mesh = {Animals ; *Transglutaminases/genetics/metabolism/chemistry ; *Porifera/enzymology/genetics ; *Multigene Family ; Reactive Oxygen Species/metabolism ; }, abstract = {Transglutaminases are enzymes that carry out post-translational modifications of proteins and participate in the regulation of their activities. Here, we show for the first time that the transglutaminase genes in the basal metazoan, the sea sponge Halisarca dujardinii, are organized in a cluster, similarly to mammalian transglutaminases. The regulatory regions of six transglutaminase genes and their differential expression in the course of the life cycle of H. dujardinii suggest independent regulation of these genes. The decrease in transglutaminase activities by cystamine facilitates restoration of the multicellular structures of this sponge after its mechanical dissociation. For the first time we observed that this decrease in transglutaminase activities was accompanied by generation of the reactive oxygen species in the cells of a basal metazoan. The study of transglutaminases in the basal metazoans and other sea-dwelling organisms might provide better understanding of the evolution and specific functions of these enzymes in higher animals.}, } @article {pmid39964480, year = {2025}, author = {Raynal, F and Sengupta, K and Plewczynski, D and Aliaga, B and Pancaldi, V}, title = {Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer.}, journal = {Nucleic acids research}, volume = {53}, number = {4}, pages = {}, pmid = {39964480}, issn = {1362-4962}, support = {//Fondation Toulouse Cancer Santé/ ; //Pierre Fabre Foundation for Research/ ; ANR-23-CE12-0023//Agence Nationale de la Recherche/ ; //Warsaw University of Technology/ ; 2020/37/B/NZ2/03757//National Science Centre/ ; }, mesh = {Humans ; *Cell Differentiation/genetics ; *Chromatin/genetics/metabolism ; *Evolution, Molecular ; *Gene Expression Regulation, Neoplastic ; RNA Polymerase II/metabolism/genetics ; *Chromatin Assembly and Disassembly/genetics ; Polycomb-Group Proteins/metabolism/genetics ; Epigenesis, Genetic ; *Neoplasms/genetics ; Colorectal Neoplasms/genetics/pathology ; }, abstract = {Cancer cells are highly plastic, favoring adaptation to changing conditions. Genes related to basic cellular processes evolved in ancient species, while more specialized genes appeared later with multicellularity (metazoan genes) or even after mammals evolved. Transcriptomic analyses have shown that ancient genes are up-regulated in cancer, while metazoan-origin genes are inactivated. Despite the importance of these observations, the underlying mechanisms remain unexplored. Here, we study local and global epigenomic mechanisms that may regulate genes from specific evolutionary periods. Using evolutionary gene age data, we characterize the epigenomic landscape, gene expression regulation, and chromatin organization in several cell types: human embryonic stem cells, normal primary B-cells, primary chronic lymphocytic leukemia malignant B-cells, and primary colorectal cancer samples. We identify topological changes in chromatin organization during differentiation observing patterns in Polycomb repression and RNA polymerase II pausing, which are reversed during oncogenesis. Beyond the non-random organization of genes and chromatin features in the 3D epigenome, we suggest that these patterns lead to preferential interactions among ancient, intermediate, and recent genes, mediated by RNA polymerase II, Polycomb, and the lamina, respectively. Our findings shed light on gene regulation according to evolutionary age and suggest this organization changes across differentiation and oncogenesis.}, } @article {pmid39947017, year = {2025}, author = {Zunjarrao, S and Gambetta, MC}, title = {Principles of long-range gene regulation.}, journal = {Current opinion in genetics & development}, volume = {91}, number = {}, pages = {102323}, doi = {10.1016/j.gde.2025.102323}, pmid = {39947017}, issn = {1879-0380}, mesh = {Animals ; *Promoter Regions, Genetic/genetics ; *Gene Expression Regulation ; Drosophila/genetics ; Transcription, Genetic ; Humans ; Evolution, Molecular ; Genome ; }, abstract = {Transcription from gene promoters occurs in specific spatiotemporal patterns in multicellular organisms, controlled by genomic regulatory elements. The communication between a regulatory element and a promoter requires a certain degree of physical proximity between them; hence, most gene regulation occurs locally in the genome. However, recent discoveries have revealed long-range gene regulation strategies that enhance interactions between regulatory elements and promoters by overcoming the distances between them in the linear genome. These new findings challenge the traditional view of how gene expression patterns are controlled. This review examines long-range gene regulation strategies recently reported in Drosophila and mammals, offering insights into their mechanisms and evolution.}, } @article {pmid39939306, year = {2025}, author = {Bijonowski, BM and Park, J and Bergert, M and Teubert, C and Diz-Muñoz, A and Galic, M and Wegner, SV}, title = {Intercellular adhesion boots collective cell migration through elevated membrane tension.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1588}, pmid = {39939306}, issn = {2041-1723}, support = {757593//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; GA2268/4-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 386797833//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {*Cell Movement/physiology ; *Cell Adhesion/physiology ; *Cell Membrane/metabolism/physiology ; Animals ; Humans ; Cytoskeleton/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; Phospholipase D/metabolism ; *Cell Communication/physiology ; Fibroblasts ; }, abstract = {In multicellular systems, the migration pattern of individual cells critically relies on the interactions with neighboring cells. Depending on the strength of these interactions, cells either move as a collective, as observed during morphogenesis and wound healing, or migrate individually, as it is the case for immune cells and fibroblasts. Mediators of cell-cell adhesions, such as cadherins coordinate collective dynamics by linking the cytoskeleton of neighboring cells. However, whether intercellular binding alone triggers signals that originate from within the plasma membrane itself, remains unclear. Here, we address this question through artificial photoswitchable cell-cell adhesions that selectively connect adjacent plasma membranes without linking directly to cytoskeletal elements. We find that these intercellular adhesions are sufficient to achieve collective cell migration. Linking adjacent cells increases membrane tension, which activates the enzyme phospholipase D2. The resulting increase in phosphatidic acid, in turn, stimulates the mammalian target of rapamycin, a known actuator of collective cell migration. Collectively, these findings introduce a membrane-based signaling axis as promotor of collective cell dynamics, which is independent of the direct coupling of cell-cell adhesions to the cytoskeleton.}, } @article {pmid39932998, year = {2025}, author = {Loiodice, M and Drula, E and McIver, Z and Antonyuk, S and Baslé, A and Lima, M and Yates, EA and Byrne, DP and Coughlan, J and Leech, A and Mesdaghi, S and Rigden, DJ and Drouillard, S and Helbert, W and Henrissat, B and Terrapon, N and Wright, GSA and Couturier, M and Cartmell, A}, title = {Bacterial polysaccharide lyase family 33: Specificity from an evolutionarily conserved binding tunnel.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {7}, pages = {e2421623122}, pmid = {39932998}, issn = {1091-6490}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Polysaccharide-Lyases/metabolism/chemistry/genetics ; Substrate Specificity ; *Bacterial Proteins/chemistry/metabolism/genetics ; Evolution, Molecular ; Models, Molecular ; Glycosaminoglycans/metabolism ; Binding Sites ; Amino Acid Sequence ; }, abstract = {Acidic glycans are essential for the biology of multicellular eukaryotes. To utilize them, microbial life including symbionts and pathogens has evolved polysaccharide lyases (PL) that cleave their 1,4 glycosidic linkages via a β-elimination mechanism. PL family 33 (PL33) enzymes have the unusual ability to target a diverse range of glycosaminoglycans (GAGs), as well as the bacterial polymer, gellan gum. In order to gain more detailed insight into PL33 activities we recombinantly expressed 10 PL33 members derived from all major environments and further elucidated the detailed biochemical and biophysical properties of five, showing that their substrate specificity is conferred by variations in tunnel length and topography. The key amino acids involved in catalysis and substrate interactions were identified, and employing a combination of complementary biochemical, structural, and modeling approaches, we show that the tunnel topography is induced by substrate binding to the glycan. Structural and bioinformatic analyses revealed that these features are conserved across several lyase families as well as in mammalian GAG epimerases.}, } @article {pmid39898884, year = {2025}, author = {Vanhoeijen, R and Okkelman, IA and Rogier, N and Sedlačík, T and Stöbener, DD and Devriendt, B and Dmitriev, RI and Hoogenboom, R}, title = {Poly(2-alkyl-2-oxazoline) Hydrogels as Synthetic Matrices for Multicellular Spheroid and Intestinal Organoid Cultures.}, journal = {Biomacromolecules}, volume = {26}, number = {3}, pages = {1860-1872}, doi = {10.1021/acs.biomac.4c01627}, pmid = {39898884}, issn = {1526-4602}, mesh = {*Hydrogels/chemistry ; *Organoids/cytology/drug effects ; *Spheroids, Cellular/cytology/drug effects ; Humans ; Extracellular Matrix/chemistry ; Cell Proliferation/drug effects ; *Intestines/cytology ; Animals ; Cell Culture Techniques ; *Oxazoles/chemistry ; }, abstract = {The extracellular matrix (ECM) plays a crucial role in organoid cultures by supporting cell proliferation and differentiation. A key feature of the ECM is its mechanical influence on the surrounding cells, directly affecting their behavior. Matrigel, the most commonly used ECM, is limited by its animal-derived origin, batch variability, and uncontrollable mechanical properties, restricting its use in 3D cell-model-based mechanobiological studies. Poly(2-alkyl-2-oxazoline) (PAOx) synthetic hydrogels represent an appealing alternative because of their reproducibility and versatile chemistry, enabling tuning of hydrogel stiffness and functionalization. Here, we studied PAOx hydrogels with differing compressive moduli for their potential to support 3D cell growth. PAOx hydrogels support spheroid and organoid growth over several days without the addition of ECM components. Furthermore, we discovered intestinal organoid epithelial polarity reversion in PAOx hydrogels and demonstrate how the tunable mechanical properties of PAOx can be used to study effects on the morphology and oxygenation of live multicellular spheroids.}, } @article {pmid39890889, year = {2025}, author = {Paul, CD and Yankaskas, C and Shahi Thakuri, P and Balhouse, B and Salen, S and Bullock, A and Beam, S and Chatman, A and Djikeng, S and Yang, XJ and Wong, G and Dey, I and Holmes, S and Dockey, A and Bailey-Steinitz, L and Zheng, L and Li, W and Chandra, V and Nguyen, J and Sharp, J and Willems, E and Kennedy, M and Dallas, MR and Kuninger, D}, title = {Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {3933}, pmid = {39890889}, issn = {2045-2322}, mesh = {Humans ; *Organoids/pathology/metabolism ; *Neoplasms/pathology/genetics ; Cell Line, Tumor ; Female ; Cell Culture Techniques/methods ; }, abstract = {Tumoroids, sometimes referred to as cancer organoids, are patient-derived cancer cells grown as 3D, self-organized multicellular structures that maintain key characteristics (e.g., genotype, gene expression levels) of the tumor from which they originated. These models have emerged as valuable tools for studying tumor biology, cytotoxicity, and response of patient-derived cells to cancer therapies. However, the establishment and maintenance of tumoroids has historically been challenging, labor intensive, and highly variable from lab to lab, hindering their widespread use. Here, we characterize the establishment and/or expansion of colorectal, lung, head and neck, breast, pancreas, and endometrial tumoroids using the standardized, serum-free Gibco OncoPro Tumoroid Culture Medium. Newly derived tumoroid lines (n = 20) were analyzed by targeted genomic profiling and RNA sequencing and were representative of tumor tissue samples. Tumoroid lines were stable for over 250 days in culture and freeze-thaw competent. Previously established tumoroid lines were also transitioned to OncoPro medium and exhibited, on average, similar growth rates and conserved donor-specific characteristics when compared to original media systems. Additionally, OncoPro medium was compatible with both embedded culture in extracellular matrix and growth in a suspension format for facile culture and scale up. An example application of these models for assessing the cytotoxicity of a natural killer cell line and primary natural killer cells over time and at various doses demonstrated the compatibility of these models with assays used in compound and cell therapy development. We anticipate that the standardization and versatility of this approach will have important benefits for basic cancer research, drug discovery, and personalized medicine and help make tumoroid models more accessible to the cancer research community.}, } @article {pmid39884276, year = {2025}, author = {Van Goor, J and Turdiev, A and Speir, SJ and Manning, J and Haag, ES}, title = {Male secreted short glycoproteins link sperm competition to the reproductive isolation of species.}, journal = {Current biology : CB}, volume = {35}, number = {4}, pages = {911-917.e5}, doi = {10.1016/j.cub.2024.12.040}, pmid = {39884276}, issn = {1879-0445}, mesh = {Animals ; Male ; *Spermatozoa/physiology/metabolism ; *Reproductive Isolation ; Female ; *Caenorhabditis/physiology/genetics ; *Glycoproteins/metabolism/genetics ; *Helminth Proteins/metabolism/genetics ; }, abstract = {Sperm competition is found across multicellular organisms[1][,][2][,][3][,][4] using both external and internal fertilization.[5][,][6] Sperm competition and post-copulatory cryptic female choice can promote incompatibility between species due to the antagonistic coevolution of the sexes within a species.[7][,][8][,][9][,][10][,][11] This between-species incompatibility is accelerated and markedly asymmetrical when sexual mode differs, producing the "weak inbreeder, strong outcrosser" (WISO) pattern.[12] Here, we show that male secreted short (MSS) sperm glycoproteins of nematodes constitute a gametic effector of WISO. In obligately outcrossing Caenorhabditis, MSS is dispensable for baseline fertility but required for intraspecific sperm competitiveness.[13] MSS is lost in self-fertile lineages, likely as a response to selection for a hermaphrodite-biased sex ratio.[14] Selfing hermaphrodites that mate with males of closely related outcrossing species are rapidly sterilized due to ovarian sperm invasion.[11] The simplification of the male proteome in selfing species suggests that many factors could contribute to invasivity.[13][,][15][,][16] However, restoration of just MSS to the self-fertile C. briggsae is sufficient to induce mild invasivity. Further, MSS+ sperm appear to derive their competitive advantage from this behavior, directly linking interspecies incompatibility with intraspecific competition. MSS-related proteins (MSRPs) remaining in the C. briggsae genome are similar in structure, expression, and localization to MSS but are not necessary for normal sperm competitiveness. Further, overexpression of the MSRP most similar to MSS, Cbr-MSRP-3, is insufficient to enhance competitiveness. We conclude that outcrossing species retain sperm competition factors that contribute to their reproductive isolation from selfing relatives that lost them.}, } @article {pmid39883703, year = {2025}, author = {Wong, W and Bravo, P and Yunker, PJ and Ratcliff, WC and Burnetti, AJ}, title = {Oxygen-binding proteins aid oxygen diffusion to enhance fitness of a yeast model of multicellularity.}, journal = {PLoS biology}, volume = {23}, number = {1}, pages = {e3002975}, pmid = {39883703}, issn = {1545-7885}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; }, mesh = {*Oxygen/metabolism ; *Myoglobin/metabolism/genetics ; *Saccharomyces cerevisiae/metabolism/genetics ; Diffusion ; *Hemerythrin/metabolism/genetics ; Oxygen Consumption ; Biological Evolution ; Models, Biological ; }, abstract = {Oxygen availability is a key factor in the evolution of multicellularity, as larger and more sophisticated organisms often require mechanisms allowing efficient oxygen delivery to their tissues. One such mechanism is the presence of oxygen-binding proteins, such as globins and hemerythrins, which arose in the ancestor of bilaterian animals. Despite their importance, the precise mechanisms by which oxygen-binding proteins influenced the early stages of multicellular evolution under varying environmental oxygen levels are not yet clear. We address this knowledge gap by heterologously expressing the oxygen-binding proteins myoglobin and myohemerythrin in snowflake yeast, a model system of simple, undifferentiated multicellularity. These proteins increased the depth and rate of oxygen diffusion, increasing the fitness of snowflake yeast growing aerobically. Experiments show that, paradoxically, oxygen-binding proteins confer a greater fitness benefit for larger organisms when O2 is least limiting. We show via biophysical modeling that this is because facilitated diffusion is more efficient when oxygen is abundant, transporting a greater quantity of O2 which can be used for metabolism. By alleviating anatomical diffusion limitations to oxygen consumption, the evolution of oxygen-binding proteins in the oxygen-rich Neoproterozoic may have been a key breakthrough enabling the evolution of increasingly large, complex multicellular metazoan lineages.}, } @article {pmid39883596, year = {2025}, author = {Pullen, RM and Decker, SR and Subramanian, V and Adler, MJ and Tobias, AV and Perisin, M and Sund, CJ and Servinsky, MD and Kozlowski, MT}, title = {Considerations for Domestication of Novel Strains of Filamentous Fungi.}, journal = {ACS synthetic biology}, volume = {14}, number = {2}, pages = {343-362}, pmid = {39883596}, issn = {2161-5063}, mesh = {*Fungi/genetics/metabolism ; Synthetic Biology/methods ; Biotechnology/methods ; Metabolic Engineering/methods ; Genome, Fungal ; }, abstract = {Fungi, especially filamentous fungi, are a relatively understudied, biotechnologically useful resource with incredible potential for commercial applications. These multicellular eukaryotic organisms have long been exploited for their natural production of useful commodity chemicals and proteins such as enzymes used in starch processing, detergents, food and feed production, pulping and paper making and biofuels production. The ability of filamentous fungi to use a wide range of feedstocks is another key advantage. As chassis organisms, filamentous fungi can express cellular machinery, and metabolic and signal transduction pathways from both prokaryotic and eukaryotic origins. Their genomes abound with novel genetic elements and metabolic processes that can be harnessed for biotechnology applications. Synthetic biology tools are becoming inexpensive, modular, and expansive while systems biology is beginning to provide the level of understanding required to design increasingly complex synthetic systems. This review covers the challenges of working in filamentous fungi and offers a perspective on the approaches needed to exploit fungi as microbial cell factories.}, } @article {pmid39877976, year = {2025}, author = {Pereira Lobo, F and Benjamim, DM and da Silva, TTM and de Oliveira, MD}, title = {Molecular and Functional Convergences Associated with Complex Multicellularity in Eukarya.}, journal = {Molecular biology and evolution}, volume = {42}, number = {2}, pages = {}, pmid = {39877976}, issn = {1537-1719}, mesh = {Phylogeny ; *Eukaryota/genetics ; *Biological Evolution ; Animals ; Evolution, Molecular ; }, abstract = {A key trait of Eukarya is the independent evolution of complex multicellularity in animals, land plants, fungi, brown algae, and red algae. This phenotype is characterized by the initial exaptation of cell-cell adhesion genes followed by the emergence of mechanisms for cell-cell communication, together with the expansion of transcription factor gene families responsible for cell and tissue identity. The number of cell types is commonly used as a quantitative proxy for biological complexity in comparative genomics studies. While expansions of individual gene families have been associated with variations in the number of cell types within individual complex multicellular lineages, the molecular and functional roles responsible for the independent evolution of complex multicellular across Eukarya remain poorly understood. We employed a phylogeny-aware strategy to conduct a genomic-scale search for associations between the number of cell types and the abundance of genomic components across a phylogenetically diverse set of 81 eukaryotic species, including species from all complex multicellular lineages. Our annotation schemas represent 2 complimentary aspects of genomic information: homology, represented by conserved sequences, and function, represented by Gene Ontology terms. We found many gene families sharing common biological themes that define complex multicellular to be independently expanded in 2 or more complex multicellular lineages, such as components of the extracellular matrix, cell-cell communication mechanisms, and developmental pathways. Additionally, we describe many previously unknown associations of biological themes and biological complexity, such as expansions of genes playing roles in wound response, immunity, cell migration, regulatory processes, and response to natural rhythms. Together, our findings unveil a set of functional and molecular convergences independently expanded in complex multicellular lineages likely due to the common selective pressures in their lifestyles.}, } @article {pmid39868713, year = {2024}, author = {Montagné, N}, title = {[The role of volatile organic compounds in plant-insect communication].}, journal = {Biologie aujourd'hui}, volume = {218}, number = {3-4}, pages = {141-144}, doi = {10.1051/jbio/2024016}, pmid = {39868713}, issn = {2105-0686}, mesh = {Animals ; *Volatile Organic Compounds/metabolism ; *Insecta/physiology ; *Plants/metabolism/parasitology/chemistry ; *Animal Communication ; *Plant Physiological Phenomena ; Herbivory/physiology ; Biological Evolution ; Host-Parasite Interactions/physiology ; }, abstract = {Insects and flowering plants are the most abundant and diverse multicellular organisms on Earth, accounting for 75% of known species. Their evolution has been largely interdependent since the so-called Angiosperm Terrestrial Revolution (100-50 Mya), when the explosion of plant diversity stimulated the evolution of pollinating and herbivorous insects. Plant-insect interactions rely heavily on chemical communication via volatile organic compounds (VOCs). These molecules are synthesised by the secondary metabolism of plants through various pathways and include terpenes, benzenoids and aliphatic compounds. As of today, more than 1,700 of these VOCs have notably been identified in flowers. Plants use these molecules to attract pollinators or repel herbivorous insects. VOCs also act as chemical signals for insects, helping them to find food or egg-laying sites. Chemical communication has thus played an important role in the evolutionary history of insects and flowering plants. Tritrophic interactions are a fascinating example of VOC-driven communication. When plants are attacked by herbivores, they emit herbivore-induced volatiles, such as green leaf volatiles and specific terpenes. These signals attract predators or parasitoids of the herbivores, acting as a chemical distress call. For example, parasitoid wasps can identify plants that have been attacked by their host herbivores, even in the absence of the herbivores themselves, thanks to the plant's odour profile. But herbivore-induced volatiles also affect the herbivores themselves. Female moths, for example, use these olfactory cues to avoid laying eggs on plants that have already been attacked. Insects detect VOCs using highly sensitive odorant receptors on their antennae. Herbivorous insects, such as the model moth species S. littoralis, have receptors specific for floral VOCs and herbivore-induced volatiles. Current research aims to understand how the evolution of these receptors has contributed to the adaptation of insects to plant volatiles. In moths, receptors for benzenoids appear to be more ancient and conserved, whereas receptors for terpenes and aliphatic molecules show more recent diversification in response to plant evolution. Research into plant-insect communication also opens up avenues for sustainable agriculture, as VOCs can be used to attract natural pest predators or deter herbivores, reducing the need for chemical pesticides.}, } @article {pmid39863161, year = {2025}, author = {Dubey, A and Muthu, G and Seshasayee, ASN}, title = {Evolution of Transcription Factor-containing Superfamilies in Eukaryotes.}, journal = {Journal of molecular biology}, volume = {437}, number = {5}, pages = {168959}, doi = {10.1016/j.jmb.2025.168959}, pmid = {39863161}, issn = {1089-8638}, mesh = {*Transcription Factors/genetics/metabolism ; *Evolution, Molecular ; *Eukaryota/genetics/metabolism ; Animals ; Phylogeny ; Multigene Family ; Protein Binding ; }, abstract = {Regulation of gene expression helps determine various phenotypes in most cellular life forms. It is orchestrated at different levels and at the point of transcription initiation by transcription factors (TFs). TFs bind to DNA through domains that are evolutionarily related, by shared membership of the same superfamilies (TF-SFs), to those found in other nucleic acid binding and protein-binding functions (nTFs for non-TFs). Here we ask how TF DNA binding sequence families in eukaryotes have evolved in relation to their nTF relatives. TF numbers scale by power law with the total number of protein-coding genes differently in different clades, with fungi usually showing sub-linear powers whereas chordates show super-linear scaling. The LECA probably encoded a complex regulatory machinery with both TFs and nTFs, but with an excess of nTFs when compared to the relative distribution of TFs and nTFs in extant organisms. Losses drive the evolution of TFs and nTFs, with the possible exception of TFs in animals for some tree topologies. TFs are highly dynamic in evolution, showing higher gain and loss rates than nTFs in some TF-SFs though both are conserved to similar extents. Gains of TFs and nTFs are driven by the appearance of a large number of new sequence clusters in a small number of nodes, which determine the presence of as many as a third of extant TFs and nTFs as well as the relative presence of TFs and nTFs. Whereas nodes showing explosion of TF numbers belong to multicellular clades, those for nTFs lie among the fungi and the protists.}, } @article {pmid39853129, year = {2025}, author = {Espinoza Miranda, SS and Abbaszade, G and Hess, WR and Drescher, K and Saliba, A-E and Zaburdaev, V and Chai, L and Dreisewerd, K and Grünberger, A and Westendorf, C and Müller, S and Mascher, T}, title = {Resolving spatiotemporal dynamics in bacterial multicellular populations: approaches and challenges.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {89}, number = {1}, pages = {e0013824}, pmid = {39853129}, issn = {1098-5557}, support = {503267551, 504049752//Deutsche Forschungsgemeinschaft (DFG)/ ; 503905203//Deutsche Forschungsgemeinschaft (DFG)/ ; 503940974//Deutsche Forschungsgemeinschaft (DFG)/ ; 504222949//Deutsche Forschungsgemeinschaft (DFG)/ ; 504072468//Deutsche Forschungsgemeinschaft (DFG)/ ; 504017689//Deutsche Forschungsgemeinschaft (DFG)/ ; 503995533//Deutsche Forschungsgemeinschaft (DFG)/ ; }, mesh = {*Bacteria/genetics/cytology/growth & development ; Single-Cell Analysis/methods ; *Bacterial Physiological Phenomena ; Spatio-Temporal Analysis ; Flow Cytometry ; Microscopy/methods ; }, abstract = {SUMMARYThe development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole. During colony differentiation, an almost infinite number of ecological and physiological population-forming forces are at work, creating complex, intricate colony structures with divergent functions. Understanding the assembly and dynamics of such populations requires resolving individual cells or cell groups within such macroscopic structures. Addressing how each cell contributes to the collective action requires pushing the resolution boundaries of key technologies that will be presented in this review. In particular, single-cell techniques provide powerful tools for studying bacterial multicellularity with unprecedented spatial and temporal resolution. These advancements include novel microscopic techniques, mass spectrometry imaging, flow cytometry, spatial transcriptomics, single-bacteria RNA sequencing, and the integration of spatiotemporal transcriptomics with microscopy, alongside advanced microfluidic cultivation systems. This review encourages exploring the synergistic potential of the new technologies in the study of bacterial multicellularity, with a particular focus on individuals in differentiated bacterial biofilms (colonies). It highlights how resolving population structures at the single-cell level and understanding their respective functions can elucidate the overarching functions of bacterial multicellular populations.}, } @article {pmid39849824, year = {2025}, author = {Ndinyanka Fabrice, T and Buczak, K and Schmidt, A and Pieters, J}, title = {T cell population size control by coronin 1 uncovered: from a spot identified by two-dimensional gel electrophoresis to quantitative proteomics.}, journal = {Expert review of proteomics}, volume = {22}, number = {1}, pages = {35-44}, doi = {10.1080/14789450.2025.2450812}, pmid = {39849824}, issn = {1744-8387}, mesh = {*Proteomics/methods ; Humans ; Electrophoresis, Gel, Two-Dimensional/methods ; *Microfilament Proteins/metabolism/genetics ; Proteome/metabolism ; Mycobacterium tuberculosis/pathogenicity ; Animals ; }, abstract = {INTRODUCTION: Recent work identified members of the evolutionarily conserved coronin protein family as key regulators of cell population size. This work originated ~25 years ago through the identification, by two-dimensional gel electrophoresis, of coronin 1 as a host protein involved in the virulence of Mycobacterium tuberculosis. We here describe the journey from a spot on a 2D gel to the recent realization that coronin proteins represent key controllers of eukaryotic cell population sizes, using ever more sophisticated proteomic techniques.

AREAS COVERED: We discuss the value of 'old school' proteomics using relatively simple and cost-effective technologies that allowed to gain insights into subcellular proteomes and describe how label-free quantitative (phospho)proteomics using mass spectrometry allowed to disentangle the role for coronin 1 in eukaryotic cell population size control. Finally, we mention potential implications of coronin-mediated cell population size control for health and disease.

EXPERT OPINION: Proteome analysis has been revolutionized by the advent of modern-day mass spectrometers and is indispensable for a better understanding of biology. Here, we discuss how careful dissection of physio-pathological processes by a combination of proteomics, genomics, biochemistry and cell biology may allow to zoom in on the unexplored, thereby possibly tackling hitherto unasked questions and defining novel mechanisms.}, } @article {pmid39838007, year = {2025}, author = {McCaig, CD}, title = {Epithelia Are Scaffolds for Electricity-Dependent Molecular Interactions.}, journal = {Reviews of physiology, biochemistry and pharmacology}, volume = {187}, number = {}, pages = {47-52}, pmid = {39838007}, issn = {0303-4240}, mesh = {Humans ; Animals ; Epithelium/physiology ; *Electricity ; Basement Membrane/physiology ; *Epithelial Cells/physiology ; }, abstract = {Once multicellularity was thriving, a key development involved the emergence of epithelial layers that separated "inside" from "outside". Most epithelia then generate their own transepithelial electrical signals. So electrical forces were instrumental in the development of epithelial tissues, which themselves generate further electrical signals. Epithelia also developed extracellular basement membranes which act as spatially diverse scaffolds to organize multiple molecular interactions, dependent on electrical forces.Epithelia and basement membranes were constructed using electrical forces and their evolution had electrophysiological consequences.}, } @article {pmid39833858, year = {2025}, author = {Hure, V and Piron-Prunier, F and Yehouessi, T and Vitte, C and Kornienko, AE and Adam, G and Nordborg, M and Déléris, A}, title = {Alternative silencing states of transposable elements in Arabidopsis associated with H3K27me3.}, journal = {Genome biology}, volume = {26}, number = {1}, pages = {11}, pmid = {39833858}, issn = {1474-760X}, mesh = {*DNA Transposable Elements ; *Arabidopsis/genetics/metabolism ; *Histones/metabolism ; *Gene Silencing ; DNA Methylation ; Gene Expression Regulation, Plant ; Epigenesis, Genetic ; Arabidopsis Proteins/metabolism/genetics ; Polycomb-Group Proteins/metabolism ; }, abstract = {BACKGROUND: The DNA/H3K9 methylation and Polycomb-group proteins (PcG)-H3K27me3 silencing pathways have long been considered mutually exclusive and specific to transposable elements (TEs) and genes, respectively in mammals, plants, and fungi. However, H3K27me3 can be recruited to many TEs in the absence of DNA/H3K9 methylation machinery and sometimes also co-occur with DNA methylation.

RESULTS: In this study, we show that TEs can also be solely targeted and silenced by H3K27me3 in wild-type Arabidopsis plants. These H3K27me3-marked TEs not only comprise degenerate relics but also seemingly intact copies that display the epigenetic features of responsive PcG target genes as well as an active H3K27me3 regulation. We also show that H3K27me3 can be deposited on newly inserted transgenic TE sequences in a TE-specific manner indicating that silencing is determined in cis. Finally, a comparison of Arabidopsis natural accessions reveals the existence of a category of TEs-which we refer to as "bifrons"-that are marked by DNA methylation or H3K27me3 depending on the accession. This variation can be linked to intrinsic TE features and to trans-acting factors and reveals a change in epigenetic status across the TE lifespan.

CONCLUSIONS: Our study sheds light on an alternative mode of TE silencing associated with H3K27me3 instead of DNA methylation in flowering plants. It also suggests dynamic switching between the two epigenetic marks at the species level, a new paradigm that might extend to other multicellular eukaryotes.}, } @article {pmid39826309, year = {2025}, author = {Mendes, M and Morais, AS and Carlos, A and Sousa, JJ and Pais, AC and Mihăilă, SM and Vitorino, C}, title = {Organ-on-a-chip: Quo vademus? Applications and regulatory status.}, journal = {Colloids and surfaces. B, Biointerfaces}, volume = {249}, number = {}, pages = {114507}, doi = {10.1016/j.colsurfb.2025.114507}, pmid = {39826309}, issn = {1873-4367}, mesh = {Humans ; *Lab-On-A-Chip Devices ; Animals ; Tissue Engineering ; Microphysiological Systems ; }, abstract = {Organ-on-a-chip systems, also referred to as microphysiological systems (MPS), represent an advance in bioengineering microsystems designed to mimic key aspects of human organ physiology and function. Drawing inspiration from the intricate and hierarchical architecture of the human body, these innovative platforms have emerged as invaluable in vitro tools with wide-ranging applications in drug discovery and development, as well as in enhancing our understanding of disease physiology. The facility to replicate human tissues within physiologically relevant three-dimensional multicellular environments empowers organ-on-a-chip systems with versatility throughout different stages of the drug development process. Moreover, these systems can be tailored to mimic specific disease states, facilitating the investigation of disease progression, drug responses, and potential therapeutic interventions. In particular, they can demonstrate, in early-phase pre-clinical studies, the safety and toxicity profiles of potential therapeutic compounds. Furthermore, they play a pivotal role in the in vitro evaluation of drug efficacy and the modeling of human diseases. One of the most promising prospects of organ-on-a-chip technology is to simulate the pathophysiology of specific subpopulations and even individual patients, thereby being used in personalized medicine. By mimicking the physiological responses of diverse patient groups, these systems hold the promise of revolutionizing therapeutic strategies, guiding them towards tailored intervention to the unique needs of each patient. This review presents the development status and evolution of microfluidic platforms that have facilitated the transition from cells to organs recreated on chips and some of the opportunities and applications offered by organ-on-a-chip technology. Additionally, the current potential and future perspectives of these microphysiological systems and the challenges this technology still faces are discussed.}, } @article {pmid39817858, year = {2025}, author = {Yang, X and Yan, A and Liu, X and Volkening, A and Zhou, Y}, title = {Single cell-derived multicellular meristem: insights into male-to-hermaphrodite conversion and de novo meristem formation in Ceratopteris.}, journal = {Development (Cambridge, England)}, volume = {152}, number = {3}, pages = {}, pmid = {39817858}, issn = {1477-9129}, support = {NSF DMS 1764421//Northwestern University/ ; R01 GM157611/GM/NIGMS NIH HHS/United States ; SFARI 597491-RWC//Simons Foundation/ ; R01GM157611/GM/NIGMS NIH HHS/United States ; IOS 1931114//National Science Foundation/ ; }, mesh = {*Meristem/cytology/growth & development ; *Pteridaceae/cytology ; Germ Cells, Plant/cytology ; Cell Lineage ; Cell Division ; Single-Cell Analysis ; }, abstract = {Land plants alternate between asexual sporophytes and sexual gametophytes. Unlike seed plants, ferns develop free-living gametophytes. Gametophytes of the model fern Ceratopteris exhibit two sex types: hermaphrodites with pluripotent meristems and males lacking meristems. In the absence of the pheromone antheridiogen, males convert to hermaphrodites by forming de novo meristems, although the mechanisms remain unclear. Using long-term time-lapse imaging and computational analyses, we captured male-to-hermaphrodite conversion at single-cell resolution and reconstructed the lineage and division atlas of newly formed meristems. Lineage tracing revealed that the de novo-formed meristem originates from a single non-antheridium cell: the meristem progenitor cell (MPC). During conversion, the MPC lineage showed increased mitotic activity, with marginal cells proliferating faster than inner cells. A mathematical model suggested that stochastic variation in cell division, combined with strong inhibitory signals from dividing marginal cells, is sufficient to explain gametophyte dynamics. Experimental disruption of division timing agreed with the model, showing that precise cell cycle progression is essential for MPC establishment and sex-type conversion. These findings reveal cellular mechanisms governing sex conversion and de novo meristem formation in land plants.}, } @article {pmid39793585, year = {2025}, author = {Liesner, D and Cossard, GG and Zheng, M and Godfroy, O and Barrera-Redondo, J and Haas, FB and Coelho, SM}, title = {Developmental pathways underlying sexual differentiation in the U/V sex chromosome system of giant kelp.}, journal = {Developmental cell}, volume = {60}, number = {8}, pages = {1142-1152.e6}, doi = {10.1016/j.devcel.2024.12.022}, pmid = {39793585}, issn = {1878-1551}, mesh = {*Sex Chromosomes/genetics ; Male ; Female ; *Sex Differentiation/genetics ; *Kelp/genetics/growth & development ; Animals ; Transcriptome/genetics ; Sex Determination Processes/genetics ; Gene Expression Regulation, Developmental ; }, abstract = {In many multicellular organisms, sexual development is not determined by XX/XY or ZW/ZZ systems but by U/V sex chromosomes. In U/V systems, sex determination occurs in the haploid phase, with U chromosomes in females and V chromosomes in males. Here, we explore several male, female, and partially sex-reversed male lines of giant kelp to decipher how U/V sex chromosomes and autosomes initiate male versus female development. We identify a key set of genes on the sex chromosomes involved in triggering sexual development and characterize autosomal effector genes underlying sexual differentiation. We show that male, but not female, development involves large-scale transcriptome reorganization with pervasive enrichment in regulatory genes, faster evolutionary rates, and high species-specificity of male-biased genes. Our observations imply that a female-like phenotype is the "ground state", which is complemented by the presence of a U-chromosome but overridden by a dominant male developmental program triggered by the V-chromosome.}, } @article {pmid39772683, year = {2025}, author = {Colgren, J and Burkhardt, P}, title = {Electrical signaling and coordinated behavior in the closest relative of animals.}, journal = {Science advances}, volume = {11}, number = {2}, pages = {eadr7434}, pmid = {39772683}, issn = {2375-2548}, mesh = {*Choanoflagellata/physiology ; Animals ; Calcium/metabolism ; Cilia/physiology/metabolism ; Signal Transduction ; }, abstract = {The transition from simple to complex multicellularity involves division of labor and specialization of cell types. In animals, complex sensory-motor systems are primarily built around specialized cells of muscles and neurons, though the evolutionary origins of these and their integration remain unclear. Here, to investigate sensory-behavior coupling in the closest relatives of animals, we established a line of the choanoflagellate, Salpingoeca rosetta, which stably expresses the calcium indicator RGECO1. Using this, we identify a previously unknown cellular behavior associated with electrical signaling, in which ciliary arrest is coupled with apical-basal contraction of the cell. This behavior and the associated calcium transients are synchronized in the multicellular state and result in coordinated ciliary arrest and colony-wide contraction, suggesting that information is spread among the cells. Our work reveals fundamental insights into how choanoflagellates sense and respond to their environment and enhances our understanding of the integration of cellular and organism-wide behavior in the closest protistan relatives of animals.}, } @article {pmid39763889, year = {2024}, author = {Park, J and Prokopchuk, G and Popchock, AR and Hao, J and Liao, TW and Yan, S and Hedman, DJ and Larson, JD and Walther, BK and Becker, NA and Basu, A and Maher, LJ and Wheeler, RJ and Asbury, CL and Biggins, S and Lukeš, J and Ha, T}, title = {Probing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39763889}, issn = {2692-8205}, support = {R35 GM143949/GM/NIGMS NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R35 GM122569/GM/NIGMS NIH HHS/United States ; R35 GM134842/GM/NIGMS NIH HHS/United States ; }, abstract = {Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence. Further, the model predicts intrinsic bending direction in 3D space. Using this tool, we aimed to probe mechanical selection - that is, the evolutionary selection of DNA sequence based on its mechanical properties - in diverse circumstances. First, we found that the intrinsic bend direction of DNA sequences correlated with the observed bending in known protein-DNA complex structures, suggesting that many proteins co-evolved with their DNA partners to capture DNA in its intrinsically preferred bent conformation. We then applied our model to large-scale yeast population genetics data and showed that centromere DNA element II, whose consensus sequence is unknown, leaving its sequence-specific role unclear, is under mechanical selection to increase the stability of inner-kinetochore structure and to facilitate centromeric histone recruitment. Finally, in silico evolution under strong mechanical selection discovered hallucinated sequences with cyclizability values so extreme that they required experimental validation, yet, found in nature in the densely packed mitochondrial(mt) DNA of Namystynia karyoxenos, an ocean-dwelling protist with extreme mitochondrial gene fragmentation. The need to transmit an extraordinarily large amount of mtDNA, estimated to be > 600 Mb, in combination with the absence of mtDNA compaction proteins may have pushed mechanical selection to the extreme. Similarly extreme DNA mechanics are observed in bird microchromosomes, although the functional consequence is not yet clear. The discovery of eccentric DNA mechanics in unrelated unicellular and multicellular eukaryotes suggests that we can predict extreme natural biology which can arise through strong selection. Our methods offer a way to study the biological functions of DNA mechanics in any genome and to engineer DNA sequences with desired mechanical properties.}, } @article {pmid39752622, year = {2025}, author = {Bandyadka, S and Lebo, DPV and Mondragon, AA and Serizier, SB and Kwan, J and Peterson, JS and Chasse, AY and Jenkins, VK and Calikyan, A and Ortega, AJ and Campbell, JD and Emili, A and McCall, K}, title = {Multi-modal comparison of molecular programs driving nurse cell death and clearance in Drosophila melanogaster oogenesis.}, journal = {PLoS genetics}, volume = {21}, number = {1}, pages = {e1011220}, pmid = {39752622}, issn = {1553-7404}, support = {F31 GM115177/GM/NIGMS NIH HHS/United States ; R01 LM013154/LM/NLM NIH HHS/United States ; R35 GM127338/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Drosophila melanogaster/genetics/growth & development ; *Oogenesis/genetics ; Female ; Apoptosis/genetics ; Drosophila Proteins/genetics/metabolism ; Oocytes/metabolism/cytology ; Ovarian Follicle/cytology/metabolism/growth & development ; Cell Death/genetics ; }, abstract = {The death and clearance of nurse cells is a consequential milestone in Drosophila melanogaster oogenesis. In preparation for oviposition, the germline-derived nurse cells bequeath to the developing oocyte all their cytoplasmic contents and undergo programmed cell death. The death of the nurse cells is controlled non-autonomously and is precipitated by epithelial follicle cells of somatic origin acquiring a squamous morphology and acidifying the nurse cells externally. Alternatively, stressors such as starvation can induce the death of nurse cells earlier in mid-oogenesis, manifesting apoptosis signatures, followed by their engulfment by epithelial follicle cells. To identify and contrast the molecular pathways underlying these morphologically and genetically distinct cell death paradigms, both mediated by follicle cells, we compared their genome-wide transcriptional, translational, and secretion profiles before and after differentiating to acquire a phagocytic capability, as well as during well-fed and nutrient-deprived conditions. By coupling the GAL4-UAS system to Translating Ribosome Affinity Purification (TRAP-seq) and proximity labeling (HRP-KDEL) followed by Liquid Chromatography tandem mass-spectrometry, we performed high-throughput screens to identify pathways selectively activated or repressed by follicle cells to employ nurse cell-clearance routines. We also integrated two publicly available single-cell RNAseq atlases of the Drosophila ovary to define the transcriptomic profiles of follicle cells. In this report, we describe the genes and major pathways identified in the screens and the striking consequences to Drosophila melanogaster oogenesis caused by RNAi perturbation of prioritized candidates. To our knowledge, our study is the first of its kind to comprehensively characterize two distinct apoptotic and non-apoptotic cell death paradigms in the same multi-cellular system. Beyond molecular differences in cell death, our investigation may also provide insights into how key systemic trade-offs are made between survival and reproduction when faced with physiological stress.}, } @article {pmid39741147, year = {2024}, author = {Solé, R and Conde-Pueyo, N and Pla-Mauri, J and Garcia-Ojalvo, J and Montserrat, N and Levin, M}, title = {Open problems in synthetic multicellularity.}, journal = {NPJ systems biology and applications}, volume = {10}, number = {1}, pages = {151}, pmid = {39741147}, issn = {2056-7189}, support = {ERCCoG-2020 101002478 ENGINORG//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; Grant 62212//John Templeton Foundation (JTF)/ ; }, mesh = {Animals ; Humans ; Bioengineering/methods ; Biological Evolution ; Models, Biological ; *Synthetic Biology/methods ; Systems Biology/methods ; }, abstract = {Multicellularity is one of the major evolutionary transitions, and its rise provided the ingredients for the emergence of a biosphere inhabited by complex organisms. Over the last decades, the potential for bioengineering multicellular systems has been instrumental in interrogating nature and exploring novel paths to regeneration, disease, cognition, and behaviour. Here, we provide a list of open problems that encapsulate many of the ongoing and future challenges in the field and suggest conceptual approaches that may facilitate progress.}, } @article {pmid39737561, year = {2025}, author = {Horiuchi, Y and Umakawa, N and Otani, R and Tamada, Y and Kosetsu, K and Hiwatashi, Y and Wakisaka, R and Yoshida, S and Murata, T and Hasebe, M and Ishikawa, M and Kofuji, R}, title = {Physcomitrium LATERAL SUPPRESSOR genes promote formative cell divisions to produce germ cell lineages in both male and female gametangia.}, journal = {The New phytologist}, volume = {245}, number = {5}, pages = {2004-2015}, pmid = {39737561}, issn = {1469-8137}, mesh = {*Bryopsida/genetics/cytology ; *Cell Division/genetics ; *Cell Lineage/genetics ; *Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant ; *Germ Cells, Plant/cytology ; *Genes, Plant ; *Ovule/cytology/genetics ; Phylogeny ; Mutation/genetics ; Phenotype ; }, abstract = {The evolution of green plants from aquatic to terrestrial environments is thought to have been facilitated by the acquisition of gametangia, specialized multicellular organs housing gametes. Antheridia and archegonia, responsible for producing and protecting sperm and egg cells, undergo formative cell divisions to produce a cell to differentiate into germ cell lineages and the other cell to give rise to surrounding structures. However, the genes governing this process remain unidentified. We isolated genes expressed during gametangia development from previously established gene-trap lines of Physcomitrium patens and characterized their function during gametangia formation. We identified P. patens LATERAL SUPPRESSOR 1 (PpLAS1) from the gene-trap library, encoding a GRAS transcription factor. The double-deletion mutant with its paralog PpLAS2 failed to form inner cells in both gametangia. PpLASs are expressed in cells undergoing formative cell division, and introducing PpLAS1 into the double-deletion mutant successfully rescued the phenotype. These findings underscore the pivotal role of PpLASs in regulating formative cell divisions, ensuring the separation of reproductive cell lineages from surrounding cells in antheridia and archegonia. Furthermore, they suggest a link between PpLASs and the evolutionary origin of male and female gametangia in the common ancestor of land plants.}, } @article {pmid39732540, year = {2025}, author = {Golomb, R and Dahan, O and Dahary, D and Pilpel, Y}, title = {Cell-autonomous adaptation: an overlooked avenue of adaptation in human evolution.}, journal = {Trends in genetics : TIG}, volume = {41}, number = {1}, pages = {12-22}, doi = {10.1016/j.tig.2024.10.009}, pmid = {39732540}, issn = {0168-9525}, mesh = {Animals ; Humans ; *Adaptation, Physiological/genetics ; *Biological Evolution ; Evolution, Molecular ; Mitochondria/genetics/metabolism ; Selection, Genetic/genetics ; }, abstract = {Adaptation to environmental conditions occurs over diverse evolutionary timescales. In multi-cellular organisms, adaptive traits are often studied in tissues/organs relevant to the environmental challenge. We argue for the importance of an underappreciated layer of evolutionary adaptation manifesting at the cellular level. Cell-autonomous adaptations (CAAs) are inherited traits that boost organismal fitness by enhancing individual cell function. For instance, the cell-autonomous enhancement of mitochondrial oxygen utilization in hypoxic environments differs from an optimized erythropoiesis response, which involves multiple tissues. We explore the breadth of CAAs across challenges and highlight their counterparts in unicellular organisms. Applying these insights, we mine selection signals in Andean highlanders, revealing novel candidate CAAs. The conservation of CAAs across species may reveal valuable insights into multi-cellular evolution.}, } @article {pmid39715844, year = {2025}, author = {Doctrove, Q and Park, Y and Calame, DG and Kitzman, J and Lenk, GM and Meisler, MH}, title = {Protein family FAM241 in human and mouse.}, journal = {Mammalian genome : official journal of the International Mammalian Genome Society}, volume = {36}, number = {1}, pages = {83-92}, pmid = {39715844}, issn = {1432-1777}, support = {R01 GM24872/NH/NIH HHS/United States ; K12 NS098482/NS/NINDS NIH HHS/United States ; R01 GM024872/GM/NIGMS NIH HHS/United States ; 873841//Muscular Dystrophy Association/ ; K12NS098482/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Mice, Knockout ; Phylogeny ; Lysosomes/metabolism/genetics ; *Proteins/genetics/metabolism ; }, abstract = {FAM241B was isolated in a genome-wide inactivation screen for generation of enlarged lysosomes. FAM241B and FAM241A comprise protein family FAM241 encoding proteins of 121 and 132 amino acid residues, respectively. The proteins exhibit 25% amino acid sequence identity and contain a domain of unknown function (DUF4605; pfam15378) that is conserved from primitive multicellular eukaryotes through vertebrates. Phylogenetic comparison indicates that duplication of the ancestral FAM241B gene occurred prior to the origin of fish. FAM241B has been deleted from the avian lineage. Fam241a and Fam241b are widely expressed in mouse tissues. Experimental knockout of mouse Fam241a, Fam241b, and the double knockout, did not generate a visible phenotype. Knockout of Fam241A and Fam241B did not exacerbate the phenotype of FIG4 null mice. RNAseq of brain RNA from double knockout mice detected reduced expression of several genes including Arke1e1 and RnaseL. The human variant p.Val115Gly in FAM241B was identified in a patient with developmental delay. Lysosome morphology in patient-derived fibroblasts was normal. In previous studies, FAM241A and FAM241B appeared to co-localize with proteins of the endoplasmic reticulum. The molecular function of this ancient protein family remains to be determined.}, } @article {pmid39707854, year = {2024}, author = {Ustyantsev, IG and Borodulina, OR and Kramerov, DA}, title = {[Participation of Proteins of the CPSF Complex in Polyadenylation of Transcripts Read by RNA Polymerase III from SINEs].}, journal = {Molekuliarnaia biologiia}, volume = {58}, number = {3}, pages = {437-447}, pmid = {39707854}, issn = {0026-8984}, mesh = {Humans ; *Polyadenylation ; HeLa Cells ; *Cleavage And Polyadenylation Specificity Factor/metabolism/genetics ; *RNA Polymerase III/metabolism/genetics ; *RNA, Messenger/genetics/metabolism ; mRNA Cleavage and Polyadenylation Factors/metabolism/genetics ; Alu Elements/genetics ; Gene Knockdown Techniques ; Nuclear Proteins ; }, abstract = {SINEs are mobile genetic elements of multicellular eukaryotes that arose during evolution from various tRNAs, as well as from 5S rRNA and 7SL RNA. Like the genes of these RNAs, SINEs are transcribed by RNA polymerase III. The transcripts of some mammalian SINEs have the capability of AAUAAA-dependent polyadenylation, which is unique for transcript generated by RNA polymerase III. Despite a certain similarity with canonical polyadenylation of mRNAs (transcripts of RNA polymerase II), these processes apparently differ significantly. The purpose of this work is to evaluate how important for polyadenylation of SINE transcripts are proteins of the CPSF complex formed by mPSF and mCF subcomplexes which direct mRNA polyadenylation. In HeLa cells, siRNA knockdowns of the CPSF components were carried out, after which the cells were transfected with plasmid constructs containing SINEs. A decrease in polyadenylation of the SINE transcripts as a result of the knockdown of the proteins was evaluated by Northern-hybridization. It turned out that the CPSF components, such as Wdr33 and CPSF30, contributed to the polyadenylation of SINE transcriptions, while the knockdown of CPSF100, CPSF73, and symplekin did not reduce the polyadenylation of these transcripts. Wdr33 and CPSF30, along with the CPSF160 and Fip1 previously studied, are components of the subcomplex mPSF responsible for mRNA polyadenylation. Thus, the available data suggest the importance of all mPSF proteins for polyadenylation of SINE transcripts. At the same time, CPSF100, CPSF73, and symplekin, forming the subcomplex mCF, are responsible for the cleavage of pre-mRNA; therefore, their non-participation in the polyadenylation of SINE transcriptions seems quite natural.}, } @article {pmid39702750, year = {2024}, author = {Nguyen, NM and Farge, E}, title = {Mechanical induction in metazoan development and evolution: from earliest multi-cellular organisms to modern animal embryos.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {10695}, pmid = {39702750}, issn = {2041-1723}, mesh = {Animals ; *Biological Evolution ; Biomechanical Phenomena ; Body Patterning/physiology ; Embryo, Nonmammalian ; *Embryonic Development/physiology ; Morphogenesis ; }, abstract = {The development and origin of animal body forms have long been intensely explored, from the analysis of morphological traits during antiquity to Newtonian mechanical conceptions of morphogenesis. Advent of molecular biology then focused most interests on the biochemical patterning and genetic regulation of embryonic development. Today, a view is arising of development of multicellular living forms as a phenomenon emerging from non-hierarchical, reciprocal mechanical and mechanotransductive interactions between biochemical patterning and biomechanical morphogenesis. Here we discuss the nature of these processes and put forward findings on how early biochemical and biomechanical patterning of metazoans may have emerged from a primitive behavioural mechanotransducive feeding response to marine environment which might have initiated the development of first animal multicellular organisms.}, } @article {pmid39675229, year = {2025}, author = {Hirashima, T and W P, S and Noda, T}, title = {Collective sperm movement in mammalian reproductive tracts.}, journal = {Seminars in cell & developmental biology}, volume = {166}, number = {}, pages = {13-21}, doi = {10.1016/j.semcdb.2024.12.002}, pmid = {39675229}, issn = {1096-3634}, mesh = {*Sperm Motility/physiology ; Animals ; Male ; Humans ; *Spermatozoa/physiology/metabolism ; Mammals ; Female ; }, abstract = {Mammalian sperm cells travel from their origin in the male reproductive tract to fertilization in the female tract through a complex process driven by coordinated mechanical and biochemical mechanisms. Recent experimental and theoretical advances have illuminated the collective behaviors of sperm both in vivo and in vitro. However, our understanding of the underlying mechano-chemical processes remains incomplete. This review integrates current insights into sperm group movement, examining both immotile and motile states, which are essential for passive transport and active swimming through the reproductive tracts. We provide an overview of the current understanding of collective sperm movement, focusing on the experimental and theoretical mechanisms behind these behaviors. We also explore how sperm motility is regulated through the coordination of mechanical and chemical processes. Emerging evidence highlights the mechanosensitive properties of a sperm flagellum, suggesting that mechanical stimuli regulate flagellar beating at both individual and collective levels. This self-regulatory, mechano-chemical system reflects a broader principle observed in multicellular systems, offering a system-level insight into the regulation of motility and collective dynamics in biological systems.}, } @article {pmid39671305, year = {2024}, author = {Sun, Y and Chen, Z and Jin, M and Xie, H and Zhao, C}, title = {Ciliary length regulation by intraflagellar transport in zebrafish.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {39671305}, issn = {2050-084X}, support = {32125015//National Natural Science Foundation of China/ ; 31991194//National Natural Science Foundation of China/ ; 32100661//National Natural Science Foundation of China/ ; 2023M733344//China Postdoctoral Science Foundation/ ; }, mesh = {*Zebrafish/embryology ; Animals ; *Cilia/metabolism ; *Animals, Genetically Modified ; Biological Transport ; Zebrafish Proteins/metabolism/genetics ; Flagella/metabolism ; }, abstract = {How cells regulate the size of their organelles remains a fundamental question in cell biology. Cilia, with their simple structure and surface localization, provide an ideal model for investigating organelle size control. However, most studies on cilia length regulation are primarily performed on several single-celled organisms. In contrast, the mechanism of length regulation in cilia across diverse cell types within multicellular organisms remains a mystery. Similar to humans, zebrafish contain diverse types of cilia with variable lengths. Taking advantage of the transparency of zebrafish embryos, we conducted a comprehensive investigation into intraflagellar transport (IFT), an essential process for ciliogenesis. By generating a transgenic line carrying Ift88-GFP transgene, we observed IFT in multiple types of cilia with varying lengths. Remarkably, cilia exhibited variable IFT speeds in different cell types, with longer cilia exhibiting faster IFT speeds. This increased IFT speed in longer cilia is likely not due to changes in common factors that regulate IFT, such as motor selection, BBSome proteins, or tubulin modification. Interestingly, longer cilia in the ear cristae tend to form larger IFT compared to shorter spinal cord cilia. Reducing the size of IFT particles by knocking down Ift88 slowed IFT speed and resulted in the formation of shorter cilia. Our study proposes an intriguing model of cilia length regulation via controlling IFT speed through the modulation of the size of the IFT complex. This discovery may provide further insights into our understanding of how organelle size is regulated in higher vertebrates.}, } @article {pmid39653763, year = {2025}, author = {Forrester, JV and McMenamin, PG}, title = {Evolution of the ocular immune system.}, journal = {Eye (London, England)}, volume = {39}, number = {3}, pages = {468-477}, pmid = {39653763}, issn = {1476-5454}, mesh = {Humans ; Animals ; *Eye/immunology ; *Biological Evolution ; *Immune System/physiology ; Immunity, Innate ; Adaptive Immunity ; }, abstract = {The evolution of the ocular immune system should be viewed within the context of the evolution of the immune system, and indeed organisms, as a whole. Since the earliest time, the most primitive responses of single cell organisms involved molecules such as anti-microbial peptides and behaviours such as phagocytosis. Innate immunity took shape ~2.5 billion years ago while adaptive immunity and antigen specificity appeared with vertebrate evolution ~ 500 million years ago. The invention of the microscope and the germ theory of disease precipitated debate on cellular versus humoral immunity, resolved by the discovery of B and T cells. Most recently, our understanding of the microbiome and consideration of the host existing symbiotically with trillions of microbial genes (the holobiont), suggests that the immune system is a sensor of homoeostasis rather than simply a responder to pathogens. Each tissue type in multicellular organisms, such as vertebrates, has a customised response to immune challenge, with powerful reactions most evident in barrier tissues such as the skin and gut mucosa, while the eye and brain occupy the opposite extreme where responses are attenuated. The experimental background which historically led to the concept of immune privilege is discussed in this review; however, we propose that the ocular immune response should not be viewed as unique but simply an example of how the tissues variably respond in nature, more or less to the same challenge (or danger).}, } @article {pmid39650545, year = {2024}, author = {Bourrat, P and Takacs, P and Doulcier, G and Nitschke, MC and Black, AJ and Hammerschmidt, K and Rainey, PB}, title = {Individuality Through Ecology: Rethinking the Evolution of Complex Life From an Externalist Perspective.}, journal = {Ecology and evolution}, volume = {14}, number = {12}, pages = {e70661}, pmid = {39650545}, issn = {2045-7758}, abstract = {The evolution of complex life forms, exemplified by multicellular organisms, can be traced through a series of evolutionary transitions in individuality, beginning with the origin of life, followed by the emergence of the eukaryotic cell, and, among other transitions, culminating in the shift from unicellularity to multicellularity. Several attempts have been made to explain the origins of such transitions, many of which have been internalist (i.e., based largely on internal properties of ancestral entities). Here, we show how externalist perspectives can shed new light on questions pertaining to evolutionary transitions in individuality. We do this by presenting the ecological scaffolding framework in which properties of complex life forms arise from an external scaffold. Ultimately, we anticipate that progress will come from recognition of the importance of both the internalist and externalist modes of explanation. We illustrate this by considering an extension of the ecological scaffolding model in which cells modify the environment that later becomes the scaffold giving rise to multicellular individuality.}, } @article {pmid39642877, year = {2025}, author = {Torruella, G and Galindo, LJ and Moreira, D and López-García, P}, title = {Phylogenomics of neglected flagellated protists supports a revised eukaryotic tree of life.}, journal = {Current biology : CB}, volume = {35}, number = {1}, pages = {198-207.e4}, doi = {10.1016/j.cub.2024.10.075}, pmid = {39642877}, issn = {1879-0445}, mesh = {*Phylogeny ; *Eukaryota/genetics/classification ; Biological Evolution ; }, abstract = {Eukaryotes evolved from prokaryotic predecessors in the early Proterozoic[1][,][2] and radiated from their already complex last common ancestor,[3] diversifying into several supergroups with unresolved deep evolutionary connections.[4] They evolved extremely diverse lifestyles, playing crucial roles in the carbon cycle.[5][,][6] Heterotrophic flagellates are arguably the most diverse eukaryotes[4][,][7][,][8][,][9] and often occupy basal positions in phylogenetic trees. However, many of them remain undersampled[4][,][10] and/or incertae sedis.[4][,][11][,][12][,][13][,][14][,][15][,][16][,][17][,][18] Progressive improvement of phylogenomic methods and a wider protist sampling have reshaped and consolidated major clades in the eukaryotic tree.[13][,][14][,][15][,][16][,][17][,][18][,][19] This is illustrated by the Opimoda,[14] one of the largest eukaryotic supergroups (Amoebozoa, Ancyromonadida, Apusomonadida, Breviatea, CRuMs [Collodictyon-Rigifila-Mantamonas], Malawimonadida, and Opisthokonta-including animals and fungi).[4][,][14][,][19][,][20][,][21][,][22] However, their deepest evolutionary relationships still remain uncertain. Here, we sequenced transcriptomes of poorly studied flagellates[23][,][24] (14 apusomonads,[25][,][26] 7 ancyromonads,[27] and 1 cultured Mediterranean strain of Meteora sporadica[17]) and conducted comprehensive phylogenomics analyses with an expanded taxon sampling of early-branching protists. Our findings support the monophyly of Opimoda, with CRuMs being sister to the Amorphea (amoebozoans, breviates, apusomonads, and opisthokonts) and ancyromonads and malawimonads forming a moderately supported clade. By mapping key complex phenotypic traits onto this phylogenetic framework, we infer an opimodan biflagellate ancestor with an excavate-like feeding groove, which ancyromonads subsequently lost. Although breviates and apusomonads retained the ancestral biflagellate state, some early-diverging Amorphea lost one or both flagella, facilitating the evolution of amoeboid morphologies, novel feeding modes, and palintomic cell division resulting in multinucleated cells. These innovations likely facilitated the subsequent evolution of fungal and metazoan multicellularity.}, } @article {pmid39623209, year = {2025}, author = {Manzano, C and Morimoto, KW and Shaar-Moshe, L and Mason, GA and Cantó-Pastor, A and Gouran, M and De Bellis, D and Ursache, R and Kajala, K and Sinha, N and Bailey-Serres, J and Geldner, N and Del Pozo, JC and Brady, SM}, title = {Regulation and function of a polarly localized lignin barrier in the exodermis.}, journal = {Nature plants}, volume = {11}, number = {1}, pages = {118-130}, pmid = {39623209}, issn = {2055-0278}, support = {HHMI 55108506//Howard Hughes Medical Institute (HHMI)/ ; 55108506//Howard Hughes Medical Institute (HHMI)/ ; NSF 2118017//National Science Foundation (NSF)/ ; PGRP IOS-211980//National Science Foundation (NSF)/ ; PGRP IOS-1856749//National Science Foundation (NSF)/ ; PRFB IOS-1907008//National Science Foundation (NSF)/ ; 655406//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 700057//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; FI-570-2018//United States - Israel Binational Agricultural Research and Development Fund (BARD)/ ; RGP0067/2021//Human Frontier Science Program (HFSP)/ ; Long-term Fellowship ALTF 1046-2015//European Molecular Biology Organization (EMBO)/ ; }, mesh = {*Lignin/metabolism ; *Solanum lycopersicum/metabolism/genetics ; *Plant Roots/metabolism/genetics ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism/genetics ; Transcription Factors/metabolism/genetics ; Arabidopsis/metabolism/genetics ; }, abstract = {Multicellular organisms control environmental interactions through specialized barriers in specific cell types. A conserved barrier in plant roots is the endodermal Casparian strip (CS), a ring-like structure made of polymerized lignin that seals the endodermal apoplastic space. Most angiosperms have another root cell type, the exodermis, that is reported to form a barrier. Our understanding of exodermal developmental and molecular regulation and function is limited as this cell type is absent from Arabidopsis thaliana. We demonstrate that in tomato (Solanum lycopersicum), the exodermis does not form a CS. Instead, it forms a polar lignin cap (PLC) with equivalent barrier function to the endodermal CS but distinct genetic control. Repression of the exodermal PLC in inner cortical layers is conferred by the SlSCZ and SlEXO1 transcription factors, and these two factors genetically interact to control its polar deposition. Several target genes that act downstream of SlSCZ and SlEXO1 in the exodermis are identified. Although the exodermis and endodermis produce barriers that restrict mineral ion uptake, the exodermal PLC is unable to fully compensate for the lack of a CS. The presence of distinct lignin structures acting as apoplastic barriers has exciting implications for a root's response to abiotic and biotic stimuli.}, } @article {pmid39617193, year = {2025}, author = {Chandra, S and Rutaganira, FU}, title = {Glycerol improves the viability of a cryopreserved choanoflagellate.}, journal = {Cryobiology}, volume = {118}, number = {}, pages = {105183}, doi = {10.1016/j.cryobiol.2024.105183}, pmid = {39617193}, issn = {1090-2392}, mesh = {*Cryopreservation/methods ; *Choanoflagellata/drug effects/physiology/cytology ; *Cryoprotective Agents/pharmacology ; *Glycerol/pharmacology ; Dimethyl Sulfoxide/pharmacology ; Cell Survival/drug effects ; }, abstract = {The colonial choanoflagellate Salpingoeca rosetta is a tractable model system for studying the origins of multicellularity, but long-term storage strategies for this species have not been tested. In this study, we probed each stage of cryopreservation (cooling, long-term storage, recovery) to identify the optimal protocol for recovery of S. rosetta and co-cultured bacterial cells. Dimethyl sulfoxide (Me2SO; commonly referred to as DMSO), the current cryoprotective agent (CPA) standard, proved to be worse than glycerol at comparable concentrations. Samples treated with either CPA at 5 % showed the poorest recovery. Our results identified 15 % glycerol as the most effective CPA for both S. rosetta and Echinicola pacifica. We also determined that ultra-low temperature freezers can be sufficient for short-term storage. We propose 15 % glycerol and liquid phase nitrogen as the standard cryopreservation protocol for S. rosetta cultures and as a starting point for testing long-term storage strategies for other choanoflagellates and heterotrophic protists.}, } @article {pmid39614268, year = {2024}, author = {He, R and Liu, Y and Fu, W and He, X and Liu, S and Xiao, D and Tao, Y}, title = {Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.}, journal = {Molecular cancer}, volume = {23}, number = {1}, pages = {267}, pmid = {39614268}, issn = {1476-4598}, mesh = {Humans ; *Neoplasms/genetics/pathology/metabolism ; *Epigenesis, Genetic ; Animals ; *Disease Progression ; *Regulated Cell Death/genetics ; Gene Expression Regulation, Neoplastic ; Signal Transduction ; }, abstract = {Cell death is a fundamental part of life for metazoans. To maintain the balance between cell proliferation and metabolism of human bodies, a certain number of cells need to be removed regularly. Hence, the mechanisms of cell death have been preserved during the evolution of multicellular organisms. Tumorigenesis is closely related with exceptional inhibition of cell death. Mutations or defects in cell death-related genes block the elimination of abnormal cells and enhance the resistance of malignant cells to chemotherapy. Therefore, the investigation of cell death mechanisms enables the development of drugs that directly induce tumor cell death. In the guidelines updated by the Cell Death Nomenclature Committee (NCCD) in 2018, cell death was classified into 12 types according to morphological, biochemical and functional classification, including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, PARP-1 parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence and mitotic catastrophe. The mechanistic relationships between epigenetic controls and cell death in cancer progression were previously unclear. In this review, we will summarize the mechanisms of cell death pathways and corresponding epigenetic regulations. Also, we will explore the extensive interactions between these pathways and discuss the mechanisms of cell death in epigenetics which bring benefits to tumor therapy.}, } @article {pmid39604729, year = {2024}, author = {Yang, R and Hunker, O and Wise, M and Bleichert, F}, title = {Multiple mechanisms for licensing human replication origins.}, journal = {Nature}, volume = {636}, number = {8042}, pages = {488-498}, pmid = {39604729}, issn = {1476-4687}, support = {F31 CA278331/CA/NCI NIH HHS/United States ; R01 GM141313/GM/NIGMS NIH HHS/United States ; S10 OD023603/OD/NIH HHS/United States ; T32 GM008283/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; DNA/metabolism/chemistry ; *DNA Replication ; Microscopy, Electron ; *Minichromosome Maintenance Proteins/chemistry ; Models, Molecular ; *Origin Recognition Complex/chemistry ; Protein Multimerization ; *Replication Origin ; Cryoelectron Microscopy ; Protein Structure, Quaternary ; }, abstract = {Loading of replicative helicases is obligatory for the assembly of DNA replication machineries. The eukaryotic MCM2-7 replicative helicase motor is deposited onto DNA by the origin recognition complex (ORC) and co-loader proteins as a head-to-head double hexamer to license replication origins. Although extensively studied in budding yeast[1-4], the mechanisms of origin licensing in multicellular eukaryotes remain poorly defined. Here we use biochemical reconstitution and electron microscopy to reconstruct the human MCM loading pathway. We find that unlike in yeast, the ORC6 subunit of the ORC is not essential for-but enhances-human MCM loading. Electron microscopy analyses identify several intermediates en route to MCM double hexamer formation in the presence and absence of ORC6, including a DNA-loaded, closed-ring MCM single hexamer intermediate that can mature into a head-to-head double hexamer through multiple mechanisms. ORC6 and ORC3 facilitate the recruitment of the ORC to the dimerization interface of the first hexamer into MCM-ORC (MO) complexes that are distinct from the yeast MO complex[5,6] and may orient the ORC for second MCM hexamer loading. Additionally, MCM double hexamer formation can proceed through dimerization of independently loaded MCM single hexamers, promoted by a propensity of human MCM2-7 hexamers to self-dimerize. This flexibility in human MCM loading may provide resilience against cellular replication stress, and the reconstitution system will enable studies addressing outstanding questions regarding DNA replication initiation and replication-coupled events in the future.}, } @article {pmid39603922, year = {2025}, author = {Ryu, J and Kim, Y and Ju, YS}, title = {A more elaborate genetic clock for clonal species.}, journal = {Trends in genetics : TIG}, volume = {41}, number = {4}, pages = {268-270}, doi = {10.1016/j.tig.2024.11.002}, pmid = {39603922}, issn = {0168-9525}, mesh = {*Evolution, Molecular ; *Reproduction, Asexual/genetics ; Animals ; }, abstract = {The genetic clock is a well-established tool used in evolutionary biology for estimating divergence times between species, individuals, or cells based on DNA sequence changes. Yu et al. have revisited the clock to make it applicable to clonal multicellular organisms that expand through asexual reproduction mechanisms, enabling more comprehensive evolutionary tracking.}, } @article {pmid39596672, year = {2024}, author = {Madhani, H and Nejad Kourki, A}, title = {The Evolution of Complex Multicellularity in Land Plants.}, journal = {Genes}, volume = {15}, number = {11}, pages = {}, pmid = {39596672}, issn = {2073-4425}, mesh = {*Embryophyta/genetics/growth & development ; *Biological Evolution ; }, abstract = {The evolution of complex multicellularity in land plants represents a pivotal event in the history of life on Earth, characterized by significant increases in biological complexity. This transition, classified as a Major Evolutionary Transition (MET), is best understood through the framework of Evolutionary Transitions in Individuality (ETIs), which focuses on formerly independent entities forming higher-level units that lose their reproductive autonomy. While much of the ETI literature has concentrated on the early stages of multicellularity, such as the formation and maintenance stages, this paper seeks to address the less explored transformation stage. To do so, we apply an approach that we call Transitions in Structural Complexity (TSCs), which focuses on the emergence of new units of organization via the three key evolutionary processes of modularization, subfunctionalization, and integration to the evolution of land plants. To lay the groundwork, we first explore the relationships between sex, individuality, and units of selection to highlight a sexual life cycle-based perspective on ETIs by examining the early stages of the transition to multicellularity (formation) in the sexual life cycle of the unicellular common ancestor of land plants, emphasizing the differences between the transition to multicellularity in eumetazoans and land plants. We then directly apply the TSC approach in this group, identifying key evolutionary events such as the distinct evolutionary innovations like shoot, root, vascular systems, and specialized reproductive structures, arguing that bringing these under the broader rubric of TSCs affords a degree of explanatory unification. By examining these evolutionary processes, this paper provides a new perspective on the evolution of multicellularity in land plants, highlighting both parallels and distinctions with the animal kingdom.}, } @article {pmid39596652, year = {2024}, author = {Stein, WD}, title = {An Orthologics Study of the Notch Signaling Pathway.}, journal = {Genes}, volume = {15}, number = {11}, pages = {}, pmid = {39596652}, issn = {2073-4425}, mesh = {*Signal Transduction ; *Receptors, Notch/metabolism/genetics ; Animals ; Humans ; Evolution, Molecular ; Membrane Proteins/genetics/metabolism ; Phylogeny ; }, abstract = {The Notch signaling pathway plays a major role in embryological development and in the ongoing life processes of many animals. Its role is to provide cell-to-cell communication in which a Sender cell, bearing membrane-embedded ligands, instructs a Receiver cell, bearing membrane-embedded receptors, to adopt one of two available fates. Elucidating the evolution of this pathway is the topic of this paper, which uses an orthologs approach, providing a comprehensive basis for the study. Using BLAST searches, orthologs were identified for all the 49 components of the Notch signaling pathway. The historical time course of integration of these proteins, as the animals evolved, was elucidated. Insofar as cell-to-cell communication is of relevance only in multicellular animals, it is not surprising that the Notch system became functional only with the evolutionary appearance of Metazoa, the first multicellular animals. Porifera contributed a quarter of the Notch pathway proteins, the Cnidaria brought the total to one-half, but the system reached completion only when humans appeared. A literature search elucidated the roles of the Notch system's components in modern descendants of the ortholog-contributing ancestors. A single protein, the protein tyrosine kinase (PTK) of the protozoan Ministeria vibrans, was identified as a possible pre-Metazoan ancestor of all three of the Notch pathway proteins, DLL, JAG, and NOTCH. A scenario for the evolution of the Notch signaling pathway is presented and described as the co-option of its components, clade by clade, in a repurposing of genes already present in ancestral unicellular organisms.}, } @article {pmid39595611, year = {2024}, author = {Dahlin, P and Ruthes, AC}, title = {Loss of Sterol Biosynthesis in Economically Important Plant Pests and Pathogens: A Review of a Potential Target for Pest Control.}, journal = {Biomolecules}, volume = {14}, number = {11}, pages = {}, pmid = {39595611}, issn = {2218-273X}, mesh = {Animals ; Insecta/metabolism ; Nematoda/metabolism ; Oomycetes/metabolism ; *Pest Control ; Plant Diseases/parasitology/microbiology ; *Plants/metabolism/parasitology ; *Sterols/metabolism/biosynthesis ; }, abstract = {Sterol biosynthesis is a crucial metabolic pathway in plants and various plant pathogens. Their vital physiological role in multicellular organisms and their effects on growth and reproduction underline their importance as membrane compounds, hormone precursors, and signaling molecules. Insects, nematodes, and oomycetes of the Peronosporales group, which harbor important agricultural pests and pathogens, have lost the ability to synthesize their own sterols. These organisms rely on the acquisition of sterols from their host and are dependent on the sterol composition of the host. It is thought that sterol-synthesizing enzymes were lost during co-evolution with the hosts, which provided the organisms with sufficient amounts of the required sterols. To meet the essential requirements of these organisms, some sterol auxotrophs retained a few remaining sterol-modifying enzymes. Several molecular and biochemical investigations have suggested promising avenues for pest and pathogen control by targeting host sterol composition, sterol uptake, or sterol modification in organisms that have lost the ability to biosynthesize sterol de novo. This review examines the loss of sterol biosynthesis de novo in insects, nematodes, and oomycetes with the aim of investigating the sterol metabolic constraints and sterol acquisition of these organisms. This will shed light on its potential as a control target for the management of sterol-dependent organisms in a comprehensive agronomic approach.}, } @article {pmid39591964, year = {2025}, author = {Lu, X and Zhang, Q and Wang, Z and Cheng, X and Yan, H and Cai, S and Zhang, H and Liu, Q}, title = {Development of an inducible DNA barcoding system to understand lineage changes in Arabidopsis regeneration.}, journal = {Developmental cell}, volume = {60}, number = {2}, pages = {305-319.e5}, doi = {10.1016/j.devcel.2024.10.023}, pmid = {39591964}, issn = {1878-1551}, mesh = {*Arabidopsis/genetics/physiology/cytology ; *DNA Barcoding, Taxonomic/methods ; *Cell Lineage/genetics ; *Regeneration/genetics/physiology ; }, abstract = {Plants demonstrate a high degree of developmental plasticity, capable of regenerating entire individuals from detached somatic tissues-a regenerative phenomenon rarely observed in metazoa. Consequently, elucidating the lineage relationship between somatic founder cells and descendant cells in regenerated plant organs has long been a pursuit. In this study, we developed and optimized both DNA barcode- and multi-fluorescence-based cell-lineage tracing toolsets, employing an inducible method to mark individual cells in Arabidopsis donor somatic tissues at the onset of regeneration. Utilizing these complementary methods, we scrutinized cell identities at the single-cell level and presented compelling evidence that all cells in the regenerated Arabidopsis plants, irrespective of their organ types, originated from a single progenitor cell in the donor somatic tissue. Our discovery suggests a single-cell passage directing the transition from multicellular donor tissue to regenerated plants, thereby creating opportunities for cell-cell competition during plant regeneration-a strategy for maximizing survival.}, } @article {pmid39589477, year = {2024}, author = {Krueger, KE}, title = {Survey for Activating Oncogenic Mutation Variants in Metazoan Germline Genes.}, journal = {Journal of molecular evolution}, volume = {92}, number = {6}, pages = {930-943}, pmid = {39589477}, issn = {1432-1432}, mesh = {Animals ; *Germ-Line Mutation/genetics ; Humans ; Neoplasms/genetics ; Oncogenes/genetics ; Mutation, Missense/genetics ; Germ Cells/metabolism ; }, abstract = {Most cancers present with mutations or amplifications in distinctive tumor promoter genes that activate principal cell-signaling cascades promoting cell proliferation, dedifferentiation, cell survival, and replicative immortality. Somatic mutations found in this these driver proto-oncogenes invariably result in constitutive activation of the encoded protein. A salient feature of the activating mutations observed throughout many thousands of clinical tumor specimens reveals these driver missense mutations are recurrent and restricted to just one or very few codons of the entire gene, suggesting they have been positively selected during the course of tumor development. The purpose of this study is to investigate whether these characteristic oncogenic driver mutations are observed in the germline genes of any metazoan species. Six well-known tumor promoter genes were chosen for this survey including BRAF, KRAS, JAK2, PIK3CA, EGFR, and IDH1/2. The sites of all driver mutations were found to occur in highly conserved regions of each gene comparing protein sequences throughout diverse phyla of metazoan species. None of the oncogenic missense mutations were found in germlines of any species of current genome and protein databases. Despite many tumors readily selecting these somatic mutations, the conclusion drawn from this study is that these variants are negatively rejected if encountered as a germline mutation. While cancer expansion ensues from dysregulated growth elicited by these mutations, this effect is likely detrimental to embryonic development and/or survival of multicellular organisms. Although all oncogenic mutations considered here are gain-of-function where five of the six increase activity of the encoded proteins, clonal advancement promotes tumor growth by these genomic changes without conferring selection advantages benefiting the organism or species.}, } @article {pmid39587099, year = {2024}, author = {Sheikh, S and Fu, CJ and Brown, MW and Baldauf, SL}, title = {The Acrasis kona genome and developmental transcriptomes reveal deep origins of eukaryotic multicellular pathways.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {10197}, pmid = {39587099}, issn = {2041-1723}, support = {VR 2017-04351//Vetenskapsrådet (Swedish Research Council)/ ; 2100888//National Science Foundation (NSF)/ ; }, mesh = {*Transcriptome ; *Dictyostelium/genetics/growth & development ; Genome, Protozoan ; Amoeba/genetics ; Phylogeny ; Gene Transfer, Horizontal ; Protozoan Proteins/genetics/metabolism ; Proteome/metabolism/genetics ; Genome ; }, abstract = {Acrasids are amoebae with the capacity to form multicellular fruiting bodies in a process known as aggregative multicellularity (AGM). This makes acrasids the only known example of multicellularity among the earliest branches of eukaryotes (the former Excavata). Here, we report the Acrasis kona genome sequence plus transcriptomes from pre-, mid- and post-developmental stages. The genome is rich in novelty and genes with strong signatures of horizontal transfer, and multigene families encode nearly half of the amoeba's predicted proteome. Development in A. kona appears molecularly simple relative to the AGM model, Dictyostelium discoideum. However, the acrasid also differs from the dictyostelid in that it does not appear to be starving during development. Instead, developing A. kona appears to be very metabolically active, does not induce autophagy and does not up-regulate its proteasomal genes. Together, these observations strongly suggest that starvation is not essential for AGM development. Nonetheless, development in the two amoebae appears to employ remarkably similar pathways for signaling, motility and, potentially, construction of an extracellular matrix surrounding the developing cell mass. Much of this similarity is also shared with animal development, suggesting that much of the basic tool kit for multicellular development arose early in eukaryote evolution.}, } @article {pmid39571576, year = {2024}, author = {Denoeud, F and Godfroy, O and Cruaud, C and Heesch, S and Nehr, Z and Tadrent, N and Couloux, A and Brillet-Guéguen, L and Delage, L and Mckeown, D and Motomura, T and Sussfeld, D and Fan, X and Mazéas, L and Terrapon, N and Barrera-Redondo, J and Petroll, R and Reynes, L and Choi, SW and Jo, J and Uthanumallian, K and Bogaert, K and Duc, C and Ratchinski, P and Lipinska, A and Noel, B and Murphy, EA and Lohr, M and Khatei, A and Hamon-Giraud, P and Vieira, C and Avia, K and Akerfors, SS and Akita, S and Badis, Y and Barbeyron, T and Belcour, A and Berrabah, W and Blanquart, S and Bouguerba-Collin, A and Bringloe, T and Cattolico, RA and Cormier, A and Cruz de Carvalho, H and Dallet, R and De Clerck, O and Debit, A and Denis, E and Destombe, C and Dinatale, E and Dittami, S and Drula, E and Faugeron, S and Got, J and Graf, L and Groisillier, A and Guillemin, ML and Harms, L and Hatchett, WJ and Henrissat, B and Hoarau, G and Jollivet, C and Jueterbock, A and Kayal, E and Knoll, AH and Kogame, K and Le Bars, A and Leblanc, C and Le Gall, L and Ley, R and Liu, X and LoDuca, ST and Lopez, PJ and Lopez, P and Manirakiza, E and Massau, K and Mauger, S and Mest, L and Michel, G and Monteiro, C and Nagasato, C and Nègre, D and Pelletier, E and Phillips, N and Potin, P and Rensing, SA and Rousselot, E and Rousvoal, S and Schroeder, D and Scornet, D and Siegel, A and Tirichine, L and Tonon, T and Valentin, K and Verbruggen, H and Weinberger, F and Wheeler, G and Kawai, H and Peters, AF and Yoon, HS and Hervé, C and Ye, N and Bapteste, E and Valero, M and Markov, GV and Corre, E and Coelho, SM and Wincker, P and Aury, JM and Cock, JM}, title = {Evolutionary genomics of the emergence of brown algae as key components of coastal ecosystems.}, journal = {Cell}, volume = {187}, number = {24}, pages = {6943-6965.e39}, doi = {10.1016/j.cell.2024.10.049}, pmid = {39571576}, issn = {1097-4172}, mesh = {*Phaeophyceae/genetics ; *Ecosystem ; *Phylogeny ; *Genomics ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genome/genetics ; }, abstract = {Brown seaweeds are keystone species of coastal ecosystems, often forming extensive underwater forests, and are under considerable threat from climate change. In this study, analysis of multiple genomes has provided insights across the entire evolutionary history of this lineage, from initial emergence, through later diversification of the brown algal orders, down to microevolutionary events at the genus level. Emergence of the brown algal lineage was associated with a marked gain of new orthologous gene families, enhanced protein domain rearrangement, increased horizontal gene transfer events, and the acquisition of novel signaling molecules and key metabolic pathways, the latter notably related to biosynthesis of the alginate-based extracellular matrix, and halogen and phlorotannin biosynthesis. We show that brown algal genome diversification is tightly linked to phenotypic divergence, including changes in life cycle strategy and zoid flagellar structure. The study also showed that integration of large viral genomes has had a significant impact on brown algal genome content throughout the emergence of the lineage.}, } @article {pmid39570883, year = {2024}, author = {Petersen, M and Reyes-Vigil, F and Campo, M and Brusés, JL}, title = {Classical cadherins evolutionary constraints in primates is associated with their expression in the central nervous system.}, journal = {PloS one}, volume = {19}, number = {11}, pages = {e0313428}, pmid = {39570883}, issn = {1932-6203}, mesh = {Animals ; *Cadherins/genetics/metabolism ; *Primates/genetics ; *Evolution, Molecular ; Mice ; *Central Nervous System/metabolism ; Humans ; Phylogeny ; Selection, Genetic ; }, abstract = {Classical cadherins (CDH) comprise a family of single-pass transmembrane glycoproteins that contribute to tissue morphogenesis by regulating cell-cell adhesion, cytoskeletal dynamics, and cell signaling. CDH are grouped into type I (CDH 1, 2, 3, 4 and 15) and type II (CDH 5, 6, 7, 8, 9, 10, 11, 12, 18, 20, 22 and 24), based on the folding of the cadherin binding domain involved in trans-dimer formation. CDH are exclusively found in metazoans, and the origin and expansion of the gene family coincide with the emergence of multicellularity and vertebrates respectively. This study examined the evolutionary changes of CDH orthologs in primates and the factors that influence selective pressure to investigate the varying constraints exerted among CDH. Pairwise comparisons of the number of amino acid substitutions and of the ratio of non-synonymous substitutions per non-synonymous sites (dN) over synonymous substitutions per synonymous sites (dS), show that CDH2, CDH4, and most type II CDH have been under significantly higher negative selective pressure as compared to CDH1, CDH3, CDH5 and CDH19. Evaluation of gene essentiality as determined by the effect of germline deletion on animal viability, morphogenic phenotype, and reproductive fitness, show no correlation with the with extent of negative selection observed on CDH. Spearman's correlation analysis shows a positive correlation between CDH expression levels (E) in mouse and human tissues and their rate of evolution (R), as observed in most proteins expressed on the cell surface. However, CDH expression in the CNS show a significant E-R negative correlation, indicating that the strong negative selection exerted on CDH2, CDH4, and most type II CDH is associated with their expression in the CNS. CDH participate in a variety of cellular processes in the CNS including neuronal migration and functional assembly of neural circuits, which could profoundly influence animal fitness. Therefore, our findings suggest that the unusually high negative selective pressure exerted on CDH2, CDH4 and most type II CDH is due to their role in CNS formation and function and may have contributed to shape the evolution of the CNS in primates.}, } @article {pmid39543096, year = {2024}, author = {Gao, Y and Tan, DS and Girbig, M and Hu, H and Zhou, X and Xie, Q and Yeung, SW and Lee, KS and Ho, SY and Cojocaru, V and Yan, J and Hochberg, GKA and de Mendoza, A and Jauch, R}, title = {The emergence of Sox and POU transcription factors predates the origins of animal stem cells.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {9868}, pmid = {39543096}, issn = {2041-1723}, support = {C7064-22G//Research Grants Council, University Grants Committee (RGC, UGC)/ ; }, mesh = {Animals ; Mice ; *SOX Transcription Factors/metabolism/genetics ; *Induced Pluripotent Stem Cells/metabolism/cytology ; *SOXB1 Transcription Factors/metabolism/genetics ; POU Domain Factors/metabolism/genetics ; Octamer Transcription Factor-3/metabolism/genetics ; Humans ; Evolution, Molecular ; Phylogeny ; Stem Cells/metabolism/cytology ; Cellular Reprogramming/genetics ; }, abstract = {Stem cells are a hallmark of animal multicellularity. Sox and POU transcription factors are associated with stemness and were believed to be animal innovations, reported absent in their unicellular relatives. Here we describe unicellular Sox and POU factors. Choanoflagellate and filasterean Sox proteins have DNA-binding specificity similar to mammalian Sox2. Choanoflagellate-but not filasterean-Sox can replace Sox2 to reprogram mouse somatic cells into induced pluripotent stem cells (iPSCs) through interacting with the mouse POU member Oct4. In contrast, choanoflagellate POU has a distinct DNA-binding profile and cannot generate iPSCs. Ancestrally reconstructed Sox proteins indicate that iPSC formation capacity is pervasive among resurrected sequences, thus loss of Sox2-like properties fostered Sox family subfunctionalization. Our findings imply that the evolution of animal stem cells might have involved the exaptation of a pre-existing set of transcription factors, where pre-animal Sox was biochemically similar to extant Sox, whilst POU factors required evolutionary innovations.}, } @article {pmid39539009, year = {2024}, author = {Kosztyo, BS and Richards, EJ}, title = {Structural Diversity and Distribution of Nuclear Matrix Constituent Protein Class Nuclear Lamina Proteins in Streptophytic Algae.}, journal = {Genome biology and evolution}, volume = {16}, number = {11}, pages = {}, pmid = {39539009}, issn = {1759-6653}, support = {URoL-2022048//National Science Foundation/ ; }, mesh = {*Streptophyta/metabolism/genetics ; Plant Proteins/genetics/metabolism/chemistry ; Nuclear Lamina/metabolism ; Nuclear Matrix/metabolism ; Algal Proteins/metabolism/chemistry/genetics ; Phylogeny ; Nuclear Proteins/metabolism/genetics/chemistry ; Amino Acid Sequence ; Evolution, Molecular ; Proteome ; }, abstract = {Nuclear matrix constituent proteins in plants function like animal lamins, providing the structural foundation of the nuclear lamina and regulating nuclear organization and morphology. Although they are well characterized in angiosperms, the presence and structure of nuclear matrix constituent proteins in more distantly related species, such as streptophytic algae, are relatively unknown. The rapid evolution of nuclear matrix constituent proteins throughout the plant lineage has caused a divergence in protein sequence that makes similarity-based searches less effective. Structural features are more likely to be conserved compared to primary amino acid sequence; therefore, we developed a filtration protocol to search for diverged nuclear matrix constituent proteins based on four physical characteristics: intrinsically disordered content, isoelectric point, number of amino acids, and the presence of a central coiled-coil domain. By setting parameters to recognize the properties of bona fide nuclear matrix constituent protein proteins in angiosperms, we filtered eight complete proteomes from streptophytic algae species and identified strong nuclear matrix constituent protein candidates in six taxa in the Classes Zygnematophyceae, Charophyceae, and Klebsormidiophyceae. Through analysis of these proteins, we observed structural variance in domain size between nuclear matrix constituent proteins in algae and land plants, as well as a single block of amino acid conservation. Our analysis indicates that nuclear matrix constituent proteins are absent in the Mesostigmatophyceae. The presence versus absence of nuclear matrix constituent protein proteins does not correlate with the distribution of different forms of mitosis (e.g. closed/semi-closed/open) but does correspond to the transition from unicellularity to multicellularity in the streptophytic algae, suggesting that a nuclear matrix constituent protein-based nucleoskeleton plays important roles in supporting cell-to-cell interactions.}, } @article {pmid39536081, year = {2024}, author = {Huang, J and Larmore, CJ and Priest, SJ and Xu, Z and Dietrich, FS and Yadav, V and Magwene, PM and Sun, S and Heitman, J}, title = {Distinct evolutionary trajectories following loss of RNA interference in Cryptococcus neoformans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {47}, pages = {e2416656121}, pmid = {39536081}, issn = {1091-6490}, support = {R37 AI039115/AI/NIAID NIH HHS/United States ; AI050113-20//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 AI039115/AI/NIAID NIH HHS/United States ; AI039115-27//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 AI100272/AI/NIAID NIH HHS/United States ; AI133654-07//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 AI133654/AI/NIAID NIH HHS/United States ; R01 AI050113/AI/NIAID NIH HHS/United States ; }, mesh = {*Cryptococcus neoformans/genetics ; *RNA Interference ; Evolution, Molecular ; DNA Transposable Elements/genetics ; Retroelements/genetics ; Fungal Proteins/genetics/metabolism ; Loss of Function Mutation ; Mutation ; Drug Resistance, Fungal/genetics ; }, abstract = {While increased mutation rates typically have negative consequences in multicellular organisms, hypermutation can be advantageous for microbes adapting to the environment. Previously, we identified two hypermutator Cryptococcus neoformans clinical isolates that rapidly develop drug resistance due to transposition of a retrotransposon, Cnl1. Cnl1-mediated hypermutation is caused by a nonsense mutation in a gene encoding an RNA interference (RNAi) component, ZNF3, combined with a tremendous transposon burden. To elucidate adaptive mechanisms following RNAi loss, two bioinformatic pipelines were developed to identify RNAi loss-of-function (LOF) mutations in a collection of 387 sequenced C. neoformans isolates. Remarkably, several RNAi-loss isolates were identified that are not hypermutators and have not accumulated transposons. To test whether these RNAi LOF mutations can cause hypermutation, the mutations were introduced into a nonhypermutator strain with a high transposon burden, which resulted in a hypermutator phenotype. To further investigate whether RNAi-loss isolates can become hypermutators, in vitro passaging was performed. Although no hypermutators were found in two C. neoformans RNAi-loss strains after short-term passage, hypermutation was observed in a passaged Cryptococcus deneoformans strain with an increased transposon burden. Consistent with a two-step evolution, when an RNAi-loss isolate was crossed with an isolate containing a high Cnl1 burden, F1 hypermutator progeny inheriting a high transposon burden were identified. In addition to Cnl1 transpositions, insertions of a gigantic DNA transposon KDZ1 (~11 kb) contributed to hypermutation in the progeny. Our results suggest that RNAi loss is relatively common (7/387, ~1.8%) and enables distinct evolutionary trajectories: hypermutation following transposon accumulation or survival without hypermutation.}, } @article {pmid39515324, year = {2024}, author = {Smith, ML and Marting, PR and Bailey, CS and Chuttong, B and Maul, ER and Molinari, R and Prathibha, P and Rowe, EB and Spott, MR and Koger, B}, title = {Form, function, and evolutionary origins of architectural symmetry in honey bee nests.}, journal = {Current biology : CB}, volume = {34}, number = {24}, pages = {5813-5821.e5}, doi = {10.1016/j.cub.2024.10.022}, pmid = {39515324}, issn = {1879-0445}, mesh = {Animals ; Bees/physiology/anatomy & histology ; *Nesting Behavior ; *Biological Evolution ; }, abstract = {Symmetry is pervasive across the tree of life,[1][,][2][,][3][,][4][,][5] and organisms (including humans) build symmetrical structures for reproduction, locomotion, or aesthetics.[6][,][7][,][8][,][9] Symmetry, however, does not necessarily span across levels of biological organization (e.g., symmetrical body plans often have asymmetric organs).[10] If and how symmetry exists in structures built by social insect collectives, where there is no blueprint or central organizer, remains an open question.[11] Here, we show that honey bees actively organize nest contents symmetrically on either side of their double-sided comb; 79% ± 7% of cell contents match their backside counterpart, creating a mirror image inside the nest. Experimentally restricting colonies to opposite sides of comb, we find that independent colonies will symmetrically mimic each other's nest organization. We then examine the mechanism by which independent colonies can indirectly coordinate nest symmetry, showing that 100% of colonies (n = 6) perfectly co-localize their brood nest with a randomly positioned heat source, indicating that heat drives nest site initiation and early brood production. Nest symmetry also has adaptive benefits: two-sided nests grow more quickly, rear more brood, and have a more stable thermal environment than one-sided nests do. Finally, examining the evolutionary origins, we show that symmetry persists in three-dimensional (3D) nests of Apis mellifera and across multiple Apis species, coinciding with the onset of double-sided combs, which made it possible to symmetrically stockpile nest contents. This work shows that, similar to molecular mechanisms that create symmetry in multicellular organisms, there are behavioral processes that create functional symmetry in the collective organization of animal architecture.}, } @article {pmid39508768, year = {2024}, author = {Lynch, M}, title = {The bioenergetic cost of building a metazoan.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {46}, pages = {e2414742121}, pmid = {39508768}, issn = {1091-6490}, support = {2R35GM122566//HHS | National Institutes of Health (NIH)/ ; R35 GM122566/GM/NIGMS NIH HHS/United States ; IOS-1922914//NSF | BIO | Division of Integrative Organismal Systems (IOS)/ ; BSR 83-06072//NSF | BIO | Division of Environmental Biology (DEB)/ ; 735927//Gordon and Betty Moore Foundation (GBMF)/ ; BSR 89-11038//NSF | BIO | Division of Environmental Biology (DEB)/ ; DBI-2119963//NSF | BIO | Division of Environmental Biology (DEB)/ ; }, mesh = {Animals ; *Energy Metabolism ; *Adenosine Triphosphate/metabolism ; *Biomass ; Daphnia/growth & development/metabolism/physiology ; Phylogeny ; }, abstract = {All life forms depend on the conversion of energy into biomass used in growth and reproduction. For unicellular heterotrophs, the energetic cost associated with building a cell scales slightly sublinearly with cell weight. However, observations on multiple Daphnia species and numerous other metazoans suggest that although a similar size-specific scaling is retained in multicellular heterotrophs, there is a quantum leap in the energy required to build a replacement soma, presumably owing to the added investment in nonproductive features such as cell adhesion, support tissue, and intercellular communication and transport. Thus, any context-dependent ecological advantages that accompany the evolution of multicellularity come at a high baseline bioenergetic cost. At the phylogenetic level, for both unicellular and multicellular eukaryotes, the energetic expense per unit biomass produced declines with increasing adult size of a species, but there is a countergradient scaling within the developmental trajectories of individual metazoan species, with the cost of biomass production increasing with size. Translation of the results into the universal currency of adenosine triphosphate (ATP) hydrolyses provides insight into the demands on the electron-transport/ATP-synthase machinery per organism and on the minimum doubling times for biomass production imposed by the costs of duplicating the energy-producing infrastructure.}, } @article {pmid39508584, year = {2024}, author = {Thomas, F and Asselin, K and MacDonald, N and Brazier, L and Meliani, J and Ujvari, B and Dujon, AM}, title = {Oncogenic processes: a neglected parameter in the evolutionary ecology of animals.}, journal = {Comptes rendus biologies}, volume = {347}, number = {}, pages = {137-157}, doi = {10.5802/crbiol.159}, pmid = {39508584}, issn = {1768-3238}, mesh = {Animals ; *Biological Evolution ; *Neoplasms/genetics/veterinary ; *Carcinogenesis/genetics ; Humans ; Ecosystem ; Ecology ; *Oncogenes/physiology ; }, abstract = {Cancer is a biological process that emerged at the end of the Precambrian era with the rise of multicellular organisms. Traditionally, cancer has been viewed primarily as a disease relevant to human and domesticated animal health, attracting attention mainly from oncologists. In recent years, however, the community of ecologists and evolutionary biologists has recognized the pivotal role of cancer-related issues in the evolutionary paths of various species, influencing multiple facets of their biology. It has become evident that overlooking these issues is untenable for a comprehensive understanding of species evolution and ecosystem functioning. In this article, we highlight some significant advancements in this field, also underscoring the pressing need to consider reciprocal interactions not only between cancer cells and their hosts but also with all entities comprising the holobiont. This reflection gains particular relevance as ecosystems face increasing pollution from mutagenic substances, resulting in a resurgence of cancer cases in wildlife.}, } @article {pmid39508203, year = {2024}, author = {Neumann, SA and Gaspin, C and Sáez-Vásquez, J}, title = {Plant ribosomes as a score to fathom the melody of 2'-O-methylation across evolution.}, journal = {RNA biology}, volume = {21}, number = {1}, pages = {70-81}, pmid = {39508203}, issn = {1555-8584}, support = {ANR-20-CE12-0024-01//ANR (Agence Nationale de la Recherche) MetRibo/ ; ANR-10-LABX-41//“Laboratoires d’Excellence (LABEX) TULIP/ ; }, mesh = {Methylation ; *Ribosomes/metabolism ; *RNA, Ribosomal/metabolism/genetics/chemistry ; *Plants/metabolism/genetics ; Humans ; Evolution, Molecular ; Methyltransferases/metabolism/genetics/chemistry ; RNA, Plant/metabolism/genetics/chemistry ; Archaea/genetics/metabolism ; RNA, Transfer/metabolism/genetics/chemistry ; }, abstract = {2'-O-ribose methylation (2'-O-Me) is one of the most common RNA modifications detected in ribosomal RNAs (rRNA) from bacteria to eukaryotic cells. 2'-O-Me favours a specific RNA conformation and protects RNA from hydrolysis. Moreover, rRNA 2'-O-Me might stabilize its interactions with messenger RNA (mRNA), transfer RNA (tRNA) or proteins. The extent of rRNA 2'-O-Me fluctuates between species from 3-4 sites in bacteria to tens of sites in archaea, yeast, algae, plants and human. Depending on the organism as well as the rRNA targeting site and position, the 2'-O-Me reaction can be carried out by several site-specific RNA methyltransferases (RMTase) or by a single RMTase associated to specific RNA guides. Here, we review current progresses in rRNA 2'-O-Me (sites/Nm and RMTases) in plants and compare the results with molecular clues from unicellular (bacteria, archaea, algae and yeast) as well as multicellular (human and plants) organisms.}, } @article {pmid39506108, year = {2024}, author = {Olivetta, M and Bhickta, C and Chiaruttini, N and Burns, J and Dudin, O}, title = {A multicellular developmental program in a close animal relative.}, journal = {Nature}, volume = {635}, number = {8038}, pages = {382-389}, pmid = {39506108}, issn = {1476-4687}, mesh = {Animals ; Biological Evolution ; *Embryonic Development ; *Eukaryota/classification/cytology/genetics/growth & development ; Gene Expression Profiling ; Single-Cell Analysis ; Transcriptome ; Zygote/cytology/growth & development/metabolism ; *Phylogeny ; Time Factors ; }, abstract = {All animals develop from a single-celled zygote into a complex multicellular organism through a series of precisely orchestrated processes[1,2]. Despite the remarkable conservation of early embryogenesis across animals, the evolutionary origins of how and when this process first emerged remain elusive. Here, by combining time-resolved imaging and transcriptomic profiling, we show that single cells of the ichthyosporean Chromosphaera perkinsii-a close relative that diverged from animals about 1 billion years ago[3,4]-undergo symmetry breaking and develop through cleavage divisions to produce a prolonged multicellular colony with distinct co-existing cell types. Our findings about the autonomous and palintomic developmental program of C. perkinsii hint that such multicellular development either is much older than previously thought or evolved convergently in ichthyosporeans.}, } @article {pmid39498496, year = {2024}, author = {Hojo, H and Tani, S and Ohba, S}, title = {Modeling of skeletal development and diseases using human pluripotent stem cells.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {40}, number = {1}, pages = {5-19}, pmid = {39498496}, issn = {1523-4681}, support = {20H03885//Japan Society for the Promotion of Science/ ; //Rising Star Award from American Society for Bone and Mineral Research/ ; JP21bm0704071//Japan Agency for Medical Research and Development/ ; JPMJFR225N//Japan Science and Technology Agency/ ; JPMJER2401//JST ERATO program/ ; }, mesh = {Humans ; *Pluripotent Stem Cells/metabolism/cytology ; *Models, Biological ; *Bone Development ; Bone Diseases/pathology ; Bone and Bones/metabolism/embryology ; Animals ; }, abstract = {Human skeletal elements are formed from distinct origins at distinct positions of the embryo. For example, the neural crest produces the facial bones, the paraxial mesoderm produces the axial skeleton, and the lateral plate mesoderm produces the appendicular skeleton. During skeletal development, different combinations of signaling pathways are coordinated from distinct origins during the sequential developmental stages. Models for human skeletal development have been established using human pluripotent stem cells (hPSCs) and by exploiting our understanding of skeletal development. Stepwise protocols for generating skeletal cells from different origins have been designed to mimic developmental trails. Recently, organoid methods have allowed the multicellular organization of skeletal cell types to recapitulate complicated skeletal development and metabolism. Similarly, several genetic diseases of the skeleton have been modeled using patient-derived induced pluripotent stem cells and genome-editing technologies. Model-based drug screening is a powerful tool for identifying drug candidates. This review briefly summarizes our current understanding of the embryonic development of skeletal tissues and introduces the current state-of-the-art hPSC methods for recapitulating skeletal development, metabolism, and diseases. We also discuss the current limitations and future perspectives for applications of the hPSC-based modeling system in precision medicine in this research field.}, } @article {pmid39496747, year = {2024}, author = {Yao, M and Su, Y and Xiong, R and Zhang, X and Zhu, X and Chen, YC and Ao, P}, title = {Deciphering the topological landscape of glioma using a network theory framework.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26724}, pmid = {39496747}, issn = {2045-2322}, support = {16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; 16Z103060007//National Natural Science Foundation of China/ ; }, mesh = {*Glioma/pathology/genetics/metabolism ; Humans ; *Gene Regulatory Networks ; *Neoplastic Stem Cells/metabolism/pathology ; *Brain Neoplasms/pathology/metabolism ; Gene Expression Regulation, Neoplastic ; Astrocytes/metabolism ; }, abstract = {Glioma stem cells have been recognized as key players in glioma recurrence and therapeutic resistance, presenting a promising target for novel treatments. However, the limited understanding of the role glioma stem cells play in the glioma hierarchy has drawn controversy and hindered research translation into therapies. Despite significant advances in our understanding of gene regulatory networks, the dynamics of these networks and their implications for glioma remain elusive. This study employs a systemic theoretical perspective to integrate experimental knowledge into a core endogenous network model for glioma, thereby elucidating its energy landscape through network dynamics computation. The model identifies two stable states corresponding to astrocytic-like and oligodendrocytic-like tumor cells, connected by a transition state with the feature of high stemness, which serves as one of the energy barriers between astrocytic-like and oligodendrocytic-like states, indicating the instability of glioma stem cells in vivo. We also obtained various stable states further supporting glioma's multicellular origins and uncovered a group of transition states that could potentially induce tumor heterogeneity and therapeutic resistance. This research proposes that the transition states linking both glioma stable states are central to glioma heterogeneity and therapy resistance. Our approach may contribute to the advancement of glioma therapy by offering a novel perspective on the complex landscape of glioma biology.}, } @article {pmid39480878, year = {2024}, author = {Petit, C and Kojak, E and Webster, S and Marra, M and Sweeney, B and Chaikin, C and Jemc, JC and Kanzok, SM}, title = {The evolutionarily conserved PhLP3 is essential for sperm development in Drosophila melanogaster.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0306676}, pmid = {39480878}, issn = {1932-6203}, mesh = {Animals ; *Drosophila melanogaster/genetics/metabolism/growth & development ; Male ; *Drosophila Proteins/genetics/metabolism ; *Spermatogenesis/genetics ; *Spermatozoa/metabolism ; Evolution, Molecular ; Testis/metabolism ; Conserved Sequence ; }, abstract = {Phosducin-like proteins (PhLP) are thioredoxin domain-containing proteins that are highly conserved across unicellular and multicellular organisms. PhLP family proteins are hypothesized to function as co-chaperones in the folding of cytoskeletal proteins. Here, we present the initial molecular, biochemical, and functional characterization of CG4511 as Drosophila melanogaster PhLP3. We cloned the gene into a bacterial expression vector and produced enzymatically active recombinant PhLP3, which showed similar kinetics to previously characterized orthologues. A fly strain homozygous for a P-element insertion in the 5' UTR of the PhLP3 gene exhibited significant downregulation of PhLP3 expression. We found these male flies to be sterile. Microscopic analysis revealed altered testes morphology and impairment of spermiogenesis, leading to a lack of mature sperm. Among the most significant observations was the lack of actin cones during sperm maturation. Excision of the P-element insertion in PhLP3 restored male fertility, spermiogenesis, and seminal vesicle size. Given the high level of conservation of PhLP3, our data suggests PhLP3 may be an important regulator of sperm development across species.}, } @article {pmid39486632, year = {2025}, author = {Barlow, LA}, title = {Development of ectodermal and endodermal taste buds.}, journal = {Developmental biology}, volume = {518}, number = {}, pages = {20-27}, pmid = {39486632}, issn = {1095-564X}, support = {R01 DC018489/DC/NIDCD NIH HHS/United States ; R01 DC021865/DC/NIDCD NIH HHS/United States ; R21 CA236480/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Ectoderm/cytology/embryology/metabolism ; *Endoderm/cytology/embryology/metabolism ; Gene Expression Regulation, Developmental ; *Taste Buds/embryology ; Tongue/cytology/embryology ; }, abstract = {The sense of taste is mediated primarily by taste buds on the tongue. These multicellular sensory organs are induced, patterned and become innervated during embryogenesis such that a functional taste system is present at birth when animals begin to feed. While taste buds have been considered ectodermal appendages, this is only partly accurate as only fungiform taste buds in the anterior tongue arise from the ectoderm. Taste buds found in the posterior tongue actually derive from endoderm. Nonetheless, both anterior and posterior buds are functionally similar, despite their disparate embryonic origins. In this review, I compare the development of ectodermal vs endodermal taste buds, highlighting the many differences in the cellular and molecular genetic mechanisms governing their formation.}, } @article {pmid39468575, year = {2024}, author = {Wolnik, J and Adamska, P and Oleksy, A and Sanetra, AM and Palus-Chramiec, K and Lewandowski, MH and Dulak, J and Biniecka, M}, title = {A novel 3D cardiac microtissue model for investigation of cardiovascular complications in rheumatoid arthritis.}, journal = {Stem cell research & therapy}, volume = {15}, number = {1}, pages = {382}, pmid = {39468575}, issn = {1757-6512}, support = {UMO-2017/25/B/NZ5/02243//Narodowe Centrum Nauki/ ; }, mesh = {Humans ; *Arthritis, Rheumatoid/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism/cytology ; *Myocytes, Cardiac/metabolism/pathology/cytology ; *Cell Differentiation ; *Fibroblasts/metabolism/pathology ; Cardiovascular Diseases/pathology/metabolism ; Endothelial Cells/metabolism/pathology ; Cells, Cultured ; }, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects not only the joints but also has significant cardiovascular (CV) manifestations. The mechanistic interplay between RA and cardiovascular complications is not yet well understood due to the lack of relevant in vitro models. In this study, we established RA cardiac microtisses (cMTs) from iPSC-derived cardiomyocytes (CMs), endothelial cells (ECs) and cardiac fibroblasts (CFs) to investigate whether this fully human 3D multicellular system could serve as a platform to elucidate the connection between RA and CV disorders.

METHODS: PBMC and FLS from healthy and RA donors were reprogrammed to hiPSCs with Sendai vectors. hiPSCs pluripotency was assessed by IF, FACS, spontaneous embryoid bodies formation and teratoma assay. hiPSCs were differentiated to cardiac derivatives such as CMs, ECs and CFs, followed by cell markers characterizations (IF, FACS, qRT-PCR) and functional assessments. 3D cMTs were generated by aggregation of 70% CMs, 15% ECs and 15% CFs. After 21 days in culture, structural and metabolic properties of 3D cMTs were examined by IF, qRT-PCR and Seahorse bioanalyzer.

RESULTS: hiPSCs demonstrated typical colony-like morphology, normal karyotype, presence of pluripotency markers, and ability to differentiate into cells originating from all three germ layers. hiPSC-CMs showed spontaneous beating and expression of cardiac markers (cTnT, MYL7, NKX2.5, MYH7). hiPSC-ECs formed sprouting spheres and tubes and expressed CD31 and CD144. hiPSC-CFs presented spindle-shaped morphology and expression of vimentin, collagen 1 and DDR2. Self-aggregation of CMs/ECs/CFs allowed development of contracting 3D cMTs, demonstrating spherical organization of the cells, which partially resembled the cardiac muscle, both in structure and function. IF analysis confirmed the expression of cTnT, CD31, CD144 and DDR2 in generated 3D cMTs. RA cMTs exhibited significantly greater formation of capillary-like structures, mimicking enhanced vascularization-key RA feature-compared to control cMTs. Seahorse examination of cMTs revealed changes in mitochondrial and glycolytic rates in the presence of metabolic substrates and inhibitors.

CONCLUSIONS: The cMTs model may represent an advanced human stem cell-based platform for modeling CV complications in RA. The highly developed capillary-like structures observed within RA cMTs highlight a critical feature of inflammation-induced CV dysfunction in chronic inflammatory diseases.}, } @article {pmid39465534, year = {2024}, author = {Erard, M and Favard, C and Lavis, LD and Recher, G and Rigneault, H and Sage, D}, title = {Back to the future - 20 years of progress and developments in photonic microscopy and biological imaging.}, journal = {Journal of cell science}, volume = {137}, number = {20}, pages = {}, doi = {10.1242/jcs.262344}, pmid = {39465534}, issn = {1477-9137}, mesh = {Animals ; Humans ; *Microscopy/history/instrumentation/methods/trends ; *Photons ; History, 21st Century ; }, abstract = {In 2023, the ImaBio consortium (imabio-cnrs.fr), an interdisciplinary life microscopy research group at the Centre National de la Recherche Scientifique, celebrated its 20th anniversary. ImaBio contributes to the biological imaging community through organization of MiFoBio conferences, which are interdisciplinary conferences featuring lectures and hands-on workshops that attract specialists from around the world. MiFoBio conferences provide the community with an opportunity to reflect on the evolution of the field, and the 2023 event offered retrospective talks discussing the past 20 years of topics in microscopy, including imaging of multicellular assemblies, image analysis, quantification of molecular motions and interactions within cells, advancements in fluorescent labels, and laser technology for multiphoton and label-free imaging of thick biological samples. In this Perspective, we compile summaries of these presentations overviewing 20 years of advancements in a specific area of microscopy, each of which concludes with a brief look towards the future. The full presentations are available on the ImaBio YouTube channel (youtube.com/@gdrimabio5724).}, } @article {pmid39460541, year = {2024}, author = {Symonds, K and Wali, U and Duff, L and Snedden, WA}, title = {Characterization of the Calmodulin-Like Protein Family in Chara braunii and their Conserved Interaction with the Calmodulin-Binding Transcription Activator Family.}, journal = {Plant & cell physiology}, volume = {65}, number = {12}, pages = {2040-2053}, pmid = {39460541}, issn = {1471-9053}, support = {RGPIN-2018-04928, RGPIN-2017-04551//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {*Calmodulin/metabolism/genetics ; *Plant Proteins/metabolism/genetics ; *Calcium/metabolism ; *Chara/metabolism/genetics ; Phylogeny ; Amino Acid Sequence ; Protein Binding ; Calmodulin-Binding Proteins/metabolism/genetics ; Protein Isoforms/metabolism/genetics ; }, abstract = {Calcium sensor proteins play important roles by detecting changes in intracellular calcium and relaying that information onto downstream targets through protein-protein interaction. Very little is known about calcium sensors from plant species that predate land colonization and the evolution of embryophytes. Here, we examined the genome of the multicellular algae, Chara braunii, for orthologs to the evolutionarily conserved calcium sensor calmodulin (CaM) and for CaM-like (CML) proteins. We identified one CaM and eight CML isoforms that range in size from 16.4 to 21.3 kDa and are predicted to have between two to four calcium-binding (EF-hand) domains. Using recombinant protein, we tested whether CbCaM and CbCML1-CbCML7 possess biochemical properties of typical calcium sensors. CbCaM and the CbCMLs all displayed high-affinity calcium binding with estimated global KD,app values in the physiological µM range. In response to calcium binding, CbCaM and the CbCMLs exhibited varying degrees of increase in exposed hydrophobicity, suggesting that different calcium-induced conformational changes occur among isoforms. We found many examples of putative CaM targets encoded in the C. braunii genome and explored the ability of CbCaM and CbCMLs to interact in planta with a representative putative target, a C. braunii CaM-binding transcription factor (CbCAMTA1). CbCaM, CbCML2 and CbCML4 each associated with the C-terminal region of CbCAMTA1. Collectively, our data support the hypothesis that complex calcium signaling and sensing networks involving CaM and CMLs evolved early in the green lineage. Similarly, it seems likely that calcium-mediated regulation of transcription occurs in C. braunii via CAMTAs and is an ancient trait predating embryophytic emergence.}, } @article {pmid39447574, year = {2024}, author = {Dierschke, T and Levins, J and Lampugnani, ER and Ebert, B and Zachgo, S and Bowman, JL}, title = {Control of sporophyte secondary cell wall development in Marchantia by a Class II KNOX gene.}, journal = {Current biology : CB}, volume = {34}, number = {22}, pages = {5213-5222.e5}, doi = {10.1016/j.cub.2024.09.061}, pmid = {39447574}, issn = {1879-0445}, mesh = {*Cell Wall/metabolism/genetics ; *Marchantia/genetics/growth & development ; *Plant Proteins/genetics/metabolism ; Gene Expression Regulation, Plant ; Germ Cells, Plant/growth & development/metabolism ; }, abstract = {Land plants evolved from an ancestral alga around 470 mya, evolving complex multicellularity in both haploid gametophyte and diploid sporophyte generations. The evolution of water-conducting tissues in the sporophyte generation was crucial for the success of land plants, paving the way for the colonization of a variety of terrestrial habitats. Class II KNOX (KNOX2) genes are major regulators of secondary cell wall formation and seed mucilage (pectin) deposition in flowering plants. Here, we show that, in the liverwort Marchantia polymorpha, loss-of-function alleles of the KNOX2 ortholog, MpKNOX2, or its dimerization partner, MpBELL1, have defects in capsule wall secondary cell wall and spore pectin biosynthesis. Both genes are expressed in the gametophytic calyptra surrounding the sporophyte and exert maternal effects, suggesting intergenerational regulation from the maternal gametophyte to the sporophytic embryo. These findings also suggest the presence of a secondary wall genetic program in the non-vascular liverwort capsule wall, with attributes of secondary walls in vascular tissues.}, } @article {pmid39445720, year = {2025}, author = {Compton, ZT and Mellon, W and Harris, VK and Rupp, S and Mallo, D and Kapsetaki, SE and Wilmot, M and Kennington, R and Noble, K and Baciu, C and Ramirez, LN and Peraza, A and Martins, B and Sudhakar, S and Aksoy, S and Furukawa, G and Vincze, O and Giraudeau, M and Duke, EG and Spiro, S and Flach, E and Davidson, H and Li, CI and Zehnder, A and Graham, TA and Troan, BV and Harrison, TM and Tollis, M and Schiffman, JD and Aktipis, CA and Abegglen, LM and Maley, CC and Boddy, AM}, title = {Cancer Prevalence across Vertebrates.}, journal = {Cancer discovery}, volume = {15}, number = {1}, pages = {227-244}, pmid = {39445720}, issn = {2159-8290}, support = {T32 CA272303/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; OTKA K143421//Agence Nationale de la Recherche (ANR)/ ; COVER ANR-23-CE02-0019//Agence Nationale de la Recherche (ANR)/ ; U54 CA217376/CA/NCI NIH HHS/United States ; ADHS18-198847//Arizona Biomedical Research Commission (ABRC)/ ; U2C CA233254/CA/NCI NIH HHS/United States ; //Hyundai Hope On Wheels (Hope On Wheels)/ ; BC132057//Congressionally Directed Medical Research Programs (CDMRP)/ ; R01 CA140657/CA/NCI NIH HHS/United States ; R21 CA257980/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Neoplasms/epidemiology/genetics/veterinary ; Prevalence ; *Vertebrates ; Humans ; }, abstract = {Cancer is pervasive across multicellular species, but what explains the differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades of tetrapods (amphibians, sauropsids, and mammals), we found that neoplasia and malignancy prevalence increases with adult mass (contrary to Peto's paradox) and somatic mutation rate but decreases with gestation time. The relationship between adult mass and malignancy prevalence was only apparent when we controlled for gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%), the black-footed penguin (<0.4%), ferrets (63%), and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer. Significance: Evolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records, we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes. See related commentary by Metzger, p. 14.}, } @article {pmid39445133, year = {2024}, author = {Lee, SH and Dubey, N and Jeon, J}, title = {The Unknown within the Known: Nucleolus, Understudied Compartment in the Filamentous Fungi.}, journal = {Mycobiology}, volume = {52}, number = {4}, pages = {214-221}, pmid = {39445133}, issn = {1229-8093}, abstract = {Nucleolus is the most conspicuous sub-nuclear compartment that is well known as the site of RNA polymerase I-mediated rDNA transcription and assembly of ribosome subunits in eukaryotes. Recent studies on mammalian cells suggest that functions of nucleolus are not limited to ribosome biogenesis, and that nucleolus is involved in a diverse array of nuclear and cellular processes such as DNA repair, stress responses, and protein sequestration. In fungi, knowledge of nucleolus and its functions was primarily gleaned from the budding yeast. However, little is known about nucleolus of the filamentous fungi. Considering that the filamentous fungi are multi-cellular eukaryotes and thus distinct from the yeast in many aspects, researches on nucleoli of filamentous fungi would have the potential to uncover the evolution of nucleolus and its roles in the diverse cellular processes. Here we provide a brief up-to-date overview of nucleolus in general, and evidence suggesting their roles in fungal physiology and development.}, } @article {pmid39443791, year = {2024}, author = {Lotharukpong, JS and Zheng, M and Luthringer, R and Liesner, D and Drost, HG and Coelho, SM}, title = {A transcriptomic hourglass in brown algae.}, journal = {Nature}, volume = {635}, number = {8037}, pages = {129-135}, pmid = {39443791}, issn = {1476-4687}, mesh = {Animals ; Cell Differentiation/genetics ; Embryonic Development ; Evolution, Molecular ; Fungi/growth & development ; Gene Expression Profiling ; *Life Cycle Stages/genetics ; *Phaeophyceae/cytology/genetics/growth & development ; Phylogeny ; Plant Development ; Time Factors ; *Transcriptome/genetics ; }, abstract = {Complex multicellularity has emerged independently across a few eukaryotic lineages and is often associated with the rise of elaborate, tightly coordinated developmental processes[1,2]. How multicellularity and development are interconnected in evolution is a major question in biology. The hourglass model of embryonic evolution depicts how developmental processes are conserved during evolution, and predicts morphological and molecular divergence in early and late embryogenesis, bridged by a conserved mid-embryonic (phylotypic) period linked to the formation of the basic body plan[3,4]. Initially found in animal embryos[5-8], molecular hourglass patterns have recently been proposed for land plants and fungi[9,10]. However, whether the hourglass pattern is an intrinsic feature of all complex multicellular eukaryotes remains unknown. Here we tested the presence of a molecular hourglass in the brown algae, a eukaryotic lineage that has evolved multicellularity independently from animals, fungi and plants[1,11,12]. By exploring transcriptome evolution patterns of brown algae with distinct morphological complexities, we uncovered an hourglass pattern during embryogenesis in morphologically complex species. Filamentous algae without canonical embryogenesis display transcriptome conservation in multicellular stages of the life cycle, whereas unicellular stages are more rapidly evolving. Our findings suggest that transcriptome conservation in brown algae is associated with cell differentiation stages, but is not necessarily linked to embryogenesis. Together with previous work in animals, plants and fungi, we provide further evidence for the generality of a developmental hourglass pattern across complex multicellular eukaryotes.}, } @article {pmid39441990, year = {2024}, author = {Uppal, S and Waterworth, SC and Nick, A and Vogel, H and Flórez, LV and Kaltenpoth, M and Kwan, JC}, title = {Repeated horizontal acquisition of lagriamide-producing symbionts in Lagriinae beetles.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {39441990}, issn = {1751-7370}, support = {ERC CoG 819585//European Research Council through an ERC Consolidator/ ; 1845890//National Science Foundation/ ; }, mesh = {Animals ; *Symbiosis ; *Coleoptera/microbiology ; *Burkholderia/genetics/metabolism/classification/physiology ; Phylogeny ; Metagenomics ; Genome, Bacterial ; Gene Transfer, Horizontal ; }, abstract = {Microbial symbionts associate with multicellular organisms on a continuum from facultative associations to mutual codependency. In the oldest intracellular symbioses there is exclusive vertical symbiont transmission, and co-diversification of symbiotic partners over millions of years. Such symbionts often undergo genome reduction due to low effective population sizes, frequent population bottlenecks, and reduced purifying selection. Here, we describe multiple independent acquisition events of closely related defensive symbionts followed by genome erosion in a group of Lagriinae beetles. Previous work in Lagria villosa revealed the dominant genome-eroded symbiont of the genus Burkholderia produces the antifungal compound lagriamide, protecting the beetle's eggs and larvae from antagonistic fungi. Here, we use metagenomics to assemble 11 additional genomes of lagriamide-producing symbionts from 7 different host species within Lagriinae from 5 countries, to unravel the evolutionary history of this symbiotic relationship. In each host, we detected one dominant genome-eroded Burkholderia symbiont encoding the lagriamide biosynthetic gene cluster. However, we did not find evidence for host-symbiont co-diversification or for monophyly of the lagriamide-producing symbionts. Instead, our analyses support a single ancestral acquisition of the gene cluster followed by at least four independent symbiont acquisitions and subsequent genome erosion in each lineage. By contrast, a clade of plant-associated relatives retained large genomes but secondarily lost the lagriamide gene cluster. Our results, therefore, reveal a dynamic evolutionary history with multiple independent symbiont acquisitions characterized by a high degree of specificity and highlight the importance of the specialized metabolite lagriamide for the establishment and maintenance of this defensive symbiosis.}, } @article {pmid39431545, year = {2024}, author = {Usmanova, DR and Plata, G and Vitkup, D}, title = {Functional Optimization in Distinct Tissues and Conditions Constrains the Rate of Protein Evolution.}, journal = {Molecular biology and evolution}, volume = {41}, number = {10}, pages = {}, pmid = {39431545}, issn = {1537-1719}, support = {R01 MH124923/MH/NIMH NIH HHS/United States ; R35 GM131884/GM/NIGMS NIH HHS/United States ; R35GM131884/GM/NIGMS NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; Animals ; Proteins/genetics/metabolism ; Humans ; }, abstract = {Understanding the main determinants of protein evolution is a fundamental challenge in biology. Despite many decades of active research, the molecular and cellular mechanisms underlying the substantial variability of evolutionary rates across cellular proteins are not currently well understood. It also remains unclear how protein molecular function is optimized in the context of multicellular species and why many proteins, such as enzymes, are only moderately efficient on average. Our analysis of genomics and functional datasets reveals in multiple organisms a strong inverse relationship between the optimality of protein molecular function and the rate of protein evolution. Furthermore, we find that highly expressed proteins tend to be substantially more functionally optimized. These results suggest that cellular expression costs lead to more pronounced functional optimization of abundant proteins and that the purifying selection to maintain high levels of functional optimality significantly slows protein evolution. We observe that in multicellular species both the rate of protein evolution and the degree of protein functional efficiency are primarily affected by expression in several distinct cell types and tissues, specifically, in developed neurons with upregulated synaptic processes in animals and in young and fast-growing tissues in plants. Overall, our analysis reveals how various constraints from the molecular, cellular, and species' levels of biological organization jointly affect the rate of protein evolution and the level of protein functional adaptation.}, } @article {pmid39427812, year = {2024}, author = {Dvořáček, J and Kodrík, D}, title = {Brain and cognition: The need for a broader biological perspective to overcome old biases.}, journal = {Neuroscience and biobehavioral reviews}, volume = {167}, number = {}, pages = {105928}, doi = {10.1016/j.neubiorev.2024.105928}, pmid = {39427812}, issn = {1873-7528}, mesh = {*Cognition/physiology ; *Brain/physiology ; Animals ; Humans ; *Biological Evolution ; Neurons/physiology ; Intelligence/physiology ; }, abstract = {Even with accumulating knowledge, no consensus regarding the understanding of intelligence or cognition exists, and the universal brain bases for these functions remain unclear. Traditionally, our understanding of cognition is based on self-evident principles that appear indisputable when looking only at our species; however, this can distance us from understanding its essence (anthropocentrism, corticocentrism, intellectocentrism, neurocentrism, and idea of orthogenesis of brain evolution). Herein, we use several examples from biology to demonstrate the usefulness of comparative ways of thinking in relativizing these biases. We discuss the relationship between the number of neurons and cognition and draw attention to the highly developed cognitive performance of animals with small brains, to some "tricks" of evolution, to how animals cope with small hardware, to some animals with high-quality brains with an alternative architecture to vertebrates, and to surprising basal cognitive skills in aneural, unicellular organisms. Cognition can be supplemented by the idea of a multicellular organism as a continuum, with many levels of cognitive function, including the possible basal learning in single cells.}, } @article {pmid39414948, year = {2025}, author = {Laisné, M and Lupien, M and Vallot, C}, title = {Epigenomic heterogeneity as a source of tumour evolution.}, journal = {Nature reviews. Cancer}, volume = {25}, number = {1}, pages = {7-26}, pmid = {39414948}, issn = {1474-1768}, mesh = {Animals ; Humans ; *Epigenesis, Genetic ; *Genetic Heterogeneity ; *Neoplasms/genetics/pathology ; }, abstract = {In the past decade, remarkable progress in cancer medicine has been achieved by the development of treatments that target DNA sequence variants. However, a purely genetic approach to treatment selection is hampered by the fact that diverse cell states can emerge from the same genotype. In multicellular organisms, cell-state heterogeneity is driven by epigenetic processes that regulate DNA-based functions such as transcription; disruption of these processes is a hallmark of cancer that enables the emergence of defective cell states. Advances in single-cell technologies have unlocked our ability to quantify the epigenomic heterogeneity of tumours and understand its mechanisms, thereby transforming our appreciation of how epigenomic changes drive cancer evolution. This Review explores the idea that epigenomic heterogeneity and plasticity act as a reservoir of cell states and therefore as a source of tumour evolution. Best practices to quantify epigenomic heterogeneity and explore its various causes and consequences are discussed, including epigenomic reprogramming, stochastic changes and lasting memory. The design of new therapeutic approaches to restrict epigenomic heterogeneity, with the long-term objective of limiting cancer development and progression, is also addressed.}, } @article {pmid39390408, year = {2024}, author = {Mazéas, L and Bouguerba-Collin, A and Cock, JM and Denoeud, F and Godfroy, O and Brillet-Guéguen, L and Barbeyron, T and Lipinska, AP and Delage, L and Corre, E and Drula, E and Henrissat, B and Czjzek, M and Terrapon, N and Hervé, C}, title = {Candidate genes involved in biosynthesis and degradation of the main extracellular matrix polysaccharides of brown algae and their probable evolutionary history.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {950}, pmid = {39390408}, issn = {1471-2164}, support = {ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-10-INBS-09//Agence Nationale de la Recherche/ ; ANR-10-INBS-09//Agence Nationale de la Recherche/ ; ANR-11-INBS-0013//Agence Nationale de la Recherche/ ; ANR-11-INBS-0013//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-11-INBS-0013//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; ANR-20-CE44-0011//Agence Nationale de la Recherche/ ; 638240/ERC_/European Research Council/International ; }, mesh = {*Phaeophyceae/genetics/metabolism ; *Phylogeny ; *Polysaccharides/biosynthesis/metabolism ; *Extracellular Matrix/metabolism ; *Evolution, Molecular ; Alginates/metabolism ; Genomics/methods ; }, abstract = {BACKGROUND: Brown algae belong to the Stramenopiles phylum and are phylogenetically distant from plants and other multicellular organisms. This independent evolutionary history has shaped brown algae with numerous metabolic characteristics specific to this group, including the synthesis of peculiar polysaccharides contained in their extracellular matrix (ECM). Alginates and fucose-containing sulphated polysaccharides (FCSPs), the latter including fucans, are the main components of ECMs. However, the metabolic pathways of these polysaccharides remain poorly described due to a lack of genomic data.

RESULTS: An extensive genomic dataset has been recently released for brown algae and their close sister species, for which we previously performed an expert annotation of key genes involved in ECM-carbohydrate metabolisms. Here we provide a deeper analysis of this set of genes using comparative genomics, phylogenetics analyses, and protein modelling. Two key gene families involved in both the synthesis and degradation of alginate were suggested to have been acquired by the common ancestor of brown algae and their closest sister species Schizocladia ischiensis. Our analysis indicates that this assumption can be extended to additional metabolic steps, and thus to the whole alginate metabolic pathway. The pathway for the biosynthesis of fucans still remains biochemically unresolved and we also investigate putative fucosyltransferase genes that may harbour a fucan synthase activity in brown algae.

CONCLUSIONS: Our analysis is the first extensive survey of carbohydrate-related enzymes in brown algae, and provides a valuable resource for future research into the glycome and ECM of brown algae. The expansion of specific families related to alginate metabolism may have represented an important prerequisite for the evolution of developmental complexity in brown algae. Our analysis questions the possible occurrence of FCSPs outside brown algae, notably within their closest sister taxon and in other Stramenopiles such as diatoms. Filling this knowledge gap in the future will help determine the origin and evolutionary history of fucan synthesis in eukaryotes.}, } @article {pmid39381908, year = {2024}, author = {Staps, M and Tarnita, CE and Kawakatsu, M}, title = {Ecological principles for the evolution of communication in collective systems.}, journal = {Proceedings. Biological sciences}, volume = {291}, number = {2032}, pages = {20241562}, pmid = {39381908}, issn = {1471-2954}, support = {//James S. McDonnell Foundation/ ; }, mesh = {Animals ; *Animal Communication ; *Biological Evolution ; Bees/physiology ; Ants/physiology ; Models, Biological ; Social Behavior ; }, abstract = {Communication allows members of a collective to share information about their environment. Advanced collective systems, such as multicellular organisms and social insect colonies, vary in whether they use communication at all and, if they do, in what types of signals they use, but the origins of these differences are poorly understood. Here, we develop a theoretical framework to investigate the evolution and diversity of communication strategies under collective-level selection. We find that whether communication can evolve depends on a collective's external environment: communication only evolves in sufficiently stable environments, where the costs of sensing are high enough to disfavour independent sensing but not so high that the optimal strategy is to ignore the environment altogether. Moreover, we find that the evolution of diverse signalling strategies-including those relying on prolonged signalling (e.g. honeybee waggle dance), persistence of signals in the environment (e.g. ant trail pheromones) and brief but frequent communicative interactions (e.g. ant antennal contacts)-can be explained theoretically in terms of the interplay between the demands of the environment and internal constraints on the signal. Altogether, we provide a general framework for comparing communication strategies found in nature and uncover simple ecological principles that may contribute to their diversity.}, } @article {pmid39378102, year = {2025}, author = {Laporte, D and Sagot, I}, title = {Microtubule Reorganization and Quiescence: an Intertwined Relationship.}, journal = {Physiology (Bethesda, Md.)}, volume = {40}, number = {2}, pages = {0}, doi = {10.1152/physiol.00036.2024}, pmid = {39378102}, issn = {1548-9221}, support = {ANR-21-CE13-0023-01//Agence Nationale de la Recherche (ANR)/ ; }, mesh = {*Microtubules/metabolism ; Humans ; Animals ; Cell Proliferation/physiology ; }, abstract = {Quiescence is operationally defined as a reversible proliferation arrest. This cellular state is central to both organism development and homeostasis, and its dysregulation causes many pathologies. The quiescent state encompasses very diverse cellular situations depending on the cell type and its environment. Further, quiescent cell properties evolve with time, a process that is thought to be the origin of aging in multicellular organisms. Microtubules are found in all eukaryotes and are essential for cell proliferation as they support chromosome segregation and intracellular trafficking. Upon proliferation cessation and quiescence establishment, the microtubule cytoskeleton was shown to undergo significant remodeling. The purpose of this review is to examine the literature in search of evidence to determine whether the observed microtubule reorganizations are merely a consequence of quiescence establishment or if they somehow participate in this cell fate decision.}, } @article {pmid39373528, year = {2024}, author = {Ros-Rocher, N}, title = {The evolution of multicellularity and cell differentiation symposium: bridging evolutionary cell biology and computational modelling using emerging model systems.}, journal = {Biology open}, volume = {13}, number = {10}, pages = {}, pmid = {39373528}, issn = {2046-6390}, support = {101106415//European Union's Horizon Europe research and innovation funding program/ ; //Institute Pasteur: Institut Pasteur; Baylor College of Medicine/ ; }, mesh = {*Cell Differentiation/genetics ; *Biological Evolution ; Animals ; Computational Biology/methods ; Humans ; Cell Biology ; Models, Biological ; Computer Simulation ; Genomics/methods ; }, abstract = {'The evolution of multicellularity and cell differentiation' symposium, organized as part of the EuroEvoDevo 2024 meeting on June 25-28th in Helsinki (Finland), addressed recent advances on the molecular and mechanistic basis for the evolution of multicellularity and cell differentiation in eukaryotes. The symposium involved over 100 participants and brought together 10 speakers at diverse career stages. Talks covered various topics at the interface of developmental biology, evolutionary cell biology, comparative genomics, computational biology, and ecology using animal, protist, algal and mathematical models. This symposium offered a unique opportunity for interdisciplinary dialog among researchers working on different systems, especially in promoting collaborations and aligning strategies for studying emerging model species. Moreover, it fostered opportunities to promote early career researchers in the field and opened discussions of ongoing work and unpublished results. In this Meeting Review, we aim to promote the research, capture the spirit of the meeting, and present key topics discussed within this dynamic, growing and open community.}, } @article {pmid39366767, year = {2024}, author = {Mazur-Marzec, H and Andersson, AF and Błaszczyk, A and Dąbek, P and Górecka, E and Grabski, M and Jankowska, K and Jurczak-Kurek, A and Kaczorowska, AK and Kaczorowski, T and Karlson, B and Kataržytė, M and Kobos, J and Kotlarska, E and Krawczyk, B and Łuczkiewicz, A and Piwosz, K and Rybak, B and Rychert, K and Sjöqvist, C and Surosz, W and Szymczycha, B and Toruńska-Sitarz, A and Węgrzyn, G and Witkowski, A and Węgrzyn, A}, title = {Biodiversity of microorganisms in the Baltic Sea: the power of novel methods in the identification of marine microbes.}, journal = {FEMS microbiology reviews}, volume = {48}, number = {5}, pages = {}, pmid = {39366767}, issn = {1574-6976}, support = {2021/03/Y/NZ8/00076//National Science Centre/ ; 2021-05563//Swedish Research Council/ ; }, mesh = {*Biodiversity ; *Seawater/microbiology ; *Oceans and Seas ; *Bacteria/classification/genetics/isolation & purification ; Microbiota/genetics ; Fungi/classification/genetics/isolation & purification ; }, abstract = {Until recently, the data on the diversity of the entire microbial community from the Baltic Sea were relatively rare and very scarce. However, modern molecular methods have provided new insights into this field with interesting results. They can be summarized as follows. (i) Although low salinity causes a reduction in the biodiversity of multicellular species relative to the populations of the North-East Atlantic, no such reduction occurs in bacterial diversity. (ii) Among cyanobacteria, the picocyanobacterial group dominates when considering gene abundance, while filamentous cyanobacteria dominate in means of biomass. (iii) The diversity of diatoms and dinoflagellates is significantly larger than described a few decades ago; however, molecular studies on these groups are still scarce. (iv) Knowledge gaps in other protistan communities are evident. (v) Salinity is the main limiting parameter of pelagic fungal community composition, while the benthic fungal diversity is shaped by water depth, salinity, and sediment C and N availability. (vi) Bacteriophages are the predominant group of viruses, while among viruses infecting eukaryotic hosts, Phycodnaviridae are the most abundant; the Baltic Sea virome is contaminated with viruses originating from urban and/or industrial habitats. These features make the Baltic Sea microbiome specific and unique among other marine environments.}, } @article {pmid39366961, year = {2024}, author = {Jin, M and Li, W and Ji, Z and Di, G and Yuan, M and Zhang, Y and Kang, Y and Zhao, C}, title = {Coordinated cellular behavior regulated by epinephrine neurotransmitters in the nerveless placozoa.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8626}, pmid = {39366961}, issn = {2041-1723}, support = {Nos. 32125015//National Natural Science Foundation of China (National Science Foundation of China)/ ; Nos. 31991194//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32200415//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {*Epinephrine/pharmacology/metabolism ; Animals ; *Placozoa/metabolism ; *Neurotransmitter Agents/metabolism ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Signal Transduction/drug effects ; Cilia/metabolism/drug effects ; Calcium Signaling/drug effects ; Cell Communication/drug effects ; Humans ; }, abstract = {Understanding how cells communicated before the evolution of nervous systems in early metazoans is key to unraveling the origins of multicellular life. We focused on Trichoplax adhaerens, one of the earliest multicellular animals, to explore this question. Through screening a small compound library targeting G protein-coupled receptors (GPCRs), we found that Trichoplax exhibits distinctive rotational movements when exposed to epinephrine. Further studies suggested that, akin to those in humans, this basal organism also utilizes adrenergic signals to regulate its negative taxis behavior, with the downstream signaling pathway being more straightforward and efficient. Mechanistically, the binding of ligands activates downstream calcium signaling, subsequently modulating ciliary redox signals. This process ultimately regulates the beating direction of cilia, governing the coordinated movement of the organism. Our findings not only highlight the enduring presence of adrenergic signaling in stress responses during evolution but also underscore the importance of early metazoan expansion of GPCR families. This amplification empowers us with the ability to sense external cues and modulate cellular communication effectively.}, } @article {pmid39345370, year = {2024}, author = {Leon, F and Espinoza-Esparza, JM and Deng, V and Coyle, MC and Espinoza, S and Booth, DS}, title = {Cell differentiation controls iron assimilation in a choanoflagellate.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39345370}, issn = {2692-8205}, support = {R35 GM147404/GM/NIGMS NIH HHS/United States ; S10 OD018174/OD/NIH HHS/United States ; T32 GM139786/GM/NIGMS NIH HHS/United States ; }, abstract = {Marine microeukaryotes have evolved diverse cellular features that link their life histories to surrounding environments. How those dynamic life histories intersect with the ecological functions of microeukaryotes remains a frontier to understand their roles in essential biogeochemical cycles[1,2]. Choanoflagellates, phagotrophs that cycle nutrients through filter feeding, provide models to explore this intersection, for many choanoflagellate species transition between life history stages by differentiating into distinct cell types[3-6]. Here we report that cell differentiation in the marine choanoflagellate Salpingoeca rosetta endows one of its cell types with the ability to utilize insoluble ferric colloids for improved growth through the expression of a cytochrome b561 iron reductase (cytb561a). This gene is an ortholog of the mammalian duodenal cytochrome b561 (DCYTB) that reduces ferric cations prior to their uptake in gut epithelia[7] and is part of an iron utilization toolkit that choanoflagellates and their closest living relatives, the animals, inherited from a last common eukaryotic ancestor. In a database of oceanic metagenomes[8,9], the abundance of cytb561a transcripts from choanoflagellates positively correlates with upwellings, which are a major source of ferric colloids in marine environments[10]. As this predominant form of iron[11,12] is largely inaccessible to cell-walled microbes[13,14], choanoflagellates and other phagotrophic eukaryotes may serve critical ecological roles by first acquiring ferric colloids through phagocytosis and then cycling this essential nutrient through iron utilization pathways[13-15]. These findings provide insight into the ecological roles choanoflagellates perform and inform reconstructions of early animal evolution where functionally distinct cell types became an integrated whole at the origin of animal multicellularity[16-22].}, } @article {pmid39345214, year = {2024}, author = {Mathieu, J and Huynh, JR}, title = {Incomplete divisions between sister germline cells require Usp8 function.}, journal = {Comptes rendus biologies}, volume = {347}, number = {}, pages = {109-117}, doi = {10.5802/crbiol.161}, pmid = {39345214}, issn = {1768-3238}, mesh = {*Germ Cells ; Animals ; Cell Division ; Endosomal Sorting Complexes Required for Transport/genetics ; Humans ; Ubiquitin Thiolesterase/genetics/metabolism ; }, abstract = {Cytokinetic abscission is the final step of cell division, resulting in two separate daughter cells. While abscission is typically complete across most cell types, germline cells, which produce sexual gametes, do not finish cytokinesis, maintaining connections between sister cells. These connections are essential for sharing cytoplasm as they differentiate into oocyte and sperm. First, we outline the molecular events of cytokinesis during both complete and delayed abscission, highlighting the role of the ESCRT-III proteins. We then focus on recent discoveries that reveal the molecular mechanisms blocking abscission in Drosophila germline cells. The enzyme Usp8 was identified as vital for ensuring incomplete cytokinesis through the regulation of ESCRT-III ubiquitination and localization. Finally, we explore how the processes of incomplete cytokinesis could hold evolutionary importance, suggesting additional studies into choanoflagellates to comprehend the origins of multicellularity.}, } @article {pmid39343888, year = {2024}, author = {Ahmad, F and Abdullah, M and Khan, Z and Stępień, P and Rehman, SU and Akram, U and Rahman, MHU and Ali, Z and Ahmad, D and Gulzar, RMA and Ali, MA and Salama, EAA}, title = {Genome-wide analysis and prediction of chloroplast and mitochondrial RNA editing sites of AGC gene family in cotton (Gossypium hirsutum L.) for abiotic stress tolerance.}, journal = {BMC plant biology}, volume = {24}, number = {1}, pages = {888}, pmid = {39343888}, issn = {1471-2229}, support = {32130075//National Natural Science Foundation of China/ ; 32130075//National Natural Science Foundation of China/ ; 32130075//National Natural Science Foundation of China/ ; 2021AB008, 2020CB003//Science Technology and Achievement Transformation Project of the Xinjiang Production and Construction Corps/ ; 2021AB008, 2020CB003//Science Technology and Achievement Transformation Project of the Xinjiang Production and Construction Corps/ ; 2021AB008, 2020CB003//Science Technology and Achievement Transformation Project of the Xinjiang Production and Construction Corps/ ; ADP-LO21002838 Punjab, Pak//ADP Funded Project entitled National Crop Genomics and Speed Breeding Center for Agri-cultural Sustainability/ ; ADP-LO21002838 Punjab, Pak//ADP Funded Project entitled National Crop Genomics and Speed Breeding Center for Agri-cultural Sustainability/ ; ADP-LO21002838 Punjab, Pak//ADP Funded Project entitled National Crop Genomics and Speed Breeding Center for Agri-cultural Sustainability/ ; ADP-LO21002838 Punjab, Pak//ADP Funded Project entitled National Crop Genomics and Speed Breeding Center for Agri-cultural Sustainability/ ; ADP-LO21002838 Punjab, Pak//ADP Funded Project entitled National Crop Genomics and Speed Breeding Center for Agri-cultural Sustainability/ ; RSP2024R306//King Saud University, Riyadh, Saudi Arabia/ ; }, mesh = {*Gossypium/genetics/physiology ; *RNA Editing/genetics ; *Stress, Physiological/genetics ; *Phylogeny ; *Chloroplasts/genetics ; Genome, Plant ; Mitochondria/genetics ; Plant Proteins/genetics/metabolism ; Multigene Family ; Genome-Wide Association Study ; Gene Expression Regulation, Plant ; RNA, Mitochondrial/genetics ; Genes, Plant ; }, abstract = {BACKGROUND: Cotton is one of the topmost fiber crops throughout the globe. During the last decade, abrupt changes in the climate resulted in drought, heat, and salinity. These stresses have seriously affected cotton production and significant losses all over the textile industry. The GhAGC kinase, a subfamily of AGC group and member of serine/threonine (Ser/Thr) protein kinases group and is highly conserved among eukaryotic organisms. The AGC kinases are compulsory elements of cell development, metabolic processes, and cell death in mammalian systems. The investigation of RNA editing sites within the organelle genomes of multicellular vascular plants, such as Gossypium hirsutum holds significant importance in understanding the regulation of gene expression at the post-transcriptional level.

METHODS: In present work, we characterized twenty-eight GhAGC genes in cotton and constructed phylogenetic tree using nine different species from the most primitive to the most recent.

RESULTS: In sequence logos analyses, highly conserved amino acid residues were found in G. hirsutum, G. arboretum, G. raimondii and A. thaliana. The occurrence of cis-acting growth and stress-related elements in the promoter regions of GhAGCs highlight the significance of these factors in plant development and abiotic stress tolerance. Ka/Ks levels demonstrated that purifying selection pressure resulting from segmental events was applied to GhAGC with little functional divergence. We focused on identifying RNA editing sites in G. hirsutum organelles, specifically in the chloroplast and mitochondria, across all 28 AGC genes.

CONCLUSION: The positive role of GhAGCs was explored by quantifying the expression in the plant tissues under abiotic stress. These findings help in understanding the role of GhAGC genes under abiotic stresses which may further be used in cotton breeding for the development of climate smart varieties in abruptly changing climate.}, } @article {pmid39341686, year = {2025}, author = {Kalita, AI and Keller Valsecchi, CI}, title = {Dosage compensation in non-model insects - progress and perspectives.}, journal = {Trends in genetics : TIG}, volume = {41}, number = {1}, pages = {76-98}, doi = {10.1016/j.tig.2024.08.010}, pmid = {39341686}, issn = {0168-9525}, mesh = {Animals ; *Dosage Compensation, Genetic ; *Insecta/genetics ; Sex Chromosomes/genetics ; Evolution, Molecular ; Drosophila melanogaster/genetics ; }, abstract = {In many multicellular eukaryotes, heteromorphic sex chromosomes are responsible for determining the sexual characteristics and reproductive functions of individuals. Sex chromosomes can cause a dosage imbalance between sexes, which in some species is re-equilibrated by dosage compensation (DC). Recent genomic advances have extended our understanding of DC mechanisms in insects beyond model organisms such as Drosophila melanogaster. We review current knowledge of insect DC, focusing on its conservation and divergence across orders, the evolutionary dynamics of neo-sex chromosomes, and the diversity of molecular mechanisms. We propose a framework to uncover DC regulators in non-model insects that relies on integrating evolutionary, genomic, and functional approaches. This comprehensive approach will facilitate a deeper understanding of the evolution and essentiality of gene regulatory mechanisms.}, } @article {pmid39302967, year = {2024}, author = {Zhang, H and Wang, X and Qu, M and Yu, H and Yin, J and Liu, X and Liu, Y and Zhang, B and Zhang, Y and Wei, Z and Yang, F and Wang, J and Shi, C and Fan, G and Sun, J and Long, L and Hutchins, DA and Bowler, C and Lin, S and Wang, D and Lin, Q}, title = {Genome of Halimeda opuntia reveals differentiation of subgenomes and molecular bases of multinucleation and calcification in algae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {39}, pages = {e2403222121}, pmid = {39302967}, issn = {1091-6490}, support = {2022YFC3102403//the National Key Research and Development Programm of China/ ; 42230409//the National Natural Science Foundation of China/ ; 4980.01//the Gordon and Betty Moore Foundation/ ; 42030404//the National Natural Science Foundation of China/ ; 42076155//the National Natural Science Foundation of China/ ; 42425004//the National Natural Science Foundation of China/ ; }, mesh = {*Calcification, Physiologic/genetics ; Chlorophyta/genetics/metabolism ; Phylogeny ; Genome, Plant ; Photosynthesis/genetics ; }, abstract = {Algae mostly occur either as unicellular (microalgae) or multicellular (macroalgae) species, both being uninucleate. There are important exceptions, however, as some unicellular algae are multinucleate and macroscopic, some of which inhabit tropical seas and contribute to biocalcification and coral reef robustness. The evolutionary mechanisms and ecological significance of multinucleation and associated traits (e.g., rapid wound healing) are poorly understood. Here, we report the genome of Halimeda opuntia, a giant multinucleate unicellular chlorophyte characterized by interutricular calcification. We achieve a high-quality genome assembly that shows segregation into four subgenomes, with evidence for polyploidization concomitant with historical sea level and climate changes. We further find myosin VIII missing in H. opuntia and three other unicellular multinucleate chlorophytes, suggesting a potential mechanism that may underpin multinucleation. Genome analysis provides clues about how the unicellular alga could survive fragmentation and regenerate, as well as potential signatures for extracellular calcification and the coupling of calcification with photosynthesis. In addition, proteomic alkalinity shifts were found to potentially confer plasticity of H. opuntia to ocean acidification (OA). Our study provides crucial genetic information necessary for understanding multinucleation, cell regeneration, plasticity to OA, and different modes of calcification in algae and other organisms, which has important implications in reef conservation and bioengineering.}, } @article {pmid39302848, year = {2024}, author = {Batista, RA and Wang, L and Bogaert, KA and Coelho, SM}, title = {Insights into the molecular bases of multicellular development from brown algae.}, journal = {Development (Cambridge, England)}, volume = {151}, number = {20}, pages = {}, doi = {10.1242/dev.203004}, pmid = {39302848}, issn = {1477-9129}, support = {//Max-Planck-Institut für Bildungsforschung/ ; 864038/ERC_/European Research Council/International ; //Gordon and Betty Moore Foundation/ ; //Fondation Bettencourt Schueller/ ; }, mesh = {*Phaeophyceae/genetics ; Biological Evolution ; }, abstract = {The transition from simple to complex multicellularity represents a major evolutionary step that occurred in only a few eukaryotic lineages. Comparative analyses of these lineages provide insights into the molecular and cellular mechanisms driving this transition, but limited understanding of the biology of some complex multicellular lineages, such as brown algae, has hampered progress. This Review explores how recent advances in genetic and genomic technologies now allow detailed investigations into the molecular bases of brown algae development. We highlight how forward genetic techniques have identified mutants that enhance our understanding of pattern formation and sexual differentiation in these organisms. Additionally, the existence and nature of morphogens in brown algae and the potential influence of the microbiome in key developmental processes are examined. Outstanding questions, such as the identity of master regulators, the definition and characterization of cell types, and the molecular bases of developmental plasticity are discussed, with insights into how recent technical advances could provide answers. Overall, this Review highlights how brown algae are emerging as alternative model organisms, contributing to our understanding of the evolution of multicellular life and the diversity of body plans.}, } @article {pmid39289870, year = {2024}, author = {Karin, O}, title = {EnhancerNet: a predictive model of cell identity dynamics through enhancer selection.}, journal = {Development (Cambridge, England)}, volume = {151}, number = {19}, pages = {}, pmid = {39289870}, issn = {1477-9129}, support = {//Imperial College London/ ; }, mesh = {*Enhancer Elements, Genetic/genetics ; *Cell Differentiation/genetics ; Animals ; *Transcription Factors/metabolism/genetics ; Chromatin/metabolism ; Cell Lineage/genetics ; Humans ; Models, Biological ; Models, Genetic ; }, abstract = {Understanding how cell identity is encoded by the genome and acquired during differentiation is a central challenge in cell biology. I have developed a theoretical framework called EnhancerNet, which models the regulation of cell identity through the lens of transcription factor-enhancer interactions. I demonstrate that autoregulation in these interactions imposes a constraint on the model, resulting in simplified dynamics that can be parameterized from observed cell identities. Despite its simplicity, EnhancerNet recapitulates a broad range of experimental observations on cell identity dynamics, including enhancer selection, cell fate induction, hierarchical differentiation through multipotent progenitor states and direct reprogramming by transcription factor overexpression. The model makes specific quantitative predictions, reproducing known reprogramming recipes and the complex haematopoietic differentiation hierarchy without fitting unobserved parameters. EnhancerNet provides insights into how new cell types could evolve and highlights the functional importance of distal regulatory elements with dynamic chromatin in multicellular evolution.}, } @article {pmid39288812, year = {2024}, author = {Castelli, M and Nardi, T and Giovannini, M and Sassera, D}, title = {Addictive manipulation: a perspective on the role of reproductive parasitism in the evolution of bacteria-eukaryote symbioses.}, journal = {Biology letters}, volume = {20}, number = {9}, pages = {20240310}, pmid = {39288812}, issn = {1744-957X}, mesh = {Animals ; *Arthropods/microbiology/physiology ; *Biological Evolution ; *Reproduction ; *Symbiosis/physiology ; Toxin-Antitoxin Systems/genetics ; *Wolbachia/physiology/genetics ; }, abstract = {Wolbachia bacteria encompass noteworthy reproductive manipulators of their arthropod hosts. which influence host reproduction to favour their own transmission, also exploiting toxin-antitoxin systems. Recently, multiple other bacterial symbionts of arthropods have been shown to display comparable manipulative capabilities. Here, we wonder whether such phenomena are truly restricted to arthropod hosts. We focused on protists, primary models for evolutionary investigations on eukaryotes due to their diversity and antiquity, but still overall under-investigated. After a thorough re-examination of the literature on bacterial-protist interactions with this question in mind, we conclude that such bacterial 'addictive manipulators' of protists do exist, are probably widespread, and have been overlooked until now as a consequence of the fact that investigations are commonly host-centred, thus ineffective to detect such behaviour. Additionally, we posit that toxin-antitoxin systems are crucial in these phenomena of addictive manipulation of protists, as a result of recurrent evolutionary repurposing. This indicates intriguing functional analogy and molecular homology with plasmid-bacterial interplays. Finally, we remark that multiple addictive manipulators are affiliated with specific bacterial lineages with ancient associations with diverse eukaryotes. This suggests a possible role of addictive manipulation of protists in paving the way to the evolution of bacteria associated with multicellular organisms.}, } @article {pmid39288797, year = {2024}, author = {Ågren, JA and Arnqvist, G and Rowe, L}, title = {The resolution of evolutionary conflicts within species.}, journal = {Proceedings. Biological sciences}, volume = {291}, number = {2031}, pages = {20241594}, pmid = {39288797}, issn = {1471-2954}, mesh = {*Biological Evolution ; Animals ; Population Dynamics ; Humans ; }, abstract = {Evolutionary conflicts of interest occur at all levels, scales and forms of biological organization. They are a fundamental component of the living world and range from conflicts between genetic elements and cells, to conflicts between the sexes and between competing individuals. Yet, the existence of admirably well functioning genomes, bodies, mating pairs and societies suggests that processes must exist to resolve or mitigate such conflicts. We organized this special feature 'The resolution of evolutionary conflicts within species' to encourage the flow of knowledge between fields that traditionally have often taken different approaches to study evolutionary conflicts. Contributed papers discuss data from bacteria, plants and animals (including humans) and present theory, molecular mechanisms and population dynamics of how conflicts are resolved in nature. Together, they contribute to a synthetic theory of conflict resolution.}, } @article {pmid39288541, year = {2024}, author = {Wen, T and Cheong, KH}, title = {Parrondo's paradox reveals counterintuitive wins in biology and decision making in society.}, journal = {Physics of life reviews}, volume = {51}, number = {}, pages = {33-59}, doi = {10.1016/j.plrev.2024.08.002}, pmid = {39288541}, issn = {1873-1457}, mesh = {Humans ; Animals ; *Decision Making ; Biological Evolution ; Ecosystem ; Biology ; }, abstract = {Parrondo's paradox refers to the paradoxical phenomenon of combining two losing strategies in a certain manner to obtain a winning outcome. It has been applied to uncover unexpected outcomes across various disciplines, particularly at different spatiotemporal scales within ecosystems. In this article, we provide a comprehensive review of recent developments in Parrondo's paradox within the interdisciplinary realm of the physics of life, focusing on its significant applications across biology and the broader life sciences. Specifically, we examine its relevance from genetic pathways and phenotypic regulation, to intercellular interaction within multicellular organisms, and finally to the competition between populations and species in ecosystems. This phenomenon, spanning multiple biological domains and scales, enhances our understanding of the unified characteristics of life and reveals that adaptability in a drastically changing environment, rather than the inherent excellence of a trait, underpins survival in the process of evolution. We conclude by summarizing our findings and discussing future research directions that hold promise for advancing the field.}, } @article {pmid39277710, year = {2024}, author = {Ueki, N and Wakabayashi, KI}, title = {Multicellularity and increasing Reynolds number impact on the evolutionary shift in flash-induced ciliary response in Volvocales.}, journal = {BMC ecology and evolution}, volume = {24}, number = {1}, pages = {119}, pmid = {39277710}, issn = {2730-7182}, mesh = {*Cilia/physiology ; *Biological Evolution ; Chlorophyta/physiology/genetics ; Volvox/genetics/physiology ; Light ; }, abstract = {BACKGROUND: Volvocales in green algae have evolved by multicellularity of Chlamydomonas-like unicellular ancestor. Those with various cell numbers exist, such as unicellular Chlamydomonas, four-celled Tetrabaena, and Volvox species with different cell numbers (~1,000, ~5,000, and ~10,000). Each cell of these organisms shares two cilia and an eyespot, which are used for swimming and photosensing. They are all freshwater microalgae but inhabit different fluid environments: unicellular species live in low Reynolds-number (Re) environments where viscous forces dominate, whereas multicellular species live in relatively higher Re where inertial forces become non-negligible. Despite significant changes in the physical environment, during the evolution of multicellularity, they maintained photobehaviors (i.e., photoshock and phototactic responses), which allows them to survive under changing light conditions.

RESULTS: In this study, we utilized high-speed imaging to observe flash-induced changes in the ciliary beating manner of 27 Volvocales strains. We classified flash-induced ciliary responses in Volvocales into four patterns: "1: temporal waveform conversion", "2: no obvious response", "3: pause in ciliary beating", and "4: temporal changes in ciliary beating directions". We found that which species exhibit which pattern depends on Re, which is associated with the individual size of each species rather than phylogenetic relationships.

CONCLUSIONS: These results suggest that only organisms that acquired different patterns of ciliary responses survived the evolutionary transition to multicellularity with a greater number of cells while maintaining photobehaviors. This study highlights the significance of the Re as a selection pressure in evolution and offers insights for designing propulsion systems in biomimetic micromachines.}, } @article {pmid39273111, year = {2024}, author = {Kasperski, A and Heng, HH}, title = {The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers.}, journal = {International journal of molecular sciences}, volume = {25}, number = {17}, pages = {}, pmid = {39273111}, issn = {1422-0067}, mesh = {*Neoplasms/genetics ; Humans ; *Chromosomal Instability ; Biological Evolution ; Animals ; Mutation ; Evolution, Molecular ; Epigenesis, Genetic ; Genomic Instability ; }, abstract = {If one must prioritize among the vast array of contributing factors to cancer evolution, environmental-stress-mediated chromosome instability (CIN) should easily surpass individual gene mutations. CIN leads to the emergence of genomically unstable life forms, enabling them to grow dominantly within the stable life form of the host. In contrast, stochastic gene mutations play a role in aiding the growth of the cancer population, with their importance depending on the initial emergence of the new system. Furthermore, many specific gene mutations among the many available can perform this function, decreasing the clinical value of any specific gene mutation. Since these unstable life forms can respond to treatment differently than stable ones, cancer often escapes from drug treatment by forming new systems, which leads to problems during the treatment for patients. To understand how diverse factors impact CIN-mediated macroevolution and genome integrity-ensured microevolution, the concept of two-phased cancer evolution is used to reconcile some major characteristics of cancer, such as bioenergetic, unicellular, and multicellular evolution. Specifically, the spiral of life function model is proposed, which integrates major historical evolutionary innovations and conservation with information management. Unlike normal organismal evolution in the microevolutionary phase, where a given species occupies a specific location within the spiral, cancer populations are highly heterogenous at multiple levels, including epigenetic levels. Individual cells occupy different levels and positions within the spiral, leading to supersystems of mixed cellular populations that exhibit both macro and microevolution. This analysis, utilizing karyotype to define the genetic networks of the cellular system and CIN to determine the instability of the system, as well as considering gene mutation and epigenetics as modifiers of the system for information amplification and usage, explores the high evolutionary potential of cancer. It provides a new, unified understanding of cancer as a supersystem, encouraging efforts to leverage the dynamics of CIN to develop improved treatment options. Moreover, it offers a historically contingent model for organismal evolution that reconciles the roles of both evolutionary innovation and conservation through macroevolution and microevolution, respectively.}, } @article {pmid39271268, year = {2024}, author = {Mo, J and Bae, J and Saqib, J and Hwang, D and Jin, Y and Park, B and Park, J and Kim, J}, title = {Current computational methods for spatial transcriptomics in cancer biology.}, journal = {Advances in cancer research}, volume = {163}, number = {}, pages = {71-106}, doi = {10.1016/bs.acr.2024.06.006}, pmid = {39271268}, issn = {2162-5557}, mesh = {Humans ; *Neoplasms/genetics/pathology ; *Transcriptome/genetics ; *Computational Biology/methods ; Gene Expression Profiling/methods ; Tumor Microenvironment/genetics ; Animals ; }, abstract = {Cells in multicellular organisms constitute a self-organizing society by interacting with their neighbors. Cancer originates from malfunction of cellular behavior in the context of such a self-organizing system. The identities or characteristics of individual tumor cells can be represented by the hallmark of gene expression or transcriptome, which can be addressed using single-cell dissociation followed by RNA sequencing. However, the dissociation process of single cells results in losing the cellular address in tissue or neighbor information of each tumor cell, which is critical to understanding the malfunctioning cellular behavior in the microenvironment. Spatial transcriptomics technology enables measuring the transcriptome which is tagged by the address within a tissue. However, to understand cellular behavior in a self-organizing society, we need to apply mathematical or statistical methods. Here, we provide a review on current computational methods for spatial transcriptomics in cancer biology.}, } @article {pmid39265037, year = {2024}, author = {Aravind, L and Nicastro, GG and Iyer, LM and Burroughs, AM}, title = {The Prokaryotic Roots of Eukaryotic Immune Systems.}, journal = {Annual review of genetics}, volume = {58}, number = {1}, pages = {365-389}, doi = {10.1146/annurev-genet-111523-102448}, pmid = {39265037}, issn = {1545-2948}, mesh = {Animals ; *Prokaryotic Cells/immunology/metabolism ; *Eukaryota/genetics/immunology ; Humans ; *Immunity, Innate/genetics ; Immune System/immunology/metabolism ; Bacteria/genetics/immunology/metabolism ; Evolution, Molecular ; Phylogeny ; Biological Evolution ; }, abstract = {Over the past two decades, studies have revealed profound evolutionary connections between prokaryotic and eukaryotic immune systems, challenging the notion of their unrelatedness. Immune systems across the tree of life share an operational framework, shaping their biochemical logic and evolutionary trajectories. The diversification of immune genes in the prokaryotic superkingdoms, followed by lateral transfer to eukaryotes, was central to the emergence of innate immunity in the latter. These include protein domains related to nucleotide second messenger-dependent systems, NAD+/nucleotide degradation, and P-loop NTPase domains of the STAND and GTPase clades playing pivotal roles in eukaryotic immunity and inflammation. Moreover, several domains orchestrating programmed cell death, ultimately of prokaryotic provenance, suggest an intimate link between immunity and the emergence of multicellularity in eukaryotes such as animals. While eukaryotes directly adopted some proteins from bacterial immune systems, they repurposed others for new immune functions from bacterial interorganismal conflict systems. These emerging immune components hold substantial biotechnological potential.}, } @article {pmid39262521, year = {2024}, author = {Mary Martin, T and K, MS}, title = {Seaweeds and Their Secondary Metabolites: A Promising Drug Candidate With Novel Mechanisms Against Cancers and Tumor Angiogenesis.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66662}, pmid = {39262521}, issn = {2168-8184}, abstract = {Cancer continually remains a severe threat to public health and requires constant demand for novel therapeutic drug candidates. Due to their multi-target orientation, lesser toxicity, and easy availability, natural compounds attract more attention from current scientific research interest than synthetic drug molecules. The plants and microorganisms produce a huge variety of secondary metabolites because of their physiological diversification, and the seaweeds occupy a prominent position as effective drug resources. Seaweeds comprise microscopic or macroscopic photosynthetic, multicellular, eukaryotic marine algae that commonly inhabit the coastal regions. Several molecules (such as polysaccharides, lipids, proteinaceous fractions, phenolic compounds, and alkaloids) are derived from seaweeds, and those small molecules are well attractive and more effective in cancer research programs. Their structural variation, derivative diversity, and quantity vary with seaweed species and geographical origin. Their smaller molecular weight, unique derivatives, hydrophobicity, and degree of sulfation are reported to be causes of their crucial role against different cancer cells in vitro. Several reports showed that those compounds selectively discriminate between normal and cancer cells based on receptor variations, enzyme deficiency, and structural properties. The present review aimed to give a concise explanation regarding their structural diversity, extractability, and mechanism of action related to their anti-cancer activities based on recently published data.}, } @article {pmid39242229, year = {2025}, author = {Araujo, G and Montoya, JM and Thomas, T and Webster, NS and Lurgi, M}, title = {A mechanistic framework for complex microbe-host symbioses.}, journal = {Trends in microbiology}, volume = {33}, number = {1}, pages = {96-111}, doi = {10.1016/j.tim.2024.08.002}, pmid = {39242229}, issn = {1878-4380}, mesh = {*Symbiosis ; *Microbiota/physiology ; *Host Microbial Interactions/physiology ; *Biological Evolution ; Animals ; Humans ; Bacteria/genetics/classification ; Biodiversity ; Models, Biological ; }, abstract = {Virtually all multicellular organisms on Earth live in symbiotic associations with complex microbial communities: the microbiome. This ancient relationship is of fundamental importance for both the host and the microbiome. Recently, the analyses of numerous microbiomes have revealed an incredible diversity and complexity of symbionts, with different mechanisms identified as potential drivers of this diversity. However, the interplay of ecological and evolutionary forces generating these complex associations is still poorly understood. Here we explore and summarise the suite of ecological and evolutionary mechanisms identified as relevant to different aspects of microbiome complexity and diversity. We argue that microbiome assembly is a dynamic product of ecology and evolution at various spatio-temporal scales. We propose a theoretical framework to classify mechanisms and build mechanistic host-microbiome models to link them to empirical patterns. We develop a cohesive foundation for the theoretical understanding of the combined effects of ecology and evolution on the assembly of complex symbioses.}, } @article {pmid39236709, year = {2024}, author = {Gallo, E and De Renzis, S and Sharpe, J and Mayor, R and Hartmann, J}, title = {Versatile system cores as a conceptual basis for generality in cell and developmental biology.}, journal = {Cell systems}, volume = {15}, number = {9}, pages = {790-807}, doi = {10.1016/j.cels.2024.08.001}, pmid = {39236709}, issn = {2405-4720}, support = {MR/S007792/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Developmental Biology/methods ; Animals ; Humans ; Morphogenesis ; Cell Biology ; Gastrulation/physiology ; Models, Biological ; Biological Evolution ; }, abstract = {The discovery of general principles underlying the complexity and diversity of cellular and developmental systems is a central and long-standing aim of biology. While new technologies collect data at an ever-accelerating rate, there is growing concern that conceptual progress is not keeping pace. We contend that this is due to a paucity of conceptual frameworks that support meaningful generalizations. This led us to develop the core and periphery (C&P) hypothesis, which posits that many biological systems can be decomposed into a highly versatile core with a large behavioral repertoire and a specific periphery that configures said core to perform one particular function. Versatile cores tend to be widely reused across biology, which confers generality to theories describing them. Here, we introduce this concept and describe examples at multiple scales, including Turing patterning, actomyosin dynamics, multi-cellular morphogenesis, and vertebrate gastrulation. We also sketch its evolutionary basis and discuss key implications and open questions. We propose that the C&P hypothesis could unlock new avenues of conceptual progress in mesoscale biology.}, } @article {pmid39228078, year = {2024}, author = {Evans, SD and Hughes, IV and Hughes, EB and Dzaugis, PW and Dzaugis, MP and Gehling, JG and García-Bellido, DC and Droser, ML}, title = {A new motile animal with implications for the evolution of axial polarity from the Ediacaran of South Australia.}, journal = {Evolution & development}, volume = {26}, number = {6}, pages = {e12491}, doi = {10.1111/ede.12491}, pmid = {39228078}, issn = {1525-142X}, support = {//Australian Research Council/ ; //Agouron Institute/ ; /NASA/NASA/United States ; 80NSSC19K0472//NASA Exobiology/ ; DP22010277//Agouron Geobiology Fellowship/ ; DP22010277//Australian Research Council Discovery Project/ ; /NASA/NASA/United States ; }, mesh = {Animals ; *Fossils/anatomy & histology ; South Australia ; *Biological Evolution ; Body Patterning ; Phylogeny ; }, abstract = {Fossils of the Ediacara Biota preserve the oldest evidence for complex, macroscopic animals. Most are difficult to constrain phylogenetically, however, the presence of rare, derived groups suggests that many more fossils from this period represent extant groups than are currently appreciated. One approach to recognize such early animals is to instead focus on characteristics widespread in animals today, for example multicellularity, motility, and axial polarity. Here, we describe a new taxon, Quaestio simpsonorum gen. et sp. nov. from the Ediacaran of South Australia. Quaestio is reconstructed with a thin external membrane connecting more resilient tissues with anterior-posterior polarity, left-right asymmetry and tentative evidence for dorsoventral differentiation. Associated trace fossils indicate an epibenthic and motile lifestyle. Our results suggest that Quaestio was a motile eumetazoan with a body plan not previously recognized in the Ediacaran, including definitive evidence of chirality. This organization, combined with previous evidence for axial patterning in a variety of other Ediacara taxa, demonstrates that metazoan body plans were well established in the Precambrian.}, } @article {pmid39201358, year = {2024}, author = {Kaminskaya, AN and Evpak, AS and Belogurov, AA and Kudriaeva, AA}, title = {Tracking of Ubiquitin Signaling through 3.5 Billion Years of Combinatorial Conjugation.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201358}, issn = {1422-0067}, mesh = {Humans ; *Ubiquitin/metabolism ; *Ubiquitination ; *Evolution, Molecular ; Animals ; *Signal Transduction ; *Ubiquitin-Conjugating Enzymes/metabolism/genetics/chemistry ; Ubiquitin-Protein Ligases/metabolism/genetics/chemistry ; Protein Processing, Post-Translational ; Phylogeny ; }, abstract = {Ubiquitination is an evolutionary, ancient system of post-translational modification of proteins that occurs through a cascade involving ubiquitin activation, transfer, and conjugation. The maturation of this system has followed two main pathways. The first is the conservation of a universal structural fold of ubiquitin and ubiquitin-like proteins, which are present in both Archaea and Bacteria, as well as in multicellular Eukaryotes. The second is the rise of the complexity of the superfamily of ligases, which conjugate ubiquitin-like proteins to substrates, in terms of an increase in the number of enzyme variants, greater variation in structural organization, and the diversification of their catalytic domains. Here, we examine the diversity of the ubiquitination system among different organisms, assessing the variety and conservation of the key domains of the ubiquitination enzymes and ubiquitin itself. Our data show that E2 ubiquitin-conjugating enzymes of metazoan phyla are highly conservative, whereas the homology of E3 ubiquitin ligases with human orthologues gradually decreases depending on "molecular clock" timing and evolutionary distance. Surprisingly, Chordata and Echinodermata, which diverged over 0.5 billion years ago during the Cambrian explosion, share almost the same homology with humans in the amino acid sequences of E3 ligases but not in their adaptor proteins. These observations may suggest that, firstly, the E2 superfamily already existed in its current form in the last common metazoan ancestor and was generally not affected by purifying selection in metazoans. Secondly, it may indicate convergent evolution of the ubiquitination system and highlight E3 adaptor proteins as the "upper deck" of the ubiquitination system, which plays a crucial role in chordate evolution.}, } @article {pmid39198502, year = {2024}, author = {Takeuchi, Y and Hata, H and Sasaki, M and Mvula, A and Mizuhara, S and Rusuwa, B and Maruyama, A}, title = {Preying on cyprinid snout warts (pearl organs) as a novel and peculiar habit in the Lake Malawi cichlid Docimodus evelynae.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {19300}, pmid = {39198502}, issn = {2045-2322}, support = {202210033//Mitsubishi Foundation/ ; 20K06851//Japan Society for the Promotion of Science/ ; 23KK0131//Japan Society for the Promotion of Science/ ; 18KK0208//Japan Society for the Promotion of Science/ ; 23-6406//Toray Science Foundation/ ; }, mesh = {Animals ; *Cichlids ; *Lakes ; Malawi ; Predatory Behavior ; Phylogeny ; Feeding Behavior ; Gastrointestinal Contents ; }, abstract = {Cichlid fishes in the African Great Lakes have undergone explosive speciation, acquiring markedly varying ecologies and diets. There are multiple lineages of scale-eating cichlids, and their natural history and evolutionary ecology is only partially understood. We examined the feeding habit of Docimodus evelynae, a known scale eater, in Lake Malawi. The stomach contents of young individuals mainly consisted of unknown 1 mm hard, white warts (> 30%). To clarify the origin of these warts, we conducted an X-ray fluorometer analysis, and found they were rich in sulphur but low in silicon and calcium, suggesting they were epidermal tissues. Histological and morphological analyses revealed they were multicellular and cup-shaped. These characteristics matched only those of the pearl organs of the coexisting cyprinid Labeo cylindricus. DNA was extracted from the warts found in the stomach of five D. evelynae individuals, followed by PCR using primers targeting the partial COI gene of L. cylindricus. The resulting sequences exhibited 98% similarity to those of L. cylindricus. Pearl organs, never reported as a primary food for fish, could offer a substantial nutritional source based on calorific calculations. Understanding how this peculiar diet is foraged is essential for full comprehension of the food-web structure in this lake.}, } @article {pmid39194023, year = {2024}, author = {Appleton, E and Mehdipour, N and Daifuku, T and Briers, D and Haghighi, I and Moret, M and Chao, G and Wannier, T and Chiappino-Pepe, A and Huang, J and Belta, C and Church, GM}, title = {Algorithms for Autonomous Formation of Multicellular Shapes from Single Cells.}, journal = {ACS synthetic biology}, volume = {13}, number = {9}, pages = {2753-2763}, doi = {10.1021/acssynbio.4c00037}, pmid = {39194023}, issn = {2161-5063}, mesh = {Humans ; *Algorithms ; Gene Regulatory Networks ; Single-Cell Analysis/methods ; Tissue Engineering/methods ; Computer-Aided Design ; Cell Shape ; }, abstract = {Multicellular organisms originate from a single cell, ultimately giving rise to mature organisms of heterogeneous cell type composition in complex structures. Recent work in the areas of stem cell biology and tissue engineering has laid major groundwork in the ability to convert certain types of cells into other types, but there has been limited progress in the ability to control the morphology of cellular masses as they grow. Contemporary approaches to this problem have included the use of artificial scaffolds, 3D bioprinting, and complex media formulations; however, there are no existing approaches to controlling this process purely through genetics and from a single-cell starting point. Here we describe a computer-aided design approach, called CellArchitect, for designing recombinase-based genetic circuits for controlling the formation of multicellular masses into arbitrary shapes in human cells.}, } @article {pmid39187609, year = {2024}, author = {Bell-Roberts, L and Turner, JFR and Werner, GDA and Downing, PA and Ross, L and West, SA}, title = {Larger colony sizes favoured the evolution of more worker castes in ants.}, journal = {Nature ecology & evolution}, volume = {8}, number = {10}, pages = {1959-1971}, pmid = {39187609}, issn = {2397-334X}, support = {834164/ERC_/European Research Council/International ; 834164//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; BB/M011224/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; }, mesh = {*Ants/physiology ; Animals ; *Biological Evolution ; *Population Density ; Social Behavior ; }, abstract = {The size-complexity hypothesis is a leading explanation for the evolution of complex life on earth. It predicts that in lineages that have undergone a major transition in organismality, larger numbers of lower-level subunits select for increased division of labour. Current data from multicellular organisms and social insects support a positive correlation between the number of cells and number of cell types and between colony size and the number of castes. However, the implication of these results is unclear, because colony size and number of cells are correlated with other variables which may also influence selection for division of labour, and causality could be in either direction. Here, to resolve this problem, we tested multiple causal hypotheses using data from 794 ant species. We found that larger colony sizes favoured the evolution of increased division of labour, resulting in more worker castes and greater variation in worker size. By contrast, our results did not provide consistent support for alternative hypotheses regarding either queen mating frequency or number of queens per colony explaining variation in division of labour. Overall, our results provide strong support for the size-complexity hypothesis.}, } @article {pmid39187082, year = {2024}, author = {Dujon, AM and Boutry, J and Tissot, S and Meliani, J and Miltiadous, A and Tokolyi, J and Ujvari, B and Thomas, F}, title = {The widespread vulnerability of Hydra oligactis to tumourigenesis confirms its value as a model for studying the effects of tumoural processes on the ecology and evolution of species.}, journal = {The Science of the total environment}, volume = {951}, number = {}, pages = {175785}, doi = {10.1016/j.scitotenv.2024.175785}, pmid = {39187082}, issn = {1879-1026}, mesh = {*Hydra ; Animals ; *Carcinogenesis ; *Biological Evolution ; Neoplasms ; Australia ; Ecology ; Ecosystem ; }, abstract = {Tumoural processes, ubiquitous phenomena in multicellular organisms, influence evolutionary trajectories of all species. To gain a holistic understanding of their impact on species' biology, suitable laboratory models are required. Such models are characterised by a widespread availability, ease of cultivation, and reproducible tumour induction. It is especially important to explore, through experimental approaches, how tumoural processes alter ecosystem functioning. The cnidarian Hydra oligactis is currently emerging as a promising model due to its development of both transmissible and non-transmissible tumours and the wide breadth of experiments that can be conducted with this species (at the individual, population, mechanistic, and evolutionary levels). However, tumoural hydras are, so far, only documented in Europe, and it is not clear if the phenomenon is local or widespread. In this study we demonstrate that Australian hydras from two independent river networks develop tumours in the laboratory consisting of interstitial stem cells and display phenotypic alterations (supernumerary tentacles) akin to European counterparts. This finding confirms the value of this model for ecological and evolutionary research on host-tumour interactions.}, } @article {pmid39151881, year = {2024}, author = {Shirokawa, Y}, title = {Evolutionary stability of developmental commitment.}, journal = {Bio Systems}, volume = {244}, number = {}, pages = {105309}, doi = {10.1016/j.biosystems.2024.105309}, pmid = {39151881}, issn = {1872-8324}, mesh = {*Dictyostelium/physiology/growth & development ; *Biological Evolution ; Models, Biological ; Mutation ; }, abstract = {Evolution of unicellular to multicellular organisms must resolve conflicts in reproductive interests between individual cells and the group. The social amoeba Dictyostelium discoideum is a soil-living eukaryote with facultative sociality. While cells grow in the presence of nutrients, cells aggregate under starvation to form fruiting bodies containing spores and altruistic stalk cells. Once cells socially committed, they complete formation of fruiting bodies, even if a new source of nutrients becomes available. The persistence of this social commitment raises questions as it inhibits individual cells from swiftly returning to solitary growth. I hypothesize that traits enabling premature de-commitment are hindered from being selected. Recent work has revealed outcomes of the premature de-commitment through forced refeeding; The de-committed cells take an altruistic prestalk-like position due to their reduced cohesiveness through interactions with socially committed cells. I constructed an evolutionary model assuming their division of labor. The results revealed a valley in the fitness landscape that prevented invasion of de-committing mutants, indicating evolutionary stability of the social commitment. The findings provide a general scheme that maintains multicellularity by evolving a specific division of labor, in which less cohesive individuals become altruists.}, } @article {pmid39140743, year = {2024}, author = {Hake, KH and West, PT and McDonald, K and Laundon, D and Reyes-Rivera, J and Garcia De Las Bayonas, A and Feng, C and Burkhardt, P and Richter, DJ and Banfield, JF and King, N}, title = {A large colonial choanoflagellate from Mono Lake harbors live bacteria.}, journal = {mBio}, volume = {15}, number = {9}, pages = {e0162324}, pmid = {39140743}, issn = {2150-7511}, support = {n/a//Howard Hughes Medical Institute (HHMI)/ ; DGE 1106400//National Science Foundation (NSF)/ ; DGE 1752814//National Science Foundation (NSF)/ ; 100010434//'la Caixa' Foundation ('la Caixa')/ ; }, mesh = {*Choanoflagellata/classification/physiology ; *Lakes/microbiology ; California ; *Phylogeny ; Gammaproteobacteria/isolation & purification/classification/genetics/physiology ; RNA, Ribosomal, 16S/genetics ; Bacteria/classification/isolation & purification/genetics ; Alphaproteobacteria/classification/isolation & purification/genetics ; Sequence Analysis, DNA ; }, abstract = {UNLABELLED: As the closest living relatives of animals, choanoflagellates offer insights into the ancestry of animal cell physiology. Here, we report the isolation and characterization of a colonial choanoflagellate from Mono Lake, California. The choanoflagellate forms large spherical colonies that are an order of magnitude larger than those formed by the closely related choanoflagellate Salpingoeca rosetta. In cultures maintained in the laboratory, the lumen of the spherical colony is filled with a branched network of extracellular matrix and colonized by bacteria, including diverse Gammaproteobacteria and Alphaproteobacteria. We propose to erect Barroeca monosierra gen. nov., sp. nov. Hake, Burkhardt, Richter, and King to accommodate this extremophile choanoflagellate. The physical association between bacteria and B. monosierra in culture presents a new experimental model for investigating interactions among bacteria and eukaryotes. Future work will investigate the nature of these interactions in wild populations and the mechanisms underpinning the colonization of B. monosierra spheres by bacteria.

IMPORTANCE: The diversity of organisms that live in the extreme environment of Mono Lake (California, USA) is limited. We sought to investigate whether the closest living relatives of animals, the choanoflagellates, exist in Mono Lake, a hypersaline, alkaline, arsenic-rich environment. We repeatedly isolated members of a new species of choanoflagellate, which we have named Barroeca monosierra. Characterization of B. monosierra revealed that it forms large spherical colonies containing diverse co-isolated bacteria, providing an opportunity to investigate mechanisms underlying physical associations between eukaryotes and bacteria.}, } @article {pmid39127170, year = {2024}, author = {Cravero, BH and Prez, G and Lombardo, VA and Guastaferri, FV and Delprato, CB and Altabe, S and de Mendoza, D and Binolfi, A}, title = {A high-resolution [13]C NMR approach for profiling fatty acid unsaturation in lipid extracts and in live Caenorhabditiselegans.}, journal = {Journal of lipid research}, volume = {65}, number = {9}, pages = {100618}, pmid = {39127170}, issn = {1539-7262}, mesh = {Animals ; *Caenorhabditis elegans/metabolism ; *Fatty Acids, Unsaturated/metabolism/analysis ; Carbon-13 Magnetic Resonance Spectroscopy ; Fatty Acids/metabolism/analysis ; Lipids/analysis/chemistry ; }, abstract = {Unsaturated fatty acids (UFA) play a crucial role in central cellular processes in animals, including membrane function, development, and disease. Disruptions in UFA homeostasis can contribute to the onset of metabolic, cardiovascular, and neurodegenerative disorders. Consequently, there is a high demand for analytical techniques to study lipid compositions in live cells and multicellular organisms. Conventional analysis of UFA compositions in cells, tissues, and organisms involves solvent extraction procedures coupled with analytical techniques such as gas chromatography, MS and/or NMR spectroscopy. As a nondestructive and nontargeted technique, NMR spectroscopy is uniquely capable of characterizing the chemical profiling of living cells and multicellular organisms. Here, we use NMR spectroscopy to analyze Caenorhabditis elegans, enabling the determination of their lipid compositions and fatty acid unsaturation levels both in cell-free lipid extracts and in vivo. The NMR spectra of lipid extracts from WT and fat-3 mutant C. elegans strains revealed notable differences due to the absence of Δ-6 fatty acid desaturase activity, including the lack of arachidonic and eicosapentaenoic acyl chains. Uniform [13]C-isotope labeling and high-resolution 2D solution-state NMR of live worms confirmed these findings, indicating that the signals originated from fast-tumbling lipid molecules within lipid droplets. Overall, this strategy permits the analysis of lipid storage in intact worms and has enough resolution and sensitivity to identify differences between WT and mutant animals with impaired fatty acid desaturation. Our results establish methodological benchmarks for future investigations of fatty acid regulation in live C. elegans using NMR.}, } @article {pmid39117360, year = {2024}, author = {Li, XC and Srinivasan, V and Laiker, I and Misunou, N and Frankel, N and Pallares, LF and Crocker, J}, title = {TF-High-Evolutionary: In Vivo Mutagenesis of Gene Regulatory Networks for the Study of the Genetics and Evolution of the Drosophila Regulatory Genome.}, journal = {Molecular biology and evolution}, volume = {41}, number = {8}, pages = {}, pmid = {39117360}, issn = {1537-1719}, support = {//European Molecular Biology Laboratory Interdisciplinary Postdoc Programme/ ; //European Molecular Biology Laboratory/ ; //Max Planck Society/ ; }, mesh = {Animals ; *Gene Regulatory Networks ; *Transcription Factors/genetics/metabolism ; Genome, Insect ; Mutagenesis ; Drosophila/genetics ; Evolution, Molecular ; Drosophila melanogaster/genetics ; }, abstract = {Understanding the evolutionary potential of mutations in gene regulatory networks is essential to furthering the study of evolution and development. However, in multicellular systems, genetic manipulation of regulatory networks in a targeted and high-throughput way remains challenging. In this study, we designed TF-High-Evolutionary (HighEvo), a transcription factor (TF) fused with a base editor (activation-induced deaminase), to continuously induce germline mutations at TF-binding sites across regulatory networks in Drosophila. Populations of flies expressing TF-HighEvo in their germlines accumulated mutations at rates an order of magnitude higher than natural populations. Importantly, these mutations accumulated around the targeted TF-binding sites across the genome, leading to distinct morphological phenotypes consistent with the developmental roles of the tagged TFs. As such, this TF-HighEvo method allows the interrogation of the mutational space of gene regulatory networks at scale and can serve as a powerful reagent for experimental evolution and genetic screens focused on the regulatory genome.}, } @article {pmid39098975, year = {2024}, author = {Oishi, R and Takeda, I and Ode, Y and Okada, Y and Kato, D and Nakashima, H and Imagama, S and Wake, H}, title = {Neuromodulation with transcranial direct current stimulation contributes to motor function recovery via microglia in spinal cord injury.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {18031}, pmid = {39098975}, issn = {2045-2322}, support = {20H05899//Japan Society for the Promotion of Science/ ; PMJCR22P6//Japan Science and Technology Agency/ ; 19H04753, 19H05219, and 25110732//Grants-in-Aid for Scientific Research on Innovative Areas/ ; JPMJCR1755, JPMJCR22P6//JST CREST/ ; }, mesh = {*Spinal Cord Injuries/therapy/physiopathology ; Animals ; *Microglia/metabolism ; *Transcranial Direct Current Stimulation/methods ; Mice ; *Motor Cortex/physiopathology ; *Recovery of Function ; *Mice, Inbred C57BL ; Disease Models, Animal ; Male ; Spinal Cord/physiopathology/pathology ; Female ; }, abstract = {Spinal cord injury (SCI) is damage or trauma to the spinal cord, which often results in loss of function, sensation, or mobility below the injury site. Transcranial direct current stimulation (tDCS) is a non-invasive and affordable brain stimulation technique used to modulate neuronal circuits, which changes the morphology and activity of microglia in the cerebral cortex. However, whether similar morphological changes can be observed in the spinal cord remains unclear. Therefore, we evaluated neuronal population activity in layer 5 (L5) of M1 following SCI and investigated whether changes in the activities of L5 neurons affect microglia-axon interactions using C57BL/6J mice. We discovered that L5 of the primary motor cortex (corticospinal neurons) exhibited reduced synchronized activity after SCI that correlates with microglial morphology, which was recovered using tDCS. This indicates that tDCS promotes changes in the morphological properties and recovery of microglia after SCI. Combining immunotherapy with tDCS may be effective in treating SCI.}, } @article {pmid39068338, year = {2024}, author = {Yousefi Taemeh, S and Dehdilani, N and Goshayeshi, L and Dehghani, H}, title = {Exploring the Function of Gene Promoter Regulatory Elements Using CRISPR Tools.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2844}, number = {}, pages = {145-156}, pmid = {39068338}, issn = {1940-6029}, mesh = {*Promoter Regions, Genetic ; *CRISPR-Cas Systems ; Animals ; Humans ; Gene Expression Regulation ; Enhancer Elements, Genetic ; Ovalbumin/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; }, abstract = {Gene promoters serve as pivotal regulators of transcription, orchestrating the initiation, rate, and specificity of gene expression, resulting in cellular diversity found among distinct cell types within multicellular organisms. Identification of the sequence and function of promoters' regulatory elements and their complex interaction with transcription factors, enhancers, silencers, and insulators is fundamental to coordinated transcriptional processes within cells. Identifying these regulatory elements and scrutinizing their functions and interactions through the use of synthetic promoters can pave the way for researchers in various fields ranging from uncovering the origins of diseases associated with promoter mutations to harnessing these regulatory components in biotechnological applications.In this chapter, we describe the manipulation of regulatory elements within promoters, with a specific focus on the use of CRISPR technology on enhancers and silencer elements of the Ovalbumin gene promoter. We explain and discuss processes for the deletion of/interference with regulatory elements within the promoter, employing CRISPR-based approaches. Furthermore, we demonstrate that a CRISPR/Cas-manipulated promoter can activate gene transcription in cell types where it is normally inactive. This confirms that CRISPR technology can be effectively used to engineer synthetic promoters with desired characteristics, such as inducibility, tissue-specificity, or enhanced transcriptional strength. Such an approach provides valuable insights into the mechanisms and dynamics of gene expression, thereby offering new opportunities in the fields of biotechnology and medicine.}, } @article {pmid39067992, year = {2024}, author = {Hariom, SK and Nelson, EJR}, title = {Cardiovascular adaptations in microgravity conditions.}, journal = {Life sciences in space research}, volume = {42}, number = {}, pages = {64-71}, doi = {10.1016/j.lssr.2024.05.001}, pmid = {39067992}, issn = {2214-5532}, mesh = {Humans ; *Weightlessness ; *Adaptation, Physiological ; Animals ; Cardiovascular System/physiopathology ; Weightlessness Simulation ; Cardiovascular Deconditioning/physiology ; Orthostatic Intolerance/physiopathology ; Space Flight ; }, abstract = {Gravity has had a significant impact on the evolution of life on Earth with organisms developing necessary biological adaptations over billions of years to counter this ever-existing force. There has been an exponential increase in experiments using real and simulated gravity environments in the recent years. Although an understanding followed by discovery of counter measures to negate diminished gravity in space had been the driving force of research initially, there has since been a phenomenal leap wherein a force unearthly as microgravity is beginning to show promising potential. The current review summarizes pathophysiological changes that occur in multiple aspects of the cardiovascular system when exposed to an altered gravity environment leading to cardiovascular deconditioning and orthostatic intolerance. Gravity influences not just the complex multicellular systems but even the survival of organisms at the molecular level by intervening fundamental cellular processes, directly affecting those linked to actin and microtubule organization via mechano-transduction pathways. The reach of gravity ranges from cytoskeletal rearrangement that regulates cell adhesion and migration to intracellular dynamics that dictate cell fate commitment and differentiation. An understanding that microgravity itself is not present on Earth propels the scope of simulated gravity conditions to be a unique and useful environment that could be explored for enhancing the potential of stem cells for a wide range of applications as has been highlighted here.}, } @article {pmid39060315, year = {2024}, author = {Jia, Z and Wang, J and Meng, X and Yang, X and Tian, Y and Wang, B and Chen, M and Yang, J and Das, D and Cao, Y}, title = {Evolution and stress response potential of the plant splicing factor U1C.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {17212}, pmid = {39060315}, issn = {2045-2322}, support = {32172104//National Natural Science Foundation of China/ ; 3217150246//National Natural Science Foundation of China/ ; 32172104//National Natural Science Foundation of China/ ; 32172104//National Natural Science Foundation of China/ ; 32172104//National Natural Science Foundation of China/ ; 3217150246//National Natural Science Foundation of China/ ; 32172104//National Natural Science Foundation of China/ ; 32172104//National Natural Science Foundation of China/ ; 3217150246//National Natural Science Foundation of China/ ; KFJN2325//Large Instruments Open Foundation of Nantong University/ ; KFJN2325//Large Instruments Open Foundation of Nantong University/ ; SBK2020042924//Natural Science Foundation of Jiangsu Province/ ; SBK2020042924//Natural Science Foundation of Jiangsu Province/ ; SBK2020042924//Natural Science Foundation of Jiangsu Province/ ; }, mesh = {*Stress, Physiological/genetics ; *Gene Expression Regulation, Plant ; *Phylogeny ; *Plant Proteins/genetics/metabolism ; Evolution, Molecular ; Oryza/genetics/metabolism ; Alternative Splicing ; Droughts ; Promoter Regions, Genetic ; }, abstract = {Alternative splicing is a crucial process in multicellular eukaryote, facilitated by the assembly of spliceosomal complexes comprising numerous small ribonucleoproteins. At an early stage, U1C is thought to be required for 5' splice site recognition and base pairing. However, a systematic analysis of the U1C gene family in response to developmental cues and stress conditions has not yet been conducted in plants. This study identified 114 U1C genes in 72 plant species using basic bioinformatics analyses. Phylogenetic analysis was used to compare gene and protein structures, promoter motifs, and tissue- and stress-specific expression levels, revealing their functional commonalities or diversity in response to developmental cues, such as embryonic expression, or stress treatments, including drought and heat. Fluorescence quantitative expression analysis showed that U1C gene expression changed under salt, low temperature, drought, and Cd stress in rice seedlings. However, gene expression in shoots and roots was not consistent under different stress conditions, suggesting a complex regulatory mechanism. This research provides foundational insights into the U1C gene family's role in plant development and stress responses, highlighting potential targets for future studies.}, } @article {pmid39052757, year = {2024}, author = {Hehmeyer, J and Plessier, F and Marlow, H}, title = {Adaptive Cellular Radiations and the Genetic Mechanisms Underlying Animal Nervous System Diversification.}, journal = {Annual review of cell and developmental biology}, volume = {40}, number = {1}, pages = {407-425}, doi = {10.1146/annurev-cellbio-111822-124041}, pmid = {39052757}, issn = {1530-8995}, mesh = {Animals ; *Nervous System/metabolism ; Biological Evolution ; Humans ; Signal Transduction/genetics ; }, abstract = {In animals, the nervous system evolved as the primary interface between multicellular organisms and the environment. As organisms became larger and more complex, the primary functions of the nervous system expanded to include the modulation and coordination of individual responsive cells via paracrine and synaptic functions as well as to monitor and maintain the organism's own internal environment. This was initially accomplished via paracrine signaling and eventually through the assembly of multicell circuits in some lineages. Cells with similar functions and centralized nervous systems have independently arisen in several lineages. We highlight the molecular mechanisms that underlie parallel diversifications of the nervous system.}, } @article {pmid39032813, year = {2024}, author = {Yamauchi, A}, title = {Evolution of labor division in reproduction and multiple group tasks.}, journal = {Journal of theoretical biology}, volume = {593}, number = {}, pages = {111910}, doi = {10.1016/j.jtbi.2024.111910}, pmid = {39032813}, issn = {1095-8541}, mesh = {*Reproduction/physiology ; *Biological Evolution ; Animals ; Fertility/physiology ; Models, Biological ; }, abstract = {Labor division is a phenomenon observed across various biological contexts, including examples such as the differentiation between germ/somatic cells in multicellular organisms and the division between reproductive/worker individuals within social animal groups. In such cases, certain members contribute to tasks that enhance the viability of the entire group, even if this requires a reduction in their individual reproductive efforts. Given that group members have the potential to adopt varying contribution levels, a comprehensive analysis of the evolution becomes intricate due to the problem's high dimensionality. In this paper, I introduce a novel method for analyzing the evolution of the distribution of contribution levels to group viability, with a particular formulation centered on the success of clonal strains. The analysis demonstrates that the curvature of the fecundity function in relation to contributions to the group plays a pivotal role in determining the occurrence of labor division between reproductive and non-reproductive tasks, aligning in part with results from prior research. Furthermore, I extend this analysis to encompass contributions to multiple categories of tasks for group viability. My findings indicate that investments in non-reproductive tasks are selected based on the average contributions for each task, with individual variation playing a less significant role as long as average values remain consistent. Additionally, I explore the impact of group size and relatedness within the group on labor division. The results highlight that increases in group size and relatedness have a positive influence on the evolution of cooperation, although their effects are not directly tied to labor division itself.}, } @article {pmid39006742, year = {2024}, author = {Obregon-Perko, V and Mannino, A and Ladner, JT and Hodara, V and Ebrahimi, D and Parodi, L and Callery, J and Palacios, G and Giavedoni, LD}, title = {Adaptation of SIVmac to baboon primary cells results in complete absence of in vivo baboon infectivity.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1408245}, pmid = {39006742}, issn = {2235-2988}, support = {P51 OD011133/OD/NIH HHS/United States ; R01 AI179465/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Simian Immunodeficiency Virus/genetics/physiology ; *Virus Replication ; *Simian Acquired Immunodeficiency Syndrome/virology/immunology ; *Papio ; Leukocytes, Mononuclear/virology/immunology ; Receptors, CCR5/metabolism/genetics ; CD4-Positive T-Lymphocytes/virology/immunology ; Cells, Cultured ; Serial Passage ; }, abstract = {While simian immunodeficiency virus (SIV) infection is non-pathogenic in naturally infected African nonhuman primate hosts, experimental or accidental infection in rhesus macaques often leads to AIDS. Baboons, widely distributed throughout Africa, do not naturally harbor SIV, and experimental infection of baboons with SIVmac results in transient low-level viral replication. Elucidation of mechanisms of natural immunity in baboons could uncover new targets of antiviral intervention. We tested the hypothesis that an SIVmac adapted to replicate in baboon primary cells will gain the capacity to establish chronic infections in vivo. Here, we generated SIVmac variants in baboon cells through serial passage in PBMC from different donors (SIVbn-PBMC s1), in PBMC from the same donors (SIVbn-PBMC s2), or in isolated CD4 cells from the same donors used for series 2 (SIVbn-CD4). While SIVbn-PBMC s1 and SIVbn-CD4 demonstrated increased replication capacity, SIVbn-PBMC s2 did not. Pharmacological blockade of CCR5 revealed SIVbn-PBMC s1 could more efficiently use available CCR5 than SIVmac, a trait we hypothesize arose to circumvent receptor occupation by chemokines. Sequencing analysis showed that all three viruses accumulated different types of mutations, and that more non-synonymous mutations became fixed in SIVbn-PBMC s1 than SIVbn-PBMC s2 and SIVbn-CD4, supporting the notion of stronger fitness pressure in PBMC from different genetic backgrounds. Testing the individual contribution of several newly fixed SIV mutations suggested that is the additive effect of these mutations in SIVbn-PBMC s1 that contributed to its enhanced fitness, as recombinant single mutant viruses showed no difference in replication capacity over the parental SIVmac239 strain. The replicative capacity of SIVbn-PBMC passage 4 (P4) s1 was tested in vivo by infecting baboons intravenously with SIVbn-PBMC P4 s1 or SIVmac251. While animals infected with SIVmac251 showed the known pattern of transient low-level viremia, animals infected with SIVbn-PBMC P4 s1 had undetectable viremia or viral DNA in lymphoid tissue. These studies suggest that adaptation of SIV to grow in baboon primary cells results in mutations that confer increased replicative capacity in the artificial environment of cell culture but make the virus unable to avoid the restrictive factors generated by a complex multicellular organism.}, } @article {pmid39004296, year = {2024}, author = {Zhang, M and Sun, J and Zhang, F and Zhang, Y and Wu, M and Kong, W and Guan, X and Liu, M}, title = {Molecular mechanism of TRIM32 in antiviral immunity in rainbow trout (Oncorhynchus mykiss).}, journal = {Fish & shellfish immunology}, volume = {153}, number = {}, pages = {109765}, doi = {10.1016/j.fsi.2024.109765}, pmid = {39004296}, issn = {1095-9947}, mesh = {Animals ; *Oncorhynchus mykiss/immunology ; *Fish Diseases/immunology ; *Fish Proteins/genetics/immunology ; *Rhabdoviridae Infections/immunology/veterinary ; *Immunity, Innate/genetics ; *Tripartite Motif Proteins/genetics/immunology ; Ubiquitin-Protein Ligases/genetics/immunology ; Gene Expression Regulation/immunology ; Gene Expression Profiling/veterinary ; Infectious hematopoietic necrosis virus/immunology/physiology ; Sequence Alignment/veterinary ; Phylogeny ; }, abstract = {TRIM family proteins are widely found in multicellular organisms and are involved in a wide range of life activities, and also act as crucial regulators in the antiviral natural immune response. This study aimed to reveal the molecular mechanism of rainbow trout TRIM protein in the anti-IHNV process. The results demonstrated that 99.1 % homology between the rainbow trout and the chinook salmon (Oncorhynchus tshawytscha) TRIM32. When rainbow trout were infected with IHNV, the TRIM32 was highly expressed in the gill, spleen, kidney and blood. Meanwhile, rainbow trout TRIM32 has E3 ubiquitin ligase activity and undergoes K29-linked polyubiquitination modifications dependent on the RING structural domain was determined by immunoprecipitation. TRIM32 could interact with the NV protein of IHNV and degrade NV protein through the ubiquitin-proteasome pathway, and was also able to activate NF-κB transcription, thereby inhibiting the replication of IHNV. Moreover, the results of the animal studies showed that the survival rate of rainbow trout overexpressing TRIM32 was 70.2 % which was significantly higher than that of the control group, and stimulating the body to produce high levels of IgM when the host was infected with the virus. In addition, TRIM32 can activate the NF-κB signalling pathway and participate in the antiviral natural immune response. The results of this study will help us to understand the molecular mechanism of TRIM protein resistance in rainbow trout, and provide new ideas for disease resistance breeding, vaccine development and immune formulation development in rainbow trout.}, } @article {pmid38991084, year = {2024}, author = {Landis, JB and Guercio, AM and Brown, KE and Fiscus, CJ and Morrell, PL and Koenig, D}, title = {Natural selection drives emergent genetic homogeneity in a century-scale experiment with barley.}, journal = {Science (New York, N.Y.)}, volume = {385}, number = {6705}, pages = {eadl0038}, doi = {10.1126/science.adl0038}, pmid = {38991084}, issn = {1095-9203}, mesh = {*Hordeum/genetics ; *Selection, Genetic ; *Genetic Variation ; *Alleles ; Genotype ; Crosses, Genetic ; Genome, Plant ; }, abstract = {Direct observation is central to our understanding of adaptation, but evolution is rarely documented in a large, multicellular organism for more than a few generations. In this study, we observed evolution across a century-scale competition experiment, barley composite cross II (CCII). CCII was founded in 1929 in Davis, California, with thousands of genotypes, but we found that natural selection has massively reduced genetic diversity, leading to a single lineage constituting most of the population by generation 50. Selection favored alleles originating from climates similar to that of Davis and targeted loci contributing to reproductive development, including the barley diversification loci Vrs1, HvCEN, Ppd-H1, and Vrn-H2. Our findings point to selection as the predominant force shaping genomic variation in one of the world's oldest biological experiments.}, } @article {pmid38990205, year = {2024}, author = {Sims, NA}, title = {Osteoclast-derived coupling factors: origins and state-of-play Louis V Avioli lecture, ASBMR 2023.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {39}, number = {10}, pages = {1377-1385}, pmid = {38990205}, issn = {1523-4681}, support = {//National Health and Medical Research Council/ ; //St. Vincent's Institute Foundation/ ; //Victorian State Government's Operational Infrastructure Support Program/ ; }, mesh = {Animals ; Humans ; Bone Remodeling ; *Osteoclasts/metabolism ; }, abstract = {Coupling, the mechanism that controls the sequence of events in bone remodeling, is a fundamental theory for understanding the way the skeleton changes throughout life. This review is an adapted version of the Louis V Avioli lecture, delivered at the Annual Scientific Meeting of the American Society of Bone and Mineral Research in 2023. It outlines the history of the coupling concept, details how coupling is thought to occur within trabecular and cortical bone, and describes its multiple contexts and the many mechanisms suggested to couple bone-forming osteoblasts to the prior action of osteoclasts on the same bone surface. These mechanisms include signals produced at each stage of the remodeling sequence (resorption, reversal, and formation), such as factors released by osteoclasts through their resorptive action and through protein synthesis, molecules deposited in the cement line during the reversal phase, and potential signals from osteocytes within the local bone environment. The review highlights two examples of coupling factors (Cardiotrophin 1 and EphrinB2:EphB4) to illustrate the limited data available, the need to integrate the many functions of these factors within the basic multicellular unit (BMU), and the multiple origins of these factors, including the other cell types present during the remodeling sequence (such as osteocytes, macrophages, endothelial cells, and T-cells).}, } @article {pmid38985841, year = {2024}, author = {Valencia-Montoya, WA and Pierce, NE and Bellono, NW}, title = {Evolution of Sensory Receptors.}, journal = {Annual review of cell and developmental biology}, volume = {40}, number = {1}, pages = {353-379}, pmid = {38985841}, issn = {1530-8995}, support = {R01 NS129060/NS/NINDS NIH HHS/United States ; R35 GM142697/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Sensory Receptor Cells/metabolism ; *Biological Evolution ; Humans ; Chemoreceptor Cells/metabolism ; }, abstract = {Sensory receptors are at the interface between an organism and its environment and thus represent key sites for biological innovation. Here, we survey major sensory receptor families to uncover emerging evolutionary patterns. Receptors for touch, temperature, and light constitute part of the ancestral sensory toolkit of animals, often predating the evolution of multicellularity and the nervous system. In contrast, chemoreceptors exhibit a dynamic history of lineage-specific expansions and contractions correlated with the disparate complexity of chemical environments. A recurring theme includes independent transitions from neurotransmitter receptors to sensory receptors of diverse stimuli from the outside world. We then provide an overview of the evolutionary mechanisms underlying sensory receptor diversification and highlight examples where signatures of natural selection are used to identify novel sensory adaptations. Finally, we discuss sensory receptors as evolutionary hotspots driving reproductive isolation and speciation, thereby contributing to the stunning diversity of animals.}, } @article {pmid38981695, year = {2024}, author = {Kulakova, MA and Maslakov, GP and Poliushkevich, LO}, title = {Irreducible Complexity of Hox Gene: Path to the Canonical Function of the Hox Cluster.}, journal = {Biochemistry. Biokhimiia}, volume = {89}, number = {6}, pages = {987-1001}, doi = {10.1134/S0006297924060014}, pmid = {38981695}, issn = {1608-3040}, mesh = {Animals ; *Genes, Homeobox ; Homeodomain Proteins/genetics/metabolism ; Multigene Family ; Humans ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; }, abstract = {The evolution of major taxa is often associated with the emergence of new gene families. In all multicellular animals except sponges and comb jellies, the genomes contain Hox genes, which are crucial regulators of development. The canonical function of Hox genes involves colinear patterning of body parts in bilateral animals. This general function is implemented through complex, precisely coordinated mechanisms, not all of which are evolutionarily conserved and fully understood. We suggest that the emergence of this regulatory complexity was preceded by a stage of cooperation between more ancient morphogenetic programs or their individual elements. Footprints of these programs may be present in modern animals to execute non-canonical Hox functions. Non-canonical functions of Hox genes are involved in maintaining terminal nerve cell specificity, autophagy, oogenesis, pre-gastrulation embryogenesis, vertical signaling, and a number of general biological processes. These functions are realized by the basic properties of homeodomain protein and could have triggered the evolution of ParaHoxozoa and Nephrozoa subsequently. Some of these non-canonical Hox functions are discussed in our review.}, } @article {pmid38977899, year = {2024}, author = {Kollmar, M and Welz, T and Ravi, A and Kaufmann, T and Alzahofi, N and Hatje, K and Alghamdi, A and Kim, J and Briggs, DA and Samol-Wolf, A and Pylypenko, O and Hume, AN and Burkhardt, P and Faix, J and Kerkhoff, E}, title = {Actomyosin organelle functions of SPIRE actin nucleators precede animal evolution.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {832}, pmid = {38977899}, issn = {2399-3642}, support = {KE 447/18-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; FA 330/12-3//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; KE 447/10-2//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; KE 447/21-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; KO 2251/13-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Organelles/metabolism ; *Actomyosin/metabolism ; Microfilament Proteins/metabolism/genetics ; Myosin Type V/metabolism/genetics ; Actins/metabolism ; Humans ; Choanoflagellata/metabolism ; Actin Cytoskeleton/metabolism ; Biological Evolution ; Evolution, Molecular ; Formins/metabolism ; rab GTP-Binding Proteins/metabolism ; Phylogeny ; Nuclear Proteins ; }, abstract = {An important question in cell biology is how cytoskeletal proteins evolved and drove the development of novel structures and functions. Here we address the origin of SPIRE actin nucleators. Mammalian SPIREs work with RAB GTPases, formin (FMN)-subgroup actin assembly proteins and class-5 myosin (MYO5) motors to transport organelles along actin filaments towards the cell membrane. However, the origin and extent of functional conservation of SPIRE among species is unknown. Our sequence searches show that SPIRE exist throughout holozoans (animals and their closest single-celled relatives), but not other eukaryotes. SPIRE from unicellular holozoans (choanoflagellate), interacts with RAB, FMN and MYO5 proteins, nucleates actin filaments and complements mammalian SPIRE function in organelle transport. Meanwhile SPIRE and MYO5 proteins colocalise to organelles in Salpingoeca rosetta choanoflagellates. Based on these observations we propose that SPIRE originated in unicellular ancestors of animals providing an actin-myosin driven exocytic transport mechanism that may have contributed to the evolution of complex multicellular animals.}, } @article {pmid38975338, year = {2024}, author = {Amanya, SB and Oyewole-Said, D and Ernste, KJ and Bisht, N and Murthy, A and Vazquez-Perez, J and Konduri, V and Decker, WK}, title = {The mARS complex: a critical mediator of immune regulation and homeostasis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1423510}, pmid = {38975338}, issn = {1664-3224}, support = {R01 AI127387/AI/NIAID NIH HHS/United States ; R01 AI153326/AI/NIAID NIH HHS/United States ; }, mesh = {*Homeostasis/immunology ; Animals ; Humans ; *Amino Acyl-tRNA Synthetases/immunology/metabolism ; Immunomodulation ; }, abstract = {Over the course of evolution, many proteins have undergone adaptive structural changes to meet the increasing homeostatic regulatory demands of multicellularity. Aminoacyl tRNA synthetases (aaRS), enzymes that catalyze the attachment of each amino acid to its cognate tRNA, are such proteins that have acquired new domains and motifs that enable non-canonical functions. Through these new domains and motifs, aaRS can assemble into large, multi-subunit complexes that enhance the efficiency of many biological functions. Moreover, because the complexity of multi-aminoacyl tRNA synthetase (mARS) complexes increases with the corresponding complexity of higher eukaryotes, a contribution to regulation of homeostatic functions in multicellular organisms is hypothesized. While mARS complexes in lower eukaryotes may enhance efficiency of aminoacylation, little evidence exists to support a similar role in chordates or other higher eukaryotes. Rather, mARS complexes are reported to regulate multiple and variegated cellular processes that include angiogenesis, apoptosis, inflammation, anaphylaxis, and metabolism. Because all such processes are critical components of immune homeostasis, it is important to understand the role of mARS complexes in immune regulation. Here we provide a conceptual analysis of the current understanding of mARS complex dynamics and emerging mARS complex roles in immune regulation, the increased understanding of which should reveal therapeutic targets in immunity and immune-mediated disease.}, } @article {pmid38971878, year = {2024}, author = {Wang, P and Driscoll, WW and Travisano, M}, title = {Genomic sequencing reveals convergent adaptation during experimental evolution in two budding yeast species.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {825}, pmid = {38971878}, issn = {2399-3642}, support = {1724011//Center for Hierarchical Manufacturing, National Science Foundation (Center for Hierarchical Manufacturing)/ ; 16-IDEAS16-0002//National Aeronautics and Space Administration (NASA)/ ; }, mesh = {*Kluyveromyces/genetics/physiology ; Saccharomyces cerevisiae/genetics ; Genome, Fungal ; Mutation ; Evolution, Molecular ; Adaptation, Physiological/genetics ; Selection, Genetic ; Biological Evolution ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Genomics/methods ; }, abstract = {Convergent evolution is central in the origins of multicellularity. Identifying the basis for convergent multicellular evolution is challenging because of the diverse evolutionary origins and environments involved. Haploid Kluyveromyces lactis populations evolve multicellularity during selection for increased settling in liquid media. Strong genomic and phenotypic convergence is observed between K. lactis and previously selected S. cerevisiae populations under similar selection, despite their >100-million-year divergence. We find K. lactis multicellularity is conferred by mutations in genes ACE2 or AIM44, with ACE2 being predominant. They are a subset of the six genes involved in the S. cerevisiae multicellularity. Both ACE2 and AIM44 regulate cell division, indicating that the genetic convergence is likely due to conserved cellular replication mechanisms. Complex population dynamics involving multiple ACE2/AIM44 genotypes are found in most K. lactis lineages. The results show common ancestry and natural selection shape convergence while chance and contingency determine the degree of divergence.}, } @article {pmid38971670, year = {2024}, author = {Babonis, LS}, title = {On the evolutionary developmental biology of the cell.}, journal = {Trends in genetics : TIG}, volume = {40}, number = {10}, pages = {822-833}, pmid = {38971670}, issn = {0168-9525}, support = {R35 GM147253/GM/NIGMS NIH HHS/United States ; }, mesh = {*Developmental Biology ; *Biological Evolution ; Animals ; Humans ; Single-Cell Analysis/methods ; }, abstract = {Organisms are complex assemblages of cells, cells that produce light, shoot harpoons, and secrete glue. Therefore, identifying the mechanisms that generate novelty at the level of the individual cell is essential for understanding how multicellular life evolves. For decades, the field of evolutionary developmental biology (Evo-Devo) has been developing a framework for connecting genetic variation that arises during embryonic development to the emergence of diverse adult forms. With increasing access to new single cell 'omics technologies and an array of techniques for manipulating gene expression, we can now extend these inquiries inward to the level of the individual cell. In this opinion, I argue that applying an Evo-Devo framework to single cells makes it possible to explore the natural history of cells, where this was once only possible at the organismal level.}, } @article {pmid38971326, year = {2024}, author = {Prosdocimi, F and de Farias, ST}, title = {Major evolutionary transitions before cells: A journey from molecules to organisms.}, journal = {Progress in biophysics and molecular biology}, volume = {191}, number = {}, pages = {11-24}, doi = {10.1016/j.pbiomolbio.2024.07.002}, pmid = {38971326}, issn = {1873-1732}, mesh = {*Biological Evolution ; Evolution, Molecular ; }, abstract = {Basing on logical assumptions and necessary steps of complexification along biological evolution, we propose here an evolutionary path from molecules to cells presenting four ages and three major transitions. At the first age, the basic biomolecules were formed and become abundant. The first transition happened with the event of a chemical symbiosis between nucleic acids and peptides worlds, which marked the emergence of both life and the process of organic encoding. FUCA, the first living process, was composed of self-replicating RNAs linked to amino acids and capable to catalyze their binding. The second transition, from the age of FUCA to the age of progenotes, involved the duplication and recombination of proto-genomes, leading to specialization in protein production and the exploration of protein to metabolite interactions in the prebiotic soup. Enzymes and metabolic pathways were incorporated into biology from protobiotic reactions that occurred without chemical catalysts, step by step. Then, the fourth age brought origin of organisms and lineages, occurring when specific proteins capable to stackle together facilitated the formation of peptidic capsids. LUCA was constituted as a progenote capable to operate the basic metabolic functions of a cell, but still unable to interact with lipid molecules. We present evidence that the evolution of lipid interaction pathways occurred at least twice, with the development of bacterial-like and archaeal-like membranes. Also, data in literature suggest at least two paths for the emergence of DNA biosynthesis, allowing the stabilization of early life strategies in viruses, archaeas and bacterias. Two billion years later, the eukaryotes arouse, and after 1,5 billion years of evolution, they finally learn how to evolve multicellularity via tissue specialization.}, } @article {pmid38970827, year = {2024}, author = {Ernesto Alvarez, F and Clairambault, J}, title = {Phenotype divergence and cooperation in isogenic multicellularity and in cancer.}, journal = {Mathematical medicine and biology : a journal of the IMA}, volume = {41}, number = {2}, pages = {135-155}, doi = {10.1093/imammb/dqae005}, pmid = {38970827}, issn = {1477-8602}, mesh = {*Neoplasms/pathology/physiopathology ; Humans ; *Phenotype ; Animals ; *Models, Biological ; Cell Differentiation/physiology ; Mathematical Concepts ; Cell Communication/physiology ; Biological Evolution ; }, abstract = {We discuss the mathematical modelling of two of the main mechanisms that pushed forward the emergence of multicellularity: phenotype divergence in cell differentiation and between-cell cooperation. In line with the atavistic theory of cancer, this disease being specific of multicellular animals, we set special emphasis on how both mechanisms appear to be reversed, however not totally impaired, rather hijacked, in tumour cell populations. Two settings are considered: the completely innovating, tinkering, situation of the emergence of multicellularity in the evolution of species, which we assume to be constrained by external pressure on the cell populations, and the completely planned-in the body plan-situation of the physiological construction of a developing multicellular animal from the zygote, or of bet hedging in tumours, assumed to be of clonal formation, although the body plan is largely-but not completely-lost in its constituting cells. We show how cancer impacts these two settings and we sketch mathematical models for them. We present here our contribution to the question at stake with a background from biology, from mathematics and from philosophy of science.}, } @article {pmid38969311, year = {2024}, author = {Bhattacharya, R and Brown, JS and Gatenby, RA and Ibrahim-Hashim, A}, title = {A gene for all seasons: The evolutionary consequences of HIF-1 in carcinogenesis, tumor growth and metastasis.}, journal = {Seminars in cancer biology}, volume = {102-103}, number = {}, pages = {17-24}, doi = {10.1016/j.semcancer.2024.06.003}, pmid = {38969311}, issn = {1096-3650}, support = {R01 CA239219/CA/NCI NIH HHS/United States ; R21 CA269415/CA/NCI NIH HHS/United States ; R01 CA258089/CA/NCI NIH HHS/United States ; U54 CA274507/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Neoplasms/pathology/genetics/metabolism ; Animals ; *Neoplasm Metastasis ; *Carcinogenesis/genetics/pathology ; Hypoxia-Inducible Factor 1/metabolism/genetics ; Neovascularization, Pathologic/genetics/pathology/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Tumor Microenvironment/genetics ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; }, abstract = {Oxygen played a pivotal role in the evolution of multicellularity during the Cambrian Explosion. Not surprisingly, responses to fluctuating oxygen concentrations are integral to the evolution of cancer-a disease characterized by the breakdown of multicellularity. Poorly organized tumor vasculature results in chaotic patterns of blood flow characterized by large spatial and temporal variations in intra-tumoral oxygen concentrations. Hypoxia-inducible growth factor (HIF-1) plays a pivotal role in enabling cells to adapt, metabolize, and proliferate in low oxygen conditions. HIF-1 is often constitutively activated in cancers, underscoring its importance in cancer progression. Here, we argue that the phenotypic changes mediated by HIF-1, in addition to adapting the cancer cells to their local environment, also "pre-adapt" them for proliferation at distant, metastatic sites. HIF-1-mediated adaptations include a metabolic shift towards anaerobic respiration or glycolysis, activation of cell survival mechanisms like phenotypic plasticity and epigenetic reprogramming, and formation of tumor vasculature through angiogenesis. Hypoxia induced epigenetic reprogramming can trigger epithelial to mesenchymal transition in cancer cells-the first step in the metastatic cascade. Highly glycolytic cells facilitate local invasion by acidifying the tumor microenvironment. New blood vessels, formed due to angiogenesis, provide cancer cells a conduit to the circulatory system. Moreover, survival mechanisms acquired by cancer cells in the primary site allow them to remodel tissue at the metastatic site generating tumor promoting microenvironment. Thus, hypoxia in the primary tumor promoted adaptations conducive to all stages of the metastatic cascade from the initial escape entry into a blood vessel, intravascular survival, extravasation into distant tissues, and establishment of secondary tumors.}, } @article {pmid38960448, year = {2024}, author = {Parker, J}, title = {Organ Evolution: Emergence of Multicellular Function.}, journal = {Annual review of cell and developmental biology}, volume = {40}, number = {1}, pages = {51-74}, doi = {10.1146/annurev-cellbio-111822-121620}, pmid = {38960448}, issn = {1530-8995}, mesh = {Animals ; *Biological Evolution ; Humans ; }, abstract = {Instances of multicellularity across the tree of life have fostered the evolution of complex organs composed of distinct cell types that cooperate, producing emergent biological functions. How organs originate is a fundamental evolutionary problem that has eluded deep mechanistic and conceptual understanding. Here I propose a cell- to organ-level transitions framework, whereby cooperative division of labor originates and becomes entrenched between cell types through a process of functional niche creation, cell-type subfunctionalization, and irreversible ratcheting of cell interdependencies. Comprehending this transition hinges on explaining how these processes unfold molecularly in evolving populations. Recent single-cell transcriptomic studies and analyses of terminal fate specification indicate that cellular functions are conferred by modular gene expression programs. These discrete components of functional variation may be deployed or combined within cells to introduce new properties into multicellular niches, or partitioned across cells to establish division of labor. Tracing gene expression program evolution at the level of single cells in populations may reveal transitions toward organ complexity.}, } @article {pmid38951023, year = {2025}, author = {Brückner, DB and Hannezo, E}, title = {Tissue Active Matter: Integrating Mechanics and Signaling into Dynamical Models.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {17}, number = {4}, pages = {}, pmid = {38951023}, issn = {1943-0264}, mesh = {*Models, Biological ; *Signal Transduction ; Animals ; Biomechanical Phenomena ; Morphogenesis ; Humans ; }, abstract = {The importance of physical forces in the morphogenesis, homeostatic function, and pathological dysfunction of multicellular tissues is being increasingly characterized, both theoretically and experimentally. Analogies between biological systems and inert materials such as foams, gels, and liquid crystals have provided striking insights into the core design principles underlying multicellular organization. However, these connections can seem surprising given that a key feature of multicellular systems is their ability to constantly consume energy, providing an active origin for the forces that they produce. Key emerging questions are, therefore, to understand whether and how this activity grants tissues novel properties that do not have counterparts in classical materials, as well as their consequences for biological function. Here, we review recent discoveries at the intersection of active matter and tissue biology, with an emphasis on how modeling and experiments can be combined to understand the dynamics of multicellular systems. These approaches suggest that a number of key biological tissue-scale phenomena, such as morphogenetic shape changes, collective migration, or fate decisions, share unifying design principles that can be described by physical models of tissue active matter.}, } @article {pmid38924758, year = {2024}, author = {Crockett, WW and Shaw, JO and Simpson, C and Kempes, CP}, title = {Physical constraints during Snowball Earth drive the evolution of multicellularity.}, journal = {Proceedings. Biological sciences}, volume = {291}, number = {2025}, pages = {20232767}, pmid = {38924758}, issn = {1471-2954}, mesh = {*Biological Evolution ; Ice Cover ; Eukaryota/physiology ; Earth, Planet ; Fossils ; Temperature ; }, abstract = {Molecular and fossil evidence suggests that complex eukaryotic multicellularity evolved during the late Neoproterozoic era, coincident with Snowball Earth glaciations, where ice sheets covered most of the globe. During this period, environmental conditions-such as seawater temperature and the availability of photosynthetically active light in the oceans-likely changed dramatically. Such changes would have had significant effects on both resource availability and optimal phenotypes. Here, we construct and apply mechanistic models to explore (i) how environmental changes during Snowball Earth and biophysical constraints generated selective pressures, and (ii) how these pressures may have had differential effects on organisms with different forms of biological organization. By testing a series of alternative-and commonly debated-hypotheses, we demonstrate how multicellularity was likely acquired differently in eukaryotes and prokaryotes owing to selective differences on their size due to the biophysical and metabolic regimes they inhabit: decreasing temperatures and resource availability instigated by the onset of glaciations generated selective pressures towards smaller sizes in organisms in the diffusive regime and towards larger sizes in motile heterotrophs. These results suggest that changing environmental conditions during Snowball Earth glaciations gave multicellular eukaryotes an evolutionary advantage, paving the way for the complex multicellular lineages that followed.}, } @article {pmid38923935, year = {2024}, author = {Ghosh, S and Mellado Sanchez, M and Sue-Ob, K and Roy, D and Jones, A and Blazquez, MA and Sadanandom, A}, title = {Charting the evolutionary path of the SUMO modification system in plants reveals molecular hardwiring of development to stress adaptation.}, journal = {The Plant cell}, volume = {36}, number = {9}, pages = {3131-3144}, pmid = {38923935}, issn = {1532-298X}, support = {BB/V003534/1//BBSRC/ ; }, mesh = {*Sumoylation ; *Plants/metabolism/genetics ; Plant Proteins/metabolism/genetics ; Small Ubiquitin-Related Modifier Proteins/metabolism/genetics ; Stress, Physiological ; Adaptation, Physiological/genetics ; Evolution, Molecular ; Protein Processing, Post-Translational ; Plant Development/genetics ; }, abstract = {SUMO modification is part of the spectrum of Ubiquitin-like (UBL) systems that give rise to proteoform complexity through post-translational modifications (PTMs). Proteoforms are essential modifiers of cell signaling for plant adaptation to changing environments. Exploration of the evolutionary emergence of Ubiquitin-like (UBL) systems unveils their origin from prokaryotes, where it is linked to the mechanisms that enable sulfur uptake into biomolecules. We explore the emergence of the SUMO machinery across the plant lineage from single-cell to land plants. We reveal the evolutionary point at which plants acquired the ability to form SUMO chains through the emergence of SUMO E4 ligases, hinting at its role in facilitating multicellularity. Additionally, we explore the possible mechanism for the neofunctionalization of SUMO proteases through the fusion of conserved catalytic domains with divergent sequences. We highlight the pivotal role of SUMO proteases in plant development and adaptation, offering new insights into target specificity mechanisms of SUMO modification during plant evolution. Correlating the emergence of adaptive traits in the plant lineage with established experimental evidence for SUMO in developmental processes, we propose that SUMO modification has evolved to link developmental processes to adaptive functions in land plants.}, } @article {pmid38908045, year = {2024}, author = {Mascarenhas, DP and Zamboni, DS}, title = {Innate immune responses and monocyte-derived phagocyte recruitment in protective immunity to pathogenic bacteria: insights from Legionella pneumophila.}, journal = {Current opinion in microbiology}, volume = {80}, number = {}, pages = {102495}, doi = {10.1016/j.mib.2024.102495}, pmid = {38908045}, issn = {1879-0364}, mesh = {*Legionella pneumophila/immunology/pathogenicity ; *Immunity, Innate ; Humans ; Animals ; *Legionnaires' Disease/immunology/microbiology ; Phagocytes/immunology/microbiology ; Type IV Secretion Systems/immunology/genetics/metabolism ; Inflammasomes/immunology/metabolism ; Monocytes/immunology/microbiology ; Virulence Factors/immunology/metabolism ; Macrophages/immunology/microbiology ; Host-Pathogen Interactions/immunology ; }, abstract = {Legionella species are Gram-negative intracellular bacteria that evolved in soil and freshwater environments, where they infect and replicate within various unicellular protozoa. The primary virulence factor of Legionella is the expression of a type IV secretion system (T4SS), which contributes to the translocation of effector proteins that subvert biological processes of the host cells. Because of its evolution in unicellular organisms, T4SS effector proteins are not adapted to subvert specific mammalian signaling pathways and immunity. Consequently, Legionella pneumophila has emerged as an interesting infection model for investigating immune responses against pathogenic bacteria in multicellular organisms. This review highlights recent advances in our understanding of mammalian innate immunity derived from studies involving L. pneumophila. This includes recent insights into inflammasome-mediated mechanisms restricting bacterial replication in macrophages, mechanisms inducing cell death in response to infection, induction of effector-triggered immunity, activation of specific pulmonary cell types in mammalian lungs, and the protective role of recruiting monocyte-derived cells to infected lungs.}, } @article {pmid38907301, year = {2024}, author = {Martinez, P and Bailly, X and Sprecher, SG and Hartenstein, V}, title = {The Acoel nervous system: morphology and development.}, journal = {Neural development}, volume = {19}, number = {1}, pages = {9}, pmid = {38907301}, issn = {1749-8104}, support = {PID2021-124415NB-I00//Spanish "Ministerio de Ciencia, Innovación y Universidades"/ ; 310030_219348/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Animals ; *Nervous System/growth & development/embryology ; *Neurogenesis/physiology ; Platyhelminths/growth & development/physiology ; Biological Evolution ; Neurons/cytology/physiology ; }, abstract = {Acoel flatworms have played a relevant role in classical (and current) discussions on the evolutionary origin of bilaterian animals. This is mostly derived from the apparent simplicity of their body architectures. This tenet has been challenged over the last couple of decades, mostly because detailed studies of their morphology and the introduction of multiple genomic technologies have unveiled a complexity of cell types, tissular arrangements and patterning mechanisms that were hidden below this 'superficial' simplicity. One tissue that has received a particular attention has been the nervous system (NS). The combination of ultrastructural and single cell methodologies has revealed unique cellular diversity and developmental trajectories for most of their neurons and associated sensory systems. Moreover, the great diversity in NS architectures shown by different acoels offers us with a unique group of animals where to study key aspects of neurogenesis and diversification od neural systems over evolutionary time.In this review we revisit some recent developments in the characterization of the acoel nervous system structure and the regulatory mechanisms that contribute to their embryological development. We end up by suggesting some promising avenues to better understand how this tissue is organized in its finest cellular details and how to achieve a deeper knowledge of the functional roles that genes and gene networks play in its construction.}, } @article {pmid38894655, year = {2024}, author = {Murayama, F and Asai, H and Patra, AK and Wake, H and Miyata, T and Hattori, Y}, title = {A novel preparation for histological analyses of intraventricular macrophages in the embryonic brain.}, journal = {Development, growth & differentiation}, volume = {66}, number = {5}, pages = {329-337}, pmid = {38894655}, issn = {1440-169X}, support = {JPMJCR22P6//Core Research for Evolutional Science and Technology/ ; JPMJFR214C//Fusion Oriented REsearch for disruptive Science and Technology/ ; JP20H05899//Japan Society for the Promotion of Science/ ; JP21H02656//Japan Society for the Promotion of Science/ ; JP23H02658//Japan Society for the Promotion of Science/ ; JP23H04161//Japan Society for the Promotion of Science/ ; //The Uehara Memorial Foundation/ ; //Takeda Science Foundation/ ; //The Sumitomo Foundation/ ; //The Nakajima Foundation/ ; //Tokai Pathways to Global Excellence (T-GEx)/ ; }, mesh = {Animals ; *Macrophages/cytology ; Mice ; *Brain/embryology/cytology ; Microglia/cytology/metabolism ; Cerebral Ventricles/embryology/cytology ; }, abstract = {Microglia colonize the brain starting on embryonic day (E) 9.5 in mice, and their population increases with development. We have previously demonstrated that some microglia are derived from intraventricular macrophages, which frequently infiltrate the pallium at E12.5. To address how the infiltration of intraventricular macrophages is spatiotemporally regulated, histological analyses detecting how these cells associate with the surrounding cells at the site of infiltration into the pallial surface are essential. Using two-photon microscopy-based in vivo imaging, we demonstrated that most intraventricular macrophages adhere to the ventricular surface. This is a useful tool for imaging intraventricular macrophages maintaining their original position, but this method cannot be used for observing deeper brain regions. Meanwhile, we found that conventional cryosection-based and naked pallial slice-based observation resulted in unexpected detachment from the ventricular surface of intraventricular macrophages and their mislocation, suggesting that previous histological analyses might have failed to determine their physiological number and location in the ventricular space. To address this, we sought to establish a methodological preparation that enables us to delineate the structure and cellular interactions when intraventricular macrophages infiltrate the pallium. Here, we report that brain slices pretreated with agarose-embedding maintained adequate density and proper positioning of intraventricular macrophages on the ventricular surface. This method also enabled us to perform the immunostaining. We believe that this is helpful for conducting histological analyses to elucidate the mechanisms underlying intraventricular macrophage infiltration into the pallium and their cellular properties, leading to further understanding of the process of microglial colonization into the developing brain.}, } @article {pmid38883608, year = {2024}, author = {Puginier, E and Leal-Fischer, K and Gaitan, J and Lallouet, M and Scotti, PA and Raoux, M and Lang, J}, title = {Extracellular electrophysiology on clonal human β-cell spheroids.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1402880}, pmid = {38883608}, issn = {1664-2392}, mesh = {Humans ; *Insulin-Secreting Cells/physiology/metabolism/cytology ; *Spheroids, Cellular ; Electrophysiological Phenomena ; Insulin Secretion/physiology ; Glucose/metabolism/pharmacology ; Insulin/metabolism ; Action Potentials/physiology ; Animals ; }, abstract = {BACKGROUND: Pancreatic islets are important in nutrient homeostasis and improved cellular models of clonal origin may very useful especially in view of relatively scarce primary material. Close 3D contact and coupling between β-cells are a hallmark of physiological function improving signal/noise ratios. Extracellular electrophysiology using micro-electrode arrays (MEA) is technically far more accessible than single cell patch clamp, enables dynamic monitoring of electrical activity in 3D organoids and recorded multicellular slow potentials (SP) provide unbiased insight in cell-cell coupling.

OBJECTIVE: We have therefore asked whether 3D spheroids enhance clonal β-cell function such as electrical activity and hormone secretion using human EndoC-βH1, EndoC-βH5 and rodent INS-1 832/13 cells.

METHODS: Spheroids were formed either by hanging drop or proprietary devices. Extracellular electrophysiology was conducted using multi-electrode arrays with appropriate signal extraction and hormone secretion measured by ELISA.

RESULTS: EndoC-βH1 spheroids exhibited increased signals in terms of SP frequency and especially amplitude as compared to monolayers and even single cell action potentials (AP) were quantifiable. Enhanced electrical signature in spheroids was accompanied by an increase in the glucose stimulated insulin secretion index. EndoC-βH5 monolayers and spheroids gave electrophysiological profiles similar to EndoC-βH1, except for a higher electrical activity at 3 mM glucose, and exhibited moreover a biphasic profile. Again, physiological concentrations of GLP-1 increased AP frequency. Spheroids also exhibited a higher secretion index. INS-1 cells did not form stable spheroids, but overexpression of connexin 36, required for cell-cell coupling, increased glucose responsiveness, dampened basal activity and consequently augmented the stimulation index.

CONCLUSION: In conclusion, spheroid formation enhances physiological function of the human clonal β-cell lines and these models may provide surrogates for primary islets in extracellular electrophysiology.}, } @article {pmid38875896, year = {2024}, author = {Ajay, A and Begum, T and Arya, A and Kumar, K and Ahmad, S}, title = {Global and local genomic features together modulate the spontaneous single nucleotide mutation rate.}, journal = {Computational biology and chemistry}, volume = {112}, number = {}, pages = {108107}, doi = {10.1016/j.compbiolchem.2024.108107}, pmid = {38875896}, issn = {1476-928X}, mesh = {*Base Composition ; Mutation Rate ; Genomics ; Genome/genetics ; Nucleotides/genetics ; Prokaryotic Cells/metabolism ; CpG Islands/genetics ; Animals ; }, abstract = {Spontaneous mutations are evolutionary engines as they generate variants for the evolutionary downstream processes that give rise to speciation and adaptation. Single nucleotide mutations (SNM) are the most abundant type of mutations among them. Here, we perform a meta-analysis to quantify the influence of selected global genomic parameters (genome size, genomic GC content, genomic repeat fraction, number of coding genes, gene count, and strand bias in prokaryotes) and local genomic features (local GC content, repeat content, CpG content and the number of SNM at CpG islands) on spontaneous SNM rates across the tree of life (prokaryotes, unicellular eukaryotes, multicellular eukaryotes) using wild-type sequence data in two different taxon classification systems. We find that the spontaneous SNM rates in our data are correlated with many genomic features in prokaryotes and unicellular eukaryotes irrespective of their sample sizes. On the other hand, only the number of coding genes was correlated with the spontaneous SNM rates in multicellular eukaryotes primarily contributed by vertebrates data. Considering local features, we notice that local GC content and CpG content significantly were correlated with the spontaneous SNM rates in the unicellular eukaryotes, while local repeat fraction is an important feature in prokaryotes and certain specific uni- and multi-cellular eukaryotes. Such predictive features of the spontaneous SNM rates often support non-linear models as the best fit compared to the linear model. We also observe that the strand asymmetry in prokaryotes plays an important role in determining the spontaneous SNM rates but the SNM spectrum does not.}, } @article {pmid38848676, year = {2024}, author = {Patel, AS and Yanai, I}, title = {A developmental constraint model of cancer cell states and tumor heterogeneity.}, journal = {Cell}, volume = {187}, number = {12}, pages = {2907-2918}, pmid = {38848676}, issn = {1097-4172}, support = {R01 LM013522/LM/NLM NIH HHS/United States ; R21 CA264361/CA/NCI NIH HHS/United States ; U01 CA260432/CA/NCI NIH HHS/United States ; U54 CA263001/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Carcinogenesis/pathology/genetics ; *Models, Biological ; *Neoplasms/pathology/genetics/metabolism ; Single-Cell Analysis ; Transcriptome/genetics ; Neoplastic Stem Cells/pathology ; }, abstract = {Cancer is a disease that stems from a fundamental liability inherent to multicellular life forms in which an individual cell is capable of reneging on the interests of the collective organism. Although cancer is commonly described as an evolutionary process, a less appreciated aspect of tumorigenesis may be the constraints imposed by the organism's developmental programs. Recent work from single-cell transcriptomic analyses across a range of cancer types has revealed the recurrence, plasticity, and co-option of distinct cellular states among cancer cell populations. Here, we note that across diverse cancer types, the observed cell states are proximate within the developmental hierarchy of the cell of origin. We thus posit a model by which cancer cell states are directly constrained by the organism's "developmental map." According to this model, a population of cancer cells traverses the developmental map, thereby generating a heterogeneous set of states whose interactions underpin emergent tumor behavior.}, } @article {pmid38844553, year = {2024}, author = {Liao, H and Choi, J and Shendure, J}, title = {Molecular recording using DNA Typewriter.}, journal = {Nature protocols}, volume = {19}, number = {10}, pages = {2833-2862}, pmid = {38844553}, issn = {1750-2799}, mesh = {Humans ; *DNA/genetics ; *Gene Editing/methods ; HEK293 Cells ; RNA, Guide, CRISPR-Cas Systems/genetics ; CRISPR-Cas Systems ; }, abstract = {Recording molecular information to genomic DNA is a powerful means of investigating topics ranging from multicellular development to cancer evolution. With molecular recording based on genome editing, events such as cell divisions and signaling pathway activity drive specific alterations in a cell's DNA, marking the genome with information about a cell's history that can be read out after the fact. Although genome editing has been used for molecular recording, capturing the temporal relationships among recorded events in mammalian cells remains challenging. The DNA Typewriter system overcomes this limitation by leveraging prime editing to facilitate sequential insertions to an engineered genomic region. DNA Typewriter includes three distinct components: DNA Tape as the 'substrate' to which edits accrue in an ordered manner, the prime editor enzyme, and prime editing guide RNAs, which program insertional edits to DNA Tape. In this protocol, we describe general design considerations for DNA Typewriter, step-by-step instructions on how to perform recording experiments by using DNA Typewriter in HEK293T cells, and example scripts for analyzing DNA Typewriter data (https://doi.org/10.6084/m9.figshare.22728758). This protocol covers two main applications of DNA Typewriter: recording sequential transfection events with programmed barcode insertions by using prime editing and recording lineage information during the expansion of a single cell to many. Compared with other methods that are compatible with mammalian cells, DNA Typewriter enables the recording of temporal information with higher recording capacities and can be completed within 4-6 weeks with basic expertise in molecular cloning, mammalian cell culturing and DNA sequencing data analysis.}, } @article {pmid38839375, year = {2024}, author = {Errbii, M and Gadau, J and Becker, K and Schrader, L and Oettler, J}, title = {Causes and consequences of a complex recombinational landscape in the ant Cardiocondyla obscurior.}, journal = {Genome research}, volume = {34}, number = {6}, pages = {863-876}, pmid = {38839375}, issn = {1549-5469}, mesh = {Animals ; *Ants/genetics ; *Recombination, Genetic ; Chromosome Mapping ; Haplotypes ; Genetic Variation ; Genome, Insect ; Selection, Genetic ; Evolution, Molecular ; }, abstract = {Eusocial Hymenoptera have the highest recombination rates among all multicellular animals studied so far, but it is unclear why this is and how this affects the biology of individual species. A high-resolution linkage map for the ant Cardiocondyla obscurior corroborates genome-wide high recombination rates reported for ants (8.1 cM/Mb). However, recombination is locally suppressed in regions that are enriched with TEs, that have strong haplotype divergence, or that show signatures of epistatic selection in C. obscurior The results do not support the hypotheses that high recombination rates are linked to phenotypic plasticity or to modulating selection efficiency. Instead, genetic diversity and the frequency of structural variants correlate positively with local recombination rates, potentially compensating for the low levels of genetic variation expected in haplodiploid social Hymenoptera with low effective population size. Ultimately, the data show that recombination contributes to within-population polymorphism and to the divergence of the lineages within C. obscurior.}, } @article {pmid38832756, year = {2024}, author = {Bierenbroodspot, MJ and Pröschold, T and Fürst-Jansen, JMR and de Vries, S and Irisarri, I and Darienko, T and de Vries, J}, title = {Phylogeny and evolution of streptophyte algae.}, journal = {Annals of botany}, volume = {134}, number = {3}, pages = {385-400}, pmid = {38832756}, issn = {1095-8290}, support = {509535047//German Research Foundation/ ; 852725//European Union's Horizon 2020 research and innovation/ ; }, mesh = {*Phylogeny ; *Streptophyta/genetics/physiology ; *Biological Evolution ; }, abstract = {The Streptophyta emerged about a billion years ago. Nowadays, this branch of the green lineage is most famous for one of its clades, the land plants (Embryophyta). Although Embryophyta make up the major share of species numbers in Streptophyta, there is a diversity of probably >5000 species of streptophyte algae that form a paraphyletic grade next to land plants. Here, we focus on the deep divergences that gave rise to the diversity of streptophytes, hence particularly on the streptophyte algae. Phylogenomic efforts have not only clarified the position of streptophyte algae relative to land plants, but recent efforts have also begun to unravel the relationships and major radiations within streptophyte algal diversity. We illustrate how new phylogenomic perspectives have changed our view on the evolutionary emergence of key traits, such as intricate signalling networks that are intertwined with multicellular growth and the chemodiverse hotbed from which they emerged. These traits are key for the biology of land plants but were bequeathed from their algal progenitors.}, } @article {pmid38820160, year = {2024}, author = {Stillinovic, M and Sarangdhar, MA and Andina, N and Tardivel, A and Greub, F and Bombaci, G and Ansermet, C and Zatti, M and Saha, D and Xiong, J and Sagae, T and Yokogawa, M and Osawa, M and Heller, M and Keogh, A and Keller, I and Angelillo-Scherrer, A and Allam, R}, title = {Ribonuclease inhibitor and angiogenin system regulates cell type-specific global translation.}, journal = {Science advances}, volume = {10}, number = {22}, pages = {eadl0320}, pmid = {38820160}, issn = {2375-2548}, mesh = {*Ribonuclease, Pancreatic/metabolism/genetics ; Humans ; *Protein Biosynthesis ; Animals ; Mice ; *Ribosomes/metabolism ; RNA, Messenger/genetics/metabolism ; Gene Expression Regulation ; Cell Line ; Organ Specificity ; Carrier Proteins ; }, abstract = {Translation of mRNAs is a fundamental process that occurs in all cell types of multicellular organisms. Conventionally, it has been considered a default step in gene expression, lacking specific regulation. However, recent studies have documented that certain mRNAs exhibit cell type-specific translation. Despite this, it remains unclear whether global translation is controlled in a cell type-specific manner. By using human cell lines and mouse models, we found that deletion of the ribosome-associated protein ribonuclease inhibitor 1 (RNH1) decreases global translation selectively in hematopoietic-origin cells but not in the non-hematopoietic-origin cells. RNH1-mediated cell type-specific translation is mechanistically linked to angiogenin-induced ribosomal biogenesis. Collectively, this study unravels the existence of cell type-specific global translation regulators and highlights the complex translation regulation in vertebrates.}, } @article {pmid38813885, year = {2024}, author = {Bennett, GM and Kwak, Y and Maynard, R}, title = {Endosymbioses Have Shaped the Evolution of Biological Diversity and Complexity Time and Time Again.}, journal = {Genome biology and evolution}, volume = {16}, number = {6}, pages = {}, pmid = {38813885}, issn = {1759-6653}, support = {NSF-1347116//National Science Foundation/ ; GT15982/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Symbiosis ; *Biological Evolution ; Animals ; Bacteria/genetics ; Biodiversity ; Evolution, Molecular ; }, abstract = {Life on Earth comprises prokaryotes and a broad assemblage of endosymbioses. The pages of Molecular Biology and Evolution and Genome Biology and Evolution have provided an essential window into how these endosymbiotic interactions have evolved and shaped biological diversity. Here, we provide a current perspective on this knowledge by drawing on decades of revelatory research published in Molecular Biology and Evolution and Genome Biology and Evolution, and insights from the field at large. The accumulated work illustrates how endosymbioses provide hosts with novel phenotypes that allow them to transition between adaptive landscapes to access environmental resources. Such endosymbiotic relationships have shaped and reshaped life on Earth. The early serial establishment of mitochondria and chloroplasts through endosymbioses permitted massive upscaling of cellular energetics, multicellularity, and terrestrial planetary greening. These endosymbioses are also the foundation upon which all later ones are built, including everything from land-plant endosymbioses with fungi and bacteria to nutritional endosymbioses found in invertebrate animals. Common evolutionary mechanisms have shaped this broad range of interactions. Endosymbionts generally experience adaptive and stochastic genome streamlining, the extent of which depends on several key factors (e.g. mode of transmission). Hosts, in contrast, adapt complex mechanisms of resource exchange, cellular integration and regulation, and genetic support mechanisms to prop up degraded symbionts. However, there are significant differences between endosymbiotic interactions not only in how partners have evolved with each other but also in the scope of their influence on biological diversity. These differences are important considerations for predicting how endosymbioses will persist and adapt to a changing planet.}, } @article {pmid38811562, year = {2024}, author = {Li, XC and Gandara, L and Ekelöf, M and Richter, K and Alexandrov, T and Crocker, J}, title = {Rapid response of fly populations to gene dosage across development and generations.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4551}, pmid = {38811562}, issn = {2041-1723}, mesh = {Animals ; *Drosophila Proteins/genetics/metabolism ; *Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Female ; *Drosophila melanogaster/genetics/growth & development/embryology ; *Gene Dosage ; Homeodomain Proteins/genetics/metabolism ; Phenotype ; Male ; Embryo, Nonmammalian/metabolism ; Drosophila/genetics/embryology/metabolism ; Mutagenesis ; Trans-Activators ; }, abstract = {Although the effects of genetic and environmental perturbations on multicellular organisms are rarely restricted to single phenotypic layers, our current understanding of how developmental programs react to these challenges remains limited. Here, we have examined the phenotypic consequences of disturbing the bicoid regulatory network in early Drosophila embryos. We generated flies with two extra copies of bicoid, which causes a posterior shift of the network's regulatory outputs and a decrease in fitness. We subjected these flies to EMS mutagenesis, followed by experimental evolution. After only 8-15 generations, experimental populations have normalized patterns of gene expression and increased survival. Using a phenomics approach, we find that populations were normalized through rapid increases in embryo size driven by maternal changes in metabolism and ovariole development. We extend our results to additional populations of flies, demonstrating predictability. Together, our results necessitate a broader view of regulatory network evolution at the systems level.}, } @article {pmid38798503, year = {2024}, author = {Perotti, O and Esparza, GV and Booth, DS}, title = {A red algal polysaccharide influences the multicellular development of the choanoflagellate Salpingoeca rosetta.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38798503}, issn = {2692-8205}, support = {R24 GM137782/GM/NIGMS NIH HHS/United States ; T32 GM139786/GM/NIGMS NIH HHS/United States ; }, abstract = {We uncovered an interaction between a choanoflagellate and alga, in which porphyran, a polysaccharide produced by the red alga Porphyra umbilicalis, induces multicellular development in the choanoflagellate Salpingoeca rosetta. We first noticed this possible interaction when we tested the growth of S. rosetta in media that was steeped with P. umbilicalis as a nutritional source. Under those conditions, S. rosetta formed multicellular rosette colonies even in the absence of any bacterial species that can induce rosette development. In biochemical purifications, we identified porphyran, a extracellular polysaccharide produced by red algae, as the rosette inducing factor The response of S. rosetta to porphyran provides a biochemical insight for associations between choanoflagellates and algae that have been observed since the earliest descriptions of choanoflagellates. Moreover, this work provides complementary evidence to ecological and geochemical studies that show the profound impact algae have exerted on eukaryotes and their evolution, including a rise in algal productivity that coincided with the origin of animals, the closest living relatives of choanoflagellates.}, } @article {pmid38791309, year = {2024}, author = {Bibo-Verdugo, B and Salvesen, G}, title = {Evolution of Caspases and the Invention of Pyroptosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791309}, issn = {1422-0067}, mesh = {*Pyroptosis ; Humans ; *Caspases/metabolism ; Animals ; *Immunity, Innate ; Evolution, Molecular ; Apoptosis ; }, abstract = {The protein scaffold that includes the caspases is ancient and found in all domains of life. However, the stringent specificity that defines the caspase biologic function is relatively recent and found only in multicellular animals. During the radiation of the Chordata, members of the caspase family adopted roles in immunity, events coinciding with the development of substrates that define the modern innate immune response. This review focuses on the switch from the non-inflammatory cellular demise of apoptosis to the highly inflammatory innate response driven by distinct members of the caspase family, and the interplay between these two regulated cell death pathways.}, } @article {pmid38790063, year = {2024}, author = {Zhang, B and Xiao, L and Lyu, L and Zhao, F and Miao, M}, title = {Exploring the landscape of symbiotic diversity and distribution in unicellular ciliated protists.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {96}, pmid = {38790063}, issn = {2049-2618}, mesh = {*Symbiosis ; *Ciliophora/genetics/classification/physiology ; *Bacteria/genetics/classification ; Archaea/genetics/classification ; Phylogeny ; Metagenome ; Biodiversity ; }, abstract = {BACKGROUND: The eukaryotic-bacterial symbiotic system plays an important role in various physiological, developmental, and evolutionary processes. However, our current understanding is largely limited to multicellular eukaryotes without adequate consideration of diverse unicellular protists, including ciliates.

RESULTS: To investigate the bacterial profiles associated with unicellular organisms, we collected 246 ciliate samples spanning the entire Ciliophora phylum and conducted single-cell based metagenome sequencing. This effort has yielded the most extensive collection of bacteria linked to unicellular protists to date. From this dataset, we identified 883 bacterial species capable of cohabiting with ciliates, unveiling the genomes of 116 novel bacterial cohabitants along with 7 novel archaeal cohabitants. Highlighting the intimate relationship between ciliates and their cohabitants, our study unveiled that over 90% of ciliates coexist with bacteria, with individual hosts fostering symbiotic relationships with multiple bacteria concurrently, resulting in the observation of seven distinct symbiotic patterns among bacteria. Our exploration of symbiotic mechanisms revealed the impact of host digestion on the intracellular diversity of cohabitants. Additionally, we identified the presence of eukaryotic-like proteins in bacteria as a potential contributing factor to their resistance against host digestion, thereby expanding their potential host range.

CONCLUSIONS: As the first large-scale analysis of prokaryotic associations with ciliate protists, this study provides a valuable resource for future research on eukaryotic-bacterial symbioses. Video Abstract.}, } @article {pmid38778808, year = {2023}, author = {Ondracka, A and Dudin, O and Bråte, J}, title = {Time-resolved small RNA transcriptomics of the ichthyosporean Sphaeroforma arctica.}, journal = {F1000Research}, volume = {12}, number = {}, pages = {542}, pmid = {38778808}, issn = {2046-1402}, mesh = {*Transcriptome ; Mesomycetozoea/genetics ; MicroRNAs/genetics ; Gene Expression Profiling ; }, abstract = {Ichthyosporea, a clade of holozoans, represent a clade closely related to animals, and thus hold a key phylogenetic position for understanding the origin of animals. We have previously discovered that an ichthyosporean, Sphaeroforma arctica, contains microRNAs (miRNAs) as well as the miRNA processing machinery. This was the first discovery of miRNAs among the closest single-celled relatives of animals and raised intriguing questions about the roles of regulatory small RNAs in cell development and differentiation in unicellular eukaryotes. Like many ichthyosporeans, S. arctica also undergoes a transient multicellular developmental life cycle. As miRNAs are, among other roles, key regulators of gene expression during development in animals, we wanted to investigate the dynamics of miRNAs during the developmental cycle in S. arctica. Here we have therefore collected a comprehensive time-resolved small RNA transcriptome linked to specific life stages with a substantially higher sequencing depth than before, which can enable further discovery of functionally relevant small RNAs. The data consists of Illumina-sequenced small RNA libraries from two independent biological replicates of the entire life cycle of S. arctica with high temporal resolution. The dataset is directly linked and comes from the same samples as a previously published mRNA-seq dataset, thus enabling direct cross-functional analyses.}, } @article {pmid38773319, year = {2024}, author = {Cho, CJ and Brown, JW and Mills, JC}, title = {Origins of cancer: ain't it just mature cells misbehaving?.}, journal = {The EMBO journal}, volume = {43}, number = {13}, pages = {2530-2551}, pmid = {38773319}, issn = {1460-2075}, support = {R01 CA239645/CA/NCI NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R21 AI156236/AI/NIAID NIH HHS/United States ; W81XWH2210327//DOD | USA | MEDCOM | CDMRP | DOD Peer Reviewed Cancer Research Program (PRCRP)/ ; P30 DK052574/DK/NIDDK NIH HHS/United States ; K08 DK132496/DK/NIDDK NIH HHS/United States ; R01 DK105129/DK/NIDDK NIH HHS/United States ; R01DK105129//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; R01 DK134531/DK/NIDDK NIH HHS/United States ; W81XWH-20-1-0630//DOD | USA | MEDCOM | CDMRP | DOD Peer Reviewed Cancer Research Program (PRCRP)/ ; R01DK134531//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; }, mesh = {Humans ; Animals ; *Neoplasms/pathology/genetics ; *Cell Differentiation ; Tumor Suppressor Protein p53/metabolism/genetics ; Cell Transformation, Neoplastic/genetics/pathology ; Stem Cells ; Carcinogenesis/pathology ; }, abstract = {A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells. First, we examine the unique characteristics of differentiated cell division, focusing on why differentiated cells are more susceptible than stem cells to accumulating mutations. Next, we investigate why the evolution of multicellularity in animals likely required plastic differentiated cells that maintain the capacity to return to the cell cycle and required the tumor suppressor p53. Finally, we examine an example of an evolutionarily conserved program for the plasticity of differentiated cells, paligenosis, which helps explain the origins of cancers that arise in adults. Altogether, we highlight new perspectives for understanding the development of cancer and new strategies for preventing carcinogenic cellular transformations from occurring.}, } @article {pmid38773187, year = {2024}, author = {MacDonald, N and Raven, N and Diep, W and Evans, S and Pannipitiya, S and Bramwell, G and Vanbeek, C and Thomas, F and Russell, T and Dujon, AM and Telonis-Scott, M and Ujvari, B}, title = {The molecular evolution of cancer associated genes in mammals.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {11650}, pmid = {38773187}, issn = {2045-2322}, mesh = {Animals ; *Evolution, Molecular ; *Mammals/genetics ; *Neoplasms/genetics ; *Phylogeny ; Humans ; Selection, Genetic ; Oncogenes/genetics ; Genes, Tumor Suppressor ; Genetic Predisposition to Disease ; }, abstract = {Cancer is a disease that many multicellular organisms have faced for millions of years, and species have evolved various tumour suppression mechanisms to control oncogenesis. Although cancer occurs across the tree of life, cancer related mortality risks vary across mammalian orders, with Carnivorans particularly affected. Evolutionary theory predicts different selection pressures on genes associated with cancer progression and suppression, including oncogenes, tumour suppressor genes and immune genes. Therefore, we investigated the evolutionary history of cancer associated gene sequences across 384 mammalian taxa, to detect signatures of selection across categories of oncogenes (GRB2, FGL2 and CDC42), tumour suppressors (LITAF, Casp8 and BRCA2) and immune genes (IL2, CD274 and B2M). This approach allowed us to conduct a fine scale analysis of gene wide and site-specific signatures of selection across mammalian lineages under the lens of cancer susceptibility. Phylogenetic analyses revealed that for most species the evolution of cancer associated genes follows the species' evolution. The gene wide selection analyses revealed oncogenes being the most conserved, tumour suppressor and immune genes having similar amounts of episodic diversifying selection. Despite BRCA2's status as a key caretaker gene, episodic diversifying selection was detected across mammals. The site-specific selection analyses revealed that the two apoptosis associated domains of the Casp8 gene of bats (Chiroptera) are under opposing forces of selection (positive and negative respectively), highlighting the importance of site-specific selection analyses to understand the evolution of highly complex gene families. Our results highlighted the need to critically assess different types of selection pressure on cancer associated genes when investigating evolutionary adaptations to cancer across the tree of life. This study provides an extensive assessment of cancer associated genes in mammals with highly representative, and substantially large sample size for a comparative genomic analysis in the field and identifies various avenues for future research into the mechanisms of cancer resistance and susceptibility in mammals.}, } @article {pmid38735988, year = {2024}, author = {Aprile, D and Patrone, D and Peluso, G and Galderisi, U}, title = {Multipotent/pluripotent stem cell populations in stromal tissues and peripheral blood: exploring diversity, potential, and therapeutic applications.}, journal = {Stem cell research & therapy}, volume = {15}, number = {1}, pages = {139}, pmid = {38735988}, issn = {1757-6512}, support = {PE0000006 MNESYS//European Commission/ ; }, mesh = {Humans ; *Pluripotent Stem Cells/cytology/metabolism ; *Multipotent Stem Cells/cytology/metabolism ; Cell Differentiation ; Stromal Cells/cytology/metabolism ; Animals ; }, abstract = {The concept of "stemness" incorporates the molecular mechanisms that regulate the unlimited self-regenerative potential typical of undifferentiated primitive cells. These cells possess the unique ability to navigate the cell cycle, transitioning in and out of the quiescent G0 phase, and hold the capacity to generate diverse cell phenotypes. Stem cells, as undifferentiated precursors endow with extraordinary regenerative capabilities, exhibit a heterogeneous and tissue-specific distribution throughout the human body. The identification and characterization of distinct stem cell populations across various tissues have revolutionized our understanding of tissue homeostasis and regeneration. From the hematopoietic to the nervous and musculoskeletal systems, the presence of tissue-specific stem cells underlines the complex adaptability of multicellular organisms. Recent investigations have revealed a diverse cohort of non-hematopoietic stem cells (non-HSC), primarily within bone marrow and other stromal tissue, alongside established hematopoietic stem cells (HSC). Among these non-HSC, a rare subset exhibits pluripotent characteristics. In vitro and in vivo studies have demonstrated the remarkable differentiation potential of these putative stem cells, known by various names including multipotent adult progenitor cells (MAPC), marrow-isolated adult multilineage inducible cells (MIAMI), small blood stem cells (SBSC), very small embryonic-like stem cells (VSELs), and multilineage differentiating stress enduring cells (MUSE). The diverse nomenclatures assigned to these primitive stem cell populations may arise from different origins or varied experimental methodologies. This review aims to present a comprehensive comparison of various subpopulations of multipotent/pluripotent stem cells derived from stromal tissues. By analysing isolation techniques and surface marker expression associated with these populations, we aim to delineate the similarities and distinctions among stromal tissue-derived stem cells. Understanding the nuances of these tissue-specific stem cells is critical for unlocking their therapeutic potential and advancing regenerative medicine. The future of stem cells research should prioritize the standardization of methodologies and collaborative investigations in shared laboratory environments. This approach could mitigate variability in research outcomes and foster scientific partnerships to fully exploit the therapeutic potential of pluripotent stem cells.}, } @article {pmid38734320, year = {2024}, author = {Lenz, G}, title = {Heterogeneity generating capacity in tumorigenesis and cancer therapeutics.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {5}, pages = {167226}, doi = {10.1016/j.bbadis.2024.167226}, pmid = {38734320}, issn = {1879-260X}, mesh = {Humans ; *Neoplasms/genetics/pathology/therapy/metabolism ; *Carcinogenesis/genetics/pathology ; Genetic Heterogeneity ; Oncogenes/genetics ; Animals ; Cell Transformation, Neoplastic/genetics/metabolism ; Genes, Tumor Suppressor ; Gene Expression Regulation, Neoplastic ; }, abstract = {Cells of multicellular organisms generate heterogeneity in a controlled and transient fashion during embryogenesis, which can be reactivated in pathologies such as cancer. Although genomic heterogeneity is an important part of tumorigenesis, continuous generation of phenotypic heterogeneity is central for the adaptation of cancer cells to the challenges of tumorigenesis and response to therapy. Here I discuss the capacity of generating heterogeneity, hereafter called cell hetness, in cancer cells both as the activation of hetness oncogenes and inactivation of hetness tumor suppressor genes, which increase the generation of heterogeneity, ultimately producing an increase in adaptability and cell fitness. Transcriptomic high hetness states in therapy-tolerant cell states denote its importance in cancer resistance to therapy. The definition of the concept of hetness will allow the understanding of its origins, its control during embryogenesis, its loss of control in tumorigenesis and cancer therapeutics and its active targeting.}, } @article {pmid38720073, year = {2024}, author = {Yaron-Barir, TM and Joughin, BA and Huntsman, EM and Kerelsky, A and Cizin, DM and Cohen, BM and Regev, A and Song, J and Vasan, N and Lin, TY and Orozco, JM and Schoenherr, C and Sagum, C and Bedford, MT and Wynn, RM and Tso, SC and Chuang, DT and Li, L and Li, SS and Creixell, P and Krismer, K and Takegami, M and Lee, H and Zhang, B and Lu, J and Cossentino, I and Landry, SD and Uduman, M and Blenis, J and Elemento, O and Frame, MC and Hornbeck, PV and Cantley, LC and Turk, BE and Yaffe, MB and Johnson, JL}, title = {The intrinsic substrate specificity of the human tyrosine kinome.}, journal = {Nature}, volume = {629}, number = {8014}, pages = {1174-1181}, pmid = {38720073}, issn = {1476-4687}, support = {P01 CA117969/CA/NCI NIH HHS/United States ; P01 CA120964/CA/NCI NIH HHS/United States ; R35 ES028374/ES/NIEHS NIH HHS/United States ; R01 GM104047/GM/NIGMS NIH HHS/United States ; R01 GM135331/GM/NIGMS NIH HHS/United States ; R35 CA197588/CA/NCI NIH HHS/United States ; R01 CA226898/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Humans ; Amino Acid Motifs ; Evolution, Molecular ; Mass Spectrometry ; Phosphoproteins/chemistry/metabolism ; Phosphorylation ; *Phosphotyrosine/metabolism ; *Protein-Tyrosine Kinases/drug effects/metabolism ; Proteome/chemistry/metabolism ; Proteomics ; Signal Transduction ; src Homology Domains ; *Substrate Specificity ; *Tyrosine/metabolism/chemistry ; }, abstract = {Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth[1]. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome[1-3]. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood[4-7]. Here we used combinatorial peptide arrays to profile the substrate sequence specificity of all human Tyr kinases. Globally, the Tyr kinases demonstrate considerable diversity in optimal patterns of residues surrounding the site of phosphorylation, revealing the functional organization of the human Tyr kinome by substrate motif preference. Using this information, Tyr kinases that are most compatible with phosphorylating any Tyr site can be identified. Analysis of mass spectrometry phosphoproteomic datasets using this compendium of kinase specificities accurately identifies specific Tyr kinases that are dysregulated in cells after stimulation with growth factors, treatment with anti-cancer drugs or expression of oncogenic variants. Furthermore, the topology of known Tyr signalling networks naturally emerged from a comparison of the sequence specificities of the Tyr kinases and the SH2 phosphotyrosine (pTyr)-binding domains. Finally we show that the intrinsic substrate specificity of Tyr kinases has remained fundamentally unchanged from worms to humans, suggesting that the fidelity between Tyr kinases and their protein substrate sequences has been maintained across hundreds of millions of years of evolution.}, } @article {pmid38713735, year = {2024}, author = {Oszoli, I and Zachar, I}, title = {Group-selection via aggregative propagule-formation enables cooperative multicellularity in an individual based, spatial model.}, journal = {PLoS computational biology}, volume = {20}, number = {5}, pages = {e1012107}, pmid = {38713735}, issn = {1553-7358}, mesh = {*Models, Biological ; *Biological Evolution ; Computational Biology ; Ecosystem ; Animals ; Predatory Behavior/physiology ; Selection, Genetic ; Computer Simulation ; }, abstract = {The emergence of multicellularity is one of the major transitions in evolution that happened multiple times independently. During aggregative multicellularity, genetically potentially unrelated lineages cooperate to form transient multicellular groups. Unlike clonal multicellularity, aggregative multicellular organisms do not rely on kin selection instead other mechanisms maintain cooperation against cheater phenotypes that benefit from cooperators but do not contribute to groups. Spatiality with limited diffusion can facilitate group selection, as interactions among individuals are restricted to local neighbourhoods only. Selection for larger size (e.g. avoiding predation) may facilitate the emergence of aggregation, though it is unknown, whether and how much role such selection played during the evolution of aggregative multicellularity. We have investigated the effect of spatiality and the necessity of predation on the stability of aggregative multicellularity via individual-based modelling on the ecological timescale. We have examined whether aggregation facilitates the survival of cooperators in a temporally heterogeneous environment against cheaters, where only a subset of the population is allowed to periodically colonize a new, resource-rich habitat. Cooperators constitutively produce adhesive molecules to promote aggregation and propagule-formation while cheaters spare this expense to grow faster but cannot aggregate on their own, hence depending on cooperators for long-term survival. We have compared different population-level reproduction modes with and without individual selection (predation) to evaluate the different hypotheses. In a temporally homogeneous environment without propagule-based colonization, cheaters always win. Predation can benefit cooperators, but it is not enough to maintain the necessary cooperator amount in successive dispersals, either randomly or by fragmentation. Aggregation-based propagation however can ensure the adequate ratio of cooperators-to-cheaters in the propagule and is sufficient to do so even without predation. Spatiality combined with temporal heterogeneity helps cooperators via group selection, thus facilitating aggregative multicellularity. External stress selecting for larger size (e.g. predation) may facilitate aggregation, however, according to our results, it is neither necessary nor sufficient for aggregative multicellularity to be maintained when there is effective group-selection.}, } @article {pmid38705386, year = {2024}, author = {Enström, A and Carlsson, R and Buizza, C and Lewi, M and Paul, G}, title = {Pericyte-Specific Secretome Profiling in Hypoxia Using TurboID in a Multicellular in Vitro Spheroid Model.}, journal = {Molecular & cellular proteomics : MCP}, volume = {23}, number = {6}, pages = {100782}, pmid = {38705386}, issn = {1535-9484}, mesh = {*Pericytes/metabolism ; Humans ; *Spheroids, Cellular/metabolism ; *Coculture Techniques ; *Cell Hypoxia ; Secretome/metabolism ; Endothelial Cells/metabolism ; Astrocytes/metabolism ; Proteomics/methods ; Cell Communication ; Blood-Brain Barrier/metabolism ; Cells, Cultured ; Brain/metabolism ; Mass Spectrometry ; Signal Transduction ; }, abstract = {Cellular communication within the brain is imperative for maintaining homeostasis and mounting effective responses to pathological triggers like hypoxia. However, a comprehensive understanding of the precise composition and dynamic release of secreted molecules has remained elusive, confined primarily to investigations using isolated monocultures. To overcome these limitations, we utilized the potential of TurboID, a non-toxic biotin ligation enzyme, to capture and enrich secreted proteins specifically originating from human brain pericytes in spheroid cocultures with human endothelial cells and astrocytes. This approach allowed us to characterize the pericyte secretome within a more physiologically relevant multicellular setting encompassing the constituents of the blood-brain barrier. Through a combination of mass spectrometry and multiplex immunoassays, we identified a wide spectrum of different secreted proteins by pericytes. Our findings demonstrate that the pericytes secretome is profoundly shaped by their intercellular communication with other blood-brain barrier-residing cells. Moreover, we identified substantial differences in the secretory profiles between hypoxic and normoxic pericytes. Mass spectrometry analysis showed that hypoxic pericytes in coculture increase their release of signals related to protein secretion, mTOR signaling, and the complement system, while hypoxic pericytes in monocultures showed an upregulation in proliferative pathways including G2M checkpoints, E2F-, and Myc-targets. In addition, hypoxic pericytes show an upregulation of proangiogenic proteins such as VEGFA but display downregulation of canonical proinflammatory cytokines such as CXCL1, MCP-1, and CXCL6. Understanding the specific composition of secreted proteins in the multicellular brain microvasculature is crucial for advancing our knowledge of brain homeostasis and the mechanisms underlying pathology. This study has implications for the identification of targeted therapeutic strategies aimed at modulating microvascular signaling in brain pathologies associated with hypoxia.}, } @article {pmid38702020, year = {2024}, author = {Pozdnyakov, IR and Selyuk, AO and Kalashnikova, VA and Karpov, SA}, title = {HMG-B transcription factors of unicellular opisthokonts and their relatedness to the Sox-Tcf/Lef-Mata proteins of Metazoa and fungi.}, journal = {Gene}, volume = {921}, number = {}, pages = {148520}, doi = {10.1016/j.gene.2024.148520}, pmid = {38702020}, issn = {1879-0038}, mesh = {*Phylogeny ; Animals ; *Evolution, Molecular ; Fungi/genetics/metabolism ; HMGB Proteins/genetics/metabolism ; SOX Transcription Factors/genetics/metabolism ; Transcription Factors/genetics/metabolism ; Fungal Proteins/genetics/metabolism ; Wnt Signaling Pathway ; }, abstract = {A phylogenetic analysis of transcription factors of the Sox-Tcf/Lef-Mata (STM) family of the HMG-B superfamily was carried out in order to clarify the evolutionary roots of the Wnt signaling pathway in unicellular organisms. The data set for analysis included protein sequences of metazoans, fungi, unicellular opisthokonts, apusomonads and amoebozoans. The topology of the phylogenetic tree suggests that STM-related proteins arose in the common ancestor of Opisthokonta and Amoebozoa, two of amoebozoan STM proteins are sister-related to opisthokont ones and the three known lineages of STM transcription factors (STM family in narrow sence) are found in Opisthokonta only. Of these, the holozoan Sox protein branch is the result of either the first or second branching, that originated in the common ancestor of Opisthokonta. The lineage containing Tcf/Lef proteins (holozoan) and the lineage containing Mata proteins (holomycotan) are sister. They derived either at the time of the Holozoa and Holomycota divergence or originate from two paralogs of the common ancestor of Opisthokonta, which arose after the separation of the Sox lineage. Interaction with Armadillo-like proteins may be an original feature of the STM protein family and existed in the unicellular ancestors of multicellular animals; a connection is possible between the presence of Mata-related proteins in Aphelidium protococcorum and specific genome feature of this species.}, } @article {pmid38700417, year = {2024}, author = {Maloney, KM and Halverson, GP and Lechte, M and Gibson, TM and Bui, TH and Schiffbauer, JD and Laflamme, M}, title = {The paleoredox context of early eukaryotic evolution: insights from the Tonian Mackenzie Mountains Supergroup, Canada.}, journal = {Geobiology}, volume = {22}, number = {3}, pages = {e12598}, doi = {10.1111/gbi.12598}, pmid = {38700417}, issn = {1472-4669}, support = {//National Science Foundation/ ; //Polar Continental Shelf Program/ ; //Queen Elizabeth II Graduate Scholarship in Science & Technology (QEII-GSST)/ ; //Agouron Institute/ ; //Geological Society of America Graduate Research Grant/ ; GH RGPIN2017-04025//National Science and Engineering Research Council of Canada (NSERC)/ ; ML RGPIN435402//National Science and Engineering Research Council of Canada (NSERC)/ ; NSF IF 1636643//Northern Scientific Training Program/ ; }, mesh = {*Oxidation-Reduction ; *Fossils ; *Biological Evolution ; Geologic Sediments/chemistry/analysis ; Eukaryota ; Canada ; Ecosystem ; Chlorophyta ; }, abstract = {Tonian (ca. 1000-720 Ma) marine environments are hypothesised to have experienced major redox changes coinciding with the evolution and diversification of multicellular eukaryotes. In particular, the earliest Tonian stratigraphic record features the colonisation of benthic habitats by multicellular macroscopic algae, which would have been powerful ecosystem engineers that contributed to the oxygenation of the oceans and the reorganisation of biogeochemical cycles. However, the paleoredox context of this expansion of macroalgal habitats in Tonian nearshore marine environments remains uncertain due to limited well-preserved fossils and stratigraphy. As such, the interdependent relationship between early complex life and ocean redox state is unclear. An assemblage of macrofossils including the chlorophyte macroalga Archaeochaeta guncho was recently discovered in the lower Mackenzie Mountains Supergroup in Yukon (Canada), which archives marine sedimentation from ca. 950-775 Ma, permitting investigation into environmental evolution coincident with eukaryotic ecosystem evolution and expansion. Here we present multi-proxy geochemical data from the lower Mackenzie Mountains Supergroup to constrain the paleoredox environment within which these large benthic macroalgae thrived. Two transects show evidence for basin-wide anoxic (ferruginous) oceanic conditions (i.e., high FeHR/FeT, low Fepy/FeHR), with muted redox-sensitive trace metal enrichments and possible seasonal variability. However, the weathering of sulfide minerals in the studied samples may obscure geochemical signatures of euxinic conditions. These results suggest that macroalgae colonized shallow environments in an ocean that remained dominantly anoxic with limited evidence for oxygenation until ca. 850 Ma. Collectively, these geochemical results provide novel insights into the environmental conditions surrounding the evolution and expansion of benthic macroalgae and the eventual dominance of oxygenated oceanic conditions required for the later emergence of animals.}, } @article {pmid38693345, year = {2024}, author = {Feng, X and Zheng, J and Irisarri, I and Yu, H and Zheng, B and Ali, Z and de Vries, S and Keller, J and Fürst-Jansen, JMR and Dadras, A and Zegers, JMS and Rieseberg, TP and Dhabalia Ashok, A and Darienko, T and Bierenbroodspot, MJ and Gramzow, L and Petroll, R and Haas, FB and Fernandez-Pozo, N and Nousias, O and Li, T and Fitzek, E and Grayburn, WS and Rittmeier, N and Permann, C and Rümpler, F and Archibald, JM and Theißen, G and Mower, JP and Lorenz, M and Buschmann, H and von Schwartzenberg, K and Boston, L and Hayes, RD and Daum, C and Barry, K and Grigoriev, IV and Wang, X and Li, FW and Rensing, SA and Ben Ari, J and Keren, N and Mosquna, A and Holzinger, A and Delaux, PM and Zhang, C and Huang, J and Mutwil, M and de Vries, J and Yin, Y}, title = {Genomes of multicellular algal sisters to land plants illuminate signaling network evolution.}, journal = {Nature genetics}, volume = {56}, number = {5}, pages = {1018-1031}, pmid = {38693345}, issn = {1546-1718}, support = {R01GM140370//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; RE 1697/16-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; RE 1697/18-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 1933521//National Science Foundation (NSF)/ ; R21AI171952//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; DE-AC02-05CH11231//U.S. Department of Energy (DOE)/ ; 852725//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; R01 GM140370/GM/NIGMS NIH HHS/United States ; R21 AI171952/AI/NIAID NIH HHS/United States ; P34181-B//Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)/ ; 58-8042-9-089//United States Department of Agriculture | Agricultural Research Service (USDA Agricultural Research Service)/ ; ANR-10-LABX-41//LABoratoires d'EXcellence ARCANE (Labex ARCANE)/ ; 410739858//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; TH417/12-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 440231723//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; OPP1172165//Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)/ ; 101001675//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 440540015//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {*Signal Transduction/genetics ; *Embryophyta/genetics ; *Evolution, Molecular ; *Phylogeny ; Gene Regulatory Networks ; Genome/genetics ; Genome, Plant ; }, abstract = {Zygnematophyceae are the algal sisters of land plants. Here we sequenced four genomes of filamentous Zygnematophyceae, including chromosome-scale assemblies for three strains of Zygnema circumcarinatum. We inferred traits in the ancestor of Zygnematophyceae and land plants that might have ushered in the conquest of land by plants: expanded genes for signaling cascades, environmental response, and multicellular growth. Zygnematophyceae and land plants share all the major enzymes for cell wall synthesis and remodifications, and gene gains shaped this toolkit. Co-expression network analyses uncover gene cohorts that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution.}, } @article {pmid38691595, year = {2024}, author = {Yu, P and Li, Y and Fang, W and Feng, XQ and Li, B}, title = {Mechanochemical dynamics of collective cells and hierarchical topological defects in multicellular lumens.}, journal = {Science advances}, volume = {10}, number = {18}, pages = {eadn0172}, pmid = {38691595}, issn = {2375-2548}, mesh = {*Mechanotransduction, Cellular ; *Models, Biological ; *Morphogenesis ; Biomechanical Phenomena ; Animals ; }, abstract = {Collective cell dynamics is essential for tissue morphogenesis and various biological functions. However, it remains incompletely understood how mechanical forces and chemical signaling are integrated to direct collective cell behaviors underlying tissue morphogenesis. Here, we propose a three-dimensional (3D) mechanochemical theory accounting for biochemical reaction-diffusion and cellular mechanotransduction to investigate the dynamics of multicellular lumens. We show that the interplay between biochemical signaling and mechanics can trigger either pitchfork or Hopf bifurcation to induce diverse static mechanochemical patterns or generate oscillations with multiple modes both involving marked mechanical deformations in lumens. We uncover the crucial role of mechanochemical feedback in emerging morphodynamics and identify the evolution and morphogenetic functions of hierarchical topological defects including cell-level hexatic defects and tissue-level orientational defects. Our theory captures the common mechanochemical traits of collective dynamics observed in experiments and could provide a mechanistic context for understanding morphological symmetry breaking in 3D lumen-like tissues.}, } @article {pmid38690760, year = {2024}, author = {}, title = {Transitions in development - an interview with Thibaut Brunet.}, journal = {Development (Cambridge, England)}, volume = {151}, number = {9}, pages = {}, doi = {10.1242/dev.202942}, pmid = {38690760}, issn = {1477-9129}, mesh = {Animals ; *Biological Evolution ; *Developmental Biology/history ; *Choanoflagellata ; History, 21st Century ; Morphogenesis ; History, 20th Century ; }, abstract = {Thibaut Brunet is a group leader at the Institut Pasteur in Paris, France, where he works on choanoflagellates (known as 'choanos' for short). These unicellular organisms are close relatives of animals that have the potential to form multicellular assemblies under certain conditions, and Thibaut's lab are leveraging them to gain insights into how animal morphogenesis evolved. We met with Thibaut over Zoom to discuss his career path so far, and learnt how an early interest in dinosaurs contributed to his life-long fascination with evolutionary biology.}, } @article {pmid38685127, year = {2024}, author = {Trigos, AS and Bongiovanni, F and Zhang, Y and Zethoven, M and Tothill, R and Pearson, R and Papenfuss, AT and Goode, DL}, title = {Disruption of metazoan gene regulatory networks in cancer alters the balance of co-expression between genes of unicellular and multicellular origins.}, journal = {Genome biology}, volume = {25}, number = {1}, pages = {110}, pmid = {38685127}, issn = {1474-760X}, support = {MCRF17005//Victorian Cancer Agency/ ; 2003115//National Health and Medical Research Council/ ; 2003887//National Health and Medical Research Council/ ; }, mesh = {*Gene Regulatory Networks ; *Neoplasms/genetics ; Humans ; Animals ; Gene Expression Regulation, Neoplastic ; Evolution, Molecular ; }, abstract = {BACKGROUND: Metazoans inherited genes from unicellular ancestors that perform essential biological processes such as cell division, metabolism, and protein translation. Multicellularity requires careful control and coordination of these unicellular genes to maintain tissue integrity and homeostasis. Gene regulatory networks (GRNs) that arose during metazoan evolution are frequently altered in cancer, resulting in over-expression of unicellular genes. We propose that an imbalance in co-expression of unicellular (UC) and multicellular (MC) genes is a driving force in cancer.

RESULTS: We combine gene co-expression analysis to infer changes to GRNs in cancer with protein sequence conservation data to distinguish genes with UC and MC origins. Co-expression networks created using RNA sequencing data from 31 tumor types and normal tissue samples are divided into modules enriched for UC genes, MC genes, or mixed UC-MC modules. The greatest differences between tumor and normal tissue co-expression networks occur within mixed UC-MC modules. MC and UC genes not commonly co-expressed in normal tissues form distinct co-expression modules seen only in tumors. The degree of rewiring of genes within mixed UC-MC modules increases with tumor grade and stage. Mixed UC-MC modules are enriched for somatic mutations in cancer genes, particularly amplifications, suggesting an important driver of the rewiring observed in tumors is copy number changes.

CONCLUSIONS: Our study shows the greatest changes to gene co-expression patterns during tumor progression occur between genes of MC and UC origins, implicating the breakdown and rewiring of metazoan gene regulatory networks in cancer development and progression.}, } @article {pmid38678594, year = {2024}, author = {Tsuchikane, Y and Watanabe, M and Kawaguchi, YW and Uehara, K and Nishiyama, T and Sekimoto, H and Tsuchimatsu, T}, title = {Diversity of genome size and chromosome number in homothallic and heterothallic strains of the Closterium peracerosum-strigosum-littorale complex (Desmidiales, Zygnematophyceae, Streptophyta).}, journal = {Journal of phycology}, volume = {60}, number = {3}, pages = {654-667}, doi = {10.1111/jpy.13457}, pmid = {38678594}, issn = {1529-8817}, support = {25304012//Japan Society for the Promotion of Science/ ; 26650147//Japan Society for the Promotion of Science/ ; 18K06367//Japan Society for the Promotion of Science/ ; 19K22446//Japan Society for the Promotion of Science/ ; 19K22448//Japan Society for the Promotion of Science/ ; 15H05237//Japan Society for the Promotion of Science/ ; 16H04836//Japan Society for the Promotion of Science/ ; 16K02518//Japan Society for the Promotion of Science/ ; 18K19365//Japan Society for the Promotion of Science/ ; 20K21451//Japan Society for the Promotion of Science/ ; 21H02549//Japan Society for the Promotion of Science/ ; 22H05177//Japan Society for the Promotion of Science/ ; 19K06827//Japan Society for the Promotion of Science/ ; 24K09588//Japan Society for the Promotion of Science/ ; 15K18583//Japan Society for the Promotion of Science/ ; 17K15165//Japan Society for the Promotion of Science/ ; 22K21352//Japan Society for the Promotion of Science/ ; }, mesh = {*Genome Size ; *Phylogeny ; Closterium/genetics ; }, abstract = {The evolutionary transitions of mating systems between outcrossing and self-fertilization are often suggested to associate with the cytological and genomic changes, but the empirical reports are limited in multicellular organisms. Here we used the unicellular zygnematophycean algae, the Closterium peracerosum-strigosum-littorale (C. psl.) complex, to address whether genomic properties such as genome sizes and chromosome numbers are associated with mating system transitions between homothallism (self-fertility) and heterothallism (self-sterility). Phylogenetic analysis revealed the polyphyly of homothallic strains, suggesting multiple transitions between homothallism and heterothallism in the C. psl. complex. Flow cytometry analysis identified a more than 2-fold genome size variation, ranging from 0.53 to 1.42 Gbp, which was positively correlated with chromosome number variation between strains. Although we did not find consistent trends in genome size change and mating system transitions, the mean chromosome sizes tend to be smaller in homothallic strains than in their relative heterothallic strains. This result suggests that homothallic strains possibly have more fragmented chromosomes, which is consistent with the argument that self-fertilizing populations may tolerate more chromosomal rearrangements.}, } @article {pmid38662765, year = {2024}, author = {Singleton, MD and Eisen, MB}, title = {Evolutionary analyses of intrinsically disordered regions reveal widespread signals of conservation.}, journal = {PLoS computational biology}, volume = {20}, number = {4}, pages = {e1012028}, pmid = {38662765}, issn = {1553-7358}, mesh = {Drosophila melanogaster/genetics ; *Intrinsically Disordered Proteins/chemistry/genetics/metabolism ; *Drosophila Proteins/chemistry/genetics/metabolism ; Evolution, Molecular ; Sequence Homology ; Amino Acid Sequence ; }, abstract = {Intrinsically disordered regions (IDRs) are segments of proteins without stable three-dimensional structures. As this flexibility allows them to interact with diverse binding partners, IDRs play key roles in cell signaling and gene expression. Despite the prevalence and importance of IDRs in eukaryotic proteomes and various biological processes, associating them with specific molecular functions remains a significant challenge due to their high rates of sequence evolution. However, by comparing the observed values of various IDR-associated properties against those generated under a simulated model of evolution, a recent study found most IDRs across the entire yeast proteome contain conserved features. Furthermore, it showed clusters of IDRs with common "evolutionary signatures," i.e. patterns of conserved features, were associated with specific biological functions. To determine if similar patterns of conservation are found in the IDRs of other systems, in this work we applied a series of phylogenetic models to over 7,500 orthologous IDRs identified in the Drosophila genome to dissect the forces driving their evolution. By comparing models of constrained and unconstrained continuous trait evolution using the Brownian motion and Ornstein-Uhlenbeck models, respectively, we identified signals of widespread constraint, indicating conservation of distributed features is mechanism of IDR evolution common to multiple biological systems. In contrast to the previous study in yeast, however, we observed limited evidence of IDR clusters with specific biological functions, which suggests a more complex relationship between evolutionary constraints and function in the IDRs of multicellular organisms.}, } @article {pmid38659912, year = {2024}, author = {Tong, K and Datta, S and Cheng, V and Haas, DJ and Gourisetti, S and Yopp, HL and Day, TC and Lac, DT and Conlin, PL and Bozdag, GO and Ratcliff, WC}, title = {Whole-genome duplication in the Multicellularity Long Term Evolution Experiment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38659912}, issn = {2692-8205}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; }, abstract = {Whole-genome duplication (WGD) is widespread across eukaryotes and can promote adaptive evolution[1-4]. However, given the instability of newly-formed polyploid genomes[5-7], understanding how WGDs arise in a population, persist, and underpin adaptations remains a challenge. Using our ongoing Multicellularity Long Term Evolution Experiment (MuLTEE)[8], we show that diploid snowflake yeast (Saccharomyces cerevisiae) under selection for larger multicellular size rapidly undergo spontaneous WGD. From its origin within the first 50 days of the experiment, tetraploids persist for the next 950 days (nearly 5,000 generations, the current leading edge of our experiment) in ten replicate populations, despite being genomically unstable. Using synthetic reconstruction, biophysical modeling, and counter-selection experiments, we found that tetraploidy evolved because it confers immediate fitness benefits in this environment, by producing larger, longer cells that yield larger clusters. The same selective benefit also maintained tetraploidy over long evolutionary timescales, inhibiting the reversion to diploidy that is typically seen in laboratory evolution experiments. Once established, tetraploidy facilitated novel genetic routes for adaptation, playing a key role in the evolution of macroscopic multicellular size via the origin of evolutionarily conserved aneuploidy. These results provide unique empirical insights into the evolutionary dynamics and impacts of WGD, showing how it can initially arise due to its immediate adaptive benefits, be maintained by selection, and fuel long-term innovations by creating additional dimensions of heritable genetic variation.}, } @article {pmid38657942, year = {2024}, author = {Wu, T and Huang, J and Li, Y and Guo, Y and Wang, H and Zhang, Y}, title = {Prenatal acetaminophen exposure and the developing ovary: Time, dose, and course consequences for fetal mice.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {189}, number = {}, pages = {114679}, doi = {10.1016/j.fct.2024.114679}, pmid = {38657942}, issn = {1873-6351}, mesh = {Female ; Animals ; Pregnancy ; Mice ; *Acetaminophen/toxicity ; *Ovary/drug effects/metabolism ; Dose-Response Relationship, Drug ; Oocytes/drug effects ; Prenatal Exposure Delayed Effects/chemically induced ; Bone Morphogenetic Protein 15/genetics ; Growth Differentiation Factor 9/genetics/metabolism ; Cell Proliferation/drug effects ; }, abstract = {Acetaminophen is an emerging endocrine disrupting chemical and has been detected in various natural matrices. Numerous studies have documented developmental toxicity associated with prenatal acetaminophen exposure (PAcE). In this study, we established a PAcE Kunming mouse model at different time (middle pregnancy and third trimester), doses (low, middle, high) and courses (single or multi-) to systematically investigate their effects on fetal ovarian development. The findings indicated PAcE affected ovarian development, reduced fetal ovarian oocyte number and inhibited cell proliferation. A reduction in mRNA expression was observed for genes associated with oocyte markers (NOBOX and Figlα), follicular development markers (BMP15 and GDF9), and pre-granulosa cell steroid synthase (SF1 and StAR). Notably, exposure in middle pregnancy, high dose, multi-course resulted in the most pronounced inhibition of oocyte development; exposure in third trimester, high dose and multi-course led to the most pronounced inhibition of follicular development; and in third trimester, low dose and single course, the inhibition of pre-granulosa cell function was most pronounced. Mechanistic investigations revealed that PAcE had the most pronounced suppression of the ovarian Notch signaling pathway. Overall, PAcE caused fetal ovarian multicellular toxicity and inhibited follicular development with time, dose and course differences.}, } @article {pmid38654432, year = {2024}, author = {Chen, C and Chen, H and Wang, P and Wang, X and Wang, X and Chen, C}, title = {Ca[2+] Overload Decreased Cellular Viability in Magnetic Hyperthermia without a Macroscopic Temperature Rise.}, journal = {ACS biomaterials science & engineering}, volume = {10}, number = {5}, pages = {2995-3005}, doi = {10.1021/acsbiomaterials.3c01875}, pmid = {38654432}, issn = {2373-9878}, mesh = {*Calcium/metabolism ; *Cell Survival ; *Reactive Oxygen Species/metabolism ; *TRPV Cation Channels/metabolism ; Humans ; *Hyperthermia, Induced/methods ; *Magnetic Fields ; Temperature ; Ferritins/metabolism ; Hyperthermia/metabolism ; }, abstract = {Magnetic hyperthermia is a crucial medical engineering technique for treating diseases, which usually uses alternating magnetic fields (AMF) to interplay with magnetic substances to generate heat. Recently, it has been found that in some cases, there is no detectable temperature increment after applying an AMF, which caused corresponding effects surprisingly. The mechanisms involved in this phenomenon are not yet fully understood. In this study, we aimed to explore the role of Ca[2+] overload in the magnetic hyperthermia effect without a perceptible temperature rise. A cellular system expressing the fusion proteins TRPV1 and ferritin was prepared. The application of an AMF (518 kHz, 16 kA/m) could induce the fusion protein to release a large amount of iron ions, which then participates in the production of massive reactive oxygen radicals (ROS). Both ROS and its induced lipid oxidation enticed the opening of ion channels, causing intracellular Ca[2+] overload, which further led to decreased cellular viability. Taken together, Ca[2+] overload triggered by elevated ROS and the induced oxidation of lipids contributes to the magnetic hyperthermia effect without a perceptible temperature rise. These findings would be beneficial for expanding the application of temperature-free magnetic hyperthermia, such as in cellular and neural regulation, design of new cancer treatment methods.}, } @article {pmid38652695, year = {2024}, author = {Xin, H and Wang, Y and Zhang, W and Bao, Y and Neumann, P and Ning, Y and Zhang, T and Wu, Y and Jiang, N and Jiang, J and Xi, M}, title = {Celine, a long interspersed nuclear element retrotransposon, colonizes in the centromeres of poplar chromosomes.}, journal = {Plant physiology}, volume = {195}, number = {4}, pages = {2787-2798}, pmid = {38652695}, issn = {1532-2548}, support = {IOS-1740874//National Science Foundation/ ; MICL2707//United States Department of Agriculture National Institute of Food and Agriculture and AgBioResearch at Michigan State University/ ; ISO-2029959//NSF/ ; //National Natural Science Foundation of China/ ; }, mesh = {*Populus/genetics ; *Centromere/genetics/metabolism ; *Chromosomes, Plant/genetics ; *Retroelements/genetics ; Long Interspersed Nucleotide Elements/genetics ; Phylogeny ; Histones/metabolism/genetics ; }, abstract = {Centromeres in most multicellular eukaryotes are composed of long arrays of repetitive DNA sequences. Interestingly, several transposable elements, including the well-known long terminal repeat centromeric retrotransposon of maize (CRM), were found to be enriched in functional centromeres marked by the centromeric histone H3 (CENH3). Here, we report a centromeric long interspersed nuclear element (LINE), Celine, in Populus species. Celine has colonized preferentially in the CENH3-associated chromatin of every poplar chromosome, with 84% of the Celine elements localized in the CENH3-binding domains. In contrast, only 51% of the CRM elements were bound to CENH3 domains in Populus trichocarpa. These results suggest different centromere targeting mechanisms employed by Celine and CRM elements. Nevertheless, the high target specificity seems to be detrimental to further amplification of the Celine elements, leading to a shorter life span and patchy distribution among plant species compared with the CRM elements. Using a phylogenetically guided approach, we were able to identify Celine-like LINE elements in tea plant (Camellia sinensis) and green ash tree (Fraxinus pennsylvanica). The centromeric localization of these Celine-like LINEs was confirmed in both species. We demonstrate that the centromere targeting property of Celine-like LINEs is of primitive origin and has been conserved among distantly related plant species.}, } @article {pmid38651959, year = {2024}, author = {Thomas, F and Ujvari, B and Dujon, AM}, title = {[Evolution of cancer resistance in the animal kingdom].}, journal = {Medecine sciences : M/S}, volume = {40}, number = {4}, pages = {343-350}, doi = {10.1051/medsci/2024038}, pmid = {38651959}, issn = {1958-5381}, mesh = {Animals ; *Neoplasms/genetics/pathology ; Humans ; *Biological Evolution ; Disease Resistance/genetics/physiology ; Selection, Genetic ; Mole Rats/physiology/genetics ; Elephants/genetics ; }, abstract = {Cancer is an inevitable collateral problem inherent in the evolution of multicellular organisms, which appeared at the end of the Precambrian. Faced to this constraint, a range of diverse anticancer defenses has evolved across the animal kingdom. Today, investigating how animal organisms, especially those of large size and long lifespan, manage cancer-related issues has both fundamental and applied outcomes, as it could inspire strategies for preventing or treating human cancers. In this article, we begin by presenting the conceptual framework for understanding evolutionary theories regarding the development of anti-cancer defenses. We then present a number of examples that have been extensively studied in recent years, including naked mole rats, elephants, whales, placozoa, xenarthras (such as sloths, armadillos and anteaters) and bats. The contributions of comparative genomics to understanding evolutionary convergences are also discussed. Finally, we emphasize that natural selection has also favored anti-cancer adaptations aimed at avoiding mutagenic environments, for example by maximizing immediate reproductive efforts in the event of cancer. Exploring these adaptive solutions holds promise for identifying novel approaches to improve human health.}, } @article {pmid38648729, year = {2024}, author = {Chen, C and Chen, H and Wang, P and Wang, X and Wang, X and Chen, C and Pan, W}, title = {Reactive Oxygen Species Activate a Ferritin-Linked TRPV4 Channel under a Static Magnetic Field.}, journal = {ACS chemical biology}, volume = {19}, number = {5}, pages = {1151-1160}, doi = {10.1021/acschembio.4c00090}, pmid = {38648729}, issn = {1554-8937}, mesh = {*TRPV Cation Channels/metabolism ; Humans ; *Reactive Oxygen Species/metabolism ; HEK293 Cells ; *Ferritins/metabolism/chemistry ; *Magnetic Fields ; Iron/metabolism ; Calcium/metabolism ; }, abstract = {Magnetogenetics has shown great potential for cell function and neuromodulation using heat or force effects under different magnetic fields; however, there is still a contradiction between experimental effects and underlying mechanisms by theoretical computation. In this study, we aimed to investigate the role of reactive oxygen species (ROS) in mechanical force-dependent regulation from a physicochemical perspective. The transient receptor potential vanilloid 4 (TRPV4) cation channels fused to ferritin (T4F) were overexpressed in HEK293T cells and exposed to static magnetic fields (sMF, 1.4-5.0 mT; gradient: 1.62 mT/cm). An elevation of ROS levels was found under sMF in T4F-overexpressing cells, which could lead to lipid oxidation. Compared with the overexpression of TRPV4, ferritin in T4F promoted the generation of ROS under the stimulation of sMF, probably related to the release of iron ions from ferritin. Then, the resulting ROS regulated the opening of the TRPV4 channel, which was attenuated by the direct addition of ROS inhibitors or an iron ion chelator, highlighting a close relationship among iron release, ROS production, and TRPV4 channel activation. Taken together, these findings indicate that the produced ROS under sMF act on the TRPV4 channel, regulating the influx of calcium ions. The study would provide a scientific basis for the application of magnetic regulation in cellular or neural regulation and disease treatment and contribute to the development of the more sensitive regulatory technology.}, } @article {pmid38644621, year = {2024}, author = {Daignan-Fornier, B and Pradeu, T}, title = {Critically assessing atavism, an evolution-centered and deterministic hypothesis on cancer.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {46}, number = {6}, pages = {e2300221}, doi = {10.1002/bies.202300221}, pmid = {38644621}, issn = {1521-1878}, support = {//NewMoon research program of the University of Bordeaux/ ; GBMF9021//Gordon and Betty Moore Foundation/ ; }, mesh = {*Neoplasms/genetics/pathology ; Humans ; Animals ; Biological Evolution ; Mutation ; Cell Proliferation/genetics ; }, abstract = {Cancer is most commonly viewed as resulting from somatic mutations enhancing proliferation and invasion. Some hypotheses further propose that these new capacities reveal a breakdown of multicellularity allowing cancer cells to escape proliferation and cooperation control mechanisms that were implemented during evolution of multicellularity. Here we critically review one such hypothesis, named "atavism," which puts forward the idea that cancer results from the re-expression of normally repressed genes forming a program, or toolbox, inherited from unicellular or simple multicellular ancestors. This hypothesis places cancer in an interesting evolutionary perspective that has not been widely explored and deserves attention. Thinking about cancer within an evolutionary framework, especially the major transitions to multicellularity, offers particularly promising perspectives. It is therefore of the utmost important to analyze why one approach that tries to achieve this aim, the atavism hypothesis, has not so far emerged as a major theory on cancer. We outline the features of the atavism hypothesis that, would benefit from clarification and, if possible, unification.}, } @article {pmid38621413, year = {2024}, author = {Egorova, KS and Kibardin, AV and Posvyatenko, AV and Ananikov, VP}, title = {Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms.}, journal = {Chemical reviews}, volume = {124}, number = {8}, pages = {4679-4733}, doi = {10.1021/acs.chemrev.3c00420}, pmid = {38621413}, issn = {1520-6890}, mesh = {Animals ; Humans ; Apoptosis/drug effects ; *Ionic Liquids/chemistry/pharmacology ; Oxidative Stress/drug effects ; }, abstract = {The review presents a detailed discussion of the evolving field studying interactions between ionic liquids (ILs) and biological systems. Originating from molten salt electrolytes to present multiapplication substances, ILs have found usage across various fields due to their exceptional physicochemical properties, including excellent tunability. However, their interactions with biological systems and potential influence on living organisms remain largely unexplored. This review examines the cytotoxic effects of ILs on cell cultures, biomolecules, and vertebrate and invertebrate organisms. Our understanding of IL toxicity, while growing in recent years, is yet nascent. The established findings include correlations between harmful effects of ILs and their ability to disturb cellular membranes, their potential to trigger oxidative stress in cells, and their ability to cause cell death via apoptosis. Future research directions proposed in the review include studying the distribution of various ILs within cellular compartments and organelles, investigating metabolic transformations of ILs in cells and organisms, detailed analysis of IL effects on proteins involved in oxidative stress and apoptosis, correlation studies between IL doses, exposure times and resulting adverse effects, and examination of effects of subtoxic concentrations of ILs on various biological objects. This review aims to serve as a critical analysis of the current body of knowledge on IL-related toxicity mechanisms. Furthermore, it can guide researchers toward the design of less toxic ILs and the informed use of ILs in drug development and medicine.}, } @article {pmid38604731, year = {2024}, author = {Reis-Cunha, JL and Pimenta-Carvalho, SA and Almeida, LV and Coqueiro-Dos-Santos, A and Marques, CA and Black, JA and Damasceno, J and McCulloch, R and Bartholomeu, DC and Jeffares, DC}, title = {Ancestral aneuploidy and stable chromosomal duplication resulting in differential genome structure and gene expression control in trypanosomatid parasites.}, journal = {Genome research}, volume = {34}, number = {3}, pages = {441-453}, pmid = {38604731}, issn = {1549-5469}, support = {/WT_/Wellcome Trust/United Kingdom ; /MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/T016019/1/MRC_/Medical Research Council/United Kingdom ; 224501/Z/21/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Aneuploidy ; *Chromosome Duplication ; *Gene Expression Regulation ; *Genome, Protozoan ; Evolution, Molecular ; Trypanosomatina/genetics ; Phylogeny ; }, abstract = {Aneuploidy is widely observed in both unicellular and multicellular eukaryotes, usually associated with adaptation to stress conditions. Chromosomal duplication stability is a tradeoff between the fitness cost of having unbalanced gene copies and the potential fitness gained from increased dosage of specific advantageous genes. Trypanosomatids, a family of protozoans that include species that cause neglected tropical diseases, are a relevant group to study aneuploidies. Their life cycle has several stressors that could select for different patterns of chromosomal duplications and/or losses, and their nearly universal use of polycistronic transcription increases their reliance on gene expansion/contraction, as well as post-transcriptional control as mechanisms for gene expression regulation. By evaluating the data from 866 isolates covering seven trypanosomatid genera, we have revealed that aneuploidy tolerance is an ancestral characteristic of trypanosomatids but has a reduced occurrence in a specific monophyletic clade that has undergone large genomic reorganization and chromosomal fusions. We have also identified an ancient chromosomal duplication that was maintained across these parasite's speciation, named collectively as the trypanosomatid ancestral supernumerary chromosome (TASC). TASC has most genes in the same coding strand, is expressed as a disomic chromosome (even having four copies), and has increased potential for functional variation, but it purges highly deleterious mutations more efficiently than other chromosomes. The evidence of stringent control over gene expression in this chromosome suggests that these parasites have adapted to mitigate the fitness cost associated with this ancient chromosomal duplication.}, } @article {pmid38600528, year = {2024}, author = {Lindsey, CR and Knoll, AH and Herron, MD and Rosenzweig, F}, title = {Fossil-calibrated molecular clock data enable reconstruction of steps leading to differentiated multicellularity and anisogamy in the Volvocine algae.}, journal = {BMC biology}, volume = {22}, number = {1}, pages = {79}, pmid = {38600528}, issn = {1741-7007}, support = {80NSSC20K0621//Ames Research Center/ ; 80NSSC23K1357//Ames Research Center/ ; OAC-1828187//National Science Foundation/ ; }, mesh = {Phylogeny ; Biological Evolution ; *Volvox/genetics ; Fossils ; Plants ; *Chlorophyceae ; Cell Differentiation ; }, abstract = {BACKGROUND: Throughout its nearly four-billion-year history, life has undergone evolutionary transitions in which simpler subunits have become integrated to form a more complex whole. Many of these transitions opened the door to innovations that resulted in increased biodiversity and/or organismal efficiency. The evolution of multicellularity from unicellular forms represents one such transition, one that paved the way for cellular differentiation, including differentiation of male and female gametes. A useful model for studying the evolution of multicellularity and cellular differentiation is the volvocine algae, a clade of freshwater green algae whose members range from unicellular to colonial, from undifferentiated to completely differentiated, and whose gamete types can be isogamous, anisogamous, or oogamous. To better understand how multicellularity, differentiation, and gametes evolved in this group, we used comparative genomics and fossil data to establish a geologically calibrated roadmap of when these innovations occurred.

RESULTS: Our ancestral-state reconstructions, show that multicellularity arose independently twice in the volvocine algae. Our chronograms indicate multicellularity evolved during the Carboniferous-Triassic periods in Goniaceae + Volvocaceae, and possibly as early as the Cretaceous in Tetrabaenaceae. Using divergence time estimates we inferred when, and in what order, specific developmental changes occurred that led to differentiated multicellularity and oogamy. We find that in the volvocine algae the temporal sequence of developmental changes leading to differentiated multicellularity is much as proposed by David Kirk, and that multicellularity is correlated with the acquisition of anisogamy and oogamy. Lastly, morphological, molecular, and divergence time data suggest the possibility of cryptic species in Tetrabaenaceae.

CONCLUSIONS: Large molecular datasets and robust phylogenetic methods are bringing the evolutionary history of the volvocine algae more sharply into focus. Mounting evidence suggests that extant species in this group are the result of two independent origins of multicellularity and multiple independent origins of cell differentiation. Also, the origin of the Tetrabaenaceae-Goniaceae-Volvocaceae clade may be much older than previously thought. Finally, the possibility of cryptic species in the Tetrabaenaceae provides an exciting opportunity to study the recent divergence of lineages adapted to live in very different thermal environments.}, } @article {pmid38598600, year = {2024}, author = {Wang, H and Marucci, G and Munke, A and Hassan, MM and Lalle, M and Okamoto, K}, title = {High-resolution comparative atomic structures of two Giardiavirus prototypes infecting G. duodenalis parasite.}, journal = {PLoS pathogens}, volume = {20}, number = {4}, pages = {e1012140}, pmid = {38598600}, issn = {1553-7374}, mesh = {*Giardia lamblia/ultrastructure/pathogenicity ; *Giardiavirus/genetics ; Cryoelectron Microscopy ; Animals ; Capsid/ultrastructure/metabolism ; Humans ; Phylogeny ; }, abstract = {The Giardia lamblia virus (GLV) is a non-enveloped icosahedral dsRNA and endosymbiont virus that infects the zoonotic protozoan parasite Giardia duodenalis (syn. G. lamblia, G. intestinalis), which is a pathogen of mammals, including humans. Elucidating the transmission mechanism of GLV is crucial for gaining an in-depth understanding of the virulence of the virus in G. duodenalis. GLV belongs to the family Totiviridae, which infects yeast and protozoa intracellularly; however, it also transmits extracellularly, similar to the phylogenetically, distantly related toti-like viruses that infect multicellular hosts. The GLV capsid structure is extensively involved in the longstanding discussion concerning extracellular transmission in Totiviridae and toti-like viruses. Hence, this study constructed the first high-resolution comparative atomic models of two GLV strains, namely GLV-HP and GLV-CAT, which showed different intracellular localization and virulence phenotypes, using cryogenic electron microscopy single-particle analysis. The atomic models of the GLV capsids presented swapped C-terminal extensions, extra surface loops, and a lack of cap-snatching pockets, similar to those of toti-like viruses. However, their open pores and absence of the extra crown protein resemble those of other yeast and protozoan Totiviridae viruses, demonstrating the essential structures for extracellular cell-to-cell transmission. The structural comparison between GLV-HP and GLV-CAT indicates the first evidence of critical structural motifs for the transmission and virulence of GLV in G. duodenalis.}, } @article {pmid38582791, year = {2024}, author = {Wang, H and Guan, Z and Zheng, L}, title = {Single-cell RNA sequencing explores the evolution of the ecosystem from leukoplakia to head and neck squamous cell carcinoma.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {8097}, pmid = {38582791}, issn = {2045-2322}, support = {SBGJ202102175//the Henan Provincial Medical Science and Technology Research Plan/ ; }, mesh = {Humans ; Squamous Cell Carcinoma of Head and Neck/genetics ; *Ecosystem ; Leukoplakia ; *Head and Neck Neoplasms/genetics ; Sequence Analysis, RNA ; Prognosis ; Tumor Microenvironment/genetics ; }, abstract = {It has been found that progression from leukoplakia to head and neck squamous cell carcinoma (HNSCC) is a long-term process that may involve changes in the multicellular ecosystem. We acquired scRNA-seq samples information from gene expression omnibus and UCSC Xena database. The BEAM function was used to construct the pseudotime trajectory and analyze the differentially expressed genes in different branches. We used the ssGSEA method to explore the correlation between each cell subgroup and survival time, and obtained the cell subgroup related to prognosis. During the progression from leukoplakia to HNSCC, we found several prognostic cell subgroups, such as AURKB + epithelial cells, SFRP1 + fibroblasts, SLC7A8 + macrophages, FCER1A + CD1C + dendritic cells, and TRGC2 + NK/T cells. All cell subgroups had two different fates, one tending to cell proliferation, migration, and enhancement of angiogenesis capacity, and the other tending to inflammatory immune response, leukocyte chemotaxis, and T cell activation. Tumor-promoting genes such as CD163 and CD209 were highly expressed in the myeloid cells, and depletion marker genes such as TIGIT, LAG3 were highly expressed in NK/T cells. Our study may provide a reference for the molecular mechanism of HNSCC and theoretical basis for the development of new therapeutic strategies.}, } @article {pmid38554705, year = {2024}, author = {Deng, Y and Xia, L and Zhang, J and Deng, S and Wang, M and Wei, S and Li, K and Lai, H and Yang, Y and Bai, Y and Liu, Y and Luo, L and Yang, Z and Chen, Y and Kang, R and Gan, F and Pu, Q and Mei, J and Ma, L and Lin, F and Guo, C and Liao, H and Zhu, Y and Liu, Z and Liu, C and Hu, Y and Yuan, Y and Zha, Z and Yuan, G and Zhang, G and Chen, L and Cheng, Q and Shen, S and Liu, L}, title = {Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.}, journal = {Cell reports. Medicine}, volume = {5}, number = {4}, pages = {101489}, pmid = {38554705}, issn = {2666-3791}, mesh = {Humans ; *Lung Neoplasms/genetics ; *Adenocarcinoma/genetics/pathology ; CD8-Positive T-Lymphocytes/pathology ; Ecotype ; Retrospective Studies ; *Adenocarcinoma of Lung ; }, abstract = {Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8[+] T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8[+] T cells, driven by specific stromal cells such as CTHCR1[+] fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8[+] T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.}, } @article {pmid38553457, year = {2024}, author = {Kapsetaki, SE and Cisneros, LH and Maley, CC}, title = {Cell-in-cell phenomena across the tree of life.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {7535}, pmid = {38553457}, issn = {2045-2322}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; U54 CA217376/GF/NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; R21 CA257980/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Child, Preschool ; *Biological Evolution ; *Neoplasms ; }, abstract = {Cells in obligately multicellular organisms by definition have aligned fitness interests, minimum conflict, and cannot reproduce independently. However, some cells eat other cells within the same body, sometimes called cell cannibalism. Such cell-in-cell events have not been thoroughly discussed in the framework of major transitions to multicellularity. We performed a systematic screening of 508 articles, from which we chose 115 relevant articles in a search for cell-in-cell events across the tree of life, the age of cell-in-cell-related genes, and whether cell-in-cell events are associated with normal multicellular development or cancer. Cell-in-cell events are found across the tree of life, from some unicellular to many multicellular organisms, including non-neoplastic and neoplastic tissue. Additionally, out of the 38 cell-in-cell-related genes found in the literature, 14 genes were over 2.2 billion years old, i.e., older than the common ancestor of some facultatively multicellular taxa. All of this suggests that cell-in-cell events may have originated before the origins of obligate multicellularity. Thus, our results show that cell-in-cell events exist in obligate multicellular organisms, but are not a defining feature of them. The idea of eradicating cell-in-cell events from obligate multicellular organisms as a way of treating cancer, without considering that cell-in-cell events are also part of normal development, should be abandoned.}, } @article {pmid38547507, year = {2024}, author = {Odelgard, A and Hägglund, E and Guy, L and Andersson, SGE}, title = {Phylogeny and Expansion of Serine/Threonine Kinases in Phagocytotic Bacteria in the Phylum Planctomycetota.}, journal = {Genome biology and evolution}, volume = {16}, number = {4}, pages = {}, pmid = {38547507}, issn = {1759-6653}, support = {//Swedish Research Council/ ; 2017.0322//Knut and Alice Wallenberg Foundation/ ; }, mesh = {*Protein Serine-Threonine Kinases/genetics/metabolism ; Phylogeny ; *Planctomycetes ; Proteome/genetics ; Bacteria/genetics/metabolism ; Threonine/genetics ; Serine/genetics ; }, abstract = {The recently isolated bacterium "Candidatus Uabimicrobium amorphum" is the only known prokaryote that can engulf other bacterial cells. Its proteome contains a high fraction of proteins involved in signal transduction systems, which is a feature normally associated with multicellularity in eukaryotes. Here, we present a protein-based phylogeny which shows that "Ca. Uabimicrobium amorphum" represents an early diverging lineage that clusters with the Saltatorellus clade within the phylum Planctomycetota. A gene flux analysis indicated a gain of 126 protein families for signal transduction functions in "Ca. Uabimicrobium amorphum", of which 66 families contained eukaryotic-like Serine/Threonine kinases with Pkinase domains. In total, we predicted 525 functional Serine/Threonine kinases in "Ca. Uabimicrobium amorphum", which represent 8% of the proteome and is the highest fraction of Serine/Threonine kinases in a bacterial proteome. The majority of Serine/Threonine kinases in this species are membrane proteins and 30% contain long, tandem arrays of WD40 or TPR domains. The pKinase domain was predicted to be located in the cytoplasm, while the WD40 and TPR domains were predicted to be located in the periplasm. Such domain combinations were also identified in the Serine/Threonine kinases of other species in the Planctomycetota, although in much lower abundances. A phylogenetic analysis of the Serine/Threonine kinases in the Planctomycetota inferred from the Pkinase domain alone provided support for lineage-specific expansions of the Serine/Threonine kinases in "Ca. Uabimicrobium amorphum". The results imply that expansions of eukaryotic-like signal transduction systems are not restricted to multicellular organisms, but have occurred in parallel in prokaryotes with predatory lifestyles and phagocytotic-like behaviors.}, } @article {pmid38537926, year = {2024}, author = {Shao, S and Liu, K and Du, J and Yin, C and Wang, M and Wang, Y}, title = {Functional characterization of serine proteinase inhibitor Kazal-Type in the red claw crayfish Cherax quadricarinatus.}, journal = {Fish & shellfish immunology}, volume = {148}, number = {}, pages = {109525}, doi = {10.1016/j.fsi.2024.109525}, pmid = {38537926}, issn = {1095-9947}, mesh = {Humans ; Animals ; *Serine Proteinase Inhibitors/genetics/chemistry ; *Astacoidea ; Phylogeny ; Escherichia coli ; Recombinant Proteins/genetics ; Bacteria/metabolism ; }, abstract = {Serine protease inhibitors Kazal type (SPINKs) function in physiological and immunological processes across multicellular organisms. In the present study, we identified a SPINK gene, designated as CqSPINK, in the red claw crayfish Cherax quadricarinatus, which is the ortholog of human SPINK5. The deduced CqSPINK contains two Kazal domains consisting of 45 amino acid residues with a typical signature motif C-X3-C-X5-PVCG-X5-Y-X3-C-X6-C-X12-14-C. Each Kazal domain contains six conserved cysteine residues forming three pairs of disulfide bonds, segmenting the structure into three rings. Phylogenetic analysis revealed CqSPINK as a homolog of human SPINK5. CqSPINK expression was detected exclusively in hepatopancreas and epithelium, with rapid up-regulation in hepatopancreas upon Vibrio parahaemolyticus E1 challenge. Recombinant CqSPINK protein (rCqSPINK) was heterologously expressed in Escherichia coli and purified for further study. Proteinase inhibition assays demonstrated that rCqSPINK could potently inhibit proteinase K and subtilisin A, weakly inhibit α-chymotrypsin and elastase, but extremely weak inhibit trypsin. Furthermore, CqSPINK inhibited bacterial secretory proteinase activity from Bacillus subtilis, E. coli, and Staphylococcus aureus, and inhibited B. subtilis growth. These findings suggest CqSPINK's involvement in antibacterial immunity through direct inhibition of bacterial proteases, contributing to resistance against pathogen invasion.}, } @article {pmid38531970, year = {2024}, author = {Domazet-Lošo, M and Široki, T and Šimičević, K and Domazet-Lošo, T}, title = {Macroevolutionary dynamics of gene family gain and loss along multicellular eukaryotic lineages.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2663}, pmid = {38531970}, issn = {2041-1723}, support = {IP-2016-06-5924//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; KK.01.1.1.01.0009 DATACROSS//EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj)/ ; }, mesh = {*Biological Evolution ; *Genome ; Phylogeny ; Evolution, Molecular ; }, abstract = {The gain and loss of genes fluctuate over evolutionary time in major eukaryotic clades. However, the full profile of these macroevolutionary trajectories is still missing. To give a more inclusive view on the changes in genome complexity across the tree of life, here we recovered the evolutionary dynamics of gene family gain and loss ranging from the ancestor of cellular organisms to 352 eukaryotic species. We show that in all considered lineages the gene family content follows a common evolutionary pattern, where the number of gene families reaches the highest value at a major evolutionary and ecological transition, and then gradually decreases towards extant organisms. This supports theoretical predictions and suggests that the genome complexity is often decoupled from commonly perceived organismal complexity. We conclude that simplification by gene family loss is a dominant force in Phanerozoic genomes of various lineages, probably underpinned by intense ecological specializations and functional outsourcing.}, } @article {pmid38519635, year = {2024}, author = {}, title = {Multicellularity drives ecological diversity in a long-term evolution experiment.}, journal = {Nature ecology & evolution}, volume = {8}, number = {5}, pages = {856-857}, pmid = {38519635}, issn = {2397-334X}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Biodiversity ; Animals ; }, } @article {pmid38517944, year = {2024}, author = {Phillips, JE and Pan, D}, title = {The Hippo kinase cascade regulates a contractile cell behavior and cell density in a close unicellular relative of animals.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38517944}, issn = {2050-084X}, support = {R01 EY015708/EY/NEI NIH HHS/United States ; EY015708/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Signal Transduction/genetics ; *Protein Serine-Threonine Kinases/genetics/metabolism ; Hippo Signaling Pathway ; Biological Evolution ; Cell Proliferation ; }, abstract = {The genomes of close unicellular relatives of animals encode orthologs of many genes that regulate animal development. However, little is known about the function of such genes in unicellular organisms or the evolutionary process by which these genes came to function in multicellular development. The Hippo pathway, which regulates cell proliferation and tissue size in animals, is present in some of the closest unicellular relatives of animals, including the amoeboid organism Capsaspora owczarzaki. We previously showed that the Capsaspora ortholog of the Hippo pathway nuclear effector Yorkie/YAP/TAZ (coYki) regulates actin dynamics and the three-dimensional morphology of Capsaspora cell aggregates, but is dispensable for cell proliferation control (Phillips et al., 2022). However, the function of upstream Hippo pathway components, and whether and how they regulate coYki in Capsaspora, remained unknown. Here, we analyze the function of the upstream Hippo pathway kinases coHpo and coWts in Capsaspora by generating mutant lines for each gene. Loss of either kinase results in increased nuclear localization of coYki, indicating an ancient, premetazoan origin of this Hippo pathway regulatory mechanism. Strikingly, we find that loss of either kinase causes a contractile cell behavior and increased density of cell packing within Capsaspora aggregates. We further show that this increased cell density is not due to differences in proliferation, but rather actomyosin-dependent changes in the multicellular architecture of aggregates. Given its well-established role in cell density-regulated proliferation in animals, the increased density of cell packing in coHpo and coWts mutants suggests a shared and possibly ancient and conserved function of the Hippo pathway in cell density control. Together, these results implicate cytoskeletal regulation but not proliferation as an ancestral function of the Hippo pathway kinase cascade and uncover a novel role for Hippo signaling in regulating cell density in a proliferation-independent manner.}, } @article {pmid38514634, year = {2024}, author = {Carreira de Paula, J and García Olmedo, P and Gómez-Moracho, T and Buendía-Abad, M and Higes, M and Martín-Hernández, R and Osuna, A and de Pablos, LM}, title = {Promastigote EPS secretion and haptomonad biofilm formation as evolutionary adaptations of trypanosomatid parasites for colonizing honeybee hosts.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {27}, pmid = {38514634}, issn = {2055-5008}, mesh = {Humans ; Bees ; Animals ; *Parasites ; Ecosystem ; *Trypanosomatina/parasitology ; Biological Evolution ; }, abstract = {Bees are major pollinators involved in the maintenance of all terrestrial ecosystems. Biotic and abiotic factors placing these insects at risk is a research priority for ecological and agricultural sustainability. Parasites are one of the key players of this global decline and the study of their mechanisms of action is essential to control honeybee colony losses. Trypanosomatid parasites and particularly the Lotmaria passim are widely spread in honeybees, however their lifestyle is poorly understood. In this work, we show how these parasites are able to differentiate into a new parasitic lifestyle: the trypanosomatid biofilms. Using different microscopic techniques, we demonstrated that the secretion of Extracellular Polymeric Substances by free-swimming unicellular promastigote forms is a prerequisite for the generation and adherence of multicellular biofilms to solid surfaces in vitro and in vivo. Moreover, compared to human-infective trypanosomatid parasites our study shows how trypanosomatid parasites of honeybees increases their resistance and thus resilience to drastic changes in environmental conditions such as ultralow temperatures and hypoosmotic shock, which would explain their success thriving within or outside their hosts. These results set up the basis for the understanding of the success of this group of parasites in nature and to unveil the impact of such pathogens in honeybees, a keystones species in most terrestrial ecosystems.}, } @article {pmid38513719, year = {2024}, author = {Brown, AL and Meiborg, AB and Franz-Wachtel, M and Macek, B and Gordon, S and Rog, O and Weadick, CJ and Werner, MS}, title = {Characterization of the Pristionchus pacificus "epigenetic toolkit" reveals the evolutionary loss of the histone methyltransferase complex PRC2.}, journal = {Genetics}, volume = {227}, number = {1}, pages = {}, pmid = {38513719}, issn = {1943-2631}, support = {R35GM150720/GM/NIGMS NIH HHS/United States ; R35 GM128804/GM/NIGMS NIH HHS/United States ; T32-GM122740/GF/NIH HHS/United States ; R35 GM150720/GM/NIGMS NIH HHS/United States ; T32 GM122740/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Caenorhabditis elegans/genetics ; Polycomb Repressive Complex 2/genetics/metabolism ; Histone Methyltransferases/metabolism/genetics ; Nematoda/genetics ; Helminth Proteins/genetics/metabolism ; }, abstract = {Comparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation-or lack thereof-of developmental networks, the conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematode Pristionchus pacificus has emerged as a model system of plasticity and epigenetic regulation as it exhibits a bacterivorous or omnivorous morph depending on its environment. Here, we determined the "epigenetic toolkit" available to P. pacificus as a resource for future functional work on plasticity, and as a comparison with Caenorhabditis elegans to investigate the conservation of epigenetic mechanisms. Broadly, we observed a similar cast of genes with putative epigenetic function between C. elegans and P. pacificus. However, we also found striking differences. Most notably, the histone methyltransferase complex PRC2 appears to be missing in P. pacificus. We described the deletion/pseudogenization of the PRC2 genes mes-2 and mes-6 and concluded that both were lost in the last common ancestor of P. pacificus and a related species P. arcanus. Interestingly, we observed the enzymatic product of PRC2 (H3K27me3) by mass spectrometry and immunofluorescence, suggesting that a currently unknown methyltransferase has been co-opted for heterochromatin silencing. Altogether, we have provided an inventory of epigenetic genes in P. pacificus to compare with C. elegans. This inventory will enable reverse-genetic experiments related to plasticity and has revealed the first loss of PRC2 in a multicellular organism.}, } @article {pmid38513029, year = {2024}, author = {Luthringer, R and Raphalen, M and Guerra, C and Colin, S and Martinho, C and Zheng, M and Hoshino, M and Badis, Y and Lipinska, AP and Haas, FB and Barrera-Redondo, J and Alva, V and Coelho, SM}, title = {Repeated co-option of HMG-box genes for sex determination in brown algae and animals.}, journal = {Science (New York, N.Y.)}, volume = {383}, number = {6689}, pages = {eadk5466}, doi = {10.1126/science.adk5466}, pmid = {38513029}, issn = {1095-9203}, mesh = {Animals ; Biological Evolution ; *Phaeophyceae/genetics ; *Sex Chromosomes/genetics ; *Sex Determination Processes/genetics ; Y Chromosome ; *HMGB Proteins/genetics ; Chromosomes, Plant/genetics ; HMG-Box Domains ; *Edible Seaweeds/genetics ; *Laminaria/genetics ; Pollen/genetics ; }, abstract = {In many eukaryotes, genetic sex determination is not governed by XX/XY or ZW/ZZ systems but by a specialized region on the poorly studied U (female) or V (male) sex chromosomes. Previous studies have hinted at the existence of a dominant male-sex factor on the V chromosome in brown algae, a group of multicellular eukaryotes distantly related to animals and plants. The nature of this factor has remained elusive. Here, we demonstrate that an HMG-box gene acts as the male-determining factor in brown algae, mirroring the role HMG-box genes play in sex determination in animals. Over a billion-year evolutionary timeline, these lineages have independently co-opted the HMG box for male determination, representing a paradigm for evolution's ability to recurrently use the same genetic "toolkit" to accomplish similar tasks.}, } @article {pmid38498818, year = {2024}, author = {Bozdag, GO and Szeinbaum, N and Conlin, PL and Chen, K and Fos, SM and Garcia, A and Penev, PI and Schaible, GA and Trubl, G}, title = {Chapter 5: Major Biological Innovations in the History of Life on Earth.}, journal = {Astrobiology}, volume = {24}, number = {S1}, pages = {S107-S123}, pmid = {38498818}, issn = {1557-8070}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; }, mesh = {Phylogeny ; *Biological Evolution ; *Earth, Planet ; Oxygen ; Photosynthesis ; }, abstract = {All organisms living on Earth descended from a single, common ancestral population of cells, known as LUCA-the last universal common ancestor. Since its emergence, the diversity and complexity of life have increased dramatically. This chapter focuses on four key biological innovations throughout Earth's history that had a significant impact on the expansion of phylogenetic diversity, organismal complexity, and ecospace habitation. First is the emergence of the last universal common ancestor, LUCA, which laid the foundation for all life-forms on Earth. Second is the evolution of oxygenic photosynthesis, which resulted in global geochemical and biological transformations. Third is the appearance of a new type of cell-the eukaryotic cell-which led to the origin of a new domain of life and the basis for complex multicellularity. Fourth is the multiple independent origins of multicellularity, resulting in the emergence of a new level of complex individuality. A discussion of these four key events will improve our understanding of the intertwined history of our planet and its inhabitants and better inform the extent to which we can expect life at different degrees of diversity and complexity elsewhere.}, } @article {pmid38497809, year = {2024}, author = {Hörandl, E}, title = {Apomixis and the paradox of sex in plants.}, journal = {Annals of botany}, volume = {134}, number = {1}, pages = {1-18}, pmid = {38497809}, issn = {1095-8290}, support = {HO 4395/10-2//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Apomixis/genetics/physiology ; *Magnoliopsida/genetics/physiology ; Reproduction, Asexual ; Biological Evolution ; Ferns/genetics/physiology ; Reproduction/physiology ; Phylogeny ; Meiosis ; Plants/genetics ; }, abstract = {BACKGROUND: The predominance of sex in eukaryotes, despite the high costs of meiosis and mating, remains an evolutionary enigma. Many theories have been proposed, none of them being conclusive on its own, and they are, in part, not well applicable to land plants. Sexual reproduction is obligate in embryophytes for the great majority of species.

SCOPE: This review compares the main forms of sexual and asexual reproduction in ferns and angiosperms, based on the generation cycling of sporophyte and gametophyte (leaving vegetative propagation aside). The benefits of sexual reproduction for maintenance of genomic integrity in comparison to asexuality are discussed in the light of developmental, evolutionary, genetic and phylogenetic studies.

CONCLUSIONS: Asexual reproduction represents modifications of the sexual pathway, with various forms of facultative sexuality. For sexual land plants, meiosis provides direct DNA repair mechanisms for oxidative damage in reproductive tissues. The ploidy alternations of meiosis-syngamy cycles and prolonged multicellular stages in the haploid phase in the gametophytes provide a high efficiency of purifying selection against recessive deleterious mutations. Asexual lineages might buffer effects of such mutations via polyploidy and can purge the mutational load via facultative sexuality. The role of organelle-nuclear genome compatibility for maintenance of genome integrity is not well understood. In plants in general, the costs of mating are low because of predominant hermaphroditism. Phylogenetic patterns in the archaeplastid clade suggest that high frequencies of sexuality in land plants are concomitant with a stepwise increase of intrinsic and extrinsic stress factors. Furthermore, expansion of genome size in land plants would increase the potential mutational load. Sexual reproduction appears to be essential for keeping long-term genomic integrity, and only rare combinations of extrinsic and intrinsic factors allow for shifts to asexuality.}, } @article {pmid38493178, year = {2024}, author = {Bing, J and Guan, Z and Zheng, T and Ennis, CL and Nobile, CJ and Chen, C and Chu, H and Huang, G}, title = {Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2381}, pmid = {38493178}, issn = {2041-1723}, support = {31930005 and 82272359//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32170193 and 32000018//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32170193 and 32000018//National Natural Science Foundation of China (National Science Foundation of China)/ ; R35GM124594//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Animals ; Mice ; Candida/genetics ; *Candidiasis/microbiology ; Candida auris ; Saccharomyces cerevisiae ; Phenotype ; *Sepsis ; Antifungal Agents ; Microbial Sensitivity Tests ; Mammals ; }, abstract = {Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.}, } @article {pmid38492155, year = {2024}, author = {Li, X and Gao, T and Ma, X and Zhong, J and Qin, L and Nian, Y and Wang, X and Luo, Y}, title = {Extraction and identification of exosomes from three different sources of human ovarian granulosa cells and analysis of their differential miRNA expression profiles.}, journal = {Journal of assisted reproduction and genetics}, volume = {41}, number = {5}, pages = {1371-1385}, pmid = {38492155}, issn = {1573-7330}, support = {81660806//National Natural Science Foundation of China/ ; 82260947//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Female ; *Exosomes/genetics/metabolism/ultrastructure ; *Granulosa Cells/metabolism ; *MicroRNAs/genetics ; *Cell Proliferation/genetics ; Gene Expression Profiling ; Cell Line ; }, abstract = {OBJECTIVE: As important functional cells in the ovary, ovarian granulosa cells are involved in the regulation of oocyte growth and development and play an important role in the study of female fertility preservation. Based on the importance of granulosa cell functionalism, in this study, we analyzed the exosome secretion capacity of human ovarian granulosa cells (SVOG/KGN-cell line, PGC-primary cells) and the differences in their miRNA expression.

METHODS: Cells were identified by hematoxylin-eosin staining (HE) and FSHR immunofluorescence staining; CCK8 and colony-forming assay were performed to compare cell proliferation capacity; exosomes were extracted and identified by ultra-high speed centrifugation, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot analysis (WB), and the expression profile of each cellular exosomal miRNA was analyzed by miRNA high-throughput sequencing.

RESULTS: The proliferative abilities of the three granulosa cells differed, but all had the ability to secrete exosomes. In the exosomes of SVOG, KGN, and PGC cells, 218, 327, and 471 miRNAs were detected, respectively. When compared to the exosomal miRNAs of PGC cells, 111 miRNAs were significantly different in SVOG, and 70 miRNAs were washed two significantly different in KGN cells. These differential miRNA functions were mainly enriched in the cell cycle, cell division/differentiation, multicellular biogenesis, and protein binding.

CONCLUSION: Human ovarian granulosa cells of different origins are capable of secreting exosomes, but there are still some differences in their exosomes and exosomal miRNAs, and experimental subjects should be selected rationally according to the actual situation.}, } @article {pmid38486107, year = {2024}, author = {Pineau, RM and Libby, E and Demory, D and Lac, DT and Day, TC and Bravo, P and Yunker, PJ and Weitz, JS and Bozdag, GO and Ratcliff, WC}, title = {Emergence and maintenance of stable coexistence during a long-term multicellular evolution experiment.}, journal = {Nature ecology & evolution}, volume = {8}, number = {5}, pages = {1010-1020}, pmid = {38486107}, issn = {2397-334X}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Saccharomyces cerevisiae/genetics/physiology ; Ecosystem ; }, abstract = {The evolution of multicellular life spurred evolutionary radiations, fundamentally changing many of Earth's ecosystems. Yet little is known about how early steps in the evolution of multicellularity affect eco-evolutionary dynamics. Through long-term experimental evolution, we observed niche partitioning and the adaptive divergence of two specialized lineages from a single multicellular ancestor. Over 715 daily transfers, snowflake yeast were subjected to selection for rapid growth, followed by selection favouring larger group size. Small and large cluster-forming lineages evolved from a monomorphic ancestor, coexisting for over ~4,300 generations, specializing on divergent aspects of a trade-off between growth rate and survival. Through modelling and experimentation, we demonstrate that coexistence is maintained by a trade-off between organismal size and competitiveness for dissolved oxygen. Taken together, this work shows how the evolution of a new level of biological individuality can rapidly drive adaptive diversification and the expansion of a nascent multicellular niche, one of the most historically impactful emergent properties of this evolutionary transition.}, } @article {pmid38481381, year = {2024}, author = {Wu, Z and Liu, D and Ou, Y and Xu, Z and Heng, G and Liu, W and Fu, N and Wang, J and Jiang, D and Gan, L and Dong, J and Wang, X and Chen, Z and Zhang, L and Zhang, C}, title = {Mechanism and endoscopic-treatment-induced evolution of biliary non-anastomotic stricture after liver transplantation revealed by single-cell RNA sequencing.}, journal = {Clinical and translational medicine}, volume = {14}, number = {3}, pages = {e1622}, pmid = {38481381}, issn = {2001-1326}, support = {2022TIAD-GPX0236//Technical Innovation and Application of Chongqing/ ; 2022TIAD-GPX0238//Technical Innovation and Application of Chongqing/ ; 82270687//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Liver Transplantation/adverse effects ; Constriction, Pathologic/surgery/etiology ; Retrospective Studies ; Endothelial Cells ; Sequence Analysis, RNA ; Bile Acids and Salts ; }, abstract = {BACKGROUND: Biliary complications, especially non-anastomotic stricture (NAS), are the main complications after liver transplantation. Insufficient sampling and no recognized animal models obstruct the investigation. Thus, the mechanisms and alterations that occur during endoscopic treatment (ET) of NAS remain unclear.

METHODS: Samples were obtained with endoscopic forceps from the hilar bile ducts of NAS patients receiving continuous biliary stent implantation after diagnosis. Retrospective analysis of multiple studies indicated that the duration of ET for NAS was approximately 1-2 years. Thus, we divided the patients into short-term treatment (STT) and long-term treatment (LTT) groups based on durations of less or more than 1 year. Samples were subjected to single-cell RNA sequencing. Transcriptomic differences between STT and normal groups were defined as the NAS mechanism. Similarly, alterations from STT to LTT groups were regarded as endoscopic-treatment-induced evolution.

RESULTS: In NAS, inflammation and immune-related pathways were upregulated in different cell types, with nonimmune cells showing hypoxia pathway upregulation and immune cells showing ATP metabolism pathway upregulation, indicating heterogeneity. We confirmed a reduction in bile acid metabolism-related SPP1[+] epithelial cells in NAS. Increases in proinflammatory and profibrotic fibroblast subclusters indicated fibrotic progression in NAS. Furthermore, immune disorders in NAS were exacerbated by an increase in plasma cells and dysfunction of NK and NKT cells. ET downregulated multicellular immune and inflammatory responses and restored epithelial and endothelial cell proportions.

CONCLUSIONS: This study reveals the pathophysiological and genetic mechanisms and evolution of NAS induced by ET, thereby providing preventive and therapeutic insights into NAS.

HIGHLIGHTS: For the first time, single-cell transcriptome sequencing was performed on the bile ducts of patients with biliary complications. scRNA-seq analysis revealed distinct changes in the proportion and phenotype of multiple cell types during Nonanastomotic stricture (NAS) and endoscopic treatment. A reduction in bile acid metabolism-related SPP1+ epithelial cells and VEGFA+ endothelial cells, along with explosive infiltration of plasma cells and dysfunction of T and NK cells in NAS patients. SPP1+ macrophages and BST2+ T cells might serve as a surrogate marker for predicting endoscopic treatment.}, } @article {pmid38474088, year = {2024}, author = {Jiménez-López, D and Xoconostle-Cázares, B and Calderón-Pérez, B and Vargas-Hernández, BY and Núñez-Muñoz, LA and Ramírez-Pool, JA and Ruiz-Medrano, R}, title = {Evolutionary and Structural Analysis of PP16 in Viridiplantae.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38474088}, issn = {1422-0067}, support = {781282//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; }, mesh = {*Plant Proteins/genetics ; Phloem/metabolism ; Plants/metabolism ; Biological Transport ; *Viridiplantae/metabolism ; }, abstract = {Members of the phloem protein 16 (PP16) gene family are induced by elicitors in rice and the corresponding proteins from cucurbits, which display RNA binding and intercellular transport activities, are accumulated in phloem sap. These proteins facilitate the movement of protein complexes through the phloem translocation flow and may be involved in the response to water deficit, among other functions. However, there is scant information regarding their function in other plants, including the identification of paralog genes in non-vascular plants and chlorophytes. In the present work, an evolutionary and structural analysis of the PP16 family in green plants (Viridiplantae) was carried out. Data mining in different databases indicated that PP16 likely originated from a larger gene present in an ancestral lineage that gave rise to chlorophytes and multicellular plants. This gene encodes a protein related to synaptotagmin, which is involved in vesicular transport in animal systems, although other members of this family play a role in lipid turnover in endomembranes and organelles. These proteins contain a membrane-binding C2 domain shared with PP16 proteins in vascular plants. In silico analysis of the predicted structure of the PP16 protein family identified several β-sheets, one α-helix, and intrinsically disordered regions. PP16 may have been originally involved in vesicular trafficking and/or membrane maintenance but specialized in long-distance signaling during the emergence of the plant vascular system.}, } @article {pmid38471558, year = {2024}, author = {Jung, J and Loschko, T and Reich, S and Rassoul-Agha, M and Werner, MS}, title = {Newly identified nematodes from the Great Salt Lake are associated with microbialites and specially adapted to hypersaline conditions.}, journal = {Proceedings. Biological sciences}, volume = {291}, number = {2018}, pages = {20232653}, pmid = {38471558}, issn = {1471-2954}, mesh = {Animals ; *Ecosystem ; Lakes/chemistry ; Phylogeny ; *Nematoda ; Bacteria ; }, abstract = {Extreme environments enable the study of simplified food-webs and serve as models for evolutionary bottlenecks and early Earth ecology. We investigated the biodiversity of invertebrate meiofauna in the benthic zone of the Great Salt Lake (GSL), Utah, USA, one of the most hypersaline lake systems in the world. The hypersaline bays within the GSL are currently thought to support only two multicellular animals: brine fly larvae and brine shrimp. Here, we report the presence, habitat, and microbial interactions of novel free-living nematodes. Nematode diversity drops dramatically along a salinity gradient from a freshwater river into the south arm of the lake. In Gilbert Bay, nematodes primarily inhabit reef-like organosedimentary structures built by bacteria called microbialites. These structures likely provide a protective barrier to UV and aridity, and bacterial associations within them may support life in hypersaline environments. Notably, sampling from Owens Lake, another terminal lake in the Great Basin that lacks microbialites, did not recover nematodes from similar salinities. Phylogenetic divergence suggests that GSL nematodes represent previously undescribed members of the family Monhysteridae-one of the dominant fauna of the abyssal zone and deep-sea hydrothermal vents. These findings update our understanding of halophile ecosystems and the habitable limit of animals.}, } @article {pmid38465473, year = {2024}, author = {Borland, G and Wilkie, SE and Thomson, J and Wang, Z and Tullet, JMA and Alic, N and Selman, C}, title = {Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan.}, journal = {Aging cell}, volume = {23}, number = {5}, pages = {e14141}, pmid = {38465473}, issn = {1474-9726}, support = {BB/S014357/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/N013166/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Female ; Male ; Mice ; *Aging/genetics ; *Heterozygote ; *Longevity/genetics ; Mice, Inbred C57BL ; *RNA Polymerase III/genetics/metabolism ; }, abstract = {The genetic pathways that modulate ageing in multicellular organisms are typically highly conserved across wide evolutionary distances. Recently RNA polymerase III (Pol III) was shown to promote ageing in yeast, C. elegans and D. melanogaster. In this study we investigated the role of Pol III in mammalian ageing using C57BL/6N mice heterozygous for Pol III (Polr3b[+/-]). We identified sexually dimorphic, organ-specific beneficial as well as detrimental effects of the Polr3b[+/-] mutation on health. Female Polr3b[+/-] mice displayed improved bone health during ageing, but their ability to maintain an effective gut barrier function was compromised and they were susceptible to idiopathic dermatitis (ID). In contrast, male Polr3b[+/-] mice were lighter than wild-type (WT) males and had a significantly improved gut barrier function in old age. Several metabolic parameters were affected by both age and sex, but no genotype differences were detected. Neither male nor female Polr3b[+/-] mice were long-lived compared to WT controls. Overall, we find no evidence that a reduced Pol III activity extends mouse lifespan but we do find some potential organ- and sex-specific benefits for old-age health.}, } @article {pmid38462458, year = {2023}, author = {Libertini, G}, title = {Phenoptosis and the Various Types of Natural Selection.}, journal = {Biochemistry. Biokhimiia}, volume = {88}, number = {12}, pages = {2007-2022}, doi = {10.1134/S0006297923120052}, pmid = {38462458}, issn = {1608-3040}, mesh = {Animals ; Bees ; *Aging/genetics ; Ecosystem ; Selection, Genetic ; *Ants ; Reproduction ; Biological Evolution ; }, abstract = {In the first description of evolution, the fundamental mechanism is the natural selection favoring the individuals best suited for survival and reproduction (selection at the individual level or classical Darwinian selection). However, this is a very reductive description of natural selection that does not consider or explain a long series of known phenomena, including those in which an individual sacrifices or jeopardizes his life on the basis of genetically determined mechanisms (i.e., phenoptosis). In fact, in addition to (i) selection at the individual level, it is essential to consider other types of natural selection such as those concerning: (ii) kin selection and some related forms of group selection; (iii) the interactions between the innumerable species that constitute a holobiont; (iv) the origin of the eukaryotic cell from prokaryotic organisms; (v) the origin of multicellular eukaryotic organisms from unicellular organisms; (vi) eusociality (e.g., in many species of ants, bees, termites); (vii) selection at the level of single genes, or groups of genes; (viii) the interactions between individuals (or more precisely their holobionts) of the innumerable species that make up an ecosystem. These forms of natural selection, which are all effects and not violations of the classical Darwinian selection, also show how concepts as life, species, individual, and phenoptosis are somewhat not entirely defined and somehow arbitrary. Furthermore, the idea of organisms selected on the basis of their survival and reproduction capabilities is intertwined with that of organisms also selected on the basis of their ability to cooperate and interact, even by losing their lives or their distinct identities.}, } @article {pmid38459017, year = {2024}, author = {Stanojković, A and Skoupý, S and Johannesson, H and Dvořák, P}, title = {The global speciation continuum of the cyanobacterium Microcoleus.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2122}, pmid = {38459017}, issn = {2041-1723}, support = {19-12994Y//Grantová Agentura České Republiky (Grant Agency of the Czech Republic)/ ; 23-06507S//Grantová Agentura České Republiky (Grant Agency of the Czech Republic)/ ; }, mesh = {*Genetic Speciation ; *Genetic Drift ; Gene Flow ; Genome ; Phylogeny ; }, abstract = {Speciation is a continuous process driven by genetic, geographic, and ecological barriers to gene flow. It is widely investigated in multicellular eukaryotes, yet we are only beginning to comprehend the relative importance of mechanisms driving the emergence of barriers to gene flow in microbial populations. Here, we explored the diversification of the nearly ubiquitous soil cyanobacterium Microcoleus. Our dataset consisted of 291 genomes, of which 202 strains and eight herbarium specimens were sequenced for this study. We found that Microcoleus represents a global speciation continuum of at least 12 lineages, which radiated during Eocene/Oligocene aridification and exhibit varying degrees of divergence and gene flow. The lineage divergence has been driven by selection, geographical distance, and the environment. Evidence of genetic divergence and selection was widespread across the genome, but we identified regions of exceptional differentiation containing candidate genes associated with stress response and biosynthesis of secondary metabolites.}, } @article {pmid38447933, year = {2024}, author = {Park, S and Cho, SW}, title = {Bioengineering toolkits for potentiating organoid therapeutics.}, journal = {Advanced drug delivery reviews}, volume = {208}, number = {}, pages = {115238}, doi = {10.1016/j.addr.2024.115238}, pmid = {38447933}, issn = {1872-8294}, mesh = {Animals ; Mice ; *Organoids ; Tissue Engineering/methods ; Regenerative Medicine ; Bioengineering ; *Neoplasms ; }, abstract = {Organoids are three-dimensional, multicellular constructs that recapitulate the structural and functional features of specific organs. Because of these characteristics, organoids have been widely applied in biomedical research in recent decades. Remarkable advancements in organoid technology have positioned them as promising candidates for regenerative medicine. However, current organoids still have limitations, such as the absence of internal vasculature, limited functionality, and a small size that is not commensurate with that of actual organs. These limitations hinder their survival and regenerative effects after transplantation. Another significant concern is the reliance on mouse tumor-derived matrix in organoid culture, which is unsuitable for clinical translation due to its tumor origin and safety issues. Therefore, our aim is to describe engineering strategies and alternative biocompatible materials that can facilitate the practical applications of organoids in regenerative medicine. Furthermore, we highlight meaningful progress in organoid transplantation, with a particular emphasis on the functional restoration of various organs.}, } @article {pmid38436556, year = {2024}, author = {Matsumoto, H and Ueda, M}, title = {Polarity establishment in the plant zygote at a glance.}, journal = {Journal of cell science}, volume = {137}, number = {5}, pages = {}, doi = {10.1242/jcs.261809}, pmid = {38436556}, issn = {1477-9137}, support = {//Japan Advanced Plant Science Network/ ; JP21K20650//Japan Society for the Promotion of Science/ ; JPMJCR2121//Japan Science and Technology Agency/ ; //Suntory Rising Stars Encouragement Program in Life Sciences/ ; 20-6102//Toray Science Foundation/ ; }, mesh = {*Zygote ; Seeds ; *Arabidopsis/genetics ; Meristem ; Transcriptional Activation ; }, abstract = {The complex structures of multicellular organisms originate from a unicellular zygote. In most angiosperms, including Arabidopsis thaliana, the zygote is distinctly polar and divides asymmetrically to produce an apical cell, which generates the aboveground part of the plant body, and a basal cell, which generates the root tip and extraembryonic suspensor. Thus, zygote polarity is pivotal for establishing the apical-basal axis running from the shoot apex to the root tip of the plant body. The molecular mechanisms and spatiotemporal dynamics behind zygote polarization remain elusive. However, advances in live-cell imaging of plant zygotes have recently made significant insights possible. In this Cell Science at a Glance article and the accompanying poster, we summarize our understanding of the early steps in apical-basal axis formation in Arabidopsis, with a focus on de novo transcriptional activation after fertilization and the intracellular dynamics leading to the first asymmetric division of the zygote.}, } @article {pmid38424063, year = {2024}, author = {Bayer, EM and Benitez-Alfonso, Y}, title = {Plasmodesmata: Channels Under Pressure.}, journal = {Annual review of plant biology}, volume = {75}, number = {1}, pages = {291-317}, doi = {10.1146/annurev-arplant-070623-093110}, pmid = {38424063}, issn = {1545-2123}, support = {MR/T04263X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Plasmodesmata/metabolism/physiology ; *Cell Communication ; Plant Development/physiology ; Plants/metabolism ; Plant Physiological Phenomena ; }, abstract = {Multicellularity has emerged multiple times in evolution, enabling groups of cells to share a living space and reducing the burden of solitary tasks. While unicellular organisms exhibit individuality and independence, cooperation among cells in multicellular organisms brings specialization and flexibility. However, multicellularity also necessitates intercellular dependence and relies on intercellular communication. In plants, this communication is facilitated by plasmodesmata: intercellular bridges that allow the direct (cytoplasm-to-cytoplasm) transfer of information between cells. Plasmodesmata transport essential molecules that regulate plant growth, development, and stress responses. They are embedded in the extracellular matrix but exhibit flexibility, adapting intercellular flux to meet the plant's needs.In this review, we delve into the formation and functionality of plasmodesmata and examine the capacity of the plant communication network to respond to developmental and environmental cues. We illustrate how environmental pressure shapes cellular interactions and aids the plant in adapting its growth.}, } @article {pmid38400751, year = {2024}, author = {Woudenberg, S and Hadid, F and Weijers, D and Borassi, C}, title = {The maternal embrace: the protection of plant embryos.}, journal = {Journal of experimental botany}, volume = {75}, number = {14}, pages = {4210-4218}, pmid = {38400751}, issn = {1460-2431}, support = {//Graduate School Experimental Plant Sciences/ ; /ERC_/European Research Council/International ; ENW-KLEIN2//Netherlands Organization for Scientific Research/ ; }, mesh = {*Seeds/growth & development ; Embryophyta/growth & development ; Biological Evolution ; }, abstract = {All land plants-the embryophytes-produce multicellular embryos, as do other multicellular organisms, such as brown algae and animals. A unique characteristic of plant embryos is their immobile and confined nature. Their embedding in maternal tissues may offer protection from the environment, but also physically constrains development. Across the different land plants, a huge discrepancy is present between their reproductive structures whilst leading to similarly complex embryos. Therefore, we review the roles that maternal tissues play in the control of embryogenesis across land plants. These nurturing, constraining, and protective roles include both direct and indirect effects. In this review, we explore how the maternal surroundings affect embryogenesis and which chemical and mechanical barriers are in place. We regard these questions through the lens of evolution, and identify key questions for future research.}, } @article {pmid38388648, year = {2024}, author = {Ratajczak, MZ and Ratajczak, J}, title = {Leukemogenesis occurs in a microenvironment enriched by extracellular microvesicles/exosomes: recent discoveries and questions to be answered.}, journal = {Leukemia}, volume = {38}, number = {4}, pages = {692-698}, pmid = {38388648}, issn = {1476-5551}, support = {R01 DK074720/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Exosomes/metabolism ; *Cell-Derived Microparticles ; Cell Communication ; Signal Transduction ; Proteins/metabolism ; *Extracellular Vesicles/metabolism ; }, abstract = {In single-cell organisms, extracellular microvesicles (ExMVs) were one of the first cell-cell communication platforms that emerged very early during evolution. Multicellular organisms subsequently adapted this mechanism. Evidence indicates that all types of cells secrete these small circular structures surrounded by a lipid membrane that may be encrusted by ligands and receptors interacting with target cells and harboring inside a cargo comprising RNA species, proteins, bioactive lipids, signaling nucleotides, and even entire organelles "hijacked" from the cells of origin. ExMVs are secreted by normal cells and at higher levels by malignant cells, and there are some differences in their cargo. On the one hand, ExMVs secreted from malignant cells interact with cells in the microenvironment, and in return, they are exposed by a "two-way mechanism" to ExMVs secreted by non-leukemic cells. Therefore, leukemogenesis occurs and progresses in ExMVs enriched microenvironments, and this biological fact has pathologic, diagnostic, and therapeutic implications. We are still trying to decipher this intriguing cell-cell communication language better. We will present a current point of view on this topic and review some selected most recent discoveries and papers.}, } @article {pmid38386708, year = {2024}, author = {Ilker, E and Hinczewski, M}, title = {Bioenergetic costs and the evolution of noise regulation by microRNAs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {9}, pages = {e2308796121}, pmid = {38386708}, issn = {1091-6490}, mesh = {*Eukaryota ; *MicroRNAs/genetics ; Mutant Proteins ; RNA, Messenger ; Energy Metabolism/genetics ; }, abstract = {Noise control, together with other regulatory functions facilitated by microRNAs (miRNAs), is believed to have played important roles in the evolution of multicellular eukaryotic organisms. miRNAs can dampen protein fluctuations via enhanced degradation of messenger RNA (mRNA), but this requires compensation by increased mRNA transcription to maintain the same expression levels. The overall mechanism is metabolically expensive, leading to questions about how it might have evolved in the first place. We develop a stochastic model of miRNA noise regulation, coupled with a detailed analysis of the associated metabolic costs. Additionally, we calculate binding free energies for a range of miRNA seeds, the short sequences which govern target recognition. We argue that natural selection may have fine-tuned the Michaelis-Menten constant [Formula: see text] describing miRNA-mRNA affinity and show supporting evidence from analysis of experimental data. [Formula: see text] is constrained by seed length, and optimal noise control (minimum protein variance at a given energy cost) is achievable for seeds of 6 to 7 nucleotides in length, the most commonly observed types. Moreover, at optimality, the degree of noise reduction approaches the theoretical bound set by the Wiener-Kolmogorov linear filter. The results illustrate how selective pressure toward energy efficiency has potentially shaped a crucial regulatory pathway in eukaryotes.}, } @article {pmid38385784, year = {2024}, author = {Hesse, E and O'Brien, S}, title = {Ecological dependencies and the illusion of cooperation in microbial communities.}, journal = {Microbiology (Reading, England)}, volume = {170}, number = {2}, pages = {}, pmid = {38385784}, issn = {1465-2080}, mesh = {Humans ; *Illusions ; *Microbiota ; Amino Acids ; Biological Evolution ; Nitrogen ; }, abstract = {Ecological dependencies - where organisms rely on other organisms for survival - are a ubiquitous feature of life on earth. Multicellular hosts rely on symbionts to provide essential vitamins and amino acids. Legume plants similarly rely on nitrogen-fixing rhizobia to convert atmospheric nitrogen to ammonia. In some cases, dependencies can arise via loss-of-function mutations that allow one partner to benefit from the actions of another. It is common in microbiology to label ecological dependencies between species as cooperation - making it necessary to invoke cooperation-specific frameworks to explain the phenomenon. However, in many cases, such traits are not (at least initially) cooperative, because they are not selected for because of the benefits they confer on a partner species. In contrast, dependencies in microbial communities may originate from fitness benefits gained from genomic-streamlining (i.e. Black Queen Dynamics). Here, we outline how the Black Queen Hypothesis predicts the formation of metabolic dependencies via loss-of-function mutations in microbial communities, without needing to invoke any cooperation-specific explanations. Furthermore we outline how the Black Queen Hypothesis can act as a blueprint for true cooperation as well as discuss key outstanding questions in the field. The nature of interactions in microbial communities can predict the ability of natural communities to withstand and recover from disturbances. Hence, it is vital to gain a deeper understanding of the factors driving these dynamic interactions over evolutionary time.}, } @article {pmid38382824, year = {2024}, author = {Mikhailovsky, GE}, title = {Life, its definition, origin, evolution, and four-dimensional hierarchical structure.}, journal = {Bio Systems}, volume = {237}, number = {}, pages = {105158}, doi = {10.1016/j.biosystems.2024.105158}, pmid = {38382824}, issn = {1872-8324}, mesh = {*Biological Evolution ; Thermodynamics ; *Eukaryota ; Prokaryotic Cells ; }, abstract = {The main unique features of biological systems are reviewed, and four necessary and sufficient attributes of life are formulated, based on the ideas of Ervin Bauer. The possibility of the occurrence of each of these attributes during the origin of life is analyzed. As a result, different scenarios for the origin of life are presented, with their pros and cons. Next, the mainstream of biological evolution is discussed, considering it as a special case of general complexification, and structuredness is defined as a quantitative measure of structural complexity. By introducing the concepts of post-dissipative structure and ratcheting process based on "frozen" patterns, their role in the generation of biological structures underlying biological evolution is demonstrated. Furthermore, it is proposed that all living things can be divided into micro- (unicellular) and macro- (multicellular) creatures, which differ from each other even more radically than the difference between prokaryotes and unicellular eukaryotes. Then the fifth, sufficient, but not necessary attribute of life, hierarchicality, is formulated, which is fully applicable only to macrolife. It is also shown that living organisms are primarily chemodynamic rather than thermodynamic systems, and three basic laws of biochemodynamics are formulated. Finally, fifteen basic features of living beings, grouped into four basic blocks, are summarized.}, } @article {pmid38379073, year = {2024}, author = {Deng, S and Gong, H and Zhang, D and Zhang, M and He, X}, title = {A statistical method for quantifying progenitor cells reveals incipient cell fate commitments.}, journal = {Nature methods}, volume = {21}, number = {4}, pages = {597-608}, pmid = {38379073}, issn = {1548-7105}, support = {32293190//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32200492//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; Mice ; Phylogeny ; Cell Differentiation/genetics ; *Stem Cells ; *Embryonic Development ; Cell Division ; }, abstract = {Quantifying the number of progenitor cells that found an organ, tissue or cell population is of fundamental importance for understanding the development and homeostasis of a multicellular organism. Previous efforts rely on marker genes that are specifically expressed in progenitors. This strategy is, however, often hindered by the lack of ideal markers. Here we propose a general statistical method to quantify the progenitors of any tissues or cell populations in an organism, even in the absence of progenitor-specific markers, by exploring the cell phylogenetic tree that records the cell division history during development. The method, termed targeting coalescent analysis (TarCA), computes the probability that two randomly sampled cells of a tissue coalesce within the tissue-specific monophyletic clades. The inverse of this probability then serves as a measure of the progenitor number of the tissue. Both mathematic modeling and computer simulations demonstrated the high accuracy of TarCA, which was then validated using real data from nematode, fruit fly and mouse, all with related cell phylogenetic trees. We further showed that TarCA can be used to identify lineage-specific upregulated genes during embryogenesis, revealing incipient cell fate commitments in mouse embryos.}, } @article {pmid38377113, year = {2024}, author = {Nino Barreat, JG and Katzourakis, A}, title = {Ecological and evolutionary dynamics of cell-virus-virophage systems.}, journal = {PLoS computational biology}, volume = {20}, number = {2}, pages = {e1010925}, pmid = {38377113}, issn = {1553-7358}, mesh = {Humans ; *Virophages ; Apoptosis ; Biological Evolution ; *Coinfection ; Antiviral Agents ; }, abstract = {Microbial eukaryotes, giant viruses and virophages form a unique hyperparasitic system. Virophages are parasites of the virus transcription machinery and can interfere with virus replication, resulting in a benefit to the eukaryotic host population. Surprisingly, virophages can integrate into the genomes of their cell or virus hosts, and have been shown to reactivate during coinfection. This raises questions about the role of integration in the dynamics of cell-virus-virophage systems. We use mathematical models and computational simulations to understand the effect of virophage integration on populations of cells and viruses. We also investigate multicellularity and programmed cell-death (PCD) as potential antiviral defence strategies used by cells. We found that virophages which enter the cell independently of the host virus, such as Mavirus, are expected to integrate commonly into the genomes of their cell hosts. Our models suggest that integrations from virophages without an independent mode of entry like Sputnik, are less likely to become fixed in the cell host population. Alternatively, we found that Sputnik virophages can stably persist integrated in the virus population, as long as they do not completely inhibit virus replication. We also show that increasing virophage inhibition can stabilise oscillatory dynamics, which may explain the long-term persistence of viruses and virophages in the environment. Our results demonstrate that inhibition by virophages and multicellularity are effective antiviral strategies that may act in synergy against viral infection in microbial species.}, } @article {pmid38375870, year = {2024}, author = {Edelbroek, B and Kjellin, J and Biryukova, I and Liao, Z and Lundberg, T and Noegel, AA and Eichinger, L and Friedländer, MR and Söderbom, F}, title = {Evolution of microRNAs in Amoebozoa and implications for the origin of multicellularity.}, journal = {Nucleic acids research}, volume = {52}, number = {6}, pages = {3121-3136}, pmid = {38375870}, issn = {1362-4962}, support = {2021-05793//Swedish Research Council/ ; //Uppsala University/ ; }, mesh = {*Amoebozoa/classification/genetics ; Dictyostelium/genetics ; *MicroRNAs/genetics ; Phylogeny ; *Evolution, Molecular ; *RNA, Protozoan/genetics ; Conserved Sequence/genetics ; RNA Interference ; }, abstract = {MicroRNAs (miRNAs) are important and ubiquitous regulators of gene expression in both plants and animals. They are thought to have evolved convergently in these lineages and hypothesized to have played a role in the evolution of multicellularity. In line with this hypothesis, miRNAs have so far only been described in few unicellular eukaryotes. Here, we investigate the presence and evolution of miRNAs in Amoebozoa, focusing on species belonging to Acanthamoeba, Physarum and dictyostelid taxonomic groups, representing a range of unicellular and multicellular lifestyles. miRNAs that adhere to both the stringent plant and animal miRNA criteria were identified in all examined amoebae, expanding the total number of protists harbouring miRNAs from 7 to 15. We found conserved miRNAs between closely related species, but the majority of species feature only unique miRNAs. This shows rapid gain and/or loss of miRNAs in Amoebozoa, further illustrated by a detailed comparison between two evolutionary closely related dictyostelids. Additionally, loss of miRNAs in the Dictyostelium discoideum drnB mutant did not seem to affect multicellular development and, hence, demonstrates that the presence of miRNAs does not appear to be a strict requirement for the transition from uni- to multicellular life.}, } @article {pmid38352462, year = {2024}, author = {Kidner, RQ and Goldstone, EB and Laidemitt, MR and Sanchez, MC and Gerdt, C and Brokaw, LP and Ros-Rocher, N and Morris, J and Davidson, WS and Gerdt, JP}, title = {Host lipids regulate multicellular behavior of a predator of a human pathogen.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38352462}, issn = {2692-8205}, support = {R37 AI101438/AI/NIAID NIH HHS/United States ; R01 HL062542/HL/NHLBI NIH HHS/United States ; T32 GM131994/GM/NIGMS NIH HHS/United States ; S10 OD024988/OD/NIH HHS/United States ; P30 GM110907/GM/NIGMS NIH HHS/United States ; R35 GM138376/GM/NIGMS NIH HHS/United States ; HHSN272201700014C/AI/NIAID NIH HHS/United States ; }, abstract = {As symbionts of animals, microbial eukaryotes benefit and harm their hosts in myriad ways. A model microeukaryote (Capsaspora owczarzaki) is a symbiont of Biomphalaria glabrata snails and may prevent transmission of parasitic schistosomes from snails to humans. However, it is unclear which host factors determine Capsaspora's ability to colonize snails. Here, we discovered that Capsaspora forms multicellular aggregates when exposed to snail hemolymph. We identified a molecular cue for aggregation: a hemolymph-derived phosphatidylcholine, which becomes elevated in schistosome-infected snails. Therefore, Capsaspora aggregation may be a response to the physiological state of its host, and it may determine its ability to colonize snails and exclude parasitic schistosomes. Furthermore, Capsaspora is an evolutionary model organism whose aggregation may be ancestral to animals. This discovery, that a prevalent lipid induces Capsaspora multicellularity, suggests that this aggregation phenotype may be ancient. Additionally, the specific lipid will be a useful tool for further aggregation studies.}, } @article {pmid38351630, year = {2024}, author = {Iwaï, H and Beyer, HM and Johansson, JEM and Li, M and Wlodawer, A}, title = {The three-dimensional structure of the Vint domain from Tetrahymena thermophila suggests a ligand-regulated cleavage mechanism by the HINT fold.}, journal = {FEBS letters}, volume = {598}, number = {8}, pages = {864-874}, doi = {10.1002/1873-3468.14817}, pmid = {38351630}, issn = {1873-3468}, support = {75N91019D00024/CA/NCI NIH HHS/United States ; 75N91019D00024/CA/NCI NIH HHS/United States ; }, mesh = {*Tetrahymena thermophila/metabolism/genetics ; *Protozoan Proteins/chemistry/metabolism/genetics ; *Protein Domains ; Ligands ; Models, Molecular ; Hedgehog Proteins/metabolism/chemistry/genetics ; Amino Acid Sequence ; Protein Folding ; }, abstract = {Vint proteins have been identified in unicellular metazoans as a novel hedgehog-related gene family, merging the von Willebrand factor type A domain and the Hedgehog/INTein (HINT) domains. We present the first three-dimensional structure of the Vint domain from Tetrahymena thermophila corresponding to the auto-processing domain of hedgehog proteins, shedding light on the unique features, including an adduct recognition region (ARR). Our results suggest a potential binding between the ARR and sulfated glycosaminoglycans like heparin sulfate. Moreover, we uncover a possible regulatory role of the ARR in the auto-processing by Vint domains, expanding our understanding of the HINT domain evolution and their use in biotechnological applications. Vint domains might have played a crucial role in the transition from unicellular to multicellular organisms.}, } @article {pmid38334416, year = {2024}, author = {Földi, C and Merényi, Z and Balázs, B and Csernetics, Á and Miklovics, N and Wu, H and Hegedüs, B and Virágh, M and Hou, Z and Liu, X-B and Galgóczy, L and Nagy, LG}, title = {Snowball: a novel gene family required for developmental patterning of fruiting bodies of mushroom-forming fungi (Agaricomycetes).}, journal = {mSystems}, volume = {9}, number = {3}, pages = {e0120823}, pmid = {38334416}, issn = {2379-5077}, support = {LP2019-13/2019//Hungarian Academy of Sciences/ ; KDP-17-4/PALY-2021//Ministry of Innovation and Technology (Hungary)/ ; OTKA 142188//National Research Development and Innovation Office (Hungary)/ ; }, mesh = {Fruiting Bodies, Fungal/genetics ; Phylogeny ; Fungal Proteins/genetics ; *Agaricales/genetics ; *Basidiomycota/metabolism ; *Ascomycota/metabolism ; }, abstract = {UNLABELLED: The morphogenesis of sexual fruiting bodies of fungi is a complex process determined by a genetically encoded program. Fruiting bodies reached the highest complexity levels in the Agaricomycetes; yet, the underlying genetics is currently poorly known. In this work, we functionally characterized a highly conserved gene termed snb1, whose expression level increases rapidly during fruiting body initiation. According to phylogenetic analyses, orthologs of snb1 are present in almost all agaricomycetes and may represent a novel conserved gene family that plays a substantial role in fruiting body development. We disrupted snb1 using CRISPR/Cas9 in the agaricomycete model organism Coprinopsis cinerea. snb1 deletion mutants formed unique, snowball-shaped, rudimentary fruiting bodies that could not differentiate caps, stipes, and lamellae. We took advantage of this phenotype to study fruiting body differentiation using RNA-Seq analyses. This revealed differentially regulated genes and gene families that, based on wild-type RNA-Seq data, were upregulated early during development and showed tissue-specific expression, suggesting a potential role in differentiation. Taken together, the novel gene family of snb1 and the differentially expressed genes in the snb1 mutants provide valuable insights into the complex mechanisms underlying developmental patterning in the Agaricomycetes.

IMPORTANCE: Fruiting bodies of mushroom-forming fungi (Agaricomycetes) are complex multicellular structures, with a spatially and temporally integrated developmental program that is, however, currently poorly known. In this study, we present a novel, conserved gene family, Snowball (snb), termed after the unique, differentiation-less fruiting body morphology of snb1 knockout strains in the model mushroom Coprinopsis cinerea. snb is a gene of unknown function that is highly conserved among agaricomycetes and encodes a protein of unknown function. A comparative transcriptomic analysis of the early developmental stages of differentiated wild-type and non-differentiated mutant fruiting bodies revealed conserved differentially expressed genes which may be related to tissue differentiation and developmental patterning fruiting body development.}, } @article {pmid38334408, year = {2024}, author = {Wang, R and Meng, Q and Wang, X and Xiao, Y and Sun, R and Zhang, Z and Fu, Y and Di Giuseppe, G and Liang, A}, title = {Comparative genomic analysis of symbiotic and free-living Fluviibacter phosphoraccumulans strains provides insights into the evolutionary origins of obligate Euplotes-bacterial endosymbioses.}, journal = {Applied and environmental microbiology}, volume = {90}, number = {3}, pages = {e0190023}, pmid = {38334408}, issn = {1098-5336}, support = {32270447//MOST | National Natural Science Foundation of China (NSFC)/ ; 31372199//MOST | National Natural Science Foundation of China (NSFC)/ ; 20220302121320//Fundamental Research Program of Shanxi Province/ ; }, mesh = {Phylogeny ; Symbiosis/genetics ; *Euplotes/genetics/microbiology ; *Betaproteobacteria/genetics ; Bacteria/genetics ; Genome, Bacterial ; Genomics ; }, abstract = {UNLABELLED: Endosymbiosis is a widespread and important phenomenon requiring diverse model systems. Ciliates are a widespread group of protists that often form symbioses with diverse microorganisms. Endosymbioses between the ciliate Euplotes and heritable bacterial symbionts are common in nature, and four essential symbionts were described: Polynucleobacter necessarius, "Candidatus Protistobacter heckmanni," "Ca. Devosia symbiotica," and "Ca. Devosia euplotis." Among them, only the genus Polynucleobacter comprises very close free-living and symbiotic representatives, which makes it an excellent model for investigating symbiont replacements and recent symbioses. In this article, we characterized a novel endosymbiont inhabiting the cytoplasm of Euplotes octocarinatus and found that it is a close relative of the free-living bacterium Fluviibacter phosphoraccumulans (Betaproteobacteria and Rhodocyclales). We present the complete genome sequence and annotation of the symbiotic Fluviibacter. Comparative analyses indicate that the genome of symbiotic Fluviibacter is small in size and rich in pseudogenes when compared with free-living strains, which seems to fit the prediction for recently established endosymbionts undergoing genome erosion. Further comparative analysis revealed reduced metabolic capacities in symbiotic Fluviibacter, which implies that the symbiont relies on the host Euplotes for carbon sources, organic nitrogen and sulfur, and some cofactors. We also estimated substitution rates between symbiotic and free-living Fluviibacter pairs for 233 genes; the results showed that symbiotic Fluviibacter displays higher dN/dS mean value than free-living relatives, which suggested that genetic drift is the main driving force behind molecular evolution in endosymbionts.

IMPORTANCE: In the long history of symbiosis research, most studies focused mainly on organelles or bacteria within multicellular hosts. The single-celled protists receive little attention despite harboring an immense diversity of symbiotic associations with bacteria and archaea. One subgroup of the ciliate Euplotes species is strictly dependent on essential symbionts for survival and has emerged as a valuable model for understanding symbiont replacements and recent symbioses. However, almost all of our knowledge about the evolution and functions of Euplotes symbioses comes from the Euplotes-Polynucleobacter system. In this article, we report a novel essential symbiont, which also has very close free-living relatives. Genome analysis indicated that it is a recently established endosymbiont undergoing genome erosion and relies on the Euplotes host for many essential molecules. Our results provide support for the notion that essential symbionts of the ciliate Euplotes evolve from free-living progenitors in the natural water environment.}, } @article {pmid38333966, year = {2024}, author = {Bowles, AMC and Williamson, CJ and Williams, TA and Donoghue, PCJ}, title = {Cryogenian Origins of Multicellularity in Archaeplastida.}, journal = {Genome biology and evolution}, volume = {16}, number = {2}, pages = {}, pmid = {38333966}, issn = {1759-6653}, support = {NE/P013678/1//Natural Environment Research Council/ ; 62220//John Templeton Foundation/ ; //Natural Science Foundation of China/ ; URF\R\201024//University Research Fellowship to T.W/ ; GBMF9741//Gordon and Betty Moore Foundation/ ; RPG-2020-199//Leverhulme Trust/ ; BB/T012773/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N000919/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; //Biosphere Evolution, Transitions and Resilience/ ; }, mesh = {Phylogeny ; Biological Evolution ; Plants ; *Embryophyta ; *Chlorophyta ; Fossils ; Evolution, Molecular ; }, abstract = {Earth was impacted by global glaciations during the Cryogenian (720 to 635 million years ago; Ma), events invoked to explain both the origins of multicellularity in Archaeplastida and radiation of the first land plants. However, the temporal relationship between these environmental and biological events is poorly established, due to a paucity of molecular and fossil data, precluding resolution of the phylogeny and timescale of archaeplastid evolution. We infer a time-calibrated phylogeny of early archaeplastid evolution based on a revised molecular dataset and reappraisal of the fossil record. Phylogenetic topology testing resolves deep archaeplastid relationships, identifying two clades of Viridiplantae and placing Bryopsidales as sister to the Chlorophyceae. Our molecular clock analysis infers an origin of Archaeplastida in the late-Paleoproterozoic to early-Mesoproterozoic (1712 to 1387 Ma). Ancestral state reconstruction of cytomorphological traits on this time-calibrated tree reveals many of the independent origins of multicellularity span the Cryogenian, consistent with the Cryogenian multicellularity hypothesis. Multicellular rhodophytes emerged 902 to 655 Ma while crown-Anydrophyta (Zygnematophyceae and Embryophyta) originated 796 to 671 Ma, broadly compatible with the Cryogenian plant terrestrialization hypothesis. Our analyses resolve the timetree of Archaeplastida with age estimates for ancestral multicellular archaeplastids coinciding with the Cryogenian, compatible with hypotheses that propose a role of Snowball Earth in plant evolution.}, } @article {pmid38327154, year = {2024}, author = {Gupta, P and Bermejo-Rodriguez, C and Kocher, H and Pérez-Mancera, PA and Velliou, EG}, title = {Chemotherapy Assessment in Advanced Multicellular 3D Models of Pancreatic Cancer: Unravelling the Importance of Spatiotemporal Mimicry of the Tumor Microenvironment.}, journal = {Advanced biology}, volume = {8}, number = {7}, pages = {e2300580}, doi = {10.1002/adbi.202300580}, pmid = {38327154}, issn = {2701-0198}, support = {MR/V028553/1/MRC_/Medical Research Council/United Kingdom ; MR/R025762/1//3D bioNet UKRI/ ; NC/V001167/1//National Centre for the Replacement Refinement and Reduction of Animals in Research/ ; }, mesh = {*Tumor Microenvironment/drug effects ; Humans ; *Pancreatic Neoplasms/drug therapy/pathology/genetics ; *Carcinoma, Pancreatic Ductal/drug therapy/pathology ; Deoxycytidine/analogs & derivatives/pharmacology/therapeutic use ; Cell Line, Tumor ; Gemcitabine ; Drug Resistance, Neoplasm ; Tissue Scaffolds ; }, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is a challenge for global health with very low survival rate and high therapeutic resistance. Hence, advanced preclinical models for treatment screening are of paramount importance. Herein, chemotherapeutic (gemcitabine) assessment on novel (polyurethane) scaffold-based spatially advanced 3D multicellular PDAC models is carried out. Through comprehensive image-based analysis at the protein level, and expression analysis at the mRNA level, the importance of stromal cells is confirmed, primarily activated stellate cells in the chemoresistance of PDAC cells within the models. Furthermore, it is demonstrated that, in addition to the presence of activated stellate cells, the spatial architecture of the scaffolds, i.e., segregation/compartmentalization of the cancer and stromal zones, affect the cellular evolution and is necessary for the development of chemoresistance. These results highlight that, further to multicellularity, mapping the tumor structure/architecture and zonal complexity in 3D cancer models is important for better mimicry of the in vivo therapeutic response.}, } @article {pmid38320478, year = {2024}, author = {Donoghue, PCJ and Clark, JW}, title = {Plant evolution: Streptophyte multicellularity, ecology, and the acclimatisation of plants to life on land.}, journal = {Current biology : CB}, volume = {34}, number = {3}, pages = {R86-R89}, doi = {10.1016/j.cub.2023.12.036}, pmid = {38320478}, issn = {1879-0445}, support = {BB/T012773/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Plants ; Biological Evolution ; Phylogeny ; *Embryophyta ; Acclimatization ; }, abstract = {Land plants are celebrated as one of the three great instances of complex multicellularity, but new phylogenomic and phenotypic analyses are revealing deep evolutionary roots of multicellularity among algal relatives, prompting questions about the causal basis of this major evolutionary transition.}, } @article {pmid38315855, year = {2024}, author = {Bingham, EP and Ratcliff, WC}, title = {A nonadaptive explanation for macroevolutionary patterns in the evolution of complex multicellularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {7}, pages = {e2319840121}, pmid = {38315855}, issn = {1091-6490}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; T32 GM142616/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Genetic Drift ; Eukaryota/genetics ; Genome ; Gene Expression Regulation ; }, abstract = {"Complex multicellularity," conventionally defined as large organisms with many specialized cell types, has evolved five times independently in eukaryotes, but never within prokaryotes. A number of hypotheses have been proposed to explain this phenomenon, most of which posit that eukaryotes evolved key traits (e.g., dynamic cytoskeletons, alternative mechanisms of gene regulation, or subcellular compartments) which were a necessary prerequisite for the evolution of complex multicellularity. Here, we propose an alternative, nonadaptive hypothesis for this broad macroevolutionary pattern. By binning cells into groups with finite genetic bottlenecks between generations, the evolution of multicellularity greatly reduces the effective population size (Ne) of cellular populations, increasing the role of genetic drift in evolutionary change. While both prokaryotes and eukaryotes experience this phenomenon, they have opposite responses to drift: eukaryotes tend to undergo genomic expansion, providing additional raw genetic material for subsequent multicellular innovation, while prokaryotes generally face genomic erosion. Taken together, we hypothesize that these idiosyncratic lineage-specific evolutionary dynamics play a fundamental role in the long-term divergent evolution of complex multicellularity across the tree of life.}, } @article {pmid38306281, year = {2024}, author = {Siljestam, M and Martinossi-Allibert, I}, title = {Anisogamy Does Not Always Promote the Evolution of Mating Competition Traits in Males.}, journal = {The American naturalist}, volume = {203}, number = {2}, pages = {230-253}, doi = {10.1086/727968}, pmid = {38306281}, issn = {1537-5323}, mesh = {Male ; Female ; Humans ; *Models, Biological ; *Biological Evolution ; Semen ; Reproduction ; Fertilization ; }, abstract = {AbstractAnisogamy has evolved in most sexually reproducing multicellular organisms allowing the definition of male and female sexes, producing small and large gametes. Anisogamy, as the initial sexual dimorphism, is a good starting point to understand the evolution of further sexual dimorphisms. For instance, it is generally accepted that anisogamy sets the stage for more intense mating competition in males than in females. We argue that this idea stems from a restrictive assumption on the conditions under which anisogamy evolved in the first place: the absence of sperm limitation (assuming that all female gametes are fertilized). Here, we relax this assumption and present a model that considers the coevolution of gamete size with a mating competition trait, starting in a population without dimorphism. We vary gamete density to produce different scenarios of gamete limitation. We show that while at high gamete density the evolution of anisogamy always results in male investment in competition, gamete limitation at intermediate gamete densities allows for either females or males to invest more into mating competition. Our results thus suggest that anisogamy does not always promote mating competition among males. The conditions under which anisogamy evolves matter, as does the competition trait.}, } @article {pmid38301272, year = {2024}, author = {Mihalič, F and Arcila, D and Pettersson, ME and Farkhondehkish, P and Andersson, E and Andersson, L and Betancur-R, R and Jemth, P}, title = {Conservation of Affinity Rather Than Sequence Underlies a Dynamic Evolution of the Motif-Mediated p53/MDM2 Interaction in Ray-Finned Fishes.}, journal = {Molecular biology and evolution}, volume = {41}, number = {2}, pages = {}, pmid = {38301272}, issn = {1537-1719}, mesh = {Animals ; Humans ; *Tumor Suppressor Protein p53/genetics/chemistry/metabolism ; *Zebrafish ; Phylogeny ; Protein Structure, Tertiary ; Protein Binding ; Proto-Oncogene Proteins c-mdm2/genetics/chemistry/metabolism ; }, abstract = {The transcription factor and cell cycle regulator p53 is marked for degradation by the ubiquitin ligase MDM2. The interaction between these 2 proteins is mediated by a conserved binding motif in the disordered p53 transactivation domain (p53TAD) and the folded SWIB domain in MDM2. The conserved motif in p53TAD from zebrafish displays a 20-fold weaker interaction with MDM2, compared to the interaction in human and chicken. To investigate this apparent difference, we tracked the molecular evolution of the p53TAD/MDM2 interaction among ray-finned fishes (Actinopterygii), the largest vertebrate clade. Intriguingly, phylogenetic analyses, ancestral sequence reconstructions, and binding experiments showed that different loss-of-affinity changes in the canonical binding motif within p53TAD have occurred repeatedly and convergently in different fish lineages, resulting in relatively low extant affinities (KD = 0.5 to 5 μM). However, for 11 different fish p53TAD/MDM2 interactions, nonconserved regions flanking the canonical motif increased the affinity 4- to 73-fold to be on par with the human interaction. Our findings suggest that compensating changes at conserved and nonconserved positions within the motif, as well as in flanking regions of low conservation, underlie a stabilizing selection of "functional affinity" in the p53TAD/MDM2 interaction. Such interplay complicates bioinformatic prediction of binding and calls for experimental validation. Motif-mediated protein-protein interactions involving short binding motifs and folded interaction domains are very common across multicellular life. It is likely that the evolution of affinity in motif-mediated interactions often involves an interplay between specific interactions made by conserved motif residues and nonspecific interactions by nonconserved disordered regions.}, } @article {pmid38277698, year = {2024}, author = {Krämer, U}, title = {Metal Homeostasis in Land Plants: A Perpetual Balancing Act Beyond the Fulfilment of Metalloproteome Cofactor Demands.}, journal = {Annual review of plant biology}, volume = {75}, number = {1}, pages = {27-65}, doi = {10.1146/annurev-arplant-070623-105324}, pmid = {38277698}, issn = {1545-2123}, mesh = {*Homeostasis ; *Metals/metabolism ; *Embryophyta/metabolism/physiology ; *Metalloproteins/metabolism ; Plant Proteins/metabolism ; }, abstract = {One of life's decisive innovations was to harness the catalytic power of metals for cellular chemistry. With life's expansion, global atmospheric and biogeochemical cycles underwent dramatic changes. Although initially harmful, they permitted the evolution of multicellularity and the colonization of land. In land plants as primary producers, metal homeostasis faces heightened demands, in part because soil is a challenging environment for nutrient balancing. To avoid both nutrient metal limitation and metal toxicity, plants must maintain the homeostasis of metals within tighter limits than the homeostasis of other minerals. This review describes the present model of protein metalation and sketches its transfer from unicellular organisms to land plants as complex multicellular organisms. The inseparable connection between metal and redox homeostasis increasingly draws our attention to more general regulatory roles of metals. Mineral co-option, the use of nutrient or other metals for functions other than nutrition, is an emerging concept beyond that of nutritional immunity.}, } @article {pmid38271513, year = {2024}, author = {Pennisi, E}, title = {Tiny fossils upend timeline of multicellular life.}, journal = {Science (New York, N.Y.)}, volume = {383}, number = {6681}, pages = {352-353}, doi = {10.1126/science.ado2396}, pmid = {38271513}, issn = {1095-9203}, mesh = {*Biological Evolution ; *Eukaryota ; *Fossils ; }, abstract = {Eukaryotes organized into multicellular forms 1.6 billion years ago.}, } @article {pmid38267842, year = {2024}, author = {Chapman, H and Hsiung, KC and Rawlinson, I and Galimov, ER and Gems, D}, title = {Colony level fitness analysis identifies a trade-off between population growth rate and dauer yield in Caenorhabditis elegans.}, journal = {BMC ecology and evolution}, volume = {24}, number = {1}, pages = {13}, pmid = {38267842}, issn = {2730-7182}, mesh = {Animals ; *Caenorhabditis elegans ; *Population Growth ; Apoptosis ; Biological Assay ; }, abstract = {BACKGROUND: In the evolution from unicellular to multicellular life forms, natural selection favored reduced cell proliferation and even programmed cell death if this increased organismal fitness. Could reduced individual fertility or even programmed organismal death similarly increase the fitness of colonies of closely-related metazoan organisms? This possibility is at least consistent with evolutionary theory, and has been supported by computer modelling. Caenorhabditis elegans has a boom and bust life history, where populations of nematodes that are sometimes near clonal subsist on and consume food patches, and then generate dauer larva dispersal propagules. A recent study of an in silico model of C. elegans predicted that one determinant of colony fitness (measured as dauer yield) is minimization of futile food consumption (i.e. that which does not contribute to dauer yield). One way to achieve this is to optimize colony population structure by adjustment of individual fertility.

RESULTS: Here we describe development of a C. elegans colony fitness assay, and its use to investigate the effect of altering population structure on colony fitness after population bust. Fitness metrics measured were speed of dauer production, and dauer yield, an indirect measure of efficiency of resource utilization (i.e. conversion of food into dauers). We find that with increasing founder number, speed of dauer production increases (due to earlier bust) but dauer yield rises and falls. In addition, some dauer recovery was detected soon after the post-colony bust peak of dauer yield, suggesting possible bet hedging among dauers.

CONCLUSIONS: These results suggest the presence of a fitness trade-off at colony level between speed and efficiency of resource utilization in C. elegans. They also provide indirect evidence that population structure is a determinant of colony level fitness, potentially by affecting level of futile food consumption.}, } @article {pmid38262417, year = {2024}, author = {Choi, SW and Graf, L and Choi, JW and Jo, J and Boo, GH and Kawai, H and Choi, CG and Xiao, S and Knoll, AH and Andersen, RA and Yoon, HS}, title = {Ordovician origin and subsequent diversification of the brown algae.}, journal = {Current biology : CB}, volume = {34}, number = {4}, pages = {740-754.e4}, doi = {10.1016/j.cub.2023.12.069}, pmid = {38262417}, issn = {1879-0445}, mesh = {Phylogeny ; Eukaryota/genetics ; Plants ; *Rhodophyta/genetics ; Plastids/genetics ; *Phaeophyceae/genetics ; Evolution, Molecular ; }, abstract = {Brown algae are the only group of heterokont protists exhibiting complex multicellularity. Since their origin, brown algae have adapted to various marine habitats, evolving diverse thallus morphologies and gamete types. However, the evolutionary processes behind these transitions remain unclear due to a lack of a robust phylogenetic framework and problems with time estimation. To address these issues, we employed plastid genome data from 138 species, including heterokont algae, red algae, and other red-derived algae. Based on a robust phylogeny and new interpretations of algal fossils, we estimated the geological times for brown algal origin and diversification. The results reveal that brown algae first evolved true multicellularity, with plasmodesmata and reproductive cell differentiation, during the late Ordovician Period (ca. 450 Ma), coinciding with a major diversification of marine fauna (the Great Ordovician Biodiversification Event) and a proliferation of multicellular green algae. Despite its early Paleozoic origin, the diversification of major orders within this brown algal clade accelerated only during the Mesozoic Era, coincident with both Pangea rifting and the diversification of other heterokont algae (e.g., diatoms), coccolithophores, and dinoflagellates, with their red algal-derived plastids. The transition from ancestral isogamy to oogamy was followed by three simultaneous reappearances of isogamy during the Cretaceous Period. These are concordant with a positive character correlation between parthenogenesis and isogamy. Our new brown algal timeline, combined with a knowledge of past environmental conditions, shed new light on brown algal diversification and the intertwined evolution of multicellularity and sexual reproduction.}, } @article {pmid38255007, year = {2024}, author = {Gazzellone, A and Sangiorgi, E}, title = {From Churchill to Elephants: The Role of Protective Genes against Cancer.}, journal = {Genes}, volume = {15}, number = {1}, pages = {}, pmid = {38255007}, issn = {2073-4425}, mesh = {Humans ; Animals ; Mice ; *Elephants/genetics ; Alleles ; *Neoplastic Syndromes, Hereditary ; *Medicine ; Cetacea ; }, abstract = {Richard Peto's paradox, first described in 1975 from an epidemiological perspective, established an inverse correlation between the probability of developing cancer in multicellular organisms and the number of cells. Larger animals exhibit fewer tumors compared to smaller ones, though exceptions exist. Mice are more susceptible to cancer than humans, while elephants and whales demonstrate significantly lower cancer prevalence rates than humans. How nature and evolution have addressed the issue of cancer in the animal kingdom remains largely unexplored. In the field of medicine, much attention has been devoted to cancer-predisposing genes, as they offer avenues for intervention, including blocking, downregulating, early diagnosis, and targeted treatment. Predisposing genes also tend to manifest clinically earlier and more aggressively, making them easier to identify. However, despite significant strides in modern medicine, the role of protective genes lags behind. Identifying genes with a mild predisposing effect poses a significant challenge. Consequently, comprehending the protective function conferred by genes becomes even more elusive, and their very existence is subject to questioning. While the role of variable expressivity and penetrance defects of the same variant in a family is well-documented for many hereditary cancer syndromes, attempts to delineate the function of protective/modifier alleles have been restricted to a few instances. In this review, we endeavor to elucidate the role of protective genes observed in the animal kingdom, within certain genetic syndromes that appear to act as cancer-resistant/repressor alleles. Additionally, we explore the role of protective alleles in conditions predisposing to cancer. The ultimate goal is to discern why individuals, like Winston Churchill, managed to live up to 91 years of age, despite engaging in minimal physical activity, consuming large quantities of alcohol daily, and not abstaining from smoking.}, } @article {pmid38244543, year = {2024}, author = {Bierenbroodspot, MJ and Darienko, T and de Vries, S and Fürst-Jansen, JMR and Buschmann, H and Pröschold, T and Irisarri, I and de Vries, J}, title = {Phylogenomic insights into the first multicellular streptophyte.}, journal = {Current biology : CB}, volume = {34}, number = {3}, pages = {670-681.e7}, pmid = {38244543}, issn = {1879-0445}, mesh = {Phylogeny ; Biological Evolution ; Plants/genetics ; *Embryophyta/genetics ; *Streptophyta ; }, abstract = {Streptophytes are best known as the clade containing the teeming diversity of embryophytes (land plants).[1][,][2][,][3][,][4] Next to embryophytes are however a range of freshwater and terrestrial algae that bear important information on the emergence of key traits of land plants. Among these, the Klebsormidiophyceae stand out. Thriving in diverse environments-from mundane (ubiquitous occurrence on tree barks and rocks) to extreme (from the Atacama Desert to the Antarctic)-Klebsormidiophyceae can exhibit filamentous body plans and display remarkable resilience as colonizers of terrestrial habitats.[5][,][6] Currently, the lack of a robust phylogenetic framework for the Klebsormidiophyceae hampers our understanding of the evolutionary history of these key traits. Here, we conducted a phylogenomic analysis utilizing advanced models that can counteract systematic biases. We sequenced 24 new transcriptomes of Klebsormidiophyceae and combined them with 14 previously published genomic and transcriptomic datasets. Using an analysis built on 845 loci and sophisticated mixture models, we establish a phylogenomic framework, dividing the six distinct genera of Klebsormidiophyceae in a novel three-order system, with a deep divergence more than 830 million years ago. Our reconstructions of ancestral states suggest (1) an evolutionary history of multiple transitions between terrestrial-aquatic habitats, with stem Klebsormidiales having conquered land earlier than embryophytes, and (2) that the body plan of the last common ancestor of Klebsormidiophyceae was multicellular, with a high probability that it was filamentous whereas the sarcinoids and unicells in Klebsormidiophyceae are likely derived states. We provide evidence that the first multicellular streptophytes likely lived about a billion years ago.}, } @article {pmid38230926, year = {2024}, author = {Corrales, J and Ramos-Alonso, L and González-Sabín, J and Ríos-Lombardía, N and Trevijano-Contador, N and Engen Berg, H and Sved Skottvoll, F and Moris, F and Zaragoza, O and Chymkowitch, P and Garcia, I and Enserink, JM}, title = {Characterization of a selective, iron-chelating antifungal compound that disrupts fungal metabolism and synergizes with fluconazole.}, journal = {Microbiology spectrum}, volume = {12}, number = {2}, pages = {e0259423}, pmid = {38230926}, issn = {2165-0497}, support = {182524, 208012//Kreftforeningen (NCS)/ ; 2017064, 2018012, 2019096//Ministry of Health and Care Services | Helse Sør-Øst RHF (sorost)/ ; 2017072//Ministry of Health and Care Services | Helse Sør-Øst RHF (sorost)/ ; 261936, 301268, 262652//Norges Forskningsråd (Forskningsrådet)/ ; PID2020-114546RB//Ministerio de Ciencia e Innovación (MCIN)/ ; }, mesh = {Animals ; Humans ; Antifungal Agents/pharmacology ; Fluconazole/pharmacology ; Iron ; Candida ; *Mycoses/microbiology ; Candida albicans ; *Anti-Infective Agents/pharmacology ; Azoles/pharmacology ; Candida glabrata ; Iron Chelating Agents/pharmacology ; Drug Resistance, Fungal ; Microbial Sensitivity Tests ; Mammals ; }, abstract = {Fungal infections are a growing global health concern due to the limited number of available antifungal therapies as well as the emergence of fungi that are resistant to first-line antimicrobials, particularly azoles and echinocandins. Development of novel, selective antifungal therapies is challenging due to similarities between fungal and mammalian cells. An attractive source of potential antifungal treatments is provided by ecological niches co-inhabited by bacteria, fungi, and multicellular organisms, where complex relationships between multiple organisms have resulted in evolution of a wide variety of selective antimicrobials. Here, we characterized several analogs of one such natural compound, collismycin A. We show that NR-6226C has antifungal activity against several pathogenic Candida species, including C. albicans and C. glabrata, whereas it only has little toxicity against mammalian cells. Mechanistically, NR-6226C selectively chelates iron, which is a limiting factor for pathogenic fungi during infection. As a result, NR-6226C treatment causes severe mitochondrial dysfunction, leading to formation of reactive oxygen species, metabolic reprogramming, and a severe reduction in ATP levels. Using an in vivo model for fungal infections, we show that NR-6226C significantly increases survival of Candida-infected Galleria mellonella larvae. Finally, our data indicate that NR-6226C synergizes strongly with fluconazole in inhibition of C. albicans. Taken together, NR-6226C is a promising antifungal compound that acts by chelating iron and disrupting mitochondrial functions.IMPORTANCEDrug-resistant fungal infections are an emerging global threat, and pan-resistance to current antifungal therapies is an increasing problem. Clearly, there is a need for new antifungal drugs. In this study, we characterized a novel antifungal agent, the collismycin analog NR-6226C. NR-6226C has a favorable toxicity profile for human cells, which is essential for further clinical development. We unraveled the mechanism of action of NR-6226C and found that it disrupts iron homeostasis and thereby depletes fungal cells of energy. Importantly, NR-6226C strongly potentiates the antifungal activity of fluconazole, thereby providing inroads for combination therapy that may reduce or prevent azole resistance. Thus, NR-6226C is a promising compound for further development into antifungal treatment.}, } @article {pmid38196363, year = {2024}, author = {Howe, J and Cornwallis, CK and Griffin, AS}, title = {Conflict-reducing innovations in development enable increased multicellular complexity.}, journal = {Proceedings. Biological sciences}, volume = {291}, number = {2014}, pages = {20232466}, pmid = {38196363}, issn = {1471-2954}, mesh = {Animals ; Phylogeny ; *Cognition ; Cell Division ; *Stem Cells ; }, abstract = {Obligately multicellular organisms, where cells can only reproduce as part of the group, have evolved multiple times across the tree of life. Obligate multicellularity has only evolved when clonal groups form by cell division, rather than by cells aggregating, as clonality prevents internal conflict. Yet obligately multicellular organisms still vary greatly in 'multicellular complexity' (the number of cells and cell types): some comprise a few cells and cell types, while others have billions of cells and thousands of types. Here, we test whether variation in multicellular complexity is explained by two conflict-suppressing mechanisms, namely a single-cell bottleneck at the start of development, and a strict separation of germline and somatic cells. Examining the life cycles of 129 lineages of plants, animals, fungi and algae, we show using phylogenetic comparative analyses that an early segregation of the germline stem-cell lineage is key to the evolution of more cell types, driven by a strong correlation in the Metazoa. By contrast, the presence of a strict single-cell bottleneck was not related to either the number of cells or the number of cell types, but was associated with early germline segregation. Our results suggest that segregating the germline earlier in development enabled greater evolutionary innovation, although whether this is a consequence of conflict reduction or other non-conflict effects, such as developmental flexibility, is unclear.}, } @article {pmid38196360, year = {2024}, author = {Pequeno, PACL}, title = {Resource adaptation drives the size-complexity rule in termites.}, journal = {Proceedings. Biological sciences}, volume = {291}, number = {2014}, pages = {20232363}, pmid = {38196360}, issn = {1471-2954}, mesh = {Animals ; *Isoptera ; Food ; *Infertility ; Phenotype ; Phylogeny ; }, abstract = {The size-complexity rule posits that the evolution of larger cooperative groups should favour more division of labour. Examples include more cell types in larger multicellular organisms, and more polymorphic castes in larger eusocial colonies. However, a correlation between division of labour and group size may reflect a shared response of both traits to resource availability and/or profitability. Here, this possibility was addressed by investigating the evolution of sterile caste number (worker and soldier morphotypes) in termites, a major clade of eusocial insects in which the drivers of caste polymorphism are poorly understood. A novel dataset on 90 termite species was compiled from the published literature. The analysis showed that sterile caste number did increase markedly with colony size. However, after controlling for resource adaptations and phylogeny, there was no evidence for this relationship. Rather, sterile caste number increased with increasing nest-food separation and decreased with soil-feeding, through changes in worker (but not soldier) morphotype number. Further, colony size increased with nest-food separation, thus driving the false correlation between sterile caste number and colony size. These findings support adaptation to higher energy acquisition as key to the rise of complex insect societies, with larger size being a by-product.}, } @article {pmid38192262, year = {2024}, author = {Schuster, CD and Salvatore, F and Moens, L and Martí, MA}, title = {Globin phylogeny, evolution and function, the newest update.}, journal = {Proteins}, volume = {92}, number = {6}, pages = {720-734}, doi = {10.1002/prot.26659}, pmid = {38192262}, issn = {1097-0134}, mesh = {*Globins/genetics/chemistry/metabolism ; *Phylogeny ; *Evolution, Molecular ; Humans ; Bacteria/genetics/metabolism ; Animals ; Archaea/genetics/metabolism ; Protein Domains ; Gene Transfer, Horizontal ; }, abstract = {Our globin census update allows us to refine our vision of globin origin, evolution, and structure to function relationship in the context of the currently accepted tree of life. The modern globin domain originates as a single domain, three-over-three α-helical folded structure before the diversification of the kingdoms of life (Bacteria, Archaea, Eukarya). Together with the diversification of prokaryotes, three monophyletic globin families (M, S, and T) emerged, most likely in Proteobacteria and Actinobacteria, displaying specific sequence and structural features, and spread by vertical and horizontal gene transfer, most probably already present in the last universal common ancestor (LUCA). Non-globin domains were added, and eventually lost again, creating multi-domain structures in key branches of M- (FHb and Adgb) and the vast majority of S globins, which with their coevolved multi-domain architectures, have predominantly "sensor" functions. Single domain T-family globins diverged into four major groups and most likely display functions related to reactive nitrogen and oxygen species (RNOS) chemistry, as well as oxygen storage/transport which drives the evolution of its major branches with their characteristic key distal residues (B10, E11, E7, and G8). M-family evolution also lead to distinctive major types (FHb and Fgb, Ngb, Adgb, GbX vertebrate Gbs), and shows the shift from high oxygen affinity controlled by TyrB10-Gln/AsnE11 likely related to RNOS chemistry in microorganisms, to a moderate oxygen affinity storage/transport function controlled by hydrophobic B10/E11-HisE7 in multicellular animals.}, } @article {pmid38185860, year = {2024}, author = {Roggenbuck, EC and Hall, EA and Hanson, IB and Roby, AA and Zhang, KK and Alkatib, KA and Carter, JA and Clewner, JE and Gelfius, AL and Gong, S and Gordon, FR and Iseler, JN and Kotapati, S and Li, M and Maysun, A and McCormick, EO and Rastogi, G and Sengupta, S and Uzoma, CU and Wolkov, MA and Clowney, EJ}, title = {Let's talk about sex: Mechanisms of neural sexual differentiation in Bilateria.}, journal = {WIREs mechanisms of disease}, volume = {16}, number = {2}, pages = {e1636}, doi = {10.1002/wsbm.1636}, pmid = {38185860}, issn = {2692-9368}, support = {//McKnight Scholar Award/ ; //Pew Biomedical Scholar Award/ ; //Rita Allen Foundation Scholar Award/ ; }, mesh = {Male ; Animals ; *Sex Differentiation ; *Semen ; Reproduction ; Germ Cells ; Spermatozoa ; }, abstract = {In multicellular organisms, sexed gonads have evolved that facilitate release of sperm versus eggs, and bilaterian animals purposefully combine their gametes via mating behaviors. Distinct neural circuits have evolved that control these physically different mating events for animals producing eggs from ovaries versus sperm from testis. In this review, we will describe the developmental mechanisms that sexually differentiate neural circuits across three major clades of bilaterian animals-Ecdysozoa, Deuterosomia, and Lophotrochozoa. While many of the mechanisms inducing somatic and neuronal sex differentiation across these diverse organisms are clade-specific rather than evolutionarily conserved, we develop a common framework for considering the developmental logic of these events and the types of neuronal differences that produce sex-differentiated behaviors. This article is categorized under: Congenital Diseases > Stem Cells and Development Neurological Diseases > Stem Cells and Development.}, } @article {pmid38181075, year = {2024}, author = {Qi, Z and Lu, P and Long, X and Cao, X and Wu, M and Xin, K and Xue, T and Gao, X and Huang, Y and Wang, Q and Jiang, C and Xu, JR and Liu, H}, title = {Adaptive advantages of restorative RNA editing in fungi for resolving survival-reproduction trade-offs.}, journal = {Science advances}, volume = {10}, number = {1}, pages = {eadk6130}, pmid = {38181075}, issn = {2375-2548}, mesh = {*Codon, Nonsense ; RNA Editing/genetics ; Amino Acids ; *Magnoliopsida ; Reproduction ; }, abstract = {RNA editing in various organisms commonly restores RNA sequences to their ancestral state, but its adaptive advantages are debated. In fungi, restorative editing corrects premature stop codons in pseudogenes specifically during sexual reproduction. We characterized 71 pseudogenes and their restorative editing in Fusarium graminearum, demonstrating that restorative editing of 16 pseudogenes is crucial for germ tissue development in fruiting bodies. Our results also revealed that the emergence of premature stop codons is facilitated by restorative editing and that premature stop codons corrected by restorative editing are selectively favored over ancestral amino acid codons. Furthermore, we found that ancestral versions of pseudogenes have antagonistic effects on reproduction and survival. Restorative editing eliminates the survival costs of reproduction caused by antagonistic pleiotropy and provides a selective advantage in fungi. Our findings highlight the importance of restorative editing in the evolution of fungal complex multicellularity and provide empirical evidence that restorative editing serves as an adaptive mechanism enabling the resolution of genetic trade-offs.}, } @article {pmid38175037, year = {2024}, author = {Lyman, GH and Lyman, CH and Kuderer, NM}, title = {The Nature, Origin, and Evolution of Life: Part IV Cellular Differentiation and the Emergence of Multicellular Life.}, journal = {Cancer investigation}, volume = {42}, number = {4}, pages = {275-277}, doi = {10.1080/07357907.2024.2302201}, pmid = {38175037}, issn = {1532-4192}, mesh = {*Cell Differentiation ; Humans ; Biological Evolution ; Origin of Life ; Animals ; }, } @article {pmid38154271, year = {2024}, author = {Kong, Z and Zhu, L and Liu, Y and Liu, Y and Chen, G and Jiang, T and Wang, H}, title = {Effects of azithromycin exposure during pregnancy at different stages, doses and courses on testicular development in fetal mice.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {170}, number = {}, pages = {116063}, doi = {10.1016/j.biopha.2023.116063}, pmid = {38154271}, issn = {1950-6007}, mesh = {Mice ; Male ; Female ; Pregnancy ; Animals ; *Azithromycin/toxicity ; *Testis ; Leydig Cells ; Sertoli Cells ; Fetus ; }, abstract = {Azithromycin is a commonly used antibiotic during pregnancy, but some studies have suggested its potential developmental toxicity. Currently, the effects and mechanisms of prenatal azithromycin exposure (PAzE) on fetal testicular development are still unclear. The effects of prenatal exposure to the same drug on fetal testicular development could vary depending on different stages, doses, and courses. Hence, in this study, based on clinical medication characteristics, Kunming mice was administered intragastrically with azithromycin at different stages (mid-/late-pregnancy), doses (50, 100, 200 mg/kg·d), and courses (single-/multi-course). Fetal blood and testicular samples were collected on GD18 for relevant assessments. The results indicated that PAzE led to changes in fetal testicular morphology, reduced cell proliferation, increased apoptosis, and decreased expression of markers related to Leydig cells (Star), Sertoli cells (Wt1), and spermatogonia (Plzf). Further investigation revealed that the effects of PAzE on fetal testicular development were characterized by mid-pregnancy, high dose (clinical dose), and single course having more pronounced effects. Additionally, the TGFβ/Smad and Nrf2 signaling pathways may be involved in the changes in fetal testicular development induced by PAzE. In summary, this study confirmed that PAzE influences fetal testicular morphological development and multicellular function. It provided theoretical and experimental evidence for guiding the rational use of azithromycin during pregnancy and further exploring the mechanisms underlying its developmental toxicity on fetal testicles.}, } @article {pmid38151680, year = {2023}, author = {Bich, L}, title = {Integrating Multicellular Systems: Physiological Control and Degrees of Biological Individuality.}, journal = {Acta biotheoretica}, volume = {72}, number = {1}, pages = {1}, pmid = {38151680}, issn = {1572-8358}, mesh = {Animals ; *Biological Evolution ; *Biofilms ; }, abstract = {This paper focuses on physiological integration in multicellular systems, a notion often associated with biological individuality, but which has not received enough attention and needs a thorough theoretical treatment. Broadly speaking, physiological integration consists in how different components come together into a cohesive unit in which they are dependent on one another for their existence and activity. This paper argues that physiological integration can be understood by considering how the components of a biological multicellular system are controlled and coordinated in such a way that their activities can contribute to the maintenance of the system. The main implication of this perspective is that different ways of controlling their parts may give rise to multicellular organizations with different degrees of integration. After defining control, this paper analyses how control is realized in two examples of multicellular systems located at different ends of the spectrum of multicellularity: biofilms and animals. It focuses on differences in control ranges, and it argues that a high degree of integration implies control exerted at both medium and long ranges, and that insofar as biofilms lack long-range control (relative to their size) they can be considered as less integrated than other multicellular systems. It then discusses the implication of this account for the debate on physiological individuality and the idea that degrees of physiological integration imply degrees of individuality.}, } @article {pmid38110826, year = {2024}, author = {Kotarska, K and Gąsior, Ł and Rudnicka, J and Polański, Z}, title = {Long-run real-time PCR analysis of repetitive nuclear elements as a novel tool for DNA damage quantification in single cells: an approach validated on mouse oocytes and fibroblasts.}, journal = {Journal of applied genetics}, volume = {65}, number = {1}, pages = {181-190}, pmid = {38110826}, issn = {2190-3883}, support = {2019/03/X/NZ3/00572//Narodowe Centrum Nauki/ ; }, mesh = {Animals ; Mice ; Real-Time Polymerase Chain Reaction ; *DNA Damage/genetics ; *Fibroblasts ; Oocytes ; Genome ; }, abstract = {Since DNA damage is of great importance in various biological processes, its rate is frequently assessed both in research studies and in medical diagnostics. The most precise methods of quantifying DNA damage are based on real-time PCR. However, in the conventional version, they require a large amount of genetic material and therefore their usefulness is limited to multicellular samples. Here, we present a novel approach to long-run real-time PCR-based DNA-damage quantification (L1-LORD-Q), which consists in amplification of long interspersed nuclear elements (L1) and allows for analysis of single-cell genomes. The L1-LORD-Q was compared with alternative methods of measuring DNA breaks (Bioanalyzer system, γ-H2AX foci staining), which confirmed its accuracy. Furthermore, it was demonstrated that the L1-LORD-Q is sensitive enough to distinguish between different levels of UV-induced DNA damage. The method was validated on mouse oocytes and fibroblasts, but the general idea is universal and can be applied to various types of cells and species.}, } @article {pmid38103995, year = {2024}, author = {Yu, Y and Li, YP and Ren, K and Hao, X and Fru, EC and Rønn, R and Rivera, WL and Becker, K and Feng, R and Yang, J and Rensing, C}, title = {A brief history of metal recruitment in protozoan predation.}, journal = {Trends in microbiology}, volume = {32}, number = {5}, pages = {465-476}, doi = {10.1016/j.tim.2023.11.008}, pmid = {38103995}, issn = {1878-4380}, mesh = {*Metals/metabolism ; *Phagocytosis ; *Dictyostelium/metabolism/physiology ; Biological Evolution ; Acanthamoeba ; Animals ; Phagosomes/metabolism ; Zinc/metabolism ; Metalloids/metabolism ; Copper/metabolism ; Biological Availability ; Mitochondria/metabolism ; }, abstract = {Metals and metalloids are used as weapons for predatory feeding by unicellular eukaryotes on prokaryotes. This review emphasizes the role of metal(loid) bioavailability over the course of Earth's history, coupled with eukaryogenesis and the evolution of the mitochondrion to trace the emergence and use of the metal(loid) prey-killing phagosome as a feeding strategy. Members of the genera Acanthamoeba and Dictyostelium use metals such as zinc (Zn) and copper (Cu), and possibly metalloids, to kill their bacterial prey after phagocytosis. We provide a potential timeline on when these capacities first evolved and how they correlate with perceived changes in metal(loid) bioavailability through Earth's history. The origin of phagotrophic eukaryotes must have postdated the Great Oxidation Event (GOE) in agreement with redox-dependent modification of metal(loid) bioavailability for phagotrophic poisoning. However, this predatory mechanism is predicted to have evolved much later - closer to the origin of the multicellular metazoans and the evolutionary development of the immune systems.}, } @article {pmid38060007, year = {2023}, author = {Romei, M and Carpentier, M and Chomilier, J and Lecointre, G}, title = {Origins and Functional Significance of Eukaryotic Protein Folds.}, journal = {Journal of molecular evolution}, volume = {91}, number = {6}, pages = {854-864}, pmid = {38060007}, issn = {1432-1432}, support = {IPV program of Sorbonne University, PhD grant//Sorbonne Université/ ; }, mesh = {Animals ; Phylogeny ; *Bacteria/genetics ; *Archaea/genetics ; Proteins ; Eukaryota/genetics ; Biological Evolution ; }, abstract = {Folds are the architecture and topology of a protein domain. Categories of folds are very few compared to the astronomical number of sequences. Eukaryotes have more protein folds than Archaea and Bacteria. These folds are of two types: shared with Archaea and/or Bacteria on one hand and specific to eukaryotic clades on the other hand. The first kind of folds is inherited from the first endosymbiosis and confirms the mixed origin of eukaryotes. In a dataset of 1073 folds whose presence or absence has been evidenced among 210 species equally distributed in the three super-kingdoms, we have identified 28 eukaryotic folds unambiguously inherited from Bacteria and 40 eukaryotic folds unambiguously inherited from Archaea. Compared to previous studies, the repartition of informational function is higher than expected for folds originated from Bacteria and as high as expected for folds inherited from Archaea. The second type of folds is specifically eukaryotic and associated with an increase of new folds within eukaryotes distributed in particular clades. Reconstructed ancestral states coupled with dating of each node on the tree of life provided fold appearance rates. The rate is on average twice higher within Eukaryota than within Bacteria or Archaea. The highest rates are found in the origins of eukaryotes, holozoans, metazoans, metazoans stricto sensu, and vertebrates: the roots of these clades correspond to bursts of fold evolution. We could correlate the functions of some of the fold synapomorphies within eukaryotes with significant evolutionary events. Among them, we find evidence for the rise of multicellularity, adaptive immune system, or virus folds which could be linked to an ecological shift made by tetrapods.}, } @article {pmid38040554, year = {2024}, author = {Arnoux-Courseaux, M and Coudert, Y}, title = {Re-examining meristems through the lens of evo-devo.}, journal = {Trends in plant science}, volume = {29}, number = {4}, pages = {413-427}, doi = {10.1016/j.tplants.2023.11.003}, pmid = {38040554}, issn = {1878-4372}, mesh = {*Meristem/genetics ; *Plant Proteins/genetics ; Plants/genetics ; }, abstract = {The concept of the meristem was introduced in 1858 to characterize multicellular, formative, and proliferative tissues that give rise to the entire plant body, based on observations of vascular plants. Although its original definition did not encompass bryophytes, this concept has been used and continuously refined over the past 165 years to describe the diverse apices of all land plants. Here, we re-examine this matter in light of recent evo-devo research and show that, despite displaying high anatomical diversity, land plant meristems are unified by shared genetic control. We also propose a modular view of meristem function and highlight multiple evolutionary mechanisms that are likely to have contributed to the assembly and diversification of the varied meristems during the course of plant evolution.}, } @article {pmid38039969, year = {2023}, author = {Mulvey, H and Dolan, L}, title = {RHO of plant signaling was established early in streptophyte evolution.}, journal = {Current biology : CB}, volume = {33}, number = {24}, pages = {5515-5525.e4}, doi = {10.1016/j.cub.2023.11.007}, pmid = {38039969}, issn = {1879-0445}, mesh = {Phylogeny ; *Chlorophyta ; Plants ; *Embryophyta/genetics ; *Streptophyta/physiology ; }, abstract = {The algal ancestors of land plants underwent a transition from a unicellular to a multicellular body plan.[1] This transition likely took place early in streptophyte evolution, sometime after the divergence of the Chlorokybophyceae/Mesostigmatophyceae lineage, but before the divergence of the Klebsormidiophyceae lineage.[2] How this transition was brought about is unknown; however, it was likely facilitated by the evolution of novel mechanisms to spatially regulate morphogenesis. In land plants, RHO of plant (ROP) signaling plays a conserved role in regulating polarized cell growth and cell division orientation to orchestrate morphogenesis.[3][,][4][,][5][,][6][,][7][,][8] ROP constitutes a plant-specific subfamily of the RHO GTPases, which are more widely conserved throughout eukaryotes.[9][,][10] Although the RHO family originated in early eukaryotes,[11][,][12] how and when the ROP subfamily originated had remained elusive. Here, we demonstrate that ROP signaling was established early in the streptophyte lineage, sometime after the divergence of the Chlorokybophyceae/Mesostigmatophyceae lineage, but before the divergence of the Klebsormidiophyceae lineage. This period corresponds to when the unicellular-to-multicellular transition likely took place in the streptophytes. In addition to being critical for the complex morphogenesis of extant land plants, we speculate that ROP signaling contributed to morphological evolution in early streptophytes.}, } @article {pmid38014282, year = {2023}, author = {Bingham, EP and Ratcliff, WC}, title = {A non-adaptive explanation for macroevolutionary patterns in the evolution of complex multicellularity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38014282}, issn = {2692-8205}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; T32 GM142616/GM/NIGMS NIH HHS/United States ; }, abstract = {"Complex multicellularity", conventionally defined as large organisms with many specialized cell types, has evolved five times independently in eukaryotes, but never within prokaryotes. A number hypotheses have been proposed to explain this phenomenon, most of which posit that eukaryotes evolved key traits (e.g., dynamic cytoskeletons, alternative mechanisms of gene regulation, or subcellular compartments) which were a necessary prerequisite for the evolution of complex multicellularity. Here we propose an alternative, non-adaptive hypothesis for this broad macroevolutionary pattern. By binning cells into groups with finite genetic bottlenecks between generations, the evolution of multicellularity greatly reduces the effective population size (Ne) of cellular populations, increasing the role of genetic drift in evolutionary change. While both prokaryotes and eukaryotes experience this phenomenon, they have opposite responses to drift: mutational biases in eukaryotes tend to drive genomic expansion, providing additional raw genetic material for subsequent multicellular innovation, while prokaryotes generally face genomic erosion. These effects become more severe as organisms evolve larger size and more stringent genetic bottlenecks between generations- both of which are hallmarks of complex multicellularity. Taken together, we hypothesize that it is these idiosyncratic lineage-specific mutational biases, rather than cell-biological innovations within eukaryotes, that underpins the long-term divergent evolution of complex multicellularity across the tree of life.}, } @article {pmid38003023, year = {2023}, author = {Toch, K and Buczek, M and Labocha, MK}, title = {Genetic Interactions in Various Environmental Conditions in Caenorhabditis elegans.}, journal = {Genes}, volume = {14}, number = {11}, pages = {}, pmid = {38003023}, issn = {2073-4425}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Epistasis, Genetic ; }, abstract = {Although it is well known that epistasis plays an important role in many evolutionary processes (e.g., speciation, evolution of sex), our knowledge on the frequency and prevalent sign of epistatic interactions is mainly limited to unicellular organisms or cell cultures of multicellular organisms. This is even more pronounced in regard to how the environment can influence genetic interactions. To broaden our knowledge in that respect we studied gene-gene interactions in a whole multicellular organism, Caenorhabditis elegans. We screened over one thousand gene interactions, each one in standard laboratory conditions, and under three different stressors: heat shock, oxidative stress, and genotoxic stress. Depending on the condition, between 7% and 22% of gene pairs showed significant genetic interactions and an overall sign of epistasis changed depending on the condition. Sign epistasis was quite common, but reciprocal sign epistasis was extremally rare. One interaction was common to all conditions, whereas 78% of interactions were specific to only one environment. Although epistatic interactions are quite common, their impact on evolutionary processes will strongly depend on environmental factors.}, } @article {pmid37996670, year = {2024}, author = {Spradling, AC}, title = {The Ancient Origin and Function of Germline Cysts.}, journal = {Results and problems in cell differentiation}, volume = {71}, number = {}, pages = {3-21}, pmid = {37996670}, issn = {0080-1844}, mesh = {Female ; Animals ; Male ; Mice ; *Semen ; *Oocytes ; Germ Cells ; Spermatozoa ; Organelles ; }, abstract = {Gamete production in most animal species is initiated within an evolutionarily ancient multicellular germline structure, the germline cyst, whose interconnected premeiotic cells synchronously develop from a single progenitor arising just downstream from a stem cell. Cysts in mice, Drosophila, and many other animals protect developing sperm, while in females, cysts generate nurse cells that guard sister oocytes from transposons (TEs) and help them grow and build a Balbiani body. However, the origin and extreme evolutionary conservation of germline cysts remains a mystery. We suggest that cysts arose in ancestral animals like Hydra and Planaria whose multipotent somatic and germline stem cells (neoblasts) express genes conserved in all animal germ cells and frequently begin differentiation in cysts. A syncytial state is proposed to help multipotent stem cell chromatin transition to an epigenetic state with heterochromatic domains suitable for TE repression and specialized function. Most modern animals now lack neoblasts but have retained stem cells and cysts in their early germlines, which continue to function using this ancient epigenetic strategy.}, } @article {pmid37993452, year = {2023}, author = {Nicolas, E and Simion, P and Guérineau, M and Terwagne, M and Colinet, M and Virgo, J and Lingurski, M and Boutsen, A and Dieu, M and Hallet, B and Van Doninck, K}, title = {Horizontal acquisition of a DNA ligase improves DNA damage tolerance in eukaryotes.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {7638}, pmid = {37993452}, issn = {2041-1723}, mesh = {Animals ; Humans ; *Eukaryota/genetics ; Phylogeny ; DNA Ligases/genetics/metabolism ; Ligases/metabolism ; Proteomics ; *Rotifera/genetics ; DNA Damage ; DNA Ligase ATP/genetics/metabolism ; }, abstract = {Bdelloid rotifers are part of the restricted circle of multicellular animals that can withstand a wide range of genotoxic stresses at any stage of their life cycle. In this study, bdelloid rotifer Adineta vaga is used as a model to decipher the molecular basis of their extreme tolerance. Proteomic analysis shows that a specific DNA ligase, different from those usually involved in DNA repair in eukaryotes, is strongly over-represented upon ionizing radiation. A phylogenetic analysis reveals its orthology to prokaryotic DNA ligase E, and its horizontal acquisition by bdelloid rotifers and plausibly other eukaryotes. The fungus Mortierella verticillata, having a single copy of this DNA Ligase E homolog, also exhibits an increased radiation tolerance with an over-expression of this DNA ligase E following X-ray exposure. We also provide evidence that A. vaga ligase E is a major contributor of DNA breaks ligation activity, which is a common step of all important DNA repair pathways. Consistently, its heterologous expression in human cell lines significantly improves their radio-tolerance. Overall, this study highlights the potential of horizontal gene transfers in eukaryotes, and their contribution to the adaptation to extreme conditions.}, } @article {pmid37990147, year = {2023}, author = {Jin, H and Zhang, W and Liu, H and Bao, Y}, title = {Genome-wide identification and characteristic analysis of ETS gene family in blood clam Tegillarca granosa.}, journal = {BMC genomics}, volume = {24}, number = {1}, pages = {700}, pmid = {37990147}, issn = {1471-2164}, support = {LZ20C190001//Key Natural Science Foundation of Zhejiang/ ; 32273123//National Science Foundation of China/ ; 2021C02069-7//Zhejiang Major Program of Science and Technology/ ; LQ23C190007//Science Foundation of Zhejiang/ ; 2021S014//Ningbo Public Benefit Research Key Project/ ; }, mesh = {Humans ; Animals ; Phylogeny ; *Arcidae/genetics/metabolism ; Proto-Oncogene Proteins c-ets/genetics/metabolism ; Genome ; *Bivalvia/genetics ; }, abstract = {BACKGROUND: ETS transcription factors, known as the E26 transformation-specific factors, assume a critical role in the regulation of various vital biological processes in animals, including cell differentiation, the cell cycle, and cell apoptosis. However, their characterization in mollusks is currently lacking.

RESULTS: The current study focused on a comprehensive analysis of the ETS genes in blood clam Tegillarca granosa and other mollusk genomes. Our phylogenetic analysis revealed the absence of the SPI and ETV subfamilies in mollusks compared to humans. Additionally, several ETS genes in mollusks were found to lack the PNT domain, potentially resulting in a diminished ability of ETS proteins to bind target genes. Interestingly, the bivalve ETS1 genes exhibited significantly high expression levels during the multicellular proliferation stage and in gill tissues. Furthermore, qRT-PCR results showed that Tg-ETS-14 (ETS1) is upregulated in the high total hemocyte counts (THC) population of T. granosa, suggesting it plays a significant role in stimulating hemocyte proliferation.

CONCLUSION: Our study significantly contributes to the comprehension of the evolutionary aspects concerning the ETS gene family, while also providing valuable insights into its role in fostering hemocyte proliferation across mollusks.}, } @article {pmid37981028, year = {2024}, author = {Rossi, SA and García-Barbazán, I and Chamorro-Herrero, I and Taborda, CP and Zaragoza, Ó and Zambrano, A}, title = {Use of 2D minilungs from human embryonic stem cells to study the interaction of Cryptococcus neoformans with the respiratory tract.}, journal = {Microbes and infection}, volume = {26}, number = {3}, pages = {105260}, doi = {10.1016/j.micinf.2023.105260}, pmid = {37981028}, issn = {1769-714X}, mesh = {Humans ; *Cryptococcus neoformans/physiology ; *Human Embryonic Stem Cells ; *Cryptococcosis/microbiology ; Lung/microbiology ; Cell Culture Techniques ; }, abstract = {Organoids can meet the needs between the use of cell culture and in vivo work, bringing together aspects of multicellular tissues, providing a more similar in vitro system for the study of various components, including host-interactions with pathogens and drug response. Organoids are structures that resemble organs in vivo, originating from pluripotent stem cells (PSCs) or adult stem cells (ASCs). There is great interest in deepening the understanding of the use of this technology to produce information about fungal infections and their treatments. This work aims the use 2D human lung organoid derived from human embryonic stem cells (hESCs), to investigate Cryptococcus neoformans-host interactions. C. neoformans is an opportunistic fungus acquired by inhalation that causes systemic mycosis mainly in immunocompromised individuals. Our work highlights the suitability of human minilungs for the study of C. neoformans infection (adhesion, invasion and replication), the interaction with the surfactant and induction of the host's alveolar pro-inflammatory response.}, } @article {pmid37971931, year = {2024}, author = {Zou, Y and Sabljić, I and Horbach, N and Dauphinee, AN and Åsman, A and Sancho Temino, L and Minina, EA and Drag, M and Stael, S and Poreba, M and Ståhlberg, J and Bozhkov, PV}, title = {Thermoprotection by a cell membrane-localized metacaspase in a green alga.}, journal = {The Plant cell}, volume = {36}, number = {3}, pages = {665-687}, pmid = {37971931}, issn = {1532-298X}, support = {//Knut and Alice Wallenberg Foundation/ ; //Swedish Research Council Vetenskapsrådet/ ; //National Science Centre in Poland/ ; }, mesh = {Animals ; Plants/metabolism ; Caspases/genetics/chemistry/metabolism ; *Arabidopsis/genetics ; Cell Membrane/metabolism ; *Chlorophyta ; }, abstract = {Caspases are restricted to animals, while other organisms, including plants, possess metacaspases (MCAs), a more ancient and broader class of structurally related yet biochemically distinct proteases. Our current understanding of plant MCAs is derived from studies in streptophytes, and mostly in Arabidopsis (Arabidopsis thaliana) with 9 MCAs with partially redundant activities. In contrast to streptophytes, most chlorophytes contain only 1 or 2 uncharacterized MCAs, providing an excellent platform for MCA research. Here we investigated CrMCA-II, the single type-II MCA from the model chlorophyte Chlamydomonas (Chlamydomonas reinhardtii). Surprisingly, unlike other studied MCAs and similar to caspases, CrMCA-II dimerizes both in vitro and in vivo. Furthermore, activation of CrMCA-II in vivo correlated with its dimerization. Most of CrMCA-II in the cell was present as a proenzyme (zymogen) attached to the plasma membrane (PM). Deletion of CrMCA-II by genome editing compromised thermotolerance, leading to increased cell death under heat stress. Adding back either wild-type or catalytically dead CrMCA-II restored thermoprotection, suggesting that its proteolytic activity is dispensable for this effect. Finally, we connected the non-proteolytic role of CrMCA-II in thermotolerance to the ability to modulate PM fluidity. Our study reveals an ancient, MCA-dependent thermotolerance mechanism retained by Chlamydomonas and probably lost during the evolution of multicellularity.}, } @article {pmid37964233, year = {2023}, author = {Zhang, C and Zhu, Z and Jiang, A and Liu, Q and Chen, M}, title = {Genome-wide identification of the mitogen-activated kinase gene family from Limonium bicolor and functional characterization of LbMAPK2 under salt stress.}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {565}, pmid = {37964233}, issn = {1471-2229}, mesh = {*Plumbaginaceae/metabolism ; Mitogens/metabolism ; Salt Stress/genetics ; Mitogen-Activated Protein Kinases/genetics/metabolism ; Stress, Physiological/genetics ; Plant Growth Regulators/metabolism ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/genetics/metabolism ; }, abstract = {BACKGROUND: Mitogen-activated protein kinases (MAPKs) are ubiquitous signal transduction components in eukaryotes. In plants, MAPKs play an essential role in growth and development, phytohormone regulation, and abiotic stress responses. The typical recretohalophyte Limonium bicolor (Bunge) Kuntze has multicellular salt glands on its stems and leaves; these glands secrete excess salt ions from its cells to mitigate salt damage. The number, type, and biological function of L. bicolor MAPK genes are unknown.

RESULTS: We identified 20 candidate L. bicolor MAPK genes, which can be divided into four groups. Of these 20 genes, 17 were anchored to 7 chromosomes, while LbMAPK18, LbMAPK19, and LbMAPK20 mapped to distinct scaffolds. Structure analysis showed that the predicted protein LbMAPK19 contains the special structural motif TNY in its activation loop, whereas the other LbMAPK members harbor the conserved TEY or TDY motif. The promoters of most LbMAPK genes carry cis-acting elements related to growth and development, phytohormones, and abiotic stress. LbMAPK1, LbMAPK2, LbMAPK16, and LbMAPK20 are highly expressed in the early stages of salt gland development, whereas LbMAPK4, LbMAPK5, LbMAPK6, LbMAPK7, LbMAPK11, LbMAPK14, and LbMAPK15 are highly expressed during the late stages. These 20 LbMAPK genes all responded to salt, drought and ABA stress. We explored the function of LbMAPK2 via virus-induced gene silencing: knocking down LbMAPK2 transcript levels in L. bicolor resulted in fewer salt glands, lower salt secretion ability from leaves, and decreased salt tolerance. The expression of several genes [LbTTG1 (TRANSPARENT TESTA OF GL1), LbCPC (CAPRICE), and LbGL2 (GLABRA2)] related to salt gland development was significantly upregulated in LbMAPK2 knockdown lines, while the expression of LbEGL3 (ENHANCER OF GL3) was significantly downregulated.

CONCLUSION: These findings increase our understanding of the LbMAPK gene family and will be useful for in-depth studies of the molecular mechanisms behind salt gland development and salt secretion in L. bicolor. In addition, our analysis lays the foundation for exploring the biological functions of MAPKs in an extreme halophyte.}, } @article {pmid37963956, year = {2023}, author = {Tissot, S and Guimard, L and Meliani, J and Boutry, J and Dujon, AM and Capp, JP and Tökölyi, J and Biro, PA and Beckmann, C and Fontenille, L and Do Khoa, N and Hamede, R and Roche, B and Ujvari, B and Nedelcu, AM and Thomas, F}, title = {The impact of food availability on tumorigenesis is evolutionarily conserved.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {19825}, pmid = {37963956}, issn = {2045-2322}, mesh = {Animals ; Humans ; *Cnidaria ; Biological Evolution ; *Hydra ; Carcinogenesis ; *Neoplasms/etiology ; }, abstract = {The inability to control cell proliferation results in the formation of tumors in many multicellular lineages. Nonetheless, little is known about the extent of conservation of the biological traits and ecological factors that promote or inhibit tumorigenesis across the metazoan tree. Particularly, changes in food availability have been linked to increased cancer incidence in humans, as an outcome of evolutionary mismatch. Here, we apply evolutionary oncology principles to test whether food availability, regardless of the multicellular lineage considered, has an impact on tumorigenesis. We used two phylogenetically unrelated model systems, the cnidarian Hydra oligactis and the fish Danio rerio, to investigate the impact of resource availability on tumor occurrence and progression. Individuals from healthy and tumor-prone lines were placed on four diets that differed in feeding frequency and quantity. For both models, frequent overfeeding favored tumor emergence, while lean diets appeared more protective. In terms of tumor progression, high food availability promoted it, whereas low resources controlled it, but without having a curative effect. We discuss our results in light of current ideas about the possible conservation of basic processes governing cancer in metazoans (including ancestral life history trade-offs at the cell level) and in the framework of evolutionary medicine.}, } @article {pmid37949064, year = {2023}, author = {Liu, D and Vargas-García, CA and Singh, A and Umen, J}, title = {A cell-based model for size control in the multiple fission alga Chlamydomonas reinhardtii.}, journal = {Current biology : CB}, volume = {33}, number = {23}, pages = {5215-5224.e5}, pmid = {37949064}, issn = {1879-0445}, support = {R01 GM126557/GM/NIGMS NIH HHS/United States ; R35 GM148351/GM/NIGMS NIH HHS/United States ; }, mesh = {*Chlamydomonas reinhardtii/genetics ; Cell Division ; Cell Cycle ; *Chlamydomonas ; Cell Proliferation ; }, abstract = {Understanding how population-size homeostasis emerges from stochastic individual cell behaviors remains a challenge in biology.[1][,][2][,][3][,][4][,][5][,][6][,][7] The unicellular green alga Chlamydomonas reinhardtii (Chlamydomonas) proliferates using a multiple fission cell cycle, where a prolonged G1 phase is followed by n rounds of alternating division cycles (S/M) to produce 2[n] daughters. A "Commitment" sizer in mid-G1 phase ensures sufficient cell growth before completing the cell cycle. A mitotic sizer couples mother-cell size to division number (n) such that daughter size distributions are uniform regardless of mother size distributions. Although daughter size distributions were highly robust to altered growth conditions, ∼40% of daughter cells fell outside of the 2-fold range expected from a "perfect" multiple fission sizer.[7][,][8] A simple intuitive power law model with stochastic noise failed to reproduce individual division behaviors of tracked single cells. Through additional iterative modeling, we identified an alternative modified threshold (MT) model, where cells need to cross a threshold greater than 2-fold their median starting size to become division-competent (i.e., Committed), after which their behaviors followed a power law model. The Commitment versus mitotic size threshold uncoupling in the MT model was likely a key pre-adaptation in the evolution of volvocine algal multicellularity. A similar experimental approach was used in size mutants mat3/rbr and dp1 that are, respectively, missing repressor or activator subunits of the retinoblastoma tumor suppressor complex (RBC). Both mutants showed altered relationships between Commitment and mitotic sizer, suggesting that RBC functions to decouple the two sizers.}, } @article {pmid37947621, year = {2023}, author = {Wang, X and Xu, X and Wang, Z}, title = {The Post-Translational Role of UFMylation in Physiology and Disease.}, journal = {Cells}, volume = {12}, number = {21}, pages = {}, pmid = {37947621}, issn = {2073-4409}, support = {32090031, 32000911//NSFC/ ; }, mesh = {Animals ; Humans ; *Proteins/metabolism ; *Protein Processing, Post-Translational ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitin/metabolism ; Ubiquitins/metabolism ; Mammals/metabolism ; }, abstract = {Ubiquitin-fold modifier 1 (UFM1) is a newly identified ubiquitin-like protein that has been conserved during the evolution of multicellular organisms. In a similar manner to ubiquitin, UFM1 can become covalently linked to the lysine residue of a substrate via a dedicated enzymatic cascade. Although a limited number of substrates have been identified so far, UFM1 modification (UFMylation) has been demonstrated to play a vital role in a variety of cellular activities, including mammalian development, ribosome biogenesis, the DNA damage response, endoplasmic reticulum stress responses, immune responses, and tumorigenesis. In this review, we summarize what is known about the UFM1 enzymatic cascade and its biological functions, and discuss its recently identified substrates. We also explore the pathological role of UFMylation in human disease and the corresponding potential therapeutic targets and strategies.}, } @article {pmid37931037, year = {2023}, author = {Dupouy, G and Cashell, R and Brychkova, G and Tuteja, R and McKeown, PC and Spillane, C}, title = {PICKLE RELATED 2 is a Neofunctionalized Gene Duplicate Under Positive Selection With Antagonistic Effects to the Ancestral PICKLE Gene on the Seed Transcriptome.}, journal = {Genome biology and evolution}, volume = {15}, number = {11}, pages = {}, pmid = {37931037}, issn = {1759-6653}, mesh = {*Arabidopsis/genetics ; *Arabidopsis Proteins/genetics ; Gene Expression Regulation, Plant ; Seeds/genetics ; Transcription Factors/genetics ; Transcriptome ; Gene Duplication ; }, abstract = {The evolution and diversification of proteins capable of remodeling domains has been critical for transcriptional reprogramming during cell fate determination in multicellular eukaryotes. Chromatin remodeling proteins of the CHD3 family have been shown to have important and antagonistic impacts on seed development in the model plant, Arabidopsis thaliana, yet the basis of this functional divergence remains unknown. In this study, we demonstrate that genes encoding the CHD3 proteins PICKLE (PKL) and PICKLE-RELATED 2 (PKR2) originated from a duplication event during the diversification of crown Brassicaceae, and that these homologs have undergone distinct evolutionary trajectories since this duplication, with PKR2 fast evolving under positive selection, while PKL is subject to purifying selection. We find that the rapid evolution of PKR2 under positive selection reduces the encoded protein's intrinsic disorder, possibly suggesting a tertiary structure configuration which differs from that of PKL. Our whole genome transcriptome analysis in seeds of pkr2 and pkl mutants reveals that they act antagonistically on the expression of specific sets of genes, providing a basis for their differing roles in seed development. Our results provide insights into how gene duplication and neofunctionalization can lead to differing and antagonistic selective pressures on transcriptomes during plant reproduction, as well as on the evolutionary diversification of the CHD3 family within seed plants.}, } @article {pmid37925718, year = {2023}, author = {Fung, L and Konkol, A and Ishikawa, T and Larson, BT and Brunet, T and Goldstein, RE}, title = {Swimming, Feeding, and Inversion of Multicellular Choanoflagellate Sheets.}, journal = {Physical review letters}, volume = {131}, number = {16}, pages = {168401}, pmid = {37925718}, issn = {1079-7114}, support = {/WT_/Wellcome Trust/United Kingdom ; 207510/WT_/Wellcome Trust/United Kingdom ; 207510/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Choanoflagellata/metabolism ; Swimming ; Biological Evolution ; }, abstract = {The recent discovery of the striking sheetlike multicellular choanoflagellate species Choanoeca flexa that dynamically interconverts between two hemispherical forms of opposite orientation raises fundamental questions in cell and evolutionary biology, as choanoflagellates are the closest living relatives of animals. It similarly motivates questions in fluid and solid mechanics concerning the differential swimming speeds in the two states and the mechanism of curvature inversion triggered by changes in the geometry of microvilli emanating from each cell. Here we develop fluid dynamical and mechanical models to address these observations and show that they capture the main features of the swimming, feeding, and inversion of C. flexa colonies, which can be viewed as active, shape-shifting polymerized membranes.}, } @article {pmid37916911, year = {2023}, author = {Ekdahl, LI and Salcedo, JA and Dungan, MM and Mason, DV and Myagmarsuren, D and Murphy, HA}, title = {Selection on plastic adherence leads to hyper-multicellular strains and incidental virulence in the budding yeast.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37916911}, issn = {2050-084X}, support = {R15 GM122032/GM/NIGMS NIH HHS/United States ; R15 GM152938/GM/NIGMS NIH HHS/United States ; R15-GM122032/NH/NIH HHS/United States ; }, mesh = {Animals ; Virulence ; *Saccharomycetales ; Saccharomyces cerevisiae/genetics ; Life Cycle Stages ; Phenotype ; }, abstract = {Many disease-causing microbes are not obligate pathogens; rather, they are environmental microbes taking advantage of an ecological opportunity. The existence of microbes whose life cycle does not require a host and are not normally pathogenic, yet are well-suited to host exploitation, is an evolutionary puzzle. One hypothesis posits that selection in the environment may favor traits that incidentally lead to pathogenicity and virulence, or serve as pre-adaptations for survival in a host. An example of such a trait is surface adherence. To experimentally test the idea of 'accidental virulence', replicate populations of Saccharomyces cerevisiae were evolved to attach to a plastic bead for hundreds of generations. Along with plastic adherence, two multicellular phenotypes- biofilm formation and flor formation- increased; another phenotype, pseudohyphal growth, responded to the nutrient limitation. Thus, experimental selection led to the evolution of highly-adherent, hyper-multicellular strains. Wax moth larvae injected with evolved hyper-multicellular strains were significantly more likely to die than those injected with evolved non-multicellular strains. Hence, selection on plastic adherence incidentally led to the evolution of enhanced multicellularity and increased virulence. Our results support the idea that selection for a trait beneficial in the open environment can inadvertently generate opportunistic, 'accidental' pathogens.}, } @article {pmid37904088, year = {2023}, author = {Balasubramanian, RN and Gao, M and Umen, J}, title = {Identification of cell-type specific alternative transcripts in the multicellular alga Volvox carteri.}, journal = {BMC genomics}, volume = {24}, number = {1}, pages = {654}, pmid = {37904088}, issn = {1471-2164}, support = {1755430//Division of Integrative Organismal Systems/ ; }, mesh = {*Volvox/genetics ; Transcriptome ; Protein Isoforms/genetics ; }, abstract = {BACKGROUND: Cell type specialization is a hallmark of complex multicellular organisms and is usually established through implementation of cell-type-specific gene expression programs. The multicellular green alga Volvox carteri has just two cell types, germ and soma, that have previously been shown to have very different transcriptome compositions which match their specialized roles. Here we interrogated another potential mechanism for differentiation in V. carteri, cell type specific alternative transcript isoforms (CTSAI).

METHODS: We used pre-existing predictions of alternative transcripts and de novo transcript assembly with HISAT2 and Ballgown software to compile a list of loci with two or more transcript isoforms, identified a small subset that were candidates for CTSAI, and manually curated this subset of genes to remove false positives. We experimentally verified three candidates using semi-quantitative RT-PCR to assess relative isoform abundance in each cell type.

RESULTS: Of the 1978 loci with two or more predicted transcript isoforms 67 of these also showed cell type isoform expression biases. After curation 15 strong candidates for CTSAI were identified, three of which were experimentally verified, and their predicted gene product functions were evaluated in light of potential cell type specific roles. A comparison of genes with predicted alternative splicing from Chlamydomonas reinhardtii, a unicellular relative of V. carteri, identified little overlap between ortholog pairs with alternative splicing in both species. Finally, we interrogated cell type expression patterns of 126 V. carteri predicted RNA binding protein (RBP) encoding genes and found 40 that showed either somatic or germ cell expression bias. These RBPs are potential mediators of CTSAI in V. carteri and suggest possible pre-adaptation for cell type specific RNA processing and a potential path for generating CTSAI in the early ancestors of metazoans and plants.

CONCLUSIONS: We predicted numerous instances of alternative transcript isoforms in Volvox, only a small subset of which showed cell type specific isoform expression bias. However, the validated examples of CTSAI supported existing hypotheses about cell type specialization in V. carteri, and also suggested new hypotheses about mechanisms of functional specialization for their gene products. Our data imply that CTSAI operates as a minor but important component of V. carteri cellular differentiation and could be used as a model for how alternative isoforms emerge and co-evolve with cell type specialization.}, } @article {pmid37895205, year = {2023}, author = {Ashouri, A and Zhang, C and Gaiti, F}, title = {Decoding Cancer Evolution: Integrating Genetic and Non-Genetic Insights.}, journal = {Genes}, volume = {14}, number = {10}, pages = {}, pmid = {37895205}, issn = {2073-4425}, support = {//CIHR/Canada ; 184658//CIHR/Canada ; }, mesh = {Humans ; *Neoplasms/genetics/pathology ; Tumor Microenvironment/genetics ; }, abstract = {The development of cancer begins with cells transitioning from their multicellular nature to a state akin to unicellular organisms. This shift leads to a breakdown in the crucial regulators inherent to multicellularity, resulting in the emergence of diverse cancer cell subpopulations that have enhanced adaptability. The presence of different cell subpopulations within a tumour, known as intratumoural heterogeneity (ITH), poses challenges for cancer treatment. In this review, we delve into the dynamics of the shift from multicellularity to unicellularity during cancer onset and progression. We highlight the role of genetic and non-genetic factors, as well as tumour microenvironment, in promoting ITH and cancer evolution. Additionally, we shed light on the latest advancements in omics technologies that allow for in-depth analysis of tumours at the single-cell level and their spatial organization within the tissue. Obtaining such detailed information is crucial for deepening our understanding of the diverse evolutionary paths of cancer, allowing for the development of effective therapies targeting the key drivers of cancer evolution.}, } @article {pmid37889142, year = {2023}, author = {Pentz, JT and MacGillivray, K and DuBose, JG and Conlin, PL and Reinhardt, E and Libby, E and Ratcliff, WC}, title = {Evolutionary consequences of nascent multicellular life cycles.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37889142}, issn = {2050-084X}, support = {T32 GM142616/GM/NIGMS NIH HHS/United States ; T32GM142616/NH/NIH HHS/United States ; }, mesh = {Humans ; Animals ; *Saccharomyces cerevisiae/genetics ; *Biological Evolution ; Life Cycle Stages ; Models, Biological ; Models, Theoretical ; }, abstract = {A key step in the evolutionary transition to multicellularity is the origin of multicellular groups as biological individuals capable of adaptation. Comparative work, supported by theory, suggests clonal development should facilitate this transition, although this hypothesis has never been tested in a single model system. We evolved 20 replicate populations of otherwise isogenic clonally reproducing 'snowflake' yeast (Δace2/∆ace2) and aggregative 'floc' yeast (GAL1p::FLO1 /GAL1p::FLO1) with daily selection for rapid growth in liquid media, which favors faster cell division, followed by selection for rapid sedimentation, which favors larger multicellular groups. While both genotypes adapted to this regime, growing faster and having higher survival during the group-selection phase, there was a stark difference in evolutionary dynamics. Aggregative floc yeast obtained nearly all their increased fitness from faster growth, not improved group survival; indicating that selection acted primarily at the level of cells. In contrast, clonal snowflake yeast mainly benefited from higher group-dependent fitness, indicating a shift in the level of Darwinian individuality from cells to groups. Through genome sequencing and mathematical modeling, we show that the genetic bottlenecks in a clonal life cycle also drive much higher rates of genetic drift-a result with complex implications for this evolutionary transition. Our results highlight the central role that early multicellular life cycles play in the process of multicellular adaptation.}, } @article {pmid37882538, year = {2023}, author = {Morreale, DP and St Geme Iii, JW and Planet, PJ}, title = {Phylogenomic analysis of the understudied Neisseriaceae species reveals a poly- and paraphyletic Kingella genus.}, journal = {Microbiology spectrum}, volume = {11}, number = {6}, pages = {e0312323}, pmid = {37882538}, issn = {2165-0497}, support = {R01 AI172841/AI/NIAID NIH HHS/United States ; T32 AI141393/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Neisseriaceae/genetics ; Kingella ; Phylogeny ; Genomics ; Phenotype ; Neisseria gonorrhoeae ; }, abstract = {Understanding the evolutionary relationships between the species in the Neisseriaceae family has been a persistent challenge in bacterial systematics due to high recombination rates in these species. Previous studies of this family have focused on Neisseria meningitidis and N. gonorrhoeae. However, previously understudied Neisseriaceae species are gaining new attention, with Kingella kingae now recognized as a common human pathogen and with Alysiella and Simonsiella being unique in the bacterial world as multicellular organisms. A better understanding of the genomic evolution of the Neisseriaceae can lead to the identification of specific genes and traits that underlie the remarkable diversity of this family.}, } @article {pmid37865203, year = {2023}, author = {Liu, Y and Liu, Y and Chen, S and Kong, Z and Guo, Y and Wang, H}, title = {Prenatal exposure to acetaminophen at different doses, courses and time causes testicular dysplasia in offspring mice and its mechanism.}, journal = {Chemosphere}, volume = {345}, number = {}, pages = {140496}, doi = {10.1016/j.chemosphere.2023.140496}, pmid = {37865203}, issn = {1879-1298}, mesh = {Male ; Testosterone/metabolism ; Leydig Cells/metabolism ; Animals, Outbred Strains ; Female ; *Prenatal Exposure Delayed Effects/chemically induced/metabolism ; Pregnancy ; Humans ; Mice ; Animals ; *Testis/metabolism ; Acetaminophen/toxicity/metabolism ; }, abstract = {Epidemiological investigation suggested that the use of acetaminophen during pregnancy may cause offspring testicular dysplasia, but no systematic study has been conducted. In this study, Kunming mice were given acetaminophen at different doses (100/200/400 mg/kg.d), courses (single/multiple), time (second/third trimester) during pregnancy. Fetal blood and testes were collected on gestaional day 18 for detection. The results indicated abnormal testicular development in the PAcE (prenatal acetaminophen exposure) groups. The maximum diameter/cross-sectional area decreased, the interstitial space widened, and decreased proliferation/increased apoptosis were observed, especially in the high-dose, multi-course and second-trimester groups. Meanwhile, the serum testosterone level decreased in PAcE groups, and the steroid synthesis function in Leydig cells, Sertoli and spermatogenic cell function were inhibited, it was more significant in high-dose, multi-course and second-trimester groups. Furthermore, Wnt signal pathway was activated but Notch signal pathway was inhibited in the PAcE groups. Finally, in vitro experiment, acetaminophen could inhibit spermatogonial cell proliferation, enhance apoptosis, and change Wnt/Notch signal pathway. In conclusion, this study confirmed that PAcE can change fetal testicular development in a dose, course and time-dependent manner, and found that multicellular function impaired. This study provides theoretical and experimental basis for systematically elucidating the developmental toxicity of acetaminophen in testis.}, } @article {pmid37863060, year = {2023}, author = {Mishina, T and Chiu, MC and Hashiguchi, Y and Oishi, S and Sasaki, A and Okada, R and Uchiyama, H and Sasaki, T and Sakura, M and Takeshima, H and Sato, T}, title = {Massive horizontal gene transfer and the evolution of nematomorph-driven behavioral manipulation of mantids.}, journal = {Current biology : CB}, volume = {33}, number = {22}, pages = {4988-4994.e5}, doi = {10.1016/j.cub.2023.09.052}, pmid = {37863060}, issn = {1879-0445}, mesh = {Animals ; *Mantodea ; Host-Parasite Interactions/genetics ; Behavior Control ; Gene Transfer, Horizontal ; *Parasites ; }, abstract = {To complete their life cycle, a wide range of parasites must manipulate the behavior of their hosts.[1] This manipulation is a well-known example of the "extended phenotype,[2]" where genes in one organism have phenotypic effects on another organism. Recent studies have explored the parasite genes responsible for such manipulation of host behavior, including the potential molecular mechanisms.[3][,][4] However, little is known about how parasites have acquired the genes involved in manipulating phylogenetically distinct hosts.[4] In a fascinating example of the extended phenotype, nematomorph parasites have evolved the ability to induce their terrestrial insect hosts to enter bodies of water, where the parasite then reproduces. Here, we comprehensively analyzed nematomorphs and their mantid hosts, focusing on the transcriptomic changes associated with host manipulations and sequence similarity between host and parasite genes to test molecular mimicry. The nematomorph's transcriptome changed during host manipulation, whereas no distinct changes were found in mantids. We then discovered numerous possible host-derived genes in nematomorphs, and these genes were frequently up-regulated during host manipulation. Our findings suggest a possible general role of horizontal gene transfer (HGT) in the molecular mechanisms of host manipulation, as well as in the genome evolution of manipulative parasites. The evidence of HGT between multicellular eukaryotes remains scarce but is increasing and, therefore, elucidating its mechanisms will advance our understanding of the enduring influence of HGT on the evolution of the web of life.}, } @article {pmid37850657, year = {2024}, author = {Ma, Q and Li, Q and Zheng, X and Pan, J}, title = {CellCommuNet: an atlas of cell-cell communication networks from single-cell RNA sequencing of human and mouse tissues in normal and disease states.}, journal = {Nucleic acids research}, volume = {52}, number = {D1}, pages = {D597-D606}, pmid = {37850657}, issn = {1362-4962}, support = {CSTB2023NSCQ-MSX0289//Chongqing Medical University/ ; //Natural Science Foundation of Chongqing/ ; BJRC202214//Chongqing Medical University/ ; CXQT21016//University Innovation Research Group Project of Chongqing/ ; W0056//Chongqing Medical University/ ; }, mesh = {Animals ; Humans ; Mice ; *Cell Communication ; *Databases, Factual ; *Gene Expression Profiling/methods ; Ligands ; *Sequence Analysis, RNA/methods ; *Single-Cell Analysis/methods ; }, abstract = {Cell-cell communication, as a basic feature of multicellular organisms, is crucial for maintaining the biological functions and microenvironmental homeostasis of cells, organs, and whole organisms. Alterations in cell-cell communication contribute to many diseases, including cancers. Single-cell RNA sequencing (scRNA-seq) provides a powerful method for studying cell-cell communication by enabling the analysis of ligand-receptor interactions. Here, we introduce CellCommuNet (http://www.inbirg.com/cellcommunet/), a comprehensive data resource for exploring cell-cell communication networks in scRNA-seq data from human and mouse tissues in normal and disease states. CellCommuNet currently includes 376 single datasets from multiple sources, and 118 comparison datasets between disease and normal samples originating from the same study. CellCommuNet provides information on the strength of communication between cells and related signalling pathways and facilitates the exploration of differences in cell-cell communication between healthy and disease states. Users can also search for specific signalling pathways, ligand-receptor pairs, and cell types of interest. CellCommuNet provides interactive graphics illustrating cell-cell communication in different states, enabling differential analysis of communication strength between disease and control samples. This comprehensive database aims to be a valuable resource for biologists studying cell-cell communication networks.}, } @article {pmid37849208, year = {2023}, author = {Arenzon, JJ and Peliti, L}, title = {Emergent cooperative behavior in transient compartments.}, journal = {Physical review. E}, volume = {108}, number = {3-1}, pages = {034409}, doi = {10.1103/PhysRevE.108.034409}, pmid = {37849208}, issn = {2470-0053}, mesh = {Humans ; *Cooperative Behavior ; Population Dynamics ; *Game Theory ; Biological Evolution ; }, abstract = {We introduce a minimal model of multilevel selection on structured populations, considering the interplay between game theory and population dynamics. Through a bottleneck process, finite groups are formed with cooperators and defectors sampled from an infinite pool. After the fragmentation, these transient compartments grow until the maximal number of individuals per compartment is attained. Eventually, all compartments are merged and well mixed, and the whole process is repeated. We show that cooperators, even if interacting only through mean-field intragroup interactions that favor defectors, may perform well because of the intergroup competition and the size diversity among the compartments. These cycles of isolation and coalescence may therefore be important in maintaining diversity among different species or strategies and may help to understand the underlying mechanisms of the scaffolding processes in the transition to multicellularity.}, } @article {pmid37848052, year = {2023}, author = {Horinouchi, Y and Togashi, T}, title = {Unicellular and multicellular developmental variations in algal zygotes produce sporophytes.}, journal = {Biology letters}, volume = {19}, number = {10}, pages = {20230313}, pmid = {37848052}, issn = {1744-957X}, mesh = {Animals ; *Zygote ; Plants/genetics ; *Chlorophyta/genetics ; Reproduction ; Life Cycle Stages ; }, abstract = {The emergence of sporophytes, that is, diploid multicellular bodies in plants, facilitated plant diversification and the evolution of complexity. Although sporophytes may have evolved in an ancestral alga exhibiting a haplontic life cycle with a unicellular diploid and multicellular haploid (gametophyte) phase, the mechanism by which this novelty originated remains largely unknown. Ulotrichalean marine green algae (Ulvophyceae) are one of the few extant groups with haplontic-like life cycles. In this study, we show that zygotes of the ulotrichalean alga Monostroma angicava, which usually develop into unicellular cysts, exhibit a developmental variation producing multicellular reproductive sporophytes. Multicellular development likely occurred stochastically in individual zygotes, but its ratio responded plastically to growth conditions. Sporophytes showed identical morphological development to gametophytes, which should reflect the expression of the same genetic programme directing multicellular development. Considering that sporophytes were evolutionarily derived in Ulotrichales, this implies that sporophytes emerged by co-opting the gametophyte developmental programme to the diploid phase. This study suggests a possible mechanism of sporophyte formation in haplontic life cycles, contributing to the understanding of the evolutionary transition from unicellular to multicellular diploid body plans in green plants.}, } @article {pmid37847422, year = {2024}, author = {Baluška, F and Miller, WB and Reber, AS}, title = {Sentient cells as basic units of tissues, organs and organismal physiology.}, journal = {The Journal of physiology}, volume = {602}, number = {11}, pages = {2491-2501}, doi = {10.1113/JP284419}, pmid = {37847422}, issn = {1469-7793}, mesh = {Animals ; Humans ; *Biological Evolution ; Cell Physiological Phenomena/physiology ; }, abstract = {Cells evolved some 4 billion years ago, and since then the integrity of the structural and functional continuity of cellular life has been maintained via highly conserved and ancient processes of cell reproduction and division. The plasma membrane as well as all the cytoplasmic structures are reproduced and inherited uninterruptedly by each of the two daughter cells resulting from every cell division. Although our understanding of the evolutionary emergence of the very first cells is obscured by the extremely long timeline since that revolutionary event, the generally accepted position is that the de novo formation of cells is not possible; all present cells are products of other prior cells. This essential biological principle was first discovered by Robert Remak and then effectively coined as Omnis Cellula e Cellula (every cell of the cell) by Rudolf Virchow: all currently living cells have direct structural and functional connections to the very first cells. Based on our previous theoretical analysis, all cells are endowed with individual sentient cognition that guides their individual agency, behaviour and evolution. There is a vital consequence of this new sentient and cognitive view of cells: when cells assemble as functional tissue ecologies and organs within multicellular organisms, including plants, animals and humans, these cellular aggregates display derivative versions of aggregate tissue- and organ-specific sentience and consciousness. This innovative view of the evolution and physiology of all currently living organisms supports a singular principle: all organismal physiology is based on cellular physiology that extends from unicellular roots.}, } @article {pmid37834047, year = {2023}, author = {Borodulina, OR and Ustyantsev, IG and Kramerov, DA}, title = {SINEs as Potential Expression Cassettes: Impact of Deletions and Insertions on Polyadenylation and Lifetime of B2 and Ves SINE Transcripts Generated by RNA Polymerase III.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834047}, issn = {1422-0067}, support = {19-14-00327//Russian Scientific Foundation/ ; }, mesh = {Animals ; Humans ; *Polyadenylation/genetics ; *RNA Polymerase III/genetics ; HeLa Cells ; Short Interspersed Nucleotide Elements/genetics ; Promoter Regions, Genetic ; Mammals/metabolism ; RNA, Messenger/genetics/metabolism ; }, abstract = {Short Interspersed Elements (SINEs) are common in the genomes of most multicellular organisms. They are transcribed by RNA polymerase III from an internal promoter comprising boxes A and B. As transcripts of certain SINEs from mammalian genomes can be polyadenylated, such transcripts should contain the AATAAA sequence as well as those called β- and τ-signals. One of the goals of this work was to evaluate how autonomous and independent other SINE parts are β- and τ-signals. Extended regions outside of β- and τ-signals were deleted from SINEs B2 and Ves and the derived constructs were used to transfect HeLa cells in order to evaluate the relative levels of their transcripts as well as their polyadenylation efficiency. If the deleted regions affected boxes A and B, the 5'-flanking region of the U6 RNA gene with the external promoter was inserted upstream. Such substitution of the internal promoter in B2 completely restored its transcription. Almost all tested deletions/substitutions did not reduce the polyadenylation capacity of the transcripts, indicating a weak dependence of the function of β- and τ-signals on the neighboring sequences. A similar analysis of B2 and Ves constructs containing a 55-bp foreign sequence inserted between β- and τ-signals showed an equal polyadenylation efficiency of their transcripts compared to those of constructs without the insertion. The acquired poly(A)-tails significantly increased the lifetime and thus the cellular level of such transcripts. The data obtained highlight the potential of B2 and Ves SINEs as cassettes for the expression of relatively short sequences for various applications.}, } @article {pmid37832511, year = {2023}, author = {Walker, LM and Sherpa, RN and Ivaturi, S and Brock, DA and Larsen, TJ and Walker, JR and Strassmann, JE and Queller, DC}, title = {Parallel evolution of the G protein-coupled receptor GrlG and the loss of fruiting body formation in the social amoeba Dictyostelium discoideum evolved under low relatedness.}, journal = {G3 (Bethesda, Md.)}, volume = {14}, number = {1}, pages = {}, pmid = {37832511}, issn = {2160-1836}, support = {IOS 16-56756//National Science Foundation/ ; //McDonnell Genome Institute/ ; }, mesh = {*Amoeba ; Biological Evolution ; *Dictyostelium/genetics ; Reproduction ; }, abstract = {Aggregative multicellularity relies on cooperation among formerly independent cells to form a multicellular body. Previous work with Dictyostelium discoideum showed that experimental evolution under low relatedness profoundly decreased cooperation, as indicated by the loss of fruiting body formation in many clones and an increase of cheaters that contribute proportionally more to spores than to the dead stalk. Using whole-genome sequencing and variant analysis of these lines, we identified 38 single nucleotide polymorphisms in 29 genes. Each gene had 1 variant except for grlG (encoding a G protein-coupled receptor), which had 10 unique SNPs and 5 structural variants. Variants in the 5' half of grlG-the region encoding the signal peptide and the extracellular binding domain-were significantly associated with the loss of fruiting body formation; the association was not significant in the 3' half of the gene. These results suggest that the loss of grlG was adaptive under low relatedness and that at least the 5' half of the gene is important for cooperation and multicellular development. This is surprising given some previous evidence that grlG encodes a folate receptor involved in predation, which occurs only during the single-celled stage. However, non-fruiting mutants showed little increase in a parallel evolution experiment where the multicellular stage was prevented from happening. This shows that non-fruiting mutants are not generally selected by any predation advantage but rather by something-likely cheating-during the multicellular stage.}, } @article {pmid37817595, year = {2023}, author = {Bourke, AFG}, title = {Conflict and conflict resolution in the major transitions.}, journal = {Proceedings. Biological sciences}, volume = {290}, number = {2008}, pages = {20231420}, pmid = {37817595}, issn = {1471-2954}, mesh = {Humans ; *Negotiating ; *Biological Evolution ; Sexual Behavior ; }, abstract = {Conflict and conflict resolution have been argued to be fundamental to the major transitions in evolution. These were key events in life's history in which previously independently living individuals cooperatively formed a higher-level individual, such as a multicellular organism or eusocial colony. Conflict has its central role because, to proceed stably, the evolution of individuality in each major transition required within-individual conflict to be held in check. This review revisits the role of conflict and conflict resolution in the major transitions, addressing recent work arguing for a minor role. Inclusive fitness logic suggests that differences between the kin structures of clones and sexual families support the absence of conflict at the origin of multicellularity but, by contrast, suggest that key conflicts existed at the origin of eusociality. A principal example is conflict over replacing the founding queen (queen replacement). Following the origin of each transition, conflict remained important, because within-individual conflict potentially disrupts the attainment of maximal individuality (organismality) in the system. The conclusion is that conflict remains central to understanding the major transitions, essentially because conflict arises from differences in inclusive fitness optima while conflict resolution can help the system attain a high degree of coincidence of inclusive fitness interests.}, } @article {pmid37804416, year = {2024}, author = {Sarabia-Sánchez, MA and Robles-Flores, M}, title = {WNT Signaling in Stem Cells: A Look into the Non-Canonical Pathway.}, journal = {Stem cell reviews and reports}, volume = {20}, number = {1}, pages = {52-66}, pmid = {37804416}, issn = {2629-3277}, support = {IN229420 and IV200220//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; }, mesh = {Humans ; *Wnt Signaling Pathway ; beta Catenin/metabolism ; Neoplastic Stem Cells/metabolism ; *Neoplasms/metabolism ; Cell Differentiation ; }, abstract = {Tissue homeostasis is crucial for multicellular organisms, wherein the loss of cells is compensated by generating new cells with the capacity for proliferation and differentiation. At the origin of these populations are the stem cells, which have the potential to give rise to cells with both capabilities, and persevere for a long time through the self-renewal and quiescence. Since the discovery of stem cells, an enormous effort has been focused on learning about their functions and the molecular regulation behind them. Wnt signaling is widely recognized as essential for normal and cancer stem cell. Moreover, β-catenin-dependent Wnt pathway, referred to as canonical, has gained attention, while β-catenin-independent Wnt pathways, known as non-canonical, have remained conspicuously less explored. However, recent evidence about non-canonical Wnt pathways in stem cells begins to lay the foundations of a conceivably vast field, and on which we aim to explain this in the present review. In this regard, we addressed the different aspects in which non-canonical Wnt pathways impact the properties of stem cells, both under normal conditions and also under disease, specifically in cancer.}, } @article {pmid37797407, year = {2024}, author = {Paloschi, V and Pauli, J and Winski, G and Wu, Z and Li, Z and Botti, L and Meucci, S and Conti, P and Rogowitz, F and Glukha, N and Hummel, N and Busch, A and Chernogubova, E and Jin, H and Sachs, N and Eckstein, HH and Dueck, A and Boon, RA and Bausch, AR and Maegdefessel, L}, title = {Utilization of an Artery-on-a-Chip to Unravel Novel Regulators and Therapeutic Targets in Vascular Diseases.}, journal = {Advanced healthcare materials}, volume = {13}, number = {6}, pages = {e2302907}, pmid = {37797407}, issn = {2192-2659}, support = {R01 HL150359/HL/NHLBI NIH HHS/United States ; 1R011HL150359-01/NH/NIH HHS/United States ; }, mesh = {Humans ; Arteries ; *Aortic Aneurysm, Abdominal/drug therapy ; *Atherosclerosis/drug therapy ; Disease Progression ; Lab-On-A-Chip Devices ; }, abstract = {In this study, organ-on-chip technology is used to develop an in vitro model of medium-to-large size arteries, the artery-on-a-chip (AoC), with the objective to recapitulate the structure of the arterial wall and the relevant hemodynamic forces affecting luminal cells. AoCs exposed either to in vivo-like shear stress values or kept in static conditions are assessed to generate a panel of novel genes modulated by shear stress. Considering the crucial role played by shear stress alterations in carotid arteries affected by atherosclerosis (CAD) and abdominal aortic aneurysms (AAA) disease development/progression, a patient cohort of hemodynamically relevant specimens is utilized, consisting of diseased and non-diseased (internal control) vessel regions from the same patient. Genes activated by shear stress follow the same expression pattern in non-diseased segments of human vessels. Single cell RNA sequencing (scRNA-seq) enables to discriminate the unique cell subpopulations between non-diseased and diseased vessel portions, revealing an enrichment of flow activated genes in structural cells originating from non-diseased specimens. Furthermore, the AoC served as a platform for drug-testing. It reproduced the effects of a therapeutic agent (lenvatinib) previously used in preclinical AAA studies, therefore extending the understanding of its therapeutic effect through a multicellular structure.}, } @article {pmid37783374, year = {2023}, author = {Igamberdiev, AU and Gordon, R}, title = {Macroevolution, differentiation trees, and the growth of coding systems.}, journal = {Bio Systems}, volume = {234}, number = {}, pages = {105044}, doi = {10.1016/j.biosystems.2023.105044}, pmid = {37783374}, issn = {1872-8324}, mesh = {*Cell Differentiation/genetics ; Morphogenesis/genetics ; Phylogeny ; }, abstract = {An open process of evolution of multicellular organisms is based on the rearrangement and growth of the program of differentiation that underlies biological morphogenesis. The maintenance of the final (adult) stable non-equilibrium state (stasis) of a developmental system determines the direction of the evolutionary process. This state is achieved via the sequence of differentiation events representable as differentiation trees. A special type of morphogenetic code, acting as a metacode governing gene expression, may include electromechanical signals appearing as differentiation waves. The excessive energy due to the incorporation of mitochondria in eukaryotic cells resulted not only in more active metabolism but also in establishing the differentiation code for interconnecting cells and forming tissues, which fueled the evolutionary process. The "invention" of "continuing differentiation" distinguishes multicellular eukaryotes from other organisms. The Janus-faced control, involving both top-down control by differentiation waves and bottom-up control via the mechanical consequences of cell differentiations, underlies the process of morphogenesis and results in the achievement of functional stable final states. Duplications of branches of the differentiation tree may be the basis for continuing differentiation and macroevolution, analogous to gene duplication permitting divergence of genes. Metamorphoses, if they are proven to be fusions of disparate species, may be classified according to the topology of fusions of two differentiation trees. In the process of unfolding of morphogenetic structures, microevolution can be defined as changes of the differentiation tree that preserve topology of the tree, while macroevolution represents any change that alters the topology of the differentiation tree.}, } @article {pmid37765506, year = {2023}, author = {Wegner, L and Porth, ML and Ehlers, K}, title = {Multicellularity and the Need for Communication-A Systematic Overview on (Algal) Plasmodesmata and Other Types of Symplasmic Cell Connections.}, journal = {Plants (Basel, Switzerland)}, volume = {12}, number = {18}, pages = {}, pmid = {37765506}, issn = {2223-7747}, support = {EH 372/1-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {In the evolution of eukaryotes, the transition from unicellular to simple multicellular organisms has happened multiple times. For the development of complex multicellularity, characterized by sophisticated body plans and division of labor between specialized cells, symplasmic intercellular communication is supposed to be indispensable. We review the diversity of symplasmic connectivity among the eukaryotes and distinguish between distinct types of non-plasmodesmatal connections, plasmodesmata-like structures, and 'canonical' plasmodesmata on the basis of developmental, structural, and functional criteria. Focusing on the occurrence of plasmodesmata (-like) structures in extant taxa of fungi, brown algae (Phaeophyceae), green algae (Chlorophyta), and streptophyte algae, we present a detailed critical update on the available literature which is adapted to the present classification of these taxa and may serve as a tool for future work. From the data, we conclude that, actually, development of complex multicellularity correlates with symplasmic connectivity in many algal taxa, but there might be alternative routes. Furthermore, we deduce a four-step process towards the evolution of canonical plasmodesmata and demonstrate similarity of plasmodesmata in streptophyte algae and land plants with respect to the occurrence of an ER component. Finally, we discuss the urgent need for functional investigations and molecular work on cell connections in algal organisms.}, } @article {pmid37743376, year = {2023}, author = {Zhang, Z and Huo, W and Wang, X and Ren, Z and Zhao, J and Liu, Y and He, K and Zhang, F and Li, W and Jin, S and Yang, D}, title = {Origin, evolution, and diversification of the wall-associated kinase gene family in plants.}, journal = {Plant cell reports}, volume = {42}, number = {12}, pages = {1891-1906}, pmid = {37743376}, issn = {1432-203X}, support = {232300421116//Natural Science Foundation of Henan Province/ ; }, mesh = {*Plants/genetics ; Genes, Plant/genetics ; *Arabidopsis/genetics ; Multigene Family ; }, abstract = {The study of the origin, evolution, and diversification of the wall-associated kinase gene family in plants facilitates their functional investigations in the future. Wall-associated kinases (WAKs) make up one subfamily of receptor-like kinases (RLKs), and function directly in plant cell elongation and responses to biotic and abiotic stresses. The biological functions of WAKs have been extensively characterized in angiosperms; however, the origin and evolutionary history of the WAK family in green plants remain unclear. Here, we performed a comprehensive analysis of the WAK family to reveal its origin, evolution, and diversification in green plants. In total, 1061 WAK genes were identified in 37 species from unicellular algae to multicellular plants, and the results showed that WAK genes probably originated before bryophyte differentiation and were widely distributed in land plants, especially angiosperms. The phylogeny indicated that the land plant WAKs gave rise to five clades and underwent lineage-specific expansion after species differentiation. Cis-acting elements and expression patterns analyses of WAK genes in Arabidopsis and rice demonstrated the functional diversity of WAK genes in these two species. Many gene gains and losses have occurred in angiosperms, leading to an increase in the number of gene copies. The evolutionary trajectory of the WAK family during polyploidization was uncovered using Gossypium species. Our results provide insights into the evolution of WAK genes in green plants, facilitating their functional investigations in the future.}, } @article {pmid37741353, year = {2023}, author = {Ma, C and Li, X and Xiao, H and Li, B and Gu, H and Guo, Y and Wang, H and Wen, Y and Chen, L}, title = {Course-, dose-, and stage-dependent toxic effects of prenatal acetaminophen exposure on fetal long bone development.}, journal = {Toxicology letters}, volume = {387}, number = {}, pages = {50-62}, doi = {10.1016/j.toxlet.2023.09.007}, pmid = {37741353}, issn = {1879-3169}, mesh = {Osteogenesis ; Bone and Bones ; *Acetaminophen/toxicity ; Female ; Pregnancy ; Humans ; Mice ; Animals ; *Prenatal Exposure Delayed Effects ; Fetal Development ; Animals, Outbred Strains ; }, abstract = {Acetaminophen is a common analgesic and fever reduction medicine for pregnant women. Epidemiological studies suggest that prenatal acetaminophen exposure (PAcE) affects offspring health and development. However, the effects of PAcE on fetal long bone development and its potential mechanisms have not been elucidated. Based on clinical dosing characteristics, fetal mouse femurs were obtained for detection after oral gavage of acetaminophen at different doses (0, 100 or 400 mg/kg d), courses (single or multiple times) or stages (mid- or late pregnancy) during pregnancy in Kunming mice. The results showed that compared with the control group, PAcE reduced the length of total femur and the primary ossification center (POC), delayed the mineralization of POC and the ossification of epiphyseal region, and down-regulated the mRNA expression of osteogenic function markers (such as Runx2, Bsp, Ocn , Col1a1) in fetal femur, particularly in the high dose, multiple courses, and mid-pregnancy group. Meanwhile, the osteoclast and angiogenic function were also inhibited by PAcE at high dose, multiple courses, and mid-pregnancy, but the inhibition level was less than osteogenic function. Moreover, the alteration of canonical Wnt signalling pathway in PAcE fetal bone were consistent with its osteogenesis function changes. In conclusion, PAcE caused development toxicity and multi-cellular function inhibition in fetal long bone, particularly in the high dose, multiple treatments and mid-pregnancy group, and the alteration of canonical Wnt signalling pathway may be its potential mechanism.}, } @article {pmid37727796, year = {2023}, author = {Craig, JM and Kumar, S and Hedges, SB}, title = {The origin of eukaryotes and rise in complexity were synchronous with the rise in oxygen.}, journal = {Frontiers in bioinformatics}, volume = {3}, number = {}, pages = {1233281}, pmid = {37727796}, issn = {2673-7647}, support = {R01 GM126567/GM/NIGMS NIH HHS/United States ; R35 GM139540/GM/NIGMS NIH HHS/United States ; }, abstract = {The origin of eukaryotes was among the most important events in the history of life, spawning a new evolutionary lineage that led to all complex multicellular organisms. However, the timing of this event, crucial for understanding its environmental context, has been difficult to establish. The fossil and biomarker records are sparse and molecular clocks have thus far not reached a consensus, with dates spanning 2.1-0.91 billion years ago (Ga) for critical nodes. Notably, molecular time estimates for the last common ancestor of eukaryotes are typically hundreds of millions of years younger than the Great Oxidation Event (GOE, 2.43-2.22 Ga), leading researchers to question the presumptive link between eukaryotes and oxygen. We obtained a new time estimate for the origin of eukaryotes using genetic data of both archaeal and bacterial origin, the latter rarely used in past studies. We also avoided potential calibration biases that may have affected earlier studies. We obtained a conservative interval of 2.2-1.5 Ga, with an even narrower core interval of 2.0-1.8 Ga, for the origin of eukaryotes, a period closely aligned with the rise in oxygen. We further reconstructed the history of biological complexity across the tree of life using three universal measures: cell types, genes, and genome size. We found that the rise in complexity was temporally consistent with and followed a pattern similar to the rise in oxygen. This suggests a causal relationship stemming from the increased energy needs of complex life fulfilled by oxygen.}, } @article {pmid37727086, year = {2023}, author = {Kalambokidis, M and Travisano, M}, title = {Multispecies interactions shape the transition to multicellularity.}, journal = {Proceedings. Biological sciences}, volume = {290}, number = {2007}, pages = {20231055}, pmid = {37727086}, issn = {1471-2954}, mesh = {*Saccharomyces cerevisiae ; Coculture Techniques ; *Earth, Planet ; }, abstract = {The origin of multicellularity transformed the adaptive landscape on Earth, opening diverse avenues for further innovation. The transition to multicellular life is understood as the evolution of cooperative groups which form a new level of individuality. Despite the potential for community-level interactions, most studies have not addressed the competitive context of this transition, such as competition between species. Here, we explore how interspecific competition shapes the emergence of multicellularity in an experimental system with two yeast species, Saccharomyces cerevisiae and Kluyveromyces lactis, where multicellularity evolves in response to selection for faster settling ability. We find that the multispecies context slows the rate of the transition to multicellularity, and the transition to multicellularity significantly impacts community composition. Multicellular K. lactis emerges first and sweeps through populations in monocultures faster than in cocultures with S. cerevisiae. Following the transition, the between-species competitive dynamics shift, likely in part to intraspecific cooperation in K. lactis. Hence, we document an eco-evolutionary feedback across the transition to multicellularity, underscoring how ecological context is critical for understanding the causes and consequences of innovation. By including two species, we demonstrate that cooperation and competition across several biological scales shapes the origin and persistence of multicellularity.}, } @article {pmid37722687, year = {2023}, author = {Kulkarni, M and Hardwick, JM}, title = {Programmed Cell Death in Unicellular Versus Multicellular Organisms.}, journal = {Annual review of genetics}, volume = {57}, number = {}, pages = {435-459}, pmid = {37722687}, issn = {1545-2948}, support = {R21 AI144373/AI/NIAID NIH HHS/United States ; R21 AI183596/AI/NIAID NIH HHS/United States ; R21 NS127076/NS/NINDS NIH HHS/United States ; R56 AI168539/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Apoptosis/genetics ; *Fungi/genetics/metabolism ; Bacteria ; Mammals ; }, abstract = {Programmed cell death (self-induced) is intrinsic to all cellular life forms, including unicellular organisms. However, cell death research has focused on animal models to understand cancer, degenerative disorders, and developmental processes. Recently delineated suicidal death mechanisms in bacteria and fungi have revealed ancient origins of animal cell death that are intertwined with immune mechanisms, allaying earlier doubts that self-inflicted cell death pathways exist in microorganisms. Approximately 20 mammalian death pathways have been partially characterized over the last 35 years. By contrast, more than 100 death mechanisms have been identified in bacteria and a few fungi in recent years. However, cell death is nearly unstudied in most human pathogenic microbes that cause major public health burdens. Here, we consider how the current understanding of programmed cell death arose through animal studies and how recently uncovered microbial cell death mechanisms in fungi and bacteria resemble and differ from mechanisms of mammalian cell death.}, } @article {pmid37699344, year = {2023}, author = {Azimzadeh, J and Durand, B}, title = {Evolution: The ancient history of cilia assembly regulation.}, journal = {Current biology : CB}, volume = {33}, number = {17}, pages = {R898-R900}, doi = {10.1016/j.cub.2023.07.053}, pmid = {37699344}, issn = {1879-0445}, mesh = {Animals ; *Cilia ; }, abstract = {A new study identifies a conserved regulatory mechanism for cilia assembly in the closest unicellular relatives of animals, suggesting that this mechanism was already present in a common unicellular ancestor and was repurposed during the transition to multicellularity.}, } @article {pmid37668864, year = {2023}, author = {Garte, S}, title = {Targeted Hypermutation as a Survival Strategy: A Theoretical Approach.}, journal = {Acta biotheoretica}, volume = {71}, number = {4}, pages = {20}, pmid = {37668864}, issn = {1572-8358}, mesh = {Animals ; Mutation ; *Mutation Rate ; Probability ; *Mammals ; }, abstract = {Targeted hypermutation has proven to be a useful survival strategy for bacteria under severe stress and is also used by multicellular organisms in specific instances such as the mammalian immune system. This might appear surprising, given the generally observed deleterious effects of poor replication fidelity/high mutation rate. A previous theoretical model designed to explore the role of replication fidelity in the origin of life was applied to a simulated hypermutation scenario. The results confirmed that the same model is useful for analyzing hypermutation and can predict the effects of the same parameters (survival probability, replication fidelity, mutation effect, and others) on the survival of cellular populations undergoing hypermutation as a result of severe stress.}, } @article {pmid37666963, year = {2023}, author = {Clark, JW and Hetherington, AJ and Morris, JL and Pressel, S and Duckett, JG and Puttick, MN and Schneider, H and Kenrick, P and Wellman, CH and Donoghue, PCJ}, title = {Evolution of phenotypic disparity in the plant kingdom.}, journal = {Nature plants}, volume = {9}, number = {10}, pages = {1618-1626}, pmid = {37666963}, issn = {2055-0278}, support = {NE/N002067/1//RCUK | Natural Environment Research Council (NERC)/ ; NE/P013678/1//RCUK | Natural Environment Research Council (NERC)/ ; BB/N000919/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; BB/T012773/1//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; RF-2022-167//Leverhulme Trust/ ; RPG-2019-004//Leverhulme Trust/ ; JTF 62574//John Templeton Foundation (JTF)/ ; }, mesh = {Animals ; *Biological Evolution ; *Plants/genetics ; }, abstract = {The plant kingdom exhibits diverse bodyplans, from single-celled algae to complex multicellular land plants, but it is unclear how this phenotypic disparity was achieved. Here we show that the living divisions comprise discrete clusters within morphospace, separated largely by reproductive innovations, the extinction of evolutionary intermediates and lineage-specific evolution. Phenotypic complexity correlates not with disparity but with ploidy history, reflecting the role of genome duplication in plant macroevolution. Overall, the plant kingdom exhibits a pattern of episodically increasing disparity throughout its evolutionary history that mirrors the evolutionary floras and reflects ecological expansion facilitated by reproductive innovations. This pattern also parallels that seen in the animal and fungal kingdoms, suggesting a general pattern for the evolution of multicellular bodyplans.}, } @article {pmid37649301, year = {2023}, author = {Borg, M and Krueger-Hadfield, SA and Destombe, C and Collén, J and Lipinska, A and Coelho, SM}, title = {Red macroalgae in the genomic era.}, journal = {The New phytologist}, volume = {240}, number = {2}, pages = {471-488}, doi = {10.1111/nph.19211}, pmid = {37649301}, issn = {1469-8137}, mesh = {*Seaweed/genetics ; Genomics ; Eukaryota ; Biological Evolution ; Cytoskeleton ; }, abstract = {Rhodophyta (or red algae) are a diverse and species-rich group that forms one of three major lineages in the Archaeplastida, a eukaryotic supergroup whose plastids arose from a single primary endosymbiosis. Red algae are united by several features, such as relatively small intron-poor genomes and a lack of cytoskeletal structures associated with motility like flagella and centrioles, as well as a highly efficient photosynthetic capacity. Multicellular red algae (or macroalgae) are one of the earliest diverging eukaryotic lineages to have evolved complex multicellularity, yet despite their ecological, evolutionary, and commercial importance, they have remained a largely understudied group of organisms. Considering the increasing availability of red algal genome sequences, we present a broad overview of fundamental aspects of red macroalgal biology and posit on how this is expected to accelerate research in many domains of red algal biology in the coming years.}, } @article {pmid37645274, year = {2022}, author = {Hall, G and Kelly, S and Schaap, P and Schilde, C}, title = {Phylogeny-wide analysis of G-protein coupled receptors in social amoebas and implications for the evolution of multicellularity.}, journal = {Open research Europe}, volume = {2}, number = {}, pages = {134}, pmid = {37645274}, issn = {2732-5121}, abstract = {G-protein coupled receptors (GPCRs) are seven-transmembrane proteins and constitute the largest group of receptors within eukaryotes. The presence of a large set of GPCRs in the unicellular Amoebozoa was surprising and is indicative of the largely undiscovered environmental sensing capabilities in this group. Evolutionary transitions from unicellular to multicellular lifestyles, like we see in social amoebas, have occurred several times independently in the Amoebozoa, and GPCRs may have been co-opted for new functions in cell-cell communication. Methods We have analysed a set of GPCRs from fully sequenced Amoebozoan genomes by Bayesian inference, compared their phylogenetic distribution and domain composition, and analysed their temporal and spatial expression patterns in five species of dictyostelids. Results We found evidence that most GPCRs are conserved deeply in the Amoebozoa and are probably performing roles in general cell functions and complex environmental sensing. All families of GPCRs (apart from the family 4 fungal pheromone receptors) are present in dictyostelids with family 5 being the largest and family 2 the one with the fewest members. For the first time, we identify the presence of family 1 rhodopsin-like GPCRs in dictyostelids. Some GPCRs have been amplified in the dictyostelids and in specific lineages thereof and through changes in expression patterns may have been repurposed for signalling in multicellular development. Discussion Our phylogenetic analysis suggests that GPCR families 1, 2 and 6 already diverged early in the Amoebozoa, whereas families 3 and 5 expanded later within the dictyostelids. The family 6 cAMP receptors that have experimentally supported roles in multicellular development in dictyostelids (carA-carD; tasA/B) originated at the root of all dictyostelids and only have weakly associated homologs in Physarum polycephalum. Our analysis identified candidate GPCRs which have evolved in the dictyostelids and could have been co-opted for multicellular development.}, } @article {pmid37596740, year = {2023}, author = {Pinion, AK and Britz, R and Kubicek, KM and Siegel, DS and Conway, KW}, title = {The larval attachment organ of the bowfin Amia ocellicauda Richardson, 1836 (Amiiformes: Amiidae) and its phylogenetic significance.}, journal = {Journal of fish biology}, volume = {103}, number = {6}, pages = {1300-1311}, doi = {10.1111/jfb.15528}, pmid = {37596740}, issn = {1095-8649}, support = {HATCH TEX09452//Texas A&M Agrilife Research/ ; NSFDBI2035082//US National Science Foundation/ ; }, mesh = {Animals ; Larva ; Phylogeny ; *Fishes ; Microscopy, Electron, Scanning ; }, abstract = {Larval attachment organs (LAOs) are unicellular or multicellular organs that enable the larvae of many actinopterygian fishes to adhere to a substrate before yolk-sac absorption and the free-swimming stage. Bowfins (Amiiformes) exhibit a sizable LAO on the snout, which was first described in the late 19th and early 20th centuries. In this study, we document the LAO of Amia ocellicauda (Richardson, 1836) using a combination of scanning electron microscopy (SEM) and light microscopy, and histochemistry. We examined material representing three stages with SEM ranging in size from 5.8 to 11.2 mm in notochord length and one stage histochemically. We compare the LAO of A. ocellicauda to that of the lepisosteid Atractosteus tropicus Gill, 1863 and show that although the LAOs of A. ocellicauda and A. tropicus are both super-organs, the two differ in the ultrastructure of the entire organ. A. ocellicauda possesses two distinct lobes, with the organs arranged on the periphery with none in the middle, whereas A. tropicus also possesses two lobes, but with the organs scattered evenly across the super-organ. The individual organs of A. ocellicauda possess adhesive cells set deep to support cells with the adhesive substance released through a pore, whereas A. tropicus possesses both support cells and adhesive cells sitting at a similar level, with the adhesive substance released directly onto the surface of the organ. We additionally provide a table summarizing vertebrate genera in which attachment organs have been documented and discuss the implications of our study for hypotheses of the homology of attachment organs in the Holostei.}, } @article {pmid37586948, year = {2023}, author = {Shalev, O and Ye, X and Ratzke, C}, title = {Replaying the evolution of multicellularity.}, journal = {Trends in ecology & evolution}, volume = {38}, number = {10}, pages = {910-912}, doi = {10.1016/j.tree.2023.07.007}, pmid = {37586948}, issn = {1872-8383}, mesh = {Earth, Planet ; *Origin of Life ; *Biological Evolution ; Yeasts ; }, abstract = {The first organisms on Earth were presumably unicellular. At one point, evolution shaped these individual cells into multicellular organisms, which was a significant transition in the history of life on Earth. To investigate how this change happened, Bozdag et al. re-ran evolution in the lab and observed how single-celled yeast forms large multicellular aggregates.}, } @article {pmid37565532, year = {2023}, author = {Cervantes, S and Kesälahti, R and Kumpula, TA and Mattila, TM and Helanterä, H and Pyhäjärvi, T}, title = {Strong Purifying Selection in Haploid Tissue-Specific Genes of Scots Pine Supports the Masking Theory.}, journal = {Molecular biology and evolution}, volume = {40}, number = {8}, pages = {}, pmid = {37565532}, issn = {1537-1719}, mesh = {Haploidy ; *Selection, Genetic ; Mutation ; *Biological Evolution ; Diploidy ; Plants ; }, abstract = {The masking theory states that genes expressed in a haploid stage will be under more efficient selection. In contrast, selection will be less efficient in genes expressed in a diploid stage, where the fitness effects of recessive deleterious or beneficial mutations can be hidden from selection in heterozygous form. This difference can influence several evolutionary processes such as the maintenance of genetic variation, adaptation rate, and genetic load. Masking theory expectations have been confirmed in single-cell haploid and diploid organisms. However, in multicellular organisms, such as plants, the effects of haploid selection are not clear-cut. In plants, the great majority of studies indicating haploid selection have been carried out using male haploid tissues in angiosperms. Hence, evidence in these systems is confounded with the effects of sexual selection and intraspecific competition. Evidence from other plant groups is scarce, and results show no support for the masking theory. Here, we have used a gymnosperm Scots pine megagametophyte, a maternally derived seed haploid tissue, and four diploid tissues to test the strength of purifying selection on a set of genes with tissue-specific expression. By using targeted resequencing data of those genes, we obtained estimates of genetic diversity, the site frequency spectrum of 0-fold and 4-fold sites, and inferred the distribution of fitness effects of new mutations in haploid and diploid tissue-specific genes. Our results show that purifying selection is stronger for tissue-specific genes expressed in the haploid megagametophyte tissue and that this signal of strong selection is not an artifact driven by high expression levels.}, } @article {pmid37563336, year = {2023}, author = {Mocarski, ES}, title = {Programmed Necrosis in Host Defense.}, journal = {Current topics in microbiology and immunology}, volume = {442}, number = {}, pages = {1-40}, pmid = {37563336}, issn = {0070-217X}, mesh = {Animals ; Humans ; Immunity, Innate ; Lymphocytes ; Apoptosis/genetics ; Necrosis/metabolism ; *Herpesviridae ; *Nucleic Acids ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism ; Mammals/metabolism ; }, abstract = {Host control over infectious disease relies on the ability of cells in multicellular organisms to detect and defend against pathogens to prevent disease. Evolution affords mammals with a wide variety of independent immune mechanisms to control or eliminate invading infectious agents. Many pathogens acquire functions to deflect these immune mechanisms and promote infection. Following successful invasion of a host, cell autonomous signaling pathways drive the production of inflammatory cytokines, deployment of restriction factors and induction of cell death. Combined, these innate immune mechanisms attract dendritic cells, neutrophils and macrophages as well as innate lymphoid cells such as natural killer cells that all help control infection. Eventually, the development of adaptive pathogen-specific immunity clears infection and provides immune memory of the encounter. For obligate intracellular pathogens such as viruses, diverse cell death pathways make a pivotal contribution to early control by eliminating host cells before progeny are produced. Pro-apoptotic caspase-8 activity (along with caspase-10 in humans) executes extrinsic apoptosis, a nonlytic form of cell death triggered by TNF family death receptors (DRs). Over the past two decades, alternate extrinsic apoptosis and necroptosis outcomes have been described. Programmed necrosis, or necroptosis, occurs when receptor interacting protein kinase 3 (RIPK3) activates mixed lineage kinase-like (MLKL), causing cell leakage. Thus, activation of DRs, toll-like receptors (TLRs) or pathogen sensor Z-nucleic acid binding protein 1 (ZBP1) initiates apoptosis as well as necroptosis if not blocked by virus-encoded inhibitors. Mammalian cell death pathways are blocked by herpesvirus- and poxvirus-encoded cell death suppressors. Growing evidence has revealed the importance of Z-nucleic acid sensor, ZBP1, in the cell autonomous recognition of both DNA and RNA virus infection. This volume will explore the detente between viruses and cells to manage death machinery and avoid elimination to support dissemination within the host animal.}, } @article {pmid37552891, year = {2023}, author = {Goehring, L and Huang, TT and Smith, DJ}, title = {Transcription-Replication Conflicts as a Source of Genome Instability.}, journal = {Annual review of genetics}, volume = {57}, number = {}, pages = {157-179}, pmid = {37552891}, issn = {1545-2948}, support = {R01 ES031658/ES/NIEHS NIH HHS/United States ; R35 GM134918/GM/NIGMS NIH HHS/United States ; R35 GM139610/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Transcription, Genetic ; *DNA Replication/genetics ; Genomic Instability/genetics ; Eukaryota/genetics ; DNA Damage/genetics ; Mammals ; }, abstract = {Transcription and replication both require large macromolecular complexes to act on a DNA template, yet these machineries cannot simultaneously act on the same DNA sequence. Conflicts between the replication and transcription machineries (transcription-replication conflicts, or TRCs) are widespread in both prokaryotes and eukaryotes and have the capacity to both cause DNA damage and compromise complete, faithful replication of the genome. This review will highlight recent studies investigating the genomic locations of TRCs and the mechanisms by which they may be prevented, mitigated, or resolved. We address work from both model organisms and mammalian systems but predominantly focus on multicellular eukaryotes owing to the additional complexities inherent in the coordination of replication and transcription in the context of cell type-specific gene expression and higher-order chromatin organization.}, } @article {pmid37540742, year = {2023}, author = {Sartor, F and Xu, X and Popp, T and Dodd, AN and Kovács, ÁT and Merrow, M}, title = {The circadian clock of the bacterium B. subtilis evokes properties of complex, multicellular circadian systems.}, journal = {Science advances}, volume = {9}, number = {31}, pages = {eadh1308}, pmid = {37540742}, issn = {2375-2548}, mesh = {*Circadian Clocks ; Bacillus subtilis ; Circadian Rhythm ; Light ; Eukaryota ; }, abstract = {Circadian clocks are pervasive throughout nature, yet only recently has this adaptive regulatory program been described in nonphotosynthetic bacteria. Here, we describe an inherent complexity in the Bacillus subtilis circadian clock. We find that B. subtilis entrains to blue and red light and that circadian entrainment is separable from masking through fluence titration and frequency demultiplication protocols. We identify circadian rhythmicity in constant light, consistent with the Aschoff's rule, and entrainment aftereffects, both of which are properties described for eukaryotic circadian clocks. We report that circadian rhythms occur in wild isolates of this prokaryote, thus establishing them as a general property of this species, and that its circadian system responds to the environment in a complex fashion that is consistent with multicellular eukaryotic circadian systems.}, } @article {pmid37511419, year = {2023}, author = {Erenpreisa, J and Vainshelbaum, NM and Lazovska, M and Karklins, R and Salmina, K and Zayakin, P and Rumnieks, F and Inashkina, I and Pjanova, D and Erenpreiss, J}, title = {The Price of Human Evolution: Cancer-Testis Antigens, the Decline in Male Fertility and the Increase in Cancer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511419}, issn = {1422-0067}, mesh = {Pregnancy ; Animals ; Humans ; Male ; Female ; *Testis/metabolism ; Placenta ; Spermatogenesis/genetics ; Reproduction ; *Neoplasms/genetics/metabolism ; Mammals ; Polyploidy ; Fertility/genetics ; }, abstract = {The increasing frequency of general and particularly male cancer coupled with the reduction in male fertility seen worldwide motivated us to seek a potential evolutionary link between these two phenomena, concerning the reproductive transcriptional modules observed in cancer and the expression of cancer-testis antigens (CTA). The phylostratigraphy analysis of the human genome allowed us to link the early evolutionary origin of cancer via the reproductive life cycles of the unicellulars and early multicellulars, potentially driving soma-germ transition, female meiosis, and the parthenogenesis of polyploid giant cancer cells (PGCCs), with the expansion of the CTA multi-families, very late during their evolution. CTA adaptation was aided by retrovirus domestication in the unstable genomes of mammals, for protecting male fertility in stress conditions, particularly that of humans, as compensation for the energy consumption of a large complex brain which also exploited retrotransposition. We found that the early and late evolutionary branches of human cancer are united by the immunity-proto-placental network, which evolved in the Cambrian and shares stress regulators with the finely-tuned sex determination system. We further propose that social stress and endocrine disruption caused by environmental pollution with organic materials, which alter sex determination in male foetuses and further spermatogenesis in adults, bias the development of PGCC-parthenogenetic cancer by default.}, } @article {pmid37498572, year = {2023}, author = {Ma, X and Shi, X and Wang, Q and Zhao, M and Zhang, Z and Zhong, B}, title = {A Reinvestigation of Multiple Independent Evolution and Triassic-Jurassic Origins of Multicellular Volvocine Algae.}, journal = {Genome biology and evolution}, volume = {15}, number = {8}, pages = {}, pmid = {37498572}, issn = {1759-6653}, mesh = {*Chlorophyta/genetics ; *Phylogeny ; Time Factors ; Calibration ; }, abstract = {The evolution of multicellular organisms is considered to be a major evolutionary transition, profoundly affecting the ecology and evolution of nearly all life on earth. The volvocine algae, a unique clade of chlorophytes with diverse cell morphology, provide an appealing model for investigating the evolution of multicellularity and development. However, the phylogenetic relationship and timescale of the volvocine algae are not fully resolved. Here, we use extensive taxon and gene sampling to reconstruct the phylogeny of the volvocine algae. Our results support that the colonial volvocine algae are not monophyletic group and multicellularity independently evolve at least twice in the volvocine algae, once in Tetrabaenaceae and another in the Goniaceae + Volvocaceae. The simulation analyses suggest that incomplete lineage sorting is a major factor for the tree topology discrepancy, which imply that the multispecies coalescent model better fits the data used in this study. The coalescent-based species tree supports that the Goniaceae is monophyletic and Crucicarteria is the earliest diverging lineage, followed by Hafniomonas and Radicarteria within the Volvocales. By considering the multiple uncertainties in divergence time estimation, the dating analyses indicate that the volvocine algae occurred during the Cryogenian to Ediacaran (696.6-551.1 Ma) and multicellularity in the volvocine algae originated from the Triassic to Jurassic. Our phylogeny and timeline provide an evolutionary framework for studying the evolution of key traits and the origin of multicellularity in the volvocine algae.}, } @article {pmid37494396, year = {2023}, author = {Fichman, Y and Rowland, L and Oliver, MJ and Mittler, R}, title = {ROS are evolutionary conserved cell-to-cell stress signals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {31}, pages = {e2305496120}, pmid = {37494396}, issn = {1091-6490}, support = {R01 GM111364/GM/NIGMS NIH HHS/United States ; GM111364/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Reactive Oxygen Species ; *Hydrogen Peroxide ; *Signal Transduction ; Cell Communication ; Plants ; Mammals ; }, abstract = {Cell-to-cell communication is fundamental to multicellular organisms and unicellular organisms living in a microbiome. It is thought to have evolved as a stress- or quorum-sensing mechanism in unicellular organisms. A unique cell-to-cell communication mechanism that uses reactive oxygen species (ROS) as a signal (termed the "ROS wave") was identified in flowering plants. This process is essential for systemic signaling and plant acclimation to stress and can spread from a small group of cells to the entire plant within minutes. Whether a similar signaling process is found in other organisms is however unknown. Here, we report that the ROS wave can be found in unicellular algae, amoeba, ferns, mosses, mammalian cells, and isolated hearts. We further show that this process can be triggered in unicellular and multicellular organisms by a local stress or H2O2 treatment and blocked by the application of catalase or NADPH oxidase inhibitors and that in unicellular algae it communicates important stress-response signals between cells. Taken together, our findings suggest that an active process of cell-to-cell ROS signaling, like the ROS wave, evolved before unicellular and multicellular organisms diverged. This mechanism could have communicated an environmental stress signal between cells and coordinated the acclimation response of many different cells living in a community. The finding of a signaling process, like the ROS wave, in mammalian cells further contributes to our understanding of different diseases and could impact the development of drugs that target for example cancer or heart disease.}, } @article {pmid37481773, year = {2024}, author = {Evans, JA and Schwartz, WJ}, title = {On the origin and evolution of the dual oscillator model underlying the photoperiodic clockwork in the suprachiasmatic nucleus.}, journal = {Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology}, volume = {210}, number = {4}, pages = {503-511}, pmid = {37481773}, issn = {1432-1351}, support = {R01 GM143545/GM/NIGMS NIH HHS/United States ; R01GM143545/NH/NIH HHS/United States ; R01GM143545/NH/NIH HHS/United States ; }, mesh = {*Suprachiasmatic Nucleus/physiology ; Animals ; *Photoperiod ; *Circadian Clocks/physiology ; Humans ; Circadian Rhythm/physiology ; Biological Evolution ; Models, Biological ; }, abstract = {Decades have now passed since Colin Pittendrigh first proposed a model of a circadian clock composed of two coupled oscillators, individually responsive to the rising and setting sun, as a flexible solution to the challenge of behavioral and physiological adaptation to the changing seasons. The elegance and predictive power of this postulation has stimulated laboratories around the world in searches to identify and localize such hypothesized evening and morning oscillators, or sets of oscillators, in insects, rodents, and humans, with experimental designs and approaches keeping pace over the years with technological advances in biology and neuroscience. Here, we recount the conceptual origin and highlight the subsequent evolution of this dual oscillator model for the circadian clock in the mammalian suprachiasmatic nucleus; and how, despite our increasingly sophisticated view of this multicellular pacemaker, Pittendrigh's binary conception has remained influential in our clock models and metaphors.}, } @article {pmid37481138, year = {2023}, author = {Corallo, D and Dalla Vecchia, M and Lazic, D and Taschner-Mandl, S and Biffi, A and Aveic, S}, title = {The molecular basis of tumor metastasis and current approaches to decode targeted migration-promoting events in pediatric neuroblastoma.}, journal = {Biochemical pharmacology}, volume = {215}, number = {}, pages = {115696}, doi = {10.1016/j.bcp.2023.115696}, pmid = {37481138}, issn = {1873-2968}, support = {I 4162/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Humans ; *Neuroblastoma/drug therapy/genetics/pathology ; *Neoplasm Metastasis ; }, abstract = {Cell motility is a crucial biological process that plays a critical role in the development of multicellular organisms and is essential for tissue formation and regeneration. However, uncontrolled cell motility can lead to the development of various diseases, including neoplasms. In this review, we discuss recent advances in the discovery of regulatory mechanisms underlying the metastatic spread of neuroblastoma, a solid pediatric tumor that originates in the embryonic migratory cells of the neural crest. The highly motile phenotype of metastatic neuroblastoma cells requires targeting of intracellular and extracellular processes, that, if affected, would be helpful for the treatment of high-risk patients with neuroblastoma, for whom current therapies remain inadequate. Development of new potentially migration-inhibiting compounds and standardized preclinical approaches for the selection of anti-metastatic drugs in neuroblastoma will also be discussed.}, } @article {pmid37475643, year = {2023}, author = {Kato, D and Aoyama, Y and Nishida, K and Takahashi, Y and Sakamoto, T and Takeda, I and Tatematsu, T and Go, S and Saito, Y and Kunishima, S and Cheng, J and Hou, L and Tachibana, Y and Sugio, S and Kondo, R and Eto, F and Sato, S and Moorhouse, AJ and Yao, I and Kadomatsu, K and Setou, M and Wake, H}, title = {Regulation of lipid synthesis in myelin modulates neural activity and is required for motor learning.}, journal = {Glia}, volume = {71}, number = {11}, pages = {2591-2608}, doi = {10.1002/glia.24441}, pmid = {37475643}, issn = {1098-1136}, mesh = {Mice ; Animals ; *Myelin Sheath/metabolism ; *Galactosylceramides/metabolism ; Axons/metabolism ; Neurons/metabolism ; Oligodendroglia/physiology ; }, abstract = {Brain function relies on both rapid electrical communication in neural circuitry and appropriate patterns or synchrony of neural activity. Rapid communication between neurons is facilitated by wrapping nerve axons with insulation by a myelin sheath composed largely of different lipids. Recent evidence has indicated that the extent of myelination of nerve axons can adapt based on neural activity levels and this adaptive myelination is associated with improved learning of motor tasks, suggesting such plasticity may enhance effective learning. In this study, we examined whether another aspect of myelin plasticity-changes in myelin lipid synthesis and composition-may also be associated with motor learning. We combined a motor learning task in mice with in vivo two-photon imaging of neural activity in the primary motor cortex (M1) to distinguish early and late stages of learning and then probed levels of some key myelin lipids using mass spectrometry analysis. Sphingomyelin levels were elevated in the early stage of motor learning while galactosylceramide levels were elevated in the middle and late stages of motor learning, and these changes were correlated across individual mice with both learning performance and neural activity changes. Targeted inhibition of oligodendrocyte-specific galactosyltransferase expression, the enzyme that synthesizes myelin galactosylceramide, impaired motor learning. Our results suggest regulation of myelin lipid composition could be a novel facet of myelin adaptations associated with learning.}, } @article {pmid37475165, year = {2023}, author = {Lamża, Ł}, title = {Diversity of 'simple' multicellular eukaryotes: 45 independent cases and six types of multicellularity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {98}, number = {6}, pages = {2188-2209}, doi = {10.1111/brv.13001}, pmid = {37475165}, issn = {1469-185X}, mesh = {Phylogeny ; *Eukaryota/genetics ; *Fungi ; Biological Evolution ; }, abstract = {Multicellularity evolved multiple times in the history of life, with most reviewers agreeing that it appeared at least 20 times in eukaryotes. However, a specific list of multicellular eukaryotes with clear criteria for inclusion has not yet been published. Herein, an updated critical review of eukaryotic multicellularity is presented, based on current understanding of eukaryotic phylogeny and new discoveries in microbiology, phycology and mycology. As a result, 45 independent multicellular lineages are identified that fall into six distinct types. Functional criteria, as distinct from a purely topological definition of a cell, are introduced to bring uniformity and clarity to the existing definitions of terms such as colony, multicellularity, thallus or plasmodium. The category of clonal multicellularity is expanded to include: (i) septated multinucleated thalli found in Pseudofungi and early-branching Fungi such as Chytridiomycota and Blastocladiomycota; and (ii) multicellular reproductive structures formed by plasmotomy in intracellular parasites such as Phytomyxea. Furthermore, (iii) endogeneous budding, as found in Paramyxida, is described as a form of multicellularity. The best-known case of clonal multicellularity, i.e. (iv) non-separation of cells after cell division, as known from Metazoa and Ochrophyta, is also discussed. The category of aggregative multicellularity is expanded to include not only (v) pseudoplasmodial forms, such a sorocarp-forming Acrasida, but also (vi) meroplasmodial organisms, such as members of Variosea or Filoreta. A common set of topological, geometric, genetic and life-cycle criteria are presented that form a coherent, philosophically sound framework for discussing multicellularity. A possibility of a seventh type of multicellularity is discussed, that of multi-species superorganisms formed by protists with obligatory bacterial symbionts, such as some members of Oxymonada or Parabasalia. Its inclusion is dependent on the philosophical stance taken towards the concepts of individuality and organism in biology. Taxa that merit special attention are identified, such as colonial Centrohelea, and a new speculative form of multicellularity, possibly present in some reticulopodial amoebae, is briefly described. Because of insufficient phylogenetic and morphological data, not all lineages could be unequivocally identified, and the true total number of all multicellular eukaryotic lineages is therefore higher, likely close to a hundred.}, } @article {pmid37468829, year = {2023}, author = {Vroomans, RMA and Colizzi, ES}, title = {Evolution of selfish multicellularity: collective organisation of individual spatio-temporal regulatory strategies.}, journal = {BMC ecology and evolution}, volume = {23}, number = {1}, pages = {35}, pmid = {37468829}, issn = {2730-7182}, mesh = {Animals ; *Biological Evolution ; *Reproduction ; Cell Differentiation ; }, abstract = {BACKGROUND: The unicellular ancestors of modern-day multicellular organisms were remarkably complex. They had an extensive set of regulatory and signalling genes, an intricate life cycle and could change their behaviour in response to environmental changes. At the transition to multicellularity, some of these behaviours were co-opted to organise the development of the nascent multicellular organism. Here, we focus on the transition to multicellularity before the evolution of stable cell differentiation, to reveal how the emergence of clusters affects the evolution of cell behaviour.

RESULTS: We construct a computational model of a population of cells that can evolve the regulation of their behavioural state - either division or migration - and study both a unicellular and a multicellular context. Cells compete for reproduction and for resources to survive in a seasonally changing environment. We find that the evolution of multicellularity strongly determines the co-evolution of cell behaviour, by altering the competition dynamics between cells. When adhesion cannot evolve, cells compete for survival by rapidly migrating towards resources before dividing. When adhesion evolves, emergent collective migration alleviates the pressure on individual cells to reach resources. This allows individual cells to maximise their own replication. Migrating adhesive clusters display striking patterns of spatio-temporal cell state changes that visually resemble animal development.

CONCLUSIONS: Our model demonstrates how emergent selection pressures at the onset of multicellularity can drive the evolution of cellular behaviour to give rise to developmental patterns.}, } @article {pmid37445995, year = {2023}, author = {Endres, K and Friedland, K}, title = {Talk to Me-Interplay between Mitochondria and Microbiota in Aging.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37445995}, issn = {1422-0067}, mesh = {*Gastrointestinal Microbiome/physiology ; *Microbiota ; Mitochondria ; Bacteria/metabolism ; }, abstract = {The existence of mitochondria in eukaryotic host cells as a remnant of former microbial organisms has been widely accepted, as has their fundamental role in several diseases and physiological aging. In recent years, it has become clear that the health, aging, and life span of multicellular hosts are also highly dependent on the still-residing microbiota, e.g., those within the intestinal system. Due to the common evolutionary origin of mitochondria and these microbial commensals, it is intriguing to investigate if there might be a crosstalk based on preserved common properties. In the light of rising knowledge on the gut-brain axis, such crosstalk might severely affect brain homeostasis in aging, as neuronal tissue has a high energy demand and low tolerance for according functional decline. In this review, we summarize what is known about the impact of both mitochondria and the microbiome on the host's aging process and what is known about the aging of both entities. For a long time, bacteria were assumed to be immortal; however, recent evidence indicates their aging and similar observations have been made for mitochondria. Finally, we present pathways by which mitochondria are affected by microbiota and give information about therapeutic anti-aging approaches that are based on current knowledge.}, } @article {pmid37438660, year = {2023}, author = {Huang, L and Tu, Z and Wei, L and Sun, W and Wang, Y and Bi, S and He, F and Du, L and Chen, J and Kzhyshkowska, J and Wang, H and Chen, D and Zhang, S}, title = {Generating Functional Multicellular Organoids from Human Placenta Villi.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {10}, number = {26}, pages = {e2301565}, pmid = {37438660}, issn = {2198-3844}, support = {2022YFC2702501//National Key Research and Development Program of China/ ; 2022YFC2704500//National Key Research and Development Program of China/ ; 81830045//Key Program of National Natural Science Foundation of China/ ; 81071652//National Natural Science Foundation of China/ ; 82171666//National Natural Science Foundation of China/ ; 82201861//National Natural Science Foundation of China/ ; 82271695//National Natural Science Foundation of China/ ; M-0586//Mobility program of Sino German Center/ ; 202201020573//Science and Technology Program of Guangzhou/ ; 2023A03J0378//Science and Technology Program of Guangzhou/ ; 2021B1515120070//China Guangdong Basic and Applied Basic Research Fund/ ; }, mesh = {Pregnancy ; Female ; Humans ; *Placenta/metabolism ; *Chorionic Villi/metabolism/pathology ; Placentation ; Trophoblasts/metabolism ; Organoids/metabolism ; }, abstract = {The interaction between trophoblasts, stroma cells, and immune cells at the maternal-fetal interface constitutes the functional units of the placenta, which is crucial for successful pregnancy outcomes. However, the investigation of this intricate interplay is restricted due to the absence of efficient experimental models. To address this challenge, a robust, reliable methodology for generating placenta villi organoids (PVOs) from early, late, or diseased pregnancies using air-liquid surface culture is developed. PVOs contain cytotrophoblasts that can self-renew and differentiate directly, along with stromal elements that retain native immune cells. Analysis of scRNA sequencing and WES data reveals that PVOs faithfully recapitulate the cellular components and genetic alterations of the corresponding source tissue. Additionally, PVOs derived from patients with preeclampsia exhibit specific pathological features such as inflammation, antiangiogenic imbalance, and decreased syncytin expression. The PVO-based propagation of primary placenta villi should enable a deeper investigation of placenta development and exploration of the underlying pathogenesis and therapeutics of placenta-originated diseases.}, } @article {pmid37436957, year = {2023}, author = {Geng, S and Hamaji, T and Ferris, PJ and Gao, M and Nishimura, Y and Umen, J}, title = {A conserved RWP-RK transcription factor VSR1 controls gametic differentiation in volvocine algae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {29}, pages = {e2305099120}, pmid = {37436957}, issn = {1091-6490}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; R01GM078376/NH/NIH HHS/United States ; }, mesh = {*Seeds ; Sex ; Reproduction ; Germ Cells ; Spermatozoa ; Biotin ; *Chlamydomonas ; }, abstract = {Volvocine green algae are a model for understanding the evolution of mating types and sexes. They are facultatively sexual, with gametic differentiation occurring in response to nitrogen starvation (-N) in most genera and to sex inducer hormone in Volvox. The conserved RWP-RK family transcription factor (TF) MID is encoded by the minus mating-type locus or male sex-determining region of heterothallic volvocine species and dominantly determines minus or male gametic differentiation. However, the factor(s) responsible for establishing the default plus or female differentiation programs have remained elusive. We performed a phylo-transcriptomic screen for autosomal RWP-RK TFs induced during gametogenesis in unicellular isogamous Chlamydomonas reinhardtii (Chlamydomonas) and in multicellular oogamous Volvox carteri (Volvox) and identified a single conserved ortho-group we named Volvocine Sex Regulator 1 (VSR1). Chlamydomonas vsr1 mutants of either mating type failed to mate and could not induce expression of key mating-type-specific genes. Similarly, Volvox vsr1 mutants in either sex could initiate sexual embryogenesis, but the presumptive eggs or androgonidia (sperm packet precursors) were infertile and unable to express key sex-specific genes. Yeast two-hybrid assays identified a conserved domain in VSR1 capable of self-interaction or interaction with the conserved N terminal domain of MID. In vivo coimmunoprecipitation experiments demonstrated association of VSR1 and MID in both Chlamydomonas and Volvox. These data support a new model for volvocine sexual differentiation where VSR1 homodimers activate expression of plus/female gamete-specific-genes, but when MID is present, MID-VSR1 heterodimers are preferentially formed and activate minus/male gamete-specific-genes.}, } @article {pmid37436868, year = {2023}, author = {Mondal, A and Bansal, MS}, title = {Generalizing the Domain-Gene-Species Reconciliation Framework to Microbial Genes and Domains.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {20}, number = {6}, pages = {3511-3522}, doi = {10.1109/TCBB.2023.3294480}, pmid = {37436868}, issn = {1557-9964}, mesh = {*Gene Duplication ; *Evolution, Molecular ; Phylogeny ; Algorithms ; Genes, Microbial ; Gene Transfer, Horizontal/genetics ; Models, Genetic ; }, abstract = {Protein domains play an important role in the function and evolution of many gene families. Previous studies have shown that domains are frequently lost or gained during gene family evolution. Yet, most computational approaches for studying gene family evolution do not account for domain-level evolution within genes. To address this limitation, a new three-level reconciliation framework, called the Domain-Gene-Species (DGS) reconciliation model, has been recently developed to simultaneously model the evolution of a domain family inside one or more gene families and the evolution of those gene families inside a species tree. However, the existing model applies only to multi-cellular eukaryotes where horizontal gene transfer is negligible. In this work, we generalize the existing DGS reconciliation model by allowing for the spread of genes and domains across species boundaries through horizontal transfer. We show that the problem of computing optimal generalized DGS reconciliations, though NP-hard, is approximable to within a constant factor, where the specific approximation ratio depends on the "event costs" used. We provide two different approximation algorithms for the problem and demonstrate the impact of the generalized framework using both simulated and real biological data. Our results show that our new algorithms result in highly accurate reconstructions of domain family evolution for microbes.}, } @article {pmid37409939, year = {2023}, author = {Aanen, DK and van 't Padje, A and Auxier, B}, title = {Longevity of Fungal Mycelia and Nuclear Quality Checks: a New Hypothesis for the Role of Clamp Connections in Dikaryons.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {87}, number = {3}, pages = {e0002221}, pmid = {37409939}, issn = {1098-5557}, mesh = {*Mycelium ; *Hyphae/genetics ; Fungi ; }, abstract = {This paper addresses the stability of mycelial growth in fungi and differences between ascomycetes and basidiomycetes. Starting with general evolutionary theories of multicellularity and the role of sex, we then discuss individuality in fungi. Recent research has demonstrated the deleterious consequences of nucleus-level selection in fungal mycelia, favoring cheaters with a nucleus-level benefit during spore formation but a negative effect on mycelium-level fitness. Cheaters appear to generally be loss-of-fusion (LOF) mutants, with a higher propensity to form aerial hyphae developing into asexual spores. Since LOF mutants rely on heterokaryosis with wild-type nuclei, we argue that regular single-spore bottlenecks can efficiently select against such cheater mutants. We then zoom in on ecological differences between ascomycetes being typically fast-growing but short-lived with frequent asexual-spore bottlenecks and basidiomycetes being generally slow-growing but long-lived and usually without asexual-spore bottlenecks. We argue that these life history differences have coevolved with stricter nuclear quality checks in basidiomycetes. Specifically, we propose a new function for clamp connections, structures formed during the sexual stage in ascomycetes and basidiomycetes but during somatic growth only in basidiomycete dikaryons. During dikaryon cell division, the two haploid nuclei temporarily enter a monokaryotic phase, by alternatingly entering a retrograde-growing clamp cell, which subsequently fuses with the subapical cell to recover the dikaryotic cell. We hypothesize that clamp connections act as screening devices for nuclear quality, with both nuclei continuously testing each other for fusion ability, a test that LOF mutants will fail. By linking differences in longevity of the mycelial phase to ecology and stringency of nuclear quality checks, we propose that mycelia have a constant and low lifetime cheating risk, irrespective of their size and longevity.}, } @article {pmid37406343, year = {2023}, author = {Ruiz-Trillo, I and Kin, K and Casacuberta, E}, title = {The Origin of Metazoan Multicellularity: A Potential Microbial Black Swan Event.}, journal = {Annual review of microbiology}, volume = {77}, number = {}, pages = {499-516}, doi = {10.1146/annurev-micro-032421-120023}, pmid = {37406343}, issn = {1545-3251}, mesh = {Animals ; Retrospective Studies ; *Biological Evolution ; }, abstract = {The emergence of animals from their unicellular ancestors is a major evolutionary event. Thanks to the study of diverse close unicellular relatives of animals, we now have a better grasp of what the unicellular ancestor of animals was like. However, it is unclear how that unicellular ancestor of animals became the first animals. To explain this transition, two popular theories, the choanoblastaea and the synzoospore, have been proposed. We will revise and expose the flaws in these two theories while showing that, due to the limits of our current knowledge, the origin of animals is a biological black swan event. As such, the origin of animals defies retrospective explanations. Therefore, we should be extra careful not to fall for confirmation biases based on few data and, instead, embrace this uncertainty and be open to alternative scenarios. With the aim to broaden the potential explanations on how animals emerged, we here propose two novel and alternative scenarios. In any case, to find the answer to how animals evolved, additional data will be required, as will the hunt for microscopic creatures that are closely related to animals but have not yet been sampled and studied.}, } @article {pmid37401921, year = {2023}, author = {Stevenson, ZC and Moerdyk-Schauwecker, MJ and Banse, SA and Patel, DS and Lu, H and Phillips, PC}, title = {High-throughput library transgenesis in Caenorhabditis elegans via Transgenic Arrays Resulting in Diversity of Integrated Sequences (TARDIS).}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37401921}, issn = {2050-084X}, support = {R01AG056436/NH/NIH HHS/United States ; R35GM131838/NH/NIH HHS/United States ; R35 GM131838/GM/NIGMS NIH HHS/United States ; R01 AG056436/AG/NIA NIH HHS/United States ; T32 GM007413/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; *Caenorhabditis elegans/genetics ; *Gene Library ; *Gene Transfer Techniques ; *Transgenes/genetics ; DNA Barcoding, Taxonomic ; Genetic Variation ; Promoter Regions, Genetic/genetics ; }, abstract = {High-throughput transgenesis using synthetic DNA libraries is a powerful method for systematically exploring genetic function. Diverse synthesized libraries have been used for protein engineering, identification of protein-protein interactions, characterization of promoter libraries, developmental and evolutionary lineage tracking, and various other exploratory assays. However, the need for library transgenesis has effectively restricted these approaches to single-cell models. Here, we present Transgenic Arrays Resulting in Diversity of Integrated Sequences (TARDIS), a simple yet powerful approach to large-scale transgenesis that overcomes typical limitations encountered in multicellular systems. TARDIS splits the transgenesis process into a two-step process: creation of individuals carrying experimentally introduced sequence libraries, followed by inducible extraction and integration of individual sequences/library components from the larger library cassette into engineered genomic sites. Thus, transformation of a single individual, followed by lineage expansion and functional transgenesis, gives rise to thousands of genetically unique transgenic individuals. We demonstrate the power of this system using engineered, split selectable TARDIS sites in Caenorhabditis elegans to generate (1) a large set of individually barcoded lineages and (2) transcriptional reporter lines from predefined promoter libraries. We find that this approach increases transformation yields up to approximately 1000-fold over current single-step methods. While we demonstrate the utility of TARDIS using C. elegans, in principle the process is adaptable to any system where experimentally generated genomic loci landing pads and diverse, heritable DNA elements can be generated.}, } @article {pmid37384647, year = {2023}, author = {Kapsetaki, SE and Fortunato, A and Compton, Z and Rupp, SM and Nour, Z and Riggs-Davis, S and Stephenson, D and Duke, EG and Boddy, AM and Harrison, TM and Maley, CC and Aktipis, A}, title = {Is chimerism associated with cancer across the tree of life?.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0287901}, pmid = {37384647}, issn = {1932-6203}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; T32 CA272303/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; R21 CA257980/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Chimerism ; *Neoplasms/genetics ; Mammals ; }, abstract = {Chimerism is a widespread phenomenon across the tree of life. It is defined as a multicellular organism composed of cells from other genetically distinct entities. This ability to 'tolerate' non-self cells may be linked to susceptibility to diseases like cancer. Here we test whether chimerism is associated with cancers across obligately multicellular organisms in the tree of life. We classified 12 obligately multicellular taxa from lowest to highest chimerism levels based on the existing literature on the presence of chimerism in these species. We then tested for associations of chimerism with tumour invasiveness, neoplasia (benign or malignant) prevalence and malignancy prevalence in 11 terrestrial mammalian species. We found that taxa with higher levels of chimerism have higher tumour invasiveness, though there was no association between malignancy or neoplasia and chimerism among mammals. This suggests that there may be an important biological relationship between chimerism and susceptibility to tissue invasion by cancerous cells. Studying chimerism might help us identify mechanisms underlying invasive cancers and also could provide insights into the detection and management of emerging transmissible cancers.}, } @article {pmid37384391, year = {2023}, author = {Römling, U and Cao, LY and Bai, FW}, title = {Evolution of cyclic di-GMP signalling on a short and long term time scale.}, journal = {Microbiology (Reading, England)}, volume = {169}, number = {6}, pages = {}, pmid = {37384391}, issn = {1465-2080}, mesh = {Humans ; *Signal Transduction ; *Second Messenger Systems ; Amino Acid Substitution ; Biofilms ; Gene Transfer, Horizontal ; }, abstract = {Diversifying radiation of domain families within specific lineages of life indicates the importance of their functionality for the organisms. The foundation for the diversifying radiation of the cyclic di-GMP signalling network that occurred within the bacterial kingdom is most likely based in the outmost adaptability, flexibility and plasticity of the system. Integrative sensing of multiple diverse extra- and intracellular signals is made possible by the N-terminal sensory domains of the modular cyclic di-GMP turnover proteins, mutations in the protein scaffolds and subsequent signal reception by diverse receptors, which eventually rewires opposite host-associated as well as environmental life styles including parallel regulated target outputs. Natural, laboratory and microcosm derived microbial variants often with an altered multicellular biofilm behaviour as reading output demonstrated single amino acid substitutions to substantially alter catalytic activity including substrate specificity. Truncations and domain swapping of cyclic di-GMP signalling genes and horizontal gene transfer suggest rewiring of the network. Presence of cyclic di-GMP signalling genes on horizontally transferable elements in particular observed in extreme acidophilic bacteria indicates that cyclic di-GMP signalling and biofilm components are under selective pressure in these types of environments. On a short and long term evolutionary scale, within a species and in families within bacterial orders, respectively, the cyclic di-GMP signalling network can also rapidly disappear. To investigate variability of the cyclic di-GMP signalling system on various levels will give clues about evolutionary forces and discover novel physiological and metabolic pathways affected by this intriguing second messenger signalling system.}, } @article {pmid37382119, year = {2023}, author = {Saritas, T}, title = {The use of tissue clearing to study renal transport mechanisms and kidney remodelling.}, journal = {Current opinion in nephrology and hypertension}, volume = {32}, number = {5}, pages = {458-466}, doi = {10.1097/MNH.0000000000000904}, pmid = {37382119}, issn = {1473-6543}, mesh = {Animals ; Humans ; *Imaging, Three-Dimensional/methods ; *Kidney ; }, abstract = {PURPOSE OF REVIEW: Tissue clearing enables examination of biological structures at subcellular resolution in three dimensions. It uncovered the spatial and temporal plasticity of multicellular kidney structures that occur during homeostatic stress. This article will review the recent development in tissue clearing protocols and how it facilitated the study of renal transport mechanisms and remodelling of the kidney.

RECENT FINDINGS: Tissue clearing methods have evolved from primarily labelling proteins in thin tissue or individual organs to visualizing both RNA and protein simultaneously in whole animals or human organs. The use of small antibody fragments and innovative imaging techniques improved immunolabelling and resolution. These advances opened up new avenues for studying organ crosstalk and diseases that affect multiple parts of the organism. Accumulating evidence suggests that tubule remodelling can occur rapidly in response to homeostatic stress or injury, allowing for adjustments in the quantitative expression of renal transporters. Tissue clearing helped to better understand the development of tubule cystogenesis, renal hypertension and salt wasting syndromes, and revealed potential progenitor cells in the kidney.

SUMMARY: The continued evolution and improvement of tissue clearing methods can help to gain deep biological insights into the structure and function of the kidney, which will have clinical implications.}, } @article {pmid37379342, year = {2023}, author = {Zare, M and Mirhoseini, SZ and Ghovvati, S and Yakhkeshi, S and Hesaraki, M and Barati, M and Sayyahpour, FA and Baharvand, H and Hassani, SN}, title = {The constitutively active pSMAD2/3 relatively improves the proliferation of chicken primordial germ cells.}, journal = {Molecular reproduction and development}, volume = {90}, number = {6}, pages = {339-357}, doi = {10.1002/mrd.23689}, pmid = {37379342}, issn = {1098-2795}, mesh = {Animals ; *Chickens/metabolism ; *Transforming Growth Factor beta/metabolism ; Transcription Factors/metabolism ; Germ Cells ; Cell Proliferation ; Cells, Cultured ; }, abstract = {In many multicellular organisms, mature gametes originate from primordial germ cells (PGCs). Improvements in the culture of PGCs are important not only for developmental biology research, but also for preserving endangered species, and for genome editing and transgenic animal technologies. SMAD2/3 appear to be powerful regulators of gene expression; however, their potential positive impact on the regulation of PGC proliferation has not been taken into consideration. Here, the effect of TGF-β signaling as the upstream activator of SMAD2/3 transcription factors was evaluated on chicken PGCs' proliferation. For this, chicken PGCs at stages 26-28 Hamburger-Hamilton were obtained from the embryonic gonadal regions and cultured on different feeders or feeder-free substrates. The results showed that TGF-β signaling agonists (IDE1 and Activin-A) improved PGC proliferation to some extent while treatment with SB431542, the antagonist of TGF-β, disrupted PGCs' proliferation. However, the transfection of PGCs with constitutively active SMAD2/3 (SMAD2/3CA) resulted in improved PGC proliferation for more than 5 weeks. The results confirmed the interactions between overexpressed SMAD2/3CA and pluripotency-associated genes NANOG, OCT4, and SOX2. According to the results, the application of SMAD2/3CA could represent a step toward achieving an efficient expansion of avian PGCs.}, } @article {pmid37353784, year = {2023}, author = {Fang, H and Sun, Q and Zhou, J and Zhang, H and Song, Q and Zhang, H and Yu, G and Guo, Y and Huang, C and Mou, Y and Jia, C and Song, Y and Liu, A and Song, K and Lu, C and Tian, R and Wei, S and Yang, D and Chen, Y and Li, T and Wang, K and Yu, Y and Lv, Y and Mo, K and Sun, P and Yu, X and Song, X}, title = {m[6]A methylation reader IGF2BP2 activates endothelial cells to promote angiogenesis and metastasis of lung adenocarcinoma.}, journal = {Molecular cancer}, volume = {22}, number = {1}, pages = {99}, pmid = {37353784}, issn = {1476-4598}, mesh = {Humans ; Methylation ; Ecosystem ; Endothelial Cells ; Phosphatidylinositol 3-Kinases ; Neoplasm Recurrence, Local ; *Adenocarcinoma of Lung/genetics ; *Lung Neoplasms/genetics ; Tumor Microenvironment ; RNA-Binding Proteins/genetics ; }, abstract = {BACKGROUND: Lung adenocarcinoma (LUAD) is a common type of lung cancer with a high risk of metastasis, but the exact molecular mechanisms of metastasis are not yet understood.

METHODS: This study acquired single-cell transcriptomics profiling of 11 distal normal lung tissues, 11 primary LUAD tissues, and 4 metastatic LUAD tissues from the GSE131907 dataset. The lung multicellular ecosystems were characterized at a single-cell resolution, and the potential mechanisms underlying angiogenesis and metastasis of LUAD were explored.

RESULTS: We constructed a global single-cell landscape of 93,610 cells from primary and metastatic LUAD and found that IGF2BP2 was specifically expressed both in a LUAD cell subpopulation (termed as LUAD_IGF2BP2), and an endothelial cell subpopulation (termed as En_IGF2BP2). The LUAD_IGF2BP2 subpopulation progressively formed and dominated the ecology of metastatic LUAD during metastatic evolution. IGF2BP2 was preferentially secreted by exosomes in the LUAD_IGF2BP2 subpopulation, which was absorbed by the En_IGF2BP2 subpopulation in the tumor microenvironment. Subsequently, IGF2BP2 improved the RNA stability of FLT4 through m[6]A modification, thereby activating the PI3K-Akt signaling pathway, and eventually promoting angiogenesis and metastasis. Analysis of clinical data showed that IGF2BP2 was linked with poor overall survival and relapse-free survival for LUAD patients.

CONCLUSIONS: Overall, these findings provide a novel insight into the multicellular ecosystems of primary and metastatic LUAD, and demonstrate that a specific LUAD_IGF2BP2 subpopulation is a key orchestrator promoting angiogenesis and metastasis, with implications for the gene regulatory mechanisms of LUAD metastatic evolution, representing themselves as potential antiangiogenic targets.}, } @article {pmid37349567, year = {2023}, author = {Merényi, Z and Krizsán, K and Sahu, N and Liu, XB and Bálint, B and Stajich, JE and Spatafora, JW and Nagy, LG}, title = {Genomes of fungi and relatives reveal delayed loss of ancestral gene families and evolution of key fungal traits.}, journal = {Nature ecology & evolution}, volume = {7}, number = {8}, pages = {1221-1231}, pmid = {37349567}, issn = {2397-334X}, support = {758161/ERC_/European Research Council/International ; }, mesh = {*Genome, Fungal ; Phylogeny ; *Evolution, Molecular ; Fungi/genetics ; Eukaryota/genetics ; }, abstract = {Fungi are ecologically important heterotrophs that have radiated into most niches on Earth and fulfil key ecological services. Despite intense interest in their origins, major genomic trends of their evolutionary route from a unicellular opisthokont ancestor to derived multicellular fungi remain poorly known. Here we provide a highly resolved genome-wide catalogue of gene family changes across fungal evolution inferred from the genomes of 123 fungi and relatives. We show that a dominant trend in early fungal evolution has been the gradual shedding of protist genes and the punctuated emergence of innovation by two main gene duplication events. We find that the gene content of non-Dikarya fungi resembles that of unicellular opisthokonts in many respects, owing to the conservation of protist genes in their genomes. The most rapidly duplicating gene groups included extracellular proteins and transcription factors, as well as ones linked to the coordination of nutrient uptake with growth, highlighting the transition to a sessile osmotrophic feeding strategy and subsequent lifestyle evolution as important elements of early fungal history. These results suggest that the genomes of pre-fungal ancestors evolved into the typical filamentous fungal genome by a combination of gradual gene loss, turnover and several large duplication events rather than by abrupt changes. Consequently, the taxonomically defined Fungi represents a genomically non-uniform assemblage of species.}, } @article {pmid37338964, year = {2023}, author = {Caspi, Y and Pantazopoulou, CK and Prompers, JJ and Pieterse, CMJ and Hulshoff Pol, H and Kajala, K}, title = {Why did glutamate, GABA, and melatonin become intercellular signalling molecules in plants?.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37338964}, issn = {2050-084X}, mesh = {Animals ; *Melatonin/metabolism ; Glutamic Acid/metabolism ; Plants/metabolism ; gamma-Aminobutyric Acid/metabolism ; Signal Transduction ; }, abstract = {Intercellular signalling is an indispensable part of multicellular life. Understanding the commonalities and differences in how signalling molecules function in two remote branches of the tree of life may shed light on the reasons these molecules were originally recruited for intercellular signalling. Here we review the plant function of three highly studied animal intercellular signalling molecules, namely glutamate, γ-aminobutyric acid (GABA), and melatonin. By considering both their signalling function in plants and their broader physiological function, we suggest that molecules with an original function as key metabolites or active participants in reactive ion species scavenging have a high chance of becoming intercellular signalling molecules. Naturally, the evolution of machinery to transduce a message across the plasma membrane is necessary. This fact is demonstrated by three other well-studied animal intercellular signalling molecules, namely serotonin, dopamine, and acetylcholine, for which there is currently no evidence that they act as intercellular signalling molecules in plants.}, } @article {pmid37337232, year = {2023}, author = {Sarkar, MMH and Rahman, MS and Islam, MR and Rahman, A and Islam, MS and Banu, TA and Akter, S and Goswami, B and Jahan, I and Habib, MA and Uddin, MM and Mia, MZ and Miah, MI and Shaikh, AA and Khan, MS}, title = {Comparative phylogenetic analysis and transcriptomic profiling of Dengue (DENV-3 genotype I) outbreak in 2021 in Bangladesh.}, journal = {Virology journal}, volume = {20}, number = {1}, pages = {127}, pmid = {37337232}, issn = {1743-422X}, mesh = {Humans ; Phylogeny ; Bangladesh/epidemiology ; *Transcriptome ; *Dengue/epidemiology ; Disease Outbreaks ; Genotype ; Serogroup ; }, abstract = {BACKGROUND: The next-generation sequencing (NGS) technology facilitates in-depth study of host-pathogen metatranscriptome. We, therefore, implicated phylodynamic and transcriptomic approaches through NGS technology to know/understand the dengue virus (DENV) origin and host response with dengue fever.

METHODS: In this study, blood serum RNA was extracted from 21 dengue patients and 3 healthy individuals. Total transcriptomic data were analyzed for phylogenetic, phylodynamic, differential express gene (DEG), and gene ontology (GO) using respective bioinformatics tools.

RESULTS: The viral genome sequence revealed dengue viral genome size ranges 10647 to 10707 nucleotide. Phylogenetic and phylodynamic analysis showed that the 2021 epidemic isolates were DENV-3 genotype-I and maintained as a new clade in compared to 2019 epidemic. Transcriptome analysis showed a total of 2686 genes were DEG in dengue patients compared to control with a q-value < 0.05. DESeq2 plot counts function of the top 24 genes with the smallest q-values of differential gene expression of RNA-seq data showed that 11 genes were upregulated, whereas 13 genes were downregulated. GO analysis showed a significant upregulation (p = < 0.001) in a process of multicellular organismal, nervous system, sensory perception of chemical stimulus, and G protein-coupled receptor signaling pathways in the dengue patients. However, there were a significant downregulation (p = < 0.001) of intracellular component, cellular anatomical entity, and protein-containing complex in dengue patients. Most importantly, there was a significant increase of a class of immunoregulatory proteins in dengue patients in compared to the controls, with increased GO of immune system process. In addition, upregulation of toll receptor (TLR) signaling pathways were found in dengue patients. These TLR pathways were particularly involved for the activation of innate system coupled with adaptive immune system that probably involved the rapid elimination of dengue virus infected cells. These differentially expressed genes could be further investigated for target based prophylactic interventions for dengue.

CONCLUSION: This is a first report describing DENV complete genomic features and differentially expressed genes in patients in Bangladesh. These genes may have diagnostic and therapeutic values for dengue infection. Continual genomic surveillance is required to further investigate the shift in dominant genotypes in relation to viral pathogenesis.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-023-02030-1.}, } @article {pmid37322016, year = {2023}, author = {Chavhan, Y and Dey, S and Lind, PA}, title = {Bacteria evolve macroscopic multicellularity by the genetic assimilation of phenotypically plastic cell clustering.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3555}, pmid = {37322016}, issn = {2041-1723}, mesh = {*Biological Evolution ; *Eukaryota ; Adaptation, Physiological ; Phenotype ; Bacteria ; }, abstract = {The evolutionary transition from unicellularity to multicellularity was a key innovation in the history of life. Experimental evolution is an important tool to study the formation of undifferentiated cellular clusters, the likely first step of this transition. Although multicellularity first evolved in bacteria, previous experimental evolution research has primarily used eukaryotes. Moreover, it focuses on mutationally driven (and not environmentally induced) phenotypes. Here we show that both Gram-negative and Gram-positive bacteria exhibit phenotypically plastic (i.e., environmentally induced) cell clustering. Under high salinity, they form elongated clusters of ~ 2 cm. However, under habitual salinity, the clusters disintegrate and grow planktonically. We used experimental evolution with Escherichia coli to show that such clustering can be assimilated genetically: the evolved bacteria inherently grow as macroscopic multicellular clusters, even without environmental induction. Highly parallel mutations in genes linked to cell wall assembly formed the genomic basis of assimilated multicellularity. While the wildtype also showed cell shape plasticity across high versus low salinity, it was either assimilated or reversed after evolution. Interestingly, a single mutation could genetically assimilate multicellularity by modulating plasticity at multiple levels of organization. Taken together, we show that phenotypic plasticity can prime bacteria for evolving undifferentiated macroscopic multicellularity.}, } @article {pmid37317487, year = {2023}, author = {Fulda, FC}, title = {Agential autonomy and biological individuality.}, journal = {Evolution & development}, volume = {25}, number = {6}, pages = {353-370}, doi = {10.1111/ede.12450}, pmid = {37317487}, issn = {1525-142X}, mesh = {Humans ; Animals ; *Biological Evolution ; *Symbiosis ; }, abstract = {What is a biological individual? How are biological individuals individuated? How can we tell how many individuals there are in a given assemblage of biological entities? The individuation and differentiation of biological individuals are central to the scientific understanding of living beings. I propose a novel criterion of biological individuality according to which biological individuals are autonomous agents. First, I articulate an ecological-dynamical account of natural agency according to which, agency is the gross dynamical capacity of a goal-directed system to bias its repertoire to respond to its conditions as affordances. Then, I argue that agents or agential dynamical systems can be agentially dependent on, or agentially autonomous from, other agents and that this agential dependence/autonomy can be symmetrical or asymmetrical, strong or weak. Biological individuals, I propose, are all and only those agential dynamical systems that are strongly agentially autonomous. So, to determine how many individuals there are in a given multiagent aggregate, such as multicellular organism, a colony, symbiosis, or a swarm, we first have to identify how many agential dynamical systems there are, and then what their relations of agential dependence/autonomy are. I argue that this criterion is adequate to the extent that it vindicates the paradigmatic cases, and explains why the paradigmatic cases are paradigmatic, and why the problematic cases are problematic. Finally, I argue for the importance of distinguishing between agential and causal dependence and show the relevance of agential autonomy for understanding the explanatory structure of evolutionary developmental biology.}, } @article {pmid37295595, year = {2023}, author = {Jacob, MS}, title = {Toward a Bio-Organon: A model of interdependence between energy, information and knowledge in living systems.}, journal = {Bio Systems}, volume = {230}, number = {}, pages = {104939}, doi = {10.1016/j.biosystems.2023.104939}, pmid = {37295595}, issn = {1872-8324}, mesh = {Humans ; *Biological Evolution ; *Models, Theoretical ; }, abstract = {What is an organism? In the absence of a fundamental biological definition, what constitutes a living organism, whether it is a unicellular microbe, a multicellular being or a multi-organismal society, remains an open question. New models of living systems are needed to address the scale of this question, with implications for the relationship between humanity and planetary ecology. Here we develop a generic model of an organism that can be applied across multiple scales and through major evolutionary transitions to form a toolkit, or bio-organon, for theoretical studies of planetary-wide physiology. The tool identifies the following core organismic principles that cut across spatial scale: (1) evolvability through self-knowledge, (2) entanglement between energy and information, and (3) extrasomatic "technology" to scaffold increases in spatial scale. Living systems are generally defined by their ability to self-sustain against entropic forces of degradation. Life "knows" how to survive from the inside, not from its genetic code alone, but by utilizing this code through dynamically embodied and functionally specialized flows of information and energy. That is, entangled metabolic and communication networks bring encoded knowledge to life in order to sustain life. However, knowledge is itself evolved and is evolving. The functional coupling between knowledge, energy and information has ancient origins, enabling the original, cellular "biotechnology," and cumulative evolutionary creativity in biochemical products and forms. Cellular biotechnology also enabled the nesting of specialized cells into multicellular organisms. This nested organismal hierarchy can be extended further, suggesting that an organism of organisms, or a human "superorganism," is not only possible, but in keeping with evolutionary trends.}, } @article {pmid37285440, year = {2023}, author = {Zhang, F and Ji, Q and Chaturvedi, J and Morales, M and Mao, Y and Meng, X and Dong, L and Deng, J and Qian, SB and Xiang, Y}, title = {Human SAMD9 is a poxvirus-activatable anticodon nuclease inhibiting codon-specific protein synthesis.}, journal = {Science advances}, volume = {9}, number = {23}, pages = {eadh8502}, pmid = {37285440}, issn = {2375-2548}, support = {R21 AI153948/AI/NIAID NIH HHS/United States ; R01 AI151638/AI/NIAID NIH HHS/United States ; S10 OD021805/OD/NIH HHS/United States ; R21 AI149295/AI/NIAID NIH HHS/United States ; P30 CA054174/CA/NCI NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Anticodon/genetics ; *RNA, Transfer, Phe/genetics/metabolism ; Codon ; RNA, Transfer/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; }, abstract = {As a defense strategy against viruses or competitors, some microbes use anticodon nucleases (ACNases) to deplete essential tRNAs, effectively halting global protein synthesis. However, this mechanism has not been observed in multicellular eukaryotes. Here, we report that human SAMD9 is an ACNase that specifically cleaves phenylalanine tRNA (tRNA[Phe]), resulting in codon-specific ribosomal pausing and stress signaling. While SAMD9 ACNase activity is normally latent in cells, it can be activated by poxvirus infection or rendered constitutively active by SAMD9 mutations associated with various human disorders, revealing tRNA[Phe] depletion as an antiviral mechanism and a pathogenic condition in SAMD9 disorders. We identified the N-terminal effector domain of SAMD9 as the ACNase, with substrate specificity primarily determined by a eukaryotic tRNA[Phe]-specific 2'-O-methylation at the wobble position, making virtually all eukaryotic tRNA[Phe] susceptible to SAMD9 cleavage. Notably, the structure and substrate specificity of SAMD9 ACNase differ from known microbial ACNases, suggesting convergent evolution of a common immune defense strategy targeting tRNAs.}, } @article {pmid37264211, year = {2023}, author = {Lamolle, G and Simón, D and Iriarte, A and Musto, H}, title = {Main Factors Shaping Amino Acid Usage Across Evolution.}, journal = {Journal of molecular evolution}, volume = {91}, number = {4}, pages = {382-390}, pmid = {37264211}, issn = {1432-1432}, mesh = {Animals ; *Amino Acids/genetics ; Codon/genetics ; *Genetic Code ; Base Composition ; Proteome/genetics ; Evolution, Molecular ; Mammals/genetics ; }, abstract = {The standard genetic code determines that in most species, including viruses, there are 20 amino acids that are coded by 61 codons, while the other three codons are stop triplets. Considering the whole proteome each species features its own amino acid frequencies, given the slow rate of change, closely related species display similar GC content and amino acids usage. In contrast, distantly related species display different amino acid frequencies. Furthermore, within certain multicellular species, as mammals, intragenomic differences in the usage of amino acids are evident. In this communication, we shall summarize some of the most prominent and well-established factors that determine the differences found in the amino acid usage, both across evolution and intragenomically.}, } @article {pmid37264144, year = {2024}, author = {Dadras, N and Hasanpur, K and Razeghi, J and Kianianmomeni, A}, title = {Different transcription of novel, functional long non-coding RNA genes by UV-B in green algae, Volvox carteri.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {27}, number = {1}, pages = {213-225}, pmid = {37264144}, issn = {1618-1905}, mesh = {*Volvox/genetics/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; Biological Evolution ; }, abstract = {Long non-coding RNAs (lncRNAs) are identified as important regulatory molecules related to diverse biological processes. In recent years, benefiting from the rapid development of high-throughput sequencing technology, RNA-seq, and analysis methods, more lncRNAs have been identified and discovered in various plant and algal species. However, so far, only limited studies related to algal lncRNAs are available. Volvox carteri f. nagariensis is the best multicellular model organism to study in developmental and evolutionary biology; therefore, studying and increasing information about this species is important. This study identified lncRNAs in the multicellular green algae Volvox carteri and 1457 lncRNAs were reported, using RNA-seq data and with the help of bioinformatics tools and software. This study investigated the effect of low-dose UV-B radiation on changes in the expression profile of lncRNAs in gonidial and somatic cells. The differential expression of lncRNAs was analyzed between the treatment (UV-B) and the control (WL) groups in gonidial and somatic cells. A total of 37 and 26 lncRNAs with significant differential expression in gonidial and somatic cells, respectively, were reported. Co-expression analysis between the lncRNAs and their neighbor protein-coding genes (in the interval of ± 10 Kb) was accomplished. In gonidial cells, 184 genes with a positive correlation and 13 genes with a negative correlation (greater than 0.95), and in somatic cells, 174 genes with a positive correlation, and 18 genes with a negative correlation were detected. Functional analysis of neighboring coding genes was also performed based on gene ontology. The results of the current work may help gain deeper insight into the regulation of gene expression in the studied model organism, Volvox carteri.}, } @article {pmid37264002, year = {2023}, author = {Galand, PE and Ruscheweyh, HJ and Salazar, G and Hochart, C and Henry, N and Hume, BCC and Oliveira, PH and Perdereau, A and Labadie, K and Belser, C and Boissin, E and Romac, S and Poulain, J and Bourdin, G and Iwankow, G and Moulin, C and Armstrong, EJ and Paz-García, DA and Ziegler, M and Agostini, S and Banaigs, B and Boss, E and Bowler, C and de Vargas, C and Douville, E and Flores, M and Forcioli, D and Furla, P and Gilson, E and Lombard, F and Pesant, S and Reynaud, S and Thomas, OP and Troublé, R and Zoccola, D and Voolstra, CR and Thurber, RV and Sunagawa, S and Wincker, P and Allemand, D and Planes, S}, title = {Diversity of the Pacific Ocean coral reef microbiome.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3039}, pmid = {37264002}, issn = {2041-1723}, mesh = {Animals ; Coral Reefs ; Pacific Ocean ; *Anthozoa ; Biodiversity ; *Microbiota ; Fishes ; Plankton ; }, abstract = {Coral reefs are among the most diverse ecosystems on Earth. They support high biodiversity of multicellular organisms that strongly rely on associated microorganisms for health and nutrition. However, the extent of the coral reef microbiome diversity and its distribution at the oceanic basin-scale remains to be explored. Here, we systematically sampled 3 coral morphotypes, 2 fish species, and planktonic communities in 99 reefs from 32 islands across the Pacific Ocean, to assess reef microbiome composition and biogeography. We show a very large richness of reef microorganisms compared to other environments, which extrapolated to all fishes and corals of the Pacific, approximates the current estimated total prokaryotic diversity for the entire Earth. Microbial communities vary among and within the 3 animal biomes (coral, fish, plankton), and geographically. For corals, the cross-ocean patterns of diversity are different from those known for other multicellular organisms. Within each coral morphotype, community composition is always determined by geographic distance first, both at the island and across ocean scale, and then by environment. Our unprecedented sampling effort of coral reef microbiomes, as part of the Tara Pacific expedition, provides new insight into the global microbial diversity, the factors driving their distribution, and the biocomplexity of reef ecosystems.}, } @article {pmid37256696, year = {2023}, author = {Blomme, J and Wichard, T and Jacobs, TB and De Clerck, O}, title = {Ulva: An emerging green seaweed model for systems biology.}, journal = {Journal of phycology}, volume = {59}, number = {3}, pages = {433-440}, doi = {10.1111/jpy.13341}, pmid = {37256696}, issn = {1529-8817}, mesh = {*Ulva ; *Seaweed ; Ecosystem ; Systems Biology ; *Chlorophyta ; }, abstract = {Green seaweeds exhibit a wide range of morphologies and occupy various ecological niches, spanning from freshwater to marine and terrestrial habitats. These organisms, which predominantly belong to the class Ulvophyceae, showcase a remarkable instance of parallel evolution toward complex multicellularity and macroscopic thalli in the Viridiplantae lineage. Within the green seaweeds, several Ulva species ("sea lettuce") are model organisms for studying carbon assimilation, interactions with bacteria, life cycle progression, and morphogenesis. Ulva species are also notorious for their fast growth and capacity to dominate nutrient-rich, anthropogenically disturbed coastal ecosystems during "green tide" blooms. From an economic perspective, Ulva has garnered increasing attention as a promising feedstock for the production of food, feed, and biobased products, also as a means of removing excess nutrients from the environment. We propose that Ulva is poised to further develop as a model in green seaweed research. In this perspective, we focus explicitly on Ulva mutabilis/compressa as a model species and highlight the molecular data and tools that are currently available or in development. We discuss several areas that will benefit from future research or where exciting new developments have been reported in other Ulva species.}, } @article {pmid37256290, year = {2023}, author = {Jiang, P and Kreitman, M and Reinitz, J}, title = {The effect of mutational robustness on the evolvability of multicellular organisms and eukaryotic cells.}, journal = {Journal of evolutionary biology}, volume = {36}, number = {6}, pages = {906-924}, pmid = {37256290}, issn = {1420-9101}, support = {R01 OD010936/OD/NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; *Eukaryotic Cells ; Models, Genetic ; Mutation ; Phenotype ; }, abstract = {Canalization involves mutational robustness, the lack of phenotypic change as a result of genetic mutations. Given the large divergence in phenotype across species, understanding the relationship between high robustness and evolvability has been of interest to both theorists and experimentalists. Although canalization was originally proposed in the context of multicellular organisms, the effect of multicellularity and other classes of hierarchical organization on evolvability has not been considered by theoreticians. We address this issue using a Boolean population model with explicit representation of an environment in which individuals with explicit genotype and a hierarchical phenotype representing multicellularity evolve. Robustness is described by a single real number between zero and one which emerges from the genotype-phenotype map. We find that high robustness is favoured in constant environments, and lower robustness is favoured after environmental change. Multicellularity and hierarchical organization severely constrain robustness: peak evolvability occurs at an absolute level of robustness of about 0.99 compared with values of about 0.5 in a classical neutral network model. These constraints result in a sharp peak of evolvability in which the maximum is set by the fact that the fixation of adaptive mutations becomes more improbable as robustness decreases. When robustness is put under genetic control, robustness levels leading to maximum evolvability are selected for, but maximal relative fitness appears to require recombination.}, } @article {pmid37253212, year = {2023}, author = {Hoch, NC}, title = {Tissue Specificity of DNA Damage and Repair.}, journal = {Physiology (Bethesda, Md.)}, volume = {38}, number = {5}, pages = {0}, doi = {10.1152/physiol.00006.2023}, pmid = {37253212}, issn = {1548-9221}, mesh = {Humans ; Organ Specificity ; *DNA Damage ; *DNA Repair ; Aging/genetics ; DNA/genetics/metabolism ; }, abstract = {DNA is a remarkable biochemical macromolecule tasked with storing the genetic information that instructs life on planet Earth. However, its inherent chemical instability within the cellular milieu is incompatible with the accurate transmission of genetic information to subsequent generations. Therefore, biochemical pathways that continuously survey and repair DNA are essential to sustain life, and the fundamental mechanisms by which different DNA lesions are repaired have remained well conserved throughout evolution. Nonetheless, the emergence of multicellular organisms led to profound differences in cellular context and physiology, leading to large variations in the predominant sources of DNA damage between different cell types and in the relative contribution of different DNA repair pathways toward genome maintenance in different tissues. While we continue to make large strides into understanding how individual DNA repair mechanisms operate on a molecular level, much less attention is given to these cell type-specific differences. This short review aims to provide a broad overview of DNA damage and repair mechanisms to nonspecialists and to highlight some fundamental open questions in tissue and cell-type-specificity of these processes, which may have profound implications for our understanding of important pathophysiological processes such as cancer, neurodegeneration, and aging.}, } @article {pmid37247371, year = {2023}, author = {McCourt, RM and Lewis, LA and Strother, PK and Delwiche, CF and Wickett, NJ and de Vries, J and Bowman, JL}, title = {Green land: Multiple perspectives on green algal evolution and the earliest land plants.}, journal = {American journal of botany}, volume = {110}, number = {5}, pages = {e16175}, doi = {10.1002/ajb2.16175}, pmid = {37247371}, issn = {1537-2197}, mesh = {Biological Evolution ; Ecosystem ; *Embryophyta/genetics ; Phylogeny ; Plants/genetics ; *Chlorophyta/genetics ; Evolution, Molecular ; }, abstract = {Green plants, broadly defined as green algae and the land plants (together, Viridiplantae), constitute the primary eukaryotic lineage that successfully colonized Earth's emergent landscape. Members of various clades of green plants have independently made the transition from fully aquatic to subaerial habitats many times throughout Earth's history. The transition, from unicells or simple filaments to complex multicellular plant bodies with functionally differentiated tissues and organs, was accompanied by innovations built upon a genetic and phenotypic toolkit that have served aquatic green phototrophs successfully for at least a billion years. These innovations opened an enormous array of new, drier places to live on the planet and resulted in a huge diversity of land plants that have dominated terrestrial ecosystems over the past 500 million years. This review examines the greening of the land from several perspectives, from paleontology to phylogenomics, to water stress responses and the genetic toolkit shared by green algae and plants, to the genomic evolution of the sporophyte generation. We summarize advances on disparate fronts in elucidating this important event in the evolution of the biosphere and the lacunae in our understanding of it. We present the process not as a step-by-step advancement from primitive green cells to an inevitable success of embryophytes, but rather as a process of adaptations and exaptations that allowed multiple clades of green plants, with various combinations of morphological and physiological terrestrialized traits, to become diverse and successful inhabitants of the land habitats of Earth.}, } @article {pmid37233789, year = {2024}, author = {Wu, N and Wei, L and Zhu, Z and Liu, Q and Li, K and Mao, F and Qiao, J and Zhao, X}, title = {Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction.}, journal = {Protein & cell}, volume = {15}, number = {1}, pages = {6-20}, pmid = {37233789}, issn = {1674-8018}, support = {32170493//National Natural Science Foundation of China/ ; //National Clinical Research Center for Obstetrics and Gynecology/ ; BYSYSZKF2022005//Peking University Third Hospital/ ; //Peking University/ ; PKU2023LCXQ036//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Male ; Female ; Animals ; Humans ; Swine ; *DNA, Circular/genetics ; *Genital Neoplasms, Female ; Semen ; DNA ; Reproduction ; }, abstract = {Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.}, } @article {pmid37223732, year = {2023}, author = {Hengge, R and Pruteanu, M and Stülke, J and Tschowri, N and Turgay, K}, title = {Recent advances and perspectives in nucleotide second messenger signaling in bacteria.}, journal = {microLife}, volume = {4}, number = {}, pages = {uqad015}, pmid = {37223732}, issn = {2633-6693}, abstract = {Nucleotide second messengers act as intracellular 'secondary' signals that represent environmental or cellular cues, i.e. the 'primary' signals. As such, they are linking sensory input with regulatory output in all living cells. The amazing physiological versatility, the mechanistic diversity of second messenger synthesis, degradation, and action as well as the high level of integration of second messenger pathways and networks in prokaryotes has only recently become apparent. In these networks, specific second messengers play conserved general roles. Thus, (p)ppGpp coordinates growth and survival in response to nutrient availability and various stresses, while c-di-GMP is the nucleotide signaling molecule to orchestrate bacterial adhesion and multicellularity. c-di-AMP links osmotic balance and metabolism and that it does so even in Archaea may suggest a very early evolutionary origin of second messenger signaling. Many of the enzymes that make or break second messengers show complex sensory domain architectures, which allow multisignal integration. The multiplicity of c-di-GMP-related enzymes in many species has led to the discovery that bacterial cells are even able to use the same freely diffusible second messenger in local signaling pathways that can act in parallel without cross-talking. On the other hand, signaling pathways operating with different nucleotides can intersect in elaborate signaling networks. Apart from the small number of common signaling nucleotides that bacteria use for controlling their cellular "business," diverse nucleotides were recently found to play very specific roles in phage defense. Furthermore, these systems represent the phylogenetic ancestors of cyclic nucleotide-activated immune signaling in eukaryotes.}, } @article {pmid37220133, year = {2023}, author = {Lipińska-Zubrycka, L and Grochowski, M and Bähler, J and Małecki, M}, title = {Pervasive mRNA uridylation in fission yeast is catalysed by both Cid1 and Cid16 terminal uridyltransferases.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0285576}, pmid = {37220133}, issn = {1932-6203}, support = {095598/Z/11/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {RNA, Messenger ; *Schizosaccharomyces ; Saccharomyces cerevisiae ; RNA ; Catalysis ; UDPglucose-Hexose-1-Phosphate Uridylyltransferase ; Nucleotidyltransferases ; *Schizosaccharomyces pombe Proteins ; }, abstract = {Messenger RNA uridylation is pervasive and conserved among eukaryotes, but the consequences of this modification for mRNA fate are still under debate. Utilising a simple model organism to study uridylation may facilitate efforts to understand the cellular function of this process. Here we demonstrate that uridylation can be detected using simple bioinformatics approach. We utilise it to unravel widespread transcript uridylation in fission yeast and demonstrate the contribution of both Cid1 and Cid16, the only two annotated terminal uridyltransferases (TUT-ases) in this yeast. To detect uridylation in transcriptome data, we used a RNA-sequencing (RNA-seq) library preparation protocol involving initial linker ligation to fragmented RNA-an approach borrowed from small RNA sequencing that was commonly used in older RNA-seq protocols. We next explored the data to detect uridylation marks. Our analysis show that uridylation in yeast is pervasive, similarly to the one in multicellular organisms. Importantly, our results confirm the role of the cytoplasmic uridyltransferase Cid1 as the primary uridylation catalyst. However, we also observed an auxiliary role of the second uridyltransferase, Cid16. Thus both fission yeast uridyltransferases are involved in mRNA uridylation. Intriguingly, we found no physiological phenotype of the single and double deletion mutants of cid1 and cid16 and only minimal impact of uridylation on steady-state mRNA levels. Our work establishes fission yeast as a potent model to study uridylation in a simple eukaryote, and we demonstrate that it is possible to detect uridylation marks in RNA-seq data without the need for specific methodologies.}, } @article {pmid37219671, year = {2023}, author = {Gmiter, D and Pacak, I and Nawrot, S and Czerwonka, G and Kaca, W}, title = {Genomes comparison of two Proteus mirabilis clones showing varied swarming ability.}, journal = {Molecular biology reports}, volume = {50}, number = {7}, pages = {5817-5826}, pmid = {37219671}, issn = {1573-4978}, support = {2019/33/N/NZ6/02406//Narodowym Centrum Nauki/ ; 2017/01/X/NZ6/01141//Narodowe Centrum Nauki/ ; }, mesh = {Humans ; Proteus mirabilis/genetics ; *Urinary Tract Infections/genetics/microbiology ; Clone Cells ; *Proteus Infections/microbiology ; }, abstract = {BACKGROUND: Proteus mirabilis is a Gram-negative bacteria most noted for its involvement with catheter-associated urinary tract infections. It is also known for its multicellular migration over solid surfaces, referred to as 'swarming motility'. Here we analyzed the genomic sequences of two P. mirabilis isolates, designated K38 and K39, which exhibit varied swarming ability.

METHODS AND RESULTS: The isolates genomes were sequenced using Illumina NextSeq sequencer, resulting in about 3.94 Mbp, with a GC content of 38.6%, genomes. Genomes were subjected for in silico comparative investigation. We revealed that, despite a difference in swarming motility, the isolates showed high genomic relatedness (up to 100% ANI similarity), suggesting that one of the isolates probably originated from the other.

CONCLUSIONS: The genomic sequences will allow us to investigate the mechanism driving this intriguing phenotypic heterogeneity between closely related P. mirabilis isolates. Phenotypic heterogeneity is an adaptive strategy of bacterial cells to several environmental pressures. It is also an important factor related to their pathogenesis. Therefore, the availability of these genomic sequences will facilitate studies that focus on the host-pathogen interactions during catheter-associated urinary tract infections.}, } @article {pmid37211257, year = {2023}, author = {Fields, C and Levin, M}, title = {Regulative development as a model for origin of life and artificial life studies.}, journal = {Bio Systems}, volume = {229}, number = {}, pages = {104927}, doi = {10.1016/j.biosystems.2023.104927}, pmid = {37211257}, issn = {1872-8324}, mesh = {Humans ; *Artificial Life ; Thermodynamics ; }, abstract = {Using the formal framework of the Free Energy Principle, we show how generic thermodynamic requirements on bidirectional information exchange between a system and its environment can generate complexity. This leads to the emergence of hierarchical computational architectures in systems that operate sufficiently far from thermal equilibrium. In this setting, the environment of any system increases its ability to predict system behavior by "engineering" the system towards increased morphological complexity and hence larger-scale, more macroscopic behaviors. When seen in this light, regulative development becomes an environmentally-driven process in which "parts" are assembled to produce a system with predictable behavior. We suggest on this basis that life is thermodynamically favorable and that, when designing artificial living systems, human engineers are acting like a generic "environment".}, } @article {pmid37202179, year = {2023}, author = {Sobala, ŁF}, title = {Evolution and phylogenetic distribution of endo-α-mannosidase.}, journal = {Glycobiology}, volume = {33}, number = {9}, pages = {687-699}, pmid = {37202179}, issn = {1460-2423}, mesh = {Animals ; alpha-Mannosidase/genetics/metabolism ; Phylogeny ; *Mannosidases/genetics/metabolism ; *Polysaccharides/metabolism ; Glycosylation ; Vertebrates/metabolism ; Eukaryota/metabolism ; Golgi Apparatus/metabolism ; }, abstract = {While glycans underlie many biological processes, such as protein folding, cell adhesion, and cell-cell recognition, deep evolution of glycosylation machinery remains an understudied topic. N-linked glycosylation is a conserved process in which mannosidases are key trimming enzymes. One of them is the glycoprotein endo-α-1,2-mannosidase which participates in the initial trimming of mannose moieties from an N-linked glycan inside the cis-Golgi. It is unique as the only endo-acting mannosidase found in this organelle. Relatively little is known about its origins and evolutionary history; so far it was reported to occur only in vertebrates. In this work, a taxon-rich bioinformatic survey to unravel the evolutionary history of this enzyme, including all major eukaryotic clades and a wide representation of animals, is presented. The endomannosidase was found to be more widely distributed in animals and other eukaryotes. The protein motif changes in context of the canonical animal enzyme were tracked. Additionally, the data show the two canonical vertebrate endomannosidase genes, MANEA and MANEAL, arose at the second round of the two vertebrate genome duplications and one more vertebrate paralog, CMANEAL, is uncovered. Finally, a framework where N-glycosylation co-evolved with complex multicellularity is described. A better understanding of the evolution of core glycosylation pathways is pivotal to understanding biology of eukaryotes in general, and the Golgi apparatus in particular. This systematic analysis of the endomannosidase evolution is one step toward this goal.}, } @article {pmid37195672, year = {2023}, author = {Fernandes, J}, title = {Virus-Induced Lysis of Tumor and Other Pathogenic Unicellular Entities and Its Potential to Treat Leishmaniasis.}, journal = {DNA and cell biology}, volume = {42}, number = {6}, pages = {305-314}, doi = {10.1089/dna.2023.0048}, pmid = {37195672}, issn = {1557-7430}, mesh = {Humans ; *Leishmaniasis/drug therapy/parasitology ; *Leishmania/metabolism ; Cell Death ; *Neoplasms ; Saccharomyces cerevisiae ; *Viruses ; }, abstract = {This article is focused on the main pathways used by viruses to achieve infection and lysis of unicellular eukaryotes described as pathogenic for multicellular organisms. In light of the recent discussions on how tumor cells exhibit unicellular behavior, highly malignant cells can be considered as another unicellular pathogenic entity, but with endogenous origin. Thus, a comparative panel of viral lysis of exogenous pathogenic unicellular eukaryotes such as Acanthamoeba sp., yeast, and tumors is presented. The important intracellular parasite Leishmania sp is also presented, which, in contrast, has its virulence improved by viral infections. The possible exploitation of viral-mediated eukaryotic cell lysis to overcome infections of Leishmania sp is discussed.}, } @article {pmid37183897, year = {2023}, author = {Kaucka, M}, title = {Cis-regulatory landscapes in the evolution and development of the mammalian skull.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1880}, pages = {20220079}, pmid = {37183897}, issn = {1471-2970}, mesh = {Animals ; *Evolution, Molecular ; *Mammals/genetics ; Gene Regulatory Networks ; Skull ; Head ; }, abstract = {Extensive morphological variation found in mammals reflects the wide spectrum of their ecological adaptations. The highest morphological diversity is present in the craniofacial region, where geometry is mainly dictated by the bony skull. Mammalian craniofacial development represents complex multistep processes governed by numerous conserved genes that require precise spatio-temporal control. A central question in contemporary evolutionary biology is how a defined set of conserved genes can orchestrate formation of fundamentally different structures, and therefore how morphological variability arises. In principle, differential gene expression patterns during development are the source of morphological variation. With the emergence of multicellular organisms, precise regulation of gene expression in time and space is attributed to cis-regulatory elements. These elements contribute to higher-order chromatin structure and together with trans-acting factors control transcriptional landscapes that underlie intricate morphogenetic processes. Consequently, divergence in cis-regulation is believed to rewire existing gene regulatory networks and form the core of morphological evolution. This review outlines the fundamental principles of the genetic code and genomic regulation interplay during development. Recent work that deepened our comprehension of cis-regulatory element origin, divergence and function is presented here to illustrate the state-of-the-art research that uncovered the principles of morphological novelty. This article is part of the theme issue 'The mammalian skull: development, structure and function'.}, } @article {pmid37176080, year = {2023}, author = {Suwannachuen, N and Leetanasaksakul, K and Roytrakul, S and Phaonakrop, N and Thaisakun, S and Roongsattham, P and Jantasuriyarat, C and Sanevas, N and Sirikhachornkit, A}, title = {Palmelloid Formation and Cell Aggregation Are Essential Mechanisms for High Light Tolerance in a Natural Strain of Chlamydomonas reinhardtii.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37176080}, issn = {1422-0067}, support = {This project is funded by National Research Council of Thailand (NRCT) and Kasetsart Univer-sity : N42A650287. This research and innovation activity is funded by National Research Council of Thailand (NRCT). This research is supported in part by the Grad//This project is funded by National Research Council of Thailand (NRCT) and Kasetsart Univer-sity : N42A650287. This research and innovation activity is funded by National Research Council of Thailand (NRCT). This research is supported in part by the Grad/ ; }, mesh = {*Chlamydomonas reinhardtii/metabolism ; Reactive Oxygen Species/metabolism ; Proteomics ; *Chlamydomonas/metabolism ; Photosynthesis/physiology ; }, abstract = {Photosynthetic organisms, such as higher plants and algae, require light to survive. However, an excessive amount of light can be harmful due to the production of reactive oxygen species (ROS), which cause cell damage and, if it is not effectively regulated, cell death. The study of plants' responses to light can aid in the development of methods to improve plants' growth and productivity. Due to the multicellular nature of plants, there may be variations in the results based on plant age and tissue type. Chlamydomonas reinhardtii, a unicellular green alga, has also been used as a model organism to study photosynthesis and photoprotection. Nonetheless, the majority of the research has been conducted with strains that have been consistently utilized in laboratories and originated from the same source. Despite the availability of many field isolates of this species, very few studies have compared the light responses of field isolates. This study examined the responses of two field isolates of Chlamydomonas to high light stress. The light-tolerant strain, CC-4414, managed reactive oxygen species (ROS) slightly better than the sensitive strain, CC-2344, did. The proteomic data of cells subjected to high light revealed cellular modifications of the light-tolerant strain toward membrane proteins. The morphology of cells under light stress revealed that this strain utilized the formation of palmelloid structures and cell aggregation to shield cells from excessive light. As indicated by proteome data, morphological modifications occur simultaneously with the increase in protein degradation and autophagy. By protecting cells from stress, cells are able to continue to upregulate ROS management mechanisms and prevent cell death. This is the first report of palmelloid formation in Chlamydomonas under high light stress.}, } @article {pmid37173684, year = {2023}, author = {Foo, YZ and Lagisz, M and O'Dea, RE and Nakagawa, S}, title = {The influence of immune challenges on the mean and variance in reproductive investment: a meta-analysis of the terminal investment hypothesis.}, journal = {BMC biology}, volume = {21}, number = {1}, pages = {107}, pmid = {37173684}, issn = {1741-7007}, mesh = {Animals ; *Reproduction/physiology ; }, abstract = {Finding the optimal balance between survival and reproduction is a central puzzle in life-history theory. The terminal investment hypothesis predicts that when individuals encounter a survival threat that compromises future reproductive potential, they will increase immediate reproductive investment to maximise fitness. Despite decades of research on the terminal investment hypothesis, findings remain mixed. We examined the terminal investment hypothesis with a meta-analysis of studies that measured reproductive investment of multicellular iteroparous animals after a non-lethal immune challenge. We had two main aims. The first was to investigate whether individuals, on average, increase reproductive investment in response to an immune threat, as predicted by the terminal investment hypothesis. We also examined whether such responses vary adaptively on factors associated with the amount of reproductive opportunities left (residual reproductive value) in the individuals, as predicted by the terminal investment hypothesis. The second was to provide a quantitative test of a novel prediction based on the dynamic threshold model: that an immune threat increases between-individual variance in reproductive investment. Our results provided some support for our hypotheses. Older individuals, who are expected to have lower residual reproductive values, showed stronger mean terminal investment response than younger individuals. In terms of variance, individuals showed a divergence in responses, leading to an increase in variance. This increase in variance was especially amplified in longer-living species, which was consistent with our prediction that individuals in longer-living species should respond with greater individual variation due to increased phenotypic plasticity. We find little statistical evidence of publication bias. Together, our results highlight the need for a more nuanced view on the terminal investment hypothesis and a greater focus on the factors that drive individual responses.}, } @article {pmid37165189, year = {2023}, author = {Bozdag, GO and Zamani-Dahaj, SA and Day, TC and Kahn, PC and Burnetti, AJ and Lac, DT and Tong, K and Conlin, PL and Balwani, AH and Dyer, EL and Yunker, PJ and Ratcliff, WC}, title = {De novo evolution of macroscopic multicellularity.}, journal = {Nature}, volume = {617}, number = {7962}, pages = {747-754}, pmid = {37165189}, issn = {1476-4687}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; }, mesh = {*Acclimatization ; *Biological Evolution ; Models, Biological ; *Saccharomyces cerevisiae/cytology/metabolism ; Anaerobiosis ; Aerobiosis ; Oxygen/analysis/metabolism ; Cell Shape ; *Cell Aggregation/physiology ; }, abstract = {While early multicellular lineages necessarily started out as relatively simple groups of cells, little is known about how they became Darwinian entities capable of sustained multicellular evolution[1-3]. Here we investigate this with a multicellularity long-term evolution experiment, selecting for larger group size in the snowflake yeast (Saccharomyces cerevisiae) model system. Given the historical importance of oxygen limitation[4], our ongoing experiment consists of three metabolic treatments[5]-anaerobic, obligately aerobic and mixotrophic yeast. After 600 rounds of selection, snowflake yeast in the anaerobic treatment group evolved to be macroscopic, becoming around 2 × 10[4] times larger (approximately mm scale) and about 10[4]-fold more biophysically tough, while retaining a clonal multicellular life cycle. This occurred through biophysical adaptation-evolution of increasingly elongate cells that initially reduced the strain of cellular packing and then facilitated branch entanglements that enabled groups of cells to stay together even after many cellular bonds fracture. By contrast, snowflake yeast competing for low oxygen[5] remained microscopic, evolving to be only around sixfold larger, underscoring the critical role of oxygen levels in the evolution of multicellular size. Together, this research provides unique insights into an ongoing evolutionary transition in individuality, showing how simple groups of cells overcome fundamental biophysical limitations through gradual, yet sustained, multicellular evolution.}, } @article {pmid37160092, year = {2023}, author = {Conlin, PL and Ratcliff, WC}, title = {Evolution: Understanding the origins of facultative multicellular life cycles.}, journal = {Current biology : CB}, volume = {33}, number = {9}, pages = {R356-R358}, doi = {10.1016/j.cub.2023.03.065}, pmid = {37160092}, issn = {1879-0445}, mesh = {Animals ; *Life Cycle Stages ; *Saccharomyces cerevisiae ; }, abstract = {Multicellular organisms exhibit a fascinating diversity of life cycles, but little is known about the factors governing life-cycle evolution. New studies of wild yeast and cyanobacteria provide insight into how and why facultative multicellular life cycles arise.}, } @article {pmid37155901, year = {2023}, author = {Cooney, DB and Levin, SA and Mori, Y and Plotkin, JB}, title = {Evolutionary dynamics within and among competing groups.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {20}, pages = {e2216186120}, pmid = {37155901}, issn = {1091-6490}, mesh = {Humans ; *Cooperative Behavior ; *Biological Evolution ; Selection, Genetic ; Game Theory ; }, abstract = {Biological and social systems are structured at multiple scales, and the incentives of individuals who interact in a group may diverge from the collective incentive of the group as a whole. Mechanisms to resolve this tension are responsible for profound transitions in evolutionary history, including the origin of cellular life, multicellular life, and even societies. Here, we synthesize a growing literature that extends evolutionary game theory to describe multilevel evolutionary dynamics, using nested birth-death processes and partial differential equations to model natural selection acting on competition within and among groups of individuals. We analyze how mechanisms known to promote cooperation within a single group-including assortment, reciprocity, and population structure-alter evolutionary outcomes in the presence of competition among groups. We find that population structures most conducive to cooperation in multiscale systems can differ from those most conducive within a single group. Likewise, for competitive interactions with a continuous range of strategies we find that among-group selection may fail to produce socially optimal outcomes, but it can nonetheless produce second-best solutions that balance individual incentives to defect with the collective incentives for cooperation. We conclude by describing the broad applicability of multiscale evolutionary models to problems ranging from the production of diffusible metabolites in microbes to the management of common-pool resources in human societies.}, } @article {pmid37141807, year = {2023}, author = {Tsai, HH and Wang, J and Geldner, N and Zhou, F}, title = {Spatiotemporal control of root immune responses during microbial colonization.}, journal = {Current opinion in plant biology}, volume = {74}, number = {}, pages = {102369}, doi = {10.1016/j.pbi.2023.102369}, pmid = {37141807}, issn = {1879-0356}, mesh = {Humans ; *Bacteria ; Symbiosis ; Microbial Interactions ; *Arabidopsis ; Immunity ; Plant Roots/microbiology ; }, abstract = {The entire evolutionary trajectory of plants towards large and complex multi-cellular organisms has been accompanied by incessant interactions with omnipresent unicellular microbes. This led to the evolution of highly complex microbial communities, whose members display the entire spectrum of pathogenic to mutualistic behaviors. Plant roots are dynamic, fractally growing organs and even small Arabidopsis roots harbor millions of individual microbes of diverse taxa. It is evident that microbes at different positions on a root surface could experience fundamentally different environments, which, moreover, rapidly change over time. Differences in spatial scales between microbes and roots compares to humans and the cities they inhabit. Such considerations make it evident that mechanisms of root-microbe interactions can only be understood if analyzed at relevant spatial and temporal scales. This review attempts to provide an overview of the rapid recent progress that has been made in mapping and manipulating plant damage and immune responses at cellular resolution, as well as in visualizing bacterial communities and their transcriptional activities. We further discuss the impact that such approaches will have for a more predictive understanding of root-microbe interactions.}, } @article {pmid37140022, year = {2023}, author = {Krasovec, M and Hoshino, M and Zheng, M and Lipinska, AP and Coelho, SM}, title = {Low Spontaneous Mutation Rate in Complex Multicellular Eukaryotes with a Haploid-Diploid Life Cycle.}, journal = {Molecular biology and evolution}, volume = {40}, number = {6}, pages = {}, pmid = {37140022}, issn = {1537-1719}, mesh = {Animals ; Haploidy ; *Diploidy ; Mutation Rate ; Eukaryota ; Life Cycle Stages/genetics ; Plants ; *Phaeophyceae/genetics ; }, abstract = {The spontaneous mutation rate µ is a crucial parameter to understand evolution and biodiversity. Mutation rates are highly variable across species, suggesting that µ is susceptible to selection and drift and that species life cycle and life history may impact its evolution. In particular, asexual reproduction and haploid selection are expected to affect the mutation rate, but very little empirical data are available to test this expectation. Here, we sequence 30 genomes of a parent-offspring pedigree in the model brown alga Ectocarpus sp.7, and 137 genomes of an interspecific cross of the closely related brown alga Scytosiphon to have access to the spontaneous mutation rate of representative organisms of a complex multicellular eukaryotic lineage outside animals and plants, and to evaluate the potential impact of life cycle on the mutation rate. Brown algae alternate between a haploid and a diploid stage, both multicellular and free living, and utilize both sexual and asexual reproduction. They are, therefore, excellent models to empirically test expectations of the effect of asexual reproduction and haploid selection on mutation rate evolution. We estimate that Ectocarpus has a base substitution rate of µbs = 4.07 × 10-10 per site per generation, whereas the Scytosiphon interspecific cross had µbs = 1.22 × 10-9. Overall, our estimations suggest that these brown algae, despite being multicellular complex eukaryotes, have unusually low mutation rates. In Ectocarpus, effective population size (Ne) could not entirely explain the low µbs. We propose that the haploid-diploid life cycle, combined with extensive asexual reproduction, may be additional key drivers of the mutation rate in these organisms.}, } @article {pmid37107699, year = {2023}, author = {Grochau-Wright, ZI and Nedelcu, AM and Michod, RE}, title = {The Genetics of Fitness Reorganization during the Transition to Multicellularity: The Volvocine regA-like Family as a Model.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, pmid = {37107699}, issn = {2073-4425}, mesh = {Phylogeny ; *Chlorophyta ; *Volvox/genetics ; Models, Biological ; Cell Differentiation/genetics ; }, abstract = {The evolutionary transition from single-celled to multicellular individuality requires organismal fitness to shift from the cell level to a cell group. This reorganization of fitness occurs by re-allocating the two components of fitness, survival and reproduction, between two specialized cell types in the multicellular group: soma and germ, respectively. How does the genetic basis for such fitness reorganization evolve? One possible mechanism is the co-option of life history genes present in the unicellular ancestors of a multicellular lineage. For instance, single-celled organisms must regulate their investment in survival and reproduction in response to environmental changes, particularly decreasing reproduction to ensure survival under stress. Such stress response life history genes can provide the genetic basis for the evolution of cellular differentiation in multicellular lineages. The regA-like gene family in the volvocine green algal lineage provides an excellent model system to study how this co-option can occur. We discuss the origin and evolution of the volvocine regA-like gene family, including regA-the gene that controls somatic cell development in the model organism Volvox carteri. We hypothesize that the co-option of life history trade-off genes is a general mechanism involved in the transition to multicellular individuality, making volvocine algae and the regA-like family a useful template for similar investigations in other lineages.}, } @article {pmid37107559, year = {2023}, author = {Casotti, MC and Meira, DD and Zetum, ASS and Araújo, BC and Silva, DRCD and Santos, EVWD and Garcia, FM and Paula, F and Santana, GM and Louro, LS and Alves, LNR and Braga, RFR and Trabach, RSDR and Bernardes, SS and Louro, TES and Chiela, ECF and Lenz, G and Carvalho, EF and Louro, ID}, title = {Computational Biology Helps Understand How Polyploid Giant Cancer Cells Drive Tumor Success.}, journal = {Genes}, volume = {14}, number = {4}, pages = {}, pmid = {37107559}, issn = {2073-4425}, mesh = {Humans ; Cell Line, Tumor ; *Neoplasm Recurrence, Local/pathology ; *Giant Cells/metabolism/pathology ; Polyploidy ; Computational Biology ; }, abstract = {Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. Newly formed cells end up accessing numerous multicellular and unicellular programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal or diverse clone formation. An integrative literature review was carried out, searching articles in several sites, including: PUBMED, NCBI-PMC, and Google Academic, published in English, indexed in referenced databases and without a publication time filter, but prioritizing articles from the last 3 years, to answer the following questions: (i) "What is the current knowledge about polyploidy in tumors?"; (ii) "What are the applications of computational studies for the understanding of cancer polyploidy?"; and (iii) "How do PGCCs contribute to tumorigenesis?"}, } @article {pmid37098330, year = {2023}, author = {Colgren, J and Burkhardt, P}, title = {Evolution: Was the nuclear-to-cytoplasmic ratio a key factor in the origin of animal multicellularity?.}, journal = {Current biology : CB}, volume = {33}, number = {8}, pages = {R298-R300}, doi = {10.1016/j.cub.2023.03.010}, pmid = {37098330}, issn = {1879-0445}, mesh = {Animals ; *Eukaryota ; *Mesomycetozoea ; Cytoplasm ; Cytosol ; Biological Evolution ; }, abstract = {The ichthyosporean Sphaeroforma arctica, a protist closely related to animals, displays coenocytic development followed by cellularization and cell release. A new study reveals that the nuclear-to-cytoplasmic ratio drives cellularization in these fascinating organisms.}, } @article {pmid37096591, year = {2023}, author = {Stéger, A and Palmgren, M}, title = {Hypothesis paper: the development of a regulatory layer in P2B autoinhibited Ca[2+]-ATPases may have facilitated plant terrestrialization and animal multicellularization.}, journal = {Plant signaling & behavior}, volume = {18}, number = {1}, pages = {2204284}, pmid = {37096591}, issn = {1559-2324}, mesh = {Animals ; *Adenosine Triphosphatases ; *Calmodulin/metabolism ; Protein Binding ; Calcium Signaling ; Calcium/metabolism ; }, abstract = {With the appearance of plants and animals, new challenges emerged. These multicellular eukaryotes had to solve for example the difficulties of multifaceted communication between cells and adaptation to new habitats. In this paper, we are looking for one piece of the puzzle that made the development of complex multicellular eukaryotes possible with a focus on regulation of P2B autoinhibited Ca[2+]-ATPases. P2B ATPases pump Ca[2+] out of the cytosol at the expense of ATP hydrolysis, and thereby maintain a steep gradient between the extra- and intracytosolic compartments which is utilized for Ca[2+]-mediated rapid cell signaling. The activity of these enzymes is regulated by a calmodulin (CaM)-responsive autoinhibitory region, which can be located in either termini of the protein, at the C-terminus in animals and at the N-terminus in plants. When the cytoplasmic Ca[2+] level reaches a threshold, the CaM/Ca[2+] complex binds to a calmodulin-binding domain (CaMBD) in the autoinhibitor, which leads to the upregulation of pump activity. In animals, protein activity is also controlled by acidic phospholipids that bind to a cytosolic portion of the pump. Here, we analyze the appearance of CaMBDs and the phospholipid-activating sequence and show that their evolution in animals and plants was independent. Furthermore, we hypothesize that different causes may have initiated the appearance of these regulatory layers: in animals, it is linked to the appearance of multicellularity, while in plants it co-occurs with their water-to-land transition.}, } @article {pmid37094139, year = {2023}, author = {Ros-Rocher, N and Kidner, RQ and Gerdt, C and Davidson, WS and Ruiz-Trillo, I and Gerdt, JP}, title = {Chemical factors induce aggregative multicellularity in a close unicellular relative of animals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {18}, pages = {e2216668120}, pmid = {37094139}, issn = {1091-6490}, support = {R35 GM138376/GM/NIGMS NIH HHS/United States ; S10 OD024988/OD/NIH HHS/United States ; T32 GM131994/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Eukaryota/genetics ; *Biological Evolution ; Phylogeny ; }, abstract = {Regulated cellular aggregation is an essential process for development and healing in many animal tissues. In some animals and a few distantly related unicellular species, cellular aggregation is regulated by diffusible chemical cues. However, it is unclear whether regulated cellular aggregation was part of the life cycles of the first multicellular animals and/or their unicellular ancestors. To fill this gap, we investigated the triggers of cellular aggregation in one of animals' closest unicellular living relatives-the filasterean Capsaspora owczarzaki. We discovered that Capsaspora aggregation is induced by chemical cues, as observed in some of the earliest branching animals and other unicellular species. Specifically, we found that calcium ions and lipids present in lipoproteins function together to induce aggregation of viable Capsaspora cells. We also found that this multicellular stage is reversible as depletion of the cues triggers disaggregation, which can be overcome upon reinduction. Our finding demonstrates that chemically regulated aggregation is important across diverse members of the holozoan clade. Therefore, this phenotype was plausibly integral to the life cycles of the unicellular ancestors of animals.}, } @article {pmid37093889, year = {2023}, author = {Kumar, T and Sethuraman, R and Mitra, S and Ravindran, B and Narayanan, M}, title = {MultiCens: Multilayer network centrality measures to uncover molecular mediators of tissue-tissue communication.}, journal = {PLoS computational biology}, volume = {19}, number = {4}, pages = {e1011022}, pmid = {37093889}, issn = {1553-7358}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Brain ; Gene Regulatory Networks/genetics ; *Alzheimer Disease/genetics ; }, abstract = {With the evolution of multicellularity, communication among cells in different tissues and organs became pivotal to life. Molecular basis of such communication has long been studied, but genome-wide screens for genes and other biomolecules mediating tissue-tissue signaling are lacking. To systematically identify inter-tissue mediators, we present a novel computational approach MultiCens (Multilayer/Multi-tissue network Centrality measures). Unlike single-layer network methods, MultiCens can distinguish within- vs. across-layer connectivity to quantify the "influence" of any gene in a tissue on a query set of genes of interest in another tissue. MultiCens enjoys theoretical guarantees on convergence and decomposability, and performs well on synthetic benchmarks. On human multi-tissue datasets, MultiCens predicts known and novel genes linked to hormones. MultiCens further reveals shifts in gene network architecture among four brain regions in Alzheimer's disease. MultiCens-prioritized hypotheses from these two diverse applications, and potential future ones like "Multi-tissue-expanded Gene Ontology" analysis, can enable whole-body yet molecular-level systems investigations in humans.}, } @article {pmid37086724, year = {2023}, author = {Hashimoto, A and Kawamura, N and Tarusawa, E and Takeda, I and Aoyama, Y and Ohno, N and Inoue, M and Kagamiuchi, M and Kato, D and Matsumoto, M and Hasegawa, Y and Nabekura, J and Schaefer, A and Moorhouse, AJ and Yagi, T and Wake, H}, title = {Microglia enable cross-modal plasticity by removing inhibitory synapses.}, journal = {Cell reports}, volume = {42}, number = {5}, pages = {112383}, doi = {10.1016/j.celrep.2023.112383}, pmid = {37086724}, issn = {2211-1247}, support = {DP2 MH100012/MH/NIMH NIH HHS/United States ; R01 AG072489/AG/NIA NIH HHS/United States ; R01 MH118329/MH/NIMH NIH HHS/United States ; RF1 AG068558/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Microglia ; Neurons/physiology ; Synapses/physiology ; Pyramidal Cells ; *Visual Cortex/physiology ; Neuronal Plasticity/physiology ; Vibrissae/physiology ; Somatosensory Cortex/physiology ; }, abstract = {Cross-modal plasticity is the repurposing of brain regions associated with deprived sensory inputs to improve the capacity of other sensory modalities. The functional mechanisms of cross-modal plasticity can indicate how the brain recovers from various forms of injury and how different sensory modalities are integrated. Here, we demonstrate that rewiring of the microglia-mediated local circuit synapse is crucial for cross-modal plasticity induced by visual deprivation (monocular deprivation [MD]). MD relieves the usual inhibition of functional connectivity between the somatosensory cortex and secondary lateral visual cortex (V2L). This results in enhanced excitatory responses in V2L neurons during whisker stimulation and a greater capacity for vibrissae sensory discrimination. The enhanced cross-modal response is mediated by selective removal of inhibitory synapse terminals on pyramidal neurons by the microglia in the V2L via matrix metalloproteinase 9 signaling. Our results provide insights into how cortical circuits integrate different inputs to functionally compensate for neuronal damage.}, } @article {pmid37083675, year = {2023}, author = {Isaksson, H and Brännström, Å and Libby, E}, title = {Minor variations in multicellular life cycles have major effects on adaptation.}, journal = {PLoS computational biology}, volume = {19}, number = {4}, pages = {e1010698}, pmid = {37083675}, issn = {1553-7358}, mesh = {Animals ; *Life Cycle Stages ; *Models, Theoretical ; Biological Evolution ; Acclimatization ; Phenotype ; }, abstract = {Multicellularity has evolved several independent times over the past hundreds of millions of years and given rise to a wide diversity of complex life. Recent studies have found that large differences in the fundamental structure of early multicellular life cycles can affect fitness and influence multicellular adaptation. Yet, there is an underlying assumption that at some scale or categorization multicellular life cycles are similar in terms of their adaptive potential. Here, we consider this possibility by exploring adaptation in a class of simple multicellular life cycles of filamentous organisms that only differ in one respect, how many daughter filaments are produced. We use mathematical models and evolutionary simulations to show that despite the similarities, qualitatively different mutations fix. In particular, we find that mutations with a tradeoff between cell growth and group survival, i.e. "selfish" or "altruistic" traits, spread differently. Specifically, altruistic mutations more readily spread in life cycles that produce few daughters while in life cycles producing many daughters either type of mutation can spread depending on the environment. Our results show that subtle changes in multicellular life cycles can fundamentally alter adaptation.}, } @article {pmid37081145, year = {2023}, author = {Cornwallis, CK and Svensson-Coelho, M and Lindh, M and Li, Q and Stábile, F and Hansson, LA and Rengefors, K}, title = {Single-cell adaptations shape evolutionary transitions to multicellularity in green algae.}, journal = {Nature ecology & evolution}, volume = {7}, number = {6}, pages = {889-902}, pmid = {37081145}, issn = {2397-334X}, support = {2018.0138//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 60501//John Templeton Foundation (JTF)/ ; 20210788//Crafoordska Stiftelsen (Crafoord Foundation)/ ; 2022-03503//Vetenskapsrådet (Swedish Research Council)/ ; 2016-03552//Vetenskapsrådet (Swedish Research Council)/ ; }, mesh = {Animals ; *Biological Evolution ; *Chlorophyta ; Acclimatization ; Predatory Behavior ; }, abstract = {The evolution of multicellular life has played a pivotal role in shaping biological diversity. However, we know surprisingly little about the natural environmental conditions that favour the formation of multicellular groups. Here we experimentally examine how key environmental factors (predation, nitrogen and water turbulence) combine to influence multicellular group formation in 35 wild unicellular green algae strains (19 Chlorophyta species). All environmental factors induced the formation of multicellular groups (more than four cells), but there was no evidence this was adaptive, as multicellularity (% cells in groups) was not related to population growth rate under any condition. Instead, population growth was related to extracellular matrix (ECM) around single cells and palmelloid formation, a unicellular life-cycle stage where two to four cells are retained within a mother-cell wall after mitosis. ECM production increased with nitrogen levels resulting in more cells being in palmelloids and higher rates of multicellular group formation. Examining the distribution of 332 algae species across 478 lakes monitored over 55 years, showed that ECM and nitrogen availability also predicted patterns of obligate multicellularity in nature. Our results highlight that adaptations of unicellular organisms to cope with environmental challenges may be key to understanding evolutionary routes to multicellular life.}, } @article {pmid37080197, year = {2023}, author = {Cadart, C and Bartz, J and Oaks, G and Liu, MZ and Heald, R}, title = {Polyploidy in Xenopus lowers metabolic rate by decreasing total cell surface area.}, journal = {Current biology : CB}, volume = {33}, number = {9}, pages = {1744-1752.e7}, pmid = {37080197}, issn = {1879-0445}, support = {R35 GM118183/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Triploidy ; Xenopus laevis/genetics ; *Polyploidy ; Ploidies ; Diploidy ; Cell Membrane ; }, abstract = {Although polyploidization is frequent in development, cancer, and evolution, impacts on animal metabolism are poorly understood. In Xenopus frogs, the number of genome copies (ploidy) varies across species and can be manipulated within a species. Here, we show that triploid tadpoles contain fewer, larger cells than diploids and consume oxygen at a lower rate. Drug treatments revealed that the major processes accounting for tadpole energy expenditure include cell proliferation, biosynthesis, and maintenance of plasma membrane potential. While inhibiting cell proliferation did not abolish the oxygen consumption difference between diploids and triploids, treatments that altered cellular biosynthesis or electrical potential did. Combining these results with a simple mathematical framework, we propose that the decrease in total cell surface area lowered production and activity of plasma membrane components including the Na[+]/K[+] ATPase, reducing energy consumption in triploids. Comparison of Xenopus species that evolved through polyploidization revealed that metabolic differences emerged during development when cell size scaled with genome size. Thus, ploidy affects metabolism by altering the cell surface area to volume ratio in a multicellular organism.}, } @article {pmid37067637, year = {2023}, author = {Ros-Rocher, N and Brunet, T}, title = {What is it like to be a choanoflagellate? Sensation, processing and behavior in the closest unicellular relatives of animals.}, journal = {Animal cognition}, volume = {26}, number = {6}, pages = {1767-1782}, pmid = {37067637}, issn = {1435-9456}, support = {EvoMorphoCell 101040745/ERC_/European Research Council/International ; }, mesh = {Animals ; *Choanoflagellata/genetics ; Sensation ; }, abstract = {All animals evolved from a single lineage of unicellular precursors more than 600 million years ago. Thus, the biological and genetic foundations for animal sensation, cognition and behavior must necessarily have arisen by modifications of pre-existing features in their unicellular ancestors. Given that the single-celled ancestors of the animal kingdom are extinct, the only way to reconstruct how these features evolved is by comparing the biology and genomic content of extant animals to their closest living relatives. Here, we reconstruct the Umwelt (the subjective, perceptive world) inhabited by choanoflagellates, a group of unicellular (or facultatively multicellular) aquatic microeukaryotes that are the closest living relatives of animals. Although behavioral research on choanoflagellates remains patchy, existing evidence shows that they are capable of chemosensation, photosensation and mechanosensation. These processes often involve specialized sensorimotor cellular appendages (cilia, microvilli, and/or filopodia) that resemble those that underlie perception in most animal sensory cells. Furthermore, comparative genomics predicts an extensive "sensory molecular toolkit" in choanoflagellates, which both provides a potential basis for known behaviors and suggests the existence of a largely undescribed behavioral complexity that presents exciting avenues for future research. Finally, we discuss how facultative multicellularity in choanoflagellates might help us understand how evolution displaced the locus of decision-making from a single cell to a collective, and how a new space of behavioral complexity might have become accessible in the process.}, } @article {pmid37048099, year = {2023}, author = {Leitner, N and Ertl, R and Gabner, S and Fuchs-Baumgartinger, A and Walter, I and Hlavaty, J}, title = {Isolation and Characterization of Novel Canine Osteosarcoma Cell Lines from Chemotherapy-Naïve Patients.}, journal = {Cells}, volume = {12}, number = {7}, pages = {}, pmid = {37048099}, issn = {2073-4409}, mesh = {Animals ; Dogs ; Cell Line, Tumor ; *Osteosarcoma/pathology ; *MicroRNAs/genetics ; Gene Expression Profiling ; *Bone Neoplasms/metabolism ; }, abstract = {The present study aimed to establish novel canine osteosarcoma cell lines (COS3600, COS3600B, COS4074) and characterize the recently described COS4288 cells. The established D-17 cell line served as a reference. Analyzed cell lines differed notably in their biological characteristics. Calculated doubling times were between 22 h for COS3600B and 426 h for COS4074 cells. COS3600B and COS4288 cells produced visible colonies after anchorage-independent growth in soft agar. COS4288 cells were identified as cells with the highest migratory capacity. All cells displayed the ability to invade through an artificial basement membrane matrix. Immunohistochemical analyses revealed the mesenchymal origin of all COS cell lines as well as positive staining for the osteosarcoma-relevant proteins alkaline phosphatase and karyopherin α2. Expression of p53 was confirmed in all tested cell lines. Gene expression analyses of selected genes linked to cellular immune checkpoints (CD270, CD274, CD276), kinase activity (MET, ERBB2), and metastatic potential (MMP-2, MMP-9) as well as selected long non-coding RNA (MALAT1) and microRNAs (miR-9, miR-34a, miR-93) are provided. All tested cell lines were able to grow as multicellular spheroids. In all spheroids except COS4288, calcium deposition was detected by von Kossa staining. We believe that these new cell lines serve as useful biological models for future studies.}, } @article {pmid37047167, year = {2023}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047167}, issn = {1422-0067}, support = {No. 075-15-2021-1075//Ministry of Science and Higher Education of the Russian Federation/ ; }, mesh = {Animals ; Humans ; Biological Evolution ; *Brachyura ; Carcinogenesis/genetics ; Cell Transformation, Neoplastic ; *Neoplasms/genetics ; }, abstract = {Using meta-analyses, we introduce a unicellular attractor (UCA) model integrating essential features of the 'atavistic reversal', 'cancer attractor', 'somatic mutation', 'genome chaos', and 'tissue organization field' theories. The 'atavistic reversal' theory is taken as a keystone. We propose a possible mechanism of this reversal, its refinement called 'gradual atavism', and evidence for the 'serial atavism' model. We showed the gradual core-to-periphery evolutionary growth of the human interactome resulting in the higher protein interaction density and global interactome centrality in the UC center. In addition, we revealed that UC genes are more actively expressed even in normal cells. The modeling of random walk along protein interaction trajectories demonstrated that random alterations in cellular networks, caused by genetic and epigenetic changes, can result in a further gradual activation of the UC center. These changes can be induced and accelerated by cellular stress that additionally activates UC genes (especially during cell proliferation), because the genes involved in cellular stress response and cell cycle are mostly of UC origin. The functional enrichment analysis showed that cancer cells demonstrate the hyperactivation of energetics and the suppression of multicellular genes involved in communication with the extracellular environment (especially immune surveillance). Collectively, these events can unleash selfish cell behavior aimed at survival at all means. All these changes are boosted by polyploidization. The UCA model may facilitate an understanding of oncogenesis and promote the development of therapeutic strategies.}, } @article {pmid37046079, year = {2023}, author = {Li, G and Chen, L and Pang, K and Tang, Q and Wu, C and Yuan, X and Zhou, C and Xiao, S}, title = {Tonian carbonaceous compressions indicate that Horodyskia is one of the oldest multicellular and coenocytic macro-organisms.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {399}, pmid = {37046079}, issn = {2399-3642}, mesh = {*Eukaryota ; *Fossils ; China ; }, abstract = {Macrofossils with unambiguous biogenic origin and predating the one-billion-year-old multicellular fossils Bangiomorpha and Proterocladus interpreted as crown-group eukaryotes are quite rare. Horodyskia is one of these few macrofossils, and it extends from the early Mesoproterozoic Era to the terminal Ediacaran Period. The biological interpretation of this enigmatic fossil, however, has been a matter of controversy since its discovery in 1982, largely because there was no evidence for the preservation of organic walls. Here we report new carbonaceous compressions of Horodyskia from the Tonian successions (~950-720 Ma) in North China. The macrofossils herein with bona fide organic walls reinforce the biogenicity of Horodyskia. Aided by the new material, we reconstruct Horodyskia as a colonial organism composed of a chain of organic-walled vesicles that likely represent multinucleated (coenocytic) cells of early eukaryotes. Two species of Horodyskia are differentiated on the basis of vesicle sizes, and their co-existence in the Tonian assemblage provides a link between the Mesoproterozoic (H. moniliformis) and the Ediacaran (H. minor) species. Our study thus provides evidence that eukaryotes have acquired macroscopic size through the combination of coenocytism and colonial multicellularity at least ~1.48 Ga, and highlights an exceptionally long range and morphological stasis of this Proterozoic macrofossils.}, } @article {pmid37029839, year = {2023}, author = {Varilla González, JD and Macedo Alves, F and Bagnatori Sartori, ÂL and de Oliveira Arruda, RDC}, title = {Diversity and evolution of leaflet anatomical characters in the Pterocarpus clade (Fabaceae: Papilionoideae).}, journal = {Journal of plant research}, volume = {136}, number = {4}, pages = {453-481}, pmid = {37029839}, issn = {1618-0860}, support = {88882.461305/2019-01//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Phylogeny ; *Pterocarpus ; *Fabaceae ; Trichomes ; Microscopy, Electron, Scanning ; }, abstract = {The Pterocarpus clade includes 23 genera previously attributed to different Fabaceae tribes. The recent rearrangements of many genera in the clade do not recognize morphological synapomorphies. This study aimed to identify new synapomorphies for the Pterocarpus clade, to identify characters supporting inter-generic relationships currently resolved only by molecular data and to identify diagnostic characters at the genus and species levels. Subterminal leaflets of the studied genera were selected and analyzed using light and scanning electron microscopy. Ancestral reconstruction was performed using morphological and anatomical characters of 16 genera of the Pterocarpus clade. The convex epidermal relief in the region of the main vein indicated the relationship among all genera of the group. Anchor-like multicellular trichomes are features shared by Brya and Cranocarpus, which are the sister group to the other genera of the clade. Subepidermal layers are features shared by the Centrolobium, Etaballia, Paramachaerium, Pterocarpus and Tipuana genera, and the sclerenchyma sheath in the leaflet margin is reported in the Discolobium, Riedeliella and Platymiscium genera. Bulbous based glandular trichomes and vesicular glandular trichomes are diagnostic at the species level in Centrolobium and Pterocarpus, respectively. The leaflet characters investigated can be useful for the taxonomic delimitation at both the genus and species levels of the Pterocarpus clade. Our dataset provides new synapomorphies, elucidates the inter-generic relationships and reinforces the phylogenetic classification of the Pterocarpus clade resolved by molecular data.}, } @article {pmid37023182, year = {2023}, author = {Darras, H and Berney, C and Hasin, S and Drescher, J and Feldhaar, H and Keller, L}, title = {Obligate chimerism in male yellow crazy ants.}, journal = {Science (New York, N.Y.)}, volume = {380}, number = {6640}, pages = {55-58}, doi = {10.1126/science.adf0419}, pmid = {37023182}, issn = {1095-9203}, mesh = {Animals ; Male ; *Ants/cytology/genetics/growth & development ; *Chimerism ; Diploidy ; *Reproduction ; Semen/cytology ; Germ Cells/cytology ; }, abstract = {Multicellular organisms typically develop from a single fertilized egg and therefore consist of clonal cells. We report an extraordinary reproductive system in the yellow crazy ant. Males are chimeras of haploid cells from two divergent lineages: R and W. R cells are overrepresented in the males' somatic tissues, whereas W cells are overrepresented in their sperm. Chimerism occurs when parental nuclei bypass syngamy and divide separately within the same egg. When syngamy takes place, the diploid offspring either develops into a queen when the oocyte is fertilized by an R sperm or into a worker when fertilized by a W sperm. This study reveals a mode of reproduction that may be associated with a conflict between lineages to preferentially enter the germ line.}, } @article {pmid37019107, year = {2023}, author = {Barrere, J and Nanda, P and Murray, AW}, title = {Alternating selection for dispersal and multicellularity favors regulated life cycles.}, journal = {Current biology : CB}, volume = {33}, number = {9}, pages = {1809-1817.e3}, pmid = {37019107}, issn = {1879-0445}, support = {R01 GM043987/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Saccharomyces cerevisiae/physiology ; *Biological Evolution ; Phenotype ; Life Cycle Stages ; Reproduction ; }, abstract = {The evolution of complex multicellularity opened paths to increased morphological diversity and organizational novelty. This transition involved three processes: cells remained attached to one another to form groups, cells within these groups differentiated to perform different tasks, and the groups evolved new reproductive strategies.[1][,][2][,][3][,][4][,][5] Recent experiments identified selective pressures and mutations that can drive the emergence of simple multicellularity and cell differentiation,[6][,][7][,][8][,][9][,][10][,][11] but the evolution of life cycles, particularly how simple multicellular forms reproduce, has been understudied. The selective pressure and mechanisms that produced a regular alternation between single cells and multicellular collectives are still unclear.[12] To probe the factors regulating simple multicellular life cycles, we examined a collection of wild isolates of the budding yeast S. cerevisiae.[12][,][13] We found that all these strains can exist as multicellular clusters, a phenotype that is controlled by the mating-type locus and strongly influenced by the nutritional environment. Inspired by this variation, we engineered inducible dispersal in a multicellular laboratory strain and demonstrated that a regulated life cycle has an advantage over constitutively single-celled or constitutively multicellular life cycles when the environment alternates between favoring intercellular cooperation (a low sucrose concentration) and dispersal (a patchy environment generated by emulsion). Our results suggest that the separation of mother and daughter cells is under selection in wild isolates and is regulated by their genetic composition and the environments they encounter and that alternating patterns of resource availability may have played a role in the evolution of life cycles.}, } @article {pmid37011504, year = {2023}, author = {Morehouse, BR}, title = {Phage defense origin of animal immunity.}, journal = {Current opinion in microbiology}, volume = {73}, number = {}, pages = {102295}, doi = {10.1016/j.mib.2023.102295}, pmid = {37011504}, issn = {1879-0364}, mesh = {Animals ; *Bacteria/genetics ; Prokaryotic Cells ; Archaea/genetics ; Immunity, Innate ; *Bacteriophages/genetics ; }, abstract = {The innate immune system is the first line of defense against microbial pathogens. Many of the features of eukaryotic innate immunity have long been viewed as lineage-specific innovations, evolved to deal with the challenges and peculiarities of multicellular life. However, it has become increasingly apparent that in addition to evolving their own unique antiviral immune strategies, all lifeforms have some shared defense strategies in common. Indeed, critical fixtures of animal innate immunity bear striking resemblance in both structure and function to the multitude of diverse bacteriophage (phage) defense pathways discovered hidden in plain sight within the genomes of bacteria and archaea. This review will highlight many surprising examples of the recently revealed connections between prokaryotic and eukaryotic antiviral immune systems.}, } @article {pmid37005641, year = {2023}, author = {Guan, X and Zhang, L and Lai, S and Zhang, J and Wei, J and Wang, K and Zhang, W and Li, C and Tong, J and Lei, Z}, title = {Green synthesis of glyco-CuInS2 QDs with visible/NIR dual emission for 3D multicellular tumor spheroid and in vivo imaging.}, journal = {Journal of nanobiotechnology}, volume = {21}, number = {1}, pages = {118}, pmid = {37005641}, issn = {1477-3155}, support = {21965032; 22267012; 21761032; 52162034//National Natural Science Foundation of China/ ; 20JR5RA525; 20JR10RA143//Natural Science Foundation of Gansu Province/ ; 2020BSZX08//Doctoral Program Fund of Lanzhou University of Arts and Sciences/ ; }, mesh = {Humans ; Diagnostic Imaging ; *Nanoparticles ; *Quantum Dots ; HeLa Cells ; Water ; }, abstract = {Glyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the "direct" reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0-4.0 nm. They exhibited well-separated dual emission in the visible region (500-590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from - 23.9 to - 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes.}, } @article {pmid37002899, year = {2023}, author = {LeBleu, VS and Dai, J and Tsutakawa, S and MacDonald, BA and Alge, JL and Sund, M and Xie, L and Sugimoto, H and Tainer, J and Zon, LI and Kalluri, R}, title = {Identification of unique α4 chain structure and conserved antiangiogenic activity of α3NC1 type IV collagen in zebrafish.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {252}, number = {7}, pages = {1046-1060}, pmid = {37002899}, issn = {1097-0177}, support = {R01 DK055001/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Collagen Type IV/genetics ; *Zebrafish ; Endothelial Cells ; Protein Subunits/analysis/metabolism ; Basement Membrane/metabolism ; }, abstract = {BACKGROUND: Type IV collagen is an abundant component of basement membranes in all multicellular species and is essential for the extracellular scaffold supporting tissue architecture and function. Lower organisms typically have two type IV collagen genes, encoding α1 and α2 chains, in contrast with the six genes in humans, encoding α1-α6 chains. The α chains assemble into trimeric protomers, the building blocks of the type IV collagen network. The detailed evolutionary conservation of type IV collagen network remains to be studied.

RESULTS: We report on the molecular evolution of type IV collagen genes. The zebrafish α4 non-collagenous (NC1) domain, in contrast with its human ortholog, contains an additional cysteine residue and lacks the M93 and K211 residues involved in sulfilimine bond formation between adjacent protomers. This may alter α4 chain interactions with other α chains, as supported by temporal and anatomic expression patterns of collagen IV chains during the zebrafish development. Despite the divergence between zebrafish and human α3 NC1 domain (endogenous angiogenesis inhibitor, Tumstatin), the zebrafish α3 NC1 domain exhibits conserved antiangiogenic activity in human endothelial cells.

CONCLUSIONS: Our work supports type IV collagen is largely conserved between zebrafish and humans, with a possible difference involving the α4 chain.}, } @article {pmid37000909, year = {2023}, author = {Little, JC and Kaaronen, RO and Hukkinen, JI and Xiao, S and Sharpee, T and Farid, AM and Nilchiani, R and Barton, CM}, title = {Earth Systems to Anthropocene Systems: An Evolutionary, System-of-Systems, Convergence Paradigm for Interdependent Societal Challenges.}, journal = {Environmental science & technology}, volume = {57}, number = {14}, pages = {5504-5520}, doi = {10.1021/acs.est.2c06203}, pmid = {37000909}, issn = {1520-5851}, mesh = {Animals ; Humans ; *Agriculture ; *Biodiversity ; Urbanization ; Mammals ; }, abstract = {Humans have made profound changes to the Earth. The resulting societal challenges of the Anthropocene (e.g., climate change and impacts, renewable energy, adaptive infrastructure, disasters, pandemics, food insecurity, and biodiversity loss) are complex and systemic, with causes, interactions, and consequences that cascade across a globally connected system of systems. In this Critical Review, we turn to our "origin story" for insight, briefly tracing the formation of the Universe and the Earth, the emergence of life, the evolution of multicellular organisms, mammals, primates, and humans, as well as the more recent societal transitions involving agriculture, urbanization, industrialization, and computerization. Focusing on the evolution of the Earth, genetic evolution, the evolution of the brain, and cultural evolution, which includes technological evolution, we identify a nested evolutionary sequence of geophysical, biophysical, sociocultural, and sociotechnical systems, emphasizing the causal mechanisms that first formed, and then transformed, Earth systems into Anthropocene systems. Describing how the Anthropocene systems coevolved, and briefly illustrating how the ensuing societal challenges became tightly integrated across multiple spatial, temporal, and organizational scales, we conclude by proposing an evolutionary, system-of-systems, convergence paradigm for the entire family of interdependent societal challenges of the Anthropocene.}, } @article {pmid36996815, year = {2023}, author = {Olivetta, M and Dudin, O}, title = {The nuclear-to-cytoplasmic ratio drives cellularization in the close animal relative Sphaeroforma arctica.}, journal = {Current biology : CB}, volume = {33}, number = {8}, pages = {1597-1605.e3}, doi = {10.1016/j.cub.2023.03.019}, pmid = {36996815}, issn = {1879-0445}, mesh = {Animals ; *Eukaryota/genetics ; *Mesomycetozoea/genetics ; Cell Nucleus ; Cytosol ; Genome ; }, abstract = {The ratio of nuclear content to cytoplasmic volume (N/C ratio) is a key regulator driving the maternal-to-zygotic transition in most animal embryos. Altering this ratio often impacts zygotic genome activation and deregulates the timing and outcome of embryogenesis.[1][,][2][,][3] Despite being ubiquitous across animals, little is known about when the N/C ratio evolved to control multicellular development. Such capacity either originated with the emergence of animal multicellularity or was co-opted from the mechanisms present in unicellular organisms.[4] An effective strategy to tackle this question is to investigate the close relatives of animals exhibiting life cycles with transient multicellular stages.[5] Among these are ichthyosporeans, a lineage of protists undergoing coenocytic development followed by cellularization and cell release.[6][,][7][,][8] During cellularization, a transient multicellular stage resembling animal epithelia is generated, offering a unique opportunity to examine whether the N/C ratio regulates multicellular development. Here, we use time-lapse microscopy to characterize how the N/C ratio affects the life cycle of the best-studied ichthyosporean model, Sphaeroforma arctica. We uncover that the last stages of cellularization coincide with a significant increase in the N/C ratio. Increasing the N/C ratio by reducing the coenocytic volume accelerates cellularization, whereas decreasing the N/C ratio by lowering the nuclear content halts it. Moreover, centrifugation and pharmacological inhibitor experiments suggest that the N/C ratio is locally sensed at the cortex and relies on phosphatase activity. Altogether, our results show that the N/C ratio drives cellularization in S. arctica, suggesting that its capacity to control multicellular development predates animal emergence.}, } @article {pmid36996248, year = {2023}, author = {Herold, J and Behle, E and Rosenbauer, J and Ferruzzi, J and Schug, A}, title = {Development of a scoring function for comparing simulated and experimental tumor spheroids.}, journal = {PLoS computational biology}, volume = {19}, number = {3}, pages = {e1010471}, pmid = {36996248}, issn = {1553-7358}, support = {U01 CA202123/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Spheroids, Cellular ; Collagen/chemistry ; Extracellular Matrix ; *Neoplasms ; *Neoplasms, Experimental ; }, abstract = {Progress continues in the field of cancer biology, yet much remains to be unveiled regarding the mechanisms of cancer invasion. In particular, complex biophysical mechanisms enable a tumor to remodel the surrounding extracellular matrix (ECM), allowing cells to invade alone or collectively. Tumor spheroids cultured in collagen represent a simplified, reproducible 3D model system, which is sufficiently complex to recapitulate the evolving organization of cells and interaction with the ECM that occur during invasion. Recent experimental approaches enable high resolution imaging and quantification of the internal structure of invading tumor spheroids. Concurrently, computational modeling enables simulations of complex multicellular aggregates based on first principles. The comparison between real and simulated spheroids represents a way to fully exploit both data sources, but remains a challenge. We hypothesize that comparing any two spheroids requires first the extraction of basic features from the raw data, and second the definition of key metrics to match such features. Here, we present a novel method to compare spatial features of spheroids in 3D. To do so, we define and extract features from spheroid point cloud data, which we simulated using Cells in Silico (CiS), a high-performance framework for large-scale tissue modeling previously developed by us. We then define metrics to compare features between individual spheroids, and combine all metrics into an overall deviation score. Finally, we use our features to compare experimental data on invading spheroids in increasing collagen densities. We propose that our approach represents the basis for defining improved metrics to compare large 3D data sets. Moving forward, this approach will enable the detailed analysis of spheroids of any origin, one application of which is informing in silico spheroids based on their in vitro counterparts. This will enable both basic and applied researchers to close the loop between modeling and experiments in cancer research.}, } @article {pmid36980921, year = {2023}, author = {Han, M and Ren, J and Guo, H and Tong, X and Hu, H and Lu, K and Dai, Z and Dai, F}, title = {Mutation Rate and Spectrum of the Silkworm in Normal and Temperature Stress Conditions.}, journal = {Genes}, volume = {14}, number = {3}, pages = {}, pmid = {36980921}, issn = {2073-4425}, mesh = {Animals ; *Bombyx/genetics ; Temperature ; Mutation Rate ; Insecta/genetics ; Genome ; }, abstract = {Mutation rate is a crucial parameter in evolutionary genetics. However, the mutation rate of most species as well as the extent to which the environment can alter the genome of multicellular organisms remain poorly understood. Here, we used parents-progeny sequencing to investigate the mutation rate and spectrum of the domestic silkworm (Bombyx mori) among normal and two temperature stress conditions (32 °C and 0 °C). The rate of single-nucleotide mutations in the normal temperature rearing condition was 0.41 × 10[-8] (95% confidence interval, 0.33 × 10[-8]-0.49 × 10[-8]) per site per generation, which was up to 1.5-fold higher than in four previously studied insects. Moreover, the mutation rates of the silkworm under the stresses are significantly higher than in normal conditions. Furthermore, the mutation rate varies less in gene regions under normal and temperature stresses. Together, these findings expand the known diversity of the mutation rate among eukaryotes but also have implications for evolutionary analysis that assumes a constant mutation rate among species and environments.}, } @article {pmid36980213, year = {2023}, author = {Merino, MM and Garcia-Sanz, JA}, title = {Stemming Tumoral Growth: A Matter of Grotesque Organogenesis.}, journal = {Cells}, volume = {12}, number = {6}, pages = {}, pmid = {36980213}, issn = {2073-4409}, mesh = {Humans ; *Neoplasm Recurrence, Local ; *Organogenesis ; Neoplastic Stem Cells ; Cell Transformation, Neoplastic ; }, abstract = {The earliest metazoans probably evolved from single-celled organisms which found the colonial system to be a beneficial organization. Over the course of their evolution, these primary colonial organisms increased in size, and division of labour among the cells became a remarkable feature, leading to a higher level of organization: the biological organs. Primitive metazoans were the first organisms in evolution to show organ-type structures, which set the grounds for complex organs to evolve. Throughout evolution, and concomitant with organogenesis, is the appearance of tissue-specific stem cells. Tissue-specific stem cells gave rise to multicellular living systems with distinct organs which perform specific physiological functions. This setting is a constructive role of evolution; however, rebel cells can take over the molecular mechanisms for other purposes: nowadays we know that cancer stem cells, which generate aberrant organ-like structures, are at the top of a hierarchy. Furthermore, cancer stem cells are the root of metastasis, therapy resistance, and relapse. At present, most therapeutic drugs are unable to target cancer stem cells and therefore, treatment becomes a challenging issue. We expect that future research will uncover the mechanistic "forces" driving organ growth, paving the way to the implementation of new strategies to impair human tumorigenesis.}, } @article {pmid36964572, year = {2023}, author = {Barrera-Redondo, J and Lotharukpong, JS and Drost, HG and Coelho, SM}, title = {Uncovering gene-family founder events during major evolutionary transitions in animals, plants and fungi using GenEra.}, journal = {Genome biology}, volume = {24}, number = {1}, pages = {54}, pmid = {36964572}, issn = {1474-760X}, mesh = {Animals ; Phylogeny ; *Biological Evolution ; *Genomics/methods ; Fungi/genetics ; Plants/genetics ; Evolution, Molecular ; }, abstract = {We present GenEra (https://github.com/josuebarrera/GenEra), a DIAMOND-fueled gene-family founder inference framework that addresses previously raised limitations and biases in genomic phylostratigraphy, such as homology detection failure. GenEra also reduces computational time from several months to a few days for any genome of interest. We analyze the emergence of taxonomically restricted gene families during major evolutionary transitions in plants, animals, and fungi. Our results indicate that the impact of homology detection failure on inferred patterns of gene emergence is lineage-dependent, suggesting that plants are more prone to evolve novelty through the emergence of new genes compared to animals and fungi.}, } @article {pmid36959212, year = {2023}, author = {Nofech-Mozes, I and Soave, D and Awadalla, P and Abelson, S}, title = {Pan-cancer classification of single cells in the tumour microenvironment.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {1615}, pmid = {36959212}, issn = {2041-1723}, mesh = {Humans ; Female ; *Tumor Microenvironment ; *Breast Neoplasms/pathology ; Gene Expression Profiling/methods ; Transcriptome ; Stromal Cells/pathology ; }, abstract = {Single-cell RNA sequencing can reveal valuable insights into cellular heterogeneity within tumour microenvironments (TMEs), paving the way for a deep understanding of cellular mechanisms contributing to cancer. However, high heterogeneity among the same cancer types and low transcriptomic variation in immune cell subsets present challenges for accurate, high-resolution confirmation of cells' identities. Here we present scATOMIC; a modular annotation tool for malignant and non-malignant cells. We trained scATOMIC on >300,000 cancer, immune, and stromal cells defining a pan-cancer reference across 19 common cancers and employ a hierarchical approach, outperforming current classification methods. We extensively confirm scATOMIC's accuracy on 225 tumour biopsies encompassing >350,000 cancer and a variety of TME cells. Lastly, we demonstrate scATOMIC's practical significance to accurately subset breast cancers into clinically relevant subtypes and predict tumours' primary origin across metastatic cancers. Our approach represents a broadly applicable strategy to analyse multicellular cancer TMEs.}, } @article {pmid36945744, year = {2023}, author = {Li, Y and Kim, EJ and Voshall, A and Moriyama, EN and Cerutti, H}, title = {Small RNAs >26 nt in length associate with AGO1 and are upregulated by nutrient deprivation in the alga Chlamydomonas.}, journal = {The Plant cell}, volume = {35}, number = {6}, pages = {1868-1887}, pmid = {36945744}, issn = {1532-298X}, mesh = {Animals ; *Chlamydomonas/genetics/metabolism ; RNA Interference ; Gene Expression Regulation ; Argonaute Proteins/genetics/metabolism ; *Chlamydomonas reinhardtii/genetics/metabolism ; }, abstract = {Small RNAs (sRNAs) associate with ARGONAUTE (AGO) proteins forming effector complexes with key roles in gene regulation and defense responses against molecular parasites. In multicellular eukaryotes, extensive duplication and diversification of RNA interference (RNAi) components have resulted in intricate pathways for epigenetic control of gene expression. The unicellular alga Chlamydomonas reinhardtii also has a complex RNAi machinery, including 3 AGOs and 3 DICER-like proteins. However, little is known about the biogenesis and function of most endogenous sRNAs. We demonstrate here that Chlamydomonas contains uncommonly long (>26 nt) sRNAs that associate preferentially with AGO1. Somewhat reminiscent of animal PIWI-interacting RNAs, these >26 nt sRNAs are derived from moderately repetitive genomic clusters and their biogenesis is DICER-independent. Interestingly, the sequences generating these >26-nt sRNAs have been conserved and amplified in several Chlamydomonas species. Moreover, expression of these longer sRNAs increases substantially under nitrogen or sulfur deprivation, concurrently with the downregulation of predicted target transcripts. We hypothesize that the transposon-like sequences from which >26-nt sRNAs are produced might have been ancestrally targeted for silencing by the RNAi machinery but, during evolution, certain sRNAs might have fortuitously acquired endogenous target genes and become integrated into gene regulatory networks.}, } @article {pmid36912901, year = {2023}, author = {Ebinghaus, M and Dos Santos, MDM and Tonelli, GSSS and Macagnan, D and Carvalho, EA and Dianese, JC}, title = {Raveneliopsis, a new genus of ravenelioid rust fungi on Cenostigma (Caesalpinioideae) from the Brazilian Cerrado and Caatinga.}, journal = {Mycologia}, volume = {115}, number = {2}, pages = {263-276}, doi = {10.1080/00275514.2023.2177048}, pmid = {36912901}, issn = {1557-2536}, mesh = {Brazil ; Phylogeny ; *Basidiomycota/genetics ; *Fabaceae ; }, abstract = {The multicellular discoid convex teliospore heads represent a prominent generic feature of the genus Ravenelia. However, recent molecular phylogenetic work has shown that this is a convergent trait, and that this genus does not represent a natural group. In 2000, a rust fungus infecting the Caesalpinioid species Cenostigma macrophyllum (= C. gardnerianum) was described as Ravenelia cenostigmatis. This species shows some rare features, such as an extra layer of sterile cells between the cysts and the fertile teliospores, spirally ornamented urediniospores, as well as strongly incurved paraphyses giving the telia and uredinia a basket-like appearance. Using freshly collected specimens of Rav. cenostigmatis and Rav. spiralis on C. macrophyllum, our phylogenetic analyses based on the nuc 28S, nuc 18S, and mt CO3 (cytochrome c oxidase subunit 3) gene sequences demonstrated that these two rust fungi belong in a lineage within the Raveneliineae that is distinct from Ravenelia s. str. Besides proposing their recombination into the new genus Raveneliopsis (type species R. cenostigmatis) and briefly discussing their potentially close phylogenetic affiliations, we suggest that five other Ravenelia species that are morphologically and ecologically close to the type species of Raveneliopsis, i.e., Rav. corbula, Rav. corbuloides, Rav. parahybana, Rav. pileolarioides, and Rav. Striatiformis, may be recombined pending new collections and confirmation through molecular phylogenetic analyses.}, } @article {pmid36907967, year = {2023}, author = {Lu, B and Hu, X and Warren, A and Song, W and Yan, Y}, title = {From oral structure to molecular evidence: new insights into the evolutionary phylogeny of the ciliate order Sessilida (Protista, Ciliophora), with the establishment of two new families and new contributions to the poorly studied family Vaginicolidae.}, journal = {Science China. Life sciences}, volume = {66}, number = {7}, pages = {1535-1553}, pmid = {36907967}, issn = {1869-1889}, mesh = {Humans ; Phylogeny ; *Ciliophora/genetics ; *Oligohymenophorea/genetics ; DNA, Ribosomal/genetics ; Cognition ; Sequence Analysis, DNA ; }, abstract = {Ciliated protists represent one of the most primitive and diverse lineages of eukaryotes, with nuclear dimorphism, a distinctive sexual process (conjugation), and extensive genome rearrangements. Among divergent ciliate lineages, the peritrich order Sessilida includes members with a colonial lifestyle, which may hint to an independent evolutionary attempt for multicellularity, although they are still single-celled organisms. To date, the evolution and phylogeny of this group are still far from clear, in part due to the paucity of molecular and/or morphological data for many taxa. In this study, we extend taxon sampling of a loricate group of sessilids by obtaining 69 new rDNA (SSU rDNA, ITS1-5.8S rDNA-ITS2, and LSU rDNA) sequences from 20 well-characterized representative species and analyze the phylogenetic relationships within Sessilida. The main findings are: (i) the genera Rhabdostyla and Campanella each represents a unique taxon at family level, supporting the establishment of two new families, i.e., Rhabdostylidae n. fam. and Campanellidae n. fam., respectively, the former being sister to a morphologically heterogeneous clade comprising Astylozoidae and several incertae sedis species and the latter occupying the basal position within the Sessilida clade; (ii) the structure of infundibular polykinety 3 is likely to be a phylogenetically informative character for resolving evolutionary relationships among sessilids; (iii) differences between sparsely and the densely arranged silverline systems could be a suprageneric taxonomic character; (iv) the monophyly of Vaginicolidae is confirmed, which is consistent with its specialized morphology, i.e., the possession of a typical peritrich lorica which might be an apomorphy for this group; (v) within Vaginicolidae, the monotypic Cothurniopsis sensu Stokes, 1893 is a synonym of Cothurnia Ehrenberg, 1831, and a new combination is created, i.e., Cothurnia valvata nov. comb.; (vi) Vaginicola sensu lato comprises at least two distinctly divergent clades, one affiliated with Thuricola and the other with a systematically puzzling clade represented by Vaginicola tincta.}, } @article {pmid36899423, year = {2023}, author = {Ouyang, X and Wu, B and Yu, H and Dong, B}, title = {DYRK1-mediated phosphorylation of endocytic components is required for extracellular lumen expansion in ascidian notochord.}, journal = {Biological research}, volume = {56}, number = {1}, pages = {10}, pmid = {36899423}, issn = {0717-6287}, support = {2019YFE0190900//National Key Research and Development Program of China/ ; }, mesh = {Animals ; Humans ; *Ciona intestinalis/metabolism ; Notochord/metabolism ; Phosphorylation ; Embryonic Development ; Morphogenesis ; }, abstract = {BACKGROUND: The biological tube is a basal biology structure distributed in all multicellular animals, from worms to humans, and has diverse biological functions. Formation of tubular system is crucial for embryogenesis and adult metabolism. Ascidian Ciona notochord lumen is an excellent in vivo model for tubulogenesis. Exocytosis has been known to be essential for tubular lumen formation and expansion. The roles of endocytosis in tubular lumen expansion remain largely unclear.

RESULTS: In this study, we first identified a dual specificity tyrosine-phosphorylation-regulated kinase 1 (DYRK1), the protein kinase, which was upregulated and required for ascidian notochord extracellular lumen expansion. We demonstrated that DYRK1 interacted with and phosphorylated one of the endocytic components endophilin at Ser263 that was essential for notochord lumen expansion. Moreover, through phosphoproteomic sequencing, we revealed that in addition to endophilin, the phosphorylation of other endocytic components was also regulated by DYRK1. The loss of function of DYRK1 disturbed endocytosis. Then, we demonstrated that clathrin-mediated endocytosis existed and was required for notochord lumen expansion. In the meantime, the results showed that the secretion of notochord cells is vigorous in the apical membrane.

CONCLUSIONS: We found the co-existence of endocytosis and exocytosis activities in apical membrane during lumen formation and expansion in Ciona notochord. A novel signaling pathway is revealed that DYRK1 regulates the endocytosis by phosphorylation that is required for lumen expansion. Our finding thus indicates a dynamic balance between endocytosis and exocytosis is crucial to maintain apical membrane homeostasis that is essential for lumen growth and expansion in tubular organogenesis.}, } @article {pmid36897970, year = {2023}, author = {Davidescu, MR and Romanczuk, P and Gregor, T and Couzin, ID}, title = {Growth produces coordination trade-offs in Trichoplax adhaerens, an animal lacking a central nervous system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {11}, pages = {e2206163120}, pmid = {36897970}, issn = {1091-6490}, support = {R01 GM097275/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Placozoa/physiology ; Body Size ; Central Nervous System ; Biological Evolution ; }, abstract = {How collectives remain coordinated as they grow in size is a fundamental challenge affecting systems ranging from biofilms to governments. This challenge is particularly apparent in multicellular organisms, where coordination among a vast number of cells is vital for coherent animal behavior. However, the earliest multicellular organisms were decentralized, with indeterminate sizes and morphologies, as exemplified by Trichoplax adhaerens, arguably the earliest-diverged and simplest motile animal. We investigated coordination among cells in T. adhaerens by observing the degree of collective order in locomotion across animals of differing sizes and found that larger individuals exhibit increasingly disordered locomotion. We reproduced this effect of size on order through a simulation model of active elastic cellular sheets and demonstrate that this relationship is best recapitulated across all body sizes when the simulation parameters are tuned to a critical point in the parameter space. We quantify the trade-off between increasing size and coordination in a multicellular animal with a decentralized anatomy that shows evidence of criticality and hypothesize as to the implications of this on the evolution hierarchical structures such as nervous systems in larger organisms.}, } @article {pmid36877741, year = {2023}, author = {Luque, LM and Carlevaro, CM and Llamoza Torres, CJ and Lomba, E}, title = {Physics-based tissue simulator to model multicellular systems: A study of liver regeneration and hepatocellular carcinoma recurrence.}, journal = {PLoS computational biology}, volume = {19}, number = {3}, pages = {e1010920}, pmid = {36877741}, issn = {1553-7358}, mesh = {Humans ; *Carcinoma, Hepatocellular ; Liver Regeneration ; *Liver Neoplasms ; Hepatectomy ; Models, Biological ; Neoplasm Recurrence, Local ; Tumor Microenvironment ; }, abstract = {We present a multiagent-based model that captures the interactions between different types of cells with their microenvironment, and enables the analysis of the emergent global behavior during tissue regeneration and tumor development. Using this model, we are able to reproduce the temporal dynamics of regular healthy cells and cancer cells, as well as the evolution of their three-dimensional spatial distributions. By tuning the system with the characteristics of the individual patients, our model reproduces a variety of spatial patterns of tissue regeneration and tumor growth, resembling those found in clinical imaging or biopsies. In order to calibrate and validate our model we study the process of liver regeneration after surgical hepatectomy in different degrees. In the clinical context, our model is able to predict the recurrence of a hepatocellular carcinoma after a 70% partial hepatectomy. The outcomes of our simulations are in agreement with experimental and clinical observations. By fitting the model parameters to specific patient factors, it might well become a useful platform for hypotheses testing in treatments protocols.}, } @article {pmid36876435, year = {2023}, author = {Bernardo, N and Crespo, I and Cuppari, A and Meijer, WJJ and Boer, DR}, title = {A tetramerization domain in prokaryotic and eukaryotic transcription regulators homologous to p53.}, journal = {Acta crystallographica. Section D, Structural biology}, volume = {79}, number = {Pt 3}, pages = {259-267}, pmid = {36876435}, issn = {2059-7983}, support = {BIO2016-77883-C2-2-P//Ministerio de Economía y Competitividad, Agencia Estatal de Investigación/ ; PID2020-117028GB-I00//Ministerio de Economía y Competitividad, Agencia Estatal de Investigación/ ; FIS2015-72574-EXP//Ministerio de Economía y Competitividad, Agencia Estatal de Investigación/ ; PID2019-108778GB-C21//Ministerio de Economía y Competitividad, Agencia Estatal de Investigación/ ; BIO2016-77883-C2-1-P//Ministerio de Economía y Competitividad, Agencia Estatal de Investigación/ ; }, mesh = {Humans ; *Eukaryota ; Tumor Suppressor Protein p53 ; *Bacillus ; Bacillus subtilis ; Transcription Factors ; DNA ; }, abstract = {Transcriptional regulation usually requires the action of several proteins that either repress or activate a promotor of an open reading frame. These proteins can counteract each other, thus allowing tight regulation of the transcription of the corresponding genes, where tight repression is often linked to DNA looping or cross-linking. Here, the tetramerization domain of the bacterial gene repressor Rco from Bacillus subtilis plasmid pLS20 (RcopLS20) has been identified and its structure is shown to share high similarity to the tetramerization domain of the well known p53 family of human tumor suppressors, despite lacking clear sequence homology. In RcopLS20, this tetramerization domain is responsible for inducing DNA looping, a process that involves multiple tetramers. In accordance, it is shown that RcopLS20 can form octamers. This domain was named TetDloop and its occurrence was identified in other Bacillus species. The TetDloop fold was also found in the structure of a transcriptional repressor from Salmonella phage SPC32H. It is proposed that the TetDloop fold has evolved through divergent evolution and that the TetDloop originates from a common ancestor predating the occurrence of multicellular life.}, } @article {pmid36856076, year = {2023}, author = {Takeuchi, K and Senda, M and Ikeda, Y and Okuwaki, K and Fukuzawa, K and Nakagawa, S and Sasaki, M and Sasaki, AT and Senda, T}, title = {Functional molecular evolution of a GTP sensing kinase: PI5P4Kβ.}, journal = {The FEBS journal}, volume = {290}, number = {18}, pages = {4419-4428}, pmid = {36856076}, issn = {1742-4658}, support = {R01 CA255331/CA/NCI NIH HHS/United States ; R01 NS089815/NS/NINDS NIH HHS/United States ; R01 GM144426/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Guanosine Triphosphate/metabolism ; *Adenosine Triphosphate/metabolism ; *Evolution, Molecular ; Mammals/metabolism ; }, abstract = {Over 4 billion years of evolution, multiple mutations, including nucleotide substitutions, gene and genome duplications and recombination, have established de novo genes that translate into proteins with novel properties essential for high-order cellular functions. However, molecular processes through which a protein evolutionarily acquires a novel function are mostly speculative. Recently, we have provided evidence for a potential evolutionary mechanism underlying how, in mammalian cells, phosphatidylinositol 5-phosphate 4-kinase β (PI5P4Kβ) evolved into a GTP sensor from ATP-utilizing kinase. Mechanistically, PI5P4Kβ has acquired the guanine efficient association (GEA) motif by mutating its nucleotide base recognition sequence, enabling the evolutionary transition from an ATP-dependent kinase to a distinct GTP/ATP dual kinase with its KM for GTP falling into physiological GTP concentrations-the genesis of GTP sensing activity. Importantly, the GTP sensing activity of PI5P4Kβ is critical for the manifestation of cellular metabolism and tumourigenic activity in the multicellular organism. The combination of structural, biochemical and biophysical analyses used in our study provides a novel framework for analysing how a protein can evolutionarily acquire a novel activity, which potentially introduces a critical function to the cell.}, } @article {pmid36854263, year = {2023}, author = {Tang, S and Pichugin, Y and Hammerschmidt, K}, title = {An environmentally induced multicellular life cycle of a unicellular cyanobacterium.}, journal = {Current biology : CB}, volume = {33}, number = {4}, pages = {764-769.e5}, doi = {10.1016/j.cub.2023.01.069}, pmid = {36854263}, issn = {1879-0445}, mesh = {Animals ; *Cyanobacteria ; *Automobile Driving ; Biological Evolution ; Cell Death ; Life Cycle Stages ; }, abstract = {Understanding the evolutionary transition to multicellularity is a key problem in biology.[1][,][2][,][3][,][4] Nevertheless, the ecological conditions driving such transitions are not well understood. The first known transition to multicellularity occurred 2.5 billion years ago in cyanobacteria,[5][,][6][,][7] and today's cyanobacteria are characterized by enormous morphological diversity. They range from unicellular species; unicellular cyanobacteria with packet-like phenotypes, e.g., tetrads; and simple filamentous species to highly differentiated filamentous species.[8][,][9][,][10] The cyanobacterium Cyanothece sp. ATCC 51142, an isolate from the intertidal zone of the U.S. Gulf Coast,[11] was classified as a unicellular species.[12] We report a facultative life cycle of Cyanothece sp. in which multicellular filaments alternate with unicellular stages. In a series of experiments, we identified salinity and population density as environmental factors triggering the phenotypic switch between the two morphologies. Then, we used numerical models to test hypotheses regarding the nature of the environmental cues and the mechanisms underlying filament dissolution. While the results predict that the observed response is likely caused by an excreted compound in the medium, we cannot fully exclude changes in nutrient availability (as in Tuomi et al.[13] and Matz and Jürgens[14]). The best-fit modeling results show a nonlinear effect of the compound, which is characteristic of density-dependent sensing systems.[15][,][16] Furthermore, filament fragmentation is predicted to occur by connection cleavage rather than cell death of each alternating cell, which is supported by fluorescent and scanning electron microscopy results. The switch between unicellular and multicellular morphology constitutes an environmentally dependent life cycle that is likely an important step en route to permanent multicellularity.}, } @article {pmid36849252, year = {2023}, author = {Göbel, T and Goebel, B and Hyprath, M and Lamminger, I and Weisser, H and Angioni, C and Mathes, M and Thomas, D and Kahnt, AS}, title = {Three-dimensional growth reveals fine-tuning of 5-lipoxygenase by proliferative pathways in cancer.}, journal = {Life science alliance}, volume = {6}, number = {5}, pages = {}, pmid = {36849252}, issn = {2575-1077}, mesh = {Humans ; *Arachidonate 5-Lipoxygenase/genetics ; Lipid Metabolism ; *Colonic Neoplasms ; Mechanistic Target of Rapamycin Complex 2 ; Phosphatidylinositol 3-Kinases ; }, abstract = {The leukotriene (LT) pathway is positively correlated with the progression of solid malignancies, but the factors that control the expression of 5-lipoxygenase (5-LO), the central enzyme in LT biosynthesis, in tumors are poorly understood. Here, we report that 5-LO along with other members of the LT pathway is up-regulated in multicellular colon tumor spheroids. This up-regulation was inversely correlated with cell proliferation and activation of PI3K/mTORC-2- and MEK-1/ERK-dependent pathways. Furthermore, we found that E2F1 and its target gene MYBL2 were involved in the repression of 5-LO during cell proliferation. Importantly, we found that this PI3K/mTORC-2- and MEK-1/ERK-dependent suppression of 5-LO is also existent in tumor cells from other origins, suggesting that this mechanism is widely applicable to other tumor entities. Our data show that tumor cells fine-tune 5-LO and LT biosynthesis in response to environmental changes repressing the enzyme during proliferation while making use of the enzyme under cell stress conditions, implying that tumor-derived 5-LO plays a role in the manipulation of the tumor stroma to quickly restore cell proliferation.}, } @article {pmid36830620, year = {2023}, author = {van Oosten-Hawle, P}, title = {Organismal Roles of Hsp90.}, journal = {Biomolecules}, volume = {13}, number = {2}, pages = {}, pmid = {36830620}, issn = {2218-273X}, mesh = {Humans ; Animals ; *HSP90 Heat-Shock Proteins/metabolism ; *Molecular Chaperones/metabolism ; Signal Transduction ; Proteostasis ; Stress, Physiological ; Mammals/metabolism ; }, abstract = {Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone that assists in the maturation of many client proteins involved in cellular signal transduction. As a regulator of cellular signaling processes, it is vital for the maintenance of cellular proteostasis and adaptation to environmental stresses. Emerging research shows that Hsp90 function in an organism goes well beyond intracellular proteostasis. In metazoans, Hsp90, as an environmentally responsive chaperone, is involved in inter-tissue stress signaling responses that coordinate and safeguard cell nonautonomous proteostasis and organismal health. In this way, Hsp90 has the capacity to influence evolution and aging, and effect behavioral responses to facilitate tissue-defense systems that ensure organismal survival. In this review, I summarize the literature on the organismal roles of Hsp90 uncovered in multicellular organisms, from plants to invertebrates and mammals.}, } @article {pmid36822389, year = {2024}, author = {Wang, S and Chan, SY and Deng, Y and Khoo, BL and Chua, SL}, title = {Oxidative stress induced by Etoposide anti-cancer chemotherapy drives the emergence of tumor-associated bacteria resistance to fluoroquinolones.}, journal = {Journal of advanced research}, volume = {55}, number = {}, pages = {33-44}, pmid = {36822389}, issn = {2090-1224}, mesh = {Humans ; Fluoroquinolones/pharmacology ; Anti-Bacterial Agents/pharmacology ; Etoposide/pharmacology/therapeutic use ; Microbial Sensitivity Tests ; Ciprofloxacin/pharmacology ; *Pseudomonas Infections/microbiology ; Oxidative Stress ; *Lung Neoplasms/drug therapy ; Tumor Microenvironment ; }, abstract = {INTRODUCTION: Antibiotic-resistant bacterial infections, such as Pseudomonas aeruginosa and Staphylococcus aureus, are prevalent in lung cancer patients, resulting in poor clinical outcomes and high mortality. Etoposide (ETO) is an FDA-approved chemotherapy drug that kills cancer cells by damaging DNA through oxidative stress. However, it is unclear if ETO can cause unintentional side effects on tumor-associated microbial pathogens, such as inducing antibiotic resistance.

OBJECTIVES: We aimed to show that prolonged ETO treatment could unintendedly confer fluoroquinolone antibiotic resistance to P. aeruginosa, and evaluate the effect of tumor-associated P. aeruginosa on tumor progression.

METHODS: We employed experimental evolution assay to treat P. aeruginosa with prolonged ETO exposure, evaluated the ciprofloxacin resistance, and elucidated the gene mutations by DNA sequencing. We also established a lung tumor-P. aeruginosa bacterial model to study the role of ETO-evolved intra-tumoral bacteria in tumor progression using immunostaining and confocal microscopy.

RESULTS: ETO could generate oxidative stress and lead to gene mutations in P. aeruginosa, especially the gyrase (gyrA) gene, resulting in acquired fluoroquinolone resistance. We further demonstrated using a microfluidic-based lung tumor-P. aeruginosa coculture model that bacteria can evolve ciprofloxacin (CIP) resistance in a tumor microenvironment. Moreover, ETO-induced CIP-resistant (EICR) mutants could form multicellular biofilms which protected tumor cells from ETO killing and enabled tumor progression.

CONCLUSION: Overall, our preclinical proof-of-concept provides insights into how anti-cancer chemotherapy could inadvertently allow tumor-associated bacteria to acquire antibiotic resistance mutations and shed new light on the development of novel anti-cancer treatments based on anti-bacterial strategies.}, } @article {pmid36816026, year = {2023}, author = {Horjales, S and Li Calzi, M and Francia, ME and Cayota, A and Garcia-Silva, MR}, title = {piRNA pathway evolution beyond gonad context: Perspectives from apicomplexa and trypanosomatids.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1129194}, pmid = {36816026}, issn = {1664-8021}, abstract = {piRNAs function as genome defense mechanisms against transposable elements insertions within germ line cells. Recent studies have unraveled that piRNA pathways are not limited to germ cells as initially reckoned, but are instead also found in non-gonadal somatic contexts. Moreover, these pathways have also been reported in bacteria, mollusks and arthropods, associated with safeguard of genomes against transposable elements, regulation of gene expression and with direct consequences in axon regeneration and memory formation. In this Perspective we draw attention to early branching parasitic protozoa, whose genome preservation is an essential function as in late eukaryotes. However, little is known about the defense mechanisms of these genomes. We and others have described the presence of putative PIWI-related machinery members in protozoan parasites. We have described the presence of a PIWI-like protein in Trypanosoma cruzi, bound to small non-coding RNAs (sRNAs) as cargo of secreted extracellular vesicles relevant in intercellular communication and host infection. Herein, we put forward the presence of members related to Argonaute pathways in both Trypanosoma cruzi and Toxoplasma gondii. The presence of PIWI-like machinery in Trypansomatids and Apicomplexa, respectively, could be evidence of an ancestral piRNA machinery that evolved to become more sophisticated and complex in multicellular eukaryotes. We propose a model in which ancient PIWI proteins were expressed broadly and had functions independent of germline maintenance. A better understanding of current and ancestral PIWI/piRNAs will be relevant to better understand key mechanisms of genome integrity conservation during cell cycle progression and modulation of host defense mechanisms by protozoan parasites.}, } @article {pmid36813362, year = {2023}, author = {Samuel, V and Rajeev, T and Ramesh, L and Sundararaman, A}, title = {Integrin receptor trafficking in health and disease.}, journal = {Progress in molecular biology and translational science}, volume = {196}, number = {}, pages = {271-302}, doi = {10.1016/bs.pmbts.2022.09.008}, pmid = {36813362}, issn = {1878-0814}, mesh = {Humans ; Protein Transport/physiology ; *Integrins/metabolism ; Cell Membrane/metabolism ; Signal Transduction ; *Neoplasms/metabolism ; Cell Adhesion/physiology ; Cell Movement/physiology ; }, abstract = {Integrins are a family of 24 different heterodimers that are indispensable for multicellular life. Cell polarity, adhesion and migration are controlled by integrins delivered to the cell surface which in turn is regulated by the exo- and endocytic trafficking of integrins. The deep integration between trafficking and cell signaling determines the spatial and temporal output from any biochemical cue. Integrin trafficking plays a key role in development and many pathological conditions, especially cancer. Several novel regulators of integrin traffic have been discovered in recent times, including a novel class of integrin carrying vesicles, the intracellular nanovesicles (INVs). The tight regulation of trafficking pathways by cell signaling, where kinases phosphorylate key small GTPases in the trafficking pathway enable coordination of cell response to the extracellular milieu. Integrin heterodimer expression and trafficking differ in different tissues and contexts. In this Chapter, we discuss recent studies on integrin trafficking and its contribution to normal physiological and pathophysiological states.}, } @article {pmid36811171, year = {2023}, author = {Furumizu, C and Aalen, RB}, title = {Peptide signaling through leucine-rich repeat receptor kinases: insight into land plant evolution.}, journal = {The New phytologist}, volume = {238}, number = {3}, pages = {977-982}, doi = {10.1111/nph.18827}, pmid = {36811171}, issn = {1469-8137}, mesh = {*Protein Serine-Threonine Kinases/metabolism ; Plant Proteins/metabolism ; Leucine ; Phylogeny ; Signal Transduction/physiology ; Peptides/genetics ; *Embryophyta/genetics/metabolism ; }, abstract = {Multicellular organisms need mechanisms for communication between cells so that they can fulfill their purpose in the organism as a whole. Over the last two decades, several small post-translationally modified peptides (PTMPs) have been identified as components of cell-to-cell signaling modules in flowering plants. Such peptides most often influence growth and development of organs not universally conserved among land plants. PTMPs have been matched to subfamily XI leucine-rich repeat receptor-like kinases with > 20 repeats. Phylogenetic analyses, facilitated by recently published genomic sequences of non-flowering plants, have identified seven clades of such receptors with a history back to the common ancestor of bryophytes and vascular plants. This raises a number of questions: When did peptide signaling arise during land plant evolution? Have orthologous peptide-receptor pairs preserved their biological functions? Has peptide signaling contributed to major innovations, such as stomata, vasculature, roots, seeds, and flowers? Using genomic, genetic, biochemical, and structural data and non-angiosperm model species, it is now possible to address these questions. The vast number of peptides that have not yet found their partners suggests furthermore that we have far more to learn about peptide signaling in the coming decades.}, } @article {pmid36809239, year = {2023}, author = {Lambros, M and Sella, Y and Bergman, A}, title = {Phenotypic pliancy and the breakdown of epigenetic polycomb mechanisms.}, journal = {PLoS computational biology}, volume = {19}, number = {2}, pages = {e1010889}, pmid = {36809239}, issn = {1553-7358}, support = {R01 CA164468/CA/NCI NIH HHS/United States ; R01 DA033788/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; Polycomb-Group Proteins/genetics ; *Drosophila Proteins/metabolism ; Epigenesis, Genetic ; Cell Differentiation ; *Neoplasms/genetics ; Phenotype ; }, abstract = {Epigenetic regulatory mechanisms allow multicellular organisms to develop distinct specialized cell identities despite having the same total genome. Cell-fate choices are based on gene expression programs and environmental cues that cells experience during embryonic development, and are usually maintained throughout the life of the organism despite new environmental cues. The evolutionarily conserved Polycomb group (PcG) proteins form Polycomb Repressive Complexes that help orchestrate these developmental choices. Post-development, these complexes actively maintain the resulting cell fate, even in the face of environmental perturbations. Given the crucial role of these polycomb mechanisms in providing phenotypic fidelity (i.e. maintenance of cell fate), we hypothesize that their dysregulation after development will lead to decreased phenotypic fidelity allowing dysregulated cells to sustainably switch their phenotype in response to environmental changes. We call this abnormal phenotypic switching phenotypic pliancy. We introduce a general computational evolutionary model that allows us to test our systems-level phenotypic pliancy hypothesis in-silico and in a context-independent manner. We find that 1) phenotypic fidelity is an emergent systems-level property of PcG-like mechanism evolution, and 2) phenotypic pliancy is an emergent systems-level property resulting from this mechanism's dysregulation. Since there is evidence that metastatic cells behave in a phenotypically pliant manner, we hypothesize that progression to metastasis is driven by the emergence of phenotypic pliancy in cancer cells as a result of PcG mechanism dysregulation. We corroborate our hypothesis using single-cell RNA-sequencing data from metastatic cancers. We find that metastatic cancer cells are phenotypically pliant in the same manner as predicted by our model.}, } @article {pmid36797913, year = {2023}, author = {Leptos, KC and Chioccioli, M and Furlan, S and Pesci, AI and Goldstein, RE}, title = {Phototaxis of Chlamydomonas arises from a tuned adaptive photoresponse shared with multicellular Volvocine green algae.}, journal = {Physical review. E}, volume = {107}, number = {1-1}, pages = {014404}, pmid = {36797913}, issn = {2470-0053}, support = {/WT_/Wellcome Trust/United Kingdom ; 207510/WT_/Wellcome Trust/United Kingdom ; 207510/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Chlamydomonas ; Phylogeny ; Phototaxis ; *Chlorophyta ; Biological Evolution ; *Volvox ; }, abstract = {A fundamental issue in biology is the nature of evolutionary transitions from unicellular to multicellular organisms. Volvocine algae are models for this transition, as they span from the unicellular biflagellate Chlamydomonas to multicellular species of Volvox with up to 50,000 Chlamydomonas-like cells on the surface of a spherical extracellular matrix. The mechanism of phototaxis in these species is of particular interest since they lack a nervous system and intercellular connections; steering is a consequence of the response of individual cells to light. Studies of Volvox and Gonium, a 16-cell organism with a plate-like structure, have shown that the flagellar response to changing illumination of the cellular photosensor is adaptive, with a recovery time tuned to the rotation period of the colony around its primary axis. Here, combining high-resolution studies of the flagellar photoresponse of micropipette-held Chlamydomonas with 3D tracking of freely swimming cells, we show that such tuning also underlies its phototaxis. A mathematical model is developed based on the rotations around an axis perpendicular to the flagellar beat plane that occur through the adaptive response to oscillating light levels as the organism spins. Exploiting a separation of timescales between the flagellar photoresponse and phototurning, we develop an equation of motion that accurately describes the observed photoalignment. In showing that the adaptive timescales in Volvocine algae are tuned to the organisms' rotational periods across three orders of magnitude in cell number, our results suggest a unified picture of phototaxis in green algae in which the asymmetry in torques that produce phototurns arise from the individual flagella of Chlamydomonas, the flagellated edges of Gonium, and the flagellated hemispheres of Volvox.}, } @article {pmid36789784, year = {2023}, author = {Rusin, LY}, title = {Evolution of homology: From archetype towards a holistic concept of cell type.}, journal = {Journal of morphology}, volume = {284}, number = {4}, pages = {e21569}, doi = {10.1002/jmor.21569}, pmid = {36789784}, issn = {1097-4687}, mesh = {Animals ; *Biological Evolution ; Phylogeny ; *Growth and Development ; Cell Lineage ; Phenotype ; }, abstract = {The concept of homology lies in the heart of comparative biological science. The distinction between homology as structure and analogy as function has shaped the evolutionary paradigm for a century and formed the axis of comparative anatomy and embryology, which accept the identity of structure as a ground measure of relatedness. The advent of single-cell genomics overturned the classical view of cell homology by establishing a backbone regulatory identity of cell types, the basic biological units bridging the molecular and phenotypic dimensions, to reveal that the cell is the most flexible unit of living matter and that many approaches of classical biology need to be revised to understand evolution and diversity at the cellular level. The emerging theory of cell types explicitly decouples cell identity from phenotype, essentially allowing for the divergence of evolutionarily related morphotypes beyond recognition, as well as it decouples ontogenetic cell lineage from cell-type phylogeny, whereby explicating that cell types can share common descent regardless of their structure, function or developmental origin. The article succinctly summarizes current progress and opinion in this field and formulates a more generalistic view of biological cell types as avatars, transient or terminal cell states deployed in a continuum of states by the developmental programme of one and the same omnipotent cell, capable of changing or combining identities with distinct evolutionary histories or inventing ad hoc identities that never existed in evolution or development. It highlights how the new logic grounded in the regulatory nature of cell identity transforms the concepts of cell homology and phenotypic stability, suggesting that cellular evolution is inherently and massively network-like, with one-to-one homologies being rather uncommon and restricted to shallower levels of the animal tree of life.}, } @article {pmid36786569, year = {2023}, author = {Cont, A and Vermeil, J and Persat, A}, title = {Material Substrate Physical Properties Control Pseudomonas aeruginosa Biofilm Architecture.}, journal = {mBio}, volume = {14}, number = {2}, pages = {e0351822}, pmid = {36786569}, issn = {2150-7511}, mesh = {Humans ; *Pseudomonas aeruginosa/genetics ; Biofilms ; Anti-Bacterial Agents/pharmacology ; *Pseudomonas Infections/microbiology ; }, abstract = {In the wild, bacteria are most frequently found in the form of multicellular structures called biofilms. Biofilms grow at the surface of abiotic and living materials with wide-ranging mechanical properties. The opportunistic pathogen Pseudomonas aeruginosa forms biofilms on indwelling medical devices and on soft tissues, including burn wounds and the airway mucosa. Despite the critical role of substrates in the foundation of biofilms, we still lack a clear understanding of how material mechanics regulate their architecture and the physiology of resident bacteria. Here, we demonstrate that physical properties of hydrogel material substrates define P. aeruginosa biofilm architecture. We show that hydrogel mesh size regulates twitching motility, a surface exploration mechanism priming biofilms, ultimately controlling the organization of single cells in the multicellular community. The resulting architectural transitions increase P. aeruginosa's tolerance to colistin, a last-resort antibiotic. In addition, mechanical regulation of twitching motility affects P. aeruginosa clonal lineages, so that biofilms are more mixed on relatively denser materials. Our results thereby establish material properties as a factor that dramatically affects biofilm architecture, antibiotic efficacy, and evolution of the resident population. IMPORTANCE The biofilm lifestyle is the most widespread survival strategy in the bacterial world. Pseudomonas aeruginosa biofilms cause chronic infections and are highly recalcitrant to antimicrobials. The genetic requirements allowing P. aeruginosa to grow into biofilms are known, but not the physical stimuli that regulate their formation. Despite colonizing biological tissues, investigations of biofilms on soft materials are limited. In this work, we show that biofilms take unexpected forms when growing on soft substrates. The physical properties of the material shape P. aeruginosa biofilms by regulating surface-specific twitching motility. Physical control of biofilm morphogenesis ultimately influences the resilience of biofilms to antimicrobials, linking physical environment with tolerance to treatment. Altogether, our work established that the physical properties of a surface are a critical environmental regulator of biofilm biogenesis and evolution.}, } @article {pmid36786333, year = {2023}, author = {Godfroy, O and Zheng, M and Yao, H and Henschen, A and Peters, AF and Scornet, D and Colin, S and Ronchi, P and Hipp, K and Nagasato, C and Motomura, T and Cock, JM and Coelho, SM}, title = {The baseless mutant links protein phosphatase 2A with basal cell identity in the brown alga Ectocarpus.}, journal = {Development (Cambridge, England)}, volume = {150}, number = {4}, pages = {}, pmid = {36786333}, issn = {1477-9129}, support = {//Centre National de la Recherche Scientifique/ ; //Sorbonne Université/ ; //Max Planck Society/ ; 864038/ERC_/European Research Council/International ; 201608310119//China Scholarship Council/ ; }, mesh = {*Protein Phosphatase 2/genetics/metabolism ; Mutation/genetics ; Gene Expression Profiling ; Protein Processing, Post-Translational ; *Phaeophyceae/genetics/metabolism ; }, abstract = {The first mitotic division of the initial cell is a key event in all multicellular organisms and is associated with the establishment of major developmental axes and cell fates. The brown alga Ectocarpus has a haploid-diploid life cycle that involves the development of two multicellular generations: the sporophyte and the gametophyte. Each generation deploys a distinct developmental programme autonomously from an initial cell, the first cell division of which sets up the future body pattern. Here, we show that mutations in the BASELESS (BAS) gene result in multiple cellular defects during the first cell division and subsequent failure to produce basal structures during both generations. BAS encodes a type B″ regulatory subunit of protein phosphatase 2A (PP2A), and transcriptomic analysis identified potential effector genes that may be involved in determining basal cell fate. The bas mutant phenotype is very similar to that observed in distag (dis) mutants, which lack a functional Tubulin-binding co-factor Cd1 (TBCCd1) protein, indicating that TBCCd1 and PP2A are two essential components of the cellular machinery that regulates the first cell division and mediates basal cell fate determination.}, } @article {pmid36781087, year = {2023}, author = {Brown, Y and Hua, S and Tanwar, PS}, title = {Extracellular matrix in high-grade serous ovarian cancer: Advances in understanding of carcinogenesis and cancer biology.}, journal = {Matrix biology : journal of the International Society for Matrix Biology}, volume = {118}, number = {}, pages = {16-46}, doi = {10.1016/j.matbio.2023.02.004}, pmid = {36781087}, issn = {1569-1802}, mesh = {Female ; Humans ; *Ovarian Neoplasms/genetics ; *Cystadenocarcinoma, Serous/genetics ; Extracellular Matrix/pathology ; Carcinogenesis/genetics ; Biology ; Tumor Microenvironment ; }, abstract = {High-grade serous ovarian cancer (HGSOC) is notoriously known as the "silent killer" of post-menopausal women as it has an insidious progression and is the deadliest gynaecological cancer. Although a dual origin of HGSOC is now widely accepted, there is growing evidence that most cases of HGSOC originate from the fallopian tube epithelium. In this review, we will address the fallopian tube origin and involvement of the extracellular matrix (ECM) in HGSOC development. There is limited research on the role of ECM at the earliest stages of HGSOC carcinogenesis. Here we aim to synthesise current understanding of the contribution of ECM to each stage of HGSOC development and progression, beginning at serous tubal intraepithelial carcinoma (STIC) precursor lesions and proceeding across key events including dissemination of tumourigenic fallopian tube epithelial cells to the ovary, survival of these cells in peritoneal fluid as multicellular aggregates, and colonisation of the ovary. Likewise, as part of the metastatic series of events, serous ovarian cancer cells survive travel in peritoneal fluid, attach to, migrate across the mesothelium and invade into the sub-mesothelial matrix of secondary sites in the peritoneal cavity. Halting cancer at the pre-metastatic stage and finding ways to stop the dissemination of ovarian cancer cells from the primary site is critical for improving patient survival. The development of drug resistance also contributes to poor survival statistics in HGSOC. In this review, we provide an update on the involvement of the ECM in metastasis and drug resistance in HGSOC. Interplay between different cell-types, growth factor gradients as well as evolving ECM composition and organisation, creates microenvironment conditions that promote metastatic progression and drug resistance of ovarian cancer cells. By understanding ECM involvement in the carcinogenesis and chemoresistance of HGSOC, this may prompt ideas for further research for developing new early diagnostic tests and therapeutic strategies for HGSOC with the end goal of improving patient health outcomes.}, } @article {pmid36779552, year = {2023}, author = {Mitchell, RL and Kenrick, P and Pressel, S and Duckett, J and Strullu-Derrien, C and Davies, N and McMahon, WJ and Summerfield, R}, title = {Terrestrial surface stabilisation by modern analogues of the earliest land plants: A multi-dimensional imaging study.}, journal = {Geobiology}, volume = {21}, number = {4}, pages = {454-473}, doi = {10.1111/gbi.12546}, pmid = {36779552}, issn = {1472-4669}, mesh = {*Ecosystem ; *Embryophyta ; Plants ; Fungi ; Fossils ; Phylogeny ; }, abstract = {The evolution of the first plant-based terrestrial ecosystems in the early Palaeozoic had a profound effect on the development of soils, the architecture of sedimentary systems, and shifts in global biogeochemical cycles. In part, this was due to the evolution of complex below-ground (root-like) anchorage systems in plants, which expanded and promoted plant-mineral interactions, weathering, and resulting surface sediment stabilisation. However, little is understood about how these micro-scale processes occurred, because of a lack of in situ plant fossils in sedimentary rocks/palaeosols that exhibit these interactions. Some modern plants (e.g., liverworts, mosses, lycophytes) share key features with the earliest land plants; these include uni- or multicellular rhizoid-like anchorage systems or simple roots, and the ability to develop below-ground networks through prostrate axes, and intimate associations with fungi, making them suitable analogues. Here, we investigated cryptogamic ground covers in Iceland and New Zealand to better understand these interactions, and how they initiate the sediment stabilisation process. We employed multi-dimensional and multi-scale imaging, including scanning electron microscopy (SEM) and X-ray Computed Tomography (μCT) of non-vascular liverworts (Haplomitriopsida and complex thalloids) and mosses, with additional imaging of vascular lycopods. We find that plants interact with their substrate in multiple ways, including: (1) through the development of extensive surface coverings as mats; (2) entrapment of sediment grains within and between networks of rhizoids; (3) grain entwining and adherence by rhizoids, through mucilage secretions, biofilm-like envelopment of thalli on surface grains; and (4) through grain entrapment within upright 'leafy' structures. Significantly, μCT imaging allows us to ascertain that rhizoids are the main method for entrapment and stabilisation of soil grains in the thalloid liverworts. This information provides us with details of how the earliest land plants may have significantly influenced early Palaeozoic sedimentary system architectures, promoted in situ weathering and proto-soil development, and how these interactions diversified over time with the evolution of new plant organ systems. Further, this study highlights the importance of cryptogamic organisms in the early stages of sediment stabilisation and soil formation today.}, } @article {pmid36765079, year = {2023}, author = {Debit, A and Charton, F and Pierre-Elies, P and Bowler, C and Cruz de Carvalho, H}, title = {Differential expression patterns of long noncoding RNAs in a pleiomorphic diatom and relation to hyposalinity.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2440}, pmid = {36765079}, issn = {2045-2322}, mesh = {Animals ; *Diatoms/metabolism ; *RNA, Long Noncoding/genetics/metabolism ; Gene Expression Profiling ; Transcriptome ; Culture Media/metabolism ; }, abstract = {Long non-coding (lnc)RNAs have been shown to have central roles in stress responses, cell identity and developmental processes in multicellular organisms as well as in unicellular fungi. Previous works have shown the occurrence of lncRNAs in diatoms, namely in Phaeodactylum tricornutum, many of which being expressed under specific stress conditions. Interestingly, P. tricornutum is the only known diatom that has a demonstrated morphological plasticity, occurring in three distinct morphotypes: fusiform, triradiate and oval. Although the morphotypes are interchangeable, the fusiform is the dominant one while both the triradiate and the oval forms are less common, the latter often being associated with stress conditions such as low salinity and solid culture media, amongst others. Nonetheless, the molecular basis underpinning morphotype identity in P. tricornutum remains elusive. Using twelve previously published transcriptomic datasets originating from the three morphotypes of P. tricornutum, we sought to investigate the expression patterns of lncRNAs (lincRNAs and NATs) in these distinct morphotypes, using pairwise comparisons, in order to explore the putative involvement of these noncoding molecules in morphotype identity. We found that differentially expressed lncRNAs cluster according to morphotype, indicating that lncRNAs are not randomly expressed, but rather seem to provide a specific (noncoding) transcriptomic signature of the morphotype. We also present evidence to suggest that the major differences in DE genes (both noncoding and coding) between the stress related oval morphotype and the most common fusiform morphotype could be due, to a large extent, to the hyposaline culture conditions rather than to the morphotype itself. However, several lncRNAs associated to each one of the three morphotypes were identified, which could have a potential role in morphotype (or cell) identity in P. tricornutum, similar to what has been found in both animals and plant development.}, } @article {pmid36750954, year = {2023}, author = {Zhang, X and Chen, S and Zhao, Z and Ma, C and Liu, Y}, title = {Investigation of B-atp6-orfH79 distributing in Chinese populations of Oryza rufipogon and analysis of its chimeric structure.}, journal = {BMC plant biology}, volume = {23}, number = {1}, pages = {81}, pmid = {36750954}, issn = {1471-2229}, mesh = {DNA, Mitochondrial/genetics/metabolism ; Mitochondria/metabolism ; *Oryza/genetics ; Plant Breeding ; }, abstract = {BACKGROUND: The cytoplasmic male sterility (CMS) of rice is caused by chimeric mitochondrial DNA (mtDNA) that is maternally inherited in the majority of multicellular organisms. Wild rice (Oryza rufipogon Griff.) has been regarded as the ancestral progenitor of Asian cultivated rice (Oryza sativa L.). To investigate the distribution of original CMS source, and explore the origin of gametophytic CMS gene, a total of 427 individuals with seventeen representative populations of O. rufipogon were collected in from Dongxiang of Jiangxi Province to Sanya of Hainan Province, China, for the PCR amplification of atp6, orfH79 and B-atp6-orfH79, respectively.

RESULTS: The B-atp6-orfH79 and its variants (B-atp6-GSV) were detected in five among seventeen populations (i.e. HK, GZ, PS, TL and YJ) through PCR amplification, which could be divided into three haplotypes, i.e., BH1, BH2, and BH3. The BH2 haplotype was identical to B-atp6-orfH79, while the BH1 and BH3 were the novel haplotypes of B-atp6-GSV. Combined with the high-homology sequences in GenBank, a total of eighteen haplotypes have been revealed, only with ten haplotypes in orfH79 and its variants (GSV) that belong to three species (i.e. O. rufipogon, Oryza nivara and Oryza sativa). Enough haplotypes clearly demonstrated the uniform structural characteristics of the B-atp6-orfH79 as follows: except for the conserved sequence (671 bp) composed of B-atp6 (619 bp) and the downstream followed the B-atp6 (52 bp, DS), and GSV sequence, a rich variable sequence (VS, 176 bp) lies between the DS and GSV with five insertion or deletion and more than 30 single nucleotide polymorphism. Maximum likelihood analysis showed that eighteen haplotypes formed three clades with high support rate. The hierarchical analysis of molecular variance (AMOVA) indicated the occurrence of variation among all populations (FST = 1; P < 0.001), which implied that the chimeric structure occurred independently. Three haplotypes (i.e., H1, H2 and H3) were detected by the primer of orfH79, which were identical to the GVS in B-atp6-GVS structure, respectively. All seventeen haplotypes of the orfH79, belonged to six species based on our results and the existing references. Seven existed single nucleotide polymorphism in GSV section can be translated into eleven various amino acid sequences.

CONCLUSIONS: Generally, this study, indicating that orfH79 was always accompanied by the B-atp6, not only provide two original CMS sources for rice breeding, but also confirm the uniform structure of B-atp-orfH79, which contribute to revealing the origin of rice gametophytic CMS genes, and the reason about frequent recombination of mitochondrial DNA.}, } @article {pmid36717459, year = {2022}, author = {Pandey, T and Ma, DK}, title = {Stress-Induced Phenoptosis: Mechanistic Insights and Evolutionary Implications.}, journal = {Biochemistry. Biokhimiia}, volume = {87}, number = {12}, pages = {1504-1511}, doi = {10.1134/S0006297922120082}, pmid = {36717459}, issn = {1608-3040}, mesh = {Animals ; Humans ; *Caenorhabditis elegans/genetics ; *Apoptosis ; Aging/genetics ; Bacteria ; Signal Transduction ; Biological Evolution ; Mammals ; }, abstract = {Evolution by natural selection results in biological traits that enable organismic adaptation and survival under various stressful environments. External stresses can be sometimes too severe to overcome, leading to organismic death either because of failure in adapting to such stress, or alternatively, through a regulated form of organismic death (phenoptosis). While regulated cell deaths, including apoptosis, have been extensively studied, little is known about the molecular and cellular mechanisms underlying phenoptosis and its evolutionary significance for multicellular organisms. In this article, we review documented phenomena and mechanistic evidence emerging from studies of stress-induced phenoptosis in the multicellular organism C. elegans and stress-induced deaths at cellular levels in organisms ranging from bacteria to mammals, focusing on abiotic and pathogen stresses. Genes and signaling pathways involved in phenoptosis appear to promote organismic death during severe stress and aging, while conferring fitness and immune defense during mild stress and early life, consistent with their antagonistic pleiotropy actions. As cell apoptosis during development can shape tissues and organs, stress-induced phenoptosis may also contribute to possible benefits at the population level, through mechanisms including kin selection, abortive infection, and soma-to-germline resource allocation. Current models can generate experimentally testable predictions and conceptual frameworks with implications for understanding both stress-induced phenoptosis and natural aging.}, } @article {pmid36715204, year = {2023}, author = {Klure, DM and Greenhalgh, R and Parchman, TL and Matocq, MD and Galland, LM and Shapiro, MD and Dearing, MD}, title = {Hybridization in the absence of an ecotone favors hybrid success in woodrats (Neotoma spp.).}, journal = {Evolution; international journal of organic evolution}, volume = {77}, number = {4}, pages = {959-970}, pmid = {36715204}, issn = {1558-5646}, support = {T32 GM141848/GM/NIGMS NIH HHS/United States ; T32GM141848/NH/NIH HHS/United States ; }, mesh = {Humans ; Animals ; *Sigmodontinae/genetics ; *Hybridization, Genetic ; Nucleic Acid Hybridization ; }, abstract = {Hybridization is a common process that has broadly impacted the evolution of multicellular eukaryotes; however, how ecological factors influence this process remains poorly understood. Here, we report the findings of a 3-year recapture study of the Bryant's woodrat (Neotoma bryanti) and desert woodrat (Neotoma lepida), two species that hybridize within a creosote bush (Larrea tridentata) shrubland in Whitewater, CA, USA. We used a genotype-by-sequencing approach to characterize the ancestry distribution of individuals across this hybrid zone coupled with Cormack-Jolly-Seber modeling to describe demography. We identified a high frequency of hybridization at this site with ~40% of individuals possessing admixed ancestry, which is the result of multigenerational backcrossing and advanced hybrid-hybrid crossing. F1, F2, and advanced generation hybrids had apparent survival rates similar to parental N. bryanti, while parental and backcross N. lepida had lower apparent survival rates and were far less abundant. Compared to bimodal hybrid zones where hybrids are often rare and selected against, we find that hybrids at Whitewater are common and have comparable survival to the dominant parental species, N. bryanti. The frequency of hybridization at Whitewater is therefore likely limited by the abundance of the less common parental species, N. lepida, rather than selection against hybrids.}, } @article {pmid36693985, year = {2023}, author = {Trivedi, DD and Dalai, SK and Bakshi, SR}, title = {The Mystery of Cancer Resistance: A Revelation Within Nature.}, journal = {Journal of molecular evolution}, volume = {91}, number = {2}, pages = {133-155}, pmid = {36693985}, issn = {1432-1432}, mesh = {Humans ; Horses ; Animals ; Mice ; *Carcinogens, Environmental ; *Neoplasms/genetics ; Immunity, Innate ; Mole Rats ; Mammals ; Tumor Microenvironment ; }, abstract = {Cancer, a disease due to uncontrolled cell proliferation is as ancient as multicellular organisms. A 255-million-years-old fossilized forerunner mammal gorgonopsian is probably the oldest evidence of cancer, to date. Cancer seems to have evolved by adapting to the microenvironment occupied by immune sentinel, modulating the cellular behavior from cytotoxic to regulatory, acquiring resistance to chemotherapy and surviving hypoxia. The interaction of genes with environmental carcinogens is central to cancer onset, seen as a spectrum of cancer susceptibility among human population. Cancer occurs in life forms other than human also, although their exposure to environmental carcinogens can be different. Role of genetic etiology in cancer in multiple species can be interesting with regard to not only cancer susceptibility, but also genetic conservation and adaptation in speciation. The widely used model organisms for cancer research are mouse and rat which are short-lived and reproduce rapidly. Research in these cancer prone animal models has been valuable as these have led to cancer therapy. However, another rewarding area of cancer research can be the cancer-resistant animal species. The Peto's paradox and G-value paradox are evident when natural cancer resistance is observed in large mammals, like elephant and whale, small rodents viz. Naked Mole Rat and Blind Mole Rat, and Bat. The cancer resistance remains to be explored in other small or large and long-living animals like giraffe, camel, rhinoceros, water buffalo, Indian bison, Shire horse, polar bear, manatee, elephant seal, walrus, hippopotamus, turtle and tortoise, sloth, and squirrel. Indeed, understanding the molecular mechanisms of avoiding neoplastic transformation across various life forms can be potentially having translational value for human cancer management. Adapted and Modified from (Hanahan and Weinberg 2011).}, } @article {pmid36692278, year = {2022}, author = {Forterre, P and Gaïa, M}, title = {[Viruses and the evolution of modern eukaryotic cells].}, journal = {Medecine sciences : M/S}, volume = {38}, number = {12}, pages = {990-998}, doi = {10.1051/medsci/2022164}, pmid = {36692278}, issn = {1958-5381}, mesh = {Humans ; *Eukaryotic Cells ; Phylogeny ; *Viruses/genetics ; Eukaryota/genetics ; Cell Nucleus ; Evolution, Molecular ; Biological Evolution ; }, abstract = {It is now well accepted that viruses have played an important role in the evolution of modern eukaryotes. In this review, we suggest that interactions between ancient eukaryoviruses and proto-eukaryotes also played a major role in eukaryogenesis. We discuss phylogenetic analyses that highlight the viral origin of several key proteins in the molecular biology of eukaryotes. We also discuss recent observations that, by analogy, could suggest a viral origin of the cellular nucleus. Finally, we hypothesize that mechanisms of cell differentiation in multicellular organisms might have originated from mechanisms implemented by viruses to transform infected cells into virocells.}, } @article {pmid36689549, year = {2023}, author = {Tuohinto, K and DiMaio, TA and Kiss, EA and Laakkonen, P and Saharinen, P and Karnezis, T and Lagunoff, M and Ojala, PM}, title = {KSHV infection of endothelial precursor cells with lymphatic characteristics as a novel model for translational Kaposi's sarcoma studies.}, journal = {PLoS pathogens}, volume = {19}, number = {1}, pages = {e1010753}, pmid = {36689549}, issn = {1553-7374}, support = {R01 CA189986/CA/NCI NIH HHS/United States ; R01 CA217788/CA/NCI NIH HHS/United States ; R21 CA240479/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Sarcoma, Kaposi ; *Herpesvirus 8, Human/genetics ; Endothelial Cells ; Endothelium, Vascular/pathology ; }, abstract = {Kaposi's sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), a hyperplasia consisting of enlarged malformed vasculature and spindle-shaped cells, the main proliferative component of KS. While spindle cells express markers of lymphatic and blood endothelium, the origin of spindle cells is unknown. Endothelial precursor cells have been proposed as the source of spindle cells. We previously identified two types of circulating endothelial colony forming cells (ECFCs), ones that expressed markers of blood endothelium and ones that expressed markers of lymphatic endothelium. Here we examined both blood and lymphatic ECFCs infected with KSHV. Lymphatic ECFCs are significantly more susceptible to KSHV infection than the blood ECFCs and maintain the viral episomes during passage in culture while the blood ECFCs lose the viral episome. Only the KSHV-infected lymphatic ECFCs (K-ECFCLY) grew to small multicellular colonies in soft agar whereas the infected blood ECFCs and all uninfected ECFCs failed to proliferate. The K-ECFCLYs express high levels of SOX18, which supported the maintenance of high copy number of KSHV genomes. When implanted subcutaneously into NSG mice, the K-ECFCLYs persisted in vivo and recapitulated the phenotype of KS tumor cells with high number of viral genome copies and spindling morphology. These spindle cell hallmarks were significantly reduced when mice were treated with SOX18 inhibitor, SM4. These data suggest that KSHV-infected lymphatic ECFCs can be utilized as a KSHV infection model for in vivo translational studies to test novel inhibitors representing potential treatment modalities for KS.}, } @article {pmid36688394, year = {2023}, author = {McShea, DW}, title = {Four reasons for scepticism about a human major transition in social individuality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210403}, pmid = {36688394}, issn = {1471-2970}, mesh = {Animals ; Humans ; *Biological Evolution ; Eukaryota ; *Hominidae ; Selection, Genetic ; Reproduction ; }, abstract = {The 'major transitions in evolution' are mainly about the rise of hierarchy, new individuals arising at ever higher levels of nestedness, in particular the eukaryotic cell arising from prokaryotes, multicellular individuals from solitary protists and individuated societies from multicellular individuals. Some lists include human societies as a major transition, but based on a comparison with the non-human transitions, there are reasons for scepticism. (i) The foundation of the major transitions is hierarchy, but the cross-cutting interactions in human societies undermine hierarchical structure. (ii) Natural selection operates in three modes-stability, growth and reproductive success-and only the third produces the complex adaptations seen in fully individuated higher levels. But human societies probably evolve mainly in the stability and growth modes. (iii) Highly individuated entities are marked by division of labour and commitment to morphological differentiation, but in humans differentiation is mostly behavioural and mostly reversible. (iv) As higher-level individuals arise, selection drains complexity, drains parts, from lower-level individuals. But there is little evidence of a drain in humans. In sum, a comparison with the other transitions gives reasons to doubt that human social individuation has proceeded very far, or if it has, to doubt that it is a transition of the same sort. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36688393, year = {2023}, author = {Townsend, C and Ferraro, JV and Habecker, H and Flinn, MV}, title = {Human cooperation and evolutionary transitions in individuality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210414}, pmid = {36688393}, issn = {1471-2970}, mesh = {Humans ; *Biological Evolution ; *Social Behavior ; Adaptation, Physiological ; Communication ; }, abstract = {A major evolutionary transition in individuality involves the formation of a cooperative group and the transformation of that group into an evolutionary entity. Human cooperation shares principles with those of multicellular organisms that have undergone transitions in individuality: division of labour, communication, and fitness interdependence. After the split from the last common ancestor of hominoids, early hominins adapted to an increasingly terrestrial niche for several million years. We posit that new challenges in this niche set in motion a positive feedback loop in selection pressure for cooperation that ratcheted coevolutionary changes in sociality, communication, brains, cognition, kin relations and technology, eventually resulting in egalitarian societies with suppressed competition and rapid cumulative culture. The increasing pace of information innovation and transmission became a key aspect of the evolutionary niche that enabled humans to become formidable cooperators with explosive population growth, the ability to cooperate and compete in groups of millions, and emergent social norms, e.g. private property. Despite considerable fitness interdependence, the rise of private property, in concert with population explosion and socioeconomic inequality, subverts potential transition of human groups into evolutionary entities due to resurgence of latent competition and conflict. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36688387, year = {2023}, author = {Davison, DR and Michod, RE}, title = {Steps to individuality in biology and culture.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {378}, number = {1872}, pages = {20210407}, pmid = {36688387}, issn = {1471-2970}, mesh = {Animals ; Humans ; Biological Evolution ; *Hominidae ; *Cultural Evolution ; Biology ; }, abstract = {Did human culture arise through an evolutionary transition in individuality (ETI)? To address this question, we examine the steps of biological ETIs to see how they could apply to the evolution of human culture. For concreteness, we illustrate the ETI stages using a well-studied example, the evolution of multicellularity in the volvocine algae. We then consider how those stages could apply to a cultural transition involving integrated groups of cultural traditions and the hominins that create and transmit traditions. We focus primarily on the early Pleistocene and examine hominin carnivory and the cultural change from Oldowan to Acheulean technology. We use Pan behaviour as an outgroup comparison. We summarize the important similarities and differences we find between ETI stages in the biological and cultural realms. As we are not cultural anthropologists, we may overlook or be mistaken in the processes we associate with each step. We hope that by clearly describing these steps to individuality and illustrating them with cultural principles and processes, other researchers may build upon our initial exercise. Our analysis supports the hypothesis that human culture has undergone an ETI beginning with a Pan-like ancestor, continuing during the Pleistocene, and culminating in modern human culture. This article is part of the theme issue 'Human socio-cultural evolution in light of evolutionary transitions'.}, } @article {pmid36655713, year = {2023}, author = {Römling, U}, title = {Is biofilm formation intrinsic to the origin of life?.}, journal = {Environmental microbiology}, volume = {25}, number = {1}, pages = {26-39}, pmid = {36655713}, issn = {1462-2920}, mesh = {Humans ; *Biofilms ; }, abstract = {Biofilms are multicellular, often surface-associated, communities of autonomous cells. Their formation is the natural mode of growth of up to 80% of microorganisms living on this planet. Biofilms refractory towards antimicrobial agents and the actions of the immune system due to their tolerance against multiple environmental stresses. But how did biofilm formation arise? Here, I argue that the biofilm lifestyle has its foundation already in the fundamental, surface-triggered chemical reactions and energy preserving mechanisms that enabled the development of life on earth. Subsequently, prototypical biofilm formation has evolved and diversified concomitantly in composition, cell morphology and regulation with the expansion of prokaryotic organisms and their radiation by occupation of diverse ecological niches. This ancient origin of biofilm formation thus mirrors the harnessing environmental conditions that have been the rule rather than the exception in microbial life. The subsequent emergence of the association of microbes, including recent human pathogens, with higher organisms can be considered as the entry into a nutritional and largely stress-protecting heaven. Nevertheless, basic mechanisms of biofilm formation have surprisingly been conserved and refunctionalized to promote sustained survival in new environments.}, } @article {pmid36650459, year = {2023}, author = {Nozaki, H and Mori, F and Tanaka, Y and Matsuzaki, R and Yamashita, S and Yamaguchi, H and Kawachi, M}, title = {Cryopreservation of two species of the multicellular volvocine green algal genus Astrephomene.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {16}, pmid = {36650459}, issn = {1471-2180}, support = {G-2022-1-004//The Institute for Fermentation, Osaka (IFO)/ ; 20H03299//MEXT/ JSPS KAKENHI/ ; }, mesh = {*Chlorophyta/genetics ; Cryopreservation/methods ; Freezing ; Dimethylformamide ; }, abstract = {BACKGROUND: Astrephomene is an interesting green algal genus that, together with Volvox, shows convergent evolution of spheroidal multicellular bodies with somatic cells of the colonial or multicellular volvocine lineage. A recent whole-genome analysis of A. gubernaculifera resolved the molecular-genetic basis of such convergent evolution, and two species of Astrephomene were described. However, maintenance of culture strains of Astrephomene requires rapid inoculation of living cultures, and cryopreserved culture strains have not been established in public culture collections.

RESULTS: To establish cryopreserved culture strains of two species of Astrephomene, conditions for cryopreservation of the two species were investigated using immature and mature vegetative colonies and two cryoprotectants: N,N-dimethylformamide (DMF) and hydroxyacetone (HA). Rates of cell survival of the A. gubernaculifera or A. perforata strain after two-step cooling and freezing in liquid nitrogen were compared between different concentrations (3 and 6%) of DMF and HA and two types of colonies: immature colonies (small colonies newly released from the parent) and mature colonies (large colonies just before daughter colony formation). The highest rate of survival [11 ± 13% (0.36-33%) by the most probable number (MPN) method] of A. gubernaculifera strain NIES-4017 (established in 2014) was obtained when culture samples of immature colonies were subjected to cryogenic treatment with 6% DMF. In contrast, culture samples of mature colonies subjected to 3% HA cryogenic treatment showed the highest "MPN survival" [5.5 ± 5.9% (0.12-12%)] in A. perforata. Using the optimized cryopreservation conditions for each species, survival after freezing in liquid nitrogen was examined for six other strains of A. gubernaculifera (established from 1962 to 1981) and another A. perforata strain maintained in the Microbial Culture Collection at the National Institute for Environmental Studies (MCC-NIES). We obtained ≥0.1% MPN survival of the A. perforata strain. However, only two of the six strains of A. gubernaculifera showed ≥0.1% MPN survival. By using the optimal cryopreserved conditions obtained for each species, five cryopreserved strains of two species of Astrephomene were established and deposited in the MCC-NIES.

CONCLUSIONS: The optimal cryopreservation conditions differed between the two species of Astrephomene. Cryopreservation of long-term-maintained strains of A. gubernaculifera may be difficult; further studies of cryopreservation of these strains are needed.}, } @article {pmid36646908, year = {2023}, author = {Muñoz-Gómez, SA}, title = {Energetics and evolution of anaerobic microbial eukaryotes.}, journal = {Nature microbiology}, volume = {8}, number = {2}, pages = {197-203}, pmid = {36646908}, issn = {2058-5276}, mesh = {*Eukaryota ; Anaerobiosis ; *Mitochondria/metabolism ; Eukaryotic Cells/metabolism ; Fermentation ; }, abstract = {Mitochondria and aerobic respiration have been suggested to be required for the evolution of eukaryotic cell complexity. Aerobic respiration is several times more energetically efficient than fermentation. Moreover, aerobic respiration occurs at internalized mitochondrial membranes that are not constrained by a sublinear scaling with cell volume. However, diverse and complex anaerobic eukaryotes (for example, free-living and parasitic unicellular, and even small multicellular, eukaryotes) that exclusively rely on fermentation for energy generation have evolved repeatedly from aerobic ancestors. How do fermenting eukaryotes maintain their cell volumes and complexity while relying on such a low energy-yielding process? Here I propose that reduced rates of ATP generation in fermenting versus respiring eukaryotes are compensated for by longer cell cycles that satisfy lifetime energy demands. A literature survey and growth efficiency calculations show that fermenting eukaryotes divide approximately four to six times slower than aerobically respiring counterparts with similar cell volumes. Although ecological advantages such as competition avoidance offset lower growth rates and yields in the short term, fermenting eukaryotes inevitably have fewer physiological and ecological possibilities, which ultimately constrain their long-term evolutionary trajectories.}, } @article {pmid36641836, year = {2023}, author = {Barrenechea Angeles, I and Romero-Martínez, ML and Cavaliere, M and Varrella, S and Francescangeli, F and Piredda, R and Mazzocchi, MG and Montresor, M and Schirone, A and Delbono, I and Margiotta, F and Corinaldesi, C and Chiavarini, S and Montereali, MR and Rimauro, J and Parrella, L and Musco, L and Dell'Anno, A and Tangherlini, M and Pawlowski, J and Frontalini, F}, title = {Encapsulated in sediments: eDNA deciphers the ecosystem history of one of the most polluted European marine sites.}, journal = {Environment international}, volume = {172}, number = {}, pages = {107738}, doi = {10.1016/j.envint.2023.107738}, pmid = {36641836}, issn = {1873-6750}, mesh = {Humans ; Animals ; *Ecosystem ; *Biodiversity ; Biota ; Europe ; Human Activities ; Geologic Sediments ; }, abstract = {The Anthropocene is characterized by dramatic ecosystem changes driven by human activities. The impact of these activities can be assessed by different geochemical and paleontological proxies. However, each of these proxies provides only a fragmentary insight into the effects of anthropogenic impacts. It is highly challenging to reconstruct, with a holistic view, the state of the ecosystems from the preindustrial period to the present day, covering all biological components, from prokaryotes to multicellular eukaryotes. Here, we used sedimentary ancient DNA (sedaDNA) archives encompassing all trophic levels of biodiversity to reconstruct the two century-natural history in Bagnoli-Coroglio (Gulf of Pozzuoli, Tyrrhenian Sea), one of the most polluted marine-coastal sites in Europe. The site was characterized by seagrass meadows and high eukaryotic diversity until the beginning of the 20th century. Then, the ecosystem completely changed, with seagrasses and associated fauna as well as diverse groups of planktonic and benthic protists being replaced by low diversity biota dominated by dinophyceans and infaunal metazoan species. The sedaDNA analysis revealed a five-phase evolution of the area, where changes appear as the result of a multi-level cascade effect of impacts associated with industrial activities, urbanization, water circulation and land-use changes. The sedaDNA allowed to infer reference conditions that must be considered when restoration actions are to be implemented.}, } @article {pmid36637886, year = {2023}, author = {Kuzdzal-Fick, JJ and Moreno, A and Broersma, CME and Cooper, TF and Ostrowski, EA}, title = {From individual behaviors to collective outcomes: fruiting body formation in Dictyostelium as a group-level phenotype.}, journal = {Evolution; international journal of organic evolution}, volume = {77}, number = {3}, pages = {731-745}, doi = {10.1093/evolut/qpac038}, pmid = {36637886}, issn = {1558-5646}, mesh = {*Dictyostelium/genetics ; Phenotype ; Genotype ; Reproduction ; }, abstract = {Collective phenotypes, which arise from the interactions among individuals, can be important for the evolution of higher levels of biological organization. However, how a group's composition determines its collective phenotype remains poorly understood. When starved, cells of the social amoeba Dictyostelium discoideum cooperate to build a multicellular fruiting body, and the morphology of the fruiting body is likely advantageous to the surviving spores. We assessed how the number of strains, as well as their genetic and geographic relationships to one another, impact the group's morphology and productivity. We find that some strains consistently enhance or detract from the productivity of their groups, regardless of the identity of the other group members. We also detect extensive pairwise and higher-order genotype interactions, which collectively have a large influence on the group phenotype. Whereas previous work in Dictyostelium has focused almost exclusively on whether spore production is equitable when strains cooperate to form multicellular fruiting bodies, our results suggest a previously unrecognized impact of chimeric co-development on the group phenotype. Our results demonstrate how interactions among members of a group influence collective phenotypes and how group phenotypes might in turn impact selection on the individual.}, } @article {pmid36637107, year = {2023}, author = {Iyer, J and Pillai, S and Munguia-Lopez, JG and Zhang, Y and Mielkozorova, M and Tran, SD}, title = {Salivary gland bioengineering - yesterday, today, tomorrow!.}, journal = {Histology and histopathology}, volume = {38}, number = {6}, pages = {607-621}, pmid = {36637107}, issn = {1699-5848}, support = {FBD-181455//CIHR fund/ ; }, mesh = {Humans ; *Quality of Life ; Salivary Glands/physiology ; *Xerostomia/diagnosis/therapy ; Salivation ; Bioengineering ; }, abstract = {Salivary glands are specialized structures developed as an extensively compact, arborized design through classical embryogenesis, accompanied by a cascade of events channelized by numerous growth factors and genetic regulatory pathways. Salivary secretions maintain oral homeostasis and, when diminished in certain conditions, present as xerostomia or salivary hypofunction, adversely impacting the patient's quality of life. The current available treatments primarily aim at tackling the immediate symptoms providing temporary relief to the patient. Despite scientific efforts to develop permanent and effective solutions to restore salivation, a significant permanent treatment is yet to be established. Tissue engineering has proven as a promising remedial tool in several diseases, as well as in xerostomia, and aims to restore partial loss of organ function. Recapitulating the physiological cellular microenvironment to in vitro culture conditions is constantly evolving. Replicating the dynamic multicellular interactions, genetic pathways, and cytomorphogenic forces, as displayed during salivary gland development have experienced considerable barriers. Through this review, we endeavour to provide an outlook on the evolution of in vitro salivary gland research, highlighting the key bioengineering advances and the challenges faced with the current therapeutic strategies for salivary hypofunction, with an insight into our team's scientific contributions.}, } @article {pmid36611928, year = {2022}, author = {von der Heyde, B and Hallmann, A}, title = {Cell Type-Specific Pherophorins of Volvox carteri Reveal Interplay of Both Cell Types in ECM Biosynthesis.}, journal = {Cells}, volume = {12}, number = {1}, pages = {}, pmid = {36611928}, issn = {2073-4409}, mesh = {*Volvox/genetics/metabolism ; Phylogeny ; Extracellular Matrix/metabolism ; *Chlorophyta/genetics ; Extracellular Matrix Proteins/metabolism ; }, abstract = {The spheroidal green algae Volvox carteri serves as a model system to investigate the formation of a complex, multifunctional extracellular matrix (ECM) in a relatively simple, multicellular organism with cell differentiation. The V. carteri ECM is mainly composed of hydroxyproline-rich glycoproteins (HRGPs) and there are diverse region-specific, anatomically distinct structures in the ECM. One large protein family with importance for ECM biosynthesis stands out: the pherophorins. The few pherophorins previously extracted from the ECM and characterized, were specifically expressed by somatic cells. However, the localization and function of most pherophorins is unknown. Here, we provide a phylogenetic analysis of 153 pherophorins of V. carteri and its unicellular relative Chlamydomonas reinhardtii. Our analysis of cell type-specific mRNA expression of pherophorins in V. carteri revealed that, contrary to previous assumptions, only about half (52%) of the 102 investigated pherophorin-related genes show stronger expression in somatic cells, whereas about one-third (34%) of the genes show significant higher expression in reproductive cells (gonidia). We fused two pherophorin genes that are expressed by different cell types to yfp, stably expressed them in Volvox and studied the tagged proteins by live-cell imaging. In contrast to earlier biochemical approaches, this genetic approach also allows the in vivo analysis of non-extractable, covalently cross-linked ECM proteins. We demonstrate that the soma-specific pherophorin SSG185 is localized in the outermost ECM structures of the spheroid, the boundary zone and at the flagellar hillocks. SSG185:YFP is detectable as early as 1.5 h after completion of embryogenesis. It is then present for the rest of the life cycle. The gonidia-specific pherophorin PhG is localized in the gonidial cellular zone 1 ("gonidial vesicle") suggesting its involvement in the protection of gonidia and developing embryos until hatching. Even if somatic cells produce the main portion of the ECM of the spheroids, ECM components produced by gonidia are also required to cooperatively assemble the total ECM. Our results provide insights into the evolution of the pherophorin protein family and convey a more detailed picture of Volvox ECM synthesis.}, } @article {pmid36598184, year = {2023}, author = {Dang, CC and Vinh, LS}, title = {Estimating amino acid substitution models for metazoan evolutionary studies.}, journal = {Journal of evolutionary biology}, volume = {36}, number = {3}, pages = {499-506}, doi = {10.1111/jeb.14147}, pmid = {36598184}, issn = {1420-9101}, mesh = {Animals ; Phylogeny ; *Evolution, Molecular ; Amino Acid Substitution ; Bayes Theorem ; *Proteins ; Models, Genetic ; }, abstract = {Amino acid substitution models represent the substitution rates among amino acids during the evolution of protein sequences. The models are a prerequisite for maximum likelihood or Bayesian methods to analyse the phylogenetic relationships among species based on their protein sequences. Estimating amino acid substitution models requires large protein datasets and intensive computation. In this paper, we presented the estimation of both time-reversible model (Q.met) and time non-reversible model (NQ.met) for multicellular animals (Metazoa). Analyses showed that the Q.met and NQ.met models were significantly better than existing models in analysing metazoan protein sequences. Moreover, the time non-reversible model NQ.met enables us to reconstruct the rooted phylogenetic tree for Metazoa. We recommend researchers to employ the Q.met and NQ.met models in analysing metazoan protein sequences.}, } @article {pmid36587372, year = {2023}, author = {Palmiero, M and Cantarosso, I and di Blasio, L and Monica, V and Peracino, B and Primo, L and Puliafito, A}, title = {Collective directional migration drives the formation of heteroclonal cancer cell clusters.}, journal = {Molecular oncology}, volume = {17}, number = {9}, pages = {1699-1725}, pmid = {36587372}, issn = {1878-0261}, mesh = {Humans ; Cell Movement ; *Phosphatidylinositol 3-Kinases ; Actins/metabolism ; *Neoplasms ; }, abstract = {Metastasisation occurs through the acquisition of invasive and survival capabilities that allow tumour cells to colonise distant sites. While the role of multicellular aggregates in cancer dissemination is acknowledged, the mechanisms that drive the formation of multiclonal cell aggregates are not fully elucidated. Here, we show that cancer cells of different tissue of origins can perform collective directional migration and can actively form heteroclonal aggregates in 3D, through a proliferation-independent mechanism. Coalescence of distant cell clusters is mediated by subcellular actin-rich protrusions and multicellular outgrowths that extend towards neighbouring aggregates. Coherently, perturbation of cytoskeletal dynamics impairs collective migration while myosin II activation is necessary for multicellular movements. We put forward the hypothesis that cluster attraction is mediated by secreted soluble factors. Such a hypothesis is consistent with the abrogation of aggregation by inhibition of PI3K/AKT/mTOR and MEK/ERK, the chemoattracting activity of conditioned culture media and with a wide screening of secreted proteins. Our results present a novel collective migration model and shed light on the mechanisms of formation of heteroclonal aggregates in cancer.}, } @article {pmid36585440, year = {2022}, author = {Lynch, M and Trickovic, B and Kempes, CP}, title = {Evolutionary scaling of maximum growth rate with organism size.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22586}, pmid = {36585440}, issn = {2045-2322}, support = {R35 GM122566/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; *Genetic Drift ; Eukaryota/genetics ; Mutation ; Selection, Genetic ; }, abstract = {Data from nearly 1000 species reveal the upper bound to rates of biomass production achievable by natural selection across the Tree of Life. For heterotrophs, maximum growth rates scale positively with organism size in bacteria but negatively in eukaryotes, whereas for phototrophs, the scaling is negligible for cyanobacteria and weakly negative for eukaryotes. These results have significant implications for understanding the bioenergetic consequences of the transition from prokaryotes to eukaryotes, and of the expansion of some groups of the latter into multicellularity. The magnitudes of the scaling coefficients for eukaryotes are significantly lower than expected under any proposed physical-constraint model. Supported by genomic, bioenergetic, and population-genetic data and theory, an alternative hypothesis for the observed negative scaling in eukaryotes postulates that growth-diminishing mutations with small effects passively accumulate with increasing organism size as a consequence of associated increases in the power of random genetic drift. In contrast, conditional on the structural and functional features of ribosomes, natural selection has been able to promote bacteria with the fastest possible growth rates, implying minimal conflicts with both bioenergetic constraints and random genetic drift. If this extension of the drift-barrier hypothesis is correct, the interpretations of comparative studies of biological traits that have traditionally ignored differences in population-genetic environments will require revisiting.}, } @article {pmid36553613, year = {2022}, author = {Kozlov, AP}, title = {The Theory of Carcino-Evo-Devo and Its Non-Trivial Predictions.}, journal = {Genes}, volume = {13}, number = {12}, pages = {}, pmid = {36553613}, issn = {2073-4425}, mesh = {Animals ; Humans ; *Genes, Tumor Suppressor ; Oncogenes ; Cell Differentiation ; *Neoplasms/genetics ; Fishes ; }, abstract = {To explain the sources of additional cell masses in the evolution of multicellular organisms, the theory of carcino-evo-devo, or evolution by tumor neofunctionalization, has been developed. The important demand for a new theory in experimental science is the capability to formulate non-trivial predictions which can be experimentally confirmed. Several non-trivial predictions were formulated using carcino-evo-devo theory, four of which are discussed in the present paper: (1) The number of cellular oncogenes should correspond to the number of cell types in the organism. The evolution of oncogenes, tumor suppressor and differentiation gene classes should proceed concurrently. (2) Evolutionarily new and evolving genes should be specifically expressed in tumors (TSEEN genes). (3) Human orthologs of fish TSEEN genes should acquire progressive functions connected with new cell types, tissues and organs. (4) Selection of tumors for new functions in the organism is possible. Evolutionarily novel organs should recapitulate tumor features in their development. As shown in this paper, these predictions have been confirmed by the laboratory of the author. Thus, we have shown that carcino-evo-devo theory has predictive power, fulfilling a fundamental requirement for a new theory.}, } @article {pmid36550365, year = {2022}, author = {Bowman, JL}, title = {The origin of a land flora.}, journal = {Nature plants}, volume = {8}, number = {12}, pages = {1352-1369}, pmid = {36550365}, issn = {2055-0278}, mesh = {*Biological Evolution ; Phylogeny ; Plants/genetics ; *Embryophyta/genetics ; }, abstract = {The origin of a land flora fundamentally shifted the course of evolution of life on earth, facilitating terrestrialization of other eukaryotic lineages and altering the planet's geology, from changing atmospheric and hydrological cycles to transforming continental erosion processes. Despite algal lineages inhabiting the terrestrial environment for a considerable preceding period, they failed to evolve complex multicellularity necessary to conquer the land. About 470 million years ago, one lineage of charophycean alga evolved complex multicellularity via developmental innovations in both haploid and diploid generations and became land plants (embryophytes), which rapidly diversified to dominate most terrestrial habitats. Genome sequences have provided unprecedented insights into the genetic and genomic bases for embryophyte origins, with some embryophyte-specific genes being associated with the evolution of key developmental or physiological attributes, such as meristems, rhizoids and the ability to form mycorrhizal associations. However, based on the fossil record, the evolution of the defining feature of embryophytes, the embryo, and consequently the sporangium that provided a reproductive advantage, may have been most critical in their rise to dominance. The long timeframe and singularity of a land flora were perhaps due to the stepwise assembly of a large constellation of genetic innovations required to conquer the terrestrial environment.}, } @article {pmid36547392, year = {2022}, author = {Baselga-Cervera, B and Gettle, N and Travisano, M}, title = {Loss-of-heterozygosity facilitates a fitness valley crossing in experimentally evolved multicellular yeast.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1976}, pages = {20212722}, pmid = {36547392}, issn = {1471-2954}, mesh = {*Adaptation, Physiological/genetics ; *Biological Evolution ; Genotype ; Heterozygote ; *Saccharomyces cerevisiae/genetics ; *Loss of Heterozygosity ; *Genetic Fitness ; }, abstract = {Determining how adaptive possibilities do or do not become evolutionary realities is central to understanding the tempo and mode of evolutionary change. Some of the simplest evolutionary landscapes arise from underdominance at a single locus where the fitness valley consists of only one less-fit genotype. Despite their potential for rapid evolutionary change, few such examples have been investigated. We capitalized on an experimental system in which a significant evolutionary shift, the transition from uni-to-multicellularity, was observed in asexual diploid populations of Saccharomyces cerevisiae experimentally selected for increased settling rates. The multicellular phenotype results from recessive single-locus mutations that undergo loss-of-heterozygosity (LOH) events. By reconstructing the necessary heterozygous intermediate steps, we found that the evolution of multicellularity involves a decrease in size during the first steps. Heterozygous genotypes are 20% smaller in size than genotypes with functional alleles. Nevertheless, populations of heterozygotes give rise to multicellular genotypes more readily than unicellular genotypes with two functional alleles, by rapid LOH events. LOH drives adaptation that may enable rapid evolution in diploid yeast. Together these results show discordance between the phenotypic and genotypic multicellular transition. The evolutionary path to multicellularity, and the adaptive benefits of increased size, requires initial size reductions.}, } @article {pmid36542495, year = {2023}, author = {Martinez, P and Ustyantsev, K and Biryukov, M and Mouton, S and Glasenburg, L and Sprecher, SG and Bailly, X and Berezikov, E}, title = {Genome assembly of the acoel flatworm Symsagittifera roscoffensis, a model for research on body plan evolution and photosymbiosis.}, journal = {G3 (Bethesda, Md.)}, volume = {13}, number = {2}, pages = {}, pmid = {36542495}, issn = {2160-1836}, mesh = {Animals ; *Platyhelminths/genetics ; Phylogeny ; Base Sequence ; Genome Size ; Transcriptome ; Chromosomes ; }, abstract = {Symsagittifera roscoffensis is a well-known member of the order Acoela that lives in symbiosis with the algae Tetraselmis convolutae during its adult stage. Its natural habitat is the eastern coast of the Atlantic, where at specific locations thousands of individuals can be found, mostly, lying in large pools on the surface of sand at low tide. As a member of the Acoela it has been thought as a proxy for ancestral bilaterian animals; however, its phylogenetic position remains still debated. In order to understand the basic structural characteristics of the acoel genome, we sequenced and assembled the genome of aposymbiotic species S. roscoffensis. The size of this genome was measured to be in the range of 910-940 Mb. Sequencing of the genome was performed using PacBio Hi-Fi technology. Hi-C and RNA-seq data were also generated to scaffold and annotate it. The resulting assembly is 1.1 Gb large (covering 118% of the estimated genome size) and highly continuous, with N50 scaffold size of 1.04 Mb. The repetitive fraction of the genome is 61%, of which 85% (half of the genome) are LTR retrotransposons. Genome-guided transcriptome assembly identified 34,493 genes, of which 29,351 are protein coding (BUSCO score 97.6%), and 30.2% of genes are spliced leader trans-spliced. The completeness of this genome suggests that it can be used extensively to characterize gene families and conduct accurate phylogenomic reconstructions.}, } @article {pmid36539037, year = {2023}, author = {Rangarajan, ES and Smith, EW and Izard, T}, title = {The nematode α-catenin ortholog, HMP1, has an extended α-helix when bound to actin filaments.}, journal = {The Journal of biological chemistry}, volume = {299}, number = {2}, pages = {102817}, pmid = {36539037}, issn = {1083-351X}, support = {R35 GM139604/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Actin Cytoskeleton/chemistry/metabolism/ultrastructure ; Actins/chemistry/metabolism/ultrastructure ; *alpha Catenin/chemistry/metabolism ; Cadherins/metabolism ; *Caenorhabditis elegans ; Mammals ; Protein Conformation, alpha-Helical ; Protein Domains ; Cryoelectron Microscopy ; Cell Adhesion ; Cell Communication ; }, abstract = {The regulation of cell-cell junctions during epidermal morphogenesis ensures tissue integrity, a process regulated by α-catenin. This cytoskeletal protein connects the cadherin complex to filamentous actin at cell-cell junctions. The cadherin-catenin complex plays key roles in cell physiology, organism development, and disease. While mutagenesis of Caenorhabditis elegans cadherin and catenin shows that these proteins are key for embryonic morphogenesis, we know surprisingly little about their structure and attachment to the cytoskeleton. In contrast to mammalian α-catenin that functions as a dimer or monomer, the α-catenin ortholog from C. elegans, HMP1 for humpback, is a monomer. Our cryogenic electron microscopy (cryoEM) structure of HMP1/α-catenin reveals that the amino- and carboxy-terminal domains of HMP1/α-catenin are disordered and not in contact with the remaining HMP1/α-catenin middle domain. Since the carboxy-terminal HMP1/α-catenin domain is the F-actin-binding domain (FABD), this interdomain constellation suggests that HMP1/α-catenin is constitutively active, which we confirm biochemically. Our perhaps most surprising finding, given the high sequence similarity between the mammalian and nematode proteins, is our cryoEM structure of HMP1/α-catenin bound to F-actin. Unlike the structure of mammalian α-catenin bound to F-actin, binding to F-actin seems to allosterically convert a loop region of the HMP1/α-catenin FABD to extend an HMP1/α-catenin FABD α-helix. We use cryoEM and bundling assays to show for the first time how the FABD of HMP1/α-catenin bundles actin in the absence of force. Collectively, our data advance our understanding of α-catenin regulation of cell-cell contacts and additionally aid our understanding of the evolution of multicellularity in metazoans.}, } @article {pmid36531949, year = {2022}, author = {Nguyen, NM and Merle, T and Broders-Bondon, F and Brunet, AC and Battistella, A and Land, EBL and Sarron, F and Jha, A and Gennisson, JL and Röttinger, E and Fernández-Sánchez, ME and Farge, E}, title = {Mechano-biochemical marine stimulation of inversion, gastrulation, and endomesoderm specification in multicellular Eukaryota.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {992371}, pmid = {36531949}, issn = {2296-634X}, abstract = {The evolutionary emergence of the primitive gut in Metazoa is one of the decisive events that conditioned the major evolutionary transition, leading to the origin of animal development. It is thought to have been induced by the specification of the endomesoderm (EM) into the multicellular tissue and its invagination (i.e., gastrulation). However, the biochemical signals underlying the evolutionary emergence of EM specification and gastrulation remain unknown. Herein, we find that hydrodynamic mechanical strains, reminiscent of soft marine flow, trigger active tissue invagination/gastrulation or curvature reversal via a Myo-II-dependent mechanotransductive process in both the metazoan Nematostella vectensis (cnidaria) and the multicellular choanoflagellate Choanoeca flexa. In the latter, our data suggest that the curvature reversal is associated with a sensory-behavioral feeding response. Additionally, like in bilaterian animals, gastrulation in the cnidarian Nematostella vectensis is shown to participate in the biochemical specification of the EM through mechanical activation of the β-catenin pathway via the phosphorylation of Y654-βcatenin. Choanoflagellates are considered the closest living relative to metazoans, and the common ancestor of choanoflagellates and metazoans dates back at least 700 million years. Therefore, the present findings using these evolutionarily distant species suggest that the primitive emergence of the gut in Metazoa may have been initiated in response to marine mechanical stress already in multicellular pre-Metazoa. Then, the evolutionary transition may have been achieved by specifying the EM via a mechanosensitive Y654-βcatenin dependent mechanism, which appeared during early Metazoa evolution and is specifically conserved in all animals.}, } @article {pmid36529400, year = {2023}, author = {Liu, Y and Cao, M and Yan, X and Cai, X and Li, Y and Li, C and Xue, T}, title = {Genome-wide identification of gap junction (connexins and pannexins) genes in black rockfish (Sebastes schlegelii): Evolution and immune response mechanism following challenge.}, journal = {Fish & shellfish immunology}, volume = {132}, number = {}, pages = {108492}, doi = {10.1016/j.fsi.2022.108492}, pmid = {36529400}, issn = {1095-9947}, mesh = {Animals ; *Connexins/genetics ; Phylogeny ; Gap Junctions/chemistry/metabolism ; *Perciformes/metabolism ; Immunity ; }, abstract = {Cell-to-cell communication through gap junction channels is very important to coordinate the functions of cells in all multicellular biological tissues. It allows the direct exchange of ions and small molecules (including second messengers, such as Ca[2+], IP3, cyclic nucleotides, and oligonucleotides). In this study, a total of 48 members of the gap junction (GJ) protein family were identified from Sebastes schlegelii. In S. schlegelii, GJ proteins were classified into two types, connexin, and pannexin, and then connexins were divided into five subfamilies. The naming of 48 genes was verified through phylogenetic analysis and syntenic analysis. The connexin proteins contained four transmembrane fragments and two extracellular loops, the lengths of the intracellular loop and C-terminal was quite different, and the C-terminal region was highly variable after post-translational modification. PPI analysis showed that GJs interacted with tight junctions, adhesive junctions, and cell adhesions to form a complex network and participated in cell-cell junction organization, ATP binding, ion channel, voltage-gated conduction, wnt signaling pathway, Fc-γ receptor signaling pathway, and DNA replication. In addition, the S. schlegelii GJ protein was highly expressed in intestinal tissues and remarkably regulated after Edwardsiella tarda and Streptococcus iniae infection. The expression of GJs in intestinal cells of S. schlegelii was significantly regulated by LPS and poly (I:C), which was consistent with the results of intestinal tissue stimulation by pathogens. In conclusion, this study can provide valuable information for further research on the function of S. schlegelii GJ proteins.}, } @article {pmid36526191, year = {2023}, author = {Barbosa, FAS and Brait, LAS and Coutinho, FH and Ferreira, CM and Moreira, EF and de Queiroz Salles, L and Meirelles, PM}, title = {Ecological landscape explains aquifers microbial structure.}, journal = {The Science of the total environment}, volume = {862}, number = {}, pages = {160822}, doi = {10.1016/j.scitotenv.2022.160822}, pmid = {36526191}, issn = {1879-1026}, mesh = {Humans ; *Groundwater/chemistry ; Bacteria/metabolism ; Water Quality ; Gram-Negative Bacteria ; *Microbiota ; }, abstract = {Aquifers have significant social, economic, and ecological importance. They supply 30 % of the freshwater for human consumption worldwide, including agricultural and industrial use. Despite aquifers' importance, the relationships between aquifer categories and their inhabiting microbial communities are still unknown. Characterizing variations within microbial communities' function and taxonomy structure at different aquifers could give a panoramic view of patterns that may enable the detection and prediction of environmental impact caused by multiple sources. Using publicly available shotgun metagenomic datasets, we examined whether soil properties, land use, and climate variables would have a more significant influence on the taxonomy and functional structure of the microbial communities than the ecological landscapes of the aquifer (i.e., Karst, Porous, Saline, Geyser, and Porous Contaminated). We found that these categories are stronger predictors of microbial communities' structure than geographical localization. In addition, our results show that microbial richness and dominance patterns are the opposite of those found in multicellular life, where extreme habitats harbour richer functional and taxonomic microbial communities. We found that low-abundant and recently described candidate taxa, such as the chemolithoautotrophic genus Candidatus Altiarcheum and the Candidate phylum Parcubacteria, are the main contributors to aquifer microbial communities' dissimilarities. Genes related to gram-negative bacteria proteins, cell wall structures, and phage activity were the primary contributors to aquifer microbial communities' dissimilarities among the aquifers' ecological landscapes. The results reported in the present study highlight the utility of using ecological landscapes for investigating aquifer microbial communities. In addition, we suggest that functions played by recently described and low abundant bacterial groups need further investigation once they might affect water quality, geochemical cycles, and the effects of anthropogenic disturbances such as pollution and climatic events on aquifers.}, } @article {pmid36499258, year = {2022}, author = {Vainshelbaum, NM and Giuliani, A and Salmina, K and Pjanova, D and Erenpreisa, J}, title = {The Transcriptome and Proteome Networks of Malignant Tumours Reveal Atavistic Attractors of Polyploidy-Related Asexual Reproduction.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36499258}, issn = {1422-0067}, support = {1.1.1.2/VIAA/3/19/463//European Regional Development Fund/ ; 8.2.2.0/20/I/006//European Social Fund/ ; }, mesh = {Animals ; Humans ; *Gene Duplication ; Genome, Plant ; Proteome/genetics ; Evolution, Molecular ; Polyploidy ; Transcriptome ; *Neoplasms/genetics ; Mammals/genetics ; }, abstract = {The expression of gametogenesis-related (GG) genes and proteins, as well as whole genome duplications (WGD), are the hallmarks of cancer related to poor prognosis. Currently, it is not clear if these hallmarks are random processes associated only with genome instability or are programmatically linked. Our goal was to elucidate this via a thorough bioinformatics analysis of 1474 GG genes in the context of WGD. We examined their association in protein-protein interaction and coexpression networks, and their phylostratigraphic profiles from publicly available patient tumour data. The results show that GG genes are upregulated in most WGD-enriched somatic cancers at the transcriptome level and reveal robust GG gene expression at the protein level, as well as the ability to associate into correlation networks and enrich the reproductive modules. GG gene phylostratigraphy displayed in WGD+ cancers an attractor of early eukaryotic origin for DNA recombination and meiosis, and one relative to oocyte maturation and embryogenesis from early multicellular organisms. The upregulation of cancer-testis genes emerging with mammalian placentation was also associated with WGD. In general, the results suggest the role of polyploidy for soma-germ transition accessing latent cancer attractors in the human genome network, which appear as pre-formed along the whole Evolution of Life.}, } @article {pmid36497057, year = {2022}, author = {Aktas, RG and Karski, M and Issac, B and Sun, L and Rockowitz, S and Sliz, P and Vakili, K}, title = {Long-Term Characteristics of Human-Derived Biliary Organoids under a Single Continuous Culture Condition.}, journal = {Cells}, volume = {11}, number = {23}, pages = {}, pmid = {36497057}, issn = {2073-4409}, support = {N/A//CHMC Surgical Foundation/ ; }, mesh = {Humans ; Child ; *Organoids ; *Epithelial Cells ; }, abstract = {Organoids have been used to investigate the three-dimensional (3D) organization and function of their respective organs. These self-organizing 3D structures offer a distinct advantage over traditional two-dimensional (2D) culture techniques by creating a more physiologically relevant milieu to study complex biological systems. The goal of this study was to determine the feasibility of establishing organoids from various pediatric liver diseases and characterize the long-term evolution of cholangiocyte organoids (chol-orgs) under a single continuous culture condition. We established chol-orgs from 10 different liver conditions and characterized their multicellular organization into complex epithelial structures through budding, merging, and lumen formation. Immunofluorescent staining, electron microscopy, and single-nucleus RNA (snRNA-seq) sequencing confirmed the cholangiocytic nature of the chol-orgs. There were significant cell population differences in the transcript profiles of two-dimensional and organoid cultures based on snRNA-seq. Our study provides an approach for the generation and long-term maintenance of chol-orgs from various pediatric liver diseases under a single continuous culture condition.}, } @article {pmid36494694, year = {2022}, author = {Sun, H and Fang, T and Wang, T and Yu, Z and Gong, L and Wei, X and Wang, H and He, Y and Liu, L and Yan, Y and Sui, W and Xu, Y and Yi, S and Qiu, L and Hao, M}, title = {Single-cell profiles reveal tumor cell heterogeneity and immunosuppressive microenvironment in Waldenström macroglobulinemia.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {576}, pmid = {36494694}, issn = {1479-5876}, mesh = {Humans ; *Ecosystem ; *Waldenstrom Macroglobulinemia/genetics/pathology ; Bone Marrow/pathology ; Tumor Microenvironment ; B-Lymphocytes/pathology ; }, abstract = {BACKGROUND: Waldenström macroglobulinemia (WM) is a rare and incurable indolent B-cell malignancy. The molecular pathogenesis and the role of immunosuppressive microenvironment in WM development are still incompletely understood.

METHODS: The multicellular ecosystem in bone marrow (BM) of WM were delineated by single-cell RNA-sequencing (scRNA-seq) and investigated the underlying molecular characteristics.

RESULTS: Our data uncovered the heterogeneity of malignant cells in WM, and investigated the kinetic co-evolution of WM and immune cells, which played pivotal roles in disease development and progression. Two novel subpopulations of malignant cells, CD19[+]CD3[+] and CD138[+]CD3[+], co-expressing T-cell marker genes were identified at single-cell resolution. Pseudotime-ordered analysis elucidated that CD19[+]CD3[+] malignant cells presented at an early stage of WM-B cell differentiation. Colony formation assay further identified that CD19[+]CD3[+] malignant cells acted as potential WM precursors. Based on the findings of T cell marker aberrant expressed on WM tumor cells, we speculate the long-time activation of tumor antigen-induced immunosuppressive microenvironment that is involved in the pathogenesis of WM. Therefore, our study further investigated the possible molecular mechanism of immune cell dysfunction. A precursor exhausted CD8-T cells and functional deletion of NK cells were identified in WM, and CD47 would be a potential therapeutic target to reverse the dysfunction of immune cells.

CONCLUSIONS: Our study facilitates further understanding of the biological heterogeneity of tumor cells and immunosuppressive microenvironment in WM. These data may have implications for the development of novel immunotherapies, such as targeting pre-exhausted CD8-T cells in WM.}, } @article {pmid36476840, year = {2022}, author = {Nakabachi, A and Inoue, H and Hirose, Y}, title = {High-resolution Microbiome Analyses of Nine Psyllid Species of the Family Triozidae Identified Previously Unrecognized but Major Bacterial Populations, including Liberibacter and Wolbachia of Supergroup O.}, journal = {Microbes and environments}, volume = {37}, number = {4}, pages = {}, pmid = {36476840}, issn = {1347-4405}, mesh = {Humans ; Animals ; Liberibacter ; *Wolbachia/genetics ; *Hemiptera ; RNA, Ribosomal, 16S/genetics ; Europe ; }, abstract = {Psyllids (Hemiptera: Sternorrhyncha: Psylloidea) are plant sap-sucking insects that include important agricultural pests. To obtain insights into the ecological and evolutionary behaviors of microbes, including plant pathogens, in Psylloidea, high-resolution ana-lyses of the microbiomes of nine psyllid species belonging to the family Triozidae were performed using high-throughput amplicon sequencing of the 16S rRNA gene. Analyses identified various bacterial populations, showing that all nine psyllids have at least one secondary symbiont, along with the primary symbiont "Candidatus Carsonella ruddii" (Gammaproteobacteria: Oceanospirillales: Halomonadaceae). The majority of the secondary symbionts were gammaproteobacteria, particularly those of the order Enterobacterales, which included Arsenophonus and Serratia symbiotica, a bacterium formerly recognized only as a secondary symbiont of aphids (Hemiptera: Sternorrhyncha: Aphidoidea). The non-Enterobacterales gammaproteobacteria identified in the present study were Diplorickettsia (Diplorickettsiales: Diplorickettsiaceae), a potential human pathogen, and Carnimonas (Oceanospirillales: Halomonadaceae), a lineage detected for the first time in Psylloidea. Regarding alphaproteobacteria, the potential plant pathogen "Ca. Liberibacter europaeus" (Rhizobiales: Rhizobiaceae) was detected for the first time in Epitrioza yasumatsui, which feeds on the Japanese silverberry Elaeagnus umbellata (Elaeagnaceae), an aggressive invasive plant in the United States and Europe. Besides the detection of Wolbachia (Rickettsiales: Anaplasmataceae) of supergroup B in three psyllid species, a lineage belonging to supergroup O was identified for the first time in Psylloidea. These results suggest the rampant transfer of bacterial symbionts among animals and plants, thereby providing deeper insights into the evolution of interkingdom interactions among multicellular organisms and bacteria, which will facilitate the control of pest psyllids.}, } @article {pmid36460873, year = {2022}, author = {Niculescu, VF}, title = {A comment on the article Jaques et al. "Origin and evolution of animal multicellularity in light of phylogenomics and cancer genetics ".}, journal = {Medical oncology (Northwood, London, England)}, volume = {40}, number = {1}, pages = {38}, pmid = {36460873}, issn = {1559-131X}, mesh = {Animals ; Humans ; Phylogeny ; *Health Personnel ; *Neoplasms/genetics ; }, abstract = {For developmental biologists, the work of Jaques et al. is quite surprising. It suggests that cancer genetics and cancer phylogenomics may contribute to the origin and evolution of multicellularity in animals. My commentary complements the work of Jaques et al. from the perspective of evolutionary life cycle biology and recalls the statement of Douglas H. Erwin, who said that understanding life cycle evolution is (equally) crucial to subsequent steps [1].}, } @article {pmid36447160, year = {2022}, author = {Liu, Y and Ma, Y and Aray, H and Lan, H}, title = {Morphogenesis and cell wall composition of trichomes and their function in response to salt in halophyte Salsola ferganica.}, journal = {BMC plant biology}, volume = {22}, number = {1}, pages = {551}, pmid = {36447160}, issn = {1471-2229}, support = {31960037//National Natural Science Foundation of China/ ; }, mesh = {*Salsola ; Salt-Tolerant Plants/genetics ; Trichomes ; *Arabidopsis/genetics ; Sodium Chloride ; Cell Wall ; Morphogenesis ; Gossypium ; }, abstract = {BACKGROUND: To survive harsh environmental conditions, desert plants show various adaptions, such as the evolution of trichomes, which are protective epidermal protrusions. Currently, the morphogenesis and function of trichomes in desert plants are not well understood. Salsola ferganica is an annual halophyte distributed in cold deserts; at the seedling stage, its rod-shaped true leaves are covered with long and thick trichomes and are affected by habitat conditions. Therefore, we evaluated the trichomes on morphogenesis and cell wall composition of S. ferganica compared to Arabidopsis thaliana and cotton, related gene expression, and preliminary function in salt accumulation of the leaves.

RESULTS: The trichomes of S. ferganica were initiated from the epidermal primordium, followed by two to three rounds of cell division to form a multicellular trichome, while some genes associated with them were positively involved. Cell wall composition analysis showed that different polysaccharides including heavily methyl-esterified and fully de-esterified pectins (before maturation, probably in the primary wall), xyloglucans (in the mid-early and middle stages, probably in the secondary wall), and extensin (during the whole developmental period) were detected, which were different from those found in trichomes of Arabidopsis and cotton. Moreover, trichome development was affected by abiotic stress, and might accumulate salt from the mesophyll cells and secrete outside.

CONCLUSIONS: S. ferganica has multicellular, non-branched trichomes that undergo two to three rounds of cell division and are affected by abiotic stress. They have a unique cell wall composition which is different from that of Arabidopsis and cotton. Furthermore, several genes positively or negatively regulate trichome development. Our findings should contribute to our further understanding of the biogenesis and adaptation of plant accessory structures in desert plant species.}, } @article {pmid36434792, year = {2022}, author = {Zhan, A and Luo, Y and Qin, H and Lin, W and Tian, L}, title = {Hypomagnetic Field Exposure Affecting Gut Microbiota, Reactive Oxygen Species Levels, and Colonic Cell Proliferation in Mice.}, journal = {Bioelectromagnetics}, volume = {43}, number = {8}, pages = {462-475}, doi = {10.1002/bem.22427}, pmid = {36434792}, issn = {1521-186X}, support = {42074073//National Natural Science Foundation of China/ ; 41621004//National Natural Science Foundation of China/ ; XDA17010501//Strategic Priority Research Program of the Chinese Academy of Sciences/ ; }, mesh = {Animals ; Mice ; Cell Proliferation ; *Colon ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; *Reactive Oxygen Species ; }, abstract = {The gut microbiota has been considered one of the key factors in host health, which is influenced by many environmental factors. The geomagnetic field (GMF) represents one of the important environmental conditions for living organisms. Previous studies have shown that the elimination of GMF, the so-called hypomagnetic field (HMF), could affect the physiological functions and resistance to antibiotics of some microorganisms. However, whether long-term HMF exposure could alter the gut microbiota to some extent in mammals remains unclear. Here, we investigated the effects of long-term (8- and 12-week) HMF exposure on the gut microbiota in C57BL/6J mice. Our results clearly showed that 8-week HMF significantly affected the diversity and function of the mouse gut microbiota. Compared with the GMF group, the concentrations of short-chain fatty acids tended to decrease in the HMF group. Immunofluorescence analysis showed that HMF promoted colonic cell proliferation, concomitant with an increased level of reactive oxygen species (ROS). To our knowledge, this is the first in vivo finding that long-term HMF exposure could affect the mouse gut microbiota, ROS levels, and colonic cell proliferation in the colon. Moreover, the changes in gut microbiota can be restored by returning mice to the GMF environment, thus the possible harm to the microbiota caused by HMF exposure can be alleviated. © 2022 Bioelectromagnetics Society.}, } @article {pmid36433975, year = {2022}, author = {Kreider, JJ and Janzen, T and Bernadou, A and Elsner, D and Kramer, BH and Weissing, FJ}, title = {Resource sharing is sufficient for the emergence of division of labour.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {7232}, pmid = {36433975}, issn = {2041-1723}, mesh = {Animals ; Female ; Pregnancy ; *Biological Evolution ; *Labor, Obstetric ; }, abstract = {Division of labour occurs in a broad range of organisms. Yet, how division of labour can emerge in the absence of pre-existing interindividual differences is poorly understood. Using a simple but realistic model, we show that in a group of initially identical individuals, division of labour emerges spontaneously if returning foragers share part of their resources with other group members. In the absence of resource sharing, individuals follow an activity schedule of alternating between foraging and other tasks. If non-foraging individuals are fed by other individuals, their alternating activity schedule becomes interrupted, leading to task specialisation and the emergence of division of labour. Furthermore, nutritional differences between individuals reinforce division of labour. Such differences can be caused by increased metabolic rates during foraging or by dominance interactions during resource sharing. Our model proposes a plausible mechanism for the self-organised emergence of division of labour in animal groups of initially identical individuals. This mechanism could also play a role for the emergence of division of labour during the major evolutionary transitions to eusociality and multicellularity.}, } @article {pmid36430514, year = {2022}, author = {Ojosnegros, S and Alvarez, JM and Grossmann, J and Gagliardini, V and Quintanilla, LG and Grossniklaus, U and Fernández, H}, title = {The Shared Proteome of the Apomictic Fern Dryopteris affinis ssp. affinis and Its Sexual Relative Dryopteris oreades.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430514}, issn = {1422-0067}, support = {//University of Zurich/ ; Grant CESSTT1819 for International Mobility of Research Staff//University of Oviedo/ ; PRIME-XS-0002520//European Union's 7th Framework Program/ ; }, mesh = {*Dryopteris/genetics ; *Ferns/genetics ; Proteome ; Proteomics ; Plant Growth Regulators ; }, abstract = {Ferns are a diverse evolutionary lineage, sister to the seed plants, which is of great ecological importance and has a high biotechnological potential. Fern gametophytes represent one of the simplest autotrophic, multicellular plant forms and show several experimental advantages, including a simple and space-efficient in vitro culture system. However, the molecular basis of fern growth and development has hardly been studied. Here, we report on a proteomic study that identified 417 proteins shared by gametophytes of the apogamous fern Dryopteris affinis ssp. affinis and its sexual relative Dryopteris oreades. Most proteins are predicted to localize to the cytoplasm, the chloroplast, or the nucleus, and are linked to enzymatic, binding, and structural activities. A subset of 145 proteins are involved in growth, reproduction, phytohormone signaling and biosynthesis, and gene expression, including homologs of SHEPHERD (SHD), HEAT SHOCK PROTEIN 90-5 (CR88), TRP4, BOBBER 1 (BOB1), FLAVONE 3'-O-METHYLTRANSFERASE 1 (OMT1), ZEAXANTHIN EPOXIDASE (ABA1), GLUTAMATE DESCARBOXYLASE 1 (GAD), and dsRNA-BINDING DOMAIN-LIKE SUPERFAMILY PROTEIN (HLY1). Nearly 25% of the annotated proteins are associated with responses to biotic and abiotic stimuli. As for biotic stress, the proteins PROTEIN SGT1 HOMOLOG B (SGT1B), SUPPRESSOR OF SA INSENSITIVE2 (SSI2), PHOSPHOLIPASE D ALPHA 1 (PLDALPHA1), SERINE/THREONINE-PROTEIN KINASE SRK2E (OST1), ACYL CARRIER PROTEIN 4 (ACP4), and NONHOST RESISTANCE TO P. S. PHASEOLICOLA1 (GLPK) are worth mentioning. Regarding abiotic stimuli, we found proteins associated with oxidative stress: SUPEROXIDE DISMUTASE[CU-ZN] 1 (CSD1), and GLUTATHIONE S-TRANSFERASE U19 (GSTU19), light intensity SERINE HYDROXYMETHYLTRANSFERASE 1 (SHM1) and UBIQUITIN-CONJUGATING ENZYME E2 35 (UBC35), salt and heavy metal stress included MITOCHONDRIAL PHOSPHATE CARRIER PROTEIN 3 (PHT3;1), as well as drought and thermotolerance: LEA7, DEAD-BOX ATP-DEPENDENT RNA HELICASE 38 (LOS4), and abundant heat-shock proteins and other chaperones. In addition, we identified interactomes using the STRING platform, revealing protein-protein associations obtained from co-expression, co-occurrence, text mining, homology, databases, and experimental datasets. By focusing on ferns, this proteomic study increases our knowledge on plant development and evolution, and may inspire future applications in crop species.}, } @article {pmid36421702, year = {2022}, author = {Sowa, ST and Bosetti, C and Galera-Prat, A and Johnson, MS and Lehtiö, L}, title = {An Evolutionary Perspective on the Origin, Conservation and Binding Partner Acquisition of Tankyrases.}, journal = {Biomolecules}, volume = {12}, number = {11}, pages = {}, pmid = {36421702}, issn = {2218-273X}, mesh = {Humans ; Animals ; *Tankyrases/genetics/chemistry/metabolism ; Telomere Homeostasis ; Wnt Signaling Pathway ; }, abstract = {Tankyrases are poly-ADP-ribosyltransferases that regulate many crucial and diverse cellular processes in humans such as Wnt signaling, telomere homeostasis, mitotic spindle formation and glucose metabolism. While tankyrases are present in most animals, functional differences across species may exist. In this work, we confirm the widespread distribution of tankyrases throughout the branches of multicellular animal life and identify the single-celled choanoflagellates as earliest origin of tankyrases. We further show that the sequences and structural aspects of TNKSs are well-conserved even between distantly related species. We also experimentally characterized an anciently diverged tankyrase homolog from the sponge Amphimedon queenslandica and show that the basic functional aspects, such as poly-ADP-ribosylation activity and interaction with the canonical tankyrase binding peptide motif, are conserved. Conversely, the presence of tankyrase binding motifs in orthologs of confirmed interaction partners varies greatly between species, indicating that tankyrases may have different sets of interaction partners depending on the animal lineage. Overall, our analysis suggests a remarkable degree of conservation for tankyrases, and that their regulatory functions in cells have likely changed considerably throughout evolution.}, } @article {pmid36404107, year = {2023}, author = {Sepp, T and Giraudeau, M}, title = {Wild animals as an underused treasure trove for studying the genetics of cancer.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {45}, number = {2}, pages = {e2200188}, doi = {10.1002/bies.202200188}, pmid = {36404107}, issn = {1521-1878}, mesh = {Animals ; Humans ; *Animals, Wild/genetics ; Ecology ; Biodiversity ; *Neoplasms/genetics ; Genomics ; }, abstract = {Recent years have seen an emergence of the field of comparative cancer genomics. However, the advancements in this field are held back by the hesitation to use knowledge obtained from human studies to study cancer in other animals, and vice versa. Since cancer is an ancient disease that arose with multicellularity, oncogenes and tumour-suppressor genes are amongst the oldest gene classes, shared by most animal species. Acknowledging that other animals are, in terms of cancer genetics, ecology, and evolution, rather similar to humans, creates huge potential for advancing the fields of human and animal oncology, but also biodiversity conservation. Also see the video abstract here: https://youtu.be/UFqyMx5HETY.}, } @article {pmid36384644, year = {2022}, author = {Pinskey, JM and Lagisetty, A and Gui, L and Phan, N and Reetz, E and Tavakoli, A and Fu, G and Nicastro, D}, title = {Three-dimensional flagella structures from animals' closest unicellular relatives, the Choanoflagellates.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36384644}, issn = {2050-084X}, support = {F32 GM137470/GM/NIGMS NIH HHS/United States ; R01 GM083122/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Choanoflagellata/metabolism ; Cryoelectron Microscopy ; Flagella ; Axoneme ; Cilia ; }, abstract = {In most eukaryotic organisms, cilia and flagella perform a variety of life-sustaining roles related to environmental sensing and motility. Cryo-electron microscopy has provided considerable insight into the morphology and function of flagellar structures, but studies have been limited to less than a dozen of the millions of known eukaryotic species. Ultrastructural information is particularly lacking for unicellular organisms in the Opisthokonta clade, leaving a sizeable gap in our understanding of flagella evolution between unicellular species and multicellular metazoans (animals). Choanoflagellates are important aquatic heterotrophs, uniquely positioned within the opisthokonts as the metazoans' closest living unicellular relatives. We performed cryo-focused ion beam milling and cryo-electron tomography on flagella from the choanoflagellate species Salpingoeca rosetta. We show that the axonemal dyneins, radial spokes, and central pair complex in S. rosetta more closely resemble metazoan structures than those of unicellular organisms from other suprakingdoms. In addition, we describe unique features of S. rosetta flagella, including microtubule holes, microtubule inner proteins, and the flagellar vane: a fine, net-like extension that has been notoriously difficult to visualize using other methods. Furthermore, we report barb-like structures of unknown function on the extracellular surface of the flagellar membrane. Together, our findings provide new insights into choanoflagellate biology and flagella evolution between unicellular and multicellular opisthokonts.}, } @article {pmid36379956, year = {2022}, author = {Huang, J and Zhao, L and Malik, S and Gentile, BR and Xiong, V and Arazi, T and Owen, HA and Friml, J and Zhao, D}, title = {Specification of female germline by microRNA orchestrated auxin signaling in Arabidopsis.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6960}, pmid = {36379956}, issn = {2041-1723}, mesh = {*Arabidopsis/metabolism ; *Arabidopsis Proteins/metabolism ; *MicroRNAs/genetics/metabolism ; Gene Expression Regulation, Plant ; Indoleacetic Acids/metabolism ; Germ Cells/metabolism ; Transcription Factors/metabolism ; }, abstract = {Germline determination is essential for species survival and evolution in multicellular organisms. In most flowering plants, formation of the female germline is initiated with specification of one megaspore mother cell (MMC) in each ovule; however, the molecular mechanism underlying this key event remains unclear. Here we report that spatially restricted auxin signaling promotes MMC fate in Arabidopsis. Our results show that the microRNA160 (miR160) targeted gene ARF17 (AUXIN RESPONSE FACTOR17) is required for promoting MMC specification by genetically interacting with the SPL/NZZ (SPOROCYTELESS/NOZZLE) gene. Alterations of auxin signaling cause formation of supernumerary MMCs in an ARF17- and SPL/NZZ-dependent manner. Furthermore, miR160 and ARF17 are indispensable for attaining a normal auxin maximum at the ovule apex via modulating the expression domain of PIN1 (PIN-FORMED1) auxin transporter. Our findings elucidate the mechanism by which auxin signaling promotes the acquisition of female germline cell fate in plants.}, } @article {pmid36372985, year = {2022}, author = {Durbagula, S and Korlimarla, A and Ravikumar, G and Valiya Parambath, S and Kaku, SM and Visweswariah, AM}, title = {Prenatal epigenetic factors are predisposing for neurodevelopmental disorders-Considering placenta as a model.}, journal = {Birth defects research}, volume = {114}, number = {20}, pages = {1324-1342}, doi = {10.1002/bdr2.2119}, pmid = {36372985}, issn = {2472-1727}, mesh = {Animals ; Pregnancy ; Female ; *Placenta/metabolism ; *Neurodevelopmental Disorders/genetics ; Epigenomics ; Epigenesis, Genetic ; Fetal Development/physiology ; }, abstract = {The heterogeneous characteristics of neurodevelopmental disorders (NDDs) have resulted in varied perspectives on their causation. The biology behind the phenotypic heterogeneity in NDDs is not yet well-defined, but a strong genetic basis has become well accepted as causal for NDDs. Alongside this, there is growing focus on epigenetic mechanisms. The evidence mounting for in-utero origins of NDDs has promoted research focused on epigenetic mechanisms that impact genes that program early brain development. Considering that placenta is a vital organ, this review emphasizes the prenatal factors and their effects on epigenetic changes influencing the normal functioning of the placenta, and factors mediating pathology in the developing fetus. Overall, it is an attempt to bring focus on the hypothesis that "Prenatal epigenetic factors in the placenta could be predisposing to NDDs (with special interest on autism spectrum disorders)." This review finds growing evidence for epigenetic modifications in the placenta that affect glucocorticoid, nutrient, and immune signaling pathways, eventually impacting fetal brain development. This evidence largely comes from animal models. Given the multicellular nature of placenta, we conclude that, there is a need for placental research focused on employing single-cell approaches and genome-wide methylation profiles to bring insights into specific molecular pathways in the placenta that regulate early brain development.}, } @article {pmid36366977, year = {2023}, author = {Yu, L and Stachowicz, JJ and DuBois, K and Reusch, TBH}, title = {Detecting clonemate pairs in multicellular diploid clonal species based on a shared heterozygosity index.}, journal = {Molecular ecology resources}, volume = {23}, number = {3}, pages = {592-600}, doi = {10.1111/1755-0998.13736}, pmid = {36366977}, issn = {1755-0998}, support = {201704910807//China Scholarship Council/ ; RGP0042_2020//Human Frontiers of Science Program/ ; }, mesh = {Animals ; *Diploidy ; Heterozygote ; *Genome ; Reproduction ; Genetic Loci ; }, abstract = {Clonal reproduction, the formation of nearly identical individuals via mitosis in the absence of genetic recombination, is a very common reproductive mode across plants, fungi and animals. To detect clonal genetic structure, genetic similarity indices based on shared alleles are widely used, such as the Jaccard index, or identity by state. Here we propose a new pairwise genetic similarity index, the SH index, based on segregating genetic marker loci (typically single nucleotide polymorphisms) that are identically heterozygous for pairs of samples (NSH). To test our method, we analyse two old seagrass clones (Posidonia australis, estimated to be around 8500 years old; Zostera marina, >750 years old) along with two young Z. marina clones of known age (17 years old). We show that focusing on shared heterozygosity amplifies the power to distinguish sample pairs belonging to different clones compared to methods focusing on all shared alleles. Our proposed workflow can successfully detect clonemates at a location dominated by a single clone. When the collected samples involve two or more clones, the SH index shows a clear gap between clonemate pairs and interclone sample pairs. Ideally NSH should be on the order of approximately ≥3000, a number easily achievable via restriction-site associated DNA (RAD) sequencing or whole-genome resequencing. Another potential application of the SH index is to detect possible parent-descendant pairs under selfing. Our proposed workflow takes advantage of the availability of the larger number of genetic markers in the genomic era, and improves the ability to distinguish clonemates from nonclonemates in multicellular diploid clonal species.}, } @article {pmid36356576, year = {2022}, author = {Peterson, AF and Ingram, K and Huang, EJ and Parksong, J and McKenney, C and Bever, GS and Regot, S}, title = {Systematic analysis of the MAPK signaling network reveals MAP3K-driven control of cell fate.}, journal = {Cell systems}, volume = {13}, number = {11}, pages = {885-894.e4}, pmid = {36356576}, issn = {2405-4720}, support = {R35 GM133499/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *JNK Mitogen-Activated Protein Kinases/metabolism ; *MAP Kinase Signaling System ; Phosphorylation ; Mitogen-Activated Protein Kinases/metabolism ; Signal Transduction ; }, abstract = {The classic network of mitogen-activated protein kinases (MAPKs) is highly interconnected and controls a diverse array of biological processes. In multicellular eukaryotes, the MAPKs ERK, JNK, and p38 control opposing cell behaviors but are often activated simultaneously, raising questions about how input-output specificity is achieved. Here, we use multiplexed MAPK activity biosensors to investigate how cell fate control emerges from the connectivity and dynamics of the MAPK network. Through chemical and genetic perturbation, we systematically explore the outputs and functions of all the MAP3 kinases encoded in the human genome and show that MAP3Ks control cell fate by triggering unique combinations of MAPK activity. We show that these MAPK activity combinations explain the paradoxical dual role of JNK signaling as pro-apoptotic or pro-proliferative kinase. Overall, our integrative analysis indicates that the MAPK network operates as a unit to control cell fate and shifts the focus from MAPKs to MAP3Ks to better understand signaling-mediated control of cell fate.}, } @article {pmid36342925, year = {2022}, author = {Oda, AH and Tamura, M and Kaneko, K and Ohta, K and Hatakeyama, TS}, title = {Autotoxin-mediated latecomer killing in yeast communities.}, journal = {PLoS biology}, volume = {20}, number = {11}, pages = {e3001844}, pmid = {36342925}, issn = {1545-7885}, mesh = {Humans ; *Saccharomyces cerevisiae/genetics ; *Yeast, Dried ; Cell Death ; Germ Cells ; Glucose ; }, abstract = {Cellular adaptation to stressful environments such as starvation is essential to the survival of microbial communities, but the uniform response of the cell community may lead to entire cell death or severe damage to their fitness. Here, we demonstrate an elaborate response of the yeast community against glucose depletion, in which the first adapted cells kill the latecomer cells. During glucose depletion, yeast cells release autotoxins, such as leucic acid and L-2keto-3methylvalerate, which can even kill the clonal cells of the ones producing them. Although these autotoxins were likely to induce mass suicide, some cells differentiated to adapt to the autotoxins without genetic changes. If nondifferentiated latecomers tried to invade the habitat, autotoxins damaged or killed the latecomers, but the differentiated cells could selectively survive. Phylogenetically distant fission and budding yeast shared this behavior using the same autotoxins, suggesting that latecomer killing may be the universal system of intercellular communication, which may be relevant to the evolutional transition from unicellular to multicellular organisms.}, } @article {pmid36331628, year = {2022}, author = {Alvarez, FE and Carrillo, JA and Clairambault, J}, title = {Evolution of a structured cell population endowed with plasticity of traits under constraints on and between the traits.}, journal = {Journal of mathematical biology}, volume = {85}, number = {6-7}, pages = {64}, pmid = {36331628}, issn = {1432-1416}, mesh = {Animals ; Phenotype ; Population Dynamics ; *Biological Evolution ; }, abstract = {Confronted with the biological problem of managing plasticity in cell populations, which is in particular responsible for transient and reversible drug resistance in cancer, we propose a rationale consisting of an integro-differential and a reaction-advection-diffusion equation, the properties of which are studied theoretically and numerically. By using a constructive finite volume method, we show the existence and uniqueness of a weak solution and illustrate by numerical approximations and their simulations the capacity of the model to exhibit divergence of traits. This feature may be theoretically interpreted as describing a physiological step towards multicellularity in animal evolution and, closer to present-day clinical challenges in oncology, as a possible representation of bet hedging in cancer cell populations.}, } @article {pmid36329610, year = {2022}, author = {Banijamali, M and Höjer, P and Nagy, A and Hååg, P and Gomero, EP and Stiller, C and Kaminskyy, VO and Ekman, S and Lewensohn, R and Karlström, AE and Viktorsson, K and Ahmadian, A}, title = {Characterizing single extracellular vesicles by droplet barcode sequencing for protein analysis.}, journal = {Journal of extracellular vesicles}, volume = {11}, number = {11}, pages = {e12277}, pmid = {36329610}, issn = {2001-3078}, mesh = {Humans ; *Extracellular Vesicles/genetics ; Biomarkers/metabolism ; Cell Line ; Membrane Proteins/metabolism ; }, abstract = {Small extracellular vesicles (sEVs) have in recent years evolved as a source of biomarkers for disease diagnosis and therapeutic follow up. sEV samples derived from multicellular organisms exhibit a high heterogeneous repertoire of vesicles which current methods based on ensemble measurements cannot capture. In this work we present droplet barcode sequencing for protein analysis (DBS-Pro) to profile surface proteins on individual sEVs, facilitating identification of sEV-subtypes within and between samples. The method allows for analysis of multiple proteins through use of DNA barcoded affinity reagents and sequencing as readout. High throughput single vesicle profiling is enabled through compartmentalization of individual sEVs in emulsion droplets followed by droplet barcoding through PCR. In this proof-of-concept study we demonstrate that DBS-Pro allows for analysis of single sEVs, with a mixing rate below 2%. A total of over 120,000 individual sEVs obtained from a NSCLC cell line and from malignant pleural effusion (MPE) fluid of NSCLC patients have been analyzed based on their surface proteins. We also show that the method enables single vesicle surface protein profiling and by extension characterization of sEV-subtypes, which is essential to identify the cellular origin of vesicles in heterogenous samples.}, } @article {pmid36325178, year = {2022}, author = {Sakai, D and Nishikawa, J and Kakiuchida, H and Hirose, E}, title = {Stack of cellular lamellae forms a silvered cortex to conceal the opaque organ in a transparent gastropod in epipelagic habitat.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e14284}, pmid = {36325178}, issn = {2167-8359}, mesh = {Animals ; Cell Nucleus ; *Gastropoda ; Light ; Vision, Ocular ; }, abstract = {BACKGROUND: Gelatinous zooplankton in epipelagic environments often have highly transparent bodies to avoid detection by their visual predators and prey; however, the digestive systems are often exceptionally opaque even in these organisms. In a holoplanktonic gastropod, Pterotrachea coronata, the visceral nucleus is an opaque organ located at the posterior end of its alimentary system, but this organ has a mirrored surface to conceal its internal opaque tissue.

RESULTS: Our ultrastructural observation proved that the cortex of the visceral nucleus comprised a stack of thin cellular lamellae forming a Bragg reflector, and the thickness of lamellae (0.16 µm in average) and the spaces between the lamellae (0.1 µm in average) tended to become thinner toward inner lamellae. Based on the measured values, we built virtual models of the multilamellar layer comprising 50 lamellae and spaces, and the light reflection on the models was calculated using rigorous coupled wave analysis to evaluate their properties as reflectors. Our simulation supported the idea that the layer is a reflective tissue, and the thickness of the lamella/space must be chirped to reflect sunlight as white/silver light, mostly independent of the angle of incidence.

CONCLUSIONS: In P. coronata, the cortex of the visceral nucleus comprised multicellular lamellae that form a chirped Bragg reflector. It is distinct in structure from the intracellular Bragg structures of common iridophores. This novel Bragg reflector demonstrates the diversity and convergent evolution of reflective tissue using reflectin-like proteins in Mollusca.}, } @article {pmid36316013, year = {2023}, author = {Niklas, KJ and Tiffney, BH}, title = {Viridiplantae Body Plans Viewed Through the Lens of the Fossil Record and Molecular Biology.}, journal = {Integrative and comparative biology}, volume = {63}, number = {6}, pages = {1316-1330}, pmid = {36316013}, issn = {1557-7023}, mesh = {Animals ; *Fossils ; Plants ; *Embryophyta ; Molecular Biology ; Water ; Biological Evolution ; Phylogeny ; }, abstract = {A review of the fossil record coupled with insights gained from molecular and developmental biology reveal a series of body plan transformations that gave rise to the first land plants. Across diverse algal clades, including the green algae and their descendants, the plant body plan underwent a unicellular $\to $ colonial $\to $ simple multicellular → complex multicellular transformation series. The colonization of land involved increasing body size and associated cell specialization, including cells capable of hydraulic transport. The evolution of the life-cycle that characterizes all known land plant species involved a divergence in body plan phenotypes between the haploid and diploid generations, one adapted to facilitate sexual reproduction (a free-water dependent gametophyte) and another adapted to the dissemination of spores (a more water-independent sporophyte). The amplification of this phenotypic divergence, combined with indeterminate growth in body size, resulted in a desiccation-adapted branched sporophyte with a cuticularized epidermis, stomates, and vascular tissues. Throughout the evolution of the land plants, the body plans of the sporophyte generation involved "axiation," i.e., the acquisition of a cylindrical geometry and subsequent organographic specializations.}, } @article {pmid36305297, year = {2022}, author = {León-Ruiz, JA and Cruz Ramírez, A}, title = {Predicted landscape of RETINOBLASTOMA-RELATED LxCxE-mediated interactions across the Chloroplastida.}, journal = {The Plant journal : for cell and molecular biology}, volume = {112}, number = {6}, pages = {1507-1524}, doi = {10.1111/tpj.16012}, pmid = {36305297}, issn = {1365-313X}, mesh = {Animals ; *Retinoblastoma ; Retinoblastoma Protein/metabolism ; Cell Differentiation ; *Retinal Neoplasms ; }, abstract = {The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three-dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent to the birth of major plant lineages, such as the origins of vascular tissues, roots, seeds and flowers. Multicellularity, which evolved multiple times in the Chloroplastida coupled with precise spatiotemporal control of proliferation and differentiation were instrumental for the evolution of these traits. RETINOBLASTOMA-RELATED (RBR), the plant homolog of the metazoan Retinoblastoma protein (pRB), is a highly conserved and multifunctional core cell cycle regulator that has been implicated in the evolution of multicellularity in the green lineage as well as in plant multicellularity-related processes such as proliferation, differentiation, stem cell regulation and asymmetric cell division. RBR fulfills these roles through context-specific protein-protein interactions with proteins containing the Leu-x-Cys-x-Glu (LxCxE) short-linear motif (SLiM); however, how RBR-LxCxE interactions have changed throughout major innovations in the Viridiplantae kingdom is a question that remains unexplored. Here, we employ an in silico evo-devo approach to predict and analyze potential RBR-LxCxE interactions in different representative species of key Chloroplastida lineages, providing a valuable resource for deciphering RBR-LxCxE multiple functions. Furthermore, our analyses suggest that RBR-LxCxE interactions are an important component of RBR functions and that interactions with chromatin modifiers/remodelers, DNA replication and repair machinery are highly conserved throughout the Viridiplantae, while LxCxE interactions with transcriptional regulators likely diversified throughout the water-to-land transition.}, } @article {pmid36283350, year = {2022}, author = {Keller, J and Delaux, PM}, title = {Plant phylogenetics: The never-ending cycle of evolutionary gains and losses.}, journal = {Current biology : CB}, volume = {32}, number = {20}, pages = {R1028-R1029}, doi = {10.1016/j.cub.2022.09.006}, pmid = {36283350}, issn = {1879-0445}, mesh = {*Embryophyta ; Phylogeny ; Plants/genetics ; Evolution, Molecular ; Biological Evolution ; }, abstract = {The Zygnematophyceae is the sister clade to the land plants, but their biology remains mysterious. In a new study, a resolved phylogeny and a scenario for the evolution of multicellularity in that clade are proposed.}, } @article {pmid36264199, year = {2022}, author = {Whye, D and Wood, D and Kim, KH and Chen, C and Makhortova, N and Sahin, M and Buttermore, ED}, title = {Dynamic 3D Combinatorial Generation of hPSC-Derived Neuromesodermal Organoids With Diverse Regional and Cellular Identities.}, journal = {Current protocols}, volume = {2}, number = {10}, pages = {e568}, pmid = {36264199}, issn = {2691-1299}, support = {P50 HD105351/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Pregnancy ; Female ; *Organoids ; Hedgehog Proteins ; Poloxamer ; *Pluripotent Stem Cells ; Fibroblast Growth Factors ; Retinoids ; }, abstract = {Neuromesodermal progenitors represent a unique, bipotent population of progenitors residing in the tail bud of the developing embryo, which give rise to the caudal spinal cord cell types of neuroectodermal lineage as well as the adjacent paraxial somite cell types of mesodermal origin. With the advent of stem cell technologies, including induced pluripotent stem cells (iPSCs), the modeling of rare genetic disorders can be accomplished in vitro to interrogate cell-type specific pathological mechanisms in human patient conditions. Stem cell-derived models of neuromesodermal progenitors have been accomplished by several developmental biology groups; however, most employ a 2D monolayer format that does not fully reflect the complexity of cellular differentiation in the developing embryo. This article presents a dynamic 3D combinatorial method to generate robust populations of human pluripotent stem cell-derived neuromesodermal organoids with multi-cellular fates and regional identities. By utilizing a dynamic 3D suspension format for the differentiation process, the organoids differentiated by following this protocol display a hallmark of embryonic development that involves a morphological elongation known as axial extension. Furthermore, by employing a combinatorial screening assay, we dissect essential pathways for optimally directing the patterning of pluripotent stem cells into neuromesodermal organoids. This protocol highlights the influence of timing, duration, and concentration of WNT and fibroblast growth factor (FGF) signaling pathways on enhancing early neuromesodermal identity, and later, downstream cell fate specification through combined synergies of retinoid signaling and sonic hedgehog activation. Finally, through robust inhibition of the Notch signaling pathway, this protocol accelerates the acquisition of terminal cell identities. This enhanced organoid model can serve as a powerful tool for studying normal developmental processes as well as investigating complex neurodevelopmental disorders, such as neural tube defects. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Robust generation of 3D hPSC-derived spheroid populations in dynamic motion settings Support Protocol 1: Pluronic F-127 reagent preparation and coating to generate low-attachment suspension culture dishes Basic Protocol 2: Enhanced specification of hPSCs into NMP organoids Support Protocol 2: Combinatorial pathway assay for NMP organoid protocol optimization Basic Protocol 3: Differentiation of NMP organoids along diverse cellular trajectories and accelerated terminal fate specification into neurons, neural crest, and sclerotome derivatives.}, } @article {pmid36255595, year = {2022}, author = {Bano, N and Aalam, S and Bag, SK}, title = {Tubby-like proteins (TLPs) transcription factor in different regulatory mechanism in plants: a review.}, journal = {Plant molecular biology}, volume = {110}, number = {6}, pages = {455-468}, pmid = {36255595}, issn = {1573-5028}, mesh = {Animals ; *Transcription Factors/genetics/metabolism ; Amino Acid Sequence ; *Plants/genetics/metabolism ; Stress, Physiological ; Plant Growth Regulators/metabolism ; }, abstract = {Tubby-like proteins (TLPs) transcription factors are found in single-celled to multi-cellular eukaryotes in the form of large multigene families. TLPs are identified through a specific signature of carboxyl terminal tubby domain, required for plasma membrane tethering and amino terminal F-box domain communicate as functional SCF-type E3 ligases. The comprehensive distribution of TLP gene family members in diverse species indicates some conserved functions of TLPs in multicellular organisms. Plant TLPs have higher gene members than animals and these members reported important role in multiple physiological and developmental processes and various environmental stress responses. Although the TLPs are suggested to be a putative transcription factors but their functional mechanism is not much clear. This review provides significant recent updates on TLP-mediated regulation with an insight into its functional roles, origin and evolution and also phytohormones related regulation to combat with various stresses and its involvement in adaptive stress response in crop plants.}, } @article {pmid36252029, year = {2022}, author = {Günther, M and Reimer, C and Herbst, R and Kufs, JE and Rautschek, J and Ueberschaar, N and Zhang, S and Peschel, G and Reimer, L and Regestein, L and Valiante, V and Hillmann, F and Stallforth, P}, title = {Yellow polyketide pigment suppresses premature hatching in social amoeba.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {43}, pages = {e2116122119}, pmid = {36252029}, issn = {1091-6490}, mesh = {*Amoeba/genetics ; *Biological Products/metabolism ; *Dictyostelium/physiology ; Polyketide Synthases/genetics/metabolism ; *Polyketides/metabolism ; }, abstract = {Low-molecular-weight natural products from microbes are indispensable in the development of potent drugs. However, their biological roles within an ecological context often remain elusive. Here, we shed light on natural products from eukaryotic microorganisms that have the ability to transition from single cells to multicellular organisms: the social amoebae. These eukaryotes harbor a large number of polyketide biosynthetic genes in their genomes, yet virtually none of the corresponding products can be isolated or characterized. Using complementary molecular biology approaches, including CRISPR-Cas9, we generated polyketide synthase (pks5) inactivation and overproduction strains of the social amoeba Dictyostelium discoideum. Differential, untargeted metabolomics of wild-type versus mutant fruiting bodies allowed us to pinpoint candidate metabolites derived from the amoebal PKS5. Extrachromosomal expression of the respective gene led to the identification of a yellow polyunsaturated fatty acid. Analysis of the temporospatial production pattern of this compound in conjunction with detailed bioactivity studies revealed the polyketide to be a spore germination suppressor.}, } @article {pmid36237424, year = {2022}, author = {Kumar, P and Kumar, P and Mandal, D and Velayutham, R}, title = {The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {985178}, pmid = {36237424}, issn = {2235-2988}, mesh = {Adenosine Triphosphate/metabolism ; Amino Acids/metabolism ; Animals ; Antiparasitic Agents ; Caspases/metabolism ; *Cryptosporidiosis ; *Cryptosporidium ; Deubiquitinating Enzymes/genetics/metabolism ; Humans ; *Parasites/metabolism ; Phylogeny ; Polyubiquitin/genetics/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism ; Ubiquitination ; }, abstract = {Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.}, } @article {pmid36232785, year = {2022}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232785}, issn = {1422-0067}, mesh = {Animals ; Biology ; Cell Differentiation/genetics ; Embryonic Stem Cells ; Humans ; *Induced Pluripotent Stem Cells ; *Neoplasms/genetics/metabolism ; Regenerative Medicine ; }, abstract = {The biogenetic law (recapitulation law) states that ontogenesis recapitulates phylogenesis. However, this law can be distorted by the modification of development. We showed the recapitulation of phylogenesis during the differentiation of various cell types, using a meta-analysis of human single-cell transcriptomes, with the control for cell cycle activity and the improved phylostratigraphy (gene dating). The multipotent progenitors, differentiated from pluripotent embryonic stem cells (ESC), showed the downregulation of unicellular (UC) genes and the upregulation of multicellular (MC) genes, but only in the case of those originating up to the Euteleostomi (bony vertebrates). This picture strikingly resembles the evolutionary profile of regulatory gene expansion due to gene duplication in the human genome. The recapitulation of phylogenesis in the induced pluripotent stem cells (iPSC) during their differentiation resembles the ESC pattern. The unipotent erythroblasts differentiating into erythrocytes showed the downregulation of UC genes and the upregulation of MC genes originating after the Euteleostomi. The MC interactome neighborhood of a protein encoded by a UC gene reverses the gene expression pattern. The functional analysis showed that the evolved environment of the UC proteins is typical for protein modifiers and signaling-related proteins. Besides a fundamental aspect, this approach can provide a unified framework for cancer biology and regenerative/rejuvenation medicine because oncogenesis can be defined as an atavistic reversal to a UC state, while regeneration and rejuvenation require an ontogenetic reversal.}, } @article {pmid36218381, year = {2022}, author = {Silva, VSD and Machado, CR}, title = {Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids.}, journal = {Genetics and molecular biology}, volume = {45}, number = {3}, pages = {e20220065}, pmid = {36218381}, issn = {1415-4757}, abstract = {The Protist kingdom individuals are the most ancestral representatives of eukaryotes. They have inhabited Earth since ancient times and are currently found in the most diverse environments presenting a great heterogeneity of life forms. The unicellular and multicellular algae, photosynthetic and heterotrophic organisms, as well as free-living and pathogenic protozoa represents the protist group. The evolution of sex is directly associated with the origin of eukaryotes being protists the earliest protagonists of sexual reproduction on earth. In eukaryotes, the recombination through genetic exchange is a ubiquitous mechanism that can be stimulated by DNA damage. Scientific evidences support the hypothesis that reactive oxygen species (ROS) induced DNA damage can promote sexual recombination in eukaryotes which might have been a decisive factor for the origin of sex. The fact that some recombination enzymes also participate in meiotic sex in modern eukaryotes reinforces the idea that sexual reproduction emerged as consequence of specific mechanisms to cope with mutations and alterations in genetic material. In this review we will discuss about origin of sex and different strategies of evolve sexual reproduction in some protists such that cause human diseases like malaria, toxoplasmosis, sleeping sickness, Chagas disease, and leishmaniasis.}, } @article {pmid36202151, year = {2022}, author = {Wang, P and Chen, C and Wang, Q and Chen, H and Chen, C and Xu, J and Wang, X and Song, T}, title = {Tumor inhibition via magneto-mechanical oscillation by magnetotactic bacteria under a swing MF.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {351}, number = {}, pages = {941-953}, doi = {10.1016/j.jconrel.2022.09.059}, pmid = {36202151}, issn = {1873-4995}, mesh = {Animals ; *Magnetosomes/metabolism ; Gram-Negative Bacteria ; Bacteria/metabolism ; Magnetics ; Mammals ; }, abstract = {Since magnetic micro/nano-materials can serve as multifunctional transducers for remote control of cell functions by applying diverse magnetic fields, magnetic cell manipulation provides a highly promising tool in biomedical research encompassing neuromodulation, tissue regeneration engineering and tumor cell destruction. Magnetotactic bacteria (MTB), which contain natural magnetic materials, can sensitively respond to external magnetic fields via their endogenous magnetosome chains. Here, we developed a technique for magnetotactic bacteria-based cell modulation and tumor suppression combined with a swing magnetic field. We enabled MTB cells to recognize and bind to mammalian tumor cells via functional modification with RGD peptides onto the surfaces of MTB cells, and RGD-modified MTB bacteria could interact with the targeted tumor cells effectively. The magnetic torque, which was due to the interaction of the long magnetosome chain inside the MTB bacterial cell and the applied swing magnetic field, could result in obvious swing magnetic behaviors of the modified MTB bacteria bound to tumor cell surfaces and thus subsequently exert a sustained magnetomechanical oscillation on the tumor cell surfaces, which could induce a significant activation of Ca[2+] ion influx in vitro and tumor growth inhibition in vivo. These findings suggest that MTB cells mediated magnetomechanical stimulation, which is remotely controlled by dynamic magnetic fields, as an effective way to regulate cell signaling and treat tumor growth, which will shed the light on further biomedical applications utilizing whole magnetotactic bacteria.}, } @article {pmid36198374, year = {2022}, author = {Grunt, TW and Valent, P}, title = {Cancer - A devastating disease, but also an eye-opener and window into the deep mysteries of life and its origins.}, journal = {Progress in biophysics and molecular biology}, volume = {175}, number = {}, pages = {131-139}, doi = {10.1016/j.pbiomolbio.2022.09.009}, pmid = {36198374}, issn = {1873-1732}, mesh = {Humans ; *Biological Evolution ; Thermodynamics ; Entropy ; *Neoplasms ; Mutation ; }, abstract = {Although cancer is still the second leading cause of death worldwide, basic research has largely elucidated the underlying mechanisms that lead us deep into the laws of animate and inanimate nature. This review aims to demonstrate that the cancer process profoundly affects and reprograms fundamental principles and concepts of cellular life by harnessing the natural mechanisms of biological evolution. It is shown that mutation and selection - the drivers of cancer formation and progression - are mandatory consequences of Boltzmann's version of the second law of thermodynamics, which stipulates that entropy (or disorder) according to probability never decreases, followed by Darwinian evolution by filtering for the suitable geno- and karyotypes. Cancer research has shown that malignant cells can develop gradually or abruptly depending on the prevailing stress conditions. Similar principles were then observed in the evolution of species, referred to as micro- and macroevolution. Cancer cells can be related to phylogenetically older forms of life, and malignant transformation can be viewed as reverse (atavistic) evolution, accompanied by typical rearrangement of system information and loss of 'social' behavior. It becomes obvious that in nature no distinction is made between normal biology and pathobiology. Instead, everything follows the rules of natural evolution. This illustrates the depth of the cancer problem and may explain the serious difficulties faced in trying to eradicate cancer.}, } @article {pmid36196535, year = {2022}, author = {Gauthier, AE and Rotjan, RD and Kagan, JC}, title = {Lipopolysaccharide detection by the innate immune system may be an uncommon defence strategy used in nature.}, journal = {Open biology}, volume = {12}, number = {10}, pages = {220146}, pmid = {36196535}, issn = {2046-2441}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; U19 AI133524/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Immune System/metabolism ; Immunity, Innate ; *Lipopolysaccharides ; Mammals ; *Pathogen-Associated Molecular Pattern Molecules ; }, abstract = {Since the publication of the Janeway's Pattern Recognition hypothesis in 1989, study of pathogen-associated molecular patterns (PAMPs) and their immuno-stimulatory activities has accelerated. Most studies in this area have been conducted in model organisms, which leaves many open questions about the universality of PAMP biology across living systems. Mammals have evolved multiple proteins that operate as receptors for the PAMP lipopolysaccharide (LPS) from Gram-negative bacteria, but LPS is not immuno-stimulatory in all eukaryotes. In this review, we examine the history of LPS as a PAMP in mammals, recent data on LPS structure and its ability to activate mammalian innate immune receptors, and how these activities compare across commonly studied eukaryotes. We discuss why LPS may have evolved to be immuno-stimulatory in some eukaryotes but not others and propose two hypotheses about the evolution of PAMP structure based on the ecology and environmental context of the organism in question. Understanding PAMP structures and stimulatory mechanisms across multi-cellular life will provide insights into the evolutionary origins of innate immunity and may lead to the discovery of new PAMP variations of scientific and therapeutic interest.}, } @article {pmid36180988, year = {2022}, author = {Turishcheva, E and Vildanova, M and Onishchenko, G and Smirnova, E}, title = {The Role of Endoplasmic Reticulum Stress in Differentiation of Cells of Mesenchymal Origin.}, journal = {Biochemistry. Biokhimiia}, volume = {87}, number = {9}, pages = {916-931}, pmid = {36180988}, issn = {1608-3040}, mesh = {*COVID-19 ; Cell Differentiation ; *Endoplasmic Reticulum Stress ; Fibrosis ; Humans ; Unfolded Protein Response ; }, abstract = {Endoplasmic reticulum (ER) is a multifunctional membrane-enclosed organelle. One of the major ER functions is cotranslational transport and processing of secretory, lysosomal, and transmembrane proteins. Impaired protein processing caused by disturbances in the ER homeostasis results in the ER stress. Restoration of normal ER functioning requires activation of an adaptive mechanism involving cell response to misfolded proteins, the so-called unfolded protein response (UPR). Besides controlling protein folding, UPR plays a key role in other physiological processes, in particular, differentiation of cells of connective, muscle, epithelial, and neural tissues. Cell differentiation is induced by the physiological levels of ER stress, while excessive ER stress suppresses differentiation and can result in cell death. So far, it remains unknown whether UPR activation induces cell differentiation or if UPR is initiated by the upregulated synthesis of secretory proteins during cell differentiation. Cell differentiation is an important stage in the development of multicellular organisms and is tightly controlled. Suppression or excessive activation of this process can lead to the development of various pathologies in an organism. In particular, impairments in the differentiation of connective tissue cells can result in the development of fibrosis, obesity, and osteoporosis. Recently, special attention has been paid to fibrosis as one of the major complications of COVID-19. Therefore, studying the role of UPR in the activation of cell differentiation is of both theoretical and practical interest, as it might result in the identification of molecular targets for selective regulation of cell differentiation stages and as well as the potential to modulate the mechanisms involved in the development of various pathological states.}, } @article {pmid36179980, year = {2023}, author = {Hiraki, HL and Matera, DL and Wang, WY and Prabhu, ES and Zhang, Z and Midekssa, F and Argento, AE and Buschhaus, JM and Humphries, BA and Luker, GD and Pena-Francesch, A and Baker, BM}, title = {Fiber density and matrix stiffness modulate distinct cell migration modes in a 3D stroma mimetic composite hydrogel.}, journal = {Acta biomaterialia}, volume = {163}, number = {}, pages = {378-391}, pmid = {36179980}, issn = {1878-7568}, support = {R50 CA221807/CA/NCI NIH HHS/United States ; R01 CA238042/CA/NCI NIH HHS/United States ; R01 CA238023/CA/NCI NIH HHS/United States ; R00 HL124322/HL/NHLBI NIH HHS/United States ; R01 EB030474/EB/NIBIB NIH HHS/United States ; R33 CA225549/CA/NCI NIH HHS/United States ; K99 HL124322/HL/NHLBI NIH HHS/United States ; U01 CA210152/CA/NCI NIH HHS/United States ; R37 CA222563/CA/NCI NIH HHS/United States ; T32 DE007057/DE/NIDCR NIH HHS/United States ; R01 CA196018/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Hydrogels/pharmacology/chemistry ; Cell Movement ; *Neoplasms ; Biocompatible Materials/pharmacology ; Epithelial Cells ; Extracellular Matrix ; Tumor Microenvironment ; }, abstract = {The peritumoral stroma is a complex 3D tissue that provides cells with myriad biophysical and biochemical cues. Histologic observations suggest that during metastatic spread of carcinomas, these cues influence transformed epithelial cells, prompting a diversity of migration modes spanning single cell and multicellular phenotypes. Purported consequences of these variations in tumor escape strategies include differential metastatic capability and therapy resistance. Therefore, understanding how cues from the peritumoral stromal microenvironment regulate migration mode has both prognostic and therapeutic value. Here, we utilize a synthetic stromal mimetic in which matrix fiber density and bulk hydrogel mechanics can be orthogonally tuned to investigate the contribution of these two key matrix attributes on MCF10A migration mode phenotypes, epithelial-mesenchymal transition (EMT), and invasive potential. We develop an automated computational image analysis framework to extract migratory phenotypes from fluorescent images and determine 3D migration metrics relevant to metastatic spread. Using this analysis, we find that matrix fiber density and bulk hydrogel mechanics distinctly contribute to a variety of MCF10A migration modes including amoeboid, single mesenchymal, clusters, and strands. We identify combinations of physical and soluble cues that induce a variety of migration modes originating from the same MCF10A spheroid and use these settings to examine a functional consequence of migration mode -resistance to apoptosis. We find that cells migrating as strands are more resistant to staurosporine-induced apoptosis than either disconnected clusters or individual invading cells. Improved models of the peritumoral stromal microenvironment and understanding of the relationships between matrix attributes and cell migration mode can aid ongoing efforts to identify effective cancer therapeutics that address cell plasticity-based therapy resistances. STATEMENT OF SIGNIFICANCE: Stromal extracellular matrix structure dictates both cell homeostasis and activation towards migratory phenotypes. However decoupling the effects of myriad biophysical cues has been difficult to achieve. Here, we encapsulate electrospun fiber segments within an amorphous hydrogel to create a fiber-reinforced hydrogel composite in which fiber density and hydrogel stiffness can be orthogonally tuned. Quantification of 3D cell migration reveal these two parameters uniquely contribute to a diversity of migration phenotypes spanning amoeboid, single mesenchymal, multicellular cluster, and collective strand. By tuning biophysical and biochemical cues to elicit heterogeneous migration phenotypes, we find that collective strands best resist apoptosis. This work establishes a composite approach to modulate fibrous topography and bulk hydrogel mechanics and identified biomaterial parameters to direct distinct 3D cell migration phenotypes.}, } @article {pmid36127662, year = {2022}, author = {Chai, S and Aria, C and Hua, H}, title = {A stem group Codium alga from the latest Ediacaran of South China provides taxonomic insight into the early diversification of the plant kingdom.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {199}, pmid = {36127662}, issn = {1741-7007}, mesh = {Animals ; China ; *Chlorophyta/genetics ; *Ecosystem ; Eukaryotic Cells ; Fossils ; }, abstract = {BACKGROUND: In recent years, Precambrian lifeforms have generated an ever-increasing interest because they revealed a rich eukaryotic diversity prior to the Cambrian explosion of modern animals. Among them, macroalgae are known to be a conspicuous component of Neoproterozoic ecosystems, and chlorophytes in particular are already documented in the Tonian, when they were so far expected to originate. However, like for other major eukaryotic lineages, and despite predictions of molecular clock analyses placing roots of these lineages well into the Neoproterozoic, a taxonomic constraint on Precambrian green algae has remained difficult.

RESULTS: Here, we present an exceptionally preserved spherical, coenocytic unicellular alga from the latest Ediacaran Dengying Formation of South China (> ca. 541 Ma), known from both external and internal morphology, fully tridimensional and in great detail. Tomographic X-ray and electronic microscopy revealed a characteristic medulla made of intertwined siphons and tightly packed peripheral utricles, suggesting these fossils belong to the Bryopsidales genus Codium. However, its distinctly smaller size compared to extant species leads us to create Protocodium sinense gen. et sp. nov. and a phylomorphospace investigation points to a possible stem group affinity.

CONCLUSIONS: Our finding has several important implications. First, Protocodium allows for a more precise calibration of Archaeplastida and directly confirms that a group as derived as Ulvophyceae was already well diversified in various ecosystems prior to the Cambrian explosion. Details of tridimensional morphology also invite a reassessment of the identification of other Ediacaran algae, such as Chuaria, to better discriminate mono-versus multicellularity, and suggest unicellular Codium-like morphotypes could be much older and widespread. More broadly, Protocodium provides insights into the early diversification of the plant kingdom, the composition of Precambrian ecosystems, and the extreme longevity of certain eukaryotic plans of organization.}, } @article {pmid36114258, year = {2022}, author = {La Fortezza, M and Rendueles, O and Keller, H and Velicer, GJ}, title = {Hidden paths to endless forms most wonderful: ecology latently shapes evolution of multicellular development in predatory bacteria.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {977}, pmid = {36114258}, issn = {2399-3642}, mesh = {Agar ; Animals ; *Myxococcus xanthus/genetics ; Phenotype ; *Predatory Behavior ; }, abstract = {Ecological causes of developmental evolution, for example from predation, remain much investigated, but the potential importance of latent phenotypes in eco-evo-devo has received little attention. Using the predatory bacterium Myxococcus xanthus, which undergoes aggregative fruiting body development upon starvation, we tested whether adaptation to distinct growth environments that do not induce development latently alters developmental phenotypes under starvation conditions that do induce development. In an evolution experiment named MyxoEE-3, growing M. xanthus populations swarmed across agar surfaces while adapting to conditions varying at factors such as surface stiffness or prey identity. Such ecological variation during growth was found to greatly impact the latent evolution of development, including fruiting body morphology, the degree of morphological trait correlation, reaction norms, degrees of developmental plasticity and stochastic diversification. For example, some prey environments promoted retention of developmental proficiency whereas others led to its systematic loss. Our results have implications for understanding evolutionary interactions among predation, development and motility in myxobacterial life cycles, and, more broadly, how ecology can profoundly shape the evolution of developmental systems latently rather than by direct selection on developmental features.}, } @article {pmid36102042, year = {2022}, author = {Xie, Q and Xiong, C and Yang, Q and Zheng, F and Larkin, RM and Zhang, J and Wang, T and Zhang, Y and Ouyang, B and Lu, Y and Ye, J and Ye, Z and Yang, C}, title = {A novel regulatory complex mediated by Lanata (Ln) controls multicellular trichome formation in tomato.}, journal = {The New phytologist}, volume = {236}, number = {6}, pages = {2294-2310}, doi = {10.1111/nph.18492}, pmid = {36102042}, issn = {1469-8137}, mesh = {*Trichomes/metabolism ; *Solanum lycopersicum/genetics/metabolism ; Gene Expression Regulation, Plant ; Plant Proteins/genetics/metabolism ; Plant Epidermis/metabolism ; }, abstract = {Trichomes that originate from plant aerial epidermis act as mechanical and chemical barriers against herbivores. Although several regulators have recently been identified, the regulatory pathway underlying multicellular trichome formation remains largely unknown in tomato. Here, we report a novel HD-ZIP IV transcription factor, Lanata (Ln), a missense mutation which caused the hairy phenotype. Biochemical analyses demonstrate that Ln separately interacts with two trichome regulators, Woolly (Wo) and Hair (H). Genetic and molecular evidence demonstrates that Ln directly regulates the expression of H. The interaction between Ln and Wo can increase trichome density by enhancing the expression of SlCycB2 and SlCycB3, which we previously showed are involved in tomato trichome formation. Furthermore, SlCycB2 represses the transactivation of the SlCycB3 gene by Ln and vice versa. Our findings provide new insights into the novel regulatory network controlling multicellular trichome formation in tomato.}, } @article {pmid36099169, year = {2022}, author = {Ress, V and Traulsen, A and Pichugin, Y}, title = {Eco-evolutionary dynamics of clonal multicellular life cycles.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {36099169}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; *Life Cycle Stages ; Models, Theoretical ; }, abstract = {The evolution of multicellular life cycles is a central process in the course of the emergence of multicellularity. The simplest multicellular life cycle is comprised of the growth of the propagule into a colony and its fragmentation to give rise to new propagules. The majority of theoretical models assume selection among life cycles to be driven by internal properties of multicellular groups, resulting in growth competition. At the same time, the influence of interactions between groups on the evolution of life cycles is rarely even considered. Here, we present a model of colonial life cycle evolution taking into account group interactions. Our work shows that the outcome of evolution could be coexistence between multiple life cycles or that the outcome may depend on the initial state of the population - scenarios impossible without group interactions. At the same time, we found that some results of these simpler models remain relevant: evolutionary stable strategies in our model are restricted to binary fragmentation - the same class of life cycles that contains all evolutionarily optimal life cycles in the model without interactions. Our results demonstrate that while models neglecting interactions can capture short-term dynamics, they fall short in predicting the population-scale picture of evolution.}, } @article {pmid36098425, year = {2022}, author = {Noh, S and Capodanno, BJ and Xu, S and Hamilton, MC and Strassmann, JE and Queller, DC}, title = {Reduced and Nonreduced Genomes in Paraburkholderia Symbionts of Social Amoebas.}, journal = {mSystems}, volume = {7}, number = {5}, pages = {e0056222}, pmid = {36098425}, issn = {2379-5077}, support = {P20 GM103423/GM/NIGMS NIH HHS/United States ; P20GM103423//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Animals ; *Amoeba/microbiology ; *Dictyostelium/genetics ; Eukaryota ; *Burkholderiaceae/genetics ; Bacteria/genetics ; Soil ; }, abstract = {The social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. discoideum strains isolated from soil persistently carry symbiotic Paraburkholderia, recently formally described as P. agricolaris, P. bonniea, and P. hayleyella. The three facultative symbiont species of D. discoideum present a unique opportunity to study a naturally occurring symbiosis in a laboratory model protist. There is a large difference in genome size between P. agricolaris (8.7 million base pairs [Mbp]) versus P. hayleyella and P. bonniea (4.1 Mbp). We took a comparative genomics approach and compared the three genomes of D. discoideum symbionts to 12 additional Paraburkholderia genomes to test for genome evolution patterns that frequently accompany host adaptation. Overall, P. agricolaris is difficult to distinguish from other Paraburkholderia based on its genome size and content, but the reduced genomes of P. bonniea and P. hayleyella display characteristics indicative of genome streamlining rather than deterioration during adaptation to their protist hosts. In addition, D. discoideum-symbiont genomes have increased secretion system and motility genes that may mediate interactions with their host. Specifically, adjacent BurBor-like type 3 and T6SS-5-like type 6 secretion system operons shared among all three D. discoideum-symbiont genomes may be important for host interaction. Horizontal transfer of these secretion system operons within the amoeba host environment may have contributed to the unique ability of these symbionts to establish and maintain a symbiotic relationship with D. discoideum. IMPORTANCE Protists are a diverse group of typically single cell eukaryotes. Bacteria and archaea that form long-term symbiotic relationships with protists may evolve in additional ways than those in relationships with multicellular eukaryotes such as plants, animals, or fungi. Social amoebas are a predatory soil protist sometimes found with symbiotic bacteria living inside their cells. They present a unique opportunity to explore a naturally occurring symbiosis in a protist frequently used for studying host-pathogen interactions. We show that one amoeba-symbiont species is similar to other related bacteria in genome size and content, while the two reduced-genome-symbiont species show characteristics of genome streamlining rather than deterioration during adaptation to their host. We also identify sets of genes present in all three amoeba-symbiont genomes that are potentially used for host-symbiont interactions. Because the amoeba symbionts are distantly related, the amoeba host environment may be where these genes were shared among symbionts.}, } @article {pmid36077092, year = {2022}, author = {Anatskaya, OV and Vinogradov, AE}, title = {Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring.}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36077092}, issn = {1422-0067}, support = {Agreement No. 075-15-2021-1075, signed 28 September 2021//Ministry of Science and Higher Education of the Russian Federation/ ; }, mesh = {Chromatin ; Epigenesis, Genetic ; *Gene Regulatory Networks ; Humans ; *Polyploidy ; Proto-Oncogenes ; }, abstract = {Polyploid cells demonstrate biological plasticity and stress adaptation in evolution; development; and pathologies, including cardiovascular diseases, neurodegeneration, and cancer. The nature of ploidy-related advantages is still not completely understood. Here, we summarize the literature on molecular mechanisms underlying ploidy-related adaptive features. Polyploidy can regulate gene expression via chromatin opening, reawakening ancient evolutionary programs of embryonality. Chromatin opening switches on genes with bivalent chromatin domains that promote adaptation via rapid induction in response to signals of stress or morphogenesis. Therefore, stress-associated polyploidy can activate Myc proto-oncogenes, which further promote chromatin opening. Moreover, Myc proto-oncogenes can trigger polyploidization de novo and accelerate genome accumulation in already polyploid cells. As a result of these cooperative effects, polyploidy can increase the ability of cells to search for adaptive states of cellular programs through gene regulatory network rewiring. This ability is manifested in epigenetic plasticity associated with traits of stemness, unicellularity, flexible energy metabolism, and a complex system of DNA damage protection, combining primitive error-prone unicellular repair pathways, advanced error-free multicellular repair pathways, and DNA damage-buffering ability. These three features can be considered important components of the increased adaptability of polyploid cells. The evidence presented here contribute to the understanding of the nature of stress resistance associated with ploidy and may be useful in the development of new methods for the prevention and treatment of cardiovascular and oncological diseases.}, } @article {pmid36076976, year = {2022}, author = {Burzacka-Hinz, A and Narajczyk, M and Dudek, M and Szlachetko, DL}, title = {Micromorphology of Labellum in Selected Dendrobium Sw. (Orchidaceae, Dendrobieae).}, journal = {International journal of molecular sciences}, volume = {23}, number = {17}, pages = {}, pmid = {36076976}, issn = {1422-0067}, mesh = {*Dendrobium ; Flowers/anatomy & histology ; Microscopy, Electron, Scanning ; *Orchidaceae/anatomy & histology ; Phylogeny ; Trichomes ; }, abstract = {Dendrobium is one of the most species-rich genera of the Paleotropical orchids. It embraces more than 1000 species, most of which are epiphytes. The strong variation in floral characters causes many identification difficulties within this genus. One of the key structures, often sufficient in identification on a species level, is the labellum, which in many species of Dendrobium possesses a thickened callus and various types of trichomes and papillae. The aim of this study is to identify and describe the structures present on the labellum surface of the analyzed species, determine their distribution and density, as well as to check whether the obtained data have taxonomic value. In this paper, we present the results of a micromorphological study on the labellum of 21 species of Dendrobium, representing 13 sections, using scanning electron microscopy (SEM). Our studies revealed the presence of both uni- and multicellular structures on the surface of the labellum. We observed three types of trichomes (conical, cylindrical, ellipsoidal) and three types of papillae (conical, cylindrical, semicircular). Neither trichomes nor papillae were recorded for five species. In addition, we made diagrams showing the distribution and density of structures on the labellum. Based on the micromorphological results combined with the phylogenetic tree performed, we suggest that the presence/absence of labellum structures does not necessarily reflect the phylogenetic relationship and might be misleading, as in some cases, they arise due to convergence.}, } @article {pmid36055238, year = {2022}, author = {Hess, S and Williams, SK and Busch, A and Irisarri, I and Delwiche, CF and de Vries, S and Darienko, T and Roger, AJ and Archibald, JM and Buschmann, H and von Schwartzenberg, K and de Vries, J}, title = {A phylogenomically informed five-order system for the closest relatives of land plants.}, journal = {Current biology : CB}, volume = {32}, number = {20}, pages = {4473-4482.e7}, pmid = {36055238}, issn = {1879-0445}, mesh = {Phylogeny ; Biological Evolution ; *Embryophyta/genetics ; *Charophyceae/genetics ; *Streptophyta ; Plants ; Soil ; }, abstract = {The evolution of streptophytes had a profound impact on life on Earth. They brought forth those photosynthetic eukaryotes that today dominate the macroscopic flora: the land plants (Embryophyta).[1] There is convincing evidence that the unicellular/filamentous Zygnematophyceae-and not the morphologically more elaborate Coleochaetophyceae or Charophyceae-are the closest algal relatives of land plants.[2-6] Despite the species richness (>4,000), wide distribution, and key evolutionary position of the zygnematophytes, their internal phylogeny remains largely unresolved.[7,8] There are also putative zygnematophytes with interesting body plan modifications (e.g., filamentous growth) whose phylogenetic affiliations remain unknown. Here, we studied a filamentous green alga (strain MZCH580) from an Austrian peat bog with central or parietal chloroplasts that lack discernible pyrenoids. It represents Mougeotiopsis calospora PALLA, an enigmatic alga that was described more than 120 years ago[9] but never subjected to molecular analyses. We generated transcriptomic data of M. calospora strain MZCH580 and conducted comprehensive phylogenomic analyses (326 nuclear loci) for 46 taxonomically diverse zygnematophytes. Strain MZCH580 falls in a deep-branching zygnematophycean clade together with some unicellular species and thus represents a formerly unknown zygnematophycean lineage with filamentous growth. Our well-supported phylogenomic tree lets us propose a new five-order system for the Zygnematophyceae and provides evidence for at least five independent origins of true filamentous growth in the closest algal relatives of land plants. This phylogeny provides a robust and comprehensive framework for performing comparative analyses and inferring the evolution of cellular traits and body plans in the closest relatives of land plants.}, } @article {pmid36045216, year = {2022}, author = {Michla, M and Wilhelm, C}, title = {Food for thought - ILC metabolism in the context of helminth infections.}, journal = {Mucosal immunology}, volume = {15}, number = {6}, pages = {1234-1242}, pmid = {36045216}, issn = {1935-3456}, mesh = {Animals ; Humans ; Immunity, Innate ; Lymphocytes ; *Helminthiasis ; *Helminths ; Inflammation ; }, abstract = {Helminths are multicellular ancient organisms residing as parasites at mucosal surfaces of their host. Through adaptation and co-evolution with their hosts, helminths have been able to develop tolerance mechanisms to limit inflammation and avoid expulsion. The study of helminth infections as an integral part of tissue immunology allowed us to understand fundamental aspects of mucosal and barrier immunology, which led to the discovery of a new group of tissue-resident immune cells, innate lymphoid cells (ILC), over a decade ago. Here, we review the intricate interplay between helminth infections and type 2 ILC (ILC2) biology, discuss the host metabolic adaptation to helminth infections and the metabolic pathways fueling ILC2 responses. We hypothesize that nutrient competition between host and helminths may have prevented chronic inflammation in the past and argue that a detailed understanding of the metabolic restraints imposed by helminth infections may offer new therapeutic avenues in the future.}, } @article {pmid36028058, year = {2022}, author = {Senthilkumar, I and Howley, E and McEvoy, E}, title = {Thermodynamically-motivated chemo-mechanical models and multicellular simulation to provide new insight into active cell and tumour remodelling.}, journal = {Experimental cell research}, volume = {419}, number = {2}, pages = {113317}, doi = {10.1016/j.yexcr.2022.113317}, pmid = {36028058}, issn = {1090-2422}, mesh = {Computer Simulation ; Humans ; *Models, Biological ; *Neoplasms ; Tumor Microenvironment ; }, abstract = {Computational models can shape our understanding of cell and tissue remodelling, from cell spreading, to active force generation, adhesion, and growth. In this mini-review, we discuss recent progress in modelling of chemo-mechanical cell behaviour and the evolution of multicellular systems. In particular, we highlight recent advances in (i) free-energy based single cell models that can provide new fundamental insight into cell spreading, cancer cell invasion, stem cell differentiation, and remodelling in disease, and (ii) mechanical agent-based models to simulate large numbers of discrete interacting cells in proliferative tumours. We describe how new biological understanding has emerged from such theoretical models, and the trade-offs and constraints associated with current approaches. Ultimately, we aim to make a case for why theory should be integrated with an experimental workflow to optimise new in-vitro studies, to predict feedback between cells and their microenvironment, and to deepen understanding of active cell behaviour.}, } @article {pmid36011312, year = {2022}, author = {Le, NG and van Ulsen, P and van Spanning, R and Brouwer, A and van Straalen, NM and Roelofs, D}, title = {A Functional Carbohydrate Degrading Enzyme Potentially Acquired by Horizontal Gene Transfer in the Genome of the Soil Invertebrate Folsomia candida.}, journal = {Genes}, volume = {13}, number = {8}, pages = {}, pmid = {36011312}, issn = {2073-4425}, mesh = {Animals ; *Arthropods/genetics ; Bacteria/genetics ; Carbohydrates ; Escherichia coli/genetics ; Eukaryota ; *Gene Transfer, Horizontal ; Insecta ; Protein Sorting Signals/genetics ; Soil ; }, abstract = {Horizontal gene transfer (HGT) is defined as the acquisition by an organism of hereditary material from a phylogenetically unrelated organism. This process is mostly observed among bacteria and archaea, and considered less likely between microbes and multicellular eukaryotes. However, recent studies provide compelling evidence of the evolutionary importance of HGT in eukaryotes, driving functional innovation. Here, we study an HGT event in Folsomia candida (Collembola, Hexapoda) of a carbohydrate-active enzyme homologous to glycosyl hydrase group 43 (GH43). The gene encodes an N-terminal signal peptide, targeting the product for excretion, which suggests that it contributes to the diversity of digestive capacities of the detritivore host. The predicted α-L-arabinofuranosidase shows high similarity to genes in two other Collembola, an insect and a tardigrade. The gene was cloned and expressed in Escherichia coli using a cell-free protein expression system. The expressed protein showed activity against p-nitrophenyl-α-L-arabinofuranoside. Our work provides evidence for functional activity of an HGT gene in a soil-living detritivore, most likely from a bacterial donor, with genuine eukaryotic properties, such as a signal peptide. Co-evolution of metazoan GH43 genes with the Panarthropoda phylogeny suggests the HGT event took place early in the evolution of this ecdysozoan lineage.}, } @article {pmid36002568, year = {2022}, author = {Ocaña-Pallarès, E and Williams, TA and López-Escardó, D and Arroyo, AS and Pathmanathan, JS and Bapteste, E and Tikhonenkov, DV and Keeling, PJ and Szöllősi, GJ and Ruiz-Trillo, I}, title = {Divergent genomic trajectories predate the origin of animals and fungi.}, journal = {Nature}, volume = {609}, number = {7928}, pages = {747-753}, pmid = {36002568}, issn = {1476-4687}, support = {616960/ERC_/European Research Council/International ; 714774/ERC_/European Research Council/International ; 615274/ERC_/European Research Council/International ; }, mesh = {Animals ; *Evolution, Molecular ; *Fungi/genetics ; Gene Transfer, Horizontal ; Genes ; *Genome/genetics ; Genome, Fungal/genetics ; *Genomics ; Metabolism/genetics ; *Phylogeny ; }, abstract = {Animals and fungi have radically distinct morphologies, yet both evolved within the same eukaryotic supergroup: Opisthokonta[1,2]. Here we reconstructed the trajectory of genetic changes that accompanied the origin of Metazoa and Fungi since the divergence of Opisthokonta with a dataset that includes four novel genomes from crucial positions in the Opisthokonta phylogeny. We show that animals arose only after the accumulation of genes functionally important for their multicellularity, a tendency that began in the pre-metazoan ancestors and later accelerated in the metazoan root. By contrast, the pre-fungal ancestors experienced net losses of most functional categories, including those gained in the path to Metazoa. On a broad-scale functional level, fungal genomes contain a higher proportion of metabolic genes and diverged less from the last common ancestor of Opisthokonta than did the gene repertoires of Metazoa. Metazoa and Fungi also show differences regarding gene gain mechanisms. Gene fusions are more prevalent in Metazoa, whereas a larger fraction of gene gains were detected as horizontal gene transfers in Fungi and protists, in agreement with the long-standing idea that transfers would be less relevant in Metazoa due to germline isolation[3-5]. Together, our results indicate that animals and fungi evolved under two contrasting trajectories of genetic change that predated the origin of both groups. The gradual establishment of two clearly differentiated genomic contexts thus set the stage for the emergence of Metazoa and Fungi.}, } @article {pmid36002411, year = {2022}, author = {Shi, B and Huang, X and Fu, X and Wang, B}, title = {[Advances in the plant multicellular network analysis].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {38}, number = {8}, pages = {2798-2810}, doi = {10.13345/j.cjb.220127}, pmid = {36002411}, issn = {1872-2075}, mesh = {*Plants ; }, abstract = {Multicellular network analysis is a method for topological properties analysis of cells. The functions of organs are determined by their inner cells. The arrangement of cells within organs endows higher-order functionality through a structure-function relationship, though the organizational properties of these multicellular configurations remain poorly understood. Multicellular network analysis with multicellular models established by 3D scanning of plants, will further discover the plant development mechanism, and provide clues for synthesizing plant multicellular systems. In this paper, we review the development of multicellular models, summarize the process of multicellular network analysis, and describe the development and application of multicellular network analysis in plants. In addition, this review also provides perspective on future development of plant multicellular network analysis.}, } @article {pmid35999597, year = {2022}, author = {Gahan, JM and Leclère, L and Hernandez-Valladares, M and Rentzsch, F}, title = {A developmental role for the chromatin-regulating CoREST complex in the cnidarian Nematostella vectensis.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {184}, pmid = {35999597}, issn = {1741-7007}, mesh = {Animals ; Cell Differentiation ; *Chromatin ; Histone Demethylases/genetics ; Mammals/genetics ; Phylogeny ; *Sea Anemones/metabolism ; }, abstract = {BACKGROUND: Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Most chromatin modifiers, however, predate the evolution of animal multicellularity, and how they gained new functions and became integrated into the regulatory networks underlying development is unclear. One way this may occur is the evolution of new scaffolding proteins that integrate multiple chromatin regulators into larger complexes that facilitate coordinated deposition or removal of different chromatin modifications. We test this hypothesis by analyzing the evolution of the CoREST-Lsd1-HDAC complex.

RESULTS: Using phylogenetic analyses, we show that a bona fide CoREST homolog is found only in choanoflagellates and animals. We then use the sea anemone Nematostella vectensis as a model for early branching metazoans and identify a conserved CoREST complex by immunoprecipitation and mass spectrometry of an endogenously tagged Lsd1 allele. In addition to CoREST, Lsd1 and HDAC1/2 this complex contains homologs of HMG20A/B and PHF21A, two subunits that have previously only been identified in mammalian CoREST complexes. NvCoREST expression overlaps fully with that of NvLsd1 throughout development, with higher levels in differentiated neural cells. NvCoREST mutants, generated using CRISPR-Cas9, fail to develop beyond the primary polyp stage, thereby revealing essential roles during development and for the differentiation of cnidocytes that phenocopy NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach.

CONCLUSIONS: The identification of a Nematostella CoREST-Lsd1-HDAC1/2 complex, its similarity in composition with the vertebrate complex, and the near-identical expression patterns and mutant phenotypes of NvCoREST and NvLsd1 suggest that the complex was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.}, } @article {pmid35995772, year = {2022}, author = {Nyongesa, S and Weber, PM and Bernet, È and Pulido, F and Nieves, C and Nieckarz, M and Delaby, M and Viehboeck, T and Krause, N and Rivera-Millot, A and Nakamura, A and Vischer, NOE and vanNieuwenhze, M and Brun, YV and Cava, F and Bulgheresi, S and Veyrier, FJ}, title = {Evolution of longitudinal division in multicellular bacteria of the Neisseriaceae family.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {4853}, pmid = {35995772}, issn = {2041-1723}, support = {DOC 69/FWF_/Austrian Science Fund FWF/Austria ; P 28593/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; Biological Evolution ; *Cell Division ; Cell Wall/metabolism ; Mammals/microbiology ; *Neisseriaceae/cytology ; Peptidoglycan/metabolism ; }, abstract = {Rod-shaped bacteria typically elongate and divide by transverse fission. However, several bacterial species can form rod-shaped cells that divide longitudinally. Here, we study the evolution of cell shape and division mode within the family Neisseriaceae, which includes Gram-negative coccoid and rod-shaped species. In particular, bacteria of the genera Alysiella, Simonsiella and Conchiformibius, which can be found in the oral cavity of mammals, are multicellular and divide longitudinally. We use comparative genomics and ultrastructural microscopy to infer that longitudinal division within Neisseriaceae evolved from a rod-shaped ancestor. In multicellular longitudinally-dividing species, neighbouring cells within multicellular filaments are attached by their lateral peptidoglycan. In these bacteria, peptidoglycan insertion does not appear concentric, i.e. from the cell periphery to its centre, but as a medial sheet guillotining each cell. Finally, we identify genes and alleles associated with multicellularity and longitudinal division, including the acquisition of amidase-encoding gene amiC2, and amino acid changes in proteins including MreB and FtsA. Introduction of amiC2 and allelic substitution of mreB in a rod-shaped species that divides by transverse fission results in shorter cells with longer septa. Our work sheds light on the evolution of multicellularity and longitudinal division in bacteria, and suggests that members of the Neisseriaceae family may be good models to study these processes due to their morphological plasticity and genetic tractability.}, } @article {pmid35972622, year = {2022}, author = {Jacques, F and Baratchart, E and Pienta, KJ and Hammarlund, EU}, title = {Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics.}, journal = {Medical oncology (Northwood, London, England)}, volume = {39}, number = {11}, pages = {160}, pmid = {35972622}, issn = {1559-131X}, support = {U01 CA143055/CA/NCI NIH HHS/United States ; CA163124/CA/NCI NIH HHS/United States ; 949538/ERC_/European Research Council/International ; CA143055/CA/NCI NIH HHS/United States ; U54CA143803/CA/NCI NIH HHS/United States ; CA093900/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Cell Communication ; Cell Differentiation/genetics ; Eukaryota/genetics ; *Neoplasms/genetics ; Phylogeny ; }, abstract = {The rise of animals represents a major but enigmatic event in the evolutionary history of life. In recent years, numerous studies have aimed at understanding the genetic basis of this transition. However, genome comparisons of diverse animal and protist lineages suggest that the appearance of gene families that were previously considered animal specific indeed preceded animals. Animals' unicellular relatives, such as choanoflagellates, ichthyosporeans, and filastereans, demonstrate complex life cycles including transient multicellularity as well as genetic toolkits for temporal cell differentiation, cell-to-cell communication, apoptosis, and cell adhesion. This has warranted further exploration of the genetic basis underlying transitions in cellular organization. An alternative model for the study of transitions in cellular organization is tumors, which exploit physiological programs that characterize both unicellularity and multicellularity. Tumor cells, for example, switch adhesion on and off, up- or downregulate specific cell differentiation states, downregulate apoptosis, and allow cell migration within tissues. Here, we use insights from both the fields of phylogenomics and tumor biology to review the evolutionary history of the regulatory systems of multicellularity and discuss their overlap. We claim that while evolutionary biology has contributed to an increased understanding of cancer, broad investigations into tissue-normal and transformed-can also contribute the framework for exploring animal evolution.}, } @article {pmid35970862, year = {2022}, author = {Smith, TJ and Donoghue, PCJ}, title = {Evolution of fungal phenotypic disparity.}, journal = {Nature ecology & evolution}, volume = {6}, number = {10}, pages = {1489-1500}, pmid = {35970862}, issn = {2397-334X}, support = {BB/T012773/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N000919/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; *Fungi/genetics ; Phenotype ; Plants ; }, abstract = {Organismal-grade multicellularity has been achieved only in animals, plants and fungi. All three kingdoms manifest phenotypically disparate body plans but their evolution has only been considered in detail for animals. Here we tested the general relevance of hypotheses on the evolutionary assembly of animal body plans by characterizing the evolution of fungal phenotypic variety (disparity). The distribution of living fungal form is defined by four distinct morphotypes: flagellated; zygomycetous; sac-bearing; and club-bearing. The discontinuity between morphotypes is a consequence of extinction, indicating that a complete record of fungal disparity would present a more homogeneous distribution of form. Fungal disparity expands episodically through time, punctuated by a sharp increase associated with the emergence of multicellular body plans. Simulations show these temporal trends to be non-random and at least partially shaped by hierarchical contingency. These trends are decoupled from changes in gene number, genome size and taxonomic diversity. Only differences in organismal complexity, characterized as the number of traits that constitute an organism, exhibit a meaningful relationship with fungal disparity. Both animals and fungi exhibit episodic increases in disparity through time, resulting in distributions of form made discontinuous by extinction. These congruences suggest a common mode of multicellular body plan evolution.}, } @article {pmid35948712, year = {2022}, author = {Kim, H and Skinner, DJ and Glass, DS and Hamby, AE and Stuart, BAR and Dunkel, J and Riedel-Kruse, IH}, title = {4-bit adhesion logic enables universal multicellular interface patterning.}, journal = {Nature}, volume = {608}, number = {7922}, pages = {324-329}, pmid = {35948712}, issn = {1476-4687}, support = {R01 GM145893/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; *Artificial Cells/cytology ; Biofilms ; *Cell Adhesion ; Humans ; *Logic ; *Synthetic Biology/methods ; }, abstract = {Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions[1,2]. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning[3,4]. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems[5-8]. However, our ability to engineer multicellular interface patterns[2,9] is still very limited, as synthetic cell-cell adhesion toolkits and suitable patterning algorithms are underdeveloped[5,7,10-13]. Here we introduce a synthetic cell-cell adhesin logic with swarming bacteria and establish the precise engineering, predictive modelling and algorithmic programming of multicellular interface patterns. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. This synthetic 4-bit adhesion logic advances practical applications such as human-readable molecular diagnostics, spatial fluid control on biological surfaces and programmable self-growing materials[5-8,14]. Notably, a minimal set of just four adhesins represents 4 bits of information that suffice to program universal tessellation patterns, implying a low critical threshold for the evolution and engineering of complex multicellular systems[3,5].}, } @article {pmid35901418, year = {2022}, author = {Raguž, L and Peng, CC and Rutaganira, FUN and Krüger, T and Stanišić, A and Jautzus, T and Kries, H and Kniemeyer, O and Brakhage, AA and King, N and Beemelmanns, C}, title = {Total Synthesis and Functional Evaluation of IORs, Sulfonolipid-based Inhibitors of Cell Differentiation in Salpingoeca rosetta.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {61}, number = {41}, pages = {e202209105}, pmid = {35901418}, issn = {1521-3773}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cell Differentiation ; *Choanoflagellata ; Lipids ; Proteomics ; Sulfonic Acids ; Zinc ; }, abstract = {The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR-1A (six steps, 27 % overall yield), which acts as bacterial inhibitor of rosette formation in S. rosetta. The synthesis features a decarboxylative cross-coupling reaction of a sulfonic acid-containing tartaric acid derivative with alkyl zinc reagents. Synthesis of 15 modified IOR-1A derivatives, including fluorescent and photoaffinity-based probes, allowed quantification of IOR-1A, localization studies within S. rosetta cells, and evaluation of structure-activity relations. In a proof of concept study, an inhibitory bifunctional probe was employed in proteomic profiling studies, which allowed to deduce binding partners in bacteria and S. rosetta. These results showcase the power of synthetic chemistry to decipher the biochemical basis of cell differentiation processes within S. rosetta.}, } @article {pmid35894230, year = {2022}, author = {Le Gloanec, C and Collet, L and Silveira, SR and Wang, B and Routier-Kierzkowska, AL and Kierzkowski, D}, title = {Cell type-specific dynamics underlie cellular growth variability in plants.}, journal = {Development (Cambridge, England)}, volume = {149}, number = {14}, pages = {}, doi = {10.1242/dev.200783}, pmid = {35894230}, issn = {1477-9129}, mesh = {*Arabidopsis ; *Arabidopsis Proteins/genetics ; Cell Differentiation/genetics ; Cell Proliferation ; Plant Leaves ; Plant Stomata ; }, abstract = {Coordination of growth, patterning and differentiation is required for shaping organs in multicellular organisms. In plants, cell growth is controlled by positional information, yet the behavior of individual cells is often highly heterogeneous. The origin of this variability is still unclear. Using time-lapse imaging, we determined the source and relevance of cellular growth variability in developing organs of Arabidopsis thaliana. We show that growth is more heterogeneous in the leaf blade than in the midrib and petiole, correlating with higher local differences in growth rates between neighboring cells in the blade. This local growth variability coincides with developing stomata. Stomatal lineages follow a specific, time-dependent growth program that is different from that of their surroundings. Quantification of cellular dynamics in the leaves of a mutant lacking stomata, as well as analysis of floral organs, supports the idea that growth variability is mainly driven by stomata differentiation. Thus, the cell-autonomous behavior of specialized cells is the main source of local growth variability in otherwise homogeneously growing tissue. Those growth differences are buffered by the immediate neighbors of stomata and trichomes to achieve robust organ shapes.}, } @article {pmid35893123, year = {2022}, author = {Dijkwel, Y and Tremethick, DJ}, title = {The Role of the Histone Variant H2A.Z in Metazoan Development.}, journal = {Journal of developmental biology}, volume = {10}, number = {3}, pages = {}, pmid = {35893123}, issn = {2221-3759}, support = {1142399//National Health and Medical Research Council/ ; }, abstract = {During the emergence and radiation of complex multicellular eukaryotes from unicellular ancestors, transcriptional systems evolved by becoming more complex to provide the basis for this morphological diversity. The way eukaryotic genomes are packaged into a highly complex structure, known as chromatin, underpins this evolution of transcriptional regulation. Chromatin structure is controlled by a variety of different epigenetic mechanisms, including the major mechanism for altering the biochemical makeup of the nucleosome by replacing core histones with their variant forms. The histone H2A variant H2A.Z is particularly important in early metazoan development because, without it, embryos cease to develop and die. However, H2A.Z is also required for many differentiation steps beyond the stage that H2A.Z-knockout embryos die. H2A.Z can facilitate the activation and repression of genes that are important for pluripotency and differentiation, and acts through a variety of different molecular mechanisms that depend upon its modification status, its interaction with histone and nonhistone partners, and where it is deposited within the genome. In this review, we discuss the current knowledge about the different mechanisms by which H2A.Z regulates chromatin function at various developmental stages and the chromatin remodeling complexes that determine when and where H2A.Z is deposited.}, } @article {pmid35879542, year = {2022}, author = {Ní Leathlobhair, M and Lenski, RE}, title = {Population genetics of clonally transmissible cancers.}, journal = {Nature ecology & evolution}, volume = {6}, number = {8}, pages = {1077-1089}, pmid = {35879542}, issn = {2397-334X}, mesh = {Animals ; Biological Evolution ; *Genetics, Population ; Genome ; *Neoplasms/genetics ; Population Dynamics ; }, abstract = {Populations of cancer cells are subject to the same core evolutionary processes as asexually reproducing, unicellular organisms. Transmissible cancers are particularly striking examples of these processes. These unusual cancers are clonal lineages that can spread through populations via physical transfer of living cancer cells from one host individual to another, and they have achieved long-term success in the colonization of at least eight different host species. Population genetic theory provides a useful framework for understanding the shift from a multicellular sexual animal into a unicellular asexual clone and its long-term effects on the genomes of these cancers. In this Review, we consider recent findings from transmissible cancer research with the goals of developing an evolutionarily informed perspective on transmissible cancers, examining possible implications for their long-term fate and identifying areas for future research on these exceptional lineages.}, } @article {pmid35862435, year = {2022}, author = {Howe, J and Rink, JC and Wang, B and Griffin, AS}, title = {Multicellularity in animals: The potential for within-organism conflict.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {32}, pages = {e2120457119}, pmid = {35862435}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; *Cell Lineage ; Clone Cells ; Developmental Biology ; *Insecta/growth & development ; Reproduction ; }, abstract = {Metazoans function as individual organisms but also as "colonies" of cells whose single-celled ancestors lived and reproduced independently. Insights from evolutionary biology about multicellular group formation help us understand the behavior of cells: why they cooperate, and why cooperation sometimes breaks down. Current explanations for multicellularity focus on two aspects of development which promote cooperation and limit conflict among cells: a single-cell bottleneck, which creates organisms composed of clones, and a separation of somatic and germ cell lineages, which reduces the selective advantage of cheating. However, many obligately multicellular organisms thrive with neither, creating the potential for within-organism conflict. Here, we argue that the prevalence of such organisms throughout the Metazoa requires us to refine our preconceptions of conflict-free multicellularity. Evolutionary theory must incorporate developmental mechanisms across a broad range of organisms-such as unusual reproductive strategies, totipotency, and cell competition-while developmental biology must incorporate evolutionary principles. To facilitate this cross-disciplinary approach, we provide a conceptual overview from evolutionary biology for developmental biologists, using analogous examples in the well-studied social insects.}, } @article {pmid35858311, year = {2022}, author = {Belcher, LJ and Madgwick, PG and Kuwana, S and Stewart, B and Thompson, CRL and Wolf, JB}, title = {Developmental constraints enforce altruism and avert the tragedy of the commons in a social microbe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {29}, pages = {e2111233119}, pmid = {35858311}, issn = {1091-6490}, support = {WT095643AIA//Wellcome Trust (WT)/ ; BB/M007146/1//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; NE/V012002/1//UKRI | Natural Environment Research Council (NERC)/ ; BB/M01035X/1//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Altruism ; Biological Evolution ; Cooperative Behavior ; *Dictyostelium ; Humans ; Motivation ; }, abstract = {Organisms often cooperate through the production of freely available public goods. This can greatly benefit the group but is vulnerable to the "tragedy of the commons" if individuals lack the motivation to make the necessary investment into public goods production. Relatedness to groupmates can motivate individual investment because group success ultimately benefits their genes' own self-interests. However, systems often lack mechanisms that can reliably ensure that relatedness is high enough to promote cooperation. Consequently, groups face a persistent threat from the tragedy unless they have a mechanism to enforce investment when relatedness fails to provide adequate motivation. To understand the real threat posed by the tragedy and whether groups can avert its impact, we determine how the social amoeba Dictyostelium discoideum responds as relatedness decreases to levels that should induce the tragedy. We find that, while investment in public goods declines as overall within-group relatedness declines, groups avert the expected catastrophic collapse of the commons by continuing to invest, even when relatedness should be too low to incentivize any contribution. We show that this is due to a developmental buffering system that generates enforcement because insufficient cooperation perturbs the balance of a negative feedback system controlling multicellular development. This developmental constraint enforces investment under the conditions expected to be most tragic, allowing groups to avert a collapse in cooperation. These results help explain how mechanisms that suppress selfishness and enforce cooperation can arise inadvertently as a by-product of constraints imposed by selection on different traits.}, } @article {pmid35852417, year = {2022}, author = {Chakravarty, AK and McGrail, DJ and Lozanoski, TM and Dunn, BS and Shih, DJH and Cirillo, KM and Cetinkaya, SH and Zheng, WJ and Mills, GB and Yi, SS and Jarosz, DF and Sahni, N}, title = {Biomolecular Condensation: A New Phase in Cancer Research.}, journal = {Cancer discovery}, volume = {12}, number = {9}, pages = {2031-2043}, pmid = {35852417}, issn = {2159-8290}, support = {R01 AG063418/AG/NIA NIH HHS/United States ; P50 CA217685/CA/NCI NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; K99 GM128180/GM/NIGMS NIH HHS/United States ; R35 GM137836/GM/NIGMS NIH HHS/United States ; K99 CA240689/CA/NCI NIH HHS/United States ; DRG2221-15/HHMI/Howard Hughes Medical Institute/United States ; U01 CA217842/CA/NCI NIH HHS/United States ; R35 GM133658/GM/NIGMS NIH HHS/United States ; DP2 GM119140/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Neoplasms/metabolism ; *Organelles/metabolism ; Research ; }, abstract = {UNLABELLED: Multicellularity was a watershed development in evolution. However, it also meant that individual cells could escape regulatory mechanisms that restrict proliferation at a severe cost to the organism: cancer. From the standpoint of cellular organization, evolutionary complexity scales to organize different molecules within the intracellular milieu. The recent realization that many biomolecules can "phase-separate" into membraneless organelles, reorganizing cellular biochemistry in space and time, has led to an explosion of research activity in this area. In this review, we explore mechanistic connections between phase separation and cancer-associated processes and emerging examples of how these become deranged in malignancy.

SIGNIFICANCE: One of the fundamental functions of phase separation is to rapidly and dynamically respond to environmental perturbations. Importantly, these changes often lead to alterations in cancer-relevant pathways and processes. This review covers recent advances in the field, including emerging principles and mechanisms of phase separation in cancer.}, } @article {pmid35849348, year = {2022}, author = {Wu, TY and Hoh, KL and Boonyaves, K and Krishnamoorthi, S and Urano, D}, title = {Diversification of heat shock transcription factors expanded thermal stress responses during early plant evolution.}, journal = {The Plant cell}, volume = {34}, number = {10}, pages = {3557-3576}, pmid = {35849348}, issn = {1532-298X}, mesh = {*Arabidopsis/metabolism ; Gene Expression Regulation, Plant/genetics ; Gene Regulatory Networks ; Heat Shock Transcription Factors/metabolism ; Heat-Shock Response/genetics ; *Marchantia/genetics/metabolism ; Plant Proteins/genetics/metabolism ; }, abstract = {The copy numbers of many plant transcription factor (TF) genes substantially increased during terrestrialization. This allowed TFs to acquire new specificities and thus create gene regulatory networks (GRNs) with new biological functions to help plants adapt to terrestrial environments. Through characterizing heat shock factor (HSF) genes MpHSFA1 and MpHSFB1 in the liverwort Marchantia polymorpha, we explored how heat-responsive GRNs widened their functions in M. polymorpha and Arabidopsis thaliana. An interspecies comparison of heat-induced transcriptomes and the evolutionary rates of HSFs demonstrated the emergence and subsequent rapid evolution of HSFB prior to terrestrialization. Transcriptome and metabolome analyses of M. polymorpha HSF-null mutants revealed that MpHSFA1 controls canonical heat responses such as thermotolerance and metabolic changes. MpHSFB1 also plays essential roles in heat responses, as well as regulating developmental processes including meristem branching and antheridiophore formation. Analysis of cis-regulatory elements revealed development- and stress-related TFs that function directly or indirectly downstream of HSFB. Male gametophytes of M. polymorpha showed higher levels of thermotolerance than female gametophytes, which could be explained by different expression levels of MpHSFA1U and MpHSFA1V on sex chromosome. We propose that the diversification of HSFs is linked to the expansion of HS responses, which enabled coordinated multicellular reactions in land plants.}, } @article {pmid35841659, year = {2022}, author = {Gabaldón, T and Völcker, E and Torruella, G}, title = {On the Biology, Diversity and Evolution of Nucleariid Amoebae (Amorphea, Obazoa, Opisthokonta[1].}, journal = {Protist}, volume = {173}, number = {4}, pages = {125895}, doi = {10.1016/j.protis.2022.125895}, pmid = {35841659}, issn = {1618-0941}, mesh = {*Amoeba ; Animals ; Biology ; Eukaryota ; Fungi ; Phylogeny ; }, abstract = {Nucleariids are a small group of free-living heterotrophic amoebae. Although these organisms present a variety of cell sizes and cell coverings, they are mostly spherical cells with radiating filopodia, sometimes with several nuclei. Nuclearia, the genus that gives the name to the group, contains species that are opportunistic consumers of detritus, bacteria, and algae. The beautiful Pompholyxophrys is covered with endogenous siliceous pearls. Lithocolla covers itself with sand particles, or otherwise diatom frustules. The tiny Parvularia exclusively feeds on bacteria, and Fonticula is adapted to solid substrates and presents aggregative multicellular stages. Nucleariids belong to the Opisthokonta, which comprise animals, fungi, and their protist relatives, and form the earliest branch in the holomycotan clade (fungi and closest relatives). Hence, they are key for understanding the origin and diversification of Opisthokonta, an eukaryotic supergroup that contains organisms with different feeding modes, life-styles, and cell organizations. In this review, the reader will find an introduction to nucleariids, from their discovery in the 19th century until the most recent studies. It summarizes available information on their morphology, life history, cell organisation, ecology, diversity, systematics and evolution.}, } @article {pmid35838349, year = {2022}, author = {Meléndez García, R and Haccard, O and Chesneau, A and Narassimprakash, H and Roger, J and Perron, M and Marheineke, K and Bronchain, O}, title = {A non-transcriptional function of Yap regulates the DNA replication program in Xenopus laevis.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35838349}, issn = {2050-084X}, mesh = {Animals ; DNA Replication ; DNA Replication Timing ; *Replication Origin ; S Phase/genetics ; *Telomere-Binding Proteins/genetics ; Xenopus laevis/genetics/metabolism ; }, abstract = {In multicellular eukaryotic organisms, the initiation of DNA replication occurs asynchronously throughout S-phase according to a regulated replication timing program. Here, using Xenopus egg extracts, we showed that Yap (Yes-associated protein 1), a downstream effector of the Hippo signalling pathway, is required for the control of DNA replication dynamics. We found that Yap is recruited to chromatin at the start of DNA replication and identified Rif1, a major regulator of the DNA replication timing program, as a novel Yap binding protein. Furthermore, we show that either Yap or Rif1 depletion accelerates DNA replication dynamics by increasing the number of activated replication origins. In Xenopus embryos, using a Trim-Away approach during cleavage stages devoid of transcription, we found that either Yap or Rif1 depletion triggers an acceleration of cell divisions, suggesting a shorter S-phase by alterations of the replication program. Finally, our data show that Rif1 knockdown leads to defects in the partitioning of early versus late replication foci in retinal stem cells, as we previously showed for Yap. Altogether, our findings unveil a non-transcriptional role for Yap in regulating replication dynamics. We propose that Yap and Rif1 function as brakes to control the DNA replication program in early embryos and post-embryonic stem cells.}, } @article {pmid35804300, year = {2022}, author = {Angaroni, F and Guidi, A and Ascolani, G and d'Onofrio, A and Antoniotti, M and Graudenzi, A}, title = {J-SPACE: a Julia package for the simulation of spatial models of cancer evolution and of sequencing experiments.}, journal = {BMC bioinformatics}, volume = {23}, number = {1}, pages = {269}, pmid = {35804300}, issn = {1471-2105}, support = {Bicocca 2020 Starting Grant//Università degli Studi di Milano-Bicocca/ ; 22790/CRUK_/Cancer Research UK/United Kingdom ; 22790/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Computer Simulation ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Neoplasms/genetics/pathology ; Phylogeny ; *Software ; }, abstract = {BACKGROUND: The combined effects of biological variability and measurement-related errors on cancer sequencing data remain largely unexplored. However, the spatio-temporal simulation of multi-cellular systems provides a powerful instrument to address this issue. In particular, efficient algorithmic frameworks are needed to overcome the harsh trade-off between scalability and expressivity, so to allow one to simulate both realistic cancer evolution scenarios and the related sequencing experiments, which can then be used to benchmark downstream bioinformatics methods.

RESULT: We introduce a Julia package for SPAtial Cancer Evolution (J-SPACE), which allows one to model and simulate a broad set of experimental scenarios, phenomenological rules and sequencing settings.Specifically, J-SPACE simulates the spatial dynamics of cells as a continuous-time multi-type birth-death stochastic process on a arbitrary graph, employing different rules of interaction and an optimised Gillespie algorithm. The evolutionary dynamics of genomic alterations (single-nucleotide variants and indels) is simulated either under the Infinite Sites Assumption or several different substitution models, including one based on mutational signatures. After mimicking the spatial sampling of tumour cells, J-SPACE returns the related phylogenetic model, and allows one to generate synthetic reads from several Next-Generation Sequencing (NGS) platforms, via the ART read simulator. The results are finally returned in standard FASTA, FASTQ, SAM, ALN and Newick file formats.

CONCLUSION: J-SPACE is designed to efficiently simulate the heterogeneous behaviour of a large number of cancer cells and produces a rich set of outputs. Our framework is useful to investigate the emergent spatial dynamics of cancer subpopulations, as well as to assess the impact of incomplete sampling and of experiment-specific errors. Importantly, the output of J-SPACE is designed to allow the performance assessment of downstream bioinformatics pipelines processing NGS data. J-SPACE is freely available at: https://github.com/BIMIB-DISCo/J-Space.jl .}, } @article {pmid35792830, year = {2022}, author = {Fukai, E and Yoshikawa, M and Shah, N and Sandal, N and Miyao, A and Ono, S and Hirakawa, H and Akyol, TY and Umehara, Y and Nonomura, KI and Stougaard, J and Hirochika, H and Hayashi, M and Sato, S and Andersen, SU and Okazaki, K}, title = {Widespread and transgenerational retrotransposon activation in inter- and intraspecies recombinant inbred populations of Lotus japonicus.}, journal = {The Plant journal : for cell and molecular biology}, volume = {111}, number = {5}, pages = {1397-1410}, doi = {10.1111/tpj.15896}, pmid = {35792830}, issn = {1365-313X}, mesh = {Evolution, Molecular ; Genome, Plant/genetics ; Hybridization, Genetic ; *Lotus/genetics ; Plants/genetics ; *Retroelements/genetics ; Terminal Repeat Sequences/genetics ; }, abstract = {Transposable elements (TEs) constitute a large proportion of genomes of multicellular eukaryotes, including flowering plants. TEs are normally maintained in a silenced state and their transpositions rarely occur. Hybridization between distant species has been regarded as a 'shock' that stimulates genome reorganization, including TE mobilization. However, whether crosses between genetically close parents that result in viable and fertile offspring can induce TE transpositions has remained unclear. Here, we investigated the activation of long terminal repeat (LTR) retrotransposons in three Lotus japonicus recombinant inbred line (RIL) populations. We found that at least six LTR retrotransposon families were activated and transposed in 78% of the RILs investigated. LORE1a, one of the transposed LTR retrotransposons, showed transgenerational epigenetic activation, indicating the long-term effects of epigenetic instability induced by hybridization. Our study highlights TE activation as an unexpectedly common event in plant reproduction.}, } @article {pmid35790840, year = {2022}, author = {Beljan, S and Dominko, K and Talajić, A and Hloušek-Kasun, A and Škrobot Vidaček, N and Herak Bosnar, M and Vlahoviček, K and Ćetković, H}, title = {Structure and function of cancer-related developmentally regulated GTP-binding protein 1 (DRG1) is conserved between sponges and humans.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {11379}, pmid = {35790840}, issn = {2045-2322}, mesh = {Animals ; GTP-Binding Proteins ; Genomics ; Humans ; *Neoplasms/genetics ; *Oncogenes ; RNA ; Transcription Factors ; }, abstract = {Cancer is a disease caused by errors within the multicellular system and it represents a major health issue in multicellular organisms. Although cancer research has advanced substantially, new approaches focusing on fundamental aspects of cancer origin and mechanisms of spreading are necessary. Comparative genomic studies have shown that most genes linked to human cancer emerged during the early evolution of Metazoa. Thus, basal animals without true tissues and organs, such as sponges (Porifera), might be an innovative model system for understanding the molecular mechanisms of proteins involved in cancer biology. One of these proteins is developmentally regulated GTP-binding protein 1 (DRG1), a GTPase stabilized by interaction with DRG family regulatory protein 1 (DFRP1). This study reveals a high evolutionary conservation of DRG1 gene/protein in metazoans. Our biochemical analysis and structural predictions show that both recombinant sponge and human DRG1 are predominantly monomers that form complexes with DFRP1 and bind non-specifically to RNA and DNA. We demonstrate the conservation of sponge and human DRG1 biological features, including intracellular localization and DRG1:DFRP1 binding, function of DRG1 in α-tubulin dynamics, and its role in cancer biology demonstrated by increased proliferation, migration and colonization in human cancer cells. These results suggest that the ancestor of all Metazoa already possessed DRG1 that is structurally and functionally similar to the human DRG1, even before the development of real tissues or tumors, indicating an important function of DRG1 in fundamental cellular pathways.}, } @article {pmid35778439, year = {2022}, author = {Belpaire, TER and Pešek, J and Lories, B and Verstrepen, KJ and Steenackers, HP and Ramon, H and Smeets, B}, title = {Permissive aggregative group formation favors coexistence between cooperators and defectors in yeast.}, journal = {The ISME journal}, volume = {16}, number = {10}, pages = {2305-2312}, pmid = {35778439}, issn = {1751-7370}, support = {12Z6118N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; CELSA/18/031//KU Leuven (Katholieke Universiteit Leuven)/ ; C24/18/046//KU Leuven/ ; }, mesh = {Biological Evolution ; Flocculation ; Mannose-Binding Lectins/chemistry/genetics/metabolism ; *Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism ; }, abstract = {In Saccharomyces cerevisiae, the FLO1 gene encodes flocculins that lead to formation of multicellular flocs, that offer protection to the constituent cells. Flo1p was found to preferentially bind to fellow cooperators compared to defectors lacking FLO1 expression, enriching cooperators within the flocs. Given this dual function in cooperation and kin recognition, FLO1 has been termed a "green beard gene". Because of the heterophilic nature of the Flo1p bond however, we hypothesize that kin recognition is permissive and depends on the relative stability of the FLO1[+]/flo1[-] versus FLO1[+]/FLO1[+] detachment force F. We combine single-cell measurements of adhesion, individual cell-based simulations of cluster formation, and in vitro flocculation to study the impact of relative bond stability on the evolutionary stability of cooperation. We identify a trade-off between both aspects of the green beard mechanism, with reduced relative bond stability leading to increased kin recognition at the expense of cooperative benefits. We show that the fitness of FLO1 cooperators decreases as their frequency in the population increases, arising from the observed permissive character (F+- = 0.5 F++) of the Flo1p bond. Considering the costs associated with FLO1 expression, this asymmetric selection often results in a stable coexistence between cooperators and defectors.}, } @article {pmid35728616, year = {2022}, author = {Cameron-Pack, ME and König, SG and Reyes-Guevara, A and Reyes-Prieto, A and Nedelcu, AM}, title = {A personal cost of cheating can stabilize reproductive altruism during the early evolution of clonal multicellularity.}, journal = {Biology letters}, volume = {18}, number = {6}, pages = {20220059}, pmid = {35728616}, issn = {1744-957X}, mesh = {*Altruism ; Biological Evolution ; Reproduction ; *Volvox/genetics ; }, abstract = {Understanding how cooperation evolved and is maintained remains an important and often controversial topic because cheaters that reap the benefits of cooperation without paying the costs can threaten the evolutionary stability of cooperative traits. Cooperation-and especially reproductive altruism-is particularly relevant to the evolution of multicellularity, as somatic cells give up their reproductive potential in order to contribute to the fitness of the newly emerged multicellular individual. Here, we investigated cheating in a simple multicellular species-the green alga Volvox carteri, in the context of the mechanisms that can stabilize reproductive altruism during the early evolution of clonal multicellularity. We found that the benefits cheater mutants can gain in terms of their own reproduction are pre-empted by a cost in survival due to increased sensitivity to stress. This personal cost of cheating reflects the antagonistic pleiotropic effects that the gene coding for reproductive altruism-regA-has at the cell level. Specifically, the expression of regA in somatic cells results in the suppression of their reproduction potential but also confers them with increased resistance to stress. Since regA evolved from a life-history trade-off gene, we suggest that co-opting trade-off genes into cooperative traits can provide a built-in safety system against cheaters in other clonal multicellular lineages.}, } @article {pmid35726057, year = {2022}, author = {Kaufmann, M and Schaupp, AL and Sun, R and Coscia, F and Dendrou, CA and Cortes, A and Kaur, G and Evans, HG and Mollbrink, A and Navarro, JF and Sonner, JK and Mayer, C and DeLuca, GC and Lundeberg, J and Matthews, PM and Attfield, KE and Friese, MA and Mann, M and Fugger, L}, title = {Identification of early neurodegenerative pathways in progressive multiple sclerosis.}, journal = {Nature neuroscience}, volume = {25}, number = {7}, pages = {944-955}, pmid = {35726057}, issn = {1546-1726}, support = {MC_UU_00008/3/MRC_/Medical Research Council/United Kingdom ; MC_UU_12010/3/MRC_/Medical Research Council/United Kingdom ; 100308/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {*Central Nervous System Diseases/complications ; Disease Progression ; Humans ; *Multiple Sclerosis/pathology ; Neurons/metabolism ; Proteomics ; }, abstract = {Progressive multiple sclerosis (MS) is characterized by unrelenting neurodegeneration, which causes cumulative disability and is refractory to current treatments. Drug development to prevent disease progression is an urgent clinical need yet is constrained by an incomplete understanding of its complex pathogenesis. Using spatial transcriptomics and proteomics on fresh-frozen human MS brain tissue, we identified multicellular mechanisms of progressive MS pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration. By resolving ligand-receptor interactions in local microenvironments, we discovered defunct trophic and anti-inflammatory intercellular communications within areas of early neuronal decline. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with published in vivo knockdown and central nervous system (CNS) disease models, supporting their causal role and value as potential therapeutic targets in progressive MS. Our findings provide a new framework for drug development strategies, rooted in an understanding of the complex cellular and signaling dynamics in human diseased tissue that facilitate this debilitating disease.}, } @article {pmid35725583, year = {2022}, author = {Mori, G and Delfino, D and Pibiri, P and Rivetti, C and Percudani, R}, title = {Origin and significance of the human DNase repertoire.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {10364}, pmid = {35725583}, issn = {2045-2322}, mesh = {Animals ; DNA/genetics ; Deoxyribonuclease I/genetics ; *Deoxyribonucleases/genetics ; *Evolution, Molecular ; Fishes/genetics ; Gene Duplication ; Humans ; Phylogeny ; Synteny ; Vertebrates/genetics ; }, abstract = {The human genome contains four DNase1 and two DNase2 genes. The origin and functional specialization of this repertoire are not fully understood. Here we use genomics and transcriptomics data to infer the evolutionary history of DNases and investigate their biological significance. Both DNase1 and DNase2 families have expanded in vertebrates since ~ 650 million years ago before the divergence of jawless and jawed vertebrates. DNase1, DNase1L1, and DNase1L3 co-existed in jawless fish, whereas DNase1L2 originated in amniotes by tandem duplication of DNase1. Among the non-human DNases, DNase1L4 and newly identified DNase1L5 derived from early duplications that were lost in terrestrial vertebrates. The ancestral gene of the DNase2 family, DNase2b, has been conserved in synteny with the Uox gene across 700 million years of animal evolution,while DNase2 originated in jawless fish. DNase1L1 acquired a GPI-anchor for plasma membrane attachment in bony fishes, and DNase1L3 acquired a C-terminal basic peptide for the degradation of microparticle DNA in jawed vertebrates. The appearance of DNase1L2, with a distinct low pH optimum and skin localization, is among the amniote adaptations to life on land. The expansion of the DNase repertoire in vertebrates meets the diversified demand for DNA debris removal in complex multicellular organisms.}, } @article {pmid35713948, year = {2022}, author = {Passer, AR and Clancey, SA and Shea, T and David-Palma, M and Averette, AF and Boekhout, T and Porcel, BM and Nowrousian, M and Cuomo, CA and Sun, S and Heitman, J and Coelho, MA}, title = {Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35713948}, issn = {2050-084X}, support = {R01 AI039115/AI/NIAID NIH HHS/United States ; R01 AI050113/AI/NIAID NIH HHS/United States ; R37 AI039115/AI/NIAID NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; }, mesh = {Biological Evolution ; *Cryptococcus neoformans/genetics ; *Genes, Mating Type, Fungal/genetics ; Humans ; Reproduction ; Saccharomyces cerevisiae/genetics ; }, abstract = {eLife digest. Fungi are enigmatic organisms that flourish in soil, on decaying plants, or during infection of animals or plants. Growing in myriad forms, from single-celled yeast to multicellular molds and mushrooms, fungi have also evolved a variety of strategies to reproduce. Normally, fungi reproduce in one of two ways: either they reproduce asexually, with one individual producing a new individual identical to itself, or they reproduce sexually, with two individuals of different 'mating types' contributing to produce a new individual. However, individuals of some species exhibit 'homothallism' or self-fertility: these individuals can produce reproductive cells that are universally compatible, and therefore can reproduce sexually with themselves or with any other cell in the population. Homothallism has evolved multiple times throughout the fungal kingdom, suggesting it confers advantage when population numbers are low or mates are hard to find. Yet some homothallic fungi been overlooked compared to heterothallic species, whose mating types have been well characterised. Understanding the genetic basis of homothallism and how it evolved in different species can provide insights into pathogenic species that cause fungal disease. With that in mind, Passer, Clancey et al. explored the genetic basis of homothallism in Cryptococcus depauperatus, a close relative of C. neoformans, a species that causes fungal infections in humans. A combination of genetic sequencing techniques and experiments were applied to analyse, compare, and manipulate C. depauperatus' genome to see how this species evolved self-fertility. Passer, Clancey et al. showed that C. depauperatus evolved the ability to reproduce sexually by itself via a unique evolutionary pathway. The result is a form of homothallism never reported in fungi before. C. depauperatus lost some of the genes that control mating in other species of fungi, and acquired genes from the opposing mating types of a heterothallic ancestor to become self-fertile. Passer, Clancey et al. also found that, unlike other Cryptococcus species that switch between asexual and sexual reproduction, C. depauperatus grows only as long, branching filaments called hyphae, a sexual form. The species reproduces sexually with itself throughout its life cycle and is unable to produce a yeast (asexual) form, in contrast to other closely related species. This work offers new insights into how different modes of sexual reproduction have evolved in fungi. It also provides another interesting case of how genome plasticity and evolutionary pressures can produce similar outcomes, homothallism, via different evolutionary paths. Lastly, assembling the complete genome of C. depauperatus will foster comparative studies between pathogenic and non-pathogenic Cryptococcus species.}, } @article {pmid35681485, year = {2022}, author = {Minelli, A and Valero-Gracia, A}, title = {Spatially and Temporally Distributed Complexity-A Refreshed Framework for the Study of GRN Evolution.}, journal = {Cells}, volume = {11}, number = {11}, pages = {}, pmid = {35681485}, issn = {2073-4409}, mesh = {Animals ; *Gene Regulatory Networks ; Genotype ; Phenotype ; }, abstract = {Irrespective of the heuristic value of interpretations of developmental processes in terms of gene regulatory networks (GRNs), larger-angle views often suffer from: (i) an inadequate understanding of the relationship between genotype and phenotype; (ii) a predominantly zoocentric vision; and (iii) overconfidence in a putatively hierarchical organization of animal body plans. Here, we constructively criticize these assumptions. First, developmental biology is pervaded by adultocentrism, but development is not necessarily egg to adult. Second, during development, many unicells undergo transcriptomic profile transitions that are comparable to those recorded in pluricellular organisms; thus, their study should not be neglected from the GRN perspective. Third, the putatively hierarchical nature of the animal body is mirrored in the GRN logic, but in relating genotype to phenotype, independent assessments of the dynamics of the regulatory machinery and the animal's architecture are required, better served by a combinatorial than by a hierarchical approach. The trade-offs between spatial and temporal aspects of regulation, as well as their evolutionary consequences, are also discussed. Multicellularity may derive from a unicell's sequential phenotypes turned into different but coexisting, spatially arranged cell types. In turn, polyphenism may have been a crucial mechanism involved in the origin of complex life cycles.}, } @article {pmid35678467, year = {2022}, author = {Northey, JJ and Weaver, VM}, title = {Mechanosensitive Steroid Hormone Signaling and Cell Fate.}, journal = {Endocrinology}, volume = {163}, number = {8}, pages = {}, pmid = {35678467}, issn = {1945-7170}, support = {R01 CA222508/CA/NCI NIH HHS/United States ; R01 NS109911/NS/NINDS NIH HHS/United States ; R35 CA242447/CA/NCI NIH HHS/United States ; R01 CA192914/CA/NCI NIH HHS/United States ; }, mesh = {Cell Differentiation ; Hormones/physiology ; Humans ; *Neoplasms/pathology ; *Receptors, Steroid ; Signal Transduction ; Steroids ; }, abstract = {Mechanical forces collaborate across length scales to coordinate cell fate during development and the dynamic homeostasis of adult tissues. Similarly, steroid hormones interact with their nuclear and nonnuclear receptors to regulate diverse physiological processes necessary for the appropriate development and function of complex multicellular tissues. Aberrant steroid hormone action is associated with tumors originating in hormone-sensitive tissues and its disruption forms the basis of several therapeutic interventions. Prolonged perturbations to mechanical forces may further foster tumor initiation and the evolution of aggressive metastatic disease. Recent evidence suggests that steroid hormone and mechanical signaling intersect to direct cell fate during development and tumor progression. Potential mechanosensitive steroid hormone signaling pathways along with their molecular effectors will be discussed in this context.}, } @article {pmid35660859, year = {2022}, author = {Bao, L and Ren, J and Nguyen, M and Slusarczyk, AS and Thole, JM and Martinez, SP and Huang, J and Fujita, T and Running, MP}, title = {The cellular function of ROP GTPase prenylation is important for multicellularity in the moss Physcomitrium patens.}, journal = {Development (Cambridge, England)}, volume = {149}, number = {12}, pages = {}, doi = {10.1242/dev.200279}, pmid = {35660859}, issn = {1477-9129}, mesh = {*Bryopsida/metabolism ; Cell Wall/metabolism ; *GTP Phosphohydrolases/metabolism ; Prenylation ; Signal Transduction ; }, abstract = {A complete picture of how signaling pathways lead to multicellularity is largely unknown. Previously, we generated mutations in a protein prenylation enzyme, GGB, and showed that it is essential for maintaining multicellularity in the moss Physcomitrium patens. Here, we show that ROP GTPases act as downstream factors that are prenylated by GGB and themselves play an important role in the multicellularity of P. patens. We also show that the loss of multicellularity caused by the suppression of GGB or ROP GTPases is due to uncoordinated cell expansion, defects in cell wall integrity and the disturbance of the directional control of cell plate orientation. Expressing prenylatable ROP in the ggb mutant not only rescues multicellularity in protonemata but also results in development of gametophores. Although the prenylation of ROP is important for multicellularity, a higher threshold of active ROP is required for gametophore development. Thus, our results suggest that ROP activation via prenylation by GGB is a key process at both cell and tissue levels, facilitating the developmental transition from one dimension to two dimensions and to three dimensions in P. patens.}, } @article {pmid35659869, year = {2022}, author = {Phillips, JE and Santos, M and Konchwala, M and Xing, C and Pan, D}, title = {Genome editing in the unicellular holozoan Capsaspora owczarzaki suggests a premetazoan role for the Hippo pathway in multicellular morphogenesis.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35659869}, issn = {2050-084X}, support = {R01 EY015708/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Eukaryota/genetics ; *Evolution, Molecular ; *Gene Editing ; Hippo Signaling Pathway ; Morphogenesis ; }, abstract = {Animal development is mediated by a surprisingly small set of canonical signaling pathways such as Wnt, Hedgehog, TGF-beta, Notch, and Hippo pathways. Although once thought to be present only in animals, recent genome sequencing has revealed components of these pathways in the closest unicellular relatives of animals. These findings raise questions about the ancestral functions of these developmental pathways and their potential role in the emergence of animal multicellularity. Here, we provide the first functional characterization of any of these developmental pathways in unicellular organisms by developing techniques for genetic manipulation in Capsaspora owczarzaki, a close unicellular relative of animals that displays aggregative multicellularity. We then use these tools to characterize the Capsaspora ortholog of the Hippo signaling nuclear effector YAP/TAZ/Yorkie (coYki), a key regulator of tissue size in animals. In contrast to what might be expected based on studies in animals, we show that coYki is dispensable for cell proliferation but regulates cytoskeletal dynamics and the three-dimensional (3D) shape of multicellular structures. We further demonstrate that the cytoskeletal abnormalities of individual coYki mutant cells underlie the abnormal 3D shape of coYki mutant aggregates. Taken together, these findings implicate an ancestral role for the Hippo pathway in cytoskeletal dynamics and multicellular morphogenesis predating the origin of animal multicellularity, which was co-opted during evolution to regulate cell proliferation.}, } @article {pmid35651757, year = {2022}, author = {Díaz, E and Febres, A and Giammarresi, M and Silva, A and Vanegas, O and Gomes, C and Ponte-Sucre, A}, title = {G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {812848}, pmid = {35651757}, issn = {2235-2988}, mesh = {*Calcitonin Gene-Related Peptide/pharmacology ; Cell Communication ; Humans ; *Leishmania/metabolism ; Receptor Activity-Modifying Proteins/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Substance P/pharmacology ; }, abstract = {Detection and transduction of environmental signals, constitute a prerequisite for successful parasite invasion; i.e., Leishmania transmission, survival, pathogenesis and disease manifestation and dissemination, with diverse molecules functioning as inter-cellular signaling ligands. Receptors [i.e., G protein-coupled receptors (GPCRs)] and their associated transduction mechanisms, well conserved through evolution, specialize in this function. However, canonical GPCR-related signal transduction systems have not been described in Leishmania, although orthologs, with reduced domains and function, have been identified in Trypanosomatidae. These inter-cellular communication means seem to be essential for multicellular and unicellular organism's survival. GPCRs are flexible in their molecular architecture and may interact with the so-called receptor activity-modifying proteins (RAMPs), which modulate their function, changing GPCRs pharmacology, acting as chaperones and regulating signaling and/or trafficking in a receptor-dependent manner. In the skin, vasoactive- and neuro- peptides released in response to the noxious stimuli represented by the insect bite may trigger parasite physiological responses, for example, chemotaxis. For instance, in Leishmania (V.) braziliensis, sensory [Substance P, SP, chemoattractant] and autonomic [Vasoactive Intestinal Peptide, VIP, and Neuropeptide Y, NPY, chemorepellent] neuropeptides at physiological levels stimulate in vitro effects on parasite taxis. VIP and NPY chemotactic effects are impaired by their corresponding receptor antagonists, suggesting that the stimulated responses might be mediated by putative GPCRs (with essential conserved receptor domains); the effect of SP is blocked by [(D-Pro 2, D-Trp7,9]-Substance P (10[-6] M)] suggesting that it might be mediated by neurokinin-1 transmembrane receptors. Additionally, vasoactive molecules like Calcitonin Gene-Related Peptide [CGRP] and Adrenomedullin [AM], exert a chemorepellent effect and increase the expression of a 24 kDa band recognized in western blot analysis by (human-)-RAMP-2 antibodies. In-silico search oriented towards GPCRs-like receptors and signaling cascades detected a RAMP-2-aligned sequence corresponding to Leishmania folylpolyglutamate synthase and a RAMP-3 aligned protein, a hypothetical Leishmania protein with yet unknown function, suggesting that in Leishmania, CGRP and AM activities may be modulated by RAMP- (-2) and (-3) homologs. The possible presence of proteins and molecules potentially involved in GPCRs cascades, i.e., RAMPs, signpost conservation of ancient signaling systems associated with responses, fundamental for cell survival, (i.e., taxis and migration) and may constitute an open field for description of pharmacophores against Leishmania parasites.}, } @article {pmid35628404, year = {2022}, author = {Paradžik, T and Podgorski, II and Vojvoda Zeljko, T and Paradžik, M}, title = {Ancient Origins of Cytoskeletal Crosstalk: Spectraplakin-like Proteins Precede the Emergence of Cortical Microtubule Stabilization Complexes as Crosslinkers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {10}, pages = {}, pmid = {35628404}, issn = {1422-0067}, mesh = {Actin Cytoskeleton/metabolism ; *Actins/metabolism ; Animals ; *Cytoskeleton/metabolism ; Microtubules/metabolism ; Phylogeny ; }, abstract = {Adhesion between cells and the extracellular matrix (ECM) is one of the prerequisites for multicellularity, motility, and tissue specialization. Focal adhesions (FAs) are defined as protein complexes that mediate signals from the ECM to major components of the cytoskeleton (microtubules, actin, and intermediate filaments), and their mutual communication determines a variety of cellular processes. In this study, human cytoskeletal crosstalk proteins were identified by comparing datasets with experimentally determined cytoskeletal proteins. The spectraplakin dystonin was the only protein found in all datasets. Other proteins (FAK, RAC1, septin 9, MISP, and ezrin) were detected at the intersections of FAs, microtubules, and actin cytoskeleton. Homology searches for human crosstalk proteins as queries were performed against a predefined dataset of proteomes. This analysis highlighted the importance of FA communication with the actin and microtubule cytoskeleton, as these crosstalk proteins exhibit the highest degree of evolutionary conservation. Finally, phylogenetic analyses elucidated the early evolutionary history of spectraplakins and cortical microtubule stabilization complexes (CMSCs) as model representatives of the human cytoskeletal crosstalk. While spectraplakins probably arose at the onset of opisthokont evolution, the crosstalk between FAs and microtubules is associated with the emergence of metazoans. The multiprotein complexes contributing to cytoskeletal crosstalk in animals gradually gained in complexity from the onset of metazoan evolution.}, } @article {pmid35626631, year = {2022}, author = {Paul, B and Sterner, ZR and Buchholz, DR and Shi, YB and Sachs, LM}, title = {Thyroid and Corticosteroid Signaling in Amphibian Metamorphosis.}, journal = {Cells}, volume = {11}, number = {10}, pages = {}, pmid = {35626631}, issn = {2073-4409}, mesh = {Adrenal Cortex Hormones ; Amphibians ; Animals ; *Metamorphosis, Biological/physiology ; *Thyroid Gland/metabolism ; Thyroid Hormones/metabolism ; Vertebrates/metabolism ; }, abstract = {In multicellular organisms, development is based in part on the integration of communication systems. Two neuroendocrine axes, the hypothalamic-pituitary-thyroid and the hypothalamic-pituitary-adrenal/interrenal axes, are central players in orchestrating body morphogenesis. In all vertebrates, the hypothalamic-pituitary-thyroid axis controls thyroid hormone production and release, whereas the hypothalamic-pituitary-adrenal/interrenal axis regulates the production and release of corticosteroids. One of the most salient effects of thyroid hormones and corticosteroids in post-embryonic developmental processes is their critical role in metamorphosis in anuran amphibians. Metamorphosis involves modifications to the morphological and biochemical characteristics of all larval tissues to enable the transition from one life stage to the next life stage that coincides with an ecological niche switch. This transition in amphibians is an example of a widespread phenomenon among vertebrates, where thyroid hormones and corticosteroids coordinate a post-embryonic developmental transition. The review addresses the functions and interactions of thyroid hormone and corticosteroid signaling in amphibian development (metamorphosis) as well as the developmental roles of these two pathways in vertebrate evolution.}, } @article {pmid35621103, year = {2022}, author = {Puzakov, MV and Puzakova, LV}, title = {[Prevalence, Diversity, and Evolution of L18 (DD37E) Transposons in the Genomes of Cnidarians].}, journal = {Molekuliarnaia biologiia}, volume = {56}, number = {3}, pages = {476-490}, doi = {10.31857/S0026898422030120}, pmid = {35621103}, issn = {0026-8984}, mesh = {Animals ; *Cnidaria/genetics ; *DNA Transposable Elements/genetics ; Prevalence ; }, abstract = {Transposable elements have a significant impact on the structure and functioning of multicellular genomes, and also serve as a source of new genes. Studying the diversity and evolution of transposable elements in different taxa is necessary for the fundamental understanding of their role in genomes. The Tc1/mariner elements are one of the most widespread and diverse groups of DNA transposons. In this work, the structure, distribution, diversity, and evolution of the L18 (DD37E) elements in the genomes of cnidarians (Cnidaria) were studied for the first time. As a result, it was found that the L18 group is an independent family (and not a subfamily of the TLE family, as previously thought) in the Tc1/mariner superfamily. Of the 51 detected elements, only four had potentially functional copies. It is assumed that the L18 transposons are of ancient origin, and, in addition, the elements found in the genomes of organisms of the Anthozoa and Hydrozoa classes do not come from a common ancestral transposon within the Cnidaria phylum. In organisms of the Hydrozoa class, L18 transposons appeared as a result of horizontal transfer at a later time period. An intraspecies comparison of the diversity of the L18 elements demonstrates high homogeneity with respect to "old" transposons, which have already lost their activity. At the same time, distant populations, as in the case of Hydra viridissima, have differences in the representation of DNA transposons and the number of copies. These data supplement the knowledge on the diversity and evolution of Tc1/mariner transposons and contribute to the study of the influence of mobile genetic elements on the evolution of multicellular organisms.}, } @article {pmid35588907, year = {2022}, author = {Udayantha, HMV and Samaraweera, AV and Liyanage, DS and Sandamalika, WMG and Lim, C and Yang, H and Lee, JH and Lee, S and Lee, J}, title = {Molecular characterization, antiviral activity, and UV-B damage responses of Caspase-9 from Amphiprion clarkii.}, journal = {Fish & shellfish immunology}, volume = {125}, number = {}, pages = {247-257}, doi = {10.1016/j.fsi.2022.05.023}, pmid = {35588907}, issn = {1095-9947}, mesh = {Animals ; Antiviral Agents ; Caspase 3 ; Caspase 9 ; *Cyprinidae ; *Perciformes ; Phylogeny ; Poly I-C/pharmacology ; }, abstract = {Apoptosis plays a vital role in maintaining cellular homeostasis in multicellular organisms. Caspase-9 (casp-9) is one of the major initiator caspases that induces apoptosis by activating downstream intrinsic apoptosis pathway genes. Here, we isolated the cDNA sequence (1992 bp) of caspase-9 from Amphiprion clarkii (Accasp-9) that consists of a 1305 bp coding region and encodes a 434 aa protein. In silico analysis showed that Accasp-9 has a theoretical isoelectric point of 5.81 and a molecular weight of 48.45 kDa. Multiple sequence alignment revealed that the CARD domain is located at the N-terminus, whereas the large P-20 and small P-10 domains are located at the C-terminus. Moreover, a highly conserved pentapeptide active site ([296]QACGG[301]), as well as histidine and cysteine active sites, are also retained at the C-terminus. In phylogenetic analysis, Accasp-9 formed a clade with casp-9 from different species, distinct from other caspases. Accasp-9 was highly expressed in the gill and intestine compared with other tissues analyzed in healthy A. clarkii. Accasp-9 expression was significantly elevated in the blood after stimulation with Vibrio harveyi and polyinosinic:polycytidylic acid (poly I:C; 12-48 h), but not with lipopolysaccharide. The nucleoprotein expression of the viral hemorrhagic septicemia virus was significantly reduced in Accasp-9 overexpressed fathead minnow (FHM) cells compared with that in the control. In addition, other in vitro assays revealed that cell apoptosis was significantly elevated in poly I:C and UV-B-treated Accasp-9 transfected FHM cells. However, H[248P] or C[298S] mutated Accasp-9 significantly reduced apoptosis in UV-B irradiated cells. Collectively, our results show that Accasp-9 might play a defensive role against invading pathogens and UV-B radiation and H[248] and C[298] active residues are significantly involved in apoptosis in teleosts.}, } @article {pmid35587048, year = {2022}, author = {Gardner, DS and Gray, C}, title = {Development and the art of nutritional maintenance.}, journal = {The British journal of nutrition}, volume = {128}, number = {5}, pages = {828-834}, pmid = {35587048}, issn = {1475-2662}, mesh = {Animals ; Nutritive Value ; *Nutrients ; *Energy Intake ; }, abstract = {Development from early conceptus to a complex, multi-cellular organism is a highly ordered process that is dependent on an adequate supply of nutrients. During this process, the pattern of organ growth is robust, driven by a genetic blueprint and matched to anticipated body mass with high precision and with built-in physiological reserve capacity. This apparent canalisation of the developmental process is particularly sensitive to variation in environmental stimuli, such as inappropriate drug or hormone exposure, or pattern of nutrient delivery. Significant variation in any of these factors can profoundly affect fetal and neonatal growth patterns, with later detriment for physiological function and/or reserve capacity of the resultant adult, with potential health impact. This paradigm shift in science has become known as the Developmental Origins of Health and Disease (DOHaD). Over the last 30 years, many animal and clinical studies have vastly expanded our fundamental knowledge of developmental biology, particularly in the context of later effects on health. In this horizons article, we discuss DOHaD through the lens of nutritional quality (e.g. micronutrient, amino acid, NSP intake). The concept of ‘Quality’ was considered undefinable by Robert Persig in his book, ‘Zen and the Art of Motorcycle Maintenance’. Here, development and the art of nutritional maintenance will define quality in terms of the pattern of nutrient intake, the quality of development and how each interact to influence later health outcomes.}, } @article {pmid35574025, year = {2022}, author = {Ritch, SJ and Telleria, CM}, title = {The Transcoelomic Ecosystem and Epithelial Ovarian Cancer Dissemination.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {886533}, pmid = {35574025}, issn = {1664-2392}, mesh = {Carcinoma, Ovarian Epithelial ; *Ecosystem ; Epithelial Cells/metabolism ; Female ; Humans ; Neoplasm Recurrence, Local ; *Ovarian Neoplasms/therapy ; Tumor Microenvironment ; }, abstract = {Epithelial ovarian cancer (EOC) is considered the deadliest gynecological disease and is normally diagnosed at late stages, at which point metastasis has already occurred. Throughout disease progression, EOC will encounter various ecosystems and the communication between cancer cells and these microenvironments will promote the survival and dissemination of EOC. The primary tumor is thought to develop within the ovaries or the fallopian tubes, both of which provide a microenvironment with high risk of causing DNA damage and enhanced proliferation. EOC disseminates by direct extension from the primary tumors, as single cells or multicellular aggregates. Under the influence of cellular and non-cellular factors, EOC spheroids use the natural flow of peritoneal fluid to reach distant organs within the peritoneal cavity. These cells can then implant and seed distant organs or tissues, which develop rapidly into secondary tumor nodules. The peritoneal tissue and the omentum are two common sites of EOC metastasis, providing a microenvironment that supports EOC invasion and survival. Current treatment for EOC involves debulking surgery followed by platinum-taxane combination chemotherapy; however, most patients will relapse with a chemoresistant disease with tumors developed within the peritoneum. Therefore, understanding the role of the unique microenvironments that promote EOC transcoelomic dissemination is important in improving patient outcomes from this disease. In this review article, we address the process of ovarian cancer cellular fate at the site of its origin in the secretory cells of the fallopian tube or in the ovarian surface epithelial cells, their detachment process, how the cells survive in the peritoneal fluid avoiding cell death triggers, and how cancer- associated cells help them in the process. Finally, we report the mechanisms used by the ovarian cancer cells to adhere and migrate through the mesothelial monolayer lining the peritoneum. We also discuss the involvement of the transcoelomic ecosystem on the development of chemoresistance of EOC.}, } @article {pmid35572413, year = {2022}, author = {Zhang, J and Shen, N and Li, C and Xiang, X and Liu, G and Gui, Y and Patev, S and Hibbett, DS and Barry, K and Andreopoulos, W and Lipzen, A and Riley, R and He, G and Yan, M and Grigoriev, IV and Shan Kwan, H and Kit Cheung, M and Bian, Y and Xiao, Y}, title = {Population genomics provides insights into the genetic basis of adaptive evolution in the mushroom-forming fungus Lentinula edodes.}, journal = {Journal of advanced research}, volume = {38}, number = {}, pages = {91-106}, pmid = {35572413}, issn = {2090-1224}, mesh = {*Agaricales/genetics ; Genome ; Genome-Wide Association Study ; Metagenomics ; *Shiitake Mushrooms/genetics ; }, abstract = {INTRODUCTION: Mushroom-forming fungi comprise diverse species that develop complex multicellular structures. In cultivated species, both ecological adaptation and artificial selection have driven genome evolution. However, little is known about the connections among genotype, phenotype and adaptation in mushroom-forming fungi.

OBJECTIVES: This study aimed to (1) uncover the population structure and demographic history of Lentinula edodes, (2) dissect the genetic basis of adaptive evolution in L. edodes, and (3) determine if genes related to fruiting body development are involved in adaptive evolution.

METHODS: We analyzed genomes and fruiting body-related traits (FBRTs) in 133 L. edodes strains and conducted RNA-seq analysis of fruiting body development in the YS69 strain. Combined methods of genomic scan for divergence, genome-wide association studies (GWAS), and RNA-seq were used to dissect the genetic basis of adaptive evolution.

RESULTS: We detected three distinct subgroups of L. edodes via single nucleotide polymorphisms, which showed robust phenotypic and temperature response differentiation and correlation with geographical distribution. Demographic history inference suggests that the subgroups diverged 36,871 generations ago. Moreover, L. edodes cultivars in China may have originated from the vicinity of Northeast China. A total of 942 genes were found to be related to genetic divergence by genomic scan, and 719 genes were identified to be candidates underlying FBRTs by GWAS. Integrating results of genomic scan and GWAS, 80 genes were detected to be related to phenotypic differentiation. A total of 364 genes related to fruiting body development were involved in genetic divergence and phenotypic differentiation.

CONCLUSION: Adaptation to the local environment, especially temperature, triggered genetic divergence and phenotypic differentiation of L. edodes. A general model for genetic divergence and phenotypic differentiation during adaptive evolution in L. edodes, which involves in signal perception and transduction, transcriptional regulation, and fruiting body morphogenesis, was also integrated here.}, } @article {pmid35570706, year = {2022}, author = {Heinz, MC and Peters, NA and Oost, KC and Lindeboom, RGH and van Voorthuijsen, L and Fumagalli, A and van der Net, MC and de Medeiros, G and Hageman, JH and Verlaan-Klink, I and Borel Rinkes, IHM and Liberali, P and Gloerich, M and van Rheenen, J and Vermeulen, M and Kranenburg, O and Snippert, HJG}, title = {Liver Colonization by Colorectal Cancer Metastases Requires YAP-Controlled Plasticity at the Micrometastatic Stage.}, journal = {Cancer research}, volume = {82}, number = {10}, pages = {1953-1968}, pmid = {35570706}, issn = {1538-7445}, mesh = {Animals ; *Colorectal Neoplasms/pathology ; Humans ; *Liver Neoplasms/metabolism ; Mice ; Neoplasm Micrometastasis/pathology ; Neoplastic Stem Cells/pathology ; }, abstract = {UNLABELLED: Micrometastases of colorectal cancer can remain dormant for years prior to the formation of actively growing, clinically detectable lesions (i.e., colonization). A better understanding of this step in the metastatic cascade could help improve metastasis prevention and treatment. Here we analyzed liver specimens of patients with colorectal cancer and monitored real-time metastasis formation in mouse livers using intravital microscopy to reveal that micrometastatic lesions are devoid of cancer stem cells (CSC). However, lesions that grow into overt metastases demonstrated appearance of de novo CSCs through cellular plasticity at a multicellular stage. Clonal outgrowth of patient-derived colorectal cancer organoids phenocopied the cellular and transcriptomic changes observed during in vivo metastasis formation. First, formation of mature CSCs occurred at a multicellular stage and promoted growth. Conversely, failure of immature CSCs to generate more differentiated cells arrested growth, implying that cellular heterogeneity is required for continuous growth. Second, early-stage YAP activity was required for the survival of organoid-forming cells. However, subsequent attenuation of early-stage YAP activity was essential to allow for the formation of cell type heterogeneity, while persistent YAP signaling locked micro-organoids in a cellularly homogenous and growth-stalled state. Analysis of metastasis formation in mouse livers using single-cell RNA sequencing confirmed the transient presence of early-stage YAP activity, followed by emergence of CSC and non-CSC phenotypes, irrespective of the initial phenotype of the metastatic cell of origin. Thus, establishment of cellular heterogeneity after an initial YAP-controlled outgrowth phase marks the transition to continuously growing macrometastases.

SIGNIFICANCE: Characterization of the cell type dynamics, composition, and transcriptome of early colorectal cancer liver metastases reveals that failure to establish cellular heterogeneity through YAP-controlled epithelial self-organization prohibits the outgrowth of micrometastases. See related commentary by LeBleu, p. 1870.}, } @article {pmid35563757, year = {2022}, author = {Stange, K and Keric, A and Friese, A and Röntgen, M}, title = {Preparation of Spheroids from Primary Pig Cells in a Mid-Scale Bioreactor Retaining Their Myogenic Potential.}, journal = {Cells}, volume = {11}, number = {9}, pages = {}, pmid = {35563757}, issn = {2073-4409}, mesh = {Animals ; Bioreactors ; Cell Differentiation ; *Muscle Development ; *Muscle Fibers, Skeletal ; Swine ; }, abstract = {Three-dimensional cell culture techniques mimic the in vivo cell environment more adequately than flat surfaces. Spheroids are multicellular aggregates and we aimed to produce scaffold-free spheroids of myogenic origin, called myospheres, using a mid-scale incubator and bioreactor hybrid. For the first time, we obtained spheroids from primary porcine muscle cells (PMCs) with this technology and compared their morphology and growth parameters, marker expression, and myogenic potential to C2C12-derived spheroids. Both cell types were able to form round-shaped spheroids in the bioreactor already after 24 h. The mean diameter of the C2C12 spheroids (44.6 µm) was larger than that of the PMCs (32.7 µm), and the maximum diameter exceeded 1 mm. C2C12 cells formed less aggregates than PMCs with a higher packing density (cell nuclei/mm[2]). After dissociation from the spheroids, C2C12 cells and PMCs started to proliferate again and were able to differentiate into the myogenic lineage, as shown by myotube formation and the expression of F-Actin, Desmin, MyoG, and Myosin. For C2C12, multinucleated syncytia and Myosin expression were observed in spheroids, pointing to accelerated myogenic differentiation. In conclusion, the mid-scale incubator and bioreactor system is suitable for spheroid formation and cultivation from primary muscle cells while preserving their myogenic potential.}, } @article {pmid35551578, year = {2022}, author = {Eskandari, E and Eaves, CJ}, title = {Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis.}, journal = {The Journal of cell biology}, volume = {221}, number = {6}, pages = {}, pmid = {35551578}, issn = {1540-8140}, support = {21296//Canadian Cancer Society Research Institute/ ; //University of British Columbia/ ; }, mesh = {Apoptosis/genetics ; *Carcinogenesis/genetics ; *Caspase 3/physiology ; *Cell Proliferation ; *Cell Survival/genetics ; Humans ; Saccharomyces cerevisiae ; }, abstract = {Caspase-3 is a widely expressed member of a conserved family of proteins, generally recognized for their activated proteolytic roles in the execution of apoptosis in cells responding to specific extrinsic or intrinsic inducers of this mode of cell death. However, accumulating evidence indicates that caspase-3 also plays key roles in regulating the growth and homeostatic maintenance of both normal and malignant cells and tissues in multicellular organisms. Given that yeast possess an ancestral caspase-like gene suggests that the caspase-3 protein may have acquired different functions later during evolution to better meet the needs of more complex multicellular organisms, but without necessarily losing all of the functions of its ancestral yeast precursor. This review provides an update on what has been learned about these interesting dichotomous roles of caspase-3, their evolution, and their potential relevance to malignant as well as normal cell biology.}, } @article {pmid35530508, year = {2022}, author = {de la Fuente, M and Novo, M}, title = {Understanding Diversity, Evolution, and Structure of Small Heat Shock Proteins in Annelida Through in Silico Analyses.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {817272}, pmid = {35530508}, issn = {1664-042X}, abstract = {Small heat shock proteins (sHsps) are oligomeric stress proteins characterized by an α-crystallin domain (ACD). These proteins are localized in different subcellular compartments and play critical roles in the stress physiology of tissues, organs, and whole multicellular eukaryotes. They are ubiquitous proteins found in all living organisms, from bacteria to mammals, but they have never been studied in annelids. Here, a data set of 23 species spanning the annelid tree of life, including mostly transcriptomes but also two genomes, was interrogated and 228 novel putative sHsps were identified and manually curated. The analysis revealed very high protein diversity and showed that a significant number of sHsps have a particular dimeric architecture consisting of two tandemly repeated ACDs. The phylogenetic analysis distinguished three main clusters, two of them containing both monomeric sHsps, and ACDs located downstream in the dimeric sHsps, and the other one comprising the upstream ACDs from those dimeric forms. Our results support an evolutionary history of these proteins based on duplication events prior to the Spiralia split. Monomeric sHsps 76) were further divided into five subclusters. Physicochemical properties, subcellular location predictions, and sequence conservation analyses provided insights into the differentiating elements of these putative functional groups. Strikingly, three of those subclusters included sHsps with features typical of metazoans, while the other two presented characteristics resembling non-metazoan proteins. This study provides a solid background for further research on the diversity, evolution, and function in the family of the sHsps. The characterized annelid sHsps are disclosed as essential for improving our understanding of this important family of proteins and their pleotropic functions. The features and the great diversity of annelid sHsps position them as potential powerful molecular biomarkers of environmental stress for acting as prognostic tool in a diverse range of environments.}, } @article {pmid35514085, year = {2022}, author = {Yuan, F and Wang, X and Zhao, B and Xu, X and Shi, M and Leng, B and Dong, X and Lu, C and Feng, Z and Guo, J and Han, G and Zhang, H and Huang, J and Chen, M and Wang, BS}, title = {The genome of the recretohalophyte Limonium bicolor provides insights into salt gland development and salinity adaptation during terrestrial evolution.}, journal = {Molecular plant}, volume = {15}, number = {6}, pages = {1024-1044}, doi = {10.1016/j.molp.2022.04.011}, pmid = {35514085}, issn = {1752-9867}, mesh = {Animals ; *Arabidopsis ; Plant Leaves/genetics ; *Plumbaginaceae/genetics ; Salinity ; Salt Gland ; Salt Tolerance/genetics ; Salt-Tolerant Plants/genetics ; }, abstract = {Halophytes have evolved specialized strategies to cope with high salinity. The extreme halophyte sea lavender (Limonium bicolor) lacks trichomes but possesses salt glands on its epidermis that can excrete harmful ions, such as sodium, to avoid salt damage. Here, we report a high-quality, 2.92-Gb, chromosome-scale L. bicolor genome assembly based on a combination of Illumina short reads, single-molecule, real-time long reads, chromosome conformation capture (Hi-C) data, and Bionano genome maps, greatly enriching the genomic information on recretohalophytes with multicellular salt glands. Although the L. bicolor genome contains genes that show similarity to trichome fate genes from Arabidopsis thaliana, it lacks homologs of the decision fate genes GLABRA3, ENHANCER OF GLABRA3, GLABRA2, TRANSPARENT TESTA GLABRA2, and SIAMESE, providing a molecular explanation for the absence of trichomes in this species. We identified key genes (LbHLH and LbTTG1) controlling salt gland development among classical trichome homologous genes and confirmed their roles by showing that their mutations markedly disrupted salt gland initiation, salt secretion, and salt tolerance, thus offering genetic support for the long-standing hypothesis that salt glands and trichomes may share a common origin. In addition, a whole-genome duplication event occurred in the L. bicolor genome after its divergence from Tartary buckwheat and may have contributed to its adaptation to high salinity. The L. bicolor genome resource and genetic evidence reported in this study provide profound insights into plant salt tolerance mechanisms that may facilitate the engineering of salt-tolerant crops.}, } @article {pmid35504284, year = {2022}, author = {Reyes-Rivera, J and Wu, Y and Guthrie, BGH and Marletta, MA and King, N and Brunet, T}, title = {Nitric oxide signaling controls collective contractions in a colonial choanoflagellate.}, journal = {Current biology : CB}, volume = {32}, number = {11}, pages = {2539-2547.e5}, doi = {10.1016/j.cub.2022.04.017}, pmid = {35504284}, issn = {1879-0445}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 GM127854/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Choanoflagellata/metabolism ; Cyclic GMP/metabolism ; Guanylate Cyclase/genetics ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/genetics/metabolism ; Signal Transduction/physiology ; }, abstract = {Although signaling by the gaseous molecule nitric oxide (NO) regulates key physiological processes in animals, including contractility,[1-3] immunity,[4][,][5] development,[6-9] and locomotion,[10][,][11] the early evolution of animal NO signaling remains unclear. To reconstruct the role of NO in the animal stem lineage, we set out to study NO signaling in choanoflagellates, the closest living relatives of animals.[12] In animals, NO produced by the nitric oxide synthase (NOS) canonically signals through cGMP by activating soluble guanylate cyclases (sGCs).[13][,][14] We surveyed the distribution of the NO signaling pathway components across the diversity of choanoflagellates and found three species that express NOS (of either bacterial or eukaryotic origin), sGCs, and downstream genes previously shown to be involved in the NO/cGMP pathway. One of the species coexpressing sGCs and a bacterial-type NOS, Choanoeca flexa, forms multicellular sheets that undergo collective contractions controlled by cGMP.[15] We found that treatment with NO induces cGMP synthesis and contraction in C. flexa. Biochemical assays show that NO directly binds C. flexa sGC1 and stimulates its cyclase activity. The NO/cGMP pathway acts independently from other inducers of C. flexa contraction, including mechanical stimuli and heat, but sGC activity is required for contractions induced by light-to-dark transitions. The output of NO signaling in C. flexa-contractions resulting in a switch from feeding to swimming-resembles the effect of NO in sponges[1-3] and cnidarians,[11][,][16][,][17] where it interrupts feeding and activates contractility. These data provide insights into the biology of the first animals and the evolution of NO signaling.}, } @article {pmid35486699, year = {2022}, author = {Staps, M and Tarnita, CE}, title = {When being flexible matters: Ecological underpinnings for the evolution of collective flexibility and task allocation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {18}, pages = {e2116066119}, pmid = {35486699}, issn = {1091-6490}, mesh = {Animals ; Ants ; *Behavior, Animal ; *Biological Evolution ; Ecology ; Humans ; *Social Behavior ; }, abstract = {Task allocation is a central feature of collective organization. Living collective systems, such as multicellular organisms or social insect colonies, have evolved diverse ways to allocate individuals to different tasks, ranging from rigid, inflexible task allocation that is not adjusted to changing circumstances to more fluid, flexible task allocation that is rapidly adjusted to the external environment. While the mechanisms underlying task allocation have been intensely studied, it remains poorly understood whether differences in the flexibility of task allocation can be viewed as adaptive responses to different ecological contexts—for example, different degrees of temporal variability. Motivated by this question, we develop an analytically tractable mathematical framework to explore the evolution of task allocation in dynamic environments. We find that collective flexibility is not necessarily always adaptive, and fails to evolve in environments that change too slowly (relative to how long tasks can be left unattended) or too quickly (relative to how rapidly task allocation can be adjusted). We further employ the framework to investigate how environmental variability impacts the internal organization of task allocation, which allows us to propose adaptive explanations for some puzzling empirical observations, such as seemingly unnecessary task switching under constant environmental conditions, apparent task specialization without efficiency benefits, and high levels of individual inactivity. Altogether, this work provides a general framework for probing the evolved diversity of task allocation strategies in nature and reinforces the idea that considering a system’s ecology is crucial to explaining its collective organization.}, } @article {pmid35484218, year = {2022}, author = {Farkas, Z and Kovács, K and Sarkadi, Z and Kalapis, D and Fekete, G and Birtyik, F and Ayaydin, F and Molnár, C and Horváth, P and Pál, C and Papp, B}, title = {Gene loss and compensatory evolution promotes the emergence of morphological novelties in budding yeast.}, journal = {Nature ecology & evolution}, volume = {6}, number = {6}, pages = {763-773}, pmid = {35484218}, issn = {2397-334X}, support = {098016/Z/11/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Mutation ; Phenotype ; Saccharomyces cerevisiae/genetics ; *Saccharomycetales/genetics ; }, abstract = {Deleterious mutations are generally considered to be irrelevant for morphological evolution. However, they could be compensated by conditionally beneficial mutations, thereby providing access to new adaptive paths. Here we use high-dimensional phenotyping of laboratory-evolved budding yeast lineages to demonstrate that new cellular morphologies emerge exceptionally rapidly as a by-product of gene loss and subsequent compensatory evolution. Unexpectedly, the capacities for invasive growth, multicellular aggregation and biofilm formation also spontaneously evolve in response to gene loss. These multicellular phenotypes can be achieved by diverse mutational routes and without reactivating the canonical regulatory pathways. These ecologically and clinically relevant traits originate as pleiotropic side effects of compensatory evolution and have no obvious utility in the laboratory environment. The extent of morphological diversity in the evolved lineages is comparable to that of natural yeast isolates with diverse genetic backgrounds and lifestyles. Finally, we show that both the initial gene loss and subsequent compensatory mutations contribute to new morphologies, with their synergistic effects underlying specific morphological changes. We conclude that compensatory evolution is a previously unrecognized source of morphological diversity and phenotypic novelties.}, } @article {pmid35483597, year = {2022}, author = {Wang, B and Zhu, F and Shi, Z and Huang, Z and Sun, R and Wang, Q and Ouyang, G and Ji, W}, title = {Molecular characteristics, polymorphism and expression analysis of mhc Ⅱ in yellow catfish(pelteobagrus fulvidraco)responding to Flavobacterium columnare infection.}, journal = {Fish & shellfish immunology}, volume = {125}, number = {}, pages = {90-100}, doi = {10.1016/j.fsi.2022.04.036}, pmid = {35483597}, issn = {1095-9947}, mesh = {Animals ; *Catfishes ; Fish Proteins/chemistry ; Flavobacterium/genetics ; Phylogeny ; RNA, Messenger/metabolism ; }, abstract = {The major histocompatibility complex (MHC) is an important component of the immune system of vertebrates, which plays a vital role in presenting extrinsic antigens. In this study, we cloned and characterized the mhc ⅡA and mhc ⅡB genes of yellow catfish Pelteobagrus fulvidraco. The open reading frames (ORFs) of mhc ⅡA and mhc ⅡB genes were 708 bp and 747bp in length, encoding 235 and 248 amino acids, respectively. The structure of mhc ⅡA and mhc ⅡB includes a signal peptide, an α1/β1 domain, an α2/β2 domain, a transmembrane region and a cytoplasmic region. Homologous identity analysis revealed that both mhc ⅡA and mhc ⅡB shared high protein sequence similarity with that of Chinese longsnout catfish Leiocassis longirostris. mhc ⅡA and mhc ⅡB showed similar expression patterns in different tissues, with the higher expression level in spleen, head kidney and gill and lower expression in liver, stomach, gall bladder and heart. The mRNA expression level of mhc ⅡA and mhc ⅡB in different embryonic development stages also showed the similar trends. The higher expression was detected from fertilized egg to 32 cell stage, low expression from multicellular period to 3 days post hatching (dph), and then the expression increased to a higher level from 4 dph to 14 dph. The mRNA expression levels of mhc ⅡA and mhc ⅡB were significantly up-regulated not only in the body kidney and spleen, but also in the midgut, hindgut, liver and gill after challenge of Flavobacterium columnare. The results suggest that Mhc Ⅱ plays an important role in the anti-infection process of yellow catfish P. fulvidraco.}, } @article {pmid35472432, year = {2022}, author = {Chaigne, A and Brunet, T}, title = {Incomplete abscission and cytoplasmic bridges in the evolution of eukaryotic multicellularity.}, journal = {Current biology : CB}, volume = {32}, number = {8}, pages = {R385-R397}, doi = {10.1016/j.cub.2022.03.021}, pmid = {35472432}, issn = {1879-0445}, support = {201334/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Biological Evolution ; Cytoplasm ; Cytosol ; *Eukaryota ; Eukaryotic Cells ; }, abstract = {The textbook view of cell division terminates with the final separation of the two daughter cells in the process called abscission. However, in contrast to this classical view, a variety of cell types in multicellular organisms are connected through cytoplasmic bridges, which most often form by incomplete abscission or - more rarely - by local fusion of plasma membranes. In this review, we survey the distribution, function, and formation of cytoplasmic bridges across the eukaryotic tree of life. We find that cytoplasmic bridges are widespread, and were likely ancestrally present, in almost all lineages of eukaryotes with clonal multicellularity - including the five 'complex multicellular' lineages: animals, fungi, land plants, red algae, and brown algae. In animals, cytoplasmic bridges resulting from incomplete abscission are ubiquitous in the germline and common in pluripotent cell types. Although cytoplasmic bridges have been less studied than other structural mediators of multicellularity (such as adhesion proteins and extracellular matrix), we propose that they have played a pivotal role in the repeated evolution of eukaryotic clonal multicellularity - possibly by first performing a structural role and later by allowing exchange of nutrients and/or intercellular communication, which notably buffered cell-cell competition by averaging gene expression. Bridges were eventually lost from many animal tissues in concert with the evolution of spatial cell differentiation, cell motility within the organism, and other mechanisms for intercellular distribution of signals and metabolites. Finally, we discuss the molecular basis for the evolution of incomplete abscission and examine the alternative hypotheses of single or multiple origins.}, } @article {pmid35470227, year = {2022}, author = {Mulcahey, PJ and Chen, Y and Driscoll, N and Murphy, BB and Dickens, OO and Johnson, ATC and Vitale, F and Takano, H}, title = {Multimodal, Multiscale Insights into Hippocampal Seizures Enabled by Transparent, Graphene-Based Microelectrode Arrays.}, journal = {eNeuro}, volume = {9}, number = {3}, pages = {}, pmid = {35470227}, issn = {2373-2822}, support = {R21 NS106434/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Epilepsy, Temporal Lobe ; *Graphite ; Hippocampus ; Mice ; Microelectrodes ; Seizures ; }, abstract = {Hippocampal seizures are a defining feature of mesial temporal lobe epilepsy (MTLE). Area CA1 of the hippocampus is commonly implicated in the generation of seizures, which may occur because of the activity of endogenous cell populations or of inputs from other regions within the hippocampal formation. Simultaneously observing activity at the cellular and network scales in vivo remains challenging. Here, we present a novel technology for simultaneous electrophysiology and multicellular calcium imaging of CA1 pyramidal cells (PCs) in mice enabled by a transparent graphene-based microelectrode array (Gr MEA). We examine PC firing at seizure onset, oscillatory coupling, and the dynamics of the seizure traveling wave as seizures evolve. Finally, we couple features derived from both modalities to predict the speed of the traveling wave using bootstrap aggregated regression trees. Analysis of the most important features in the regression trees suggests a transition among states in the evolution of hippocampal seizures.}, } @article {pmid35468249, year = {2022}, author = {Melnikov, NP and Bolshakov, FV and Frolova, VS and Skorentseva, KV and Ereskovsky, AV and Saidova, AA and Lavrov, AI}, title = {Tissue homeostasis in sponges: Quantitative analysis of cell proliferation and apoptosis.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {338}, number = {6}, pages = {360-381}, doi = {10.1002/jez.b.23138}, pmid = {35468249}, issn = {1552-5015}, support = {19-04-00545//Russian Foundation for Basic Research/ ; 19-04-00563//Russian Foundation for Basic Research/ ; MK-1096.2021.1.4//Fund of President of the Russian Federation/ ; 17-14-01089//Russian Science Foundation/ ; }, mesh = {Animals ; *Apoptosis ; Cell Proliferation ; Homeostasis ; *Signal Transduction ; }, abstract = {Tissues of multicellular animals are maintained due to a tight balance between cell proliferation and programmed cell death. Sponges are early branching metazoans essential to understanding the key mechanisms of tissue homeostasis. This article is dedicated to the comparative analysis of proliferation and apoptosis in intact tissues of two sponges, Halisarca dujardinii (class Demospongiae) and Leucosolenia variabilis (class Calcarea). Labeled nucleotides EdU and anti-phosphorylated histone 3 antibodies reveal a considerable number of cycling cells in intact tissues of both species. Quantitative DNA staining reveals the classic cell cycle distribution curve. The main type of cycling cells are choanocytes - flagellated cells of the aquiferous system. The rate of proliferation remains constant throughout various areas of sponge bodies that contain choanocytes. The EdU tracking experiments conducted in H. dujardinii indicate that choanocytes may give rise to mesohyl cells through migration. The number of apoptotic cells in tissues of both species is insignificant, although being comparable to the renewing tissues of other animals. In vivo studies with tetramethylrhodamine ethyl ester and CellEvent Caspase-3/7 indicate that apoptosis might be independent of mitochondrial outer membrane permeabilization. Altogether, a combination of confocal laser scanning microscopy and flow cytometry provides a quantitative description of cell proliferation and apoptosis in sponges displaying either rapid growth or cell turnover.}, } @article {pmid35421922, year = {2022}, author = {Nozaki, H and Mori, F and Tanaka, Y and Matsuzaki, R and Yamaguchi, H and Kawachi, M}, title = {Cryopreservation of vegetative cells and zygotes of the multicellular volvocine green alga Gonium pectorale.}, journal = {BMC microbiology}, volume = {22}, number = {1}, pages = {103}, pmid = {35421922}, issn = {1471-2180}, mesh = {*Chlorophyta ; Cryopreservation ; Nitrogen ; Phylogeny ; *Zygote ; }, abstract = {BACKGROUND: Colonial and multicellular volvocine green algae have been extensively studied recently in various fields of the biological sciences. However, only one species (Pandorina morum) has been cryopreserved in public culture collections.

RESULTS: Here, we investigated conditions for cryopreservation of the multicellular volvocine alga Gonium pectorale using vegetative colonies or cells and zygotes. Rates of vegetative cell survival in a G. pectorale strain after two-step cooling and freezing in liquid nitrogen were compared between different concentrations (3% and 6%) of the cryoprotectant N,N-dimethylformamide (DMF) and two types of tubes (0.2-mL polymerase chain reaction tubes and 2-mL cryotubes) used for cryopreservation. Among the four conditions investigated, the highest rate of survival [2.7 ± 3.6% (0.54-10%) by the most probable number (MPN) method] was obtained when 2.0-mL cryotubes containing 1.0 mL of culture samples with 6% DMF were subjected to cryogenic treatment. Using these optimized cryopreservation conditions, survival rates after freezing in liquid nitrogen were examined for twelve other strains of G. pectorale and twelve strains of five other Gonium species. We obtained ≥ 0.1% MPN survival in nine of the twelve G. pectorale strains tested. However, < 0.1% MPN survival was detected in eleven of twelve strains of five other Gonium species. In total, ten cryopreserved strains of G. pectorale were newly established in the Microbial Culture Collection at the National Institute for Environmental Studies. Although the cryopreservation of zygotes of volvocine algae has not been previously reported, high rates (approximately 60%) of G. pectorale zygote germination were observed after thawing zygotes that had been cryopreserved with 5% or 10% methanol as the cryoprotectant during two-step cooling and freezing in liquid nitrogen.

CONCLUSIONS: The present study demonstrated that cryopreservation of G. pectorale is possible with 6% DMF as a cryoprotectant and 1.0-mL culture samples in 2.0-mL cryotubes subjected to two-step cooling in a programmable freezer.}, } @article {pmid35420439, year = {2022}, author = {Rohkin Shalom, S and Weiss, B and Lalzar, M and Kaltenpoth, M and Chiel, E}, title = {Abundance and Localization of Symbiotic Bacterial Communities in the Fly Parasitoid Spalangia cameroni.}, journal = {Applied and environmental microbiology}, volume = {88}, number = {9}, pages = {e0254921}, pmid = {35420439}, issn = {1098-5336}, mesh = {Animals ; Enterobacteriaceae/genetics ; Female ; *Gammaproteobacteria ; In Situ Hybridization, Fluorescence ; Male ; *Rickettsia/genetics ; Symbiosis/physiology ; *Wasps/microbiology ; *Wolbachia/physiology ; }, abstract = {Multicellular eukaryotes often host multiple microbial symbionts that may cooperate or compete for host resources, such as space and nutrients. Here, we studied the abundances and localization of four bacterial symbionts, Rickettsia, Wolbachia, Sodalis, and Arsenophonus, in the parasitic wasp Spalangia cameroni. Using quantitative PCR (qPCR), we measured the symbionts' titers in wasps that harbor different combinations of these symbionts. We found that the titer of each symbiont decreased as the number of symbiont species in the community increased. Symbionts' titers were higher in females than in males. Rickettsia was the most abundant symbiont in all the communities, followed by Sodalis and Wolbachia. The titers of these three symbionts were positively correlated in some of the colonies. Fluorescence in situ hybridization was in line with the qPCR results: Rickettsia, Wolbachia, and Sodalis were observed in high densities in multiple organs, including brain, muscles, gut, Malpighian tubules, fat body, ovaries, and testes, while Arsenophonus was localized to fewer organs and in lower densities. Sodalis and Arsenophonus were observed in ovarian follicle cells but not within oocytes or laid eggs. This study highlights the connection between symbionts' abundance and localization. We discuss the possible connections between our findings to symbiont transmission success. IMPORTANCE Many insects carry intracellular bacterial symbionts (bacteria that reside within the cells of the insect). When multiple symbiont species cohabit in a host, they may compete or cooperate for space, nutrients, and transmission, and the nature of such interactions would be reflected in the abundance of each symbiont species. Given the widespread occurrence of coinfections with maternally transmitted symbionts in insects, it is important to learn more about how they interact, where they are localized, and how these two aspects affect their co-occurrence within individual insects. Here, we studied the abundance and the localization of four symbionts, Rickettsia, Wolbachia, Sodalis, and Arsenophonus, that cohabit the parasitic wasp Spalangia cameroni. We found that symbionts' titers differed between symbiotic communities. These results were corroborated by microscopy, which shows differential localization patterns. We discuss the findings in the contexts of community ecology, possible symbiont-symbiont interactions, and host control mechanisms that may shape the symbiotic community structure.}, } @article {pmid35417559, year = {2022}, author = {Kambayashi, C and Kakehashi, R and Sato, Y and Mizuno, H and Tanabe, H and Rakotoarison, A and Künzel, S and Furuno, N and Ohshima, K and Kumazawa, Y and Nagy, ZT and Mori, A and Allison, A and Donnellan, SC and Ota, H and Hoso, M and Yanagida, T and Sato, H and Vences, M and Kurabayashi, A}, title = {Geography-Dependent Horizontal Gene Transfer from Vertebrate Predators to Their Prey.}, journal = {Molecular biology and evolution}, volume = {39}, number = {4}, pages = {}, pmid = {35417559}, issn = {1537-1719}, mesh = {Animals ; Cattle ; *Gene Transfer, Horizontal ; Geography ; *Parasites/genetics ; Phylogeny ; Predatory Behavior ; Retroelements ; Vertebrates/genetics ; }, abstract = {Horizontal transfer (HT) of genes between multicellular animals, once thought to be extremely rare, is being more commonly detected, but its global geographic trend and transfer mechanism have not been investigated. We discovered a unique HT pattern of Bovine-B (BovB) LINE retrotransposons in vertebrates, with a bizarre transfer direction from predators (snakes) to their prey (frogs). At least 54 instances of BovB HT were detected, which we estimate to have occurred across time between 85 and 1.3 Ma. Using comprehensive transcontinental sampling, our study demonstrates that BovB HT is highly prevalent in one geographical region, Madagascar, suggesting important regional differences in the occurrence of HTs. We discovered parasite vectors that may plausibly transmit BovB and found that the proportion of BovB-positive parasites is also high in Madagascar where BovB thus might be physically transported by parasites to diverse vertebrates, potentially including humans. Remarkably, in two frog lineages, BovB HT occurred after migration from a non-HT area (Africa) to the HT hotspot (Madagascar). These results provide a novel perspective on how the prevalence of parasites influences the occurrence of HT in a region, similar to pathogens and their vectors in some endemic diseases.}, } @article {pmid35409376, year = {2022}, author = {Kasperski, A}, title = {Life Entrapped in a Network of Atavistic Attractors: How to Find a Rescue.}, journal = {International journal of molecular sciences}, volume = {23}, number = {7}, pages = {}, pmid = {35409376}, issn = {1422-0067}, mesh = {Cell Physiological Phenomena ; Cell Transformation, Neoplastic/metabolism ; *Energy Metabolism ; Humans ; Mitochondria/metabolism ; *Neoplasms/metabolism ; }, abstract = {In view of unified cell bioenergetics, cell bioenergetic problems related to cell overenergization can cause excessive disturbances in current cell fate and, as a result, lead to a change of cell-fate. At the onset of the problem, cell overenergization of multicellular organisms (especially overenergization of mitochondria) is solved inter alia by activation and then stimulation of the reversible Crabtree effect by cells. Unfortunately, this apparently good solution can also lead to a much bigger problem when, despite the activation of the Crabtree effect, cell overenergization persists for a long time. In such a case, cancer transformation, along with the Warburg effect, may occur to further reduce or stop the charging of mitochondria by high-energy molecules. Understanding the phenomena of cancer transformation and cancer development has become a real challenge for humanity. To date, many models have been developed to understand cancer-related mechanisms. Nowadays, combining all these models into one coherent universal model of cancer transformation and development can be considered a new challenge. In this light, the aim of this article is to present such a potentially universal model supported by a proposed new model of cellular functionality evolution. The methods of fighting cancer resulting from unified cell bioenergetics and the two presented models are also considered.}, } @article {pmid35406795, year = {2022}, author = {Zschüntzsch, J and Meyer, S and Shahriyari, M and Kummer, K and Schmidt, M and Kummer, S and Tiburcy, M}, title = {The Evolution of Complex Muscle Cell In Vitro Models to Study Pathomechanisms and Drug Development of Neuromuscular Disease.}, journal = {Cells}, volume = {11}, number = {7}, pages = {}, pmid = {35406795}, issn = {2073-4409}, mesh = {Coculture Techniques ; Drug Development ; Humans ; Muscle Cells ; *Neuromuscular Diseases/drug therapy ; *Organoids ; }, abstract = {Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine. By concentrating on idiopathic inflammatory muscle disorders, we summarize the recent evolution of the novel in vitro models to study disease mechanisms and therapeutic strategies. A particular focus is laid on the integration and simulation of multicellular interactions of muscle tissue in disease phenotypes in vitro. Finally, the requirements of a neuromuscular disease drug development workflow are discussed with a particular emphasis on cell sources, co-culture systems (including organoids), functionality, and throughput.}, } @article {pmid35396623, year = {2023}, author = {Koide, RT}, title = {On Holobionts, Holospecies, and Holoniches: the Role of Microbial Symbioses in Ecology and Evolution.}, journal = {Microbial ecology}, volume = {85}, number = {4}, pages = {1143-1149}, pmid = {35396623}, issn = {1432-184X}, mesh = {Phylogeny ; *Symbiosis ; *Adaptation, Physiological ; Eukaryota ; Biological Evolution ; }, abstract = {My goal in writing this is to increase awareness of the roles played by microbial symbionts in eukaryote ecology and evolution. Most eukaryotes host one or more species of symbiotic microorganisms, including prokaryotes and fungi. Many of these have profound impacts on the biology of their hosts. For example, microbial symbionts may expand the niches of their hosts, cause rapid adaptation of the host to the environment and re-adaptation to novel conditions via symbiont swapping, facilitate speciation, and fundamentally alter our concept of the species. In some cases, microbial symbionts and multicellular eukaryote hosts have a mutual dependency, which has obvious conservation implications. Hopefully, this contribution will stimulate a reevaluation of important ecological and evolutionary concepts including niche, adaptation, the species, speciation, and conservation of multicellular eukaryotes.}, } @article {pmid35359304, year = {2022}, author = {Ramon-Mateu, J and Edgar, A and Mitchell, D and Martindale, MQ}, title = {Studying Ctenophora WBR Using Mnemiopsis leidyi.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2450}, number = {}, pages = {95-119}, pmid = {35359304}, issn = {1940-6029}, mesh = {Animals ; Cell Lineage ; *Ctenophora/genetics ; Genome ; Phylogeny ; }, abstract = {Ctenophores, also known as comb jellies, are a clade of fragile holopelagic, carnivorous marine invertebrates, that represent one of the most ancient extant groups of multicellular animals. Ctenophores show a remarkable ability to regenerate in the adult form, being capable of replacing all body parts (i.e., whole-body regeneration) after loss/amputation. With many favorable experimental features (optical clarity, stereotyped cell lineage, multiple cell types), a full genome sequence available and their early branching phylogenetic position, ctenophores are well placed to provide information about the evolution of regenerative ability throughout the Metazoa. Here, we provide a collection of detailed protocols for use of the lobate ctenophore Mnemiopsis leidyi to study whole-body regeneration, including specimen collection, husbandry, surgical manipulation, and imaging techniques.}, } @article {pmid35358607, year = {2022}, author = {Shapiro, JA}, title = {What we have learned about evolutionary genome change in the past 7 decades.}, journal = {Bio Systems}, volume = {215-216}, number = {}, pages = {104669}, doi = {10.1016/j.biosystems.2022.104669}, pmid = {35358607}, issn = {1872-8324}, mesh = {Animals ; *Biological Evolution ; *DNA Transposable Elements/genetics ; Eukaryota/genetics ; Evolution, Molecular ; Genomics ; Hybridization, Genetic ; }, abstract = {Cytogenetics and genomics have completely transformed our understanding of evolutionary genome change since the early 1950s. The point of this paper is to outline some of the empirical findings responsible for that transformation. The discovery of transposable elements (TEs) in maize by McClintock, and their subsequent rediscovery in all forms of life, tell us that organisms have the inherent capacity to evolve dispersed genomic networks encoding complex cellular and multicellular adaptations. Genomic analysis confirms the role of TEs in wiring novel networks at major evolutionary transitions. TEs and other forms of repetitive DNA are also important contributors to genome regions that serve as transcriptional templates for regulatory and other biologically functional noncoding ncRNAs. The many functions documented for ncRNAs shows the concept of abundant "selfish" or "junk" DNA in complex genomes is mistaken. Natural and artificial speciation by interspecific hybridization demonstrates that TEs and other biochemical systems of genome restructuring are subject to rapid activation and can generate changes throughout the genomes of the novel species that emerge. In addition to TEs and hybrid species, cancer cells have taught us important lessons about chromothripsis, chromoplexy and other forms of non-random multisite genome restructuring. In many of these restructured genomes, alternative end-joining processes display the capacities of eukaryotes to generate novel combinations of templated and untemplated DNA sequences at the sites of break repair. Sequence innovation by alternative end-joining is widespread among eukaryotes from single cells to advanced plants and animals. In sum, the cellular and genomic capacities of eukaryotic cells have proven to be capable of executing rapid macroevolutionary change under a variety of conditions.}, } @article {pmid35353805, year = {2022}, author = {Burnetti, A and Ratcliff, WC}, title = {Experimental evolution is not just for model organisms.}, journal = {PLoS biology}, volume = {20}, number = {3}, pages = {e3001587}, pmid = {35353805}, issn = {1545-7885}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; }, abstract = {In a new paper published in PLOS Biology, Dudin and colleagues evolve simple multicellularity in Sphaeroforma arctica, a unicellular relative of animals. This work establishes a new and open-ended avenue for examining the evolution of multicellularity in an important but understudied group of organisms.}, } @article {pmid35349792, year = {2022}, author = {Toret, C and Picco, A and Boiero-Sanders, M and Michelot, A and Kaksonen, M}, title = {The cellular slime mold Fonticula alba forms a dynamic, multicellular collective while feeding on bacteria.}, journal = {Current biology : CB}, volume = {32}, number = {9}, pages = {1961-1973.e4}, pmid = {35349792}, issn = {1879-0445}, mesh = {Animals ; Bacteria ; *Dictyosteliida ; Eukaryota ; Fungi ; Phylogeny ; }, abstract = {Multicellularity evolved in fungi and animals, or the opisthokonts, from their common amoeboflagellate ancestor but resulted in strikingly distinct cellular organizations. The origins of this multicellularity divergence are not known. The stark mechanistic differences that underlie the two groups and the lack of information about ancestral cellular organizations limits progress in this field. We discovered a new type of invasive multicellular behavior in Fonticula alba, a unique species in the opisthokont tree, which has a simple, bacteria-feeding sorocarpic amoeba lifestyle. This invasive multicellularity follows germination dependent on the bacterial culture state, after which amoebae coalesce to form dynamic collectives that invade virgin bacterial resources. This bacteria-dependent social behavior emerges from amoeba density and allows for rapid and directed invasion. The motile collectives have animal-like properties but also hyphal-like search and invasive behavior. These surprising findings enrich the diverse multicellularities present within the opisthokont lineage and offer a new perspective on fungal origins.}, } @article {pmid35349578, year = {2022}, author = {Dudin, O and Wielgoss, S and New, AM and Ruiz-Trillo, I}, title = {Regulation of sedimentation rate shapes the evolution of multicellularity in a close unicellular relative of animals.}, journal = {PLoS biology}, volume = {20}, number = {3}, pages = {e3001551}, pmid = {35349578}, issn = {1545-7885}, mesh = {Animals ; Cell Size ; *Cytokinesis ; Phenotype ; }, abstract = {Significant increases in sedimentation rate accompany the evolution of multicellularity. These increases should lead to rapid changes in ecological distribution, thereby affecting the costs and benefits of multicellularity and its likelihood to evolve. However, how genetic and cellular traits control this process, their likelihood of emergence over evolutionary timescales, and the variation in these traits as multicellularity evolves are still poorly understood. Here, using isolates of the ichthyosporean genus Sphaeroforma-close unicellular relatives of animals with brief transient multicellular life stages-we demonstrate that sedimentation rate is a highly variable and evolvable trait affected by at least 2 distinct physical mechanisms. First, we find extensive (>300×) variation in sedimentation rates for different Sphaeroforma species, mainly driven by size and density during the unicellular-to-multicellular life cycle transition. Second, using experimental evolution with sedimentation rate as a focal trait, we readily obtained, for the first time, fast settling and multicellular Sphaeroforma arctica isolates. Quantitative microscopy showed that increased sedimentation rates most often arose by incomplete cellular separation after cell division, leading to clonal "clumping" multicellular variants with increased size and density. Strikingly, density increases also arose by an acceleration of the nuclear doubling time relative to cell size. Similar size- and density-affecting phenotypes were observed in 4 additional species from the Sphaeroforma genus, suggesting that variation in these traits might be widespread in the marine habitat. By resequencing evolved isolates to high genomic coverage, we identified mutations in regulators of cytokinesis, plasma membrane remodeling, and chromatin condensation that may contribute to both clump formation and the increase in the nuclear number-to-volume ratio. Taken together, this study illustrates how extensive cellular control of density and size drive sedimentation rate variation, likely shaping the onset and further evolution of multicellularity.}, } @article {pmid35337467, year = {2022}, author = {Booth, DS and King, N}, title = {The history of Salpingoeca rosetta as a model for reconstructing animal origins.}, journal = {Current topics in developmental biology}, volume = {147}, number = {}, pages = {73-91}, doi = {10.1016/bs.ctdb.2022.01.001}, pmid = {35337467}, issn = {1557-8933}, mesh = {Animals ; *Choanoflagellata/genetics ; Developmental Biology ; }, abstract = {Choanoflagellates, the closest living relatives of animals, have the potential to reveal the genetic and cell biological foundations of complex multicellular development in animals. Here we describe the history of research on the choanoflagellate Salpingoeca rosetta. From its original isolation in 2000 to the establishment of CRISPR-mediated genome editing in 2020, S. rosetta provides an instructive case study in the establishment of a new model organism.}, } @article {pmid35318703, year = {2022}, author = {Hammond, M and Dorrell, RG and Speijer, D and Lukeš, J}, title = {Eukaryotic cellular intricacies shape mitochondrial proteomic complexity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {44}, number = {5}, pages = {e2100258}, doi = {10.1002/bies.202100258}, pmid = {35318703}, issn = {1521-1878}, mesh = {Biological Evolution ; Eukaryota/physiology ; *Eukaryotic Cells/metabolism ; Mitochondria/metabolism ; Organelles/metabolism ; Phylogeny ; *Proteomics ; }, abstract = {Mitochondria have been fundamental to the eco-physiological success of eukaryotes since the last eukaryotic common ancestor (LECA). They contribute essential functions to eukaryotic cells, above and beyond classical respiration. Mitochondria interact with, and complement, metabolic pathways occurring in other organelles, notably diversifying the chloroplast metabolism of photosynthetic organisms. Here, we integrate existing literature to investigate how mitochondrial metabolism varies across the landscape of eukaryotic evolution. We illustrate the mitochondrial remodelling and proteomic changes undergone in conjunction with major evolutionary transitions. We explore how the mitochondrial complexity of the LECA has been remodelled in specific groups to support subsequent evolutionary transitions, such as the acquisition of chloroplasts in photosynthetic species and the emergence of multicellularity. We highlight the versatile and crucial roles played by mitochondria during eukaryotic evolution, extending from its huge contribution to the development of the LECA itself to the dynamic evolution of individual eukaryote groups, reflecting both their current ecologies and evolutionary histories.}, } @article {pmid35317961, year = {2023}, author = {Bogaert, KA and Zakka, EE and Coelho, SM and De Clerck, O}, title = {Polarization of brown algal zygotes.}, journal = {Seminars in cell & developmental biology}, volume = {134}, number = {}, pages = {90-102}, doi = {10.1016/j.semcdb.2022.03.008}, pmid = {35317961}, issn = {1096-3634}, mesh = {Animals ; Zygote ; *Arabidopsis ; *Phaeophyceae/genetics/metabolism ; Cell Polarity ; Cell Division ; Plants ; }, abstract = {Brown algae are a group of multicellular, heterokont algae that have convergently evolved developmental complexity that rivals that of embryophytes, animals or fungi. Early in development, brown algal zygotes establish a basal and an apical pole, which will become respectively the basal system (holdfast) and the apical system (thallus) of the adult alga. Brown algae are interesting models for understanding the establishment of cell polarity in a broad evolutionary context, because they exhibit a large diversity of life cycles, reproductive strategies and, importantly, their zygotes are produced in large quantities free of parental tissue, with symmetry breaking and asymmetric division taking place in a highly synchronous manner. This review describes the current knowledge about the establishment of the apical-basal axis in the model brown seaweeds Ectocarpus, Dictyota, Fucus and Saccharina, highlighting the advantages and specific interests of each system. Ectocarpus is a genetic model system that allows access to the molecular basis of early development and life-cycle control over apical-basal polarity. The oogamous brown alga Fucus, together with emerging comparative models Dictyota and Saccharina, emphasize the diversity of strategies of symmetry breaking in determining a cell polarity vector in brown algae. A comparison with symmetry-breaking mechanisms in land plants, animals and fungi, reveals that the one-step zygote polarisation of Fucus compares well to Saccharomyces budding and Arabidopsis stomata development, while the two-phased symmetry breaking in the Dictyota zygote compares to Schizosaccharomyces fission, the Caenorhabditis anterior-posterior zygote polarisation and Arabidopsis prolate pollen polarisation. The apical-basal patterning in Saccharina zygotes on the other hand, may be seen as analogous to that of land plants. Overall, brown algae have the potential to bring exciting new information on how a single cell gives rise to an entire complex body plan.}, } @article {pmid35311270, year = {2022}, author = {Chen, C and Wang, P and Chen, H and Wang, X and Halgamuge, MN and Chen, C and Song, T}, title = {Smart Magnetotactic Bacteria Enable the Inhibition of Neuroblastoma under an Alternating Magnetic Field.}, journal = {ACS applied materials & interfaces}, volume = {14}, number = {12}, pages = {14049-14058}, doi = {10.1021/acsami.1c24154}, pmid = {35311270}, issn = {1944-8252}, mesh = {Animals ; *Hyperthermia, Induced ; Magnetic Fields ; *Magnetosomes/metabolism ; Mice ; Mice, Nude ; *Neuroblastoma/metabolism/therapy ; }, abstract = {Magnetotactic bacteria are ubiquitous microorganisms in nature that synthesize intracellular magnetic nanoparticles called magnetosomes in a gene-controlled way and arrange them in chains. From in vitro to in vivo, we demonstrate that the intact body of Magnetospirillum magneticum AMB-1 has potential as a natural magnetic hyperthermia material for cancer therapy. Compared to chains of magnetosomes and individual magnetosomes, the entire AMB-1 cell exhibits superior heating capability under an alternating magnetic field. When incubating with tumor cells, the intact AMB-1 cells disperse better than the other two types of magnetosomes, decreasing cellular viability under the control of an alternating magnetic field. Furthermore, in vivo experiments in nude mice with neuroblastoma found that intact AMB-1 cells had the best antitumor activity with magnetic hyperthermia therapy compared to other treatment groups. These findings suggest that the intact body of magnetotactic bacteria has enormous promise as a natural material for tumor magnetic hyperthermia. In biomedical applications, intact and living magnetotactic bacteria play an increasingly essential function as a targeting robot due to their magnetotaxis.}, } @article {pmid35295942, year = {2022}, author = {Jiménez-Marín, B and Olson, BJSC}, title = {The Curious Case of Multicellularity in the Volvocine Algae.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {787665}, pmid = {35295942}, issn = {1664-8021}, abstract = {The evolution of multicellularity is a major evolutionary transition that underlies the radiation of many species in all domains of life, especially in eukaryotes. The volvocine green algae are an unconventional model system that holds great promise in the field given its genetic tractability, late transition to multicellularity, and phenotypic diversity. Multiple efforts at linking multicellularity-related developmental landmarks to key molecular changes, especially at the genome level, have provided key insights into the molecular innovations or lack thereof that underlie multicellularity. Twelve developmental changes have been proposed to explain the evolution of complex differentiated multicellularity in the volvocine algae. Co-option of key genes, such as cell cycle and developmental regulators has been observed, but with few exceptions, known co-option events do not seem to coincide with most developmental features observed in multicellular volvocines. The apparent lack of "master multicellularity genes" combined with no apparent correlation between gene gains for developmental processes suggest the possibility that many multicellular traits might be the product gene-regulatory and functional innovations; in other words, multicellularity can arise from shared genomic repertoires that undergo regulatory and functional overhauls.}, } @article {pmid35251134, year = {2022}, author = {Palazzo, AF and Kejiou, NS}, title = {Non-Darwinian Molecular Biology.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {831068}, pmid = {35251134}, issn = {1664-8021}, abstract = {With the discovery of the double helical structure of DNA, a shift occurred in how biologists investigated questions surrounding cellular processes, such as protein synthesis. Instead of viewing biological activity through the lens of chemical reactions, this new field used biological information to gain a new profound view of how biological systems work. Molecular biologists asked new types of questions that would have been inconceivable to the older generation of researchers, such as how cellular machineries convert inherited biological information into functional molecules like proteins. This new focus on biological information also gave molecular biologists a way to link their findings to concepts developed by genetics and the modern synthesis. However, by the late 1960s this all changed. Elevated rates of mutation, unsustainable genetic loads, and high levels of variation in populations, challenged Darwinian evolution, a central tenant of the modern synthesis, where adaptation was the main driver of evolutionary change. Building on these findings, Motoo Kimura advanced the neutral theory of molecular evolution, which advocates that selection in multicellular eukaryotes is weak and that most genomic changes are neutral and due to random drift. This was further elaborated by Jack King and Thomas Jukes, in their paper "Non-Darwinian Evolution", where they pointed out that the observed changes seen in proteins and the types of polymorphisms observed in populations only become understandable when we take into account biochemistry and Kimura's new theory. Fifty years later, most molecular biologists remain unaware of these fundamental advances. Their adaptionist viewpoint fails to explain data collected from new powerful technologies which can detect exceedingly rare biochemical events. For example, high throughput sequencing routinely detects RNA transcripts being produced from almost the entire genome yet are present less than one copy per thousand cells and appear to lack any function. Molecular biologists must now reincorporate ideas from classical biochemistry and absorb modern concepts from molecular evolution, to craft a new lens through which they can evaluate the functionality of transcriptional units, and make sense of our messy, intricate, and complicated genome.}, } @article {pmid35246710, year = {2022}, author = {Frenkel-Pinter, M and Petrov, AS and Matange, K and Travisano, M and Glass, JB and Williams, LD}, title = {Adaptation and Exaptation: From Small Molecules to Feathers.}, journal = {Journal of molecular evolution}, volume = {90}, number = {2}, pages = {166-175}, pmid = {35246710}, issn = {1432-1432}, support = {80NSSC18K1139/ImNASA/Intramural NASA/United States ; }, mesh = {Acclimatization ; *Adaptation, Physiological/genetics ; Animals ; Biological Evolution ; *Feathers ; }, abstract = {Evolution works by adaptation and exaptation. At an organismal level, exaptation and adaptation are seen in the formation of organelles and the advent of multicellularity. At the sub-organismal level, molecular systems such as proteins and RNAs readily undergo adaptation and exaptation. Here we suggest that the concepts of adaptation and exaptation are universal, synergistic, and recursive and apply to small molecules such as metabolites, cofactors, and the building blocks of extant polymers. For example, adenosine has been extensively adapted and exapted throughout biological evolution. Chemical variants of adenosine that are products of adaptation include 2' deoxyadenosine in DNA and a wide array of modified forms in mRNAs, tRNAs, rRNAs, and viral RNAs. Adenosine and its variants have been extensively exapted for various functions, including informational polymers (RNA, DNA), energy storage (ATP), metabolism (e.g., coenzyme A), and signaling (cyclic AMP). According to Gould, Vrba, and Darwin, exaptation imposes a general constraint on interpretation of history and origins; because of exaptation, extant function should not be used to explain evolutionary history. While this notion is accepted in evolutionary biology, it can also guide the study of the chemical origins of life. We propose that (i) evolutionary theory is broadly applicable from the dawn of life to the present time from molecules to organisms, (ii) exaptation and adaptation were important and simultaneous processes, and (iii) robust origin of life models can be constructed without conflating extant utility with historical basis of origins.}, } @article {pmid35235070, year = {2022}, author = {Kwantes, M and Wichard, T}, title = {The APAF1_C/WD40 repeat domain-encoding gene from the sea lettuce Ulva mutabilis sheds light on the evolution of NB-ARC domain-containing proteins in green plants.}, journal = {Planta}, volume = {255}, number = {4}, pages = {76}, pmid = {35235070}, issn = {1432-2048}, support = {SFB 1127/2 ChemBioSys//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Ecosystem ; Phylogeny ; Plant Proteins/metabolism ; Proteins/genetics ; *Ulva/genetics ; WD40 Repeats ; }, abstract = {We advance Ulva's genetic tractability and highlight its value as a model organism by characterizing its APAF1_C/WD40 domain-encoding gene, which belongs to a family that bears homology to R genes. The multicellular chlorophyte alga Ulva mutabilis (Ulvophyceae, Ulvales) is native to coastal ecosystems worldwide and attracts both high socio-economic and scientific interest. To further understand the genetic mechanisms that guide its biology, we present a protocol, based on adapter ligation-mediated PCR, for retrieving flanking sequences in U. mutabilis vector-insertion mutants. In the created insertional library, we identified a null mutant with an insertion in an apoptotic protease activating factor 1 helical domain (APAF1_C)/WD40 repeat domain-encoding gene. Protein domain architecture analysis combined with phylogenetic analysis revealed that this gene is a member of a subfamily that arose early in the evolution of green plants (Viridiplantae) through the acquisition of a gene that also encoded N-terminal nucleotide-binding adaptor shared by APAF-1, certain R-gene products and CED-4 (NB-ARC) and winged helix-like (WH-like) DNA-binding domains. Although phenotypic analysis revealed no mutant phenotype, gene expression levels in control plants correlated to the presence of bacterial symbionts, which U. mutabilis requires for proper morphogenesis. In addition, our analysis led to the discovery of a putative Ulva nucleotide-binding site and leucine-rich repeat (NBS-LRR) Resistance protein (R-protein), and we discuss how the emergence of these R proteins in green plants may be linked to the evolution of the APAF1_C/WD40 protein subfamily.}, } @article {pmid35218347, year = {2022}, author = {Spang, A and Mahendrarajah, TA and Offre, P and Stairs, CW}, title = {Evolving Perspective on the Origin and Diversification of Cellular Life and the Virosphere.}, journal = {Genome biology and evolution}, volume = {14}, number = {6}, pages = {}, pmid = {35218347}, issn = {1759-6653}, mesh = {*Archaea ; Biological Evolution ; Eukaryota ; Phylogeny ; *Viruses/genetics ; }, abstract = {The tree of life (TOL) is a powerful framework to depict the evolutionary history of cellular organisms through time, from our microbial origins to the diversification of multicellular eukaryotes that shape the visible biosphere today. During the past decades, our perception of the TOL has fundamentally changed, in part, due to profound methodological advances, which allowed a more objective approach to studying organismal and viral diversity and led to the discovery of major new branches in the TOL as well as viral lineages. Phylogenetic and comparative genomics analyses of these data have, among others, revolutionized our understanding of the deep roots and diversity of microbial life, the origin of the eukaryotic cell, eukaryotic diversity, as well as the origin, and diversification of viruses. In this review, we provide an overview of some of the recent discoveries on the evolutionary history of cellular organisms and their viruses and discuss a variety of complementary techniques that we consider crucial for making further progress in our understanding of the TOL and its interconnection with the virosphere.}, } @article {pmid35205423, year = {2022}, author = {Alfieri, JM and Wang, G and Jonika, MM and Gill, CA and Blackmon, H and Athrey, GN}, title = {A Primer for Single-Cell Sequencing in Non-Model Organisms.}, journal = {Genes}, volume = {13}, number = {2}, pages = {}, pmid = {35205423}, issn = {2073-4425}, support = {R35 GM138098/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Genotype ; *Phenotype ; }, abstract = {Single-cell sequencing technologies have led to a revolution in our knowledge of the diversity of cell types, connections between biological levels of organization, and relationships between genotype and phenotype. These advances have mainly come from using model organisms; however, using single-cell sequencing in non-model organisms could enable investigations of questions inaccessible with typical model organisms. This primer describes a general workflow for single-cell sequencing studies and considerations for using non-model organisms (limited to multicellular animals). Importantly, single-cell sequencing, when further applied in non-model organisms, will allow for a deeper understanding of the mechanisms between genotype and phenotype and the basis for biological variation.}, } @article {pmid35194081, year = {2022}, author = {Lin, HK and Cheng, JH and Wu, CC and Hsieh, FS and Dunlap, C and Chen, SH}, title = {Functional buffering via cell-specific gene expression promotes tissue homeostasis and cancer robustness.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {2974}, pmid = {35194081}, issn = {2045-2322}, mesh = {*Databases, Nucleic Acid ; *Gene Expression Regulation, Neoplastic ; *Homeostasis ; Humans ; *Neoplasms/genetics/metabolism ; Organ Specificity ; }, abstract = {Functional buffering that ensures biological robustness is critical for maintaining tissue homeostasis, organismal survival, and evolution of novelty. However, the mechanism underlying functional buffering, particularly in multicellular organisms, remains largely elusive. Here, we proposed that functional buffering can be mediated via expression of buffering genes in specific cells and tissues, by which we named Cell-specific Expression-BUffering (CEBU). We developed an inference index (C-score) for CEBU by computing C-scores across 684 human cell lines using genome-wide CRISPR screens and transcriptomic RNA-seq. We report that C-score-identified putative buffering gene pairs are enriched for members of the same duplicated gene family, pathway, and protein complex. Furthermore, CEBU is especially prevalent in tissues of low regenerative capacity (e.g., bone and neuronal tissues) and is weakest in highly regenerative blood cells, linking functional buffering to tissue regeneration. Clinically, the buffering capacity enabled by CEBU can help predict patient survival for multiple cancers. Our results suggest CEBU as a potential buffering mechanism contributing to tissue homeostasis and cancer robustness in humans.}, } @article {pmid35189700, year = {2022}, author = {Simon-Soro, A and Ren, Z and Krom, BP and Hoogenkamp, MA and Cabello-Yeves, PJ and Daniel, SG and Bittinger, K and Tomas, I and Koo, H and Mira, A}, title = {Polymicrobial Aggregates in Human Saliva Build the Oral Biofilm.}, journal = {mBio}, volume = {13}, number = {1}, pages = {e0013122}, pmid = {35189700}, issn = {2150-7511}, support = {R01 DE025220/DE/NIDCR NIH HHS/United States ; 834.13.006//NWO Earth and Life Sciences (ALW)/ ; BIO2015-68711-R//Spanish Ministry of Economy and Competitiveness/ ; }, mesh = {Bacteria ; Biofilms ; *Ecosystem ; Humans ; Phylogeny ; *Saliva/microbiology ; }, abstract = {Biofilm community development has been established as a sequential process starting from the attachment of single cells on a surface. However, microorganisms are often found as aggregates in the environment and in biological fluids. Here, we conduct a comprehensive analysis of the native structure and composition of aggregated microbial assemblages in human saliva and investigate their spatiotemporal attachment and biofilm community development. Using multiscale imaging, cell sorting, and computational approaches combined with sequencing analysis, a diverse mixture of aggregates varying in size, structure, and microbial composition, including bacteria associated with host epithelial cells, can be found in saliva in addition to a few single-cell forms. Phylogenetic analysis reveals a mixture of complex consortia of aerobes and anaerobes in which bacteria traditionally considered early and late colonizers are found mixed together. When individually tracked during colonization and biofilm initiation, aggregates rapidly proliferate and expand tridimensionally, modulating population growth, spatial organization, and community scaffolding. In contrast, most single cells remain static or are incorporated by actively growing aggregates. These results suggest an alternative biofilm development process whereby aggregates containing different species or associated with human cells collectively adhere to the surface as "growth nuclei" to build the biofilm and shape polymicrobial communities at various spatial and taxonomic scales. IMPORTANCE Microbes in biological fluids can be found as aggregates. How these multicellular structures bind to surfaces and initiate the biofilm life cycle remains understudied. Here, we investigate the structural organization of microbial aggregates in human saliva and their role in biofilm formation. We found diverse mixtures of aggregates with different sizes, structures, and compositions in addition to free-living cells. When individually tracked during binding and growth on tooth-like surfaces, most aggregates developed into structured biofilm communities, whereas most single cells remained static or were engulfed by the growing aggregates. Our results reveal that preformed microbial consortia adhere as "buds of growth," governing biofilm initiation without specific taxonomic order or cell-by-cell succession, which provide new insights into spatial and population heterogeneity development in complex ecosystems.}, } @article {pmid35188101, year = {2022}, author = {Day, TC and Höhn, SS and Zamani-Dahaj, SA and Yanni, D and Burnetti, A and Pentz, J and Honerkamp-Smith, AR and Wioland, H and Sleath, HR and Ratcliff, WC and Goldstein, RE and Yunker, PJ}, title = {Cellular organization in lab-evolved and extant multicellular species obeys a maximum entropy law.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35188101}, issn = {2050-084X}, support = {/WT_/Wellcome Trust/United Kingdom ; 207510/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; R35 GM138030/GM/NIGMS NIH HHS/United States ; R35 GM138354/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Size ; *Directed Molecular Evolution ; Phylogeny ; Volvox/cytology/*genetics/physiology ; Yeasts/cytology/*genetics/physiology ; }, abstract = {The prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth - especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved 'snowflake' yeast and the green alga Volvox carteri. We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This 'entropic' cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing.}, } @article {pmid35186015, year = {2021}, author = {Zeng, Q and Liu, H and Chu, X and Niu, Y and Wang, C and Markov, GV and Teng, L}, title = {Independent Evolution of the MYB Family in Brown Algae.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {811993}, pmid = {35186015}, issn = {1664-8021}, abstract = {Myeloblastosis (MYB) proteins represent one of the largest families of eukaryotic transcription factors and regulate important processes in growth and development. Studies on MYBs have mainly focused on animals and plants; however, comprehensive analysis across other supergroups such as SAR (stramenopiles, alveolates, and rhizarians) is lacking. This study characterized the structure, evolution, and expression of MYBs in four brown algae, which comprise the biggest multicellular lineage of SAR. Subfamily 1R-MYB comprised heterogeneous proteins, with fewer conserved motifs found outside the MYB domain. Unlike the SHAQKY subgroup of plant 1R-MYB, THAQKY comprised the largest subgroup of brown algal 1R-MYBs. Unlike the expansion of 2R-MYBs in plants, brown algae harbored more 3R-MYBs than 2R-MYBs. At least ten 2R-MYBs, fifteen 3R-MYBs, and one 6R-MYB orthologs existed in the common ancestor of brown algae. Phylogenetic analysis showed that brown algal MYBs had ancient origins and a diverged evolution. They showed strong affinity with stramenopile species, while not with red algae, green algae, or animals, suggesting that brown algal MYBs did not come from the secondary endosymbiosis of red and green plastids. Sequence comparison among all repeats of the three types of MYB subfamilies revealed that the repeat of 1R-MYBs showed higher sequence identity with the R3 of 2R-MYBs and 3R-MYBs, which supports the idea that 1R-MYB was derived from loss of the first and second repeats of the ancestor MYB. Compared with other species of SAR, brown algal MYB proteins exhibited a higher proportion of intrinsic disordered regions, which might contribute to multicellular evolution. Expression analysis showed that many MYB genes are responsive to different stress conditions and developmental stages. The evolution and expression analyses provided a comprehensive analysis of the phylogeny and functions of MYBs in brown algae.}, } @article {pmid35167804, year = {2022}, author = {Davis, JR and Ainslie, AP and Williamson, JJ and Ferreira, A and Torres-Sánchez, A and Hoppe, A and Mangione, F and Smith, MB and Martin-Blanco, E and Salbreux, G and Tapon, N}, title = {ECM degradation in the Drosophila abdominal epidermis initiates tissue growth that ceases with rapid cell-cycle exit.}, journal = {Current biology : CB}, volume = {32}, number = {6}, pages = {1285-1300.e4}, pmid = {35167804}, issn = {1879-0445}, support = {FC001175/MRC_/Medical Research Council/United Kingdom ; FC001317/WT_/Wellcome Trust/United Kingdom ; 107885/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; FC001175/WT_/Wellcome Trust/United Kingdom ; FC001175/ARC_/Arthritis Research UK/United Kingdom ; FC001317/ARC_/Arthritis Research UK/United Kingdom ; FC001317/CRUK_/Cancer Research UK/United Kingdom ; 17064/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; FC001317/MRC_/Medical Research Council/United Kingdom ; FC001175/CRUK_/Cancer Research UK/United Kingdom ; 201358/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Cycle ; Cell Division ; *Drosophila ; *Epidermal Cells ; Epidermis ; Mice ; }, abstract = {During development, multicellular organisms undergo stereotypical patterns of tissue growth in space and time. How developmental growth is orchestrated remains unclear, largely due to the difficulty of observing and quantitating this process in a living organism. Drosophila histoblast nests are small clusters of progenitor epithelial cells that undergo extensive growth to give rise to the adult abdominal epidermis and are amenable to live imaging. Our quantitative analysis of histoblast proliferation and tissue mechanics reveals that tissue growth is driven by cell divisions initiated through basal extracellular matrix degradation by matrix metalloproteases secreted by the neighboring larval epidermal cells. Laser ablations and computational simulations show that tissue mechanical tension does not decrease as the histoblasts fill the abdominal epidermal surface. During tissue growth, the histoblasts display oscillatory cell division rates until growth termination occurs through the rapid emergence of G0/G1 arrested cells, rather than a gradual increase in cell-cycle time as observed in other systems such as the Drosophila wing and mouse postnatal epidermis. Different developing tissues can therefore achieve their final size using distinct growth termination strategies. Thus, adult abdominal epidermal development is characterized by changes in the tissue microenvironment and a rapid exit from the cell cycle.}, } @article {pmid35159213, year = {2022}, author = {Ribba, AS and Fraboulet, S and Sadoul, K and Lafanechère, L}, title = {The Role of LIM Kinases during Development: A Lens to Get a Glimpse of Their Implication in Pathologies.}, journal = {Cells}, volume = {11}, number = {3}, pages = {}, pmid = {35159213}, issn = {2073-4409}, support = {R18LAFANECHERE//Ligue contre le Cancer, comité de l'Isère/ ; }, mesh = {Actin Depolymerizing Factors/metabolism ; Animals ; *Lim Kinases/metabolism ; Phosphorylation ; Phylogeny ; *Protein Kinases/metabolism ; }, abstract = {The organization of cell populations within animal tissues is essential for the morphogenesis of organs during development. Cells recognize three-dimensional positions with respect to the whole organism and regulate their cell shape, motility, migration, polarization, growth, differentiation, gene expression and cell death according to extracellular signals. Remodeling of the actin filaments is essential to achieve these cell morphological changes. Cofilin is an important binding protein for these filaments; it increases their elasticity in terms of flexion and torsion and also severs them. The activity of cofilin is spatiotemporally inhibited via phosphorylation by the LIM domain kinases 1 and 2 (LIMK1 and LIMK2). Phylogenetic analysis indicates that the phospho-regulation of cofilin has evolved as a mechanism controlling the reorganization of the actin cytoskeleton during complex multicellular processes, such as those that occur during embryogenesis. In this context, the main objective of this review is to provide an update of the respective role of each of the LIM kinases during embryonic development.}, } @article {pmid35154170, year = {2021}, author = {Žárský, J and Žárský, V and Hanáček, M and Žárský, V}, title = {Cryogenian Glacial Habitats as a Plant Terrestrialisation Cradle - The Origin of the Anydrophytes and Zygnematophyceae Split.}, journal = {Frontiers in plant science}, volume = {12}, number = {}, pages = {735020}, pmid = {35154170}, issn = {1664-462X}, abstract = {For tens of millions of years (Ma), the terrestrial habitats of Snowball Earth during the Cryogenian period (between 720 and 635 Ma before present-Neoproterozoic Era) were possibly dominated by global snow and ice cover up to the equatorial sublimative desert. The most recent time-calibrated phylogenies calibrated not only on plants but on a comprehensive set of eukaryotes indicate that within the Streptophyta, multicellular charophytes (Phragmoplastophyta) evolved in the Mesoproterozoic to the early Neoproterozoic. At the same time, Cryogenian is the time of the likely origin of the common ancestor of Zygnematophyceae and Embryophyta and later, also of the Zygnematophyceae-Embryophyta split. This common ancestor is proposed to be called Anydrophyta; here, we use anydrophytes. Based on the combination of published phylogenomic studies and estimated diversification time comparisons, we deem it highly likely that anydrophytes evolved in response to Cryogenian cooling. Also, later in the Cryogenian, secondary simplification of multicellular anydrophytes and loss of flagella resulted in Zygnematophyceae diversification as an adaptation to the extended cold glacial environment. We propose that the Marinoan geochemically documented expansion of first terrestrial flora has been represented not only by Chlorophyta but also by Streptophyta, including the anydrophytes, and later by Zygnematophyceae, thriving on glacial surfaces until today. It is possible that multicellular early Embryophyta survived in less abundant (possibly relatively warmer) refugia, relying more on mineral substrates, allowing the retention of flagella-based sexuality. The loss of flagella and sexual reproduction by conjugation evolved in Zygnematophyceae and zygomycetous fungi during the Cryogenian in a remarkably convergent way. Thus, we support the concept that the important basal cellular adaptations to terrestrial environments were exapted in streptophyte algae for terrestrialization and propose that this was stimulated by the adaptation to glacial habitats dominating the Cryogenian Snowball Earth. Including the glacial lifestyle when considering the rise of land plants increases the parsimony of connecting different ecological, phylogenetic, and physiological puzzles of the journey from aquatic algae to terrestrial floras.}, } @article {pmid35143488, year = {2022}, author = {Yaguchi, S and Taniguchi, Y and Suzuki, H and Kamata, M and Yaguchi, J}, title = {Planktonic sea urchin larvae change their swimming direction in response to strong photoirradiation.}, journal = {PLoS genetics}, volume = {18}, number = {2}, pages = {e1010033}, pmid = {35143488}, issn = {1553-7404}, mesh = {Animals ; Cilia/metabolism ; Larva/metabolism ; Light ; Locomotion/physiology ; Movement/*physiology ; Muscles/physiology ; Opsins/genetics/metabolism ; Photoreceptor Cells/*metabolism ; Plankton ; Sea Urchins/*metabolism ; }, abstract = {To survive, organisms need to precisely respond to various environmental factors, such as light and gravity. Among these, light is so important for most life on Earth that light-response systems have become extraordinarily developed during evolution, especially in multicellular animals. A combination of photoreceptors, nervous system components, and effectors allows these animals to respond to light stimuli. In most macroscopic animals, muscles function as effectors responding to light, and in some microscopic aquatic animals, cilia play a role. It is likely that the cilia-based response was the first to develop and that it has been substituted by the muscle-based response along with increases in body size. However, although the function of muscle appears prominent, it is poorly understood whether ciliary responses to light are present and/or functional, especially in deuterostomes, because it is possible that these responses are too subtle to be observed, unlike muscle responses. Here, we show that planktonic sea urchin larvae reverse their swimming direction due to the inhibitory effect of light on the cholinergic neuron signaling>forward swimming pathway. We found that strong photoirradiation of larvae that stay on the surface of seawater immediately drives the larvae away from the surface due to backward swimming. When Opsin2, which is expressed in mesenchymal cells in larval arms, is knocked down, the larvae do not show backward swimming under photoirradiation. Although Opsin2-expressing cells are not neuronal cells, immunohistochemical analysis revealed that they directly attach to cholinergic neurons, which are thought to regulate forward swimming. These data indicate that light, through Opsin2, inhibits the activity of cholinergic signaling, which normally promotes larval forward swimming, and that the light-dependent ciliary response is present in deuterostomes. These findings shed light on how light-responsive tissues/organelles have been conserved and diversified during evolution.}, } @article {pmid35135345, year = {2022}, author = {La Richelière, F and Muñoz, G and Guénard, B and Dunn, RR and Economo, EP and Powell, S and Sanders, NJ and Weiser, MD and Abouheif, E and Lessard, JP}, title = {Warm and arid regions of the world are hotspots of superorganism complexity.}, journal = {Proceedings. Biological sciences}, volume = {289}, number = {1968}, pages = {20211899}, pmid = {35135345}, issn = {1471-2954}, mesh = {Animals ; *Ants/genetics ; Desert Climate ; Neurons ; Phenotype ; }, abstract = {Biologists have long been fascinated by the processes that give rise to phenotypic complexity of organisms, yet whether there exist geographical hotspots of phenotypic complexity remains poorly explored. Phenotypic complexity can be readily observed in ant colonies, which are superorganisms with morphologically differentiated queen and worker castes analogous to the germline and soma of multicellular organisms. Several ant species have evolved 'worker polymorphism', where workers in a single colony show quantifiable differences in size and head-to-body scaling. Here, we use 256 754 occurrence points from 8990 ant species to investigate the geography of worker polymorphism. We show that arid regions of the world are the hotspots of superorganism complexity. Tropical savannahs and deserts, which are typically species-poor relative to tropical or even temperate forests, harbour the highest densities of polymorphic ants. We discuss the possible adaptive advantages that worker polymorphism provides in arid environments. Our work may provide a window into the environmental conditions that promote the emergence of highly complex phenotypes.}, } @article {pmid35107212, year = {2023}, author = {Nishizawa, H and Yamanaka, M and Igarashi, K}, title = {Ferroptosis: regulation by competition between NRF2 and BACH1 and propagation of the death signal.}, journal = {The FEBS journal}, volume = {290}, number = {7}, pages = {1688-1704}, doi = {10.1111/febs.16382}, pmid = {35107212}, issn = {1742-4658}, mesh = {Humans ; Basic-Leucine Zipper Transcription Factors/genetics/metabolism ; *Ferroptosis/genetics ; Iron/metabolism ; *Neoplasms ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress ; }, abstract = {Ferroptosis is triggered by a chain of intracellular labile iron-dependent peroxidation of cell membrane phospholipids. Ferroptosis is important not only as a cause of ischaemic and neurodegenerative diseases but also as a mechanism of cancer suppression, and a better understanding of its regulatory mechanism is required. It has become clear that ferroptosis is finely controlled by two oxidative stress-responsive transcription factors, NRF2 (NF-E2-related factor 2) and BACH1 (BTB and CNC homology 1). NRF2 and BACH1 inhibit and promote ferroptosis, respectively, by activating or suppressing the expression of genes in the major regulatory pathways of ferroptosis: intracellular labile iron metabolism, the GSH (glutathione) -GPX4 (glutathione peroxidase 4) pathway and the FSP1 (ferroptosis suppressor protein 1)-CoQ (coenzyme Q) pathway. In addition to this, NRF2 and BACH1 control ferroptosis through the regulation of lipid metabolism and cell differentiation. This multifaceted regulation of ferroptosis by NRF2 and BACH1 is considered to have been acquired during the evolution of multicellular organisms, allowing the utilization of ferroptosis for maintaining homeostasis, including cancer suppression. In terms of cell-cell interaction, it has been revealed that ferroptosis has the property of propagating to surrounding cells along with lipid peroxidation. The regulation of ferroptosis by NRF2 and BACH1 and the propagation phenomenon could be used to realize anticancer cell therapy in the future. In this review, these points will be summarized and discussed.}, } @article {pmid35053310, year = {2022}, author = {Shevyrev, D and Tereshchenko, V and Kozlov, V and Sennikov, S}, title = {Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets.}, journal = {Cells}, volume = {11}, number = {2}, pages = {}, pmid = {35053310}, issn = {2073-4409}, support = {21-75-10089//Russian Science Foundation/ ; }, mesh = {Evolution, Molecular ; Humans ; Peptides/metabolism ; *Phylogeny ; T-Lymphocyte Subsets/*metabolism ; Transcription Factors/*chemistry/classification/*metabolism ; Transcriptome/genetics ; }, abstract = {It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the "calibration" of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system.}, } @article {pmid35051729, year = {2022}, author = {Masqué-Soler, N and Gehrung, M and Kosmidou, C and Li, X and Diwan, I and Rafferty, C and Atabakhsh, E and Markowetz, F and Fitzgerald, RC}, title = {Computational pathology aids derivation of microRNA biomarker signals from Cytosponge samples.}, journal = {EBioMedicine}, volume = {76}, number = {}, pages = {103814}, pmid = {35051729}, issn = {2352-3964}, support = {28290/CRUK_/Cancer Research UK/United Kingdom ; MR/W014122/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Artificial Intelligence ; *Barrett Esophagus/genetics ; Biomarkers/metabolism ; Cross-Sectional Studies ; *Esophageal Neoplasms/diagnosis/genetics/pathology ; Humans ; *MicroRNAs/genetics ; }, abstract = {BACKGROUND: Non-endoscopic cell collection devices combined with biomarkers can detect Barrett's intestinal metaplasia and early oesophageal cancer. However, assays performed on multi-cellular samples lose information about the cell source of the biomarker signal. This cross-sectional study examines whether a bespoke artificial intelligence-based computational pathology tool could ascertain the cellular origin of microRNA biomarkers, to inform interpretation of the disease pathology, and confirm biomarker validity.

METHODS: The microRNA expression profiles of 110 targets were assessed with a custom multiplexed panel in a cohort of 117 individuals with reflux that took a Cytosponge test. A computational pathology tool quantified the amount of columnar epithelium present in pathology slides, and results were correlated with microRNA signals. An independent cohort of 139 Cytosponges, each from an individual patient, was used to validate the findings via qPCR.

FINDINGS: Seventeen microRNAs are upregulated in BE compared to healthy squamous epithelia, of which 13 remain upregulated in dysplasia. A pathway enrichment analysis confirmed association to neoplastic and cell cycle regulation processes. Ten microRNAs positively correlated with columnar epithelium content, with miRNA-192-5p and -194-5p accurately detecting the presence of gastric cells (AUC 0.97 and 0.95). In contrast, miR-196a-5p is confirmed as a specific BE marker.

INTERPRETATION: Computational pathology tools aid accurate cellular attribution of molecular signals. This innovative design with multiplex microRNA coupled with artificial intelligence has led to discovery of a quality control metric suitable for large scale application of the Cytosponge. Similar approaches could aid optimal interpretation of biomarkers for clinical use.

FUNDING: Funded by the NIHR Cambridge Biomedical Research Centre, the Medical Research Council, the Rosetrees and Stoneygate Trusts, and CRUK core grants.}, } @article {pmid39628612, year = {2022}, author = {Durairaj, P and Li, S}, title = {Functional expression and regulation of eukaryotic cytochrome P450 enzymes in surrogate microbial cell factories.}, journal = {Engineering microbiology}, volume = {2}, number = {1}, pages = {100011}, pmid = {39628612}, issn = {2667-3703}, abstract = {Cytochrome P450 (CYP) enzymes play crucial roles during the evolution and diversification of ancestral monocellular eukaryotes into multicellular eukaryotic organisms due to their essential functionalities including catalysis of housekeeping biochemical reactions, synthesis of diverse metabolites, detoxification of xenobiotics, and contribution to environmental adaptation. Eukaryotic CYPs with versatile functionalities are undeniably regarded as promising biocatalysts with great potential for biotechnological, pharmaceutical and chemical industry applications. Nevertheless, the modes of action and the challenges associated with these membrane-bound proteins have hampered the effective utilization of eukaryotic CYPs in a broader range. This review is focused on comprehensive and consolidated approaches to address the core challenges in heterologous expression of membrane-bound eukaryotic CYPs in different surrogate microbial cell factories, aiming to provide key insights for better studies and applications of diverse eukaryotic CYPs in the future. We also highlight the functional significance of the previously underrated cytochrome P450 reductases (CPRs) and provide a rational justification on the progression of CPR from auxiliary redox partner to function modulator in CYP catalysis.}, } @article {pmid35032334, year = {2022}, author = {Nemec-Venza, Z and Madden, C and Stewart, A and Liu, W and Novák, O and Pěnčík, A and Cuming, AC and Kamisugi, Y and Harrison, CJ}, title = {CLAVATA modulates auxin homeostasis and transport to regulate stem cell identity and plant shape in a moss.}, journal = {The New phytologist}, volume = {234}, number = {1}, pages = {149-163}, pmid = {35032334}, issn = {1469-8137}, mesh = {*Arabidopsis Proteins/genetics/metabolism ; *Bryophyta/metabolism ; *Bryopsida/genetics/metabolism ; Gene Expression Regulation, Plant ; Homeostasis ; Indoleacetic Acids/metabolism ; Stem Cells/metabolism ; }, abstract = {The CLAVATA pathway is a key regulator of stem cell function in the multicellular shoot tips of Arabidopsis, where it acts via the WUSCHEL transcription factor to modulate hormone homeostasis. Broad-scale evolutionary comparisons have shown that CLAVATA is a conserved regulator of land plant stem cell function, but CLAVATA acts independently of WUSCHEL-like (WOX) proteins in bryophytes. The relationship between CLAVATA, hormone homeostasis and the evolution of land plant stem cell functions is unknown. Here we show that in the moss, Physcomitrella (Physcomitrium patens), CLAVATA affects stem cell activity by modulating hormone homeostasis. CLAVATA pathway genes are expressed in the tip cells of filamentous tissues, regulating cell identity, filament branching, plant spread and auxin synthesis. The receptor-like kinase PpRPK2 plays the major role, and Pprpk2 mutants have abnormal responses to cytokinin, auxin and auxin transport inhibition, and show reduced expression of PIN auxin transporters. We propose a model whereby PpRPK2 modulates auxin gradients in filaments to determine stem cell identity and overall plant form. Our data indicate that CLAVATA-mediated auxin homeostasis is a fundamental property of plant stem cell function, probably exhibited by the last shared common ancestor of land plants.}, } @article {pmid35018470, year = {2022}, author = {von der Heyde, EL and Hallmann, A}, title = {Molecular and cellular dynamics of early embryonic cell divisions in Volvox carteri.}, journal = {The Plant cell}, volume = {34}, number = {4}, pages = {1326-1353}, pmid = {35018470}, issn = {1532-298X}, mesh = {Animals ; Cell Division/genetics ; *Volvox/genetics ; }, abstract = {Cell division is fundamental to all organisms and the green alga used here exhibits both key animal and plant functions. Specifically, we analyzed the molecular and cellular dynamics of early embryonic divisions of the multicellular green alga Volvox carteri (Chlamydomonadales). Relevant proteins related to mitosis and cytokinesis were identified in silico, the corresponding genes were cloned, fused to yfp, and stably expressed in Volvox, and the tagged proteins were studied by live-cell imaging. We reveal rearrangements of the microtubule cytoskeleton during centrosome separation, spindle formation, establishment of the phycoplast, and generation of previously unknown structures. The centrosomes participate in initiation of spindle formation and determination of spindle orientation. Although the nuclear envelope does not break down during early mitosis, intermixing of cytoplasm and nucleoplasm results in loss of nuclear identity. Finally, we present a model for mitosis in Volvox. Our study reveals enormous dynamics, clarifies spatio-temporal relationships of subcellular structures, and provides insight into the evolution of cell division.}, } @article {pmid35014399, year = {2021}, author = {Klein, S and Distel, LVR and Neuhuber, W}, title = {X-ray Dose-Enhancing Impact of Functionalized Au-Fe3O4 Nanoheterodimers on MCF-7 and A549 Multicellular Tumor Spheroids.}, journal = {ACS applied bio materials}, volume = {4}, number = {4}, pages = {3113-3123}, doi = {10.1021/acsabm.0c01494}, pmid = {35014399}, issn = {2576-6422}, mesh = {Biocompatible Materials/chemistry/*pharmacology ; Cell Survival/drug effects ; Ferric Compounds/chemistry/*pharmacology ; Gold/chemistry/*pharmacology ; Humans ; MCF-7 Cells ; Materials Testing ; Nanoparticles/*chemistry ; Particle Size ; Spheroids, Cellular/*drug effects ; *X-Rays ; }, abstract = {The efficiency of nanoparticle-enhanced radiotherapy was studied by loading MCF-7 and A549 multicellular tumor spheroids (MCTSs) with caffeic acid- and nitrosonium-functionalized Au-Fe3O4 nanoheterodimers (Au-Fe3O4 NHDs). Transmission electron microscope images of MCTS cross-sectional sections visualized the invasion and distribution of the nitrosonium- and caffeic acid-functionalized Au-Fe3O4 NHDs (NO- and CA-NHDs) in the A549 and MCF-7 MCTSs, whereas the iron content of the MCTSs were quantified using the ferrozine assay. The synergistic impact of intracellular NO- and CA-NHDs and X-ray irradiation on the growth dynamics of the A549 and MCF-7 MCTSs was surveyed by monitoring their temporal evolution under a light microscope over a period of 14 days. The emergence of hypoxia during the spheroid growth was followed by detecting the lactate efflux of MCTSs without and with NO- and CA-NHDs. The performance of the NO- and CA-NHDs as X-ray dose-enhancing agents in the A549 and MCF-7 MCTSs was clarified by performing clonogenic cell survival assays and determining the respective dose-modifying factors for X-ray doses of 0, 2, 4, and 6 Gy. The NO- and CA-NHDs were shown to perform as potent X-ray dose-enhancing agents in A549 and MCF-7 MCTSs. Moreover, the CA-NHDs boosted their radio-sensitizing efficacy by inhibiting the lactate efflux as impairing metabolic reprogramming. A synergistic effect on the MCTS destruction was observed for the combination of both NHDs since the surfactants differ in their antitumor effect.}, } @article {pmid35013306, year = {2022}, author = {Sforna, MC and Loron, CC and Demoulin, CF and François, C and Cornet, Y and Lara, YJ and Grolimund, D and Ferreira Sanchez, D and Medjoubi, K and Somogyi, A and Addad, A and Fadel, A and Compère, P and Baudet, D and Brocks, JJ and Javaux, EJ}, title = {Intracellular bound chlorophyll residues identify 1 Gyr-old fossils as eukaryotic algae.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {146}, pmid = {35013306}, issn = {2041-1723}, mesh = {Biological Evolution ; Chlorophyll/*chemistry/history ; Chlorophyta/anatomy & histology/classification/physiology/*ultrastructure ; Coordination Complexes/*chemistry ; Democratic Republic of the Congo ; Ecosystem ; Eukaryotic Cells ; *Fossils ; Geologic Sediments/analysis ; History, Ancient ; Microscopy, Electron, Transmission ; Nickel/chemistry ; Photosynthesis/*physiology ; Phylogeny ; Plant Cells/physiology/ultrastructure ; Tetrapyrroles/chemistry ; X-Ray Absorption Spectroscopy ; }, abstract = {The acquisition of photosynthesis is a fundamental step in the evolution of eukaryotes. However, few phototrophic organisms are unambiguously recognized in the Precambrian record. The in situ detection of metabolic byproducts in individual microfossils is the key for the direct identification of their metabolisms. Here, we report a new integrative methodology using synchrotron-based X-ray fluorescence and absorption. We evidence bound nickel-geoporphyrins moieties in low-grade metamorphic rocks, preserved in situ within cells of a ~1 Gyr-old multicellular eukaryote, Arctacellularia tetragonala. We identify these moieties as chlorophyll derivatives, indicating that A. tetragonala was a phototrophic eukaryote, one of the first unambiguous algae. This new approach, applicable to overmature rocks, creates a strong new proxy to understand the evolution of phototrophy and diversification of early ecosystems.}, } @article {pmid34999783, year = {2022}, author = {Leger, MM and Ros-Rocher, N and Najle, SR and Ruiz-Trillo, I}, title = {Rel/NF-κB Transcription Factors Emerged at the Onset of Opisthokonts.}, journal = {Genome biology and evolution}, volume = {14}, number = {1}, pages = {}, pmid = {34999783}, issn = {1759-6653}, mesh = {Animals ; *Eukaryota/metabolism ; *Evolution, Molecular ; *NF-kappa B/genetics/metabolism ; Transcription Factor RelA/genetics/metabolism ; Transcription Factor RelB/genetics/metabolism ; }, abstract = {The Rel/NF-κB transcription factor family has myriad roles in immunity, development, and differentiation in animals, and was considered a key innovation for animal multicellularity. Rel homology domain-containing proteins were previously hypothesized to have originated in a last common ancestor of animals and some of their closest unicellular relatives. However, key taxa were missing from previous analyses, necessitating a systematic investigation into the distribution and evolution of these proteins. Here, we address this knowledge gap by surveying taxonomically broad data from eukaryotes, with a special emphasis on lineages closely related to animals. We report an earlier origin for Rel/NF-κB proteins than previously described, in the last common ancestor of animals and fungi, and show that even in the sister group to fungi, these proteins contain elements that in animals are necessary for the subcellular regulation of Rel/NF-κB.}, } @article {pmid34998872, year = {2022}, author = {Kulkarni, P and Behal, A and Mohanty, A and Salgia, R and Nedelcu, AM and Uversky, VN}, title = {Co-opting disorder into order: Intrinsically disordered proteins and the early evolution of complex multicellularity.}, journal = {International journal of biological macromolecules}, volume = {201}, number = {}, pages = {29-36}, doi = {10.1016/j.ijbiomac.2021.12.182}, pmid = {34998872}, issn = {1879-0003}, mesh = {*Intrinsically Disordered Proteins ; *Volvox ; }, abstract = {Intrinsically disordered proteins (IDPs) are proteins that lack rigid structures yet play important roles in myriad biological phenomena. A distinguishing feature of IDPs is that they often mediate specific biological outcomes via multivalent weak cooperative interactions with multiple partners. Here, we show that several proteins specifically associated with processes that were key in the evolution of complex multicellularity in the lineage leading to the multicellular green alga Volvox carteri are IDPs. We suggest that, by rewiring cellular protein interaction networks, IDPs facilitated the co-option of ancestral pathways for specialized multicellular functions, underscoring the importance of IDPs in the early evolution of complex multicellularity.}, } @article {pmid34992624, year = {2021}, author = {Hemleben, V and Grierson, D and Borisjuk, N and Volkov, RA and Kovarik, A}, title = {Personal Perspectives on Plant Ribosomal RNA Genes Research: From Precursor-rRNA to Molecular Evolution.}, journal = {Frontiers in plant science}, volume = {12}, number = {}, pages = {797348}, pmid = {34992624}, issn = {1664-462X}, abstract = {The history of rDNA research started almost 90 years ago when the geneticist, Barbara McClintock observed that in interphase nuclei of maize the nucleolus was formed in association with a specific region normally located near the end of a chromosome, which she called the nucleolar organizer region (NOR). Cytologists in the twentieth century recognized the nucleolus as a common structure in all eukaryotic cells, using both light and electron microscopy and biochemical and genetic studies identified ribosomes as the subcellular sites of protein synthesis. In the mid- to late 1960s, the synthesis of nuclear-encoded rRNA was the only system in multicellular organisms where transcripts of known function could be isolated, and their synthesis and processing could be studied. Cytogenetic observations of NOR regions with altered structure in plant interspecific hybrids and detailed knowledge of structure and function of rDNA were prerequisites for studies of nucleolar dominance, epistatic interactions of rDNA loci, and epigenetic silencing. In this article, we focus on the early rDNA research in plants, performed mainly at the dawn of molecular biology in the 60 to 80-ties of the last century which presented a prequel to the modern genomic era. We discuss - from a personal view - the topics such as synthesis of rRNA precursor (35S pre-rRNA in plants), processing, and the organization of 35S and 5S rDNA. Cloning and sequencing led to the observation that the transcribed and processed regions of the rRNA genes vary enormously, even between populations and species, in comparison with the more conserved regions coding for the mature rRNAs. Epigenetic phenomena and the impact of hybridization and allopolyploidy on rDNA expression and homogenization are discussed. This historical view of scientific progress and achievements sets the scene for the other articles highlighting the immense progress in rDNA research published in this special issue of Frontiers in Plant Science on "Molecular organization, evolution, and function of ribosomal DNA."}, } @article {pmid34949534, year = {2022}, author = {Graham, AL and Schrom, EC and Metcalf, CJE}, title = {The evolution of powerful yet perilous immune systems.}, journal = {Trends in immunology}, volume = {43}, number = {2}, pages = {117-131}, pmid = {34949534}, issn = {1471-4981}, mesh = {Adaptation, Physiological ; Animals ; Biological Evolution ; *COVID-19 ; Cytokines/genetics ; Humans ; Immune System ; SARS-CoV-2 ; }, abstract = {The mammalian immune system packs serious punch against infection but can also cause harm: for example, coronavirus disease 2019 (COVID-19) made headline news of the simultaneous power and peril of human immune responses. In principle, natural selection leads to exquisite adaptation and therefore cytokine responsiveness that optimally balances the benefits of defense against its costs (e.g., immunopathology suffered and resources expended). Here, we illustrate how evolutionary biology can predict such optima and also help to explain when/why individuals exhibit apparently maladaptive immunopathological responses. Ultimately, we argue that the evolutionary legacies of multicellularity and life-history strategy, in addition to our coevolution with symbionts and our demographic history, together explain human susceptibility to overzealous, pathology-inducing cytokine responses. Evolutionary insight thereby complements molecular/cellular mechanistic insights into immunopathology.}, } @article {pmid34944066, year = {2021}, author = {Yeh, CY and Huang, WH and Chen, HC and Meir, YJ}, title = {Capturing Pluripotency and Beyond.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34944066}, issn = {2073-4409}, mesh = {Animals ; Blastocyst/metabolism ; Cell Differentiation/*genetics ; Cell Lineage/genetics ; Embryonic Development/*genetics ; Embryonic Stem Cells/cytology ; Gene Expression Regulation, Developmental/genetics ; Germ Layers/*growth & development ; Humans ; Mice ; Pluripotent Stem Cells/*cytology ; }, abstract = {During the development of a multicellular organism, the specification of different cell lineages originates in a small group of pluripotent cells, the epiblasts, formed in the preimplantation embryo. The pluripotent epiblast is protected from premature differentiation until exposure to inductive cues in strictly controlled spatially and temporally organized patterns guiding fetus formation. Epiblasts cultured in vitro are embryonic stem cells (ESCs), which recapitulate the self-renewal and lineage specification properties of their endogenous counterparts. The characteristics of totipotency, although less understood than pluripotency, are becoming clearer. Recent studies have shown that a minor ESC subpopulation exhibits expanded developmental potential beyond pluripotency, displaying a characteristic reminiscent of two-cell embryo blastomeres (2CLCs). In addition, reprogramming both mouse and human ESCs in defined media can produce expanded/extended pluripotent stem cells (EPSCs) similar to but different from 2CLCs. Further, the molecular roadmaps driving the transition of various potency states have been clarified. These recent key findings will allow us to understand eutherian mammalian development by comparing the underlying differences between potency network components during development. Using the mouse as a paradigm and recent progress in human PSCs, we review the epiblast's identity acquisition during embryogenesis and their ESC counterparts regarding their pluripotent fates and beyond.}, } @article {pmid34937533, year = {2021}, author = {Shilovsky, GA and Putyatina, TS and Markov, AV}, title = {Altruism and Phenoptosis as Programs Supported by Evolution.}, journal = {Biochemistry. Biokhimiia}, volume = {86}, number = {12}, pages = {1540-1552}, pmid = {34937533}, issn = {1608-3040}, mesh = {*Altruism ; Animals ; *Apoptosis ; *Biological Evolution ; *COVID-19 ; Humans ; Insecta/physiology ; *SARS-CoV-2 ; }, abstract = {Phenoptosis is a programmed death that has emerged in the process of evolution, sometimes taking the form of an altruistic program. In particular, it is believed to be a weapon against the spread of pandemics in the past and an obstacle in fighting pandemics in the present (COVID). However, on the evolutionary scale, deterministic death is not associated with random relationships (for example, bacteria with a particular mutation), but is a product of higher nervous activity or a consequence of established hierarchy that reaches its maximal expression in eusocial communities of Hymenoptera and highly social communities of mammals. Unlike a simple association of individuals, eusociality is characterized by the appearance of non-reproductive individuals as the highest form of altruism. In contrast to primitive programs for unicellular organisms, higher multicellular organisms are characterized by the development of behavior-based phenoptotic programs, especially in the case of reproduction-associated limitation of lifespan. Therefore, we can say that the development of altruism in the course of evolution of sociality leads in its extreme manifestation to phenoptosis. Development of mathematical models for the emergence of altruism and programmed death contributes to our understanding of mechanisms underlying these paradoxical counterproductive (harmful) programs. In theory, this model can be applied not only to insects, but also to other social animals and even to the human society. Adaptive death is an extreme form of altruism. We consider altruism and programmed death as programmed processes in the mechanistic and adaptive sense, respectively. Mechanistically, this is a program existing as a predetermined chain of certain responses, regardless of its adaptive value. As to its adaptive value (regardless of the degree of "phenoptoticity"), this is a characteristic of organisms that demonstrate high levels of kinship, social organization, and physical association typical for higher-order individuals, e.g., unicellular organisms forming colonies with some characteristics of multicellular animals or colonies of multicellular animals displaying features of supraorganisms.}, } @article {pmid34932575, year = {2021}, author = {Maltseva, AL and Varfolomeeva, MA and Gafarova, ER and Panova, MAZ and Mikhailova, NA and Granovitch, AI}, title = {Divergence together with microbes: A comparative study of the associated microbiomes in the closely related Littorina species.}, journal = {PloS one}, volume = {16}, number = {12}, pages = {e0260792}, pmid = {34932575}, issn = {1932-6203}, mesh = {Animals ; Bacteria/classification/genetics/*isolation & purification ; Environmental Microbiology ; *Genetic Variation ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Snails/classification/*microbiology ; Species Specificity ; }, abstract = {Any multicellular organism during its life is involved in relatively stable interactions with microorganisms. The organism and its microbiome make up a holobiont, possessing a unique set of characteristics and evolving as a whole system. This study aimed to evaluate the degree of the conservativeness of microbiomes associated with intertidal gastropods. We studied the composition and the geographic and phylogenetic variability of the gut and body surface microbiomes of five closely related sympatric Littorina (Neritrema) spp. and a more distant species, L. littorea, from the sister subgenus Littorina (Littorina). Although snail-associated microbiomes included many lineages (207-603), they were dominated by a small number of OTUs of the genera Psychromonas, Vibrio, and Psychrilyobacter. The geographic variability was greater than the interspecific differences at the same collection site. While the microbiomes of the six Littorina spp. did not differ at the high taxonomic level, the OTU composition differed between groups of cryptic species and subgenera. A few species-specific OTUs were detected within the collection sites; notably, such OTUs never dominated microbiomes. We conclude that the composition of the high-rank taxa of the associated microbiome ("scaffolding enterotype") is more evolutionarily conserved than the composition of the low-rank individual OTUs, which may be site- and / or species-specific.}, } @article {pmid34913456, year = {2022}, author = {Gurney, J and Simonet, C and Wollein Waldetoft, K and Brown, SP}, title = {Challenges and opportunities for cheat therapy in the control of bacterial infections.}, journal = {Natural product reports}, volume = {39}, number = {2}, pages = {325-334}, doi = {10.1039/d1np00053e}, pmid = {34913456}, issn = {1460-4752}, mesh = {*Bacterial Infections/drug therapy ; *Biological Evolution ; Humans ; }, abstract = {Covering: 1999 to 2021Bacterial pathogens can be highly social, communicating and cooperating within multi-cellular groups to make us sick. The requirement for collective action in pathogens presents novel therapeutic avenues that seek to undermine cooperative behavior, what we call here 'cheat therapies'. We review two broad avenues of cheat therapy: first, the introduction of genetically engineered 'cheat' strains (bio-control cheats), and second the chemical induction of 'cheat' behavior in the infecting pathogens (chemical-control cheats). Both genetically engineered and chemically induced cheats can socially exploit the cooperative wildtype infection, reducing pathogen burden and the severity of disease. We review the costs and benefits of cheat therapies, highlighting advantages of evolutionary robustness and also the challenges of low to moderate efficacy, compared to conventional antibiotic treatments. We end with a summary of what we see as the most valuable next steps, focusing on adjuvant treatments and use as alternate therapies for mild, self-resolving infections - allowing the reservation of current and highly effective antibiotics for more critical patient needs.}, } @article {pmid34890552, year = {2021}, author = {Brückner, A and Badroos, JM and Learsch, RW and Yousefelahiyeh, M and Kitchen, SA and Parker, J}, title = {Evolutionary assembly of cooperating cell types in an animal chemical defense system.}, journal = {Cell}, volume = {184}, number = {25}, pages = {6138-6156.e28}, doi = {10.1016/j.cell.2021.11.014}, pmid = {34890552}, issn = {1097-4172}, mesh = {Animals ; Benzoquinones/*metabolism ; Biological Evolution ; Biosynthetic Pathways ; Coleoptera/*metabolism ; Drosophila melanogaster/*metabolism ; Pheromones/*metabolism ; }, abstract = {How the functions of multicellular organs emerge from the underlying evolution of cell types is poorly understood. We deconstructed evolution of an organ novelty: a rove beetle gland that secretes a defensive cocktail. We show how gland function arose via assembly of two cell types that manufacture distinct compounds. One cell type, comprising a chemical reservoir within the abdomen, produces alkane and ester compounds. We demonstrate that this cell type is a hybrid of cuticle cells and ancient pheromone and adipocyte-like cells, executing its function via a mosaic of enzymes from each parental cell type. The second cell type synthesizes benzoquinones using a chimera of conserved cellular energy and cuticle formation pathways. We show that evolution of each cell type was shaped by coevolution between the two cell types, yielding a potent secretion that confers adaptive value. Our findings illustrate how cooperation between cell types arises, generating new, organ-level behaviors.}, } @article {pmid34884742, year = {2021}, author = {Troitskaya, O and Novak, D and Nushtaeva, A and Savinkova, M and Varlamov, M and Ermakov, M and Richter, V and Koval, O}, title = {EGFR Transgene Stimulates Spontaneous Formation of MCF7 Breast Cancer Cells Spheroids with Partly Loss of HER3 Receptor.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884742}, issn = {1422-0067}, support = {20-74-10039//Russian Science Foundation/ ; 121030200173-6//Russian State Funded Budget Project/ ; }, mesh = {CD24 Antigen/metabolism ; Cell Culture Techniques, Three Dimensional ; *Genes, erbB-1 ; Humans ; Hyaluronan Receptors/metabolism ; *MCF-7 Cells ; Receptor, ErbB-3/*metabolism ; Rhodamine 123 ; *Spheroids, Cellular ; Transgenes ; Tumor Cells, Cultured ; }, abstract = {Multicellular spheroids with 3D cell-cell interactions are a useful model to simulate the growth conditions of cancer. There is evidence that in tumor spheroids, the expression of various essential molecules is changed compared to the adherent form of cell cultures. These changes include growth factor receptors and ABC transporters and result in the enhanced invasiveness of the cells and drug resistance. It is known that breast adenocarcinoma MCF7 cells can spontaneously form 3D spheroids and such spheroids are characterized by high expression of EGFR/HER2, while the natural phenotype of MCF7 cells is EGFR[low]/HER2[low]. Therefore, it was interesting to reveal if high epidermal growth factor receptor (EGFR) expression is sufficient for the conversion of adherent MCF7 to spheroids. In this study, an MCF7 cell line with high expression of EGFR was engineered using the retroviral transduction method. These MCF7-EGFR cells assembled in spheroids very quickly and grew predominantly as a 3D suspension culture with no special plates, scaffolds, growth supplements, or exogenous matrixes. These spheroids were characterized by a rounded shape with a well-defined external border and 100 µM median diameter. The sphere-forming ability of MCF7-EGFR cells was up to 5 times stronger than in MCF7[wt] cells. Thus, high EGFR expression was the initiation factor of conversion of adherent MCF7[wt] cells to spheroids. MCF7-EGFR spheroids were enriched by the cells with a cancer stem cell (CSC) phenotype CD24[-/low]/CD44[-] in comparison with parental MCF7[wt] cells and MCF7-EGFR adhesive cells. We suppose that these properties of MCF7-EGFR spheroids originate from the typical features of parental MCF7 cells. We showed the decreasing of HER3 receptors in MCF7-EGFR spheroids compared to that in MCF[wt] and in adherent MCF7-EGFR cells, and the same decrease was observed in the MCF7[wt] spheroids growing under the growth factors stimulation. To summarize, the expression of EGFR transgene in MCF7 cells stimulates rapid spheroids formation; these spheroids are enriched by CSC-like CD24[-]/CD44[-] cells, they partly lose HER3 receptors, and are characterized by a lower potency in drug resistance pomp activation compared to MCF7[wt]. These MCF7-EGFR spheroids are a useful cancer model for the development of anticancer drugs, including EGFR-targeted therapeutics.}, } @article {pmid34878516, year = {2022}, author = {Suissa, JS}, title = {Fern fronds that move like pine cones: humidity-driven motion of fertile leaflets governs the timing of spore dispersal in a widespread fern species.}, journal = {Annals of botany}, volume = {129}, number = {5}, pages = {519-528}, pmid = {34878516}, issn = {1095-8290}, mesh = {*Ferns/physiology ; Germ Cells, Plant ; Humidity ; Plant Cone ; Spores/physiology ; Spores, Fungal ; }, abstract = {BACKGROUND AND AIMS: The sensitive fern, Onoclea sensibilis, is a widespread species in eastern North America and has an atypical timing of spore dispersal among temperate ferns. During early summer, this dimorphic species produces heavily modified spore-bearing fronds with leaflets tightly enveloping their sporangia and spores. These fronds senesce and persist above ground as dead mature structures until the following early spring when the leaflets finally open and spores are dispersed. While this timing of spore dispersal has been observed for over 120 years, the structural mechanisms underpinning this phenology have remained elusive.

METHODS: Based on field observations, growth chamber manipulations and scanning electron microscopy, the mechanisms underlying this distinctive timing of spore dispersal in the sensitive fern were investigated.

KEY RESULTS: I show that fertile leaflets of the sensitive fern move in direct response to changes in humidity, exhibiting structural and functional parallels with multicellular hygromorphic structures in seed plants, such as pine cones. These parallels include differences in cellulose microfibril orientation in cells on the abaxial and adaxial sides of the leaflet. The dynamics of this hygroscopic movement concomitant with regular abscission zones along the pinnules and coordinated senescence lead to the specific timing of early spring spore dispersal in the sensitive fern.

CONCLUSIONS: While hygroscopic movement is common in seed-free plants, it mostly occurs in small structures that are either one or a few cells in size, such as the leptosporangium. Given its multicellular structure and integration across many cells and tissues, the movement and construction of the sensitive fern pinnules are more similar to structures in seed plants. The evolution of this complex trait in the sensitive fern efficiently regulates the timing of spore release, leading to early spring dispersal. This phenology likely gives gametophytes and subsequent sporophytes an advantage with early germination and growth.}, } @article {pmid34873026, year = {2021}, author = {Wade, J and Byrne, DJ and Ballentine, CJ and Drakesmith, H}, title = {Temporal variation of planetary iron as a driver of evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {51}, pages = {}, pmid = {34873026}, issn = {1091-6490}, support = {MC_UU_00008/10/MRC_/Medical Research Council/United Kingdom ; MC_UU_12010/10/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biological Availability ; *Biological Evolution ; Earth, Planet ; Ecosystem ; *Evolution, Planetary ; Genetic Variation ; Geology ; Host-Pathogen Interactions ; Iron/chemistry/*metabolism ; Oxidation-Reduction ; Siderophores/metabolism ; Water/chemistry/metabolism ; }, abstract = {Iron is an irreplaceable component of proteins and enzyme systems required for life. This need for iron is a well-characterized evolutionary mechanism for genetic selection. However, there is limited consideration of how iron bioavailability, initially determined by planetary accretion but fluctuating considerably at global scale over geological time frames, has shaped the biosphere. We describe influences of iron on planetary habitability from formation events >4 Gya and initiation of biochemistry from geochemistry through oxygenation of the atmosphere to current host-pathogen dynamics. By determining the iron and transition element distribution within the terrestrial planets, planetary core formation is a constraint on both the crustal composition and the longevity of surface water, hence a planet's habitability. As such, stellar compositions, combined with metallic core-mass fraction, may be an observable characteristic of exoplanets that relates to their ability to support life. On Earth, the stepwise rise of atmospheric oxygen effectively removed gigatons of soluble ferrous iron from habitats, generating evolutionary pressures. Phagocytic, infectious, and symbiotic behaviors, dating from around the Great Oxygenation Event, refocused iron acquisition onto biotic sources, while eukaryotic multicellularity allows iron recycling within an organism. These developments allow life to more efficiently utilize a scarce but vital nutrient. Initiation of terrestrial life benefitted from the biochemical properties of abundant mantle/crustal iron, but the subsequent loss of iron bioavailability may have been an equally important driver of compensatory diversity. This latter concept may have relevance for the predicted future increase in iron deficiency across the food chain caused by elevated atmospheric CO2.}, } @article {pmid34870903, year = {2021}, author = {Prostak, SM and Fritz-Laylin, LK}, title = {Laboratory Maintenance of the Chytrid Fungus Batrachochytrium dendrobatidis.}, journal = {Current protocols}, volume = {1}, number = {12}, pages = {e309}, doi = {10.1002/cpz1.309}, pmid = {34870903}, issn = {2691-1299}, support = {//National Science Foundation/ ; }, mesh = {Amphibians ; Animals ; Batrachochytrium ; *Chytridiomycota ; Ecosystem ; Laboratories ; }, abstract = {The chytrid fungus Batrachochytrium dendrobatidis (Bd) is a causative agent of chytridiomycosis, a skin disease associated with amphibian population declines around the world. Despite the major impact Bd is having on global ecosystems, much of Bd's basic biology remains unstudied. In addition to revealing mechanisms driving the spread of chytridiomycosis, studying Bd can shed light on the evolution of key fungal traits because chytrid fungi, including Bd, diverged before the radiation of the Dikaryotic fungi (multicellular fungi and yeast). Studying Bd in the laboratory is, therefore, of growing interest to a wide range of scientists, ranging from herpetologists and disease ecologists to molecular, cell, and evolutionary biologists. This protocol describes how to maintain developmentally synchronized liquid cultures of Bd for use in the laboratory, how to grow Bd on solid media, as well as cryopreservation and revival of frozen stocks. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Reviving cryopreserved Bd cultures Basic Protocol 2: Establishing synchronized liquid cultures of Bd Basic Protocol 3: Regular maintenance of synchronous Bd in liquid culture Alternate Protocol 1: Regular maintenance of asynchronous Bd in liquid culture Basic Protocol 4: Regular maintenance of synchronous Bd on solid medium Alternate Protocol 2: Starting a culture on solid medium from a liquid culture Basic Protocol 5: Cryopreservation of Bd.}, } @article {pmid34857936, year = {2021}, author = {Liu, K and Deng, S and Ye, C and Yao, Z and Wang, J and Gong, H and Liu, L and He, X}, title = {Mapping single-cell-resolution cell phylogeny reveals cell population dynamics during organ development.}, journal = {Nature methods}, volume = {18}, number = {12}, pages = {1506-1514}, pmid = {34857936}, issn = {1548-7105}, mesh = {Alleles ; Animals ; Animals, Genetically Modified ; Cell Division ; Cell Lineage ; Computational Biology/*methods ; DNA Replication ; Drosophila melanogaster/embryology/*metabolism ; Endonucleases/metabolism ; Likelihood Functions ; Male ; Microscopy/*methods ; Mutagenesis ; *Mutation ; Phenotype ; Phylogeny ; Saccharomyces cerevisiae/genetics ; Single-Cell Analysis ; }, abstract = {Mapping the cell phylogeny of a complex multicellular organism relies on somatic mutations accumulated from zygote to adult. Available cell barcoding methods can record about three mutations per barcode, enabling only low-resolution mapping of the cell phylogeny of complex organisms. Here we developed SMALT, a substitution mutation-aided lineage-tracing system that outperforms the available cell barcoding methods in mapping cell phylogeny. We applied SMALT to Drosophila melanogaster and obtained on average more than 20 mutations on a three-kilobase-pair barcoding sequence in early-adult cells. Using the barcoding mutations, we obtained high-quality cell phylogenetic trees, each comprising several thousand internal nodes with 84-93% median bootstrap support. The obtained cell phylogenies enabled a population genetic analysis that estimates the longitudinal dynamics of the number of actively dividing parental cells (Np) in each organ through development. The Np dynamics revealed the trajectory of cell births and provided insight into the balance of symmetric and asymmetric cell division.}, } @article {pmid34853303, year = {2021}, author = {Pennemann, FL and Mussabekova, A and Urban, C and Stukalov, A and Andersen, LL and Grass, V and Lavacca, TM and Holze, C and Oubraham, L and Benamrouche, Y and Girardi, E and Boulos, RE and Hartmann, R and Superti-Furga, G and Habjan, M and Imler, JL and Meignin, C and Pichlmair, A}, title = {Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {7009}, pmid = {34853303}, issn = {2041-1723}, mesh = {Animals ; Antiviral Agents ; Drosophila melanogaster ; Evolution, Molecular ; Humans ; *Immunity, Innate ; Mice ; Nucleic Acids/*chemistry/*immunology ; Protein Serine-Threonine Kinases ; Proteomics ; RNA Interference ; RNA, Double-Stranded ; Species Specificity ; THP-1 Cells ; Viral Proteins/*chemistry/*immunology ; }, abstract = {The cell intrinsic antiviral response of multicellular organisms developed over millions of years and critically relies on the ability to sense and eliminate viral nucleic acids. Here we use an affinity proteomics approach in evolutionary distant species (human, mouse and fly) to identify proteins that are conserved in their ability to associate with diverse viral nucleic acids. This approach shows a core of orthologous proteins targeting viral genetic material and species-specific interactions. Functional characterization of the influence of 181 candidates on replication of 6 distinct viruses in human cells and flies identifies 128 nucleic acid binding proteins with an impact on virus growth. We identify the family of TAO kinases (TAOK1, -2 and -3) as dsRNA-interacting antiviral proteins and show their requirement for type-I interferon induction. Depletion of TAO kinases in mammals or flies leads to an impaired response to virus infection characterized by a reduced induction of interferon stimulated genes in mammals and impaired expression of srg1 and diedel in flies. Overall, our study shows a larger set of proteins able to mediate the interaction between viral genetic material and host factors than anticipated so far, attesting to the ancestral roots of innate immunity and to the lineage-specific pressures exerted by viruses.}, } @article {pmid34849891, year = {2021}, author = {Varahan, S and Laxman, S}, title = {Bend or break: how biochemically versatile molecules enable metabolic division of labor in clonal microbial communities.}, journal = {Genetics}, volume = {219}, number = {2}, pages = {}, pmid = {34849891}, issn = {1943-2631}, support = {/WT_/Wellcome Trust/United Kingdom ; IA/E/16/1/502996/WTDBT_/DBT-Wellcome Trust India Alliance/India ; IA/I/14/2/501523/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, mesh = {Evolution, Molecular ; *Microbial Consortia ; *Microbial Interactions ; Yeasts/genetics/metabolism/physiology ; }, abstract = {In fluctuating nutrient environments, isogenic microbial cells transition into "multicellular" communities composed of phenotypically heterogeneous cells, showing functional specialization. In fungi (such as budding yeast), phenotypic heterogeneity is often described in the context of cells switching between different morphotypes (e.g., yeast to hyphae/pseudohyphae or white/opaque transitions in Candida albicans). However, more fundamental forms of metabolic heterogeneity are seen in clonal Saccharomyces cerevisiae communities growing in nutrient-limited conditions. Cells within such communities exhibit contrasting, specialized metabolic states, and are arranged in distinct, spatially organized groups. In this study, we explain how such an organization can stem from self-organizing biochemical reactions that depend on special metabolites. These metabolites exhibit plasticity in function, wherein the same metabolites are metabolized and utilized for distinct purposes by different cells. This in turn allows cell groups to function as specialized, interdependent cross-feeding systems which support distinct metabolic processes. Exemplifying a system where cells exhibit either gluconeogenic or glycolytic states, we highlight how available metabolites can drive favored biochemical pathways to produce new, limiting resources. These new resources can themselves be consumed or utilized distinctly by cells in different metabolic states. This thereby enables cell groups to sustain contrasting, even apparently impossible metabolic states with stable transcriptional and metabolic signatures for a given environment, and divide labor in order to increase community fitness or survival. We speculate on possible evolutionary implications of such metabolic specialization and division of labor in isogenic microbial communities.}, } @article {pmid34848727, year = {2021}, author = {Benaissa, H and Ounoughi, K and Aujard, I and Fischer, E and Goïame, R and Nguyen, J and Tebo, AG and Li, C and Le Saux, T and Bertolin, G and Tramier, M and Danglot, L and Pietrancosta, N and Morin, X and Jullien, L and Gautier, A}, title = {Engineering of a fluorescent chemogenetic reporter with tunable color for advanced live-cell imaging.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6989}, pmid = {34848727}, issn = {2041-1723}, mesh = {Animals ; Biocompatible Materials ; Biosensing Techniques ; Color ; Coloring Agents ; Diagnostic Imaging/*methods ; Electronics ; Female ; *Fluorescence ; Fluorescence Resonance Energy Transfer ; Fluorescent Dyes ; Green Fluorescent Proteins ; Male ; Neurons ; Protein Engineering/*methods ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Biocompatible fluorescent reporters with spectral properties spanning the entire visible spectrum are indispensable tools for imaging the biochemistry of living cells and organisms in real time. Here, we report the engineering of a fluorescent chemogenetic reporter with tunable optical and spectral properties. A collection of fluorogenic chromophores with various electronic properties enables to generate bimolecular fluorescent assemblies that cover the visible spectrum from blue to red using a single protein tag engineered and optimized by directed evolution and rational design. The ability to tune the fluorescence color and properties through simple molecular modulation provides a broad experimental versatility for imaging proteins in live cells, including neurons, and in multicellular organisms, and opens avenues for optimizing Förster resonance energy transfer (FRET) biosensors in live cells. The ability to tune the spectral properties and fluorescence performance enables furthermore to match the specifications and requirements of advanced super-resolution imaging techniques.}, } @article {pmid34841798, year = {2021}, author = {Yu, D and Cao, H and Wang, X}, title = {[Advances and applications of organoids: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3961-3974}, doi = {10.13345/j.cjb.200764}, pmid = {34841798}, issn = {1872-2075}, mesh = {*Gene Editing ; Humans ; Models, Biological ; *Organoids ; Regenerative Medicine ; Stem Cells ; }, abstract = {Novel model systems have provided powerful tools for the research of human biology. Despite of being widely used, the conventional research models could not precisely describe the human physiological phenomenon. Organoids are three-dimensional multicellular aggregates derived from stem cells or organ progenitors that could differentiate and self-organize to recapitulate some specific functionalities and architectures of their in vivo counterpart organs. Organoids can be used to simulate organogenesis because of their human origin. In addition, the genomic stability of organoids could be well maintained during long-term amplification in vitro. Moreover, organoids can be cryopreserved as a live biobank for high-throughput screening. Combinatorial use of organoids with other emerging technologies (e.g. gene editing, organ-on-a-chip and single-cell RNA sequencing) could overcome the bottlenecks of conventional models and provide valuable information for disease modelling, pharmaceutical research, precision medicine and regenerative medicine at the organ level. This review summarizes the classifications, characteristics, current applications, combined use with other technologies and future prospects of organoids.}, } @article {pmid34838795, year = {2022}, author = {Tverskoi, D and Gavrilets, S}, title = {The evolution of germ-soma specialization under different genetic and environmental effects.}, journal = {Journal of theoretical biology}, volume = {534}, number = {}, pages = {110964}, doi = {10.1016/j.jtbi.2021.110964}, pmid = {34838795}, issn = {1095-8541}, mesh = {*Biological Evolution ; Cell Differentiation ; Climate ; Fertility ; Humans ; *Models, Biological ; }, abstract = {Division of labor exists at different levels of biological organization - from cell colonies to human societies. One of the simplest examples of the division of labor in multicellular organisms is germ-soma specialization, which plays a key role in the evolution of organismal complexity. Here we formulate and study a general mathematical model exploring the emergence of germ-soma specialization in colonies of cells. We consider a finite population of colonies competing for resources. Colonies are of the same size and are composed by asexually reproducing haploid cells. Each cell can contribute to activity and fecundity of the colony, these contributions are traded-off. We assume that all cells within a colony are genetically identical but gene effects on fecundity and activity are influenced by variation in the microenvironment experienced by individual cells. Through analytical theory and evolutionary agent-based modeling we show that the shape of the trade-off relation between somatic and reproductive functions, the type and extent of variation in within-colony microenvironment, and, in some cases, the number of genes involved, are important predictors of the extent of germ-soma specialization. Specifically, increasing convexity of the trade-off relation, the number of different environmental gradients acting within a colony, and the number of genes (in the case of random microenvironmental effects) promote the emergence of germ-soma specialization. Overall our results contribute towards a better understanding of the role of genetic, environmental, and microenvironmental factors in the evolution of germ-soma specialization.}, } @article {pmid34830470, year = {2021}, author = {Kertmen, A and Petrenko, I and Schimpf, C and Rafaja, D and Petrova, O and Sivkov, V and Nekipelov, S and Fursov, A and Stelling, AL and Heimler, K and Rogoll, A and Vogt, C and Ehrlich, H}, title = {Calcite Nanotuned Chitinous Skeletons of Giant Ianthella basta Marine Demosponge.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830470}, issn = {1422-0067}, support = {HE 394/3.//DFG/ ; }, mesh = {Animals ; Aquatic Organisms/*chemistry ; Biomineralization ; Calcium Carbonate/*chemistry ; Chitin/chemistry ; Porifera/*chemistry ; Skeleton/*chemistry ; Spectroscopy, Fourier Transform Infrared ; Tissue Scaffolds/chemistry ; X-Ray Diffraction ; }, abstract = {Marine sponges were among the first multicellular organisms on our planet and have survived to this day thanks to their unique mechanisms of chemical defense and the specific design of their skeletons, which have been optimized over millions of years of evolution to effectively inhabit the aquatic environment. In this work, we carried out studies to elucidate the nature and nanostructural organization of three-dimensional skeletal microfibers of the giant marine demosponge Ianthella basta, the body of which is a micro-reticular, durable structure that determines the ideal filtration function of this organism. For the first time, using the battery of analytical tools including three-dimensional micro-X-ray Fluorescence (3D-µXRF), X-ray diffraction (XRD), infra-red (FTIR), Raman and Near Edge X-ray Fine Structure (NEXAFS) spectroscopy, we have shown that biomineral calcite is responsible for nano-tuning the skeletal fibers of this sponge species. This is the first report on the presence of a calcitic mineral phase in representatives of verongiid sponges which belong to the class Demospongiae. Our experimental data suggest a possible role for structural amino polysaccharide chitin as a template for calcification. Our study suggests further experiments to elucidate both the origin of calcium carbonate inside the skeleton of this sponge and the mechanisms of biomineralization in the surface layers of chitin microfibers saturated with bromotyrosines, which have effective antimicrobial properties and are responsible for the chemical defense of this organism. The discovery of the calcified phase in the chitinous template of I. basta skeleton is expected to broaden the knowledge in biomineralization science where the calcium carbonate is regarded as a valuable material for applications in biomedicine, environmental science, and even in civil engineering.}, } @article {pmid34830263, year = {2021}, author = {Pereira, PHS and Garcia, CRS}, title = {Evidence of G-Protein-Coupled Receptors (GPCR) in the Parasitic Protozoa Plasmodium falciparum-Sensing the Host Environment and Coupling within Its Molecular Signaling Toolkit.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830263}, issn = {1422-0067}, support = {2017/08684-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Animals ; Antimalarials/pharmacology/therapeutic use ; Calcium/metabolism ; Calcium Signaling/drug effects/*physiology ; Host-Parasite Interactions/*physiology ; Humans ; Malaria, Falciparum/drug therapy/*metabolism/parasitology ; Molecular Targeted Therapy/methods ; Perception/drug effects/*physiology ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protozoan Proteins/*metabolism ; Receptors, G-Protein-Coupled/antagonists & inhibitors/*metabolism ; }, abstract = {Throughout evolution, the need for single-celled organisms to associate and form a single cluster of cells has had several evolutionary advantages. In complex, multicellular organisms, each tissue or organ has a specialty and function that make life together possible, and the organism as a whole needs to act in balance and adapt to changes in the environment. Sensory organs are essential for connecting external stimuli into a biological response, through the senses: sight, smell, taste, hearing, and touch. The G-protein-coupled receptors (GPCRs) are responsible for many of these senses and therefore play a key role in the perception of the cells' external environment, enabling interaction and coordinated development between each cell of a multicellular organism. The malaria-causing protozoan parasite, Plasmodium falciparum, has a complex life cycle that is extremely dependent on a finely regulated cellular signaling machinery. In this review, we summarize strong evidence and the main candidates of GPCRs in protozoan parasites. Interestingly, one of these GPCRs is a sensor for K[+] shift in Plasmodium falciparum, PfSR25. Studying this family of proteins in P. falciparum could have a significant impact, both on understanding the history of the evolution of GPCRs and on finding new targets for antimalarials.}, } @article {pmid34814752, year = {2021}, author = {Irisarri, I and Darienko, T and Pröschold, T and Fürst-Jansen, JMR and Jamy, M and de Vries, J}, title = {Unexpected cryptic species among streptophyte algae most distant to land plants.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1963}, pages = {20212168}, pmid = {34814752}, issn = {1471-2954}, mesh = {*Chlorophyta/genetics ; *Embryophyta/genetics ; Evolution, Molecular ; Genome ; Phylogeny ; Plants/genetics ; }, abstract = {Streptophytes are one of the major groups of the green lineage (Chloroplastida or Viridiplantae). During one billion years of evolution, streptophytes have radiated into an astounding diversity of uni- and multicellular green algae as well as land plants. Most divergent from land plants is a clade formed by Mesostigmatophyceae, Spirotaenia spp. and Chlorokybophyceae. All three lineages are species-poor and the Chlorokybophyceae consist of a single described species, Chlorokybus atmophyticus. In this study, we used phylogenomic analyses to shed light into the diversity within Chlorokybus using a sampling of isolates across its known distribution. We uncovered a consistent deep genetic structure within the Chlorokybus isolates, which prompted us to formally extend the Chlorokybophyceae by describing four new species. Gene expression differences among Chlorokybus species suggest certain constitutive variability that might influence their response to environmental factors. Failure to account for this diversity can hamper comparative genomic studies aiming to understand the evolution of stress response across streptophytes. Our data highlight that future studies on the evolution of plant form and function can tap into an unknown diversity at key deep branches of the streptophytes.}, } @article {pmid34811380, year = {2021}, author = {Yamashita, S and Yamamoto, K and Matsuzaki, R and Suzuki, S and Yamaguchi, H and Hirooka, S and Minakuchi, Y and Miyagishima, SY and Kawachi, M and Toyoda, A and Nozaki, H}, title = {Genome sequencing of the multicellular alga Astrephomene provides insights into convergent evolution of germ-soma differentiation.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {22231}, pmid = {34811380}, issn = {2045-2322}, support = {17J03439//Japan Society for the Promotion of Science/ ; 16H06279//Japan Society for the Promotion of Science/ ; 16H02518//Japan Society for the Promotion of Science/ ; 20H03299//Japan Society for the Promotion of Science/ ; }, mesh = {Algal Proteins/genetics/metabolism ; *Biological Evolution ; Cell Differentiation/*genetics ; Chlorophyceae/*genetics ; Chlorophyta/*genetics ; Germ Cells ; Volvox/genetics ; Whole Genome Sequencing ; }, abstract = {Germ-soma differentiation evolved independently in many eukaryotic lineages and contributed to complex multicellular organizations. However, the molecular genetic bases of such convergent evolution remain unresolved. Two multicellular volvocine green algae, Volvox and Astrephomene, exhibit convergent evolution of germ-soma differentiation. The complete genome sequence is now available for Volvox, while genome information is scarce for Astrephomene. Here, we generated the de novo whole genome sequence of Astrephomene gubernaculifera and conducted RNA-seq analysis of isolated somatic and reproductive cells. In Volvox, tandem duplication and neofunctionalization of the ancestral transcription factor gene (RLS1/rlsD) might have led to the evolution of regA, the master regulator for Volvox germ-soma differentiation. However, our genome data demonstrated that Astrephomene has not undergone tandem duplication of the RLS1/rlsD homolog or acquisition of a regA-like gene. Our RNA-seq analysis revealed the downregulation of photosynthetic and anabolic gene expression in Astrephomene somatic cells, as in Volvox. Among genes with high expression in somatic cells of Astrephomene, we identified three genes encoding putative transcription factors, which may regulate somatic cell differentiation. Thus, the convergent evolution of germ-soma differentiation in the volvocine algae may have occurred by the acquisition of different regulatory circuits that generate a similar division of labor.}, } @article {pmid34789585, year = {2021}, author = {Miller, EA and Leidholt, S and Galvin, T and Norton, A and Van Houtan, KS and Vega Thurber, R and Boustany, A}, title = {Electron microscopy reveals viral-like particles and mitochondrial degradation in scombrid puffy snout syndrome.}, journal = {Diseases of aquatic organisms}, volume = {147}, number = {}, pages = {25-31}, doi = {10.3354/dao03634}, pmid = {34789585}, issn = {0177-5103}, mesh = {Animals ; Eukaryota ; Fishes ; Microscopy, Electron/veterinary ; *Mitophagy ; *Perciformes ; }, abstract = {Aquaculture is an increasingly important food resource, but its sustainability is often limited by disease. In Scombridae fishes, puffy snout syndrome (PSS) is a debilitating condition where tumor-like collagenous growths form around the eyes, nares, and mandibles which impair vision and feeding and frequently lead to mortality. While PSS is considered an infectious or metabolic disease, no disease agents or promoters have been identified. Here, we used electron microscopy (EM) to describe the cellular pathology and search for etiological agents of PSS in Pacific mackerel Scomber japonicus, the first use of this approach for PSS. We examined aquaculture specimens across a range of apparent PSS severity, comparing the results to both wild and aquaculture asymptomatic mackerel. EM imagery consistently revealed viral-like particles in PSS samples, as well as the uniform absence of bacteria, protists, fungi, and other multicellular parasites. In addition to viral-like particles, symptomatic fish had a higher mean percentage of swollen and disintegrating mitochondria than both asymptomatic aquaculture and wild mackerel. This suggests that degraded mitochondria may be related to PSS and could be important to further understanding the origin, promoters, and prevention of PSS. This study serves as a first step in identifying the etiological agents of PSS.}, } @article {pmid34788294, year = {2021}, author = {Fortunato, A and Fleming, A and Aktipis, A and Maley, CC}, title = {Upregulation of DNA repair genes and cell extrusion underpin the remarkable radiation resistance of Trichoplax adhaerens.}, journal = {PLoS biology}, volume = {19}, number = {11}, pages = {e3001471}, pmid = {34788294}, issn = {1545-7885}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA Damage/genetics/radiation effects ; DNA Repair/*genetics/radiation effects ; Gene Expression Regulation/radiation effects ; Placozoa/anatomy & histology/*genetics/radiation effects ; Radiation Exposure ; Radiation Tolerance/*genetics ; Sequence Analysis, DNA ; Up-Regulation/*genetics/radiation effects ; Whole Genome Sequencing ; X-Rays ; }, abstract = {Trichoplax adhaerens is the simplest multicellular animal with tissue differentiation and somatic cell turnover. Like all other multicellular organisms, it should be vulnerable to cancer, yet there have been no reports of cancer in T. adhaerens or any other placozoan. We investigated the cancer resistance of T. adhaerens, discovering that they are able to tolerate high levels of radiation damage (218.6 Gy). To investigate how T. adhaerens survive levels of radiation that are lethal to other animals, we examined gene expression after the X-ray exposure, finding overexpression of genes involved in DNA repair and apoptosis including the MDM2 gene. We also discovered that T. adhaerens extrudes clusters of inviable cells after X-ray exposure. T. adhaerens is a valuable model organism for studying the molecular, genetic, and tissue-level mechanisms underlying cancer suppression.}, } @article {pmid34769394, year = {2021}, author = {Marijuán, PC and Navarro, J}, title = {From Molecular Recognition to the "Vehicles" of Evolutionary Complexity: An Informational Approach.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769394}, issn = {1422-0067}, mesh = {Animals ; *Biological Evolution ; Computational Biology/*methods ; Humans ; *Metabolic Networks and Pathways ; *Mutation ; Signal Transduction ; }, abstract = {Countless informational proposals and models have explored the singular characteristics of biological systems: from the initial choice of information terms in the early days of molecular biology to the current bioinformatic avalanche in this "omic" era. However, this was conducted, most often, within partial, specialized scopes or just metaphorically. In this paper, we attempt a consistent informational discourse, initially based on the molecular recognition paradigm, which addresses the main stages of biological organization in a new way. It considers the interconnection between signaling systems and information flows, between informational architectures and biomolecular codes, between controlled cell cycles and multicellular complexity. It also addresses, in a new way, a central issue: how new evolutionary paths are opened by the cumulated action of multiple variation engines or mutational 'vehicles' evolved for the genomic exploration of DNA sequence space. Rather than discussing the possible replacement, extension, or maintenance of traditional neo-Darwinian tenets, a genuine informational approach to evolutionary phenomena is advocated, in which systemic variation in the informational architectures may induce differential survival (self-construction, self-maintenance, and reproduction) of biological agents within their open ended environment.}, } @article {pmid34769071, year = {2021}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Growth of Biological Complexity from Prokaryotes to Hominids Reflected in the Human Genome.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769071}, issn = {1422-0067}, mesh = {Animals ; Epigenesis, Genetic ; *Evolution, Molecular ; *Gene Regulatory Networks ; *Genome, Human ; Hominidae/genetics ; Humans ; Multigene Family ; Oncogenes ; Prokaryotic Cells/metabolism ; Transcription Factors/genetics ; }, abstract = {The growth of complexity in evolution is a most intriguing phenomenon. Using gene phylostratigraphy, we showed this growth (as reflected in regulatory mechanisms) in the human genome, tracing the path from prokaryotes to hominids. Generally, the different regulatory gene families expanded at different times, yet only up to the Euteleostomi (bony vertebrates). The only exception was the expansion of transcription factors (TF) in placentals; however, we argue that this was not related to increase in general complexity. Surprisingly, although TF originated in the Prokaryota while chromatin appeared only in the Eukaryota, the expansion of epigenetic factors predated the expansion of TF. Signaling receptors, tumor suppressors, oncogenes, and aging- and disease-associated genes (indicating vulnerabilities in terms of complex organization and strongly enrichment in regulatory genes) also expanded only up to the Euteleostomi. The complexity-related gene properties (protein size, number of alternative splicing mRNA, length of untranslated mRNA, number of biological processes per gene, number of disordered regions in a protein, and density of TF-TF interactions) rose in multicellular organisms and declined after the Euteleostomi, and possibly earlier. At the same time, the speed of protein sequence evolution sharply increased in the genes that originated after the Euteleostomi. Thus, several lines of evidence indicate that molecular mechanisms of complexity growth were changing with time, and in the phyletic lineage leading to humans, the most salient shift occurred after the basic vertebrate body plan was fixed with bony skeleton. The obtained results can be useful for evolutionary medicine.}, } @article {pmid34752334, year = {2021}, author = {Pereira, PHS and Garcia, CRS and Bouvier, M}, title = {Identifying Plasmodium falciparum receptor activation using bioluminescence resonance energy transfer (BRET)-based biosensors in HEK293 cells.}, journal = {Methods in cell biology}, volume = {166}, number = {}, pages = {223-233}, doi = {10.1016/bs.mcb.2021.06.018}, pmid = {34752334}, issn = {0091-679X}, mesh = {*Biosensing Techniques ; Energy Transfer ; HEK293 Cells ; Humans ; *Plasmodium falciparum/metabolism ; Receptors, G-Protein-Coupled/genetics/metabolism ; }, abstract = {Throughout evolution the need for unicellular organisms to associate and form a single cluster of cells had several evolutionary advantages. G protein coupled receptors (GPCRs) are responsible for a large part of the senses that allow this clustering to succeed, playing a fundamental role in the perception of cell's external environment, enabling the interaction and coordinated development between each cell of a multicellular organism. GPCRs are not exclusive to complex multicellular organisms. In single-celled organisms, GPCRs are also present and have a similar function of detecting changes in the external environment and transforming them into a biological response. There are no reports of GPCRs in parasitic protozoa, such as the Plasmodium genus, and the identification of a protein of this family in P. falciparum would have a significant impact both on the understanding of the basic biology of the parasite and on the history of the evolution of GPCRs. The protocol described here was successfully applied to study a GPCR candidate in P. falciparum for the first time, and we hope that it helps other groups to use the same approach to study this deadly parasite.}, } @article {pmid34740967, year = {2021}, author = {Krespach, MKC and Stroe, MC and Flak, M and Komor, AJ and Nietzsche, S and Sasso, S and Hertweck, C and Brakhage, AA}, title = {Bacterial marginolactones trigger formation of algal gloeocapsoids, protective aggregates on the verge of multicellularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {45}, pages = {}, pmid = {34740967}, issn = {1091-6490}, mesh = {*Cell Aggregation ; Chlamydomonas reinhardtii/*physiology/ultrastructure ; Macrolides/metabolism ; Microbial Interactions ; Streptomyces/metabolism ; }, abstract = {Photosynthetic microorganisms including the green alga Chlamydomonas reinhardtii are essential to terrestrial habitats as they start the carbon cycle by conversion of CO2 to energy-rich organic carbohydrates. Terrestrial habitats are densely populated, and hence, microbial interactions mediated by natural products are inevitable. We previously discovered such an interaction between Streptomyces iranensis releasing the marginolactone azalomycin F in the presence of C. reinhardtii Whether the alga senses and reacts to azalomycin F remained unknown. Here, we report that sublethal concentrations of azalomycin F trigger the formation of a protective multicellular structure by C. reinhardtii, which we named gloeocapsoid. Gloeocapsoids contain several cells which share multiple cell membranes and cell walls and are surrounded by a spacious matrix consisting of acidic polysaccharides. After azalomycin F removal, gloeocapsoid aggregates readily disassemble, and single cells are released. The presence of marginolactone biosynthesis gene clusters in numerous streptomycetes, their ubiquity in soil, and our observation that other marginolactones such as desertomycin A and monazomycin also trigger the formation of gloeocapsoids suggests a cross-kingdom competition with ecological relevance. Furthermore, gloeocapsoids allow for the survival of C. reinhardtii at alkaline pH and otherwise lethal concentrations of azalomycin F. Their structure and polysaccharide matrix may be ancestral to the complex mucilage formed by multicellular members of the Chlamydomonadales such as Eudorina and Volvox Our finding suggests that multicellularity may have evolved to endure the presence of harmful competing bacteria. Additionally, it underlines the importance of natural products as microbial cues, which initiate interesting ecological scenarios of attack and counter defense.}, } @article {pmid34740727, year = {2022}, author = {Quan, X and Kato, D and Daria, V and Matoba, O and Wake, H}, title = {Holographic microscope and its biological application.}, journal = {Neuroscience research}, volume = {179}, number = {}, pages = {57-64}, doi = {10.1016/j.neures.2021.10.012}, pmid = {34740727}, issn = {1872-8111}, mesh = {Animals ; *Holography/methods ; Mice ; Neurons/physiology ; Optogenetics/methods ; Photic Stimulation/methods ; Photons ; }, abstract = {Holographic structured illumination combined with optogenetics enables patterned stimulation of neurons and glial cells in an intact living brain. Moreover, in vivo functional imaging of cellular activity with recent advanced microscope technologies allows for visualization of the cellular responses during learning, emotion and cognition. Integrating these techniques can be used to verify the link between cell function and behavior output. However, there are technical limitations to stimulate multiple cells with high spatial and temporal resolution with available techniques of optogenetic stimulation. Here, we summarized a two-photon microscope combined with holographic system to stimulate multiple cells with high spatial and temporal resolution for living mice and their biological application.}, } @article {pmid34725037, year = {2021}, author = {Hakala, SM and Meurville, MP and Stumpe, M and LeBoeuf, AC}, title = {Biomarkers in a socially exchanged /fluid reflect colony maturity, behavior, and distributed metabolism.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34725037}, issn = {2050-084X}, mesh = {Animals ; Ants/metabolism/*physiology ; Biomarkers/*metabolism ; Social Behavior ; }, abstract = {In cooperative systems exhibiting division of labor, such as microbial communities, multicellular organisms, and social insect colonies, individual units share costs and benefits through both task specialization and exchanged materials. Socially exchanged fluids, like seminal fluid and milk, allow individuals to molecularly influence conspecifics. Many social insects have a social circulatory system, where food and endogenously produced molecules are transferred mouth-to-mouth (stomodeal trophallaxis), connecting all the individuals in the society. To understand how these endogenous molecules relate to colony life, we used quantitative proteomics to investigate the trophallactic fluid within colonies of the carpenter ant Camponotus floridanus. We show that different stages of the colony life cycle circulate different types of proteins: young colonies prioritize direct carbohydrate processing; mature colonies prioritize accumulation and transmission of stored resources. Further, colonies circulate proteins implicated in oxidative stress, ageing, and social insect caste determination, potentially acting as superorganismal hormones. Brood-caring individuals that are also closer to the queen in the social network (nurses) showed higher abundance of oxidative stress-related proteins. Thus, trophallaxis behavior could provide a mechanism for distributed metabolism in social insect societies. The ability to thoroughly analyze the materials exchanged between cooperative units makes social insect colonies useful models to understand the evolution and consequences of metabolic division of labor at other scales.}, } @article {pmid34716269, year = {2021}, author = {Yang, H and Pegoraro, AF and Han, Y and Tang, W and Abeyaratne, R and Bi, D and Guo, M}, title = {Configurational fingerprints of multicellular living systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {44}, pages = {}, pmid = {34716269}, issn = {1091-6490}, support = {R01 GM140108/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biophysical Phenomena/*physiology ; Cell Cycle ; Cell Movement ; Cell Proliferation ; Epithelial Cells/cytology ; Humans ; Image Processing, Computer-Assisted/*methods ; Morphogenesis ; Neoplasms ; Organ Specificity/*physiology ; *Phase Transition ; Spheroids, Cellular/cytology ; Wound Healing ; }, abstract = {Cells cooperate as groups to achieve structure and function at the tissue level, during which specific material characteristics emerge. Analogous to phase transitions in classical physics, transformations in the material characteristics of multicellular assemblies are essential for a variety of vital processes including morphogenesis, wound healing, and cancer. In this work, we develop configurational fingerprints of particulate and multicellular assemblies and extract volumetric and shear order parameters based on this fingerprint to quantify the system disorder. Theoretically, these two parameters form a complete and unique pair of signatures for the structural disorder of a multicellular system. The evolution of these two order parameters offers a robust and experimentally accessible way to map the phase transitions in expanding cell monolayers and during embryogenesis and invasion of epithelial spheroids.}, } @article {pmid34716098, year = {2022}, author = {Bogaert, KA and Blomme, J and Beeckman, T and De Clerck, O}, title = {Auxin's origin: do PILS hold the key?.}, journal = {Trends in plant science}, volume = {27}, number = {3}, pages = {227-236}, doi = {10.1016/j.tplants.2021.09.008}, pmid = {34716098}, issn = {1878-4372}, mesh = {Biological Transport ; *Indoleacetic Acids/metabolism ; *Membrane Transport Proteins/genetics/metabolism ; Plants/genetics/metabolism ; }, abstract = {Auxin is a key regulator of many developmental processes in land plants and plays a strikingly similar role in the phylogenetically distant brown seaweeds. Emerging evidence shows that the PIN and PIN-like (PILS) auxin transporter families have preceded the evolution of the canonical auxin response pathway. A wide conservation of PILS-mediated auxin transport, together with reports of auxin function in unicellular algae, would suggest that auxin function preceded the advent of multicellularity. We find that PIN and PILS transporters form two eukaryotic subfamilies within a larger bacterial family. We argue that future functional characterisation of algal PIN and PILS transporters can shed light on a common origin of an auxin function followed by independent co-option in a multicellular context.}, } @article {pmid34714532, year = {2022}, author = {Cao, Y}, title = {Neural is Fundamental: Neural Stemness as the Ground State of Cell Tumorigenicity and Differentiation Potential.}, journal = {Stem cell reviews and reports}, volume = {18}, number = {1}, pages = {37-55}, pmid = {34714532}, issn = {2629-3277}, mesh = {Carcinogenesis/genetics ; Cell Differentiation/genetics ; *Germ Layers ; Humans ; *Neural Stem Cells ; }, abstract = {Tumorigenic cells are similar to neural stem cells or embryonic neural cells in regulatory networks, tumorigenicity and pluripotent differentiation potential. By integrating the evidence from developmental biology, tumor biology and evolution, I will make a detailed discussion on the observations and propose that neural stemness underlies two coupled cell properties, tumorigenicity and pluripotent differentiation potential. Neural stemness property of tumorigenic cells can hopefully integrate different observations/concepts underlying tumorigenesis. Neural stem cells and tumorigenic cells share regulatory networks; both exhibit neural stemness, tumorigenicity and pluripotent differentiation potential; both depend on expression or activation of ancestral genes; both rely primarily on aerobic glycolytic metabolism; both can differentiate into various cells/tissues that are derived from three germ layers, leading to tumor formation resembling severely disorganized or more degenerated process of embryonic tissue differentiation; both are enriched in long genes with more splice variants that provide more plastic scaffolds for cell differentiation, etc. Neural regulatory networks, which include higher levels of basic machineries of cell physiological functions and developmental programs, work concertedly to define a basic state with fast cell cycle and proliferation. This is predestined by the evolutionary advantage of neural state, the ground or initial state for multicellularity with adaptation to an ancient environment. Tumorigenesis might represent a process of restoration of neural ground state, thereby restoring a state with fast proliferation and pluripotent differentiation potential in somatic cells. Tumorigenesis and pluripotent differentiation potential might be better understood from understanding neural stemness, and cancer therapy should benefit more from targeting neural stemness.}, } @article {pmid34711923, year = {2021}, author = {Wan, X and Saito, JA and Hou, S and Geib, SM and Yuryev, A and Higa, LM and Womersley, CZ and Alam, M}, title = {The Aphelenchus avenae genome highlights evolutionary adaptation to desiccation.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {1232}, pmid = {34711923}, issn = {2399-3642}, mesh = {Adaptation, Biological/*physiology ; Animals ; Biological Evolution ; *Desiccation ; Gene Duplication/physiology ; Gene Expression Profiling ; Helminth Proteins/*genetics/metabolism ; Humidity ; Phosphotransferases/*genetics/metabolism ; Tylenchida/enzymology/*genetics ; Water/*metabolism ; }, abstract = {Some organisms can withstand complete body water loss (losing up to 99% of body water) and stay in ametabolic state for decades until rehydration, which is known as anhydrobiosis. Few multicellular eukaryotes on their adult stage can withstand life without water. We still have an incomplete understanding of the mechanism for metazoan survival of anhydrobiosis. Here we report the 255-Mb genome of Aphelenchus avenae, which can endure relative zero humidity for years. Gene duplications arose genome-wide and contributed to the expansion and diversification of 763 kinases, which represents the second largest metazoan kinome to date. Transcriptome analyses of ametabolic state of A. avenae indicate the elevation of ATP level for global recycling of macromolecules and enhancement of autophagy in the early stage of anhydrobiosis. We catalogue 74 species-specific intrinsically disordered proteins, which may facilitate A. avenae to survive through desiccation stress. Our findings refine a molecular basis evolving for survival in extreme water loss and open the way for discovering new anti-desiccation strategies.}, } @article {pmid34699573, year = {2021}, author = {Tanno, A and Tokutsu, R and Arakaki, Y and Ueki, N and Minagawa, J and Yoshimura, K and Hisabori, T and Nozaki, H and Wakabayashi, KI}, title = {The four-celled Volvocales green alga Tetrabaena socialis exhibits weak photobehavior and high-photoprotection ability.}, journal = {PloS one}, volume = {16}, number = {10}, pages = {e0259138}, pmid = {34699573}, issn = {1932-6203}, mesh = {Chlorophyta/*physiology ; Photic Stimulation ; Phototropism/*physiology ; Volvox/*physiology ; }, abstract = {Photo-induced behavioral responses (photobehaviors) are crucial to the survival of motile phototrophic organisms in changing light conditions. Volvocine green algae are excellent model organisms for studying the regulatory mechanisms of photobehavior. We recently reported that unicellular Chlamydomonas reinhardtii and multicellular Volvox rousseletii exhibit similar photobehaviors, such as phototactic and photoshock responses, via different ciliary regulations. To clarify how the regulatory systems have changed during the evolution of multicellularity, we investigated the photobehaviors of four-celled Tetrabaena socialis. Surprisingly, unlike C. reinhardtii and V. rousseletii, T. socialis did not exhibit immediate photobehaviors after light illumination. Electrophysiological analysis revealed that the T. socialis eyespot does not function as a photoreceptor. Instead, T. socialis exhibited slow accumulation toward the light source in a photosynthesis-dependent manner. Our assessment of photosynthetic activities showed that T. socialis chloroplasts possess higher photoprotection abilities against strong light than C. reinhardtii. These data suggest that C. reinhardtii and T. socialis employ different strategies to avoid high-light stress (moving away rapidly and gaining photoprotection, respectively) despite their close phylogenetic relationship.}, } @article {pmid34695730, year = {2021}, author = {Grochau-Wright, ZI and Ferris, PJ and Tumberger, J and Jiménez-Marin, B and Olson, BJSC and Michod, RE}, title = {Characterization and Transformation of reg Cluster Genes in Volvox powersii Enable Investigation of Convergent Evolution of Cellular Differentiation in Volvox.}, journal = {Protist}, volume = {172}, number = {5-6}, pages = {125834}, doi = {10.1016/j.protis.2021.125834}, pmid = {34695730}, issn = {1618-0941}, support = {GT11065/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Base Sequence ; Cell Differentiation ; *Chlorophyta ; *Volvox/genetics ; }, abstract = {The evolution of germ-soma cellular differentiation represents a key step in the evolution of multicellular individuality. Volvox carteri and its relatives, the volvocine green algae, provide a model system for studying the evolution of cellular differentiation. In V. carteri, the regA gene controls somatic cell differentiation and is found in a group of paralogs called the reg cluster, along with rlsA, rlsB, and rlsC. However, the developmental program of V. carteri is derived compared to other volvocine algae. Here we examine Volvox powersii which possesses an ancestral developmental program and independent evolution of the Volvox body plan. We sequenced the reg cluster from V. powersii wild-type and a mutant with fewer cells and altered germ-soma ratio. We found that the mutant strain's rlsB gene has a deletion predicted to cause a truncated protein product. We developed a genetic transformation procedure to insert wild-type rlsB into the mutant strain. Transformation did not result in phenotypic rescue, suggesting the rlsB mutation is insufficient for generating the mutant phenotype. The transformation techniques and sequences described here provide essential tools to study V. powersii, a species well suited for studying the evolution of cellular differentiation and convergent evolution of Volvox morphology.}, } @article {pmid34685730, year = {2021}, author = {Ni, Z and Cheng, X}, title = {Origin and Isoform Specific Functions of Exchange Proteins Directly Activated by cAMP: A Phylogenetic Analysis.}, journal = {Cells}, volume = {10}, number = {10}, pages = {}, pmid = {34685730}, issn = {2073-4409}, support = {R35 GM122536/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Conserved Sequence ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Evolution, Molecular ; Guanine Nucleotide Exchange Factors/chemistry/*metabolism ; Humans ; *Phylogeny ; Protein Domains ; Protein Isoforms/chemistry/metabolism ; }, abstract = {Exchange proteins directly activated by cAMP (EPAC1 and EPAC2) are one of the several families of cellular effectors of the prototypical second messenger cAMP. To understand the origin and molecular evolution of EPAC proteins, we performed a comprehensive phylogenetic analysis of EPAC1 and EPAC2. Our study demonstrates that unlike its cousin PKA, EPAC proteins are only present in multicellular Metazoa. Within the EPAC family, EPAC1 is only associated with chordates, while EPAC2 spans the entire animal kingdom. Despite a much more contemporary origin, EPAC1 proteins show much more sequence diversity among species, suggesting that EPAC1 has undergone more selection and evolved faster than EPAC2. Phylogenetic analyses of the individual cAMP binding domain (CBD) and guanine nucleotide exchange (GEF) domain of EPACs, two most conserved regions between the two isoforms, further reveal that EPAC1 and EPAC2 are closely clustered together within both the larger cyclic nucleotide receptor and RAPGEF families. These results support the notion that EPAC1 and EPAC2 share a common ancestor resulting from a fusion between the CBD of PKA and the GEF from RAPGEF1. On the other hand, the two terminal extremities and the RAS-association (RA) domains show the most sequence diversity between the two isoforms. Sequence diversities within these regions contribute significantly to the isoform-specific functions of EPACs. Importantly, unique isoform-specific sequence motifs within the RA domain have been identified.}, } @article {pmid34681022, year = {2021}, author = {Luna, SK and Chain, FJJ}, title = {Lineage-Specific Genes and Family Expansions in Dictyostelid Genomes Display Expression Bias and Evolutionary Diversification during Development.}, journal = {Genes}, volume = {12}, number = {10}, pages = {}, pmid = {34681022}, issn = {2073-4425}, support = {R15 GM134498/GM/NIGMS NIH HHS/United States ; }, mesh = {Dictyostelium/*genetics/growth & development ; *Evolution, Molecular ; Gene Duplication/genetics ; Gene Expression Regulation, Developmental/genetics ; Genome/genetics ; *Phylogeny ; Species Specificity ; }, abstract = {Gene duplications generate new genes that can contribute to expression changes and the evolution of new functions. Genomes often consist of gene families that undergo expansions, some of which occur in specific lineages that reflect recent adaptive diversification. In this study, lineage-specific genes and gene family expansions were studied across five dictyostelid species to determine when and how they are expressed during multicellular development. Lineage-specific genes were found to be enriched among genes with biased expression (predominant expression in one developmental stage) in each species and at most developmental time points, suggesting independent functional innovations of new genes throughout the phylogeny. Biased duplicate genes had greater expression divergence than their orthologs and paralogs, consistent with subfunctionalization or neofunctionalization. Lineage-specific expansions in particular had biased genes with both molecular signals of positive selection and high expression, suggesting adaptive genetic and transcriptional diversification following duplication. Our results present insights into the potential contributions of lineage-specific genes and families in generating species-specific phenotypes during multicellular development in dictyostelids.}, } @article {pmid34680926, year = {2021}, author = {Cock, JM}, title = {Evolution of Multicellularity.}, journal = {Genes}, volume = {12}, number = {10}, pages = {}, pmid = {34680926}, issn = {2073-4425}, mesh = {Eukaryota/classification/cytology/genetics ; *Evolution, Molecular ; Phylogeny ; }, abstract = {The emergence of multicellular organisms was, perhaps, the most spectacular of the major transitions during the evolutionary history of life on this planet [...].}, } @article {pmid34671319, year = {2021}, author = {Quinting, T and Heymann, AK and Bicker, A and Nauth, T and Bernardini, A and Hankeln, T and Fandrey, J and Schreiber, T}, title = {Myoglobin Protects Breast Cancer Cells Due to Its ROS and NO Scavenging Properties.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {732190}, pmid = {34671319}, issn = {1664-2392}, mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Cell Survival/drug effects/genetics ; Female ; Free Radical Scavengers/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Knockdown Techniques ; Humans ; Myoglobin/genetics/metabolism/*physiology ; Nitric Oxide/*metabolism ; Protective Agents/metabolism ; RNA, Small Interfering/pharmacology ; Reactive Oxygen Species/*metabolism ; Signal Transduction/drug effects/genetics ; Tumor Cells, Cultured ; }, abstract = {Myoglobin (MB) is an oxygen-binding protein usually found in cardiac myocytes and skeletal muscle fibers. It may function as a temporary storage and transport protein for O2 but could also have scavenging capacity for reactive oxygen and nitrogen species. In addition, MB has recently been identified as a hallmark in luminal breast cancer and was shown to be robustly induced under hypoxia. Cellular responses to hypoxia are regulated by the transcription factor hypoxia-inducible factor (HIF). For exploring the function of MB in breast cancer, we employed the human cell line MDA-MB-468. Cells were grown in monolayer or as 3D multicellular spheroids, which mimic the in vivo avascular tumor architecture and physiology with a heterogeneous cell population of proliferating cells in the rim and non-cycling or necrotic cells in the core region. This central necrosis was increased after MB knockdown, indicating a role for MB in hypoxic tumor regions. In addition, MB knockdown caused higher levels of HIF-1α protein after treatment with NO, which also plays an important role in cancer cell survival. MB knockdown also led to higher reactive oxygen species (ROS) levels in the cells after treatment with H2O2. To further explore the role of MB in cell survival, we performed RNA-Seq after MB knockdown and NO treatment. 1029 differentially expressed genes (DEGs), including 45 potential HIF-1 target genes, were annotated in regulatory pathways that modulate cellular function and maintenance, cell death and survival, and carbohydrate metabolism. Of these target genes, TMEFF1, TREX2, GLUT-1, MKNK-1, and RAB8B were significantly altered. Consistently, a decreased expression of GLUT-1, MKNK-1, and RAB8B after MB knockdown was confirmed by qPCR. All three genes of interest are often up regulated in cancer and correlate with a poor clinical outcome. Thus, our data indicate that myoglobin might influence the survival of breast cancer cells, possibly due to its ROS and NO scavenging properties and could be a valuable target for cancer therapy.}, } @article {pmid34665225, year = {2021}, author = {Zagoskin, MV and Wang, J}, title = {Programmed DNA elimination: silencing genes and repetitive sequences in somatic cells.}, journal = {Biochemical Society transactions}, volume = {49}, number = {5}, pages = {1891-1903}, pmid = {34665225}, issn = {1470-8752}, support = {R01 AI155588/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Chromosomes/genetics ; DNA Transposable Elements/*genetics ; Embryonic Development/genetics ; Evolution, Molecular ; Gene Expression ; Gene Expression Regulation ; *Gene Silencing ; Germ Cells ; Humans ; }, abstract = {In a multicellular organism, the genomes of all cells are in general the same. Programmed DNA elimination is a notable exception to this genome constancy rule. DNA elimination removes genes and repetitive elements in the germline genome to form a reduced somatic genome in various organisms. The process of DNA elimination within an organism is highly accurate and reproducible; it typically occurs during early embryogenesis, coincident with germline-soma differentiation. DNA elimination provides a mechanism to silence selected genes and repeats in somatic cells. Recent studies in nematodes suggest that DNA elimination removes all chromosome ends, resolves sex chromosome fusions, and may also promote the birth of novel genes. Programmed DNA elimination processes are diverse among species, suggesting DNA elimination likely has evolved multiple times in different taxa. The growing list of organisms that undergo DNA elimination indicates that DNA elimination may be more widespread than previously appreciated. These various organisms will serve as complementary and comparative models to study the function, mechanism, and evolution of programmed DNA elimination in metazoans.}, } @article {pmid34661335, year = {2022}, author = {Stüeken, EE and Viehmann, S and Hohl, SV}, title = {Contrasting nutrient availability between marine and brackish waters in the late Mesoproterozoic: Evidence from the Paranoá Group, Brazil.}, journal = {Geobiology}, volume = {20}, number = {2}, pages = {159-174}, doi = {10.1111/gbi.12478}, pmid = {34661335}, issn = {1472-4669}, mesh = {Brazil ; *Ecosystem ; Eukaryota ; Nutrients ; *Seawater ; }, abstract = {Understanding the delayed rise of eukaryotic life on Earth is one of the most fundamental questions about biological evolution. Numerous studies have presented evidence for oxygen and nutrient limitations in seawater during the Mesoproterozoic era, indicating that open marine settings may not have been able to sustain a eukaryotic biosphere with complex, multicellular organisms. However, many of these data sets represent restricted marine basins, which may bias our view of habitability. Furthermore, it remains untested whether rivers could have supplied significant nutrient fluxes to coastal habitats. To better characterize the sources of the major nutrients nitrogen and phosphorus, we turned to the late Mesoproterozoic Paranoá Group in Brazil (~1.1 Ga), which was deposited on a passive margin of the São Francisco craton. We present carbon, nitrogen and sulphur isotope data from an open shelf setting (Fazenda Funil) and from a brackish-water environment with significant riverine input (São Gabriel). Our results show that waters were well-oxygenated and nitrate was bioavailable in the open ocean setting at Fazenda Funil; the redoxcline appears to have been deeper and further offshore compared to restricted marine basins elsewhere in the Mesoproterozoic. In contrast, the brackish site at São Gabriel received only limited input of marine nitrate and sulphate. Nevertheless, previous reports of acritarchs reveal that this brackish-water setting was habitable to eukaryotic life. Paired with previously published cadmium isotope data, which can be used as a proxy for phosphorus cycling, our results suggest that complex organisms were perhaps not strictly dependent on marine nutrient supplies. Riverine influxes of P and possibly other nutrients likely rendered coastal waters perhaps equally habitable to the Mesoproterozoic open ocean. This conclusion supports the notion that eukaryotic organisms may have thrived in brackish or perhaps even freshwater environments.}, } @article {pmid34661162, year = {2021}, author = {Koya, J and Saito, Y and Kameda, T and Kogure, Y and Yuasa, M and Nagasaki, J and McClure, MB and Shingaki, S and Tabata, M and Tahira, Y and Akizuki, K and Kamiunten, A and Sekine, M and Shide, K and Kubuki, Y and Hidaka, T and Kitanaka, A and Nakano, N and Utsunomiya, A and Togashi, Y and Ogawa, S and Shimoda, K and Kataoka, K}, title = {Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1.}, journal = {Blood cancer discovery}, volume = {2}, number = {5}, pages = {450-467}, pmid = {34661162}, issn = {2643-3249}, mesh = {Animals ; Carcinogenesis/genetics ; Ecosystem ; *Human T-lymphotropic virus 1/genetics ; *Leukemia-Lymphoma, Adult T-Cell/genetics ; Mice ; Single-Cell Analysis ; }, abstract = {UNLABELLED: Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)-infected cells occurs before viral carcinogenesis. Here we characterize premalignant cells and the multicellular ecosystem in HTLV-1 infection with and without adult T-cell leukemia/lymphoma (ATL) by genome sequencing and single-cell simultaneous transcriptome and T/B-cell receptor sequencing with surface protein analysis. We distinguish malignant phenotypes caused by HTLV-1 infection and leukemogenesis and dissect clonal evolution of malignant cells with different clinical behavior. Within HTLV-1-infected cells, a regulatory T-cell phenotype associates with premalignant clonal expansion. We also delineate differences between virus- and tumor-related changes in the nonmalignant hematopoietic pool, including tumor-specific myeloid propagation. In a newly generated conditional knockout mouse model recapitulating T-cell-restricted CD274 (encoding PD-L1) gene lesions found in ATL, we demonstrate that PD-L1 overexpressed by T cells is transferred to surrounding cells, leading to their PD-L1 upregulation. Our findings provide insights into clonal evolution and immune landscape of multistep virus carcinogenesis.

SIGNIFICANCE: Our multimodal single-cell analyses comprehensively dissect the cellular and molecular alterations of the peripheral blood in HTLV-1 infection, with and without progression to leukemia. This study not only sheds light on premalignant clonal expansion in viral carcinogenesis, but also helps to devise novel diagnostic and therapeutic strategies for HTLV-1-related disorders.}, } @article {pmid34648394, year = {2021}, author = {Simpson, C}, title = {Adaptation to a Viscous Snowball Earth Ocean as a Path to Complex Multicellularity.}, journal = {The American naturalist}, volume = {198}, number = {5}, pages = {590-609}, doi = {10.1086/716634}, pmid = {34648394}, issn = {1537-5323}, mesh = {Acclimatization ; Fungi ; *Ice Cover ; *Seawater ; Viscosity ; }, abstract = {AbstractAnimals, fungi, and algae with complex multicellular bodies all evolved independently from unicellular ancestors. The early history of these major eukaryotic multicellular clades, if not their origins, co-occur with an extreme phase of global glaciations known as the Snowball Earth. Here, I propose that the long-term loss of low-viscosity environments due to several rounds global glaciation drove the multiple origins of complex multicellularity in eukaryotes and the subsequent radiation of complex multicellular groups into previously unoccupied niches. In this scenario, life adapts to Snowball Earth oceans by evolving large size and faster speeds through multicellularity, which acts to compensate for high-viscosity seawater and achieve fluid flow at sufficient levels to satisfy metabolic needs. Warm, low-viscosity seawater returned with the melting of the Snowball glaciers, and with it, by virtue of large and fast multicellular bodies, new ways of life were unveiled.}, } @article {pmid34643506, year = {2021}, author = {Gao, Y and Park, HJ and Traulsen, A and Pichugin, Y}, title = {Evolution of irreversible somatic differentiation.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34643506}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Division ; *Cell Lineage ; Gene Expression Regulation ; Germ Cells/*physiology ; *Models, Biological ; Phenotype ; }, abstract = {A key innovation emerging in complex animals is irreversible somatic differentiation: daughters of a vegetative cell perform a vegetative function as well, thus, forming a somatic lineage that can no longer be directly involved in reproduction. Primitive species use a different strategy: vegetative and reproductive tasks are separated in time rather than in space. Starting from such a strategy, how is it possible to evolve life forms which use some of their cells exclusively for vegetative functions? Here, we develop an evolutionary model of development of a simple multicellular organism and find that three components are necessary for the evolution of irreversible somatic differentiation: (i) costly cell differentiation, (ii) vegetative cells that significantly improve the organism's performance even if present in small numbers, and (iii) large enough organism size. Our findings demonstrate how an egalitarian development typical for loose cell colonies can evolve into germ-soma differentiation dominating metazoans.}, } @article {pmid34641578, year = {2021}, author = {Wofford, HA and Myers-Dean, J and Vogel, BA and Alamo, KAE and Longshore-Neate, FA and Jagodzinski, F and Amacher, JF}, title = {Domain Analysis and Motif Matcher (DAMM): A Program to Predict Selectivity Determinants in Monosiga brevicollis PDZ Domains Using Human PDZ Data.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {19}, pages = {}, pmid = {34641578}, issn = {1420-3049}, support = {CHE-1904711//National Science Foundation/ ; }, mesh = {Amino Acid Sequence ; Choanoflagellata/*chemistry/*metabolism ; Computational Biology/*methods ; Evolution, Molecular ; Humans ; *PDZ Domains ; Phylogeny ; *Protein Binding ; Protein Conformation ; Signal Transduction ; Software ; Substrate Specificity ; }, abstract = {Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational software suite, Domain Analysis and Motif Matcher (DAMM), that analyzes peptide-binding cleft sequence identity as compared with human PDZ domains and that can be used in combination with literature searches of known human PDZ-interacting sequences to predict target specificity in choanoflagellate PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with <100 μM affinity, a value commonly considered the threshold for cellular PDZ-peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contribute to investigations into choanoflagellate signaling and how it informs metazoan evolution.}, } @article {pmid34639193, year = {2021}, author = {Siletsky, SA and Borisov, VB}, title = {Proton Pumping and Non-Pumping Terminal Respiratory Oxidases: Active Sites Intermediates of These Molecular Machines and Their Derivatives.}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34639193}, issn = {1422-0067}, support = {18-04-00503 and 19-04-00094//Russian Foundation for Basic Research/ ; }, mesh = {Catalysis ; Catalytic Domain ; Electron Transport ; Oxidoreductases/chemistry/*metabolism ; Proton Pumps/chemistry/*metabolism ; *Protons ; }, abstract = {Terminal respiratory oxidases are highly efficient molecular machines. These most important bioenergetic membrane enzymes transform the energy of chemical bonds released during the transfer of electrons along the respiratory chains of eukaryotes and prokaryotes from cytochromes or quinols to molecular oxygen into a transmembrane proton gradient. They participate in regulatory cascades and physiological anti-stress reactions in multicellular organisms. They also allow microorganisms to adapt to low-oxygen conditions, survive in chemically aggressive environments and acquire antibiotic resistance. To date, three-dimensional structures with atomic resolution of members of all major groups of terminal respiratory oxidases, heme-copper oxidases, and bd-type cytochromes, have been obtained. These groups of enzymes have different origins and a wide range of functional significance in cells. At the same time, all of them are united by a catalytic reaction of four-electron reduction in oxygen into water which proceeds without the formation and release of potentially dangerous ROS from active sites. The review analyzes recent structural and functional studies of oxygen reduction intermediates in the active sites of terminal respiratory oxidases, the features of catalytic cycles, and the properties of the active sites of these enzymes.}, } @article {pmid34635955, year = {2021}, author = {Schneider, C}, title = {Tuft cell integration of luminal states and interaction modules in tissues.}, journal = {Pflugers Archiv : European journal of physiology}, volume = {473}, number = {11}, pages = {1713-1722}, pmid = {34635955}, issn = {1432-2013}, mesh = {Animals ; Chemoreceptor Cells/*physiology ; Epithelial Cells/*physiology ; Humans ; Immunity, Innate/physiology ; }, abstract = {Chemosensory processes are integral to the physiology of most organisms. This function is typically performed by specialized cells that are able to detect input signals and to convert them to an output dedicated to a particular group of target cells. Tuft cells are cholinergic chemosensory epithelial cells capable of producing immunologically relevant effector molecules. They are scattered throughout endoderm-derived hollow organs and function as sensors of luminal stimuli, which has been best studied in mucosal barrier epithelia. Given their epithelial origin and broad distribution, and based on their interplay with immune pathways, tuft cells can be considered a prototypical example of how complex multicellular organisms engage innate immune mechanisms to modulate and optimize organ physiology. In this review, I provide a concise overview of tuft cells and discuss how these cells influence organ adaptation to dynamic luminal conditions.}, } @article {pmid34628994, year = {2021}, author = {Caetano-Anollés, G and Aziz, MF and Mughal, F and Caetano-Anollés, D}, title = {Tracing protein and proteome history with chronologies and networks: folding recapitulates evolution.}, journal = {Expert review of proteomics}, volume = {18}, number = {10}, pages = {863-880}, doi = {10.1080/14789450.2021.1992277}, pmid = {34628994}, issn = {1744-8387}, mesh = {*Evolution, Molecular ; Genomics ; Humans ; Phylogeny ; Protein Folding ; *Proteome/genetics ; }, abstract = {INTRODUCTION: While the origin and evolution of proteins remain mysterious, advances in evolutionary genomics and systems biology are facilitating the historical exploration of the structure, function and organization of proteins and proteomes. Molecular chronologies are series of time events describing the history of biological systems and subsystems and the rise of biological innovations. Together with time-varying networks, these chronologies provide a window into the past.

AREAS COVERED: Here, we review molecular chronologies and networks built with modern methods of phylogeny reconstruction. We discuss how chronologies of structural domain families uncover the explosive emergence of metabolism, the late rise of translation, the co-evolution of ribosomal proteins and rRNA, and the late development of the ribosomal exit tunnel; events that coincided with a tendency to shorten folding time. Evolving networks described the early emergence of domains and a late 'big bang' of domain combinations.

EXPERT OPINION: Two processes, folding and recruitment appear central to the evolutionary progression. The former increases protein persistence. The later fosters diversity. Chronologically, protein evolution mirrors folding by combining supersecondary structures into domains, developing translation machinery to facilitate folding speed and stability, and enhancing structural complexity by establishing long-distance interactions in novel structural and architectural designs.}, } @article {pmid34596678, year = {2021}, author = {Schiller, EA and Bergstralh, DT}, title = {Interaction between Discs large and Pins/LGN/GPSM2: a comparison across species.}, journal = {Biology open}, volume = {10}, number = {11}, pages = {}, pmid = {34596678}, issn = {2046-6390}, support = {R01 GM125839/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Batrachoidiformes/genetics ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/metabolism ; Carrier Proteins/*metabolism ; Cell Cycle Proteins/*metabolism ; Cell Division/*genetics ; Cnidaria/genetics ; Drosophila Proteins/metabolism ; Guanylate Kinases/metabolism ; Phylogeny ; Spindle Apparatus/*metabolism ; }, abstract = {The orientation of the mitotic spindle determines the direction of cell division, and therefore contributes to tissue shape and cell fate. Interaction between the multifunctional scaffolding protein Discs large (Dlg) and the canonical spindle orienting factor GPSM2 (called Pins in Drosophila and LGN in vertebrates) has been established in bilaterian models, but its function remains unclear. We used a phylogenetic approach to test whether the interaction is obligate in animals, and in particular whether Pins/LGN/GPSM2 evolved in multicellular organisms as a Dlg-binding protein. We show that Dlg diverged in C. elegans and the syncytial sponge Opsacas minuta and propose that this divergence may correspond with differences in spindle orientation requirements between these organisms and the canonical pathways described in bilaterians. We also demonstrate that Pins/LGN/GPSM2 is present in basal animals, but the established Dlg-interaction site cannot be found in either Placozoa or Porifera. Our results suggest that the interaction between Pins/LGN/GPSM2 and Dlg appeared in Cnidaria, and we therefore speculate that it may have evolved to promote accurate division orientation in the nervous system. This work reveals the evolutionary history of the Pins/LGN/GPSM2-Dlg interaction and suggests new possibilities for its importance in spindle orientation during epithelial and neural tissue development.}, } @article {pmid34592312, year = {2021}, author = {Shrestha, S and Clark, AC}, title = {Evolution of the folding landscape of effector caspases.}, journal = {The Journal of biological chemistry}, volume = {297}, number = {5}, pages = {101249}, pmid = {34592312}, issn = {1083-351X}, support = {R01 GM127654/GM/NIGMS NIH HHS/United States ; }, mesh = {Caspases, Effector/*chemistry/genetics/metabolism ; *Evolution, Molecular ; Humans ; *Models, Molecular ; *Protein Folding ; *Protein Multimerization ; }, abstract = {Caspases are a family of cysteinyl proteases that control programmed cell death and maintain homeostasis in multicellular organisms. The caspase family is an excellent model to study protein evolution because all caspases are produced as zymogens (procaspases [PCPs]) that must be activated to gain full activity; the protein structures are conserved through hundreds of millions of years of evolution; and some allosteric features arose with the early ancestor, whereas others are more recent evolutionary events. The apoptotic caspases evolved from a common ancestor (CA) into two distinct subfamilies: monomers (initiator caspases) or dimers (effector caspases). Differences in activation mechanisms of the two subfamilies, and their oligomeric forms, play a central role in the regulation of apoptosis. Here, we examine changes in the folding landscape by characterizing human effector caspases and their CA. The results show that the effector caspases unfold by a minimum three-state equilibrium model at pH 7.5, where the native dimer is in equilibrium with a partially folded monomeric (PCP-7, CA) or dimeric (PCP-6) intermediate. In comparison, the unfolding pathway of PCP-3 contains both oligomeric forms of the intermediate. Overall, the data show that the folding landscape was first established with the CA and was retained for >650 million years. Partially folded monomeric or dimeric intermediates in the ancestral ensemble provide mechanisms for evolutionary changes that affect stability of extant caspases. The conserved folding landscape allows for the fine-tuning of enzyme stability in a species-dependent manner while retaining the overall caspase-hemoglobinase fold.}, } @article {pmid34592264, year = {2022}, author = {Sego, TJ and Mochan, ED and Ermentrout, GB and Glazier, JA}, title = {A multiscale multicellular spatiotemporal model of local influenza infection and immune response.}, journal = {Journal of theoretical biology}, volume = {532}, number = {}, pages = {110918}, pmid = {34592264}, issn = {1095-8541}, support = {U24 EB028887/EB/NIBIB NIH HHS/United States ; R01 GM122424/GM/NIGMS NIH HHS/United States ; }, mesh = {*COVID-19 ; Humans ; Immunity, Innate ; *Influenza, Human ; SARS-CoV-2 ; *Virus Diseases ; }, abstract = {Respiratory viral infections pose a serious public health concern, from mild seasonal influenza to pandemics like those of SARS-CoV-2. Spatiotemporal dynamics of viral infection impact nearly all aspects of the progression of a viral infection, like the dependence of viral replication rates on the type of cell and pathogen, the strength of the immune response and localization of infection. Mathematical modeling is often used to describe respiratory viral infections and the immune response to them using ordinary differential equation (ODE) models. However, ODE models neglect spatially-resolved biophysical mechanisms like lesion shape and the details of viral transport, and so cannot model spatial effects of a viral infection and immune response. In this work, we develop a multiscale, multicellular spatiotemporal model of influenza infection and immune response by combining non-spatial ODE modeling and spatial, cell-based modeling. We employ cellularization, a recently developed method for generating spatial, cell-based, stochastic models from non-spatial ODE models, to generate much of our model from a calibrated ODE model that describes infection, death and recovery of susceptible cells and innate and adaptive responses during influenza infection, and develop models of cell migration and other mechanisms not explicitly described by the ODE model. We determine new model parameters to generate agreement between the spatial and original ODE models under certain conditions, where simulation replicas using our model serve as microconfigurations of the ODE model, and compare results between the models to investigate the nature of viral exposure and impact of heterogeneous infection on the time-evolution of the viral infection. We found that using spatially homogeneous initial exposure conditions consistently with those employed during calibration of the ODE model generates far less severe infection, and that local exposure to virus must be multiple orders of magnitude greater than a uniformly applied exposure to all available susceptible cells. This strongly suggests a prominent role of localization of exposure in influenza A infection. We propose that the particularities of the microenvironment to which a virus is introduced plays a dominant role in disease onset and progression, and that spatially resolved models like ours may be important to better understand and more reliably predict future health states based on susceptibility of potential lesion sites using spatially resolved patient data of the state of an infection. We can readily integrate the immune response components of our model into other modeling and simulation frameworks of viral infection dynamics that do detailed modeling of other mechanisms like viral internalization and intracellular viral replication dynamics, which are not explicitly represented in the ODE model. We can also combine our model with available experimental data and modeling of exposure scenarios and spatiotemporal aspects of mechanisms like mucociliary clearance that are only implicitly described by the ODE model, which would significantly improve the ability of our model to present spatially resolved predictions about the progression of influenza infection and immune response.}, } @article {pmid34571874, year = {2021}, author = {Buravkova, L and Larina, I and Andreeva, E and Grigoriev, A}, title = {Microgravity Effects on the Matrisome.}, journal = {Cells}, volume = {10}, number = {9}, pages = {}, pmid = {34571874}, issn = {2073-4409}, support = {65.3//Program of Basic Research of IBMP RAS/ ; 19-29-04026//Russian Foundation for Fundamental Investigations/ ; }, mesh = {Animals ; Extracellular Matrix/*physiology ; Gravity, Altered ; Humans ; Space Flight/methods ; Weightlessness ; }, abstract = {Gravity is fundamental factor determining all processes of development and vital activity on Earth. During evolution, a complex mechanism of response to gravity alterations was formed in multicellular organisms. It includes the "gravisensors" in extracellular and intracellular spaces. Inside the cells, the cytoskeleton molecules are the principal gravity-sensitive structures, and outside the cells these are extracellular matrix (ECM) components. The cooperation between the intracellular and extracellular compartments is implemented through specialized protein structures, integrins. The gravity-sensitive complex is a kind of molecular hub that coordinates the functions of various tissues and organs in the gravitational environment. The functioning of this system is of particular importance under extremal conditions, such as spaceflight microgravity. This review covers the current understanding of ECM and associated molecules as the matrisome, the features of the above components in connective tissues, and the role of the latter in the cell and tissue responses to the gravity alterations. Special attention is paid to contemporary methodological approaches to the matrisome composition analysis under real space flights and ground-based simulation of its effects on Earth.}, } @article {pmid34564856, year = {2021}, author = {Charles Campbell, F}, title = {Untangling the complexities of micropapillary cancer[†].}, journal = {The Journal of pathology}, volume = {255}, number = {4}, pages = {343-345}, doi = {10.1002/path.5809}, pmid = {34564856}, issn = {1096-9896}, support = {C9136/A15342/CRUK_/Cancer Research UK/United Kingdom ; MR/L015110/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Adenocarcinoma of Lung ; *Carcinoma, Papillary ; Cell Polarity ; *Colorectal Neoplasms ; Humans ; *Lung Neoplasms ; }, abstract = {Distinct morphological subtypes of colorectal cancer (CRC) confer a bleak clinical outlook. In a recent issue of The Journal of Pathology, Onuma et al investigated morphological evolution of a highly fatal CRC subtype known as micropapillary cancer (MPC). This study enhances understanding of MPC biology including essential regulatory signals, cellular and multicellular phenotypes, as well as cancer behaviour. Iterative modelling in three-dimensional (3D) patient-derived CRC tissue-originated spheroids (CTOSs) revealed spatiotemporal oscillations of Rho-ROCK hyperactivity underlying reversal of membrane polarity and suppression of lumen formation during development of multicellular MPC morphology. Corroborative studies in CTOSs, xenografts, and archival human CRCs confirm human disease relevance. Although cancer morphology has previously been considered irreversible, targeted inhibition of Rho-ROCK activity restored membrane polarity, lumenized multicellular assembly, and suppressed MPC morphology in 3D CTOS cultures and xenografts. Collectively, the study identifies molecular, biophysical, and multicellular mechanisms implicated in morphological evolution of micropapillary CRC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.}, } @article {pmid34556094, year = {2021}, author = {Krishna, A and Gardiner, J and Donner, TJ and Scarpella, E}, title = {Control of vein-forming, striped gene expression by auxin signaling.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {213}, pmid = {34556094}, issn = {1741-7007}, mesh = {*Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Gene Expression ; Gene Expression Regulation, Plant ; Indoleacetic Acids ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Activation of gene expression in striped domains is a key building block of biological patterning, from the recursive formation of veins in plant leaves to that of ribs and vertebrae in our bodies. In animals, gene expression is activated in striped domains by the differential affinity of broadly expressed transcription factors for their target genes and the combinatorial interaction between such target genes. In plants, how gene expression is activated in striped domains is instead unknown. We address this question for the broadly expressed MONOPTEROS (MP) transcription factor and its target gene ARABIDOPSIS THALIANA HOMEOBOX FACTOR8 (ATHB8).

RESULTS: We find that ATHB8 promotes vein formation and that such vein-forming function depends on both levels of ATHB8 expression and width of ATHB8 expression domains. We further find that ATHB8 expression is activated in striped domains by a combination of (1) activation of ATHB8 expression through binding of peak levels of MP to a low-affinity MP-binding site in the ATHB8 promoter and (2) repression of ATHB8 expression by MP target genes of the AUXIN/INDOLE-3-ACETIC-ACID-INDUCIBLE family.

CONCLUSIONS: Our findings suggest that a common regulatory logic controls activation of gene expression in striped domains in both plants and animals despite the independent evolution of their multicellularity.}, } @article {pmid34547424, year = {2021}, author = {Kun, Á}, title = {The major evolutionary transitions and codes of life.}, journal = {Bio Systems}, volume = {210}, number = {}, pages = {104548}, doi = {10.1016/j.biosystems.2021.104548}, pmid = {34547424}, issn = {1872-8324}, mesh = {Animals ; *Biological Evolution ; Genetic Code/*genetics ; Humans ; Organelles/*physiology ; *Origin of Life ; Spheroids, Cellular/physiology ; }, abstract = {Major evolutionary transitions as well as the evolution of codes of life are key elements in macroevolution which are characterized by increase in complexity Major evolutionary transitions ensues by a transition in individuality and by the evolution of a novel mode of using, transmitting or storing information. Here is where codes of life enter the picture: they are arbitrary mappings between different (mostly) molecular species. This flexibility allows information to be employed in a variety of ways, which can fuel evolutionary innovation. The collation of the list of major evolutionary transitions and the list of codes of life show a clear pattern: codes evolved prior to a major evolutionary transition and then played roles in the transition and/or in the transformation of the new individual. The evolution of a new code of life is in itself not a major evolutionary transition but allow major evolutionary transitions to happen. This could help us to identify new organic codes.}, } @article {pmid34546795, year = {2021}, author = {Umen, J and Herron, MD}, title = {Green Algal Models for Multicellularity.}, journal = {Annual review of genetics}, volume = {55}, number = {}, pages = {603-632}, doi = {10.1146/annurev-genet-032321-091533}, pmid = {34546795}, issn = {1545-2948}, support = {R01 GM126557/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; *Chlorophyta/genetics ; Genome ; Phylogeny ; *Volvox/genetics ; }, abstract = {The repeated evolution of multicellularity across the tree of life has profoundly affected the ecology and evolution of nearly all life on Earth. Many of these origins were in different groups of photosynthetic eukaryotes, or algae. Here, we review the evolution and genetics of multicellularity in several groups of green algae, which include the closest relatives of land plants. These include millimeter-scale, motile spheroids of up to 50,000 cells in the volvocine algae; decimeter-scale seaweeds in the genus Ulva (sea lettuce); and very plantlike, meter-scale freshwater algae in the genus Chara (stoneworts). We also describe algae in the genus Caulerpa, which are giant, multinucleate, morphologically complex single cells. In each case, we review the life cycle, phylogeny, and genetics of traits relevant to the evolution of multicellularity, and genetic and genomic resources available for the group in question. Finally, we suggest routes toward developing these groups as model organisms for the evolution of multicellularity.}, } @article {pmid34545570, year = {2021}, author = {Maryenti, T and Ishii, T and Okamoto, T}, title = {Development and regeneration of wheat-rice hybrid zygotes produced by in vitro fertilization system.}, journal = {The New phytologist}, volume = {232}, number = {6}, pages = {2369-2383}, pmid = {34545570}, issn = {1469-8137}, mesh = {Fertilization in Vitro ; *Oryza/genetics ; Seeds/genetics ; Triticum/genetics ; *Zygote ; }, abstract = {Hybridization plays a decisive role in the evolution and diversification of angiosperms. However, the mechanisms of wide hybridization remain open because pre- and post-fertilization barriers limit the production and development of inter-subfamily/intergeneric zygotes, respectively. We examined hybridization between wheat and rice using an in vitro fertilization (IVF) system to bypass these barriers. Several gamete combinations of allopolyploid wheat-rice hybrid zygotes were successfully produced, and the developmental profiles of hybrid zygotes were analyzed. Hybrid zygotes derived from one rice egg cell and one wheat sperm cell ceased at the multicellular embryo-like structure stage. This developmental barrier was overcome by adding one wheat egg cell to the wheat-rice hybrid zygote. In the reciprocal combination, one wheat egg and one rice sperm cell, the resulting hybrid zygotes failed to divide. However, doubling the dosage of rice sperm cell allowed the hybrid zygotes to develop into plantlets. Rice chromosomes appeared to be progressively eliminated during the early developmental stage of these hybrid embryos, and c. 20% of regenerated plants showed abnormal morphology. These results suggest that hybrid breakdown can be overcome through optimization of gamete combinations, and the present hybrid will provide a new horizon for utilization of inter-subfamily genetic resources.}, } @article {pmid34529461, year = {2021}, author = {Leslie, AB and Simpson, C and Mander, L}, title = {Reproductive innovations and pulsed rise in plant complexity.}, journal = {Science (New York, N.Y.)}, volume = {373}, number = {6561}, pages = {1368-1372}, doi = {10.1126/science.abi6984}, pmid = {34529461}, issn = {1095-9203}, mesh = {*Biological Evolution ; Cycadopsida/anatomy & histology/genetics/growth & development ; Embryophyta/*anatomy & histology/growth & development/physiology ; Flowers/*anatomy & histology ; Fossils ; Magnoliopsida/anatomy & histology/genetics/growth & development/physiology ; Plant Structures/*anatomy & histology/growth & development ; Pollination ; Reproduction ; *Seeds ; Sporangia/anatomy & histology ; }, abstract = {Morphological complexity is a notable feature of multicellular life, although whether it evolves gradually or in early bursts is unclear. Vascular plant reproductive structures, such as flowers, are familiar examples of complex morphology. In this study, we use a simple approach based on the number of part types to analyze changes in complexity over time. We find that reproductive complexity increased in two pulses separated by ~250 million years of stasis, including an initial rise in the Devonian with the radiation of vascular plants and a pronounced increase in the Late Cretaceous that reflects flowering plant diversification. These pulses are associated with innovations that increased functional diversity, suggesting that shifts in complexity are linked to changes in function regardless of whether they occur early or late in the history of vascular plants.}, } @article {pmid34525330, year = {2021}, author = {Martinez-Miguel, VE and Lujan, C and Espie-Caullet, T and Martinez-Martinez, D and Moore, S and Backes, C and Gonzalez, S and Galimov, ER and Brown, AEX and Halic, M and Tomita, K and Rallis, C and von der Haar, T and Cabreiro, F and Bjedov, I}, title = {Increased fidelity of protein synthesis extends lifespan.}, journal = {Cell metabolism}, volume = {33}, number = {11}, pages = {2288-2300.e12}, pmid = {34525330}, issn = {1932-7420}, support = {R01 GM135599/GM/NIGMS NIH HHS/United States ; C416/A25145/CRUK_/Cancer Research UK/United Kingdom ; C7893/A28990/CRUK_/Cancer Research UK/United Kingdom ; MC_UP_1102/6/MRC_/Medical Research Council/United Kingdom ; MC_UP_1605/6/MRC_/Medical Research Council/United Kingdom ; 102532/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; BB/V006916/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 102531/Z/13/A/WT_/Wellcome Trust/United Kingdom ; MR/M02492X/1/MRC_/Medical Research Council/United Kingdom ; MC-A654-5QC80/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; R01 GM141694/GM/NIGMS NIH HHS/United States ; 201487/WT_/Wellcome Trust/United Kingdom ; 28990/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {*Longevity/genetics ; Phylogeny ; Protein Biosynthesis ; *Proteostasis/genetics ; Saccharomyces cerevisiae/genetics ; }, abstract = {Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy of translation, yet the physiological consequence of having fewer protein synthesis errors during multi-cellular organismal aging is poorly understood. Our phylogenetic analysis of RPS23, a key protein in the ribosomal decoding center, uncovered a lysine residue almost universally conserved across all domains of life, which is replaced by an arginine in a small number of hyperthermophilic archaea. When introduced into eukaryotic RPS23 homologs, this mutation leads to accurate translation, as well as heat shock resistance and longer life, in yeast, worms, and flies. Furthermore, we show that anti-aging drugs such as rapamycin, Torin1, and trametinib reduce translation errors, and that rapamycin extends further organismal longevity in RPS23 hyperaccuracy mutants. This implies a unified mode of action for diverse pharmacological anti-aging therapies. These findings pave the way for identifying novel translation accuracy interventions to improve aging.}, } @article {pmid34521896, year = {2021}, author = {Elsner, D and Hartfelder, K and Korb, J}, title = {Molecular underpinnings of division of labour among workers in a socially complex termite.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {18269}, pmid = {34521896}, issn = {2045-2322}, mesh = {Animals ; Biological Evolution ; *Evolution, Molecular ; Female ; Gene Expression ; Gene Expression Profiling ; Genes, Insect/genetics ; Isoptera/*genetics/physiology ; Male ; *Social Behavior ; Transcriptome/genetics ; }, abstract = {Division of labour characterizes all major evolutionary transitions, such as the evolution of eukaryotic cells or multicellular organisms. Social insects are characterized by reproductive division of labour, with one or a few reproducing individuals (queens) and many non-reproducing nestmates (workers) forming a colony. Among the workers, further division of labour can occur with different individuals performing different tasks such as foraging, brood care or building. While mechanisms underlying task division are intensively studied in social Hymenoptera, less is known for termites, which independently evolved eusociality. We investigated molecular mechanisms underlying task division in termite workers to test for communality with social Hymenoptera. We compared similar-aged foraging workers with builders of the fungus-growing termite Macrotermes bellicosus using transcriptomes, endocrine measures and estimators of physiological condition. Based on results for social Hymenoptera and theory, we tested the hypotheses that (i) foragers are in worse physiological conditions than builders, (ii) builders are more similar in their gene expression profile to queens than foragers are, and (iii) builders invest more in anti-ageing mechanism than foragers. Our results support all three hypotheses. We found storage proteins to underlie task division of these similar-aged termite workers and these genes also characterize reproductive division of labour between queens and workers. This implies a co-option of nutrient-based pathways to regulate division of labour across lineages of termites and social Hymenoptera, which are separated by more than 133 million years.}, } @article {pmid34520764, year = {2021}, author = {Steventon, B and Busby, L and Arias, AM}, title = {Establishment of the vertebrate body plan: Rethinking gastrulation through stem cell models of early embryogenesis.}, journal = {Developmental cell}, volume = {56}, number = {17}, pages = {2405-2418}, doi = {10.1016/j.devcel.2021.08.012}, pmid = {34520764}, issn = {1878-1551}, support = {109408/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Embryonic Development/genetics/*physiology ; Gastrulation/*physiology ; Gene Expression Regulation, Developmental/genetics/physiology ; Humans ; Morphogenesis/*physiology ; Stem Cells/*cytology ; Vertebrates/genetics ; }, abstract = {A striking property of vertebrate embryos is the emergence of a conserved body plan across a wide range of organisms through the process of gastrulation. As the body plan unfolds, gene regulatory networks (GRNs) and multicellular interactions (cell regulatory networks, CRNs) combine to generate a conserved set of morphogenetic events that lead to the phylotypic stage. Interrogation of these multilevel interactions requires manipulation of the mechanical environment, which is difficult in vivo. We review recent studies of stem cell models of early embryogenesis from different species showing that, independent of species origin, cells in culture form similar structures. The main difference between embryos and in vitro models is the boundary conditions of the multicellular ensembles. We discuss these observations and suggest that the mechanical and geometric boundary conditions of different embryos before gastrulation hide a morphogenetic ground state that is revealed in the stem-cell-based models of embryo development.}, } @article {pmid34516543, year = {2021}, author = {Henriques, GJB and van Vliet, S and Doebeli, M}, title = {Multilevel selection favors fragmentation modes that maintain cooperative interactions in multispecies communities.}, journal = {PLoS computational biology}, volume = {17}, number = {9}, pages = {e1008896}, pmid = {34516543}, issn = {1553-7358}, mesh = {*Models, Biological ; Mutation ; Plants/classification/genetics ; Reproduction/genetics ; *Selection, Genetic ; Species Specificity ; }, abstract = {Reproduction is one of the requirements for evolution and a defining feature of life. Yet, across the tree of life, organisms reproduce in many different ways. Groups of cells (e.g., multicellular organisms, colonial microbes, or multispecies biofilms) divide by releasing propagules that can be single-celled or multicellular. What conditions determine the number and size of reproductive propagules? In multicellular organisms, existing theory suggests that single-cell propagules prevent the accumulation of deleterious mutations (e.g., cheaters). However, groups of cells, such as biofilms, sometimes contain multiple metabolically interdependent species. This creates a reproductive dilemma: small daughter groups, which prevent the accumulation of cheaters, are also unlikely to contain the species diversity that is required for ecological success. Here, we developed an individual-based, multilevel selection model to investigate how such multi-species groups can resolve this dilemma. By tracking the dynamics of groups of cells that reproduce by fragmenting into smaller groups, we identified fragmentation modes that can maintain cooperative interactions. We systematically varied the fragmentation mode and calculated the maximum mutation rate that communities can withstand before being driven to extinction by the accumulation of cheaters. We find that for groups consisting of a single species, the optimal fragmentation mode consists of releasing single-cell propagules. For multi-species groups we find various optimal strategies. With migration between groups, single-cell propagules are favored. Without migration, larger propagules sizes are optimal; in this case, group-size dependent fissioning rates can prevent the accumulation of cheaters. Our work shows that multi-species groups can evolve reproductive strategies that allow them to maintain cooperative interactions.}, } @article {pmid34486115, year = {2021}, author = {Roy, SW}, title = {Digest: Three sexes from two loci in one genome: A haploid alga expands the diversity of trioecious species.}, journal = {Evolution; international journal of organic evolution}, volume = {75}, number = {11}, pages = {3002-3003}, doi = {10.1111/evo.14345}, pmid = {34486115}, issn = {1558-5646}, mesh = {Female ; *Genome ; Haploidy ; Humans ; Male ; }, abstract = {Multicellular eukaryotes exhibit a remarkable diversity of sexual systems; however, trioecy, the coexistence of male, female, and cosexual or hermaphrodite individuals in a single species, is remarkably rare. Takahashi et al. (2021) report the first known instance of trioecy in a haploid organism. In contrast to other known cases of trioecy, the authors report evidence for genetic control of all three sexes by two loci. These results complicate models for sexual system turnover and expand the known diversity of trioecy species in several ways.}, } @article {pmid34477897, year = {2021}, author = {Swiatczak, B}, title = {Struggle within: evolution and ecology of somatic cell populations.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {78}, number = {21-22}, pages = {6797-6806}, pmid = {34477897}, issn = {1420-9071}, mesh = {Adaptive Immunity/genetics ; Animals ; Biological Evolution ; DNA/genetics ; Ecology ; Humans ; Mutation/*genetics ; Selection, Genetic/genetics ; }, abstract = {The extent to which normal (nonmalignant) cells of the body can evolve through mutation and selection during the lifetime of the organism has been a major unresolved issue in evolutionary and developmental studies. On the one hand, stable multicellular individuality seems to depend on genetic homogeneity and suppression of evolutionary conflicts at the cellular level. On the other hand, the example of clonal selection of lymphocytes indicates that certain forms of somatic mutation and selection are concordant with the organism-level fitness. Recent DNA sequencing and tissue physiology studies suggest that in addition to adaptive immune cells also neurons, epithelial cells, epidermal cells, hematopoietic stem cells and functional cells in solid bodily organs are subject to evolutionary forces during the lifetime of an organism. Here we refer to these recent studies and suggest that the expanding list of somatically evolving cells modifies idealized views of biological individuals as radically different from collectives.}, } @article {pmid34476388, year = {2021}, author = {Boedicker, JQ and Gangan, M and Naughton, K and Zhao, F and Gralnick, JA and El-Naggar, MY}, title = {Engineering Biological Electron Transfer and Redox Pathways for Nanoparticle Synthesis.}, journal = {Bioelectricity}, volume = {3}, number = {2}, pages = {126-135}, pmid = {34476388}, issn = {2576-3113}, abstract = {Many species of bacteria are naturally capable of types of electron transport not observed in eukaryotic cells. Some species live in environments containing heavy metals not typically encountered by cells of multicellular organisms, such as arsenic, cadmium, and mercury, leading to the evolution of enzymes to deal with these environmental toxins. Bacteria also inhabit a variety of extreme environments, and are capable of respiration even in the absence of oxygen as a terminal electron acceptor. Over the years, several of these exotic redox and electron transport pathways have been discovered and characterized in molecular-level detail, and more recently synthetic biology has begun to utilize these pathways to engineer cells capable of detecting and processing a variety of metals and semimetals. One such application is the biologically controlled synthesis of nanoparticles. This review will introduce the basic concepts of bacterial metal reduction, summarize recent work in engineering bacteria for nanoparticle production, and highlight the most cutting-edge work in the characterization and application of bacterial electron transport pathways.}, } @article {pmid34467433, year = {2021}, author = {Wang, X and Dong, F and Liu, J and Tan, Y and Hu, S and Zhao, H}, title = {The self-healing of Bacillus subtilis biofilms.}, journal = {Archives of microbiology}, volume = {203}, number = {9}, pages = {5635-5645}, pmid = {34467433}, issn = {1432-072X}, support = {11772047//National Natural Science Foundation of China/ ; 11972074//National Natural Science Foundation of China/ ; 11620101001//National Natural Science Foundation of China/ ; }, mesh = {*Bacillus subtilis ; *Biofilms ; Humans ; }, abstract = {Self-healing is an intrinsic ability that exists widely in every multicellular biological organism. Our recent experiments have shown that bacterial biofilms also have the ability to self-heal after man-make cuts, but the mechanism of biofilm self-healing have not been studied. We find that the healing process of cuts on the biofilm depends on cut geometries like its location or direction, the biofilm itself like the biofilm age, the growing substrate properties like its hardness, and also the environments such as the competitive growth of multiple biofilms. What is more, the healing rate along the cut is heterogeneous, and the maximum healing rate can reach 260 μm/h, which is three times the undestroyed biofilm expansion rate. The cut does not change the rounded shape growth of biofilms. Further study of phenotypic evolution shows that the cut delays bacterial differentiation; motile cells perceive the cut and move to the cut area, while the cut only heals when there are enough matrix-producing cells in the cut area. Our work suggests new ideas for developing self-healing materials.}, } @article {pmid34465312, year = {2021}, author = {Lindsey, CR and Rosenzweig, F and Herron, MD}, title = {Phylotranscriptomics points to multiple independent origins of multicellularity and cellular differentiation in the volvocine algae.}, journal = {BMC biology}, volume = {19}, number = {1}, pages = {182}, pmid = {34465312}, issn = {1741-7007}, mesh = {Bayes Theorem ; Biological Evolution ; Cell Differentiation ; Chlamydomonas reinhardtii ; *Phylogeny ; Transcriptome ; Volvox/genetics ; }, abstract = {BACKGROUND: The volvocine algae, which include the single-celled species Chlamydomonas reinhardtii and the colonial species Volvox carteri, serve as a model in which to study the evolution of multicellularity and cellular differentiation. Studies reconstructing the history of this group have by and large relied on datasets of one to a few genes for phylogenetic inference and ancestral character state reconstruction. As a result, volvocine phylogenies lack concordance depending on the number and/or type of genes (i.e., chloroplast vs nuclear) chosen for phylogenetic inference. While multiple studies suggest that multicellularity evolved only once in the volvocine algae, that each of its three colonial families is monophyletic, and that there have been at least three independent origins of cellular differentiation in the group, other studies call into question one or more of these conclusions. An accurate assessment of the evolutionary history of the volvocine algae requires inference of a more robust phylogeny.

RESULTS: We performed RNA sequencing (RNA-seq) on 55 strains representing 47 volvocine algal species and obtained similar data from curated databases on 13 additional strains. We then compiled a dataset consisting of transcripts for 40 single-copy, protein-coding, nuclear genes and subjected the predicted amino acid sequences of these genes to maximum likelihood, Bayesian inference, and coalescent-based analyses. These analyses show that multicellularity independently evolved at least twice in the volvocine algae and that the colonial family Goniaceae is not monophyletic. Our data further indicate that cellular differentiation arose independently at least four, and possibly as many as six times, within the volvocine algae.

CONCLUSIONS: Altogether, our results demonstrate that multicellularity and cellular differentiation are evolutionarily labile in the volvocine algae, affirming the importance of this group as a model system for the study of major transitions in the history of life.}, } @article {pmid34463760, year = {2021}, author = {Diegmiller, R and Doherty, CA and Stern, T and Imran Alsous, J and Shvartsman, SY}, title = {Size scaling in collective cell growth.}, journal = {Development (Cambridge, England)}, volume = {148}, number = {18}, pages = {}, pmid = {34463760}, issn = {1477-9129}, support = {R01 GM134204/GM/NIGMS NIH HHS/United States ; F31 HD098835/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Cell Proliferation/*physiology ; Developmental Biology/methods ; Diptera/physiology ; Germ Cells/physiology ; Oogenesis/physiology ; Organelles/physiology ; }, abstract = {Size is a fundamental feature of living entities and is intimately tied to their function. Scaling laws, which can be traced to D'Arcy Thompson and Julian Huxley, have emerged as a powerful tool for studying regulation of the growth dynamics of organisms and their constituent parts. Yet, throughout the 20th century, as scaling laws were established for single cells, quantitative studies of the coordinated growth of multicellular structures have lagged, largely owing to technical challenges associated with imaging and image processing. Here, we present a supervised learning approach for quantifying the growth dynamics of germline cysts during oogenesis. Our analysis uncovers growth patterns induced by the groupwise developmental dynamics among connected cells, and differential growth rates of their organelles. We also identify inter-organelle volumetric scaling laws, finding that nurse cell growth is linear over several orders of magnitude. Our approach leverages the ever-increasing quantity and quality of imaging data, and is readily amenable for studies of collective cell growth in other developmental contexts, including early mammalian embryogenesis and germline development.}, } @article {pmid34462837, year = {2021}, author = {Mikhalevich, VI}, title = {Aromorphoses in the Evolution of Unicellular Eukaryotes (as Exemplified by Foraminifera D'orbigny, 1826).}, journal = {Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections}, volume = {499}, number = {1}, pages = {105-108}, pmid = {34462837}, issn = {1608-3105}, mesh = {Eukaryota ; *Foraminifera/genetics ; }, abstract = {Aromorphoses of unicellular organisms are almost unexplored. Foraminifera provide a unique opportunity of such studies, having the most complex structure and being most fully represented in the geological record. In their development, more than 10 aromorphoses (key advances) have first been discovered, which arose in different classes of Foraminifera independently and in parallel. Of these, the key ones are the emergence of an agglutinated and then secreted calcareous shell, a bifontinal (bilamellar) wall, multichamberedness, differentiation of chambers, an integrating system of channels and nuclear dualism. They represent peculiar ways of evolution at the unicellular level. Multicameredness can be compared with multicellularity; differentiation of chambers, with differentiation of tissues; a system of channels, striking in its complexity and carrying O2, with the Metazoa circulatory system.}, } @article {pmid34455760, year = {2021}, author = {Louka, A and Takan, I and Pavlopoulou, A and Georgakilas, AG}, title = {Bioinformatic approaches to the investigation of the atavistic genes implicated in cancer.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {26}, number = {8}, pages = {279-311}, doi = {10.52586/4944}, pmid = {34455760}, issn = {2768-6698}, mesh = {Biological Evolution ; *Computational Biology ; Gene Regulatory Networks ; Humans ; *Neoplasms/genetics ; Phylogeny ; }, abstract = {Introduction: Cancer is a widespread phenomenon occurring across multicellular organisms and represents a condition of atavism, wherein cells follow a path of reverse evolution that unlocks a toolkit of ancient pre-existing adaptations by disturbing hub genes of the human gene network. This results to a primitive cellular phenotype which resembles a unicellular life form. Methods: In the present study, we have employed bioinformatic approaches for the in-depth investigation of twelve atavistic hub genes (ACTG1, CTNNA1, CTNND1, CTTN, DSP, ILK, PKN2, PKP3, PLEC, RCC2, TLN1 and VASP), which exhibit highly disrupted interactions in diverse types of cancer and are associated with the formation of metastasis. To this end, phylogenetic analyses were conducted towards unravelling the evolutionary history of those hubs and tracing the origin of cancer in the Tree of Life. Results: Based on our results, most of those genes are of unicellular origin, and some of them can be traced back to the emergence of cellular life itself (atavistic theory). Our findings indicate how deep the evolutionary roots of cancer actually are, and may be exploited in the clinical setting for the design of novel therapeutic approaches and, particularly, in overcoming resistance to antineoplastic treatment.}, } @article {pmid34440622, year = {2021}, author = {Mandujano-Tinoco, EA and Sultan, E and Ottolenghi, A and Gershoni-Yahalom, O and Rosental, B}, title = {Evolution of Cellular Immunity Effector Cells; Perspective on Cytotoxic and Phagocytic Cellular Lineages.}, journal = {Cells}, volume = {10}, number = {8}, pages = {}, pmid = {34440622}, issn = {2073-4409}, support = {1416/19//Israel Science Foundation/ ; RGY0085/2019//Human Frontier Science Program/ ; }, mesh = {Animals ; Bacteria/immunology/pathogenicity ; *Cell Lineage ; Communicable Diseases/*immunology/metabolism ; *Cytotoxicity, Immunologic ; Host-Pathogen Interactions ; Humans ; *Immunity, Cellular ; *Immunity, Innate ; Parasites/immunology/pathogenicity ; Phagocytes/*immunology/metabolism ; *Phagocytosis ; Signal Transduction ; Viruses/immunology/pathogenicity ; }, abstract = {The immune system has evolved to protect organisms from infections caused by bacteria, viruses, and parasitic pathogens. In addition, it provides regenerative capacities, tissue maintenance, and self/non-self recognition of foreign tissues. Phagocytosis and cytotoxicity are two prominent cellular immune activities positioned at the base of immune effector function in mammals. Although these immune mechanisms have diversified into a wide heterogeneous repertoire of effector cells, it appears that they share some common cellular and molecular features in all animals, but also some interesting convergent mechanisms. In this review, we will explore the current knowledge about the evolution of phagocytic and cytotoxic immune lineages against pathogens, in the clearance of damaged cells, for regeneration, for histocompatibility recognition, and in killing virally infected cells. To this end, we give different immune examples of multicellular organism models, ranging from the roots of bilateral organisms to chordate invertebrates, comparing to vertebrates' lineages. In this review, we compare cellular lineage homologies at the cellular and molecular levels. We aim to highlight and discuss the diverse function plasticity within the evolved immune effector cells, and even suggest the costs and benefits that it may imply for organisms with the meaning of greater defense against pathogens but less ability to regenerate damaged tissues and organs.}, } @article {pmid34430989, year = {2021}, author = {Suthar, J and Al-Jufaili, S and Bray, RA and Frank, M and Theisen, S and Palm, HW}, title = {Redescription of Aspidogaster limacoides Diesing, 1834 (Aspidogastrea: Aspidogastridae) from freshwater fishes of northern Germany.}, journal = {Parasitology research}, volume = {120}, number = {10}, pages = {3405-3416}, pmid = {34430989}, issn = {1432-1955}, support = {MV-II. 12-LM-03//European Fisheries Fund and the Ministry of Agriculture and Environment, Mecklenburg-Western Pomerania as a part of the Project Hygiene management and health concept for surface water-dependent partial circulation systems in M.V./ ; }, mesh = {Animals ; *Cyprinidae ; Fishes ; Fresh Water ; Germany ; Phylogeny ; *Trematoda ; }, abstract = {Aspidogaster limacoides Diesing, 1834 (Aspidogastridae) is redescribed based on light and scanning electron microscopy of specimens from the stomach and intestine of Abramis brama, Rutilus rutilus and Scardinius erythrophthalmus (Actinopterygii: Cyprinidae). The fishes were sampled during 2018 and 2019 at Lake Tollense in Mecklenburg-Western Pomerania, Germany. The prevalence of A. limacoides was highest in R. rutilus (61.7%) followed by Scardinius erythrophthalmus (7.7%) and A. brama (2.9%), while it was absent in Perca fluviatilis from the same lake. The following structures of A. limacoides are described for the first time: a depression on the ventral side of the neck, variations in the number and the arrangement of alveoli, numerous pits scattered all over the body surface, the presence of a few papillae-like structures posterior lateral to the mouth, the number of marginal organs represented by openings of exocrine multicellular glands as shown in histology and the subterminal position of the excretory pore. These characters can be used to distinguish three species of Aspidogaster, namely, A. ijimai, A. conchicola and A. limacoides, suggesting that SEM is a useful and promising tool in differentiating Aspidogaster species. Comparison of molecular data of the ITS1-5.8S-ITS2 regions showed a 94% similarity to A. limacoides from the European part of Russia. Phylogenetic analysis showed that the present specimens clustered in the same clade with A. limacoides sensu stricto, forming a distinct group to the exclusion of congeners.}, } @article {pmid34411089, year = {2021}, author = {Leray, M and Wilkins, LGE and Apprill, A and Bik, HM and Clever, F and Connolly, SR and De León, ME and Duffy, JE and Ezzat, L and Gignoux-Wolfsohn, S and Herre, EA and Kaye, JZ and Kline, DI and Kueneman, JG and McCormick, MK and McMillan, WO and O'Dea, A and Pereira, TJ and Petersen, JM and Petticord, DF and Torchin, ME and Vega Thurber, R and Videvall, E and Wcislo, WT and Yuen, B and Eisen, JA}, title = {Natural experiments and long-term monitoring are critical to understand and predict marine host-microbe ecology and evolution.}, journal = {PLoS biology}, volume = {19}, number = {8}, pages = {e3001322}, pmid = {34411089}, issn = {1545-7885}, mesh = {*Acclimatization ; Animals ; Aquatic Organisms/*microbiology ; *Biological Evolution ; *Ecology ; Ecosystem ; Humans ; *Microbiota ; Symbiosis ; }, abstract = {Marine multicellular organisms host a diverse collection of bacteria, archaea, microbial eukaryotes, and viruses that form their microbiome. Such host-associated microbes can significantly influence the host's physiological capacities; however, the identity and functional role(s) of key members of the microbiome ("core microbiome") in most marine hosts coexisting in natural settings remain obscure. Also unclear is how dynamic interactions between hosts and the immense standing pool of microbial genetic variation will affect marine ecosystems' capacity to adjust to environmental changes. Here, we argue that significantly advancing our understanding of how host-associated microbes shape marine hosts' plastic and adaptive responses to environmental change requires (i) recognizing that individual host-microbe systems do not exist in an ecological or evolutionary vacuum and (ii) expanding the field toward long-term, multidisciplinary research on entire communities of hosts and microbes. Natural experiments, such as time-calibrated geological events associated with well-characterized environmental gradients, provide unique ecological and evolutionary contexts to address this challenge. We focus here particularly on mutualistic interactions between hosts and microbes, but note that many of the same lessons and approaches would apply to other types of interactions.}, } @article {pmid34404788, year = {2021}, author = {Galindo, LJ and López-García, P and Torruella, G and Karpov, S and Moreira, D}, title = {Phylogenomics of a new fungal phylum reveals multiple waves of reductive evolution across Holomycota.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4973}, pmid = {34404788}, issn = {2041-1723}, mesh = {Basal Bodies ; Blastocladiomycota ; Chytridiomycota/classification ; Flagella ; Fungi/*classification/cytology/genetics/metabolism ; Genomics ; Hepatophyta/*classification ; Hyphae ; Phenotype ; *Phylogeny ; Specimen Handling ; Transcriptome ; }, abstract = {Compared to multicellular fungi and unicellular yeasts, unicellular fungi with free-living flagellated stages (zoospores) remain poorly known and their phylogenetic position is often unresolved. Recently, rRNA gene phylogenetic analyses of two atypical parasitic fungi with amoeboid zoospores and long kinetosomes, the sanchytrids Amoeboradix gromovi and Sanchytrium tribonematis, showed that they formed a monophyletic group without close affinity with known fungal clades. Here, we sequence single-cell genomes for both species to assess their phylogenetic position and evolution. Phylogenomic analyses using different protein datasets and a comprehensive taxon sampling result in an almost fully-resolved fungal tree, with Chytridiomycota as sister to all other fungi, and sanchytrids forming a well-supported, fast-evolving clade sister to Blastocladiomycota. Comparative genomic analyses across fungi and their allies (Holomycota) reveal an atypically reduced metabolic repertoire for sanchytrids. We infer three main independent flagellum losses from the distribution of over 60 flagellum-specific proteins across Holomycota. Based on sanchytrids' phylogenetic position and unique traits, we propose the designation of a novel phylum, Sanchytriomycota. In addition, our results indicate that most of the hyphal morphogenesis gene repertoire of multicellular fungi had already evolved in early holomycotan lineages.}, } @article {pmid34394122, year = {2021}, author = {Sun, V and Sharpley, M and Kaczor-Urbanowicz, KE and Chang, P and Montel-Hagen, A and Lopez, S and Zampieri, A and Zhu, Y and de Barros, SC and Parekh, C and Casero, D and Banerjee, U and Crooks, GM}, title = {The Metabolic Landscape of Thymic T Cell Development In Vivo and In Vitro.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {716661}, pmid = {34394122}, issn = {1664-3224}, support = {UL1 TR000124/TR/NCATS NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; P30 AG028748/AG/NIA NIH HHS/United States ; T32 GM008042/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Biomarkers ; *Cell Differentiation ; Cell Line ; Computational Biology/methods ; *Energy Metabolism ; Gene Expression Profiling ; Hematopoietic Stem Cells/cytology/immunology/metabolism ; Humans ; Lymphopoiesis ; Metabolome ; Metabolomics/methods ; Mice ; Organoids ; T-Lymphocytes/*cytology/*metabolism ; Thymocytes/*cytology/immunology/*metabolism ; Tissue Culture Techniques ; }, abstract = {Although metabolic pathways have been shown to control differentiation and activation in peripheral T cells, metabolic studies on thymic T cell development are still lacking, especially in human tissue. In this study, we use transcriptomics and extracellular flux analyses to investigate the metabolic profiles of primary thymic and in vitro-derived mouse and human thymocytes. Core metabolic pathways, specifically glycolysis and oxidative phosphorylation, undergo dramatic changes between the double-negative (DN), double-positive (DP), and mature single-positive (SP) stages in murine and human thymus. Remarkably, despite the absence of the complex multicellular thymic microenvironment, in vitro murine and human T cell development recapitulated the coordinated decrease in glycolytic and oxidative phosphorylation activity between the DN and DP stages seen in primary thymus. Moreover, by inducing in vitro T cell differentiation from Rag1[-/-] mouse bone marrow, we show that reduced metabolic activity at the DP stage is independent of TCR rearrangement. Thus, our findings suggest that highly conserved metabolic transitions are critical for thymic T cell development.}, } @article {pmid34384851, year = {2021}, author = {Cisbani, G and Metherel, AH and Smith, ME and Bazinet, RP}, title = {Murine and human microglial cells are relatively enriched with eicosapentaenoic acid compared to the whole brain.}, journal = {Neurochemistry international}, volume = {150}, number = {}, pages = {105154}, doi = {10.1016/j.neuint.2021.105154}, pmid = {34384851}, issn = {1872-9754}, support = {//CIHR/Canada ; }, mesh = {Animals ; Brain/cytology/*metabolism ; Brain Chemistry/*physiology ; Eicosapentaenoic Acid/analysis/*metabolism ; Female ; Fetus ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Microglia/chemistry/*metabolism ; }, abstract = {The brain is a multicellular organ enriched with lipids. While the fatty acid composition of gross cerebral tissue is well characterized, the fatty acid composition of specific brain cells, particularly microglia cells, is less well characterized. Microglia cells are the innate immune cells of the brain, and a paucity of studies measuring their fatty acid composition using either immortalized or primary microglia cells report a higher ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) than widely observed in whole brain tissue. Here we further characterize the fatty acid composition of murine microglia cells from young male and female mice as well as of human origin and compared it with a myelin-enriched fraction from the same mice. Our results show that saturated and monounsaturated fatty acids are the most abundant followed by polyunsaturated fatty acids (PUFA), with no statistical differences between sexes. Regarding PUFA, although DHA levels did not differ between human and murine cells, EPA was statistically higher in murine microglia. Notably, the DHA to EPA ratio was about 400 times lower in microglial cells compared to the myelin-enriched fraction. Thus, our results suggest that as compared to whole brain tissue EPA is relatively abundant in microglia cells, particularly in comparison to other n-3 PUFA such as DHA. Since the fatty acid composition of microglia can influence their functionality, a better understanding of EPA and DHA metabolism in microglia and the brain could identify new targets to modify microglial activity.}, } @article {pmid34374500, year = {2021}, author = {Dzik, J}, title = {Metabolic evolutionary roots of the macrophage immune response in amoeba-bacteria interactions: The conserved role of hypoxia-induced Factor and AMP kinase.}, journal = {Acta biochimica Polonica}, volume = {68}, number = {3}, pages = {457-476}, doi = {10.18388/abp.2020_5683}, pmid = {34374500}, issn = {1734-154X}, mesh = {Adenylate Kinase/*metabolism ; Amoeba/immunology/*metabolism ; Animals ; Bacteria/immunology/*metabolism ; Cytokines/metabolism ; Glycolysis ; Humans ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1/*metabolism ; Immunity/immunology ; Legionella/immunology/metabolism ; Macrophages/*immunology ; NF-kappa B/metabolism ; Phagocytosis ; Toll-Like Receptors/metabolism ; }, abstract = {The bacteria Legionella, being able to infect both macrophages and protozoans, reduce oxidative phosphorylation and induce glycolysis, which allows pathogens to grow and replicate in these cells. In amoeba-like inflammatory macrophages (M1), the phagocytizing cells of the primary immune defense, an increase in the rate of glycolysis is followed by a decrease of oxidative phosphorylation. The opposite takes place in anti-inflammatory macrophages (M2). They change from glycolysis to oxidative metabolism when AMP-dependent kinase (AMPK) is activated by a high ratio of AMP/ATP. Stimulation of macrophages with anti-inflammatory cytokines causes activation of AMPK. Infection of macrophages with the parasitic flagellate Leishmania infantum induces a switch from an initial glycolytic phase to oxidative phase with the essential role of AMPK in this change. Activated AMPK induces catabolic pathways effectively producing ATP as well as processes requiring the energy supply. AMPK regulates the migration of cells and enhances the phagocytic activity of macrophages. In macrophages, bacterial products activate TLRs and NF-κB signaling, causing an increase of transcription of hypoxia-induced factor HIF-1α (a subunit of HIF-1). This brings about induction of the enzyme and transporter expression essential for glycolysis and the pentose phosphate pathway to proceed and makes biosynthetic processes and ROS production in macrophages possible. Hypoxia augments macrophage phagocytosis in a HIF-1α-dependent manner. Multicellular parasites experience changes in the availability of oxygen in their life cycle. In the nematode Ascaris suum, HIF participates in the pre-adaptation to hypoxic conditions after infection of their hosts. Also, the freshwater and marine invertebrates meet changes of oxygen concentrations. In the anaerobic branch of the respiratory chain of these invertebrates, fumarate serves as the terminal electron acceptor that is reduced to succinate in complex II of the ETC. In mammalian cells, accumulation of succinate under hypoxic conditions suggests that the mammalian complex II may reduce fumarate to succinate, too. The data reviewed here show that the ability to shift the cell metabolism towards glycolysis observed in activated macrophages can be traced back in evolution to metabolic changes characterizing protozoans infected with bacteria. Anabolic needs of multiplying bacteria direct host metabolism to glycolysis that produces, aside from ATP, precursors of the amino acids used by the pathogen for its protein synthesis. M1-activated mammalian macrophages behave in the same way. Regulation of metabolism in M1 and M2 macrophages is further enhanced by HIF-1 and AMPK, respectively. These archaic functions of AMPK and HIF, important also to control phagocytosis and cell migration were extended to embryonic development in multicellular organisms.}, } @article {pmid34371024, year = {2021}, author = {Bussey, KJ and Davies, PCW}, title = {Reverting to single-cell biology: The predictions of the atavism theory of cancer.}, journal = {Progress in biophysics and molecular biology}, volume = {165}, number = {}, pages = {49-55}, pmid = {34371024}, issn = {1873-1732}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/genetics ; Biological Evolution ; Gene Regulatory Networks ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {Cancer or cancer-like phenomena pervade multicellular life, implying deep evolutionary roots. Many of the hallmarks of cancer recapitulate unicellular modalities, suggesting that cancer initiation and progression represent a systematic reversion to simpler ancestral phenotypes in response to a stress or insult. This so-called atavism theory may be tested using phylostratigraphy, which can be used to assign ages to genes. Several research groups have confirmed that cancer cells tend to over-express evolutionary older genes, and rewire the architecture linking unicellular and multicellular gene networks. In addition, some of the elevated mutation rate - a well-known hallmark of cancer - is actually self-inflicted, driven by genes found to be homologs of the ancient SOS genes activated in stressed bacteria, and employed to evolve biological workarounds. These findings have obvious implications for therapy.}, } @article {pmid34359962, year = {2021}, author = {Van Goor, J and Shakes, DC and Haag, ES}, title = {Fisher vs. the Worms: Extraordinary Sex Ratios in Nematodes and the Mechanisms that Produce Them.}, journal = {Cells}, volume = {10}, number = {7}, pages = {}, pmid = {34359962}, issn = {2073-4409}, support = {IOS-1755379//National Science Foundation/ ; IOS-1122101//National Science Foundation/ ; }, mesh = {Animals ; Fertility/*physiology ; Humans ; Male ; Nematoda/*metabolism ; Reproduction/*physiology ; Selection, Genetic ; *Sex Ratio ; Spermatozoa/cytology ; }, abstract = {Parker, Baker, and Smith provided the first robust theory explaining why anisogamy evolves in parallel in multicellular organisms. Anisogamy sets the stage for the emergence of separate sexes, and for another phenomenon with which Parker is associated: sperm competition. In outcrossing taxa with separate sexes, Fisher proposed that the sex ratio will tend towards unity in large, randomly mating populations due to a fitness advantage that accrues in individuals of the rarer sex. This creates a vast excess of sperm over that required to fertilize all available eggs, and intense competition as a result. However, small, inbred populations can experience selection for skewed sex ratios. This is widely appreciated in haplodiploid organisms, in which females can control the sex ratio behaviorally. In this review, we discuss recent research in nematodes that has characterized the mechanisms underlying highly skewed sex ratios in fully diploid systems. These include self-fertile hermaphroditism and the adaptive elimination of sperm competition factors, facultative parthenogenesis, non-Mendelian meiotic oddities involving the sex chromosomes, and environmental sex determination. By connecting sex ratio evolution and sperm biology in surprising ways, these phenomena link two "seminal" contributions of G. A. Parker.}, } @article {pmid34356075, year = {2021}, author = {Kloareg, B and Badis, Y and Cock, JM and Michel, G}, title = {Role and Evolution of the Extracellular Matrix in the Acquisition of Complex Multicellularity in Eukaryotes: A Macroalgal Perspective.}, journal = {Genes}, volume = {12}, number = {7}, pages = {}, pmid = {34356075}, issn = {2073-4425}, mesh = {Animals ; *Biological Evolution ; Eukaryota/classification/*physiology ; Extracellular Matrix/*physiology ; Seaweed/classification/*physiology ; }, abstract = {Multicellular eukaryotes are characterized by an expanded extracellular matrix (ECM) with a diversified composition. The ECM is involved in determining tissue texture, screening cells from the outside medium, development, and innate immunity, all of which are essential features in the biology of multicellular eukaryotes. This review addresses the origin and evolution of the ECM, with a focus on multicellular marine algae. We show that in these lineages the expansion of extracellular matrix played a major role in the acquisition of complex multicellularity through its capacity to connect, position, shield, and defend the cells. Multiple innovations were necessary during these evolutionary processes, leading to striking convergences in the structures and functions of the ECMs of algae, animals, and plants.}, } @article {pmid34356071, year = {2021}, author = {Petroll, R and Schreiber, M and Finke, H and Cock, JM and Gould, SB and Rensing, SA}, title = {Signatures of Transcription Factor Evolution and the Secondary Gain of Red Algae Complexity.}, journal = {Genes}, volume = {12}, number = {7}, pages = {}, pmid = {34356071}, issn = {2073-4425}, mesh = {*Evolution, Molecular ; *Genetic Variation ; *Genome ; *Phylogeny ; Rhodophyta/chemistry/*classification/*genetics/metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Red algae (Rhodophyta) belong to the superphylum Archaeplastida, and are a species-rich group exhibiting diverse morphologies. Theory has it that the unicellular red algal ancestor went through a phase of genome contraction caused by adaptation to extreme environments. More recently, the classes Porphyridiophyceae, Bangiophyceae, and Florideophyceae experienced genome expansions, coinciding with an increase in morphological complexity. Transcription-associated proteins (TAPs) regulate transcription, show lineage-specific patterns, and are related to organismal complexity. To better understand red algal TAP complexity and evolution, we investigated the TAP family complement of uni- and multi-cellular red algae. We found that the TAP family complement correlates with gain of morphological complexity in the multicellular Bangiophyceae and Florideophyceae, and that abundance of the C2H2 zinc finger transcription factor family may be associated with the acquisition of morphological complexity. An expansion of heat shock transcription factors (HSF) occurred within the unicellular Cyanidiales, potentially as an adaption to extreme environmental conditions.}, } @article {pmid34343611, year = {2021}, author = {Moroz, LL and Nikitin, MA and Poličar, PG and Kohn, AB and Romanova, DY}, title = {Evolution of glutamatergic signaling and synapses.}, journal = {Neuropharmacology}, volume = {199}, number = {}, pages = {108740}, pmid = {34343611}, issn = {1873-7064}, support = {R01 NS114491/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Glutamic Acid/*physiology ; Receptors, Glutamate/*physiology ; Signal Transduction/*physiology ; Synapses/*physiology ; }, abstract = {Glutamate (Glu) is the primary excitatory transmitter in the mammalian brain. But, we know little about the evolutionary history of this adaptation, including the selection of l-glutamate as a signaling molecule in the first place. Here, we used comparative metabolomics and genomic data to reconstruct the genealogy of glutamatergic signaling. The origin of Glu-mediated communications might be traced to primordial nitrogen and carbon metabolic pathways. The versatile chemistry of L-Glu placed this molecule at the crossroad of cellular biochemistry as one of the most abundant metabolites. From there, innovations multiplied. Many stress factors or injuries could increase extracellular glutamate concentration, which led to the development of modular molecular systems for its rapid sensing in bacteria and archaea. More than 20 evolutionarily distinct families of ionotropic glutamate receptors (iGluRs) have been identified in eukaryotes. The domain compositions of iGluRs correlate with the origins of multicellularity in eukaryotes. Although L-Glu was recruited as a neuro-muscular transmitter in the early-branching metazoans, it was predominantly a non-neuronal messenger, with a possibility that glutamatergic synapses evolved more than once. Furthermore, the molecular secretory complexity of glutamatergic synapses in invertebrates (e.g., Aplysia) can exceed their vertebrate counterparts. Comparative genomics also revealed 15+ subfamilies of iGluRs across Metazoa. However, most of this ancestral diversity had been lost in the vertebrate lineage, preserving AMPA, Kainate, Delta, and NMDA receptors. The widespread expansion of glutamate synapses in the cortical areas might be associated with the enhanced metabolic demands of the complex brain and compartmentalization of Glu signaling within modular neuronal ensembles.}, } @article {pmid34343465, year = {2021}, author = {Anda, S and Boye, E and Schink, KO and Grallert, B}, title = {Cosegregation of asymmetric features during cell division.}, journal = {Open biology}, volume = {11}, number = {8}, pages = {210116}, pmid = {34343465}, issn = {2046-2441}, mesh = {*Cell Division ; Centrosome/*physiology ; *Chromosome Segregation ; Chromosomes, Fungal/*genetics ; *Mitosis ; Schizosaccharomyces/*physiology ; Spindle Apparatus/*physiology ; }, abstract = {Cellular asymmetry plays a major role in the ageing and evolution of multicellular organisms. However, it remains unknown how the cell distinguishes 'old' from 'new' and whether asymmetry is an attribute of highly specialized cells or a feature inherent in all cells. Here, we investigate the segregation of three asymmetric features: old and new DNA, the spindle pole body (SPB, the centrosome analogue) and the old and new cell ends, using a simple unicellular eukaryote, Schizosaccharomyces pombe. To our knowledge, this is the first study exploring three asymmetric features in the same cells. We show that of the three chromosomes of S. pombe, chromosome I containing the new parental strand, preferentially segregated to the cells inheriting the old cell end. Furthermore, the new SPB also preferentially segregated to the cells inheriting the old end. Our results suggest that the ability to distinguish 'old' from 'new' and to segregate DNA asymmetrically are inherent features even in simple unicellular eukaryotes.}, } @article {pmid34338785, year = {2022}, author = {Ramalho, JJ and Jones, VAS and Mutte, S and Weijers, D}, title = {Pole position: How plant cells polarize along the axes.}, journal = {The Plant cell}, volume = {34}, number = {1}, pages = {174-192}, pmid = {34338785}, issn = {1532-298X}, mesh = {Biological Evolution ; *Cell Polarity ; *Phylogeny ; Plant Cells/*physiology ; *Plant Physiological Phenomena ; Plant Proteins/*classification ; }, abstract = {Having a sense of direction is a fundamental cellular trait that can determine cell shape, division orientation, or function, and ultimately the formation of a functional, multicellular body. Cells acquire and integrate directional information by establishing discrete subcellular domains along an axis with distinct molecular profiles, a process known as cell polarization. Insight into the principles and mechanisms underlying cell polarity has been propelled by decades of extensive research mostly in yeast and animal models. Our understanding of cell polarity establishment in plants, which lack most of the regulatory molecules identified in other eukaryotes, is more limited, but significant progress has been made in recent years. In this review, we explore how plant cells coordinately establish stable polarity axes aligned with the organ axes, highlighting similarities in the molecular logic used to polarize both plant and animal cells. We propose a classification system for plant cell polarity events and nomenclature guidelines. Finally, we provide a deep phylogenetic analysis of polar proteins and discuss the evolution of polarity machineries in plants.}, } @article {pmid34302147, year = {2021}, author = {Zhao, YG and Codogno, P and Zhang, H}, title = {Machinery, regulation and pathophysiological implications of autophagosome maturation.}, journal = {Nature reviews. Molecular cell biology}, volume = {22}, number = {11}, pages = {733-750}, pmid = {34302147}, issn = {1471-0080}, mesh = {Autophagosomes/*genetics ; Autophagy/*genetics ; Endosomes/genetics ; Humans ; Lysosomes/genetics ; Neurodegenerative Diseases/*genetics/pathology ; Phagosomes/genetics ; Protein Processing, Post-Translational/genetics ; SNARE Proteins/genetics ; Transport Vesicles/*genetics ; rab GTP-Binding Proteins/genetics ; }, abstract = {Autophagy is a versatile degradation system for maintaining cellular homeostasis whereby cytosolic materials are sequestered in a double-membrane autophagosome and subsequently delivered to lysosomes, where they are broken down. In multicellular organisms, newly formed autophagosomes undergo a process called 'maturation', in which they fuse with vesicles originating from endolysosomal compartments, including early/late endosomes and lysosomes, to form amphisomes, which eventually become degradative autolysosomes. This fusion process requires the concerted actions of multiple regulators of membrane dynamics, including SNAREs, tethering proteins and RAB GTPases, and also transport of autophagosomes and late endosomes/lysosomes towards each other. Multiple mechanisms modulate autophagosome maturation, including post-translational modification of key components, spatial distribution of phosphoinositide lipid species on membranes, RAB protein dynamics, and biogenesis and function of lysosomes. Nutrient status and various stresses integrate into the autophagosome maturation machinery to coordinate the progression of autophagic flux. Impaired autophagosome maturation is linked to the pathogenesis of various human diseases, including neurodegenerative disorders, cancer and myopathies. Furthermore, invading pathogens exploit various strategies to block autophagosome maturation, thus evading destruction and even subverting autophagic vacuoles (autophagosomes, amphisomes and autolysosomes) for survival, growth and/or release. Here, we discuss the recent progress in our understanding of the machinery and regulation of autophagosome maturation, the relevance of these mechanisms to human pathophysiology and how they are harnessed by pathogens for their benefit. We also provide perspectives on targeting autophagosome maturation therapeutically.}, } @article {pmid34293333, year = {2021}, author = {Kożyczkowska, A and Najle, SR and Ocaña-Pallarès, E and Aresté, C and Shabardina, V and Ara, PS and Ruiz-Trillo, I and Casacuberta, E}, title = {Stable transfection in protist Corallochytrium limacisporum identifies novel cellular features among unicellular animals relatives.}, journal = {Current biology : CB}, volume = {31}, number = {18}, pages = {4104-4110.e5}, doi = {10.1016/j.cub.2021.06.061}, pmid = {34293333}, issn = {1879-0445}, mesh = {Animals ; Cell Nucleus Division ; *Eukaryota/genetics ; *Fungi/genetics ; Phylogeny ; Transfection ; }, abstract = {The evolutionary path from protists to multicellular animals remains a mystery. Recent work on the genomes of several unicellular relatives of animals has shaped our understanding of the genetic changes that may have occurred in this transition.[1-3] However, the specific cellular modifications that took place to accommodate these changes remain unclear. To address this, we need to compare metazoan cells with those of their extant relatives, which are choanoflagellates, filastereans, ichthyosporeans, and corallochytreans/pluriformeans. Interestingly, these lineages display a range of developmental patterns potentially homologous to animal ones. Genetic tools have already been established in three of those lineages.[4-7] However, there are no genetic tools available for Corallochytrea. We here report the development of stable transfection in the corallochytrean Corallochytrium limacisporum. Using these tools, we discern previously unknown biological features of C. limacisporum. In particular, we identify two different paths for cell division-binary fission and coenocytic growth-that reveal a non-linear life cycle. Additionally, we found that C. limacisporum is binucleate for most of its life cycle, and that, contrary to what happens in most eukaryotes, nuclear division is decoupled from cellular division. Moreover, its actin cytoskeleton shares characteristics with both fungal and animal cells. The establishment of these tools in C. limacisporum fills an important gap in the unicellular relatives of animals, opening up new avenues of research to elucidate the specific cellular changes that occurred in the evolution of animals.}, } @article {pmid34279742, year = {2021}, author = {de Souza, ID and Reis, CF and Morais, DAA and Fernandes, VGS and Cavalcante, JVF and Dalmolin, RJS}, title = {Ancestry analysis indicates two different sets of essential genes in eukaryotic model species.}, journal = {Functional & integrative genomics}, volume = {21}, number = {3-4}, pages = {523-531}, pmid = {34279742}, issn = {1438-7948}, support = {308258/2018-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics ; *Drosophila melanogaster/genetics ; *Evolution, Molecular ; *Genes, Essential ; Mice ; *Saccharomyces cerevisiae/genetics ; *Schizosaccharomyces/genetics ; }, abstract = {Essential genes are so-called because they are crucial for organism perpetuation. Those genes are usually related to essential functions to cellular metabolism or multicellular homeostasis. Deleterious alterations on essential genes produce a spectrum of phenotypes in multicellular organisms. The effects range from the impairment of the fertilization process, disruption of fetal development, to loss of reproductive capacity. Essential genes are described as more evolutionarily conserved than non-essential genes. However, there is no consensus about the relationship between gene essentiality and gene age. Here, we identified essential genes in five model eukaryotic species (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster, Caenorhabditis elegans, and Mus musculus) and estimate their evolutionary ancestry and their network properties. We observed that essential genes, on average, are older than other genes in all species investigated. The relationship of network properties and gene essentiality convey with previous findings, showing essential genes as important nodes in biological networks. As expected, we also observed that essential orthologs shared by the five species evaluated here are old. However, all the species evaluated here have a specific set of young essential genes not shared among them. Additionally, these two groups of essential genes are involved with distinct biological functions, suggesting two sets of essential genes: (i) a set of old essential genes common to all the evaluated species, regulating basic cellular functions, and (ii) a set of young essential genes exclusive to each species, which perform specific essential functions in each species.}, } @article {pmid34275698, year = {2022}, author = {Verdonck, R and Legrand, D and Jacob, S and Philippe, H}, title = {Phenotypic plasticity through disposable genetic adaptation in ciliates.}, journal = {Trends in microbiology}, volume = {30}, number = {2}, pages = {120-130}, doi = {10.1016/j.tim.2021.06.007}, pmid = {34275698}, issn = {1878-4380}, mesh = {Adaptation, Physiological/genetics ; Biological Evolution ; *Ciliophora/genetics ; *Paramecium/genetics ; }, abstract = {Ciliates have an extraordinary genetic system in which each cell harbors two distinct kinds of nucleus, a transcriptionally active somatic nucleus and a quiescent germline nucleus. The latter undergoes classical, heritable genetic adaptation, while adaptation of the somatic nucleus is only short-term and thus disposable. The ecological and evolutionary relevance of this nuclear dimorphism have never been well formalized, which is surprising given the long history of using ciliates such as Tetrahymena and Paramecium as model organisms. We present a novel, alternative explanation for ciliate nuclear dimorphism which, we argue, should be considered an instrument of phenotypic plasticity by somatic selection on the level of the ciliate clone, as if it were a diffuse multicellular organism. This viewpoint helps to put some enigmatic aspects of ciliate biology into perspective and presents the diversity of ciliates as a large natural experiment that we can exploit to study phenotypic plasticity and organismality.}, } @article {pmid34268901, year = {2021}, author = {Bik, HM}, title = {Just keep it simple? Benchmarking the accuracy of taxonomy assignment software in metabarcoding studies.}, journal = {Molecular ecology resources}, volume = {21}, number = {7}, pages = {2187-2189}, doi = {10.1111/1755-0998.13473}, pmid = {34268901}, issn = {1755-0998}, mesh = {Animals ; *Benchmarking ; Biodiversity ; *DNA Barcoding, Taxonomic ; Humans ; Phylogeny ; RNA, Ribosomal, 16S ; Software ; }, abstract = {How do you put a name on an unknown piece of DNA? From microbes to mammals, high-throughput metabarcoding studies provide a more objective view of natural communities, overcoming many of the inherent limitations of traditional field surveys and microscopy-based observations (Deiner et al., 2017). Taxonomy assignment is one of the most critical aspects of any metabarcoding study, yet this important bioinformatics task is routinely overlooked. Biodiversity surveys and conservation efforts often depend on formal species inventories: the presence (or absence) of species, and the number of individuals reported across space and time. However, computational workflows applied in eukaryotic metabarcoding studies were originally developed for use with bacterial/archaeal data sets, where microbial researchers rely on one conserved locus (nuclear 16S rRNA) and have access to vast databases with good coverage across most prokaryotic lineages - a situation not mirrored in most multicellular taxa. In this issue of Molecular Ecology Resources, Hleap et al. (2021) carry out an extensive benchmarking exercise focused on taxonomy assignment strategies for eukaryotic metabarcoding studies utilizing the mitochondrial Cytochrome C oxidase I marker gene (COI). They assess the performance and accuracy of software tools representing diverse methodological approaches: from "simple" strategies based on sequence similarity and composition, to model-based phylogenetic and probabilistic classification tools. Contrary to popular assumptions, less complex approaches (BLAST and the QIIME2 feature classifier) consistently outperformed more sophisticated mathematical algorithms and were highly accurate for assigning taxonomy at higher levels (e.g. family). Lower-level assignments at the genus and species level still pose significant challenge for most existing algorithms, and sparse eukaryotic reference databases further limit software performance. This study illuminates current best practices for metabarcoding taxonomy assignments, and underscores the need for community-driven efforts to expand taxonomic and geographic representation in reference DNA barcode databases.}, } @article {pmid34264933, year = {2021}, author = {Loidl, J}, title = {Tetrahymena meiosis: Simple yet ingenious.}, journal = {PLoS genetics}, volume = {17}, number = {7}, pages = {e1009627}, pmid = {34264933}, issn = {1553-7404}, support = {P 31606/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Chromosome Painting ; *Epigenesis, Genetic ; *Meiosis ; Reproduction/*physiology ; Tetrahymena thermophila/*genetics ; }, abstract = {The presence of meiosis, which is a conserved component of sexual reproduction, across organisms from all eukaryotic kingdoms, strongly argues that sex is a primordial feature of eukaryotes. However, extant meiotic structures and processes can vary considerably between organisms. The ciliated protist Tetrahymena thermophila, which diverged from animals, plants, and fungi early in evolution, provides one example of a rather unconventional meiosis. Tetrahymena has a simpler meiosis compared with most other organisms: It lacks both a synaptonemal complex (SC) and specialized meiotic machinery for chromosome cohesion and has a reduced capacity to regulate meiotic recombination. Despite this, it also features several unique mechanisms, including elongation of the nucleus to twice the cell length to promote homologous pairing and prevent recombination between sister chromatids. Comparison of the meiotic programs of Tetrahymena and higher multicellular organisms may reveal how extant meiosis evolved from proto-meiosis.}, } @article {pmid34257365, year = {2021}, author = {Bestová, H and Segrestin, J and von Schwartzenberg, K and Škaloud, P and Lenormand, T and Violle, C}, title = {Biological scaling in green algae: the role of cell size and geometry.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {14425}, pmid = {34257365}, issn = {2045-2322}, mesh = {*Cell Size ; *Chlorophyta/growth & development/metabolism ; Models, Biological ; Fractals ; Biological Evolution ; }, abstract = {The Metabolic Scaling Theory (MST), hypothesizes limitations of resource-transport networks in organisms and predicts their optimization into fractal-like structures. As a result, the relationship between population growth rate and body size should follow a cross-species universal quarter-power scaling. However, the universality of metabolic scaling has been challenged, particularly across transitions from bacteria to protists to multicellulars. The population growth rate of unicellulars should be constrained by external diffusion, ruling nutrient uptake, and internal diffusion, operating nutrient distribution. Both constraints intensify with increasing size possibly leading to shifting in the scaling exponent. We focused on unicellular algae Micrasterias. Large size and fractal-like morphology make this species a transitional group between unicellular and multicellular organisms in the evolution of allometry. We tested MST predictions using measurements of growth rate, size, and morphology-related traits. We showed that growth scaling of Micrasterias follows MST predictions, reflecting constraints by internal diffusion transport. Cell fractality and density decrease led to a proportional increase in surface area with body mass relaxing external constraints. Complex allometric optimization enables to maintain quarter-power scaling of population growth rate even with a large unicellular plan. Overall, our findings support fractality as a key factor in the evolution of biological scaling.}, } @article {pmid34244514, year = {2021}, author = {Bernardes, JP and John, U and Woltermann, N and Valiadi, M and Hermann, RJ and Becks, L}, title = {The evolution of convex trade-offs enables the transition towards multicellularity.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4222}, pmid = {34244514}, issn = {2041-1723}, mesh = {Animals ; *Biological Evolution ; Cell Survival/physiology ; Chlamydomonas reinhardtii/*physiology ; *Models, Biological ; Predatory Behavior ; Rotifera/physiology ; }, abstract = {The evolutionary transition towards multicellular life often involves growth in groups of undifferentiated cells followed by differentiation into soma and germ-like cells. Theory predicts that germ soma differentiation is facilitated by a convex trade-off between survival and reproduction. However, this has never been tested and these transitions remain poorly understood at the ecological and genetic level. Here, we study the evolution of cell groups in ten isogenic lines of the unicellular green algae Chlamydomonas reinhardtii with prolonged exposure to a rotifer predator. We confirm that growth in cell groups is heritable and characterized by a convex trade-off curve between reproduction and survival. Identical mutations evolve in all cell group isolates; these are linked to survival and reducing associated cell costs. Overall, we show that just 500 generations of predator selection were sufficient to lead to a convex trade-off and incorporate evolved changes into the prey genome.}, } @article {pmid34236522, year = {2021}, author = {Vigneau, J and Borg, M}, title = {The epigenetic origin of life history transitions in plants and algae.}, journal = {Plant reproduction}, volume = {34}, number = {4}, pages = {267-285}, pmid = {34236522}, issn = {2194-7961}, mesh = {Animals ; Biological Evolution ; *Chlorophyta ; Epigenesis, Genetic ; Germ Cells, Plant ; *Magnoliopsida/genetics ; Phylogeny ; Plants/genetics ; }, abstract = {Plants and algae have a complex life history that transitions between distinct life forms called the sporophyte and the gametophyte. This phenomenon-called the alternation of generations-has fascinated botanists and phycologists for over 170 years. Despite the mesmerizing array of life histories described in plants and algae, we are only now beginning to learn about the molecular mechanisms controlling them and how they evolved. Epigenetic silencing plays an essential role in regulating gene expression during multicellular development in eukaryotes, raising questions about its impact on the life history strategy of plants and algae. Here, we trace the origin and function of epigenetic mechanisms across the plant kingdom, from unicellular green algae through to angiosperms, and attempt to reconstruct the evolutionary steps that influenced life history transitions during plant evolution. Central to this evolutionary scenario is the adaption of epigenetic silencing from a mechanism of genome defense to the repression and control of alternating generations. We extend our discussion beyond the green lineage and highlight the peculiar case of the brown algae. Unlike their unicellular diatom relatives, brown algae lack epigenetic silencing pathways common to animals and plants yet display complex life histories, hinting at the emergence of novel life history controls during stramenopile evolution.}, } @article {pmid34215938, year = {2021}, author = {Machado, SR and Rodrigues, TM}, title = {Apoplasmic barrier in the extrafloral nectary of Citharexylum myrianthum (Verbenaceae).}, journal = {Planta}, volume = {254}, number = {2}, pages = {19}, pmid = {34215938}, issn = {1432-2048}, support = {401053/2016-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 303981/2018-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 308982/2020-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Biological Transport ; Cell Wall ; Plant Nectar ; Trichomes ; *Verbenaceae ; }, abstract = {The cytological changes underlying the formation of an apoplasmic barrier in the multi-layered extrafloral nectaries of Citharexylum myrianthum are compatible with the synthesis, transport and deposition of suberin. In terms of ontogenesis and function, the intermediate layers of these nectaries are homologous with the stalks of nectar-secreting trichomes. Anticlinal cell wall impregnations are common in trichomatic nectaries and their functions as endodermis-like barriers have been discussed because of possible direct effects on the nectary physiology, mainly in the nectar secretion and resorption. However, the cytological events linked to nectary wall impregnations remain little explored. This study documents the ontogenesis and the fine structure of the EFN cells, and cytological events linked to the wall impregnations of multi-layered extrafloral nectaries (EFNs) in Citharexylum myrianthum Cham. (Verbenaceae). EFNs are patelliform, and differentiated into (a) a multicellular foot, which is compound in structure and vascularised with phloem strands, (b) a bi-layered intermediate region with thickened cell walls and (c) a single-layered secretory region with palisade-like cells. EFNs are protodermal in origin, starting with a single protodermal cell and ending with the complex, multi-layered structure. The cell wall impregnations first appear in the very young EFN and increase towards maturity. Lipid patches (assumed to be suberin) are deposited on the inner faces of the primary walls, first along the anticlinal walls and then extend to the periclinal walls. On both walls, plasmodesmata remain apparently intact during the maturation of the EFNs. In the peripheral cytoplasm there are abundant polymorphic plastids, well-developed Golgi bodies often close to rough endoplasmic reticulum profiles, mitochondria and polyribosomes. Cytological events linked to the wall impregnations are consistent with suberin synthesis, transport and deposition. Our findings offer new insights into the structure-properties of specialised nectary cell walls and so should contribute to our knowledge of the physiological and protective roles of this structure in nectar glands.}, } @article {pmid34204452, year = {2021}, author = {Cricrì, G and Bellucci, L and Montini, G and Collino, F}, title = {Urinary Extracellular Vesicles: Uncovering the Basis of the Pathological Processes in Kidney-Related Diseases.}, journal = {International journal of molecular sciences}, volume = {22}, number = {12}, pages = {}, pmid = {34204452}, issn = {1422-0067}, support = {Grant P-0038//IMPACTsim S.p.A./ ; }, mesh = {Animals ; Biomarkers/*urine ; Cell Communication ; Cell-Derived Microparticles/metabolism ; Chemical Fractionation ; Disease Management ; Disease Susceptibility ; Exosomes/metabolism ; Extracellular Vesicles/*metabolism ; Humans ; Kidney Diseases/diagnosis/etiology/*metabolism/urine ; Liquid Biopsy/methods ; Precision Medicine/methods ; Urinalysis/methods ; }, abstract = {Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell types, acting both nearby and distant from their tissue/organ of origin. In the kidney, EVs are potent intercellular messengers released by all urinary system cells and are involved in cell crosstalk, contributing to physiology and pathogenesis. Moreover, urine is a reservoir of EVs coming from the circulation after crossing the glomerular filtration barrier-or originating in the kidney. Thus, urine represents an alternative source for biomarkers in kidney-related diseases, potentially replacing standard diagnostic techniques, including kidney biopsy. This review will present an overview of EV biogenesis and classification and the leading procedures for isolating EVs from body fluids. Furthermore, their role in intra-nephron communication and their use as a diagnostic tool for precision medicine in kidney-related disorders will be discussed.}, } @article {pmid34199921, year = {2021}, author = {Mikuła, A and Tomaszewicz, W and Dziurka, M and Kaźmierczak, A and Grzyb, M and Sobczak, M and Zdańkowski, P and Rybczyński, J}, title = {The Origin of the Cyathea delgadii Sternb. Somatic Embryos Is Determined by the Developmental State of Donor Tissue and Mutual Balance of Selected Metabolites.}, journal = {Cells}, volume = {10}, number = {6}, pages = {}, pmid = {34199921}, issn = {2073-4409}, mesh = {Cytokinins/*pharmacology ; Ferns/cytology/*metabolism ; *Plant Somatic Embryogenesis Techniques ; }, abstract = {Somatic embryogenesis is the formation of a plant embryo from a cell other than the product of gametic fusion. The need to recognize the determinants of somatic cell fate has prompted investigations on how endogenous factors of donor tissues can determine the pattern of somatic embryo origin. The undertaking of this study was enabled by the newly developed experimental system of somatic embryogenesis of the tree fern Cyathea delgadii Sternb., in which the embryos are produced in hormone-free medium. The contents of 89 endogenous compounds (such as sugars, auxins, cytokinins, gibberellins, stress-related hormones, phenolic acids, polyamines, and amino acids) and cytomorphological features were compared between two types of explants giving rise to somatic embryos of unicellular or multicellular origin. We found that a large content of maltose, 1-kestose, abscisic acid, biologically active gibberellins, and phenolic acids was characteristic for single-cell somatic embryo formation pattern. In contrast, high levels of starch, callose, kinetin riboside, arginine, and ethylene promoted their multicellular origin. Networks for visualization of the relations between studied compounds were constructed based on the data obtained from analyses of a Pearson correlation coefficient heatmap. Our findings present for the first time detailed features of donor tissue that can play an important role in the somatic-to-embryogenic transition and the somatic embryo origin.}, } @article {pmid34181730, year = {2021}, author = {Wu, X and Yan, A and McAdam, SAM and Banks, JA and Zhang, S and Zhou, Y}, title = {Timing of meristem initiation and maintenance determines the morphology of fern gametophytes.}, journal = {Journal of experimental botany}, volume = {72}, number = {20}, pages = {6990-7001}, doi = {10.1093/jxb/erab307}, pmid = {34181730}, issn = {1460-2431}, mesh = {Biological Evolution ; *Ferns ; Germ Cells, Plant ; Meristem ; *Pteridaceae ; }, abstract = {The alternation of generations in land plants occurs between the sporophyte phase and the gametophyte phase. The sporophytes of seed plants develop self-maintained, multicellular meristems, and these meristems determine plant architecture. The gametophytes of seed plants lack meristems and are heterotrophic. In contrast, the gametophytes of seed-free vascular plants, including ferns, are autotrophic and free-living, developing meristems to sustain their independent growth and proliferation. Compared with meristems in the sporophytes of seed plants, the cellular mechanisms underlying meristem development in fern gametophytes remain largely unknown. Here, using confocal time-lapse live imaging and computational segmentation and quantification, we determined different patterns of cell divisions associated with the initiation and proliferation of two distinct types of meristems in gametophytes of two closely related Pteridaceae ferns, Pteris vittata and Ceratopteris richardii. Our results reveal how the simple timing of a switch between two meristems has considerable consequences for the divergent gametophyte morphologies of the two ferns. They further provide evolutionary insight into the function and regulation of gametophyte meristems in seed-free vascular plants.}, } @article {pmid34161405, year = {2021}, author = {Tan, A and Liu, Q and Septiadi, D and Chu, S and Liu, T and Richards, SJ and Rothen-Rutishauser, B and Petri-Fink, A and Gibson, MI and Boyd, BJ}, title = {Understanding selectivity of metabolic labelling and click-targeting in multicellular environments as a route to tissue selective drug delivery.}, journal = {Journal of materials chemistry. B}, volume = {9}, number = {26}, pages = {5365-5373}, doi = {10.1039/d1tb00721a}, pmid = {34161405}, issn = {2050-7518}, support = {BB/M02878X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Cell Line ; Click Chemistry ; Cyclooctanes/chemistry/*metabolism ; *Drug Delivery Systems ; Epithelial Cells/chemistry/metabolism ; Fibroblasts/chemistry/metabolism ; Gold/chemistry/*metabolism ; Hexosamines/chemistry/*metabolism ; Humans ; Metal Nanoparticles/*chemistry ; Molecular Structure ; Particle Size ; Polysaccharides/chemistry/*metabolism ; Surface Properties ; }, abstract = {Cancer cells generally exhibit higher metabolic demands relative to that of normal tissue cells. This offers great possibilities to exploit metabolic glycoengineering in combination with bio-orthogonal chemistry reactions to achieve tumour site-targeted therapeutic delivery. This work addresses the selectivity of metabolic glycan labelling in diseased (i.e., cancer) versus normal cells grown in a multicellular environment. Dibenzocylooctyne (DBCO)-bearing acetylated-d-mannosamine (Ac4ManNDBCO) was synthesised to metabolically label three different types of cell lines originating from the human lung tissues: A549 adenocarcinomic alveolar basal epithelial cells, MeT5A non-cancerous mesothelial cells, and MRC5 non-cancerous fibroblasts. These cell lines displayed different labelling sensitivity, which trended with their doubling time in the following order: A549 ≈ MeT5A > MRC5. The higher metabolic labelling efficiency inherently led to a higher extent of specific binding and accumulation of the clickable N3-conjugated gold nanoparticles (N3-AuNps, core diameter = 30 nm) in the DBCO-glycan modified A549 and MeT5A cells, but to a less prominent effect in MRC5 cells. These findings demonstrate that relative rates of cell metabolism can be exploited using metabolic labelling to recruit nanotherapeutics whilst minimising non-specific targeting of surrounding tissues.}, } @article {pmid34147614, year = {2021}, author = {Shang-Guan, XY and Cai, YJ and Xu, HZ and Cheng, X and Zhang, RF and Liu, HX}, title = {A C-type lectin with a single CRD from Onychostoma macrolepis mediates immune recognition against bacterial challenge.}, journal = {Fish & shellfish immunology}, volume = {115}, number = {}, pages = {160-170}, doi = {10.1016/j.fsi.2021.06.007}, pmid = {34147614}, issn = {1095-9947}, mesh = {Aeromonas hydrophila/physiology ; Amino Acid Sequence ; Animals ; Base Sequence ; Cyprinidae/*genetics/*immunology ; Fish Diseases/*immunology ; Fish Proteins/chemistry/genetics/immunology ; Gene Expression Profiling/veterinary ; Gene Expression Regulation/*immunology ; Gram-Negative Bacterial Infections/immunology/veterinary ; Immunity, Innate/*genetics ; Lectins, C-Type/chemistry/*genetics/*immunology ; Phylogeny ; Sequence Alignment/veterinary ; }, abstract = {C-type lectins (CTL) are a large group of pattern-recognition proteins and to play important roles in glycoprotein metabolism, multicellular integration, and immunity. Based on their overall domain structure, they can be classified as different groups that possess different physiological functions. A typical C-type lectin (named as OmLec1) was identified from the fish, Onychostoma macrolepis, an important cultured fish in China. Open reading frame of OmLec1 contains a 570 bp, encoding a protein of 189 amino acids that includes a signal peptide and a single carbohydrate-recognition domain. The phylogenetic analysis showed that OmLec1 could be grouped with C-type lectin from other fish. OmLec1 was expressed in all the tissues in our study, and the expression level was highest in liver. And its relative expression levels were significantly upregulated following infection with Aeromonas hydrophila. The recombinant OmLec1 protein (rOmLec1) could agglutinate some Gram-negative bacteria and Gram-positive bacteria in vitro in the presence of Ca[2+], showing a typical Ca[2+]-dependent carbohydrate-binding protein. Furthermore, rOmLec1 purified from E. coli BL21 (DE3), strongly bound to LPS and PGN, as well as all tested bacteria in a Ca[2+]-dependent manner. These results indicate that OmLec1 plays a central role in the innate immune response and as a pattern recognition receptor that recognizes diverse pathogens among O. macrolepis.}, } @article {pmid34147034, year = {2022}, author = {Caipa Garcia, AL and Arlt, VM and Phillips, DH}, title = {Organoids for toxicology and genetic toxicology: applications with drugs and prospects for environmental carcinogenesis.}, journal = {Mutagenesis}, volume = {37}, number = {2}, pages = {143-154}, pmid = {34147034}, issn = {1464-3804}, support = {MR/N013700/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; C98/A24032/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Carcinogenesis ; Cell Culture Techniques ; Humans ; Mammals ; Models, Biological ; *Organoids ; *Pluripotent Stem Cells ; }, abstract = {Advances in three-dimensional (3D) cell culture technology have led to the development of more biologically and physiologically relevant models to study organ development, disease, toxicology and drug screening. Organoids have been derived from many mammalian tissues, both normal and tumour, from adult stem cells and from pluripotent stem cells. Tissue organoids can retain many of the cell types and much of the structure and function of the organ of origin. Organoids derived from pluripotent stem cells display increased complexity compared with organoids derived from adult stem cells. It has been shown that organoids express many functional xenobiotic-metabolising enzymes including cytochrome P450s (CYPs). This has benefitted the drug development field in facilitating pre-clinical testing of more personalised treatments and in developing large toxicity and efficacy screens for a range of compounds. In the field of environmental and genetic toxicology, treatment of organoids with various compounds has generated responses that are close to those obtained in primary tissues and in vivo models, demonstrating the biological relevance of these in vitro multicellular 3D systems. Toxicological investigations of compounds in different tissue organoids have produced promising results indicating that organoids will refine future studies on the effects of environmental exposures and carcinogenic risk to humans. With further development and standardised procedures, advancing our understanding on the metabolic capabilities of organoids will help to validate their use to investigate the modes of action of environmental carcinogens.}, } @article {pmid34133948, year = {2021}, author = {Puzakov, MV and Puzakova, LV and Cheresiz, SV and Sang, Y}, title = {The IS630/Tc1/mariner transposons in three ctenophore genomes.}, journal = {Molecular phylogenetics and evolution}, volume = {163}, number = {}, pages = {107231}, doi = {10.1016/j.ympev.2021.107231}, pmid = {34133948}, issn = {1095-9513}, mesh = {Animals ; *Ctenophora/genetics ; *Culicidae ; DNA Transposable Elements/genetics ; Phylogeny ; Transposases/genetics ; }, abstract = {Transposable elements (TEs) exert a significant effect on the structure and functioning of the genomes and also serve as a source of the new genes. The study of the TE diversity and evolution in different taxa is indispensable for the fundamental understanding of their roles in the genomes. IS630/Tc1/mariner (ITm) transposable elements represent the most prevalent and diverse group of DNA transposons. In this work, we studied the diversity, evolutionary dynamics and the phylogenetic relationships of the ITm transposons found in three ctenophore species: Mnemiopsis leidyi, Pleurobrachia bachei, Beroe ovata. We identified 29 ITm transposons, seven of which possess the terminal inverted repeats (TIRs) and an intact transposase, and, thus, are, presumably, active. Four other ITm transposons have the features of domesticated TEs. According to the results of the phylogenetic analysis, the ITm transposons of the ctenophores represent five groups - MLE/DD34D, TLE/DD34-38E, mosquito/DD37E, Visiror/DD41D and pogo/DDxD. Pogo/DDxD superfamily turnes out to be the most diverse and prevalent, since it accounts for more than 40% of the TEs identified. The data obtained in this research will fill the gap of knowledge of the diversity and evolution of the ITm transposons in the multicellular genomes and will lay the ground for the study of the TE effects on the evolution of the ctenophores.}, } @article {pmid34127736, year = {2021}, author = {Opazo, JC and Vandewege, MW and Gutierrez, J and Zavala, K and Vargas-Chacoff, L and Morera, FJ and Mardones, GA}, title = {Independent duplications of the Golgi phosphoprotein 3 oncogene in birds.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {12483}, pmid = {34127736}, issn = {2045-2322}, mesh = {Amino Acid Sequence/genetics ; Animals ; Birds/*genetics ; Carcinogenesis/genetics ; *Evolution, Molecular ; Gene Duplication ; Golgi Apparatus/*genetics ; Humans ; Membrane Proteins/*genetics ; Neoplasms/genetics ; Oncogene Proteins/*genetics ; Phosphoproteins/genetics ; Sequence Alignment ; }, abstract = {Golgi phosphoprotein 3 (GOLPH3) was the first reported oncoprotein of the Golgi apparatus. It was identified as an evolutionarily conserved protein upon its discovery about 20 years ago, but its function remains puzzling in normal and cancer cells. The GOLPH3 gene is part of a group of genes that also includes the GOLPH3L gene. Because cancer has deep roots in multicellular evolution, studying the evolution of the GOLPH3 gene family in non-model species represents an opportunity to identify new model systems that could help better understand the biology behind this group of genes. The main goal of this study is to explore the evolution of the GOLPH3 gene family in birds as a starting point to understand the evolutionary history of this oncoprotein. We identified a repertoire of three GOLPH3 genes in birds. We found duplicated copies of the GOLPH3 gene in all main groups of birds other than paleognaths, and a single copy of the GOLPH3L gene. We suggest there were at least three independent origins for GOLPH3 duplicates. Amino acid divergence estimates show that most of the variation is located in the N-terminal region of the protein. Our transcript abundance estimations show that one paralog is highly and ubiquitously expressed, and the others were variable. Our results are an example of the significance of understanding the evolution of the GOLPH3 gene family, especially for unraveling its structural and functional attributes.}, } @article {pmid34120565, year = {2021}, author = {Miguel-Tomé, S and Llinás, RR}, title = {Broadening the definition of a nervous system to better understand the evolution of plants and animals.}, journal = {Plant signaling & behavior}, volume = {16}, number = {10}, pages = {1927562}, pmid = {34120565}, issn = {1559-2324}, mesh = {Animals ; *Biological Evolution ; Electrophysiological Phenomena ; *Nervous System Physiological Phenomena ; *Plant Physiological Phenomena ; Signal Transduction ; Terminology as Topic ; }, abstract = {Most textbook definitions recognize only animals as having nervous systems. However, for the past couple decades, botanists have been meticulously studying long-distance signaling systems in plants, and some researchers have stated that plants have a simple nervous system. Thus, an academic conflict has emerged between those who defend and those who deny the existence of a nervous system in plants. This article analyses that debate, and we propose an alternative to answering yes or no: broadening the definition of a nervous system to include plants. We claim that a definition broader than the current one, which is based only on a phylogenetic viewpoint, would be helpful in obtaining a deeper understanding of how evolution has driven the features of signal generation, transmission and processing in multicellular beings. Also, we propose two possible definitions and exemplify how broader a definition allows for new viewpoints on the evolution of plants, animals and the nervous system.}, } @article {pmid34114051, year = {2021}, author = {Márquez-Zacarías, P and Conlin, PL and Tong, K and Pentz, JT and Ratcliff, WC}, title = {Why have aggregative multicellular organisms stayed simple?.}, journal = {Current genetics}, volume = {67}, number = {6}, pages = {871-876}, pmid = {34114051}, issn = {1432-0983}, support = {DEB-1845363//Directorate for Biological Sciences/ ; IOS-1656549//Directorate for Biological Sciences/ ; Packard Foundation Fellowship//David and Lucile Packard Foundation/ ; }, mesh = {*Biological Evolution ; Clonal Evolution ; Eukaryota/cytology/*physiology ; }, abstract = {Multicellularity has evolved numerous times across the tree of life. One of the most fundamental distinctions among multicellular organisms is their developmental mode: whether they stay together during growth and develop clonally, or form a group through the aggregation of free-living cells. The five eukaryotic lineages to independently evolve complex multicellularity (animals, plants, red algae, brown algae, and fungi) all develop clonally. This fact has largely been explained through social evolutionary theory's lens of cooperation and conflict, where cheating within non-clonal groups has the potential to undermine multicellular adaptation. Multicellular organisms that form groups via aggregation could mitigate the costs of cheating by evolving kin recognition systems that prevent the formation of chimeric groups. However, recent work suggests that selection for the ability to aggregate quickly may constrain the evolution of highly specific kin recognition, sowing the seeds for persistent evolutionary conflict. Importantly, other features of aggregative multicellular life cycles may independently act to constrain the evolution of complex multicellularity. All known aggregative multicellular organisms are facultatively multicellular (as opposed to obligately multicellular), allowing unicellular-level adaptation to environmental selection. Because they primarily exist in a unicellular state, it may be difficult for aggregative multicellular organisms to evolve multicellular traits that carry pleiotropic cell-level fitness costs. Thus, even in the absence of social conflict, aggregative multicellular organisms may have limited potential for the evolution of complex multicellularity.}, } @article {pmid34102596, year = {2021}, author = {Amaral-Zettler, LA and Zettler, ER and Mincer, TJ and Klaassen, MA and Gallager, SM}, title = {Biofouling impacts on polyethylene density and sinking in coastal waters: A macro/micro tipping point?.}, journal = {Water research}, volume = {201}, number = {}, pages = {117289}, doi = {10.1016/j.watres.2021.117289}, pmid = {34102596}, issn = {1879-2448}, mesh = {Animals ; *Biofouling ; Environmental Monitoring ; North Sea ; Plastics ; Polyethylene ; *Water Pollutants, Chemical/analysis ; }, abstract = {Biofouling causing an increase in plastic density and sinking is one of the hypotheses to account for the unexpectedly low amount of buoyant plastic debris encountered at the ocean surface. Field surveys show that polyethylene and polypropylene, the two most abundant buoyant plastics, both occur below the surface and in sediments, and experimental studies confirm that biofouling can cause both of these plastics to sink. However, studies quantifying the actual density of fouled plastics are rare, despite the fact that density will determine the transport and eventual fate of plastic in the ocean. Here we investigated the role of microbial biofilms in sinking of polyethylene microplastic and quantified the density changes natural biofouling communities cause in the coastal waters of the North Sea. Molecular data confirmed the variety of bacteria and eukaryotes (including animals and other multicellular organisms) colonizing the plastic over time. Fouling communities increased the density of plastic and caused sinking, and the plastic remained negatively buoyant even during the winter with lower growth rates. Relative surface area alone, however, did not predict whether a plastic piece sank. Due to patchy colonization, fragmentation of sinking pieces may result in smaller pieces regaining buoyancy and returning to the surface. Our results suggest that primarily multicellular organisms cause sinking of plastic pieces with surface area to volume ratios (SA:V) below 100 (generally pieces above a couple hundred micrometers in size), and that this is a "tipping point" at which microbial biofilms become the key players causing sinking of smaller pieces with higher SA:V ratios, including most fibers that are too small for larger (multicellular) organisms to colonize.}, } @article {pmid34102232, year = {2021}, author = {Torday, JS}, title = {Cellular evolution of language.}, journal = {Progress in biophysics and molecular biology}, volume = {167}, number = {}, pages = {140-146}, doi = {10.1016/j.pbiomolbio.2021.05.009}, pmid = {34102232}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Humans ; *Language ; Phenotype ; }, abstract = {The evolutionary origin of language remains unknown despite many efforts to determine the origin of this signature human trait. Based on epigenetic inheritance, the current article hypothesizes that language evolved from cell-cell communication as the basis for generating structure and function embryologically and phylogenetically, as did all physiologic traits. Beginning with lipids forming the first micelle, a vertical integration of the evolved properties of the cell, from multicellular organisms to the introduction of cholesterol into the cell membrane, to the evolution of the peroxisome, the water-land transition and duplication of the βAdrenergic Receptor, the evolution of endothermy, leading to bipedalism, freeing the forelimbs for toolmaking and language, selection pressure for myelinization of the central nervous system to facilitate calcium flux, bespeaks human expression, culminating in the evolution of civilization. This process is epitomized by the Area of Broca as the structural-functional site for both motor control and language formation. The mechanistic interrelationship between motor control and language formation is underscored by the role of FoxP2 gene expression in both bipedalism and language. The effect of endothermy on bipedalism, freeing the forelimbs for toolmaking and language as the vertical integration from Cosmology to Physiology as the basis for language bespeaks human expression.}, } @article {pmid34097041, year = {2021}, author = {Li, Y and Shen, XX and Evans, B and Dunn, CW and Rokas, A}, title = {Rooting the Animal Tree of Life.}, journal = {Molecular biology and evolution}, volume = {38}, number = {10}, pages = {4322-4333}, pmid = {34097041}, issn = {1537-1719}, support = {R56 AI146096/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Ctenophora ; Phylogeny ; }, abstract = {Identifying our most distant animal relatives has emerged as one of the most challenging problems in phylogenetics. This debate has major implications for our understanding of the origin of multicellular animals and of the earliest events in animal evolution, including the origin of the nervous system. Some analyses identify sponges as our most distant animal relatives (Porifera-sister hypothesis), and others identify comb jellies (Ctenophora-sister hypothesis). These analyses vary in many respects, making it difficult to interpret previous tests of these hypotheses. To gain insight into why different studies yield different results, an important next step in the ongoing debate, we systematically test these hypotheses by synthesizing 15 previous phylogenomic studies and performing new standardized analyses under consistent conditions with additional models. We find that Ctenophora-sister is recovered across the full range of examined conditions, and Porifera-sister is recovered in some analyses under narrow conditions when most outgroups are excluded and site-heterogeneous CAT models are used. We additionally find that the number of categories in site-heterogeneous models is sufficient to explain the Porifera-sister results. Furthermore, our cross-validation analyses show CAT models that recover Porifera-sister have hundreds of additional categories and fail to fit significantly better than site-heterogenuous models with far fewer categories. Systematic and standardized testing of diverse phylogenetic models suggests that we should be skeptical of Porifera-sister results both because they are recovered under such narrow conditions and because the models in these conditions fit the data no better than other models that recover Ctenophora-sister.}, } @article {pmid34077702, year = {2021}, author = {Kang, S and Tice, AK and Stairs, CW and Jones, RE and Lahr, DJG and Brown, MW}, title = {The integrin-mediated adhesive complex in the ancestor of animals, fungi, and amoebae.}, journal = {Current biology : CB}, volume = {31}, number = {14}, pages = {3073-3085.e3}, doi = {10.1016/j.cub.2021.04.076}, pmid = {34077702}, issn = {1879-0445}, support = {MOP-142349//CIHR/Canada ; }, mesh = {Amoeba ; Animals ; *Cell Adhesion ; *Eukaryota ; Evolution, Molecular ; Fungi ; *Integrins ; Phylogeny ; }, abstract = {Integrins are transmembrane receptors that activate signal transduction pathways upon extracellular matrix binding. The integrin-mediated adhesive complex (IMAC) mediates various cell physiological processes. Although the IMAC was thought to be specific to animals, in the past ten years these complexes were discovered in other lineages of Obazoa, the group containing animals, fungi, and several microbial eukaryotes. Very recently, many genomes and transcriptomes from Amoebozoa (the eukaryotic supergroup sister to Obazoa), other obazoans, orphan protist lineages, and the eukaryotes' closest prokaryotic relatives, have become available. To increase the resolution of where and when IMAC proteins exist and have emerged, we surveyed these newly available genomes and transcriptomes for the presence of IMAC proteins. Our results highlight that many of these proteins appear to have evolved earlier in eukaryote evolution than previously thought and that co-option of this apparently ancient protein complex was key to the emergence of animal-type multicellularity. The role of the IMACs in amoebozoans is unknown, but they play critical adhesive roles in at least some unicellular organisms.}, } @article {pmid34076889, year = {2021}, author = {Badis, Y and Scornet, D and Harada, M and Caillard, C and Godfroy, O and Raphalen, M and Gachon, CMM and Coelho, SM and Motomura, T and Nagasato, C and Cock, JM}, title = {Targeted CRISPR-Cas9-based gene knockouts in the model brown alga Ectocarpus.}, journal = {The New phytologist}, volume = {231}, number = {5}, pages = {2077-2091}, doi = {10.1111/nph.17525}, pmid = {34076889}, issn = {1469-8137}, mesh = {Animals ; *CRISPR-Cas Systems/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats ; Eukaryota ; Gene Knockout Techniques ; *Phaeophyceae/genetics ; }, abstract = {Brown algae are an important group of multicellular eukaryotes, phylogenetically distinct from both the animal and land plant lineages. Ectocarpus has emerged as a model organism to study diverse aspects of brown algal biology, but this system currently lacks an effective reverse genetics methodology to analyse the functions of selected target genes. Here, we report that mutations at specific target sites are generated following the introduction of CRISPR-Cas9 ribonucleoproteins into Ectocarpus cells, using either biolistics or microinjection as the delivery method. Individuals with mutations affecting the ADENINE PHOSPHORIBOSYL TRANSFERASE (APT) gene were isolated following treatment with 2-fluoroadenine, and this selection system was used to isolate individuals in which mutations had been introduced simultaneously at APT and at a second gene. This double mutation approach could potentially be used to isolate mutants affecting any Ectocarpus gene, providing an effective reverse genetics tool for this model organism. The availability of this tool will significantly enhance the utility of Ectocarpus as a model organism for this ecologically and economically important group of marine organisms. Moreover, the methodology described here should be readily transferable to other brown algal species.}, } @article {pmid34066959, year = {2021}, author = {Miller, WB and Enguita, FJ and Leitão, AL}, title = {Non-Random Genome Editing and Natural Cellular Engineering in Cognition-Based Evolution.}, journal = {Cells}, volume = {10}, number = {5}, pages = {}, pmid = {34066959}, issn = {2073-4409}, mesh = {Animals ; *Biological Evolution ; *Cell Engineering ; Cognition/*physiology ; *Gene Editing ; *Homeostasis ; Humans ; *Selection, Genetic ; }, abstract = {Neo-Darwinism presumes that biological variation is a product of random genetic replication errors and natural selection. Cognition-Based Evolution (CBE) asserts a comprehensive alternative approach to phenotypic variation and the generation of biological novelty. In CBE, evolutionary variation is the product of natural cellular engineering that permits purposive genetic adjustments as cellular problem-solving. CBE upholds that the cornerstone of biology is the intelligent measuring cell. Since all biological information that is available to cells is ambiguous, multicellularity arises from the cellular requirement to maximize the validity of available environmental information. This is best accomplished through collective measurement purposed towards maintaining and optimizing individual cellular states of homeorhesis as dynamic flux that sustains cellular equipoise. The collective action of the multicellular measurement and assessment of information and its collaborative communication is natural cellular engineering. Its yield is linked cellular ecologies and mutualized niche constructions that comprise biofilms and holobionts. In this context, biological variation is the product of collective differential assessment of ambiguous environmental cues by networking intelligent cells. Such concerted action is enabled by non-random natural genomic editing in response to epigenetic impacts and environmental stresses. Random genetic activity can be either constrained or deployed as a 'harnessing of stochasticity'. Therefore, genes are cellular tools. Selection filters cellular solutions to environmental stresses to assure continuous cellular-organismal-environmental complementarity. Since all multicellular eukaryotes are holobionts as vast assemblages of participants of each of the three cellular domains (Prokaryota, Archaea, Eukaryota) and the virome, multicellular variation is necessarily a product of co-engineering among them.}, } @article {pmid34063320, year = {2021}, author = {Mahajan, D and Kancharla, S and Kolli, P and Sharma, AK and Singh, S and Kumar, S and Mohanty, AK and Jena, MK}, title = {Role of Fibulins in Embryonic Stage Development and Their Involvement in Various Diseases.}, journal = {Biomolecules}, volume = {11}, number = {5}, pages = {}, pmid = {34063320}, issn = {2218-273X}, mesh = {Animals ; Calcium-Binding Proteins/genetics/*metabolism ; *Embryonic Development ; Extracellular Matrix/metabolism ; Gene Expression Regulation, Developmental ; Humans ; Neoplasms/*genetics/metabolism ; Protein Isoforms/metabolism ; }, abstract = {The extracellular matrix (ECM) plays an important role in the evolution of early metazoans, as it provides structural and biochemical support to the surrounding cells through the cell-cell and cell-matrix interactions. In multi-cellular organisms, ECM plays a pivotal role in the differentiation of tissues and in the development of organs. Fibulins are ECM glycoproteins, found in a variety of tissues associated with basement membranes, elastic fibers, proteoglycan aggregates, and fibronectin microfibrils. The expression profile of fibulins reveals their role in various developmental processes such as elastogenesis, development of organs during the embryonic stage, tissue remodeling, maintenance of the structural integrity of basement membrane, and elastic fibers, as well as other cellular processes. Apart from this, fibulins are also involved in the progression of human diseases such as cancer, cardiac diseases, congenital disorders, and chronic fibrotic disorders. Different isoforms of fibulins show a dual role of tumor-suppressive and tumor-promoting activities, depending on the cell type and cellular microenvironment in the body. Knockout animal models have provided deep insight into their role in development and diseases. The present review covers details of the structural and expression patterns, along with the role of fibulins in embryonic development and disease progression, with more emphasis on their involvement in the modulation of cancer diseases.}, } @article {pmid34061031, year = {2021}, author = {Kaur, G and Iyer, LM and Burroughs, AM and Aravind, L}, title = {Bacterial death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34061031}, issn = {2050-084X}, support = {F38 LM000084/LM/NLM NIH HHS/United States ; Z01 LM000084/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Apoptosis ; Bacteria/genetics/immunology/*metabolism ; Bacterial Proteins/genetics/immunology/*metabolism ; *Death Domain Superfamily ; Evolution, Molecular ; Genomics ; Host-Pathogen Interactions ; Microbial Viability ; Phylogeny ; Prokaryotic Cells/immunology/*metabolism ; Signal Transduction ; Symbiosis ; TNF Receptor-Associated Death Domain Protein/genetics/immunology/*metabolism ; }, abstract = {Several homologous domains are shared by eukaryotic immunity and programmed cell-death systems and poorly understood bacterial proteins. Recent studies show these to be components of a network of highly regulated systems connecting apoptotic processes to counter-invader immunity, in prokaryotes with a multicellular habit. However, the provenance of key adaptor domains, namely those of the Death-like and TRADD-N superfamilies, a quintessential feature of metazoan apoptotic systems, remained murky. Here, we use sensitive sequence analysis and comparative genomics methods to identify unambiguous bacterial homologs of the Death-like and TRADD-N superfamilies. We show the former to have arisen as part of a radiation of effector-associated α-helical adaptor domains that likely mediate homotypic interactions bringing together diverse effector and signaling domains in predicted bacterial apoptosis- and counter-invader systems. Similarly, we show that the TRADD-N domain defines a key, widespread signaling bridge that links effector deployment to invader-sensing in multicellular bacterial and metazoan counter-invader systems. TRADD-N domains are expanded in aggregating marine invertebrates and point to distinctive diversifying immune strategies probably directed both at RNA and retroviruses and cellular pathogens that might infect such communities. These TRADD-N and Death-like domains helped identify several new bacterial and metazoan counter-invader systems featuring underappreciated, common functional principles: the use of intracellular invader-sensing lectin-like (NPCBM and FGS), transcription elongation GreA/B-C, glycosyltransferase-4 family, inactive NTPase (serving as nucleic acid receptors), and invader-sensing GTPase switch domains. Finally, these findings point to the possibility of multicellular bacteria-stem metazoan symbiosis in the emergence of the immune/apoptotic systems of the latter.}, } @article {pmid34052880, year = {2022}, author = {Fernández, LD and Seppey, CVW and Singer, D and Fournier, B and Tatti, D and Mitchell, EAD and Lara, E}, title = {Niche Conservatism Drives the Elevational Diversity Gradient in Major Groups of Free-Living Soil Unicellular Eukaryotes.}, journal = {Microbial ecology}, volume = {83}, number = {2}, pages = {459-469}, pmid = {34052880}, issn = {1432-184X}, mesh = {Biodiversity ; *Ciliophora/genetics ; Ecosystem ; Phylogeny ; *Soil ; }, abstract = {Ancestral adaptations to tropical-like climates drive most multicellular biogeography and macroecology. Observational studies suggest that this niche conservatism could also be shaping unicellular biogeography and macroecology, although evidence is limited to Acidobacteria and testate amoebae. We tracked the phylogenetic signal of this niche conservatism in far related and functionally contrasted groups of common soil protists (Bacillariophyta, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida) along a humid but increasingly cold elevational gradient in Switzerland. Protist diversity decreased, and the size of the geographic ranges of taxa increased with elevation and associated decreasing temperature (climate), which is consistent with a macroecological pattern known as the Rapoport effect. Bacillariophyta exhibited phylogenetically overdispersed communities assembled by competitive exclusion of closely related taxa with shared (conserved) niches. By contrast, Cercomonadida, Ciliophora, Euglyphida and Kinetoplastida exhibited phylogenetically clustered communities assembled by habitat filtering, revealing the coexistence of closely related taxa with shared (conserved) adaptations to cope with the humid but temperate to cold climate of the study site. Phylobetadiversity revealed that soil protists exhibit a strong phylogenetic turnover among elevational sites, suggesting that most taxa have evolutionary constraints that prevent them from colonizing the colder and higher sites of the elevation gradient. Our results suggest that evolutionary constraints determine how soil protists colonize climates departing from warm and humid conditions. We posit that these evolutionary constraints are linked to an ancestral adaptation to tropical-like climates, which limits their survival in exceedingly cold sites. This niche conservatism possibly drives their biogeography and macroecology along latitudinal and altitudinal climatic gradients.}, } @article {pmid34050941, year = {2021}, author = {Grandhi, TSP and To, J and Romero, A and Luna, F and Barnes, W and Walker, J and Moran, R and Newlin, R and Miraglia, L and Orth, AP and Horman, SR}, title = {High-throughput CRISPR-mediated 3D enrichment platform for functional interrogation of chemotherapeutic resistance.}, journal = {Biotechnology and bioengineering}, volume = {118}, number = {8}, pages = {3187-3199}, doi = {10.1002/bit.27844}, pmid = {34050941}, issn = {1097-0290}, mesh = {Antineoplastic Agents/*pharmacology ; *Breast Neoplasms/drug therapy/genetics/metabolism ; *CRISPR-Cas Systems ; *Cell Culture Techniques ; Cell Line, Tumor ; *Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; Female ; Humans ; Spheroids, Cellular/*metabolism ; *Tumor Microenvironment ; }, abstract = {Cancer is a disease of somatic mutations. These cellular mutations compete to dominate their microenvironment and dictate the disease outcome. While a therapeutic approach to target-specific oncogenic driver mutations helps to manage the disease, subsequent molecular evolution of tumor cells threatens to overtake therapeutic progress. There is a need for rapid, high-throughput, unbiased in vitro discovery screening platforms that capture the native complexities of the tumor and rapidly identify mutations that confer chemotherapeutic drug resistance. Taking the example of the CDK4/6 inhibitor (CDK4/6i) class of drugs, we show that the pooled in vitro CRISPR screening platform enables rapid discovery of drug resistance mutations in a three-dimensional (3D) setting. Gene-edited cancer cell clones assembled into an organotypic multicellular tumor spheroid (MCTS), exposed to CDK4/6i caused selection and enrichment of the most drug-resistant phenotypes, detectable by next-gen sequencing after a span of 28 days. The platform was sufficiently sensitive to enrich for even a single drug-resistant cell within a large, drug-responsive complex 3D tumor spheroid. The genome-wide 3D CRISPR-mediated knockout screen (>18,000 genes) identified several genes whose disruptions conferred resistance to CDK4/6i. Furthermore, multiple novel candidate genes were identified as top hits only in the microphysiological 3D enrichment assay platform and not the conventional 2D assays. Taken together, these findings suggest that including phenotypic 3D resistance profiling in decision trees could improve discovery and reconfirmation of drug resistance mechanisms and afford a platform for exploring noncell autonomous interactions, selection pressures, and clonal competition.}, } @article {pmid34047647, year = {2021}, author = {Sheng, Y and Pan, B and Wei, F and Wang, Y and Gao, S}, title = {Case Study of the Response of N[6]-Methyladenine DNA Modification to Environmental Stressors in the Unicellular Eukaryote Tetrahymena thermophila.}, journal = {mSphere}, volume = {6}, number = {3}, pages = {e0120820}, pmid = {34047647}, issn = {2379-5042}, mesh = {Adenine/*analogs & derivatives/pharmacology ; Epigenesis, Genetic ; Genome, Protozoan ; Methylation ; Protein Processing, Post-Translational ; Stress, Physiological/*drug effects/genetics ; Tetrahymena thermophila/*drug effects/*genetics/metabolism ; }, abstract = {Rediscovered as a potential epigenetic mark, N[6]-methyladenine DNA modification (6mA) was recently reported to be sensitive to environmental stressors in several multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. Here, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Single-molecule, real-time (SMRT) sequencing reveals that DNA 6mA levels in starved cells are significantly reduced, especially symmetric 6mA, compared to those in vegetatively growing cells. Despite a global 6mA reduction, the fraction of asymmetric 6mA with a high methylation level was increased, which might be the driving force for stronger nucleosome positioning in starved cells. Starvation affects expression of many metabolism-related genes, the expression level change of which is associated with the amount of 6mA change, thereby linking 6mA with global transcription and starvation adaptation. The reduction of symmetric 6mA and the increase of asymmetric 6mA coincide with the downregulation of AMT1 and upregulation of AMT2 and AMT5, which are supposedly the MT-A70 methyltransferases required for symmetric and asymmetric 6mA, respectively. These results demonstrated that a regulated 6mA response to environmental cues is evolutionarily conserved in eukaryotes. IMPORTANCE Increasing evidence indicated that 6mA could respond to environmental stressors in multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive. In the present work, we characterized the dynamic changes of 6mA under starvation in the unicellular model organism Tetrahymena thermophila. Our results provide insights into how Tetrahymena fine-tunes its 6mA level and composition upon starvation, suggesting that a regulated 6mA response to environmental cues is evolutionarily conserved in eukaryotes.}, } @article {pmid34031540, year = {2021}, author = {Kumari, P and Dahiya, P and Livanos, P and Zergiebel, L and Kölling, M and Poeschl, Y and Stamm, G and Hermann, A and Abel, S and Müller, S and Bürstenbinder, K}, title = {IQ67 DOMAIN proteins facilitate preprophase band formation and division-plane orientation.}, journal = {Nature plants}, volume = {7}, number = {6}, pages = {739-747}, pmid = {34031540}, issn = {2055-0278}, mesh = {Arabidopsis/*cytology/genetics ; Arabidopsis Proteins/genetics/*metabolism ; Dinitrobenzenes ; Gene Expression Regulation, Plant ; Green Fluorescent Proteins/genetics/metabolism ; Microtubules/drug effects/metabolism ; Mutation ; Phylogeny ; Plant Cells/drug effects/metabolism ; Plants, Genetically Modified ; Prophase ; Protein Domains ; Sulfanilamides ; Nicotiana/genetics ; Vesicular Transport Proteins/metabolism ; }, abstract = {Spatiotemporal control of cell division is essential for the growth and development of multicellular organisms. In plant cells, proper cell plate insertion during cytokinesis relies on the premitotic establishment of the division plane at the cell cortex. Two plant-specific cytoskeleton arrays, the preprophase band (PPB) and the phragmoplast, play important roles in division-plane orientation and cell plate formation, respectively[1]. Microtubule organization and dynamics and their communication with membranes at the cortex and cell plate are coordinated by multiple, mostly distinct microtubule-associated proteins[2]. How division-plane selection and establishment are linked, however, is still unknown. Here, we report members of the Arabidopsis IQ67 DOMAIN (IQD) family[3] as microtubule-targeted proteins that localize to the PPB and phragmoplast and additionally reside at the cell plate and a polarized cortical region including the cortical division zone (CDZ). IQDs physically interact with PHRAGMOPLAST ORIENTING KINESIN (POK) proteins[4,5] and PLECKSTRIN HOMOLOGY GTPase ACTIVATING (PHGAP) proteins[6], which are core components of the CDZ[1]. The loss of IQD function impairs PPB formation and affects CDZ recruitment of POKs and PHGAPs, resulting in division-plane positioning defects. We propose that IQDs act as cellular scaffolds that facilitate PPB formation and CDZ set-up during symmetric cell division.}, } @article {pmid34026448, year = {2021}, author = {Jiang, S and Li, H and Zeng, Q and Xiao, Z and Zhang, X and Xu, M and He, Y and Wei, Y and Deng, X}, title = {The Dynamic Counterbalance of RAC1-YAP/OB-Cadherin Coordinates Tissue Spreading with Stem Cell Fate Patterning.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {8}, number = {10}, pages = {2004000}, pmid = {34026448}, issn = {2198-3844}, mesh = {Animals ; Cadherins/*metabolism ; Cell Adhesion/physiology ; Cell Differentiation/physiology ; Cell Lineage ; Cell Movement/physiology ; Cells, Cultured ; Mesenchymal Stem Cells/cytology/*metabolism ; Mice ; Models, Animal ; Morphogenesis ; Signal Transduction ; YAP-Signaling Proteins/*metabolism ; rac1 GTP-Binding Protein/*metabolism ; }, abstract = {Tissue spreading represents a key morphogenetic feature of embryonic development and regenerative medicine. However, how molecular signaling orchestrates the spreading dynamics and cell fate commitment of multicellular tissue remains poorly understood. Here, it is demonstrated that the dynamic counterbalance between RAC1-YAP and OB-cadherin plays a key role in coordinating heterogeneous spreading dynamics with distinct cell fate patterning during collective spreading. The spatiotemporal evolution of individual stem cells in spheroids during collective spreading is mapped. Time-lapse cell migratory trajectory analysis combined with in situ cellular biomechanics detection reveal heterogeneous patterns of collective spreading characteristics, where the cells at the periphery are faster, stiffer, and directional compared to those in the center of the spheroid. Single-cell sequencing shows that the divergent spreading result in distinct cell fate patterning, where differentiation, proliferation, and metabolism are enhanced in peripheral cells. Molecular analysis demonstrates that the increased expression of RAC1-YAP rather than OB-cadherin facilitated cell spreading and induced differentiation, and vice versa. The in vivo wound healing experiment confirms the functional role of RAC1-YAP signaling in tissue spreading. These findings shed light on the mechanism of tissue morphogenesis in the progression of development and provide a practical strategy for desirable regenerative therapies.}, } @article {pmid34023299, year = {2021}, author = {Schneider, P and Reece, SE}, title = {The private life of malaria parasites: Strategies for sexual reproduction.}, journal = {Molecular and biochemical parasitology}, volume = {244}, number = {}, pages = {111375}, pmid = {34023299}, issn = {1872-9428}, support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biological Coevolution ; Culicidae/parasitology ; Erythrocytes/parasitology ; Female ; *Gametogenesis ; Host-Parasite Interactions/genetics ; Humans ; Insect Vectors/parasitology ; Life Cycle Stages/*genetics ; Liver/parasitology ; Malaria/*parasitology/transmission ; Male ; Plasmodium berghei/genetics/*growth & development/metabolism ; Plasmodium chabaudi/genetics/*growth & development/metabolism ; Plasmodium falciparum/genetics/*growth & development/metabolism ; Plasmodium knowlesi/genetics/*growth & development/metabolism ; Reproduction, Asexual ; Sex Ratio ; }, abstract = {Malaria parasites exhibit a complex lifecycle, requiring extensive asexual replication in the liver and blood of the vertebrate host, and in the haemocoel of the insect vector. Yet, they must also undergo a single round of sexual reproduction, which occurs in the vector's midgut upon uptake of a blood meal. Sexual reproduction is obligate for infection of the vector and thus, is essential for onwards transmission to new hosts. Sex in malaria parasites involves several bottlenecks in parasite number, making the stages involved attractive targets for blocking disease transmission. Malaria parasites have evolved a suite of adaptations ("strategies") to maximise the success of sexual reproduction and transmission, which could undermine transmission-blocking interventions. Yet, understanding parasite strategies may also reveal novel opportunities for such interventions. Here, we outline how evolutionary and ecological theories, developed to explain reproductive strategies in multicellular taxa, can be applied to explain two reproductive strategies (conversion rate and sex ratio) expressed by malaria parasites within the vertebrate host.}, } @article {pmid34020820, year = {2021}, author = {Tanay, A and Sebé-Pedrós, A}, title = {Evolutionary cell type mapping with single-cell genomics.}, journal = {Trends in genetics : TIG}, volume = {37}, number = {10}, pages = {919-932}, doi = {10.1016/j.tig.2021.04.008}, pmid = {34020820}, issn = {0168-9525}, mesh = {Animals ; Cells/*classification/*metabolism ; *Evolution, Molecular ; Genome/*genetics ; *Genomics ; Humans ; Organ Specificity ; *Single-Cell Analysis ; }, abstract = {A fundamental characteristic of animal multicellularity is the spatial coexistence of functionally specialized cell types that are all encoded by a single genome sequence. Cell type transcriptional programs are deployed and maintained by regulatory mechanisms that control the asymmetric, differential access to genomic information in each cell. This genome regulation ultimately results in specific cellular phenotypes. However, the emergence, diversity, and evolutionary dynamics of animal cell types remain almost completely unexplored beyond a few species. Single-cell genomics is emerging as a powerful tool to build comprehensive catalogs of cell types and their associated gene regulatory programs in non-traditional model species. We review the current state of sampling efforts across the animal tree of life and challenges ahead for the comparative study of cell type programs. We also discuss how the phylogenetic integration of cell atlases can lead to the development of models of cell type evolution and a phylogenetic taxonomy of cells.}, } @article {pmid34007033, year = {2021}, author = {Maier, BA and Kiefer, P and Field, CM and Hemmerle, L and Bortfeld-Miller, M and Emmenegger, B and Schäfer, M and Pfeilmeier, S and Sunagawa, S and Vogel, CM and Vorholt, JA}, title = {A general non-self response as part of plant immunity.}, journal = {Nature plants}, volume = {7}, number = {5}, pages = {696-705}, pmid = {34007033}, issn = {2055-0278}, support = {668991/ERC_/European Research Council/International ; }, mesh = {Arabidopsis/*immunology/microbiology/physiology ; Bacteria/genetics/immunology ; Gene Expression Regulation, Plant ; Genes, Plant/immunology/physiology ; Metabolome ; Phylogeny ; Plant Diseases/immunology/microbiology ; Plant Immunity/genetics/physiology ; Secondary Metabolism ; Tryptophan/metabolism ; }, abstract = {Plants, like other multicellular lifeforms, are colonized by microorganisms. How plants respond to their microbiota is currently not well understood. We used a phylogenetically diverse set of 39 endogenous bacterial strains from Arabidopsis thaliana leaves to assess host transcriptional and metabolic adaptations to bacterial encounters. We identified a molecular response, which we termed the general non-self response (GNSR) that involves the expression of a core set of 24 genes. The GNSR genes are not only consistently induced by the presence of most strains, they also comprise the most differentially regulated genes across treatments and are predictive of a hierarchical transcriptional reprogramming beyond the GNSR. Using a complementary untargeted metabolomics approach we link the GNSR to the tryptophan-derived secondary metabolism, highlighting the importance of small molecules in plant-microbe interactions. We demonstrate that several of the GNSR genes are required for resistance against the bacterial pathogen Pseudomonas syringae. Our results suggest that the GNSR constitutes a defence adaptation strategy that is consistently elicited by diverse strains from various phyla, contributes to host protection and involves secondary metabolism.}, } @article {pmid33990594, year = {2021}, author = {Bozdag, GO and Libby, E and Pineau, R and Reinhard, CT and Ratcliff, WC}, title = {Oxygen suppression of macroscopic multicellularity.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2838}, pmid = {33990594}, issn = {2041-1723}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; }, mesh = {Aerobiosis ; Anaerobiosis ; *Biological Evolution ; Biophysical Phenomena ; DNA-Binding Proteins/genetics ; Directed Molecular Evolution ; Eukaryotic Cells/*cytology/*metabolism ; Gene Deletion ; Genetic Engineering ; *Models, Biological ; Oxygen/*metabolism ; Saccharomyces cerevisiae/*cytology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Selection, Genetic ; Synthetic Biology ; Transcription Factors/genetics ; }, abstract = {Atmospheric oxygen is thought to have played a vital role in the evolution of large, complex multicellular organisms. Challenging the prevailing theory, we show that the transition from an anaerobic to an aerobic world can strongly suppress the evolution of macroscopic multicellularity. Here we select for increased size in multicellular 'snowflake' yeast across a range of metabolically-available O2 levels. While yeast under anaerobic and high-O2 conditions evolved to be considerably larger, intermediate O2 constrained the evolution of large size. Through sequencing and synthetic strain construction, we confirm that this is due to O2-mediated divergent selection acting on organism size. We show via mathematical modeling that our results stem from nearly universal evolutionary and biophysical trade-offs, and thus should apply broadly. These results highlight the fact that oxygen is a double-edged sword: while it provides significant metabolic advantages, selection for efficient use of this resource may paradoxically suppress the evolution of macroscopic multicellular organisms.}, } @article {pmid33988501, year = {2021}, author = {Lu, YX and Regan, JC and Eßer, J and Drews, LF and Weinseis, T and Stinn, J and Hahn, O and Miller, RA and Grönke, S and Partridge, L}, title = {A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33988501}, issn = {2050-084X}, support = {P30 AG024824/AG/NIA NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; U01 AG022303/AG/NIA NIH HHS/United States ; U19 AG023122/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*drug effects/metabolism ; Animals ; *Autophagy ; Chromatin/metabolism ; Drosophila melanogaster ; Eukaryotic Initiation Factor-3/metabolism ; Female ; Gene Expression Regulation ; Histones/genetics/*metabolism ; Intestines ; Mechanistic Target of Rapamycin Complex 1/genetics/*metabolism ; Mice ; Sirolimus/pharmacology ; }, abstract = {Age-related changes to histone levels are seen in many species. However, it is unclear whether changes to histone expression could be exploited to ameliorate the effects of ageing in multicellular organisms. Here we show that inhibition of mTORC1 by the lifespan-extending drug rapamycin increases expression of histones H3 and H4 post-transcriptionally through eIF3-mediated translation. Elevated expression of H3/H4 in intestinal enterocytes in Drosophila alters chromatin organisation, induces intestinal autophagy through transcriptional regulation, and prevents age-related decline in the intestine. Importantly, it also mediates rapamycin-induced longevity and intestinal health. Histones H3/H4 regulate expression of an autophagy cargo adaptor Bchs (WDFY3 in mammals), increased expression of which in enterocytes mediates increased H3/H4-dependent healthy longevity. In mice, rapamycin treatment increases expression of histone proteins and Wdfy3 transcription, and alters chromatin organisation in the small intestine, suggesting that the mTORC1-histone axis is at least partially conserved in mammals and may offer new targets for anti-ageing interventions.}, } @article {pmid33984158, year = {2021}, author = {Lineweaver, CH and Bussey, KJ and Blackburn, AC and Davies, PCW}, title = {Cancer progression as a sequence of atavistic reversions.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {7}, pages = {e2000305}, pmid = {33984158}, issn = {1521-1878}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; U54-CA143682/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Eukaryota ; Eukaryotic Cells ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {It has long been recognized that cancer onset and progression represent a type of reversion to an ancestral quasi-unicellular phenotype. This general concept has been refined into the atavistic model of cancer that attempts to provide a quantitative analysis and testable predictions based on genomic data. Over the past decade, support for the multicellular-to-unicellular reversion predicted by the atavism model has come from phylostratigraphy. Here, we propose that cancer onset and progression involve more than a one-off multicellular-to-unicellular reversion, and are better described as a series of reversionary transitions. We make new predictions based on the chronology of the unicellular-eukaryote-to-multicellular-eukaryote transition. We also make new predictions based on three other evolutionary transitions that occurred in our lineage: eukaryogenesis, oxidative phosphorylation and the transition to adaptive immunity. We propose several modifications to current phylostratigraphy to improve age resolution to test these predictions. Also see the video abstract here: https://youtu.be/3unEu5JYJrQ.}, } @article {pmid33983920, year = {2021}, author = {van Gestel, J and Wagner, A}, title = {Cryptic surface-associated multicellularity emerges through cell adhesion and its regulation.}, journal = {PLoS biology}, volume = {19}, number = {5}, pages = {e3001250}, pmid = {33983920}, issn = {1545-7885}, mesh = {Animals ; Bacteria/metabolism ; Bacterial Adhesion/*physiology ; Biological Evolution ; Cell Adhesion/*physiology ; Cell Communication/physiology ; Cell Polarity/physiology ; Evolution, Molecular ; Fungi/metabolism ; Humans ; }, abstract = {The repeated evolution of multicellularity led to a wide diversity of organisms, many of which are sessile, including land plants, many fungi, and colonial animals. Sessile organisms adhere to a surface for most of their lives, where they grow and compete for space. Despite the prevalence of surface-associated multicellularity, little is known about its evolutionary origin. Here, we introduce a novel theoretical approach, based on spatial lineage tracking of cells, to study this origin. We show that multicellularity can rapidly evolve from two widespread cellular properties: cell adhesion and the regulatory control of adhesion. By evolving adhesion, cells attach to a surface, where they spontaneously give rise to primitive cell collectives that differ in size, life span, and mode of propagation. Selection in favor of large collectives increases the fraction of adhesive cells until a surface becomes fully occupied. Through kin recognition, collectives then evolve a central-peripheral polarity in cell adhesion that supports a division of labor between cells and profoundly impacts growth. Despite this spatial organization, nascent collectives remain cryptic, lack well-defined boundaries, and would require experimental lineage tracking technologies for their identification. Our results suggest that cryptic multicellularity could readily evolve and originate well before multicellular individuals become morphologically evident.}, } @article {pmid33979602, year = {2021}, author = {Joy, DA and Libby, ARG and McDevitt, TC}, title = {Deep neural net tracking of human pluripotent stem cells reveals intrinsic behaviors directing morphogenesis.}, journal = {Stem cell reports}, volume = {16}, number = {5}, pages = {1317-1330}, pmid = {33979602}, issn = {2213-6711}, support = {T32 HD007470/HD/NICHD NIH HHS/United States ; }, mesh = {Bone Morphogenetic Protein 4/pharmacology ; Cell Count ; Cell Differentiation/drug effects ; Cell Lineage/drug effects ; Cell Movement/drug effects ; Cell Tracking ; Cells, Cultured ; Humans ; Image Processing, Computer-Assisted ; Induced Pluripotent Stem Cells/*cytology/drug effects ; *Morphogenesis/drug effects ; *Neural Networks, Computer ; Smad Proteins/metabolism ; }, abstract = {Lineage tracing is a powerful tool in developmental biology to interrogate the evolution of tissue formation, but the dense, three-dimensional nature of tissue limits the assembly of individual cell trajectories into complete reconstructions of development. Human induced pluripotent stem cells (hiPSCs) can recapitulate aspects of developmental processes, providing an in vitro platform to assess the dynamic collective behaviors directing tissue morphogenesis. Here, we trained an ensemble of neural networks to track individual hiPSCs in time-lapse microscopy, generating longitudinal measures of cell and cellular neighborhood properties on timescales from minutes to days. Our analysis reveals that, while individual cell parameters are not strongly affected by pluripotency maintenance conditions or morphogenic cues, regional changes in cell behavior predict cell fate and colony organization. By generating complete multicellular reconstructions of hiPSC behavior, our tracking pipeline enables fine-grained understanding of morphogenesis by elucidating the role of regional behavior in early tissue formation.}, } @article {pmid33972551, year = {2021}, author = {Tsutsui, K and Machida, H and Nakagawa, A and Ahn, K and Morita, R and Sekiguchi, K and Miner, JH and Fujiwara, H}, title = {Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2577}, pmid = {33972551}, issn = {2041-1723}, support = {R01 DK078314/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Basement Membrane/*cytology/metabolism/ultrastructure ; Epithelial Cells/metabolism ; Extracellular Matrix/genetics/*metabolism ; Female ; Fibroblasts/metabolism ; Hair Follicle/*metabolism ; Immunohistochemistry ; Laminin/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Electron, Transmission ; Multigene Family ; Muscle Cells/metabolism ; Neurons/metabolism ; Single-Cell Analysis ; Transcriptome/*genetics ; }, abstract = {Inter-tissue interaction is fundamental to multicellularity. Although the basement membrane (BM) is located at tissue interfaces, its mode of action in inter-tissue interactions remains poorly understood, mainly because the molecular and structural details of the BM at distinct inter-tissue interfaces remain unclear. By combining quantitative transcriptomics and immunohistochemistry, we systematically identify the cellular origin, molecular identity and tissue distribution of extracellular matrix molecules in mouse hair follicles, and reveal that BM composition and architecture are exquisitely specialized for distinct inter-tissue interactions, including epithelial-fibroblast, epithelial-muscle and epithelial-nerve interactions. The epithelial-fibroblast interface, namely, hair germ-dermal papilla interface, makes asymmetrically organized side-specific heterogeneity in the BM, defined by the newly characterized interface, hook and mesh BMs. One component of these BMs, laminin α5, is required for hair cycle regulation and hair germ-dermal papilla anchoring. Our study highlights the significance of BM heterogeneity in distinct inter-tissue interactions.}, } @article {pmid33961843, year = {2021}, author = {Levin, M}, title = {Bioelectrical approaches to cancer as a problem of the scaling of the cellular self.}, journal = {Progress in biophysics and molecular biology}, volume = {165}, number = {}, pages = {102-113}, doi = {10.1016/j.pbiomolbio.2021.04.007}, pmid = {33961843}, issn = {1873-1732}, mesh = {Electrophysiological Phenomena ; Humans ; Membrane Potentials ; Morphogenesis ; *Neoplasms ; *Signal Transduction ; }, abstract = {One lens with which to understand the complex phenomenon of cancer is that of developmental biology. Cancer is the inevitable consequence of a breakdown of the communication that enables individual cells to join into computational networks that work towards large-scale, morphogenetic goals instead of more primitive, unicellular objectives. This perspective suggests that cancer may be a physiological disorder, not necessarily due to problems with the genetically-specified protein hardware. One aspect of morphogenetic coordination is bioelectric signaling, and indeed an abnormal bioelectric signature non-invasively reveals the site of incipient tumors in amphibian models. Functionally, a disruption of resting potential states triggers metastatic melanoma phenotypes in embryos with no genetic defects or carcinogen exposure. Conversely, optogenetic or molecular-biological modulation of bioelectric states can override powerful oncogenic mutations and prevent or normalize tumors. The bioelectrically-mediated information flows that harness cells toward body-level anatomical outcomes represent a very attractive and tractable endogenous control system, which is being targeted by emerging approaches to cancer.}, } @article {pmid33952585, year = {2021}, author = {Russo, M and Sogari, A and Bardelli, A}, title = {Adaptive Evolution: How Bacteria and Cancer Cells Survive Stressful Conditions and Drug Treatment.}, journal = {Cancer discovery}, volume = {11}, number = {8}, pages = {1886-1895}, doi = {10.1158/2159-8290.CD-20-1588}, pmid = {33952585}, issn = {2159-8290}, mesh = {*Bacteria ; *Biological Evolution ; *Homeostasis ; Humans ; *Neoplasms ; }, abstract = {Cancer is characterized by loss of the regulatory mechanisms that preserve homeostasis in multicellular organisms, such as controlled proliferation, cell-cell adhesion, and tissue differentiation. The breakdown of multicellularity rules is accompanied by activation of "selfish," unicellular-like life features, which are linked to the increased adaptability to environmental changes displayed by cancer cells. Mechanisms of stress response, resembling those observed in unicellular organisms, are actively exploited by mammalian cancer cells to boost genetic diversity and increase chances of survival under unfavorable conditions, such as lack of oxygen/nutrients or exposure to drugs. Unicellular organisms under stressful conditions (e.g., antibiotic treatment) stop replicating or slowly divide and transiently increase their mutation rates to foster diversity, a process known as adaptive mutability. Analogously, tumor cells exposed to drugs enter a persister phenotype and can reduce DNA replication fidelity, which in turn fosters genetic diversity. The implications of adaptive evolution are of relevance to understand resistance to anticancer therapies.}, } @article {pmid33947812, year = {2021}, author = {Hartl, B and Hübl, M and Kahl, G and Zöttl, A}, title = {Microswimmers learning chemotaxis with genetic algorithms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {19}, pages = {}, pmid = {33947812}, issn = {1091-6490}, mesh = {Algorithms ; Animals ; Caenorhabditis elegans/physiology ; Chemotaxis/*genetics/*physiology ; Computer Simulation ; Flagella/physiology ; Learning/*physiology ; Machine Learning ; Models, Biological ; Motion ; Neural Networks, Computer ; Swimming/*physiology ; }, abstract = {Various microorganisms and some mammalian cells are able to swim in viscous fluids by performing nonreciprocal body deformations, such as rotating attached flagella or by distorting their entire body. In order to perform chemotaxis (i.e., to move toward and to stay at high concentrations of nutrients), they adapt their swimming gaits in a nontrivial manner. Here, we propose a computational model, which features autonomous shape adaptation of microswimmers moving in one dimension toward high field concentrations. As an internal decision-making machinery, we use artificial neural networks, which control the motion of the microswimmer. We present two methods to measure chemical gradients, spatial and temporal sensing, as known for swimming mammalian cells and bacteria, respectively. Using the genetic algorithm NeuroEvolution of Augmenting Topologies, surprisingly simple neural networks evolve. These networks control the shape deformations of the microswimmers and allow them to navigate in static and complex time-dependent chemical environments. By introducing noisy signal transmission in the neural network, the well-known biased run-and-tumble motion emerges. Our work demonstrates that the evolution of a simple and interpretable internal decision-making machinery coupled to the environment allows navigation in diverse chemical landscapes. These findings are of relevance for intracellular biochemical sensing mechanisms of single cells or for the simple nervous system of small multicellular organisms such as Caenorhabditis elegans.}, } @article {pmid33947439, year = {2021}, author = {Wang, SY and Pollina, EA and Wang, IH and Pino, LK and Bushnell, HL and Takashima, K and Fritsche, C and Sabin, G and Garcia, BA and Greer, PL and Greer, EL}, title = {Role of epigenetics in unicellular to multicellular transition in Dictyostelium.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {134}, pmid = {33947439}, issn = {1474-760X}, support = {DP2 AG067490/AG/NIA NIH HHS/United States ; R00 AG043550/AG/NIA NIH HHS/United States ; R01 GM110174/GM/NIGMS NIH HHS/United States ; DP2 AG055947/AG/NIA NIH HHS/United States ; T32 CA009140/CA/NCI NIH HHS/United States ; K99 AG064042/AG/NIA NIH HHS/United States ; }, mesh = {Acetylation ; Animals ; Caenorhabditis elegans/cytology ; Chromatin/metabolism ; Dictyostelium/*cytology/*genetics ; *Epigenesis, Genetic ; Gene Expression Profiling ; Histones/metabolism ; Methylation ; Schizosaccharomyces/cytology ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: The evolution of multicellularity is a critical event that remains incompletely understood. We use the social amoeba, Dictyostelium discoideum, one of the rare organisms that readily transits back and forth between both unicellular and multicellular stages, to examine the role of epigenetics in regulating multicellularity.

RESULTS: While transitioning to multicellular states, patterns of H3K4 methylation and H3K27 acetylation significantly change. By combining transcriptomics, epigenomics, chromatin accessibility, and orthologous gene analyses with other unicellular and multicellular organisms, we identify 52 conserved genes, which are specifically accessible and expressed during multicellular states. We validated that four of these genes, including the H3K27 deacetylase hdaD, are necessary and that an SMC-like gene, smcl1, is sufficient for multicellularity in Dictyostelium.

CONCLUSIONS: These results highlight the importance of epigenetics in reorganizing chromatin architecture to facilitate multicellularity in Dictyostelium discoideum and raise exciting possibilities about the role of epigenetics in the evolution of multicellularity more broadly.}, } @article {pmid33947322, year = {2021}, author = {Orban, A and Weber, A and Herzog, R and Hennicke, F and Rühl, M}, title = {Transcriptome of different fruiting stages in the cultivated mushroom Cyclocybe aegerita suggests a complex regulation of fruiting and reveals enzymes putatively involved in fungal oxylipin biosynthesis.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {324}, pmid = {33947322}, issn = {1471-2164}, mesh = {*Agaricales/genetics ; Agrocybe ; Fruiting Bodies, Fungal/genetics ; Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Oxylipins ; Prospective Studies ; *Transcriptome ; }, abstract = {BACKGROUND: Cyclocybe aegerita (syn. Agrocybe aegerita) is a commercially cultivated mushroom. Its archetypal agaric morphology and its ability to undergo its whole life cycle under laboratory conditions makes this fungus a well-suited model for studying fruiting body (basidiome, basidiocarp) development. To elucidate the so far barely understood biosynthesis of fungal volatiles, alterations in the transcriptome during different developmental stages of C. aegerita were analyzed and combined with changes in the volatile profile during its different fruiting stages.

RESULTS: A transcriptomic study at seven points in time during fruiting body development of C. aegerita with seven mycelial and five fruiting body stages was conducted. Differential gene expression was observed for genes involved in fungal fruiting body formation showing interesting transcriptional patterns and correlations of these fruiting-related genes with the developmental stages. Combining transcriptome and volatilome data, enzymes putatively involved in the biosynthesis of C8 oxylipins in C. aegerita including lipoxygenases (LOXs), dioxygenases (DOXs), hydroperoxide lyases (HPLs), alcohol dehydrogenases (ADHs) and ene-reductases could be identified. Furthermore, we were able to localize the mycelium as the main source for sesquiterpenes predominant during sporulation in the headspace of C. aegerita cultures. In contrast, changes in the C8 profile detected in late stages of development are probably due to the activity of enzymes located in the fruiting bodies.

CONCLUSIONS: In this study, the combination of volatilome and transcriptome data of C. aegerita revealed interesting candidates both for functional genetics-based analysis of fruiting-related genes and for prospective enzyme characterization studies to further elucidate the so far barely understood biosynthesis of fungal C8 oxylipins.}, } @article {pmid33924996, year = {2021}, author = {Isaksson, H and Conlin, PL and Kerr, B and Ratcliff, WC and Libby, E}, title = {The Consequences of Budding versus Binary Fission on Adaptation and Aging in Primitive Multicellularity.}, journal = {Genes}, volume = {12}, number = {5}, pages = {}, pmid = {33924996}, issn = {2073-4425}, support = {R35 GM138030/GM/NIGMS NIH HHS/United States ; }, mesh = {*Adaptation, Physiological ; Aging/*genetics ; Animals ; *Cell Division ; Cellular Senescence ; *Models, Theoretical ; Mutation ; }, abstract = {Early multicellular organisms must gain adaptations to outcompete their unicellular ancestors, as well as other multicellular lineages. The tempo and mode of multicellular adaptation is influenced by many factors including the traits of individual cells. We consider how a fundamental aspect of cells, whether they reproduce via binary fission or budding, can affect the rate of adaptation in primitive multicellularity. We use mathematical models to study the spread of beneficial, growth rate mutations in unicellular populations and populations of multicellular filaments reproducing via binary fission or budding. Comparing populations once they reach carrying capacity, we find that the spread of mutations in multicellular budding populations is qualitatively distinct from the other populations and in general slower. Since budding and binary fission distribute age-accumulated damage differently, we consider the effects of cellular senescence. When growth rate decreases with cell age, we find that beneficial mutations can spread significantly faster in a multicellular budding population than its corresponding unicellular population or a population reproducing via binary fission. Our results demonstrate that basic aspects of the cell cycle can give rise to different rates of adaptation in multicellular organisms.}, } @article {pmid33923657, year = {2021}, author = {Romanova, MA and Maksimova, AI and Pawlowski, K and Voitsekhovskaja, OV}, title = {YABBY Genes in the Development and Evolution of Land Plants.}, journal = {International journal of molecular sciences}, volume = {22}, number = {8}, pages = {}, pmid = {33923657}, issn = {1422-0067}, support = {#13-04-02000, #14-04-01397, #17-04-00837//Russian Foundation for Basic Research/ ; #075-15-2020-933//the Ministry of Science and Higher Education of the Russian Federation/ ; }, mesh = {*Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Magnoliopsida/*genetics/growth & development/metabolism ; Plant Proteins/chemistry/*genetics/metabolism ; Transcription Factors/chemistry/*genetics/metabolism ; }, abstract = {Mounting evidence from genomic and transcriptomic studies suggests that most genetic networks regulating the morphogenesis of land plant sporophytes were co-opted and modified from those already present in streptophyte algae and gametophytes of bryophytes sensu lato. However, thus far, no candidate genes have been identified that could be responsible for "planation", a conversion from a three-dimensional to a two-dimensional growth pattern. According to the telome theory, "planation" was required for the genesis of the leaf blade in the course of leaf evolution. The key transcription factors responsible for leaf blade development in angiosperms are YABBY proteins, which until recently were thought to be unique for seed plants. Yet, identification of a YABBY homologue in a green alga and the recent findings of YABBY homologues in lycophytes and hornworts suggest that YABBY proteins were already present in the last common ancestor of land plants. Thus, these transcriptional factors could have been involved in "planation", which fosters our understanding of the origin of leaves. Here, we summarise the current data on functions of YABBY proteins in the vegetative and reproductive development of diverse angiosperms and gymnosperms as well as in the development of lycophytes. Furthermore, we discuss a putative role of YABBY proteins in the genesis of multicellular shoot apical meristems and in the evolution of leaves in early divergent terrestrial plants.}, } @article {pmid33880702, year = {2021}, author = {Wang, Z and Sun, X and Zhang, X and Dong, B and Yu, H}, title = {Development of a miRNA Sensor by an Inducible CRISPR-Cas9 Construct in Ciona Embryogenesis.}, journal = {Molecular biotechnology}, volume = {63}, number = {7}, pages = {613-620}, pmid = {33880702}, issn = {1559-0305}, support = {2019YFE0190900//The National Key Research and Development Program of China/ ; 2018YFD0900705//The National Key Research and Development Program of China/ ; 201961017//The Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; CRISPR-Cas Systems ; Ciona/*embryology/genetics ; Gene Editing/*methods ; Gene Silencing ; MicroRNAs/*genetics ; RNA, Guide, CRISPR-Cas Systems/genetics ; }, abstract = {MicroRNAs (miRNAs) regulate multicellular processes and diverse signaling pathways in organisms. The detection of the spatiotemporal expression of miRNA in vivo is crucial for uncovering the function of miRNA. However, most of the current detecting techniques cannot reflect the dynamics of miRNA sensitively in vivo. Here, we constructed a miRNA-induced CRISPR-Cas9 platform (MICR) used in marine chordate Ciona. The key component of MICR is a pre-single guide RNA (sgRNA) flanked by miRNA-binding sites that can be released by RNA-induced silencing complex (RISC) cleavage to form functional sgRNA in the presence of complementary miRNA. By using the miRNA-inducible CRISPR-on system (MICR-ON), we successfully detected the dynamic expression of a miRNA csa-miR-4018a during development of Ciona embryo. The detected patterns were validated to be consistent with the results by in situ hybridization. It is worth noting that the expression of csa-miR-4018a was examined by MICR-ON to be present in additional tissues, where no obvious signaling was detected by in situ hybridization, suggesting that the MICR-ON might be a more sensitive approach to detect miRNA signal in living animal. Thus, MICR-ON was demonstrated to be a sensitive and highly efficient approach for monitoring the dynamics of expression of miRNA in vivo and will facilitate the exploration of miRNA functions in biological systems.}, } @article {pmid33875673, year = {2021}, author = {Thongsripong, P and Chandler, JA and Kittayapong, P and Wilcox, BA and Kapan, DD and Bennett, SN}, title = {Metagenomic shotgun sequencing reveals host species as an important driver of virome composition in mosquitoes.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8448}, pmid = {33875673}, issn = {2045-2322}, support = {P01 AI106695/AI/NIAID NIH HHS/United States ; P20 RR018727/RR/NCRR NIH HHS/United States ; U01 AI151788/AI/NIAID NIH HHS/United States ; U54 AI065359/AI/NIAID NIH HHS/United States ; }, mesh = {Aedes/*virology ; Animals ; Culex/*virology ; *Genome, Viral ; High-Throughput Nucleotide Sequencing ; Host Specificity ; *Metagenome ; Mosquito Vectors/*virology ; Phylogeny ; RNA Viruses/*physiology ; RNA-Seq ; Thailand ; *Virome ; }, abstract = {High-throughput nucleic acid sequencing has greatly accelerated the discovery of viruses in the environment. Mosquitoes, because of their public health importance, are among those organisms whose viromes are being intensively characterized. Despite the deluge of sequence information, our understanding of the major drivers influencing the ecology of mosquito viromes remains limited. Using methods to increase the relative proportion of microbial RNA coupled with RNA-seq we characterize RNA viruses and other symbionts of three mosquito species collected along a rural to urban habitat gradient in Thailand. The full factorial study design allows us to explicitly investigate the relative importance of host species and habitat in structuring viral communities. We found that the pattern of virus presence was defined primarily by host species rather than by geographic locations or habitats. Our result suggests that insect-associated viruses display relatively narrow host ranges but are capable of spreading through a mosquito population at the geographical scale of our study. We also detected various single-celled and multicellular microorganisms such as bacteria, alveolates, fungi, and nematodes. Our study emphasizes the importance of including ecological information in viromic studies in order to gain further insights into viral ecology in systems where host specificity is driving both viral ecology and evolution.}, } @article {pmid33865960, year = {2021}, author = {Hage, H and Rosso, MN and Tarrago, L}, title = {Distribution of methionine sulfoxide reductases in fungi and conservation of the free-methionine-R-sulfoxide reductase in multicellular eukaryotes.}, journal = {Free radical biology & medicine}, volume = {169}, number = {}, pages = {187-215}, doi = {10.1016/j.freeradbiomed.2021.04.013}, pmid = {33865960}, issn = {1873-4596}, mesh = {*Eukaryota/metabolism ; Fungi/genetics ; Methionine/metabolism ; *Methionine Sulfoxide Reductases/genetics/metabolism ; Oxidation-Reduction ; Phylogeny ; }, abstract = {Methionine, either as a free amino acid or included in proteins, can be oxidized into methionine sulfoxide (MetO), which exists as R and S diastereomers. Almost all characterized organisms possess thiol-oxidoreductases named methionine sulfoxide reductase (Msr) enzymes to reduce MetO back to Met. MsrA and MsrB reduce the S and R diastereomers of MetO, respectively, with strict stereospecificity and are found in almost all organisms. Another type of thiol-oxidoreductase, the free-methionine-R-sulfoxide reductase (fRMsr), identified so far in prokaryotes and a few unicellular eukaryotes, reduces the R MetO diastereomer of the free amino acid. Moreover, some bacteria possess molybdenum-containing enzymes that reduce MetO, either in the free or protein-bound forms. All these Msrs play important roles in the protection of organisms against oxidative stress. Fungi are heterotrophic eukaryotes that colonize all niches on Earth and play fundamental functions, in organic matter recycling, as symbionts, or as pathogens of numerous organisms. However, our knowledge on fungal Msrs is still limited. Here, we performed a survey of msr genes in almost 700 genomes across the fungal kingdom. We show that most fungi possess one gene coding for each type of methionine sulfoxide reductase: MsrA, MsrB, and fRMsr. However, several fungi living in anaerobic environments or as obligate intracellular parasites were devoid of msr genes. Sequence inspection and phylogenetic analyses allowed us to identify non-canonical sequences with potentially novel enzymatic properties. Finaly, we identified several ocurences of msr horizontal gene transfer from bacteria to fungi.}, } @article {pmid33865238, year = {2021}, author = {Xu, X and Smaczniak, C and Muino, JM and Kaufmann, K}, title = {Cell identity specification in plants: lessons from flower development.}, journal = {Journal of experimental botany}, volume = {72}, number = {12}, pages = {4202-4217}, pmid = {33865238}, issn = {1460-2431}, mesh = {Cell Differentiation ; Flowers/metabolism ; Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; *Plants/genetics/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {Multicellular organisms display a fascinating complexity of cellular identities and patterns of diversification. The concept of 'cell type' aims to describe and categorize this complexity. In this review, we discuss the traditional concept of cell types and highlight the impact of single-cell technologies and spatial omics on the understanding of cellular differentiation in plants. We summarize and compare position-based and lineage-based mechanisms of cell identity specification using flower development as a model system. More than understanding ontogenetic origins of differentiated cells, an important question in plant science is to understand their position- and developmental stage-specific heterogeneity. Combinatorial action and crosstalk of external and internal signals is the key to cellular heterogeneity, often converging on transcription factors that orchestrate gene expression programs.}, } @article {pmid33861755, year = {2021}, author = {Menichelli, C and Guitard, V and Martins, RM and Lèbre, S and Lopez-Rubio, JJ and Lecellier, CH and Bréhélin, L}, title = {Identification of long regulatory elements in the genome of Plasmodium falciparum and other eukaryotes.}, journal = {PLoS computational biology}, volume = {17}, number = {4}, pages = {e1008909}, pmid = {33861755}, issn = {1553-7358}, mesh = {Eukaryota/genetics ; Gene Expression Regulation ; Gene Ontology ; Genes, Reporter ; *Genome, Protozoan ; Histones/metabolism ; Plasmodium falciparum/*genetics ; RNA Processing, Post-Transcriptional ; RNA, Antisense/genetics ; RNA, Messenger/genetics ; *Regulatory Sequences, Nucleic Acid ; Transcription, Genetic ; }, abstract = {Long regulatory elements (LREs), such as CpG islands, polydA:dT tracts or AU-rich elements, are thought to play key roles in gene regulation but, as opposed to conventional binding sites of transcription factors, few methods have been proposed to formally and automatically characterize them. We present here a computational approach named DExTER (Domain Exploration To Explain gene Regulation) dedicated to the identification of candidate LREs (cLREs) and apply it to the analysis of the genomes of P. falciparum and other eukaryotes. Our analyses show that all tested genomes contain several cLREs that are somewhat conserved along evolution, and that gene expression can be predicted with surprising accuracy on the basis of these long regions only. Regulation by cLREs exhibits very different behaviours depending on species and conditions. In P. falciparum and other Apicomplexan organisms as well as in Dictyostelium discoideum, the process appears highly dynamic, with different cLREs involved at different phases of the life cycle. For multicellular organisms, the same cLREs are involved in all tissues, but a dynamic behavior is observed along embryonic development stages. In P. falciparum, whose genome is known to be strongly depleted of transcription factors, cLREs are predictive of expression with an accuracy above 70%, and our analyses show that they are associated with both transcriptional and post-transcriptional regulation signals. Moreover, we assessed the biological relevance of one LRE discovered by DExTER in P. falciparum using an in vivo reporter assay. The source code (python) of DExTER is available at https://gite.lirmm.fr/menichelli/DExTER.}, } @article {pmid33850152, year = {2021}, author = {Brosnan, CA and Palmer, AJ and Zuryn, S}, title = {Cell-type-specific profiling of loaded miRNAs from Caenorhabditis elegans reveals spatial and temporal flexibility in Argonaute loading.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2194}, pmid = {33850152}, issn = {2041-1723}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Argonaute Proteins/*genetics/*metabolism ; Caenorhabditis elegans/*genetics ; Caenorhabditis elegans Proteins/genetics/metabolism ; Gene Expression Regulation ; MicroRNAs/*genetics/*metabolism ; Nervous System ; Protein Isoforms ; }, abstract = {Multicellularity has coincided with the evolution of microRNAs (miRNAs), small regulatory RNAs that are integrated into cellular differentiation and homeostatic gene-regulatory networks. However, the regulatory mechanisms underpinning miRNA activity have remained largely obscured because of the precise, and thus difficult to access, cellular contexts under which they operate. To resolve these, we have generated a genome-wide map of active miRNAs in Caenorhabditis elegans by revealing cell-type-specific patterns of miRNAs loaded into Argonaute (AGO) silencing complexes. Epitope-labelled AGO proteins were selectively expressed and immunoprecipitated from three distinct tissue types and associated miRNAs sequenced. In addition to providing information on biological function, we define adaptable miRNA:AGO interactions with single-cell-type and AGO-specific resolution. We demonstrate spatial and temporal dynamicism, flexibility of miRNA loading, and suggest miRNA regulatory mechanisms via AGO selectivity in different tissues and during ageing. Additionally, we resolve widespread changes in AGO-regulated gene expression by analysing translatomes specifically in neurons.}, } @article {pmid33846299, year = {2021}, author = {Shemesh, N and Jubran, J and Dror, S and Simonovsky, E and Basha, O and Argov, C and Hekselman, I and Abu-Qarn, M and Vinogradov, E and Mauer, O and Tiago, T and Carra, S and Ben-Zvi, A and Yeger-Lotem, E}, title = {The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {2180}, pmid = {33846299}, issn = {2041-1723}, mesh = {Aging/metabolism ; Animals ; Caenorhabditis elegans/metabolism ; Cell Line ; Conserved Sequence ; Evolution, Molecular ; Gene Expression Regulation ; Humans ; Mice ; Molecular Chaperones/genetics/*metabolism ; Open Reading Frames/genetics ; *Organ Specificity/genetics ; }, abstract = {The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, the organization of the chaperone system across physiological human tissues has received little attention. Through computational analyses of large-scale tissue transcriptomes, we unveil that the chaperone system is composed of core elements that are uniformly expressed across tissues, and variable elements that are differentially expressed to fit with tissue-specific requirements. We demonstrate via a proteomic analysis that the muscle-specific signature is functional and conserved. Core chaperones are significantly more abundant across tissues and more important for cell survival than variable chaperones. Together with variable chaperones, they form tissue-specific functional networks. Analysis of human organ development and aging brain transcriptomes reveals that these functional networks are established in development and decline with age. In this work, we expand the known functional organization of de novo versus stress-inducible eukaryotic chaperones into a layered core-variable architecture in multi-cellular organisms.}, } @article {pmid33839924, year = {2021}, author = {Genau, AC and Li, Z and Renzaglia, KS and Fernandez Pozo, N and Nogué, F and Haas, FB and Wilhelmsson, PKI and Ullrich, KK and Schreiber, M and Meyberg, R and Grosche, C and Rensing, SA}, title = {HAG1 and SWI3A/B control of male germ line development in P. patens suggests conservation of epigenetic reproductive control across land plants.}, journal = {Plant reproduction}, volume = {34}, number = {2}, pages = {149-173}, pmid = {33839924}, issn = {2194-7961}, support = {5R25GM107760-07/NH/NIH HHS/United States ; R25 GM107760/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; *Embryophyta ; Epigenesis, Genetic ; *Germ Cells, Plant ; Reproduction/genetics ; }, abstract = {Bryophytes as models to study the male germ line: loss-of-function mutants of epigenetic regulators HAG1 and SWI3a/b demonstrate conserved function in sexual reproduction. With the water-to-land transition, land plants evolved a peculiar haplodiplontic life cycle in which both the haploid gametophyte and the diploid sporophyte are multicellular. The switch between these phases was coined alternation of generations. Several key regulators that control the bauplan of either generation are already known. Analyses of such regulators in flowering plants are difficult due to the highly reduced gametophytic generation, and the fact that loss of function of such genes often is embryo lethal in homozygous plants. Here we set out to determine gene function and conservation via studies in bryophytes. Bryophytes are sister to vascular plants and hence allow evolutionary inferences. Moreover, embryo lethal mutants can be grown and vegetatively propagated due to the dominance of the bryophyte gametophytic generation. We determined candidates by selecting single copy orthologs that are involved in transcriptional control, and of which flowering plant mutants show defects during sexual reproduction, with a focus on the under-studied male germ line. We selected two orthologs, SWI3a/b and HAG1, and analyzed loss-of-function mutants in the moss P. patens. In both mutants, due to lack of fertile spermatozoids, fertilization and hence the switch to the diploid generation do not occur. Pphag1 additionally shows arrested male and impaired female gametangia development. We analyzed HAG1 in the dioecious liverwort M. polymorpha and found that in Mphag1 the development of gametangiophores is impaired. Taken together, we find that involvement of both regulators in sexual reproduction is conserved since the earliest divergence of land plants.}, } @article {pmid33837641, year = {2021}, author = {Abe-Fukasawa, N and Watanabe, R and Gen, Y and Nishino, T and Itasaki, N}, title = {A liquid culture cancer spheroid model reveals low PI3K/Akt pathway activity and low adhesiveness to the extracellular matrix.}, journal = {The FEBS journal}, volume = {288}, number = {19}, pages = {5650-5667}, doi = {10.1111/febs.15867}, pmid = {33837641}, issn = {1742-4658}, mesh = {Animals ; Cell Adhesion/*genetics ; *Cell Culture Techniques ; Cell Line, Tumor ; Cell Polarity/genetics ; Extracellular Matrix/genetics ; Humans ; Mice ; Neoplasm Metastasis ; Neoplasms/*genetics/pathology ; Oncogene Protein v-akt/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Signal Transduction/genetics ; Spheroids, Cellular/metabolism/*pathology ; Transplantation, Heterologous ; }, abstract = {Three-dimensional (3D) cultures of cancer cells in liquid without extracellular matrix (ECM) offer in vitro models for metastasising conditions such as those in vessels and effusion. However, liquid culturing is often hindered by cell adhesiveness, which causes large cell clumps. We previously described a liquid culture material, LA717, which prevents nonclonal cell adhesion and subsequent clumping, thus allowing clonal growth of spheroids in an anchorage-independent manner. Here, we examined such liquid culture cancer spheroids for the acquisition of apical-basal polarity, sensitivity to an Akt inhibitor (anticancer drug MK-2206) and interaction with ECM. The spheroids present apical plasma membrane on the surface, which originated from the failure of polarisation at the single-cell stage and subsequent defects in phosphorylated ezrin accumulation at the cell boundary during the first cleavage, failing internal lumen formation. At the multicellular stage, liquid culture spheroids presented bleb-like protrusion on the surface, which was enhanced by the activation of the PI3K/Akt pathway and reduced by PI3K/Akt inhibitors. Liquid culture spheroids exhibited slow proliferation speed and low endogenous pAkt levels compared with gel-cultured spheroids and 2D-cultured cells, explaining the susceptibility to the Akt-inhibiting anticancer drug. Subcutaneous xenografting and in vitro analysis demonstrated low viability and adhesive property of liquid culture spheroids to ECM, while migratory and invasive capacities were comparable with gel-cultured spheroids. These features agree with the low efficacy of circulating tumour spheroids in the settling step of metastasis. This study demonstrates the feature of anchorage-independent spheroids and validates liquid cultures as a useful method in cancer spheroid research.}, } @article {pmid33834782, year = {2021}, author = {Kwon, HY and Kumar Das, R and Jung, GT and Lee, HG and Lee, SH and Berry, SN and Tan, JKS and Park, S and Yang, JS and Park, S and Baek, K and Park, KM and Lee, JW and Choi, YK and Kim, KH and Kim, S and Kim, KP and Kang, NY and Kim, K and Chang, YT}, title = {Lipid-Oriented Live-Cell Distinction of B and T Lymphocytes.}, journal = {Journal of the American Chemical Society}, volume = {143}, number = {15}, pages = {5836-5844}, doi = {10.1021/jacs.1c00944}, pmid = {33834782}, issn = {1520-5126}, mesh = {Animals ; B-Lymphocytes/chemistry/*cytology/immunology ; Bone Marrow Cells/cytology/metabolism ; Cell Differentiation ; Cell Membrane/chemistry/*metabolism ; Flow Cytometry ; Fluorescent Dyes/*chemistry ; Lipidomics ; Mice ; T-Lymphocytes/chemistry/*cytology/immunology ; }, abstract = {The identification of each cell type is essential for understanding multicellular communities. Antibodies set as biomarkers have been the main toolbox for cell-type recognition, and chemical probes are emerging surrogates. Herein we report the first small-molecule probe, CDgB, to discriminate B lymphocytes from T lymphocytes, which was previously impossible without the help of antibodies. Through the study of the origin of cell specificity, we discovered an unexpected novel mechanism of membrane-oriented live-cell distinction. B cells maintain higher flexibility in their cell membrane than T cells and accumulate the lipid-like probe CDgB more preferably. Because B and T cells share common ancestors, we tracked the cell membrane changes of the progenitor cells and disclosed the dynamic reorganization of the membrane properties over the lymphocyte differentiation progress. This study casts an orthogonal strategy for the small-molecule cell identifier and enriches the toolbox for live-cell distinction from complex cell communities.}, } @article {pmid33802617, year = {2021}, author = {Baluška, F and Miller, WB and Reber, AS}, title = {Biomolecular Basis of Cellular Consciousness via Subcellular Nanobrains.}, journal = {International journal of molecular sciences}, volume = {22}, number = {5}, pages = {}, pmid = {33802617}, issn = {1422-0067}, mesh = {Animals ; Biological Evolution ; Cell Biology ; Cell Membrane/*physiology ; Consciousness/*physiology ; }, abstract = {Cells emerged at the very beginning of life on Earth and, in fact, are coterminous with life. They are enclosed within an excitable plasma membrane, which defines the outside and inside domains via their specific biophysical properties. Unicellular organisms, such as diverse protists and algae, still live a cellular life. However, fungi, plants, and animals evolved a multicellular existence. Recently, we have developed the cellular basis of consciousness (CBC) model, which proposes that all biological awareness, sentience and consciousness are grounded in general cell biology. Here we discuss the biomolecular structures and processes that allow for and maintain this cellular consciousness from an evolutionary perspective.}, } @article {pmid33801615, year = {2021}, author = {Kin, K and Schaap, P}, title = {Evolution of Multicellular Complexity in The Dictyostelid Social Amoebas.}, journal = {Genes}, volume = {12}, number = {4}, pages = {}, pmid = {33801615}, issn = {2073-4425}, support = {742288/ERC_/European Research Council/International ; 100293/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Amoeba/*physiology ; Biological Evolution ; Cold Temperature ; Dictyostelium/*physiology ; Evolution, Molecular ; Life Cycle Stages ; Phylogeny ; Signal Transduction ; *Stress, Physiological ; }, abstract = {Multicellularity evolved repeatedly in the history of life, but how it unfolded varies greatly between different lineages. Dictyostelid social amoebas offer a good system to study the evolution of multicellular complexity, with a well-resolved phylogeny and molecular genetic tools being available. We compare the life cycles of the Dictyostelids with closely related amoebozoans to show that complex life cycles were already present in the unicellular common ancestor of Dictyostelids. We propose frost resistance as an early driver of multicellular evolution in Dictyostelids and show that the cell signalling pathways for differentiating spore and stalk cells evolved from that for encystation. The stalk cell differentiation program was further modified, possibly through gene duplication, to evolve a new cell type, cup cells, in Group 4 Dictyostelids. Studies in various multicellular organisms, including Dictyostelids, volvocine algae, and metazoans, suggest as a common principle in the evolution of multicellular complexity that unicellular regulatory programs for adapting to environmental change serve as "proto-cell types" for subsequent evolution of multicellular organisms. Later, new cell types could further evolve by duplicating and diversifying the "proto-cell type" gene regulatory networks.}, } @article {pmid33800339, year = {2021}, author = {Patthy, L}, title = {Exon Shuffling Played a Decisive Role in the Evolution of the Genetic Toolkit for the Multicellular Body Plan of Metazoa.}, journal = {Genes}, volume = {12}, number = {3}, pages = {}, pmid = {33800339}, issn = {2073-4425}, mesh = {Animals ; *Cell Differentiation ; *Evolution, Molecular ; *Exons ; *Models, Genetic ; Transcription Factors/*genetics ; }, abstract = {Division of labor and establishment of the spatial pattern of different cell types of multicellular organisms require cell type-specific transcription factor modules that control cellular phenotypes and proteins that mediate the interactions of cells with other cells. Recent studies indicate that, although constituent protein domains of numerous components of the genetic toolkit of the multicellular body plan of Metazoa were present in the unicellular ancestor of animals, the repertoire of multidomain proteins that are indispensable for the arrangement of distinct body parts in a reproducible manner evolved only in Metazoa. We have shown that the majority of the multidomain proteins involved in cell-cell and cell-matrix interactions of Metazoa have been assembled by exon shuffling, but there is no evidence for a similar role of exon shuffling in the evolution of proteins of metazoan transcription factor modules. A possible explanation for this difference in the intracellular and intercellular toolkits is that evolution of the transcription factor modules preceded the burst of exon shuffling that led to the creation of the proteins controlling spatial patterning in Metazoa. This explanation is in harmony with the temporal-to-spatial transition hypothesis of multicellularity that proposes that cell differentiation may have predated spatial segregation of cell types in animal ancestors.}, } @article {pmid33779495, year = {2022}, author = {Porfírio-Sousa, AL and Tice, AK and Brown, MW and J G Lahr, D}, title = {Phylogenetic reconstruction and evolution of the Rab GTPase gene family in Amoebozoa.}, journal = {Small GTPases}, volume = {13}, number = {1}, pages = {100-113}, pmid = {33779495}, issn = {2154-1256}, mesh = {Phylogeny ; *rab GTP-Binding Proteins/genetics/metabolism ; Evolution, Molecular ; *Amoebozoa/genetics/metabolism ; Eukaryota/metabolism ; }, abstract = {Rab GTPase is a paralog-rich gene family that controls the maintenance of the eukaryotic cell compartmentalization system. Diverse eukaryotes have varying numbers of Rab paralogs. Currently, little is known about the evolutionary pattern of Rab GTPase in most major eukaryotic 'supergroups'. Here, we present a comprehensive phylogenetic reconstruction of the Rab GTPase gene family in the eukaryotic 'supergroup' Amoebozoa, a diverse lineage represented by unicellular and multicellular organisms. We demonstrate that Amoebozoa conserved 20 of the 23 ancestral Rab GTPases predicted to be present in the last eukaryotic common ancestor and massively expanded several 'novel' in-paralogs. Due to these 'novel' in-paralogs, the Rab family composition dramatically varies between the members of Amoebozoa; as a consequence, 'supergroup'-based studies may significantly change our current understanding of the evolution and diversity of this gene family. The high diversity of the Rab GTPase gene family in Amoebozoa makes this 'supergroup' a key lineage to study and advance our knowledge of the evolution of Rab in Eukaryotes.}, } @article {pmid33767367, year = {2021}, author = {Wang, S and Liang, H and Xu, Y and Li, L and Wang, H and Sahu, DN and Petersen, M and Melkonian, M and Sahu, SK and Liu, H}, title = {Genome-wide analyses across Viridiplantae reveal the origin and diversification of small RNA pathway-related genes.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {412}, pmid = {33767367}, issn = {2399-3642}, mesh = {*Evolution, Molecular ; Genes, Plant ; *Genome, Plant ; Phylogeny ; RNA, Small Untranslated/*genetics ; Viridiplantae/*genetics ; }, abstract = {Small RNAs play a major role in the post-transcriptional regulation of gene expression in eukaryotes. Despite the evolutionary importance of streptophyte algae, knowledge on small RNAs in this group of green algae is almost non-existent. We used genome and transcriptome data of 34 algal and plant species, and performed genome-wide analyses of small RNA (miRNA & siRNA) biosynthetic and degradation pathways. The results suggest that Viridiplantae started to evolve plant-like miRNA biogenesis and degradation after the divergence of the Mesostigmatophyceae in the streptophyte algae. We identified two major evolutionary transitions in small RNA metabolism in streptophyte algae; during the first transition, the origin of DCL-New, DCL1, AGO1/5/10 and AGO4/6/9 in the last common ancestor of Klebsormidiophyceae and all other streptophytes could be linked to abiotic stress responses and evolution of multicellularity in streptophytes. During the second transition, the evolution of DCL 2,3,4, and AGO 2,3,7 as well as DRB1 in the last common ancestor of Zygnematophyceae and embryophytes, suggests their possible contribution to pathogen defense and antibacterial immunity. Overall, the origin and diversification of DICER and AGO along with several other small RNA pathway-related genes among streptophyte algae suggested progressive adaptations of streptophyte algae during evolution to a subaerial environment.}, } @article {pmid33763054, year = {2020}, author = {Roudaire, T and Héloir, MC and Wendehenne, D and Zadoroznyj, A and Dubrez, L and Poinssot, B}, title = {Cross Kingdom Immunity: The Role of Immune Receptors and Downstream Signaling in Animal and Plant Cell Death.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {612452}, pmid = {33763054}, issn = {1664-3224}, mesh = {Animals ; Cell Death/*immunology ; Humans ; Immunity, Innate/immunology ; Inflammasomes/immunology ; Plant Cells/*immunology ; Plant Immunity/*immunology ; Plants/*immunology ; Receptors, Immunologic/*immunology ; Receptors, Pattern Recognition/immunology ; Signal Transduction/*immunology ; }, abstract = {Both plants and animals are endowed with sophisticated innate immune systems to combat microbial attack. In these multicellular eukaryotes, innate immunity implies the presence of cell surface receptors and intracellular receptors able to detect danger signal referred as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). Membrane-associated pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), C-type lectin receptors (CLRs), receptor-like kinases (RLKs), and receptor-like proteins (RLPs) are employed by these organisms for sensing different invasion patterns before triggering antimicrobial defenses that can be associated with a form of regulated cell death. Intracellularly, animals nucleotide-binding and oligomerization domain (NOD)-like receptors or plants nucleotide-binding domain (NBD)-containing leucine rich repeats (NLRs) immune receptors likely detect effectors injected into the host cell by the pathogen to hijack the immune signaling cascade. Interestingly, during the co-evolution between the hosts and their invaders, key cross-kingdom cell death-signaling macromolecular NLR-complexes have been selected, such as the inflammasome in mammals and the recently discovered resistosome in plants. In both cases, a regulated cell death located at the site of infection constitutes a very effective mean for blocking the pathogen spread and protecting the whole organism from invasion. This review aims to describe the immune mechanisms in animals and plants, mainly focusing on cell death signaling pathways, in order to highlight recent advances that could be used on one side or the other to identify the missing signaling elements between the perception of the invasion pattern by immune receptors, the induction of defenses or the transmission of danger signals to other cells. Although knowledge of plant immunity is less advanced, these organisms have certain advantages allowing easier identification of signaling events, regulators and executors of cell death, which could then be exploited directly for crop protection purposes or by analogy for medical research.}, } @article {pmid33760661, year = {2021}, author = {Barnett, AM and Mullaney, JA and Hendriks, C and Le Borgne, L and McNabb, WC and Roy, NC}, title = {Porcine colonoids and enteroids keep the memory of their origin during regeneration.}, journal = {American journal of physiology. Cell physiology}, volume = {320}, number = {5}, pages = {C794-C805}, doi = {10.1152/ajpcell.00420.2020}, pmid = {33760661}, issn = {1522-1563}, mesh = {Animals ; Biomarkers/metabolism ; *Cell Differentiation ; *Cell Lineage ; Cell Proliferation ; Colon/cytology/metabolism/*physiology ; Gene Expression Regulation ; Ileum/cytology/metabolism/*physiology ; Intestinal Mucosa/cytology/metabolism/*physiology ; Male ; Organoids/cytology/metabolism/*physiology ; Phenotype ; Signal Transduction ; Sus scrofa ; Time Factors ; Tissue Culture Techniques ; Transcriptome ; }, abstract = {The development of alternative in vitro culture methods has increased in the last decade as three-dimensional organoids of various tissues, including those of the small and large intestines. Due to their multicellular composition, organoids offer advantages over traditionally used immortalized or primary cell lines. However, organoids must be accurate models of their tissues of origin. This study compared gene expression profiles with respect to markers of specific cell types (stem cells, enterocytes, goblet, and enteroendocrine cells) and barrier maturation (tight junctions) of colonoid and enteroid cultures with their tissues of origin and colonoids with enteroids. Colonoids derived from three healthy pigs formed multilobed structures with a monolayer of cells similar to the crypt structures in colonic tissue. Colonoid and enteroid gene expression signatures were more similar to those found for the tissues of their origin than to each other. However, relative to their derived tissues, organoids had increased gene expression levels of stem cell markers Sox9 and Lgr5 encoding sex-determining region Y-box 9 and leucine-rich repeat-containing G protein-coupled rector 5, respectively. In contrast, expression levels of Occl and Zo1 encoding occludin and zonula occludens 1, respectively, were decreased. Expression levels of the cell lineage markers Atoh1, Cga, and Muc2 encoding atonal homolog 1, chromogranin A, and mucin 2, respectively, were decreased in colonoids, whereas Sglt1 and Apn encoding sodium-glucose transporter 1 and aminopeptidase A, respectively, were decreased in enteroids. These results indicate colonoid and enteroid cultures were predominantly comprised of undifferentiated cell types with decreased barrier maturation relative to their tissues of origin.}, } @article {pmid33748102, year = {2021}, author = {Dhakshinamoorthy, R and Singh, SP}, title = {Evolution of Reproductive Division of Labor - Lessons Learned From the Social Amoeba Dictyostelium discoideum During Its Multicellular Development.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {599525}, pmid = {33748102}, issn = {2296-634X}, abstract = {The origin of multicellular life from unicellular beings is an epochal step in the evolution of eukaryotes. There are several factors influencing cell fate choices during differentiation and morphogenesis of an organism. Genetic make-up of two cells that unite and fertilize is the key factor to signal the formation of various cell-types in due course of development. Although ploidy of the cell-types determines the genetics of an individual, the role of ploidy in cell fate decisions remains unclear. Dictyostelium serves as a versatile model to study the emergence of multicellular life from unicellular life forms. In this work, we investigate the role played by ploidy status of a cell on cell fate commitments during Dictyostelium development. To answer this question, we created Dictyostelium cells of different ploidy: haploid parents and derived isogenic diploids, allowing them to undergo development. The diploid strains used in this study were generated using parasexual genetics. The ploidy status of the haploids and diploids were confirmed by microscopy, flow cytometry, and karyotyping. Prior to reconstitution, we labeled the cells by two methods. First, intragenic expression of red fluorescent protein (RFP) and second, staining the amoebae with a vital, fluorescent dye carboxyfluorescein succinimidyl ester (CFSE). RFP labeled haploid cells allowed us to track the haploids in the chimeric aggregates, slugs, and fruiting bodies. The CFSE labeling method allowed us to track both the haploids and the diploids in the chimeric developmental structures. Our findings illustrate that the haploids demonstrate sturdy cell fate commitment starting from the aggregation stage. The haploids remain crowded at the aggregation centers of the haploid-diploid chimeric aggregates. At the slug stage haploids are predominantly occupying the slug posterior, and are visible in the spore population in the fruiting bodies. Our findings show that cell fate decisions during D. discoideum development are highly influenced by the ploidy status of a cell, adding a new aspect to already known factors Here, we report that ploidy status of a cell could also play a crucial role in regulating the cell fate commitments.}, } @article {pmid33745906, year = {2021}, author = {Johnson, JD and White, NL and Kangabire, A and Abrams, DM}, title = {A dynamical model for the origin of anisogamy.}, journal = {Journal of theoretical biology}, volume = {521}, number = {}, pages = {110669}, doi = {10.1016/j.jtbi.2021.110669}, pmid = {33745906}, issn = {1095-8541}, mesh = {*Biological Evolution ; Computer Simulation ; Female ; Germ Cells ; Humans ; Male ; *Models, Biological ; Reproduction ; }, abstract = {The vast majority of multi-cellular organisms are anisogamous, meaning that male and female sex cells differ in size. It remains an open question how this asymmetric state evolved, presumably from the symmetric isogamous state where all gametes are roughly the same size (drawn from the same distribution). Here, we use tools from the study of nonlinear dynamical systems to develop a simple mathematical model for this phenomenon. Unlike some prior work, we do not assume the existence of mating types. We also model frequency dependent selection via "mean-field coupling," whereby the likelihood that a gamete survives is an increasing function of its size relative to the population's mean gamete size. Using theoretical analysis and numerical simulation, we demonstrate that this mean-referenced competition will almost inevitably result in a stable anisogamous equilibrium, and thus isogamy may naturally lead to anisogamy.}, } @article {pmid33741994, year = {2021}, author = {Redmond, AK and McLysaght, A}, title = {Evidence for sponges as sister to all other animals from partitioned phylogenomics with mixture models and recoding.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1783}, pmid = {33741994}, issn = {2041-1723}, mesh = {Animals ; Biological Evolution ; Ctenophora/classification/*genetics ; Genome/*genetics ; Genomics/*methods ; Models, Genetic ; *Phylogeny ; Porifera/classification/*genetics ; Species Specificity ; }, abstract = {Resolving the relationships between the major lineages in the animal tree of life is necessary to understand the origin and evolution of key animal traits. Sponges, characterized by their simple body plan, were traditionally considered the sister group of all other animal lineages, implying a gradual increase in animal complexity from unicellularity to complex multicellularity. However, the availability of genomic data has sparked tremendous controversy as some phylogenomic studies support comb jellies taking this position, requiring secondary loss or independent origins of complex traits. Here we show that incorporating site-heterogeneous mixture models and recoding into partitioned phylogenomics alleviates systematic errors that hamper commonly-applied phylogenetic models. Testing on real datasets, we show a great improvement in model-fit that attenuates branching artefacts induced by systematic error. We reanalyse key datasets and show that partitioned phylogenomics does not support comb jellies as sister to other animals at either the supermatrix or partition-specific level.}, } @article {pmid33727612, year = {2021}, author = {Matriano, DM and Alegado, RA and Conaco, C}, title = {Detection of horizontal gene transfer in the genome of the choanoflagellate Salpingoeca rosetta.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {5993}, pmid = {33727612}, issn = {2045-2322}, mesh = {Choanoflagellata/classification/*genetics ; Computational Biology/methods ; Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genome ; Genomics/methods ; Molecular Sequence Annotation ; Phylogeny ; }, abstract = {Horizontal gene transfer (HGT), the movement of heritable materials between distantly related organisms, is crucial in eukaryotic evolution. However, the scale of HGT in choanoflagellates, the closest unicellular relatives of metazoans, and its possible roles in the evolution of animal multicellularity remains unexplored. We identified at least 175 candidate HGTs in the genome of the colonial choanoflagellate Salpingoeca rosetta using sequence-based tests. The majority of these were orthologous to genes in bacterial and microalgal lineages, yet displayed genomic features consistent with the rest of the S. rosetta genome-evidence of ancient acquisition events. Putative functions include enzymes involved in amino acid and carbohydrate metabolism, cell signaling, and the synthesis of extracellular matrix components. Functions of candidate HGTs may have contributed to the ability of choanoflagellates to assimilate novel metabolites, thereby supporting adaptation, survival in diverse ecological niches, and response to external cues that are possibly critical in the evolution of multicellularity in choanoflagellates.}, } @article {pmid33717121, year = {2021}, author = {Ramos-Martínez, E and Hernández-González, L and Ramos-Martínez, I and Pérez-Campos Mayoral, L and López-Cortés, GI and Pérez-Campos, E and Mayoral Andrade, G and Hernández-Huerta, MT and José, MV}, title = {Multiple Origins of Extracellular DNA Traps.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {621311}, pmid = {33717121}, issn = {1664-3224}, mesh = {Animals ; Biological Evolution ; Extracellular Traps/*metabolism ; Humans ; Immunity, Innate ; Neutrophils/*immunology ; Phylogeny ; }, abstract = {Extracellular DNA traps (ETs) are evolutionarily conserved antimicrobial mechanisms present in protozoa, plants, and animals. In this review, we compare their similarities in species of different taxa, and put forward the hypothesis that ETs have multiple origins. Our results are consistent with a process of evolutionary convergence in multicellular organisms through the application of a congruency test. Furthermore, we discuss why multicellularity is related to the presence of a mechanism initiating the formation of ETs.}, } @article {pmid33711511, year = {2021}, author = {Vijg, J}, title = {From DNA damage to mutations: All roads lead to aging.}, journal = {Ageing research reviews}, volume = {68}, number = {}, pages = {101316}, pmid = {33711511}, issn = {1872-9649}, support = {U01 HL145560/HL/NHLBI NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; P30 AG013319/AG/NIA NIH HHS/United States ; U01 ES029519/ES/NIEHS NIH HHS/United States ; U19 AG056278/AG/NIA NIH HHS/United States ; P30 AG038072/AG/NIA NIH HHS/United States ; P01 AG017242/AG/NIA NIH HHS/United States ; }, mesh = {Aging/genetics ; Animals ; *DNA Damage ; *DNA Repair/genetics ; Humans ; Mutagenesis ; Mutation ; }, abstract = {Damage to the repository of genetic information in cells has plagued life since its very beginning 3-4 billion years ago. Initially, in the absence of an ozone layer, especially damage from solar UV radiation must have been frequent, with other sources, most notably endogenous sources related to cell metabolism, gaining in importance over time. To cope with this high frequency of damage to the increasingly long DNA molecules that came to encode the growing complexity of cellular functions in cells, DNA repair evolved as one of the earliest genetic traits. Then as now, errors during the repair of DNA damage generated mutations, which provide the substrate for evolution by natural selection. With the emergence of multicellular organisms also the soma became a target of DNA damage and mutations. In somatic cells selection against the adverse effects of DNA damage is greatly diminished, especially in postmitotic cells after the age of first reproduction. Based on an abundance of evidence, DNA damage is now considered as the single most important driver of the degenerative processes that collectively cause aging. Here I will first briefly review the evidence for DNA damage as a cause of aging since the beginning of life. Then, after discussing the possible direct adverse effects of DNA damage and its cellular responses, I will provide an overview of the considerable progress that has recently been made in analyzing a major consequence of DNA damage in humans and other complex organisms: somatic mutations and the resulting genome mosaicism. Recent advances in studying somatic mutagenesis and genome mosaicism in different human and animal tissues will be discussed with a focus on the possible mechanisms through which loss of DNA sequence integrity could cause age-related functional decline and disease.}, } @article {pmid33690952, year = {2021}, author = {Darveau, RP and Curtis, MA}, title = {Oral biofilms revisited: A novel host tissue of bacteriological origin.}, journal = {Periodontology 2000}, volume = {86}, number = {1}, pages = {8-13}, doi = {10.1111/prd.12374}, pmid = {33690952}, issn = {1600-0757}, support = {MR/J011118/1/MRC_/Medical Research Council/United Kingdom ; MR/P012175/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Biofilms ; *Dental Plaque ; Gingiva ; Humans ; *Periodontitis ; }, abstract = {The central theme of this volume of Periodontology 2000 is that the microbial dental plaque biofilm, specifically the subgingival dental plaque biofilm, mimics a human tissue in both structure and function. As a basis for this assertion we use the definition of a tissue as an aggregate of similar cells and cell products forming a defined structure with a specific function, in a multicellular organism. Accordingly, we propose that the dental plaque biofilm represents an acquired human tissue largely of bacterial origin that maintains the health of gingival tissue. Furthermore, we acknowledge that disease can be defined as a deviation from the normal structure or an interruption to the function of any body part, organ, or system, and that is manifested by a characteristic set of symptoms and signs whose etiology, pathology, and prognosis may be known or unknown. Therefore, in this volume we present the concept that periodontitis is a disruption of the normal function of the healthy subgingival plaque biofilm with concomitant disruption to its functional properties in relation to innate defense surveillance and tissue maintenance, leading to excessive, deregulated inflammation and tissue destruction.}, } @article {pmid33683515, year = {2021}, author = {Ben-David, Y and Weihs, D}, title = {Modeling force application configurations and morphologies required for cancer cell invasion.}, journal = {Biomechanics and modeling in mechanobiology}, volume = {20}, number = {3}, pages = {1187-1194}, pmid = {33683515}, issn = {1617-7940}, support = {3-17427//Ministry of Science and Technology, Israel (IL)/ ; Polak Fund for Applied Research//Technion-Israel Institute of Technology/ ; }, mesh = {Biomechanical Phenomena/physiology ; Computer Simulation ; Elastic Modulus ; Finite Element Analysis ; Humans ; *Models, Biological ; Neoplasm Invasiveness ; Neoplasms/*pathology ; }, abstract = {We show that cell-applied, normal mechanical stresses are required for cells to penetrate into soft substrates, matching experimental observations in invasive cancer cells, while in-plane traction forces alone reproduce observations in non-cancer/noninvasive cells. Mechanobiological interactions of cells with their microenvironment drive migration and cancer invasion. We have previously shown that invasive cancer cells forcefully and rapidly push into impenetrable, physiological stiffness gels and indent them to cell-scale depths (up to 10 μm); normal, noninvasive cells indent at most to 0.7 μm. Significantly indenting cells signpost increased cancer invasiveness and higher metastatic risk in vitro and in vivo, as verified experimentally in different cancer types, yet the underlying cell-applied, force magnitudes and configurations required to produce the cell-scale gel indentations have yet to be evaluated. Hence, we have developed finite element models of forces applied onto soft, impenetrable gels using experimental cell/gel morphologies, gel mechanics, and force magnitudes. We show that in-plane traction forces can only induce small-scale indentations in soft gels (< 0.7 μm), matching experiments with various single, normal cells. Addition of a normal force (on the scale of experimental traction forces) produced cell-scale indentations that matched observations in invasive cancer cells. We note that normal stresses (force and area) determine the indentation depth, while contact area size and morphology have a minor effect, explaining the origin of experimentally observed cell morphologies. We have thus revealed controlling features facilitating invasive indentations by single cancer cells, which will allow application of our model to complex problems, such as multicellular systems.}, } @article {pmid33678014, year = {2021}, author = {Pen, I and Flatt, T}, title = {Asymmetry, division of labour and the evolution of ageing in multicellular organisms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1823}, pages = {20190729}, pmid = {33678014}, issn = {1471-2970}, mesh = {*Aging ; Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Division ; Germ Cells/physiology ; Insecta/*physiology ; Models, Biological ; }, abstract = {Between the 1930s and 1960s, evolutionary geneticists worked out the basic principles of why organisms age. Despite much progress in the evolutionary biology of ageing since that time, however, many puzzles remain. The perhaps most fundamental of these is the question of which organisms should exhibit senescence and which should not (or which should age rapidly and which should not). The evolutionary origin of ageing from a non-senescent state has been conceptually framed, for example, in terms of the separation between germ-line and soma, the distinction between parents and their offspring, and-in unicellular organisms-the unequal distribution of cellular damage at cell division. These ideas seem to be closely related to the concept of 'division of labour' between reproduction and somatic maintenance. Here, we review these concepts and develop a toy model to explore the importance of such asymmetries for the evolution of senescence. We apply our model to the simplest case of a multicellular system: an organism consisting of two totipotent cells. Notably, we find that in organisms which reproduce symmetrically and partition damage equally, senescence is still able to evolve, contrary to previous claims. Our results might have some bearing on understanding the origin of the germ-line-soma separation and the evolution of senescence in multicellular organisms and in colonial species consisting of multiple types of individuals, such as, for example, eusocial insects with their different castes. This article is part of the theme issue 'Ageing and sociality: why, when and how does sociality change ageing patterns?'}, } @article {pmid33677158, year = {2021}, author = {Li, B and Tian, Y and Wen, H and Qi, X and Wang, L and Zhang, J and Li, J and Dong, X and Zhang, K and Li, Y}, title = {Systematic identification and expression analysis of the Sox gene family in spotted sea bass (Lateolabrax maculatus).}, journal = {Comparative biochemistry and physiology. Part D, Genomics & proteomics}, volume = {38}, number = {}, pages = {100817}, doi = {10.1016/j.cbd.2021.100817}, pmid = {33677158}, issn = {1878-0407}, mesh = {Animals ; Bass/*genetics ; Fish Proteins/*genetics ; Multigene Family ; Phylogeny ; SOX Transcription Factors/*genetics ; Transcriptome ; }, abstract = {The Sox gene family encodes a set of transcription factors characterized by a conserved Sry-related high mobility group (HMG)-box domain, which performs a series of essential biological functions in diverse tissues and developmental processes. In this study, the Sox gene family was systematically characterized in spotted sea bass (Lateolabrax maculatus). A total of 26 Sox genes were identified and classified into eight subfamilies, namely, SoxB1, SoxB2, SoxC, SoxD, SoxE, SoxF, SoxH and SoxK. The phylogenetic relationship, exon-intron and domain structure analyses supported their annotation and classification. Comparison of gene copy numbers and chromosome locations among different species indicated that except tandem duplicated paralogs of Sox17/Sox32, duplicated Sox genes in spotted sea bass were generated from teleost-specific whole genome duplication during evolution. In addition, qRT-PCR was performed to detect the expression profiles of Sox genes during development and adulthood. The results showed that the expression of 16 out of 26 Sox genes was induced dramatically at different starting points after the multicellular stage, which is consistent with embryogenesis. At the early stage of sex differentiation, 9 Sox genes exhibited sexually dimorphic expression patterns, among which Sox3, Sox19 and Sox6b showed the most significant ovary-biased expression. Moreover, the distinct expression pattern of Sox genes was observed in different adult tissues. Our results provide a fundamental resource for further investigating the functions of Sox genes in embryonic processes, sex determination and differentiation as well as controlling the homeostasis of adult tissues in spotted sea bass.}, } @article {pmid33675395, year = {2021}, author = {Jong, LW and Fujiwara, T and Hirooka, S and Miyagishima, SY}, title = {Cell size for commitment to cell division and number of successive cell divisions in cyanidialean red algae.}, journal = {Protoplasma}, volume = {258}, number = {5}, pages = {1103-1118}, pmid = {33675395}, issn = {1615-6102}, support = {17H01446, 20H00477//Japan Society for the Promotion of Science (JP)/ ; 19J13366//Japan Society for the Promotion of Science/ ; }, mesh = {Biological Evolution ; Cell Division ; Cell Size ; *Chlorophyta ; *Rhodophyta ; }, abstract = {Several eukaryotic cell lineages proliferate by multiple fission cell cycles, during which cells grow to manyfold of their original size, then undergo several rounds of cell division without intervening growth. A previous study on volvocine green algae, including both unicellular and multicellular (colonial) species, showed a correlation between the minimum number of successive cell divisions without intervening cellular growth, and the threshold cell size for commitment to the first round of successive cell divisions: two times the average newly born daughter cell volume for unicellular Chlamydomonas reinhardtii, four times for four-celled Tetrabaena socialis, in which each cell in the colony produces a daughter colony by two successive cell divisions, and eight times for the eight-celled Gonium pectorale, in which each cell produces a daughter colony by three successive cell divisions. To assess whether this phenomenon is also applicable to other lineages, we have characterized cyanidialean red algae, namely, Cyanidioschyzon merolae, which proliferates by binary fission, as well as Cyanidium caldarium and Galdieria sulphuraria, which form up to four and 32 daughter cells (autospores), respectively, in a mother cell before hatching out. The result shows that there is also a correlation between the number of successive cell divisions and the threshold cell size for cell division or the first round of the successive cell divisions. In both C. merolae and C. caldarium, the cell size checkpoint for cell division(s) exists in the G1-phase, as previously shown in volvocine green algae. When C. merolae cells were arrested in the G1-phase and abnormally enlarged by conditional depletion of CDKA, the cells underwent two or more successive cell divisions without intervening cellular growth after recovery of CDKA, similarly to C. caldarium and G. sulphuraria. These results suggest that the threshold size for cell division is a major factor in determining the number of successive cell divisions and that evolutionary changes in the mechanism of cell size monitoring resulted in a variation of multiple fission cell cycle in eukaryotic algae.}, } @article {pmid33671243, year = {2021}, author = {Rathor, P and Borza, T and Stone, S and Tonon, T and Yurgel, S and Potin, P and Prithiviraj, B}, title = {A Novel Protein from Ectocarpus sp. Improves Salinity and High Temperature Stress Tolerance in Arabidopsis thaliana.}, journal = {International journal of molecular sciences}, volume = {22}, number = {4}, pages = {}, pmid = {33671243}, issn = {1422-0067}, support = {1177546//Natural Sciences and Engineering Research Council of Canada/ ; ANR-10-BTBR-04//Agence Nationale de la Recherche/ ; }, mesh = {*Adaptation, Physiological/genetics ; Algal Proteins/chemistry/genetics/*metabolism ; Arabidopsis/*genetics/growth & development/*physiology ; Electrolytes/metabolism ; Escherichia coli/metabolism ; Gene Expression Regulation, Plant ; *Hot Temperature ; Phaeophyceae/*metabolism ; Phylogeny ; Plants, Genetically Modified ; Promoter Regions, Genetic/genetics ; *Salinity ; Seedlings/genetics ; *Stress, Physiological/genetics ; Nicotiana/metabolism ; }, abstract = {Brown alga Ectocarpus sp. belongs to Phaeophyceae, a class of macroalgae that evolved complex multicellularity. Ectocarpus sp. is a dominant seaweed in temperate regions, abundant mostly in the intertidal zones, an environment with high levels of abiotic stresses. Previous transcriptomic analysis of Ectocarpus sp. revealed several genes consistently induced by various abiotic stresses; one of these genes is Esi0017_0056, which encodes a protein with unknown function. Bioinformatics analyses indicated that the protein encoded by Esi0017_0056 is soluble and monomeric. The protein was successfully expressed in Escherichia coli,Arabidopsis thaliana and Nicotiana benthamiana. In A. thaliana the gene was expressed under constitutive and stress inducible promoters which led to improved tolerance to high salinity and temperature stresses. The expression of several key abiotic stress-related genes was studied in transgenic and wild type A. thaliana by qPCR. Expression analysis revealed that genes involved in ABA-induced abiotic stress tolerance, K[+] homeostasis, and chaperon activities were significantly up-regulated in the transgenic line. This study is the first report in which an unknown function Ectocarpus sp. gene, highly responsive to abiotic stresses, was successfully expressed in A. thaliana, leading to improved tolerance to salt and temperature stress.}, } @article {pmid33657376, year = {2021}, author = {Wang, J and Sun, H and Jiang, M and Li, J and Zhang, P and Chen, H and Mei, Y and Fei, L and Lai, S and Han, X and Song, X and Xu, S and Chen, M and Ouyang, H and Zhang, D and Yuan, GC and Guo, G}, title = {Tracing cell-type evolution by cross-species comparison of cell atlases.}, journal = {Cell reports}, volume = {34}, number = {9}, pages = {108803}, doi = {10.1016/j.celrep.2021.108803}, pmid = {33657376}, issn = {2211-1247}, mesh = {Animals ; Caenorhabditis elegans/genetics/metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; *Cell Lineage ; Ciona intestinalis/genetics/metabolism ; Databases, Genetic ; *Evolution, Molecular ; *Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genomics ; Humans ; Mice ; Muscle Cells/classification/*metabolism ; Neurons/classification/*metabolism ; *Single-Cell Analysis ; Species Specificity ; Transcription Factors/*genetics/metabolism ; *Transcriptome ; Zebrafish/genetics/metabolism ; Zebrafish Proteins/genetics/metabolism ; }, abstract = {Cell types are the basic building units of multicellular life, with extensive diversities. The evolution of cell types is a crucial layer of comparative cell biology but is thus far not comprehensively studied. We define a compendium of cell atlases using single-cell RNA-seq (scRNA-seq) data from seven animal species and construct a cross-species cell-type evolutionary hierarchy. We present a roadmap for the origin and diversity of major cell categories and find that muscle and neuron cells are conserved cell types. Furthermore, we identify a cross-species transcription factor (TF) repertoire that specifies major cell categories. Overall, our study reveals conservation and divergence of cell types during animal evolution, which will further expand the landscape of comparative genomics.}, } @article {pmid33656551, year = {2021}, author = {Yang, H and Shi, X and Chen, C and Hou, J and Ji, T and Cheng, J and Birchler, JA}, title = {Predominantly inverse modulation of gene expression in genomically unbalanced disomic haploid maize.}, journal = {The Plant cell}, volume = {33}, number = {4}, pages = {901-916}, pmid = {33656551}, issn = {1532-298X}, mesh = {Chromosomes, Plant ; Dosage Compensation, Genetic ; *Gene Expression Regulation, Plant ; Genes, Plant ; Genome, Plant ; *Haploidy ; Sequence Analysis, RNA ; Zea mays/*genetics ; }, abstract = {The phenotypic consequences of the addition or subtraction of part of a chromosome is more severe than changing the dosage of the whole genome. By crossing diploid trisomies to a haploid inducer, we identified 17 distal segmental haploid disomies that cover ∼80% of the maize genome. Disomic haploids provide a level of genomic imbalance that is not ordinarily achievable in multicellular eukaryotes, allowing the impact to be stronger and more easily studied. Transcriptome size estimates revealed that a few disomies inversely modulate most of the transcriptome. Based on RNA sequencing, the expression levels of genes located on the varied chromosome arms (cis) in disomies ranged from being proportional to chromosomal dosage (dosage effect) to showing dosage compensation with no expression change with dosage. For genes not located on the varied chromosome arm (trans), an obvious trans-acting effect can be observed, with the majority showing a decreased modulation (inverse effect). The extent of dosage compensation of varied cis genes correlates with the extent of trans inverse effects across the 17 genomic regions studied. The results also have implications for the role of stoichiometry in gene expression, the control of quantitative traits, and the evolution of dosage-sensitive genes.}, } @article {pmid33624753, year = {2021}, author = {Junqueira Alves, C and Silva Ladeira, J and Hannah, T and Pedroso Dias, RJ and Zabala Capriles, PV and Yotoko, K and Zou, H and Friedel, RH}, title = {Evolution and Diversity of Semaphorins and Plexins in Choanoflagellates.}, journal = {Genome biology and evolution}, volume = {13}, number = {3}, pages = {}, pmid = {33624753}, issn = {1759-6653}, support = {R01 NS092735/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Axon Guidance ; Biodiversity ; Biological Evolution ; Cell Adhesion Molecules/chemistry/*genetics/metabolism ; Choanoflagellata/classification/*genetics/*metabolism ; Ligands ; Models, Molecular ; Nerve Tissue Proteins/chemistry/*genetics/metabolism ; Phylogeny ; Protein Conformation ; Protein Domains ; Receptors, Cell Surface/genetics ; Semaphorins/*genetics/*metabolism ; }, abstract = {Semaphorins and plexins are cell surface ligand/receptor proteins that affect cytoskeletal dynamics in metazoan cells. Interestingly, they are also present in Choanoflagellata, a class of unicellular heterotrophic flagellates that forms the phylogenetic sister group to Metazoa. Several members of choanoflagellates are capable of forming transient colonies, whereas others reside solitary inside exoskeletons; their molecular diversity is only beginning to emerge. Here, we surveyed genomics data from 22 choanoflagellate species and detected semaphorin/plexin pairs in 16 species. Choanoflagellate semaphorins (Sema-FN1) contain several domain features distinct from metazoan semaphorins, including an N-terminal Reeler domain that may facilitate dimer stabilization, an array of fibronectin type III domains, a variable serine/threonine-rich domain that is a potential site for O-linked glycosylation, and a SEA domain that can undergo autoproteolysis. In contrast, choanoflagellate plexins (Plexin-1) harbor a domain arrangement that is largely identical to metazoan plexins. Both Sema-FN1 and Plexin-1 also contain a short homologous motif near the C-terminus, likely associated with a shared function. Three-dimensional molecular models revealed a highly conserved structural architecture of choanoflagellate Plexin-1 as compared to metazoan plexins, including similar predicted conformational changes in a segment that is involved in the activation of the intracellular Ras-GAP domain. The absence of semaphorins and plexins in several choanoflagellate species did not appear to correlate with unicellular versus colonial lifestyle or ecological factors such as fresh versus salt water environment. Together, our findings support a conserved mechanism of semaphorin/plexin proteins in regulating cytoskeletal dynamics in unicellular and multicellular organisms.}, } @article {pmid33622124, year = {2021}, author = {Evans, SD and Droser, ML and Erwin, DH}, title = {Developmental processes in Ediacara macrofossils.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1945}, pages = {20203055}, pmid = {33622124}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; Biota ; *Fossils ; Nervous System ; Phylogeny ; }, abstract = {The Ediacara Biota preserves the oldest fossil evidence of abundant, complex metazoans. Despite their significance, assigning individual taxa to specific phylogenetic groups has proved problematic. To better understand these forms, we identify developmentally controlled characters in representative taxa from the Ediacaran White Sea assemblage and compare them with the regulatory tools underlying similar traits in modern organisms. This analysis demonstrates that the genetic pathways for multicellularity, axial polarity, musculature, and a nervous system were likely present in some of these early animals. Equally meaningful is the absence of evidence for major differentiation of macroscopic body units, including distinct organs, localized sensory machinery or appendages. Together these traits help to better constrain the phylogenetic position of several key Ediacara taxa and inform our views of early metazoan evolution. An apparent lack of heads with concentrated sensory machinery or ventral nerve cords in such taxa supports the hypothesis that these evolved independently in disparate bilaterian clades.}, } @article {pmid33622103, year = {2021}, author = {Ros-Rocher, N and Pérez-Posada, A and Leger, MM and Ruiz-Trillo, I}, title = {The origin of animals: an ancestral reconstruction of the unicellular-to-multicellular transition.}, journal = {Open biology}, volume = {11}, number = {2}, pages = {200359}, pmid = {33622103}, issn = {2046-2441}, mesh = {Alveolata/cytology/genetics ; Animals ; *Evolution, Molecular ; Phylogeny ; }, abstract = {How animals evolved from a single-celled ancestor, transitioning from a unicellular lifestyle to a coordinated multicellular entity, remains a fascinating question. Key events in this transition involved the emergence of processes related to cell adhesion, cell-cell communication and gene regulation. To understand how these capacities evolved, we need to reconstruct the features of both the last common multicellular ancestor of animals and the last unicellular ancestor of animals. In this review, we summarize recent advances in the characterization of these ancestors, inferred by comparative genomic analyses between the earliest branching animals and those radiating later, and between animals and their closest unicellular relatives. We also provide an updated hypothesis regarding the transition to animal multicellularity, which was likely gradual and involved the use of gene regulatory mechanisms in the emergence of early developmental and morphogenetic plans. Finally, we discuss some new avenues of research that will complement these studies in the coming years.}, } @article {pmid33617837, year = {2021}, author = {Debets, VE and Janssen, LMC and Storm, C}, title = {Enhanced persistence and collective migration in cooperatively aligning cell clusters.}, journal = {Biophysical journal}, volume = {120}, number = {8}, pages = {1483-1497}, pmid = {33617837}, issn = {1542-0086}, mesh = {Attention ; Biophysics ; Cell Movement ; Humans ; *Neoplasms ; }, abstract = {Most cells possess the capacity to locomote. Alone or collectively, this allows them to adapt, to rearrange, and to explore their surroundings. The biophysical characterization of such motile processes, in health and in disease, has so far focused mostly on two limiting cases: single-cell motility on the one hand and the dynamics of confluent tissues such as the epithelium on the other. The in-between regime of clusters, composed of relatively few cells moving as a coherent unit, has received less attention. Such small clusters are, however, deeply relevant in development but also in cancer metastasis. In this work, we use cellular Potts models and analytical active matter theory to understand how the motility of small cell clusters changes with N, the number of cells in the cluster. Modeling and theory reveal our two main findings: cluster persistence time increases with N, whereas the intrinsic diffusivity decreases with N. We discuss a number of settings in which the motile properties of more complex clusters can be analytically understood, revealing that the focusing effects of small-scale cooperation and cell-cell alignment can overcome the increased bulkiness and internal disorder of multicellular clusters to enhance overall migrational efficacy. We demonstrate this enhancement for small-cluster collective durotaxis, which is shown to proceed more effectively than for single cells. Our results may provide some novel, to our knowledge, insights into the connection between single-cell and large-scale collective motion and may point the way to the biophysical origins of the enhanced metastatic potential of small tumor cell clusters.}, } @article {pmid33602485, year = {2021}, author = {McKenna, KZ and Wagner, GP and Cooper, KL}, title = {A developmental perspective of homology and evolutionary novelty.}, journal = {Current topics in developmental biology}, volume = {141}, number = {}, pages = {1-38}, doi = {10.1016/bs.ctdb.2020.12.001}, pmid = {33602485}, issn = {1557-8933}, mesh = {Animals ; *Biological Evolution ; Crustacea/anatomy & histology ; Developmental Biology ; *Gene Regulatory Networks ; Genes, Homeobox ; Genitalia, Male/physiology ; Homeodomain Proteins/genetics ; Insecta ; Male ; Pelvis ; Phylogeny ; Transcription Factors/genetics ; Vertebrates/*anatomy & histology ; *Wings, Animal/anatomy & histology ; }, abstract = {The development and evolution of multicellular body plans is complex. Many distinct organs and body parts must be reproduced at each generation, and those that are traceable over long time scales are considered homologous. Among the most pressing and least understood phenomena in evolutionary biology is the mode by which new homologs, or "novelties" are introduced to the body plan and whether the developmental changes associated with such evolution deserve special treatment. In this chapter, we address the concepts of homology and evolutionary novelty through the lens of development. We present a series of case studies, within insects and vertebrates, from which we propose a developmental model of multicellular organ identity. With this model in hand, we make predictions regarding the developmental evolution of body plans and highlight the need for more integrative analysis of developing systems.}, } @article {pmid33600401, year = {2021}, author = {Goldberg, Y and Friedman, J}, title = {Positive interactions within and between populations decrease the likelihood of evolutionary rescue.}, journal = {PLoS computational biology}, volume = {17}, number = {2}, pages = {e1008732}, pmid = {33600401}, issn = {1553-7358}, mesh = {*Adaptation, Physiological ; Animals ; *Biological Evolution ; Computational Biology ; Computer Simulation ; *Ecosystem ; Extinction, Biological ; Humans ; *Models, Biological ; Phenotype ; Probability ; Selection, Genetic ; Stress, Physiological ; *Symbiosis ; }, abstract = {Positive interactions, including intraspecies cooperation and interspecies mutualisms, play crucial roles in shaping the structure and function of many ecosystems, ranging from plant communities to the human microbiome. While the evolutionary forces that form and maintain positive interactions have been investigated extensively, the influence of positive interactions on the ability of species to adapt to new environments is still poorly understood. Here, we use numerical simulations and theoretical analyses to study how positive interactions impact the likelihood that populations survive after an environment deteriorates, such that survival in the new environment requires quick adaptation via the rise of new mutants-a scenario known as evolutionary rescue. We find that the probability of evolutionary rescue in populations engaged in positive interactions is reduced significantly. In cooperating populations, this reduction is largely due to the fact that survival may require at least a minimal number of individuals, meaning that adapted mutants must arise and spread before the population declines below this threshold. In mutualistic populations, the rescue probability is decreased further due to two additional effects-the need for both mutualistic partners to adapt to the new environment, and competition between the two species. Finally, we show that the presence of cheaters reduces the likelihood of evolutionary rescue even further, making it extremely unlikely. These results indicate that while positive interactions may be beneficial in stable environments, they can hinder adaptation to changing environments and thereby elevate the risk of population collapse. Furthermore, these results may hint at the selective pressures that drove co-dependent unicellular species to form more adaptable organisms able to differentiate into multiple phenotypes, including multicellular life.}, } @article {pmid33593190, year = {2021}, author = {He, S and Sieksmeyer, T and Che, Y and Mora, MAE and Stiblik, P and Banasiak, R and Harrison, MC and Šobotník, J and Wang, Z and Johnston, PR and McMahon, DP}, title = {Evidence for reduced immune gene diversity and activity during the evolution of termites.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1945}, pages = {20203168}, pmid = {33593190}, issn = {1471-2954}, mesh = {Animals ; Biological Evolution ; *Cockroaches ; *Isoptera/genetics ; Phylogeny ; Social Behavior ; }, abstract = {The evolution of biological complexity is associated with the emergence of bespoke immune systems that maintain and protect organism integrity. Unlike the well-studied immune systems of cells and individuals, little is known about the origins of immunity during the transition to eusociality, a major evolutionary transition comparable to the evolution of multicellular organisms from single-celled ancestors. We aimed to tackle this by characterizing the immune gene repertoire of 18 cockroach and termite species, spanning the spectrum of solitary, subsocial and eusocial lifestyles. We find that key transitions in termite sociality are correlated with immune gene family contractions. In cross-species comparisons of immune gene expression, we find evidence for a caste-specific social defence system in termites, which appears to operate at the expense of individual immune protection. Our study indicates that a major transition in organismal complexity may have entailed a fundamental reshaping of the immune system optimized for group over individual defence.}, } @article {pmid33588307, year = {2021}, author = {Crawford, MA and Schmidt, WF and Broadhurst, CL and Wang, Y}, title = {Lipids in the origin of intracellular detail and speciation in the Cambrian epoch and the significance of the last double bond of docosahexaenoic acid in cell signaling.}, journal = {Prostaglandins, leukotrienes, and essential fatty acids}, volume = {166}, number = {}, pages = {102230}, doi = {10.1016/j.plefa.2020.102230}, pmid = {33588307}, issn = {1532-2823}, mesh = {Animals ; Brain/metabolism ; Carbon/metabolism ; Cell Membrane/metabolism ; Docosahexaenoic Acids/chemistry/*history/*metabolism ; *Electrons ; Fatty Acids, Unsaturated/chemistry/*history/*metabolism ; History, Ancient ; Humans ; Hydrogen/metabolism ; Intracellular Space/*metabolism ; Neurons/metabolism ; Retina/metabolism ; *Signal Transduction ; }, abstract = {One of the great unanswered biological questions is the absolute necessity of the polyunsaturated lipid docosahexaenoic acid (DHA; 22:6n-3) in retinal and neural tissues. Everything from the simple eye spot of dinoflagellates to cephalopods to every class of vertebrates uses DHA, yet it is abundant only in cold water marine food chains. Docosapentaenoic acids (DPAs; 22:5n-6 and especially 22:5n-3) are fairly plentiful in food chains yet cannot substitute for DHA. About 600 million years ago, multi-cellular, air breathing systems evolved rapidly and 32 phyla came into existence in a short geological time span; the "Cambrian Explosion". Eukaryotic intracellular detail requires cell membranes, which are constructed of complex lipids, and proteins. Proteins and nucleic acids would have been abundant during the first 2.5-5 billion years of anaerobic life but lipids, especially unsaturated fatty acids, would not. We hypothesize lipid biology was a key driver of the Cambrian Explosion, because it alone provides for compartmentalization and specialization within cells DHA has six methylene interrupted double bonds providing controlled electron flow at precise energy levels; this is essential for visual acuity and truthful execution of the neural pathways which make up our recollections, information processing and consciousness. The last double bond is critical for the evolution and function of the photoreceptor and neuronal and synaptic signaling systems. It completes a quantum mechanical device for the regulation of current flow with absolute signal precision based on electron tunneling (ET). DHA's methylene interruption distance is < 6 Å, making ET transfer between the π-orbitals feasible throughout the molecule. The possibility fails if one double bond is removed and replaced by a saturated bond as in the DPAs. The molecular biophysical foundation of neural signaling can also include the discrete pattern of paired spin states that arise in the DHA double bond and methylene regions. The complexity depends upon the number of C13 and H1 molecular sites in which spin states are coupled. Electron wave harmonics with entanglement and cohesion provide a mechanism for learning and memory, and power cognition and complex human brain functions.}, } @article {pmid33575354, year = {2021}, author = {Pourhasanzade, F and Sabzpoushan, SH}, title = {A New Mathematical Model for Controlling Tumor Growth Based on Microenvironment Acidity and Oxygen Concentration.}, journal = {BioMed research international}, volume = {2021}, number = {}, pages = {8886050}, pmid = {33575354}, issn = {2314-6141}, mesh = {Animals ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasms/*metabolism ; Oxygen/*metabolism ; *Tumor Microenvironment/drug effects/physiology ; }, abstract = {Hypoxia and the pH level of the tumor microenvironment have a great impact on the treatment of tumors. Here, the tumor growth is controlled by regulating the oxygen concentration and the acidity of the tumor microenvironment by introducing a two-dimensional multiscale cellular automata model of avascular tumor growth. The spatiotemporal evolution of tumor growth and metabolic variations is modeled based on biological assumptions, physical structure, states of cells, and transition rules. Each cell is allocated to one of the following states: proliferating cancer, nonproliferating cancer, necrotic, and normal cells. According to the response of the microenvironmental conditions, each cell consumes/produces metabolic factors and updates its state based on some stochastic rules. The input parameters are compatible with cancer biology using experimental data. The effect of neighborhoods during mitosis and simulating spatial heterogeneity is studied by considering multicellular layer structure of tumor. A simple Darwinist mutation is considered by introducing a critical parameter (Nmm) that affects division probability of the proliferative tumor cells based on the microenvironmental conditions and cancer hallmarks. The results show that Nmm regulation has a significant influence on the dynamics of tumor growth, the growth fraction, necrotic fraction, and the concentration levels of the metabolic factors. The model not only is able to simulate the in vivo tumor growth quantitatively and qualitatively but also can simulate the concentration of metabolic factors, oxygen, and acidity graphically. The results show the spatial heterogeneity effects on the proliferation of cancer cells and the rest of the system. By increasing Nmm, tumor shrinkage and significant increasing in the oxygen concentration and the pH value of the tumor microenvironment are observed. The results demonstrate the model's ability, providing an essential tool for simulating different tumor evolution scenarios of a patient and reliable prediction of spatiotemporal progression of tumors for utilizing in personalized therapy.}, } @article {pmid33565083, year = {2021}, author = {Bustamante, DE and Yeon Won, B and Wynne, MJ and Cho, TO}, title = {Molecular and morphological analyses reveal new taxa additions to the tribe Streblocladieae (Rhodomelaceae, Rhodophyta).}, journal = {Journal of phycology}, volume = {57}, number = {3}, pages = {817-830}, doi = {10.1111/jpy.13144}, pmid = {33565083}, issn = {1529-8817}, mesh = {Evolution, Molecular ; Phylogeny ; *Rhodophyta ; }, abstract = {The recent segregation of 12 genera in the tribe Streblocladieae suggests that the taxonomy of some species belonging to Polysiphonia sensu lato is updated with the transfer and the proposal of new combinations. Accordingly, six new additions to the tribe Streblocladieae on the basis of morphological and molecular analyses are presented as a consequence of this new segregation. These additions include the description of the new species Carradoriella platensis sp. nov., the proposal of the following new combinations Eutrichosiphonia paniculata comb. nov., E. tapinocarpa comb. nov., and the reinstatement of Vertebrata curta, V. decipiens, and V. patersonis. Additionally, our morphological observations identified additional diagnostic features for two genera of the Streblocladieae. Carradoriella has branches with sexual reproductive structures arranged adaxially on branchlets, and the recently described Eutrichosiphonia has rhizoids with multicellular digitate haptera. Our study gives insights in regards to the distribution, the diagnostic features for delimiting genera morphologically, and the molecular evolutionary relationships in the Streblocladieae.}, } @article {pmid33561386, year = {2021}, author = {Prostak, SM and Robinson, KA and Titus, MA and Fritz-Laylin, LK}, title = {The actin networks of chytrid fungi reveal evolutionary loss of cytoskeletal complexity in the fungal kingdom.}, journal = {Current biology : CB}, volume = {31}, number = {6}, pages = {1192-1205.e6}, pmid = {33561386}, issn = {1879-0445}, support = {R01 GM122917/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/*metabolism ; Actins/*metabolism ; Amphibians/microbiology ; Animals ; Chytridiomycota/*classification/*metabolism ; *Evolution, Molecular ; }, abstract = {Cells from across the eukaryotic tree use actin polymer networks for a wide variety of functions, including endocytosis, cytokinesis, and cell migration. Despite this functional conservation, the actin cytoskeleton has undergone significant diversification, highlighted by the differences in the actin networks of mammalian cells and yeast. Chytrid fungi diverged before the emergence of the Dikarya (multicellular fungi and yeast) and therefore provide a unique opportunity to study actin cytoskeletal evolution. Chytrids have two life stages: zoospore cells that can swim with a flagellum and sessile sporangial cells that, like multicellular fungi, are encased in a chitinous cell wall. Here, we show that zoospores of the amphibian-killing chytrid Batrachochytrium dendrobatidis (Bd) build dynamic actin structures resembling those of animal cells, including an actin cortex, pseudopods, and filopodia-like spikes. In contrast, Bd sporangia assemble perinuclear actin shells and actin patches similar to those of yeast. The use of specific small-molecule inhibitors indicate that nearly all of Bd's actin structures are dynamic and use distinct nucleators: although pseudopods and actin patches are Arp2/3 dependent, the actin cortex appears formin dependent and actin spikes require both nucleators. Our analysis of multiple chytrid genomes reveals actin regulators and myosin motors found in animals, but not dikaryotic fungi, as well as fungal-specific components. The presence of animal- and yeast-like actin cytoskeletal components in the genome combined with the intermediate actin phenotypes in Bd suggests that the simplicity of the yeast cytoskeleton may be due to evolutionary loss.}, } @article {pmid33550955, year = {2021}, author = {Ginsburg, S and Jablonka, E}, title = {Evolutionary transitions in learning and cognition.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190766}, pmid = {33550955}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Cognition/*physiology ; Learning/*physiology ; Phylogeny ; }, abstract = {We define a cognitive system as a system that can learn, and adopt an evolutionary-transition-oriented framework for analysing different types of neural cognition. This enables us to classify types of cognition and point to the continuities and discontinuities among them. The framework we use for studying evolutionary transitions in learning capacities focuses on qualitative changes in the integration, storage and use of neurally processed information. Although there are always grey areas around evolutionary transitions, we recognize five major neural transitions, the first two of which involve animals at the base of the phylogenetic tree: (i) the evolutionary transition from learning in non-neural animals to learning in the first neural animals; (ii) the transition to animals showing limited, elemental associative learning, entailing neural centralization and primary brain differentiation; (iii) the transition to animals capable of unlimited associative learning, which, on our account, constitutes sentience and entails hierarchical brain organization and dedicated memory and value networks; (iv) the transition to imaginative animals that can plan and learn through selection among virtual events; and (v) the transition to human symbol-based cognition and cultural learning. The focus on learning provides a unifying framework for experimental and theoretical studies of cognition in the living world. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550954, year = {2021}, author = {Jékely, G and Godfrey-Smith, P and Keijzer, F}, title = {Reafference and the origin of the self in early nervous system evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190764}, pmid = {33550954}, issn = {1471-2970}, mesh = {Animals ; Cnidaria/physiology ; Ctenophora/physiology ; Efferent Pathways/*physiology ; Nervous System/chemistry ; *Nervous System Physiological Phenomena ; Placozoa/physiology ; Porifera/physiology ; *Proprioception ; }, abstract = {Discussions of the function of early nervous systems usually focus on a causal flow from sensors to effectors, by which an animal coordinates its actions with exogenous changes in its environment. We propose, instead, that much early sensing was reafferent; it was responsive to the consequences of the animal's own actions. We distinguish two general categories of reafference-translocational and deformational-and use these to survey the distribution of several often-neglected forms of sensing, including gravity sensing, flow sensing and proprioception. We discuss sensing of these kinds in sponges, ctenophores, placozoans, cnidarians and bilaterians. Reafference is ubiquitous, as ongoing action, especially whole-body motility, will almost inevitably influence the senses. Corollary discharge-a pathway or circuit by which an animal tracks its own actions and their reafferent consequences-is not a necessary feature of reafferent sensing but a later-evolving mechanism. We also argue for the importance of reafferent sensing to the evolution of the body-self, a form of organization that enables an animal to sense and act as a single unit. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550952, year = {2021}, author = {Pezzulo, G and LaPalme, J and Durant, F and Levin, M}, title = {Bistability of somatic pattern memories: stochastic outcomes in bioelectric circuits underlying regeneration.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190765}, pmid = {33550952}, issn = {1471-2970}, mesh = {Animals ; *Cell Communication ; *Cognition ; Cognitive Science ; Electrophysiological Phenomena/physiology ; Models, Neurological ; Planarians/*physiology ; *Regeneration ; }, abstract = {Nervous systems' computational abilities are an evolutionary innovation, specializing and speed-optimizing ancient biophysical dynamics. Bioelectric signalling originated in cells' communication with the outside world and with each other, enabling cooperation towards adaptive construction and repair of multicellular bodies. Here, we review the emerging field of developmental bioelectricity, which links the field of basal cognition to state-of-the-art questions in regenerative medicine, synthetic bioengineering and even artificial intelligence. One of the predictions of this view is that regeneration and regulative development can restore correct large-scale anatomies from diverse starting states because, like the brain, they exploit bioelectric encoding of distributed goal states-in this case, pattern memories. We propose a new interpretation of recent stochastic regenerative phenotypes in planaria, by appealing to computational models of memory representation and processing in the brain. Moreover, we discuss novel findings showing that bioelectric changes induced in planaria can be stored in tissue for over a week, thus revealing that somatic bioelectric circuits in vivo can implement a long-term, re-writable memory medium. A consideration of the mechanisms, evolution and functionality of basal cognition makes novel predictions and provides an integrative perspective on the evolution, physiology and biomedicine of information processing in vivo. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550951, year = {2021}, author = {Göhde, R and Naumann, B and Laundon, D and Imig, C and McDonald, K and Cooper, BH and Varoqueaux, F and Fasshauer, D and Burkhardt, P}, title = {Choanoflagellates and the ancestry of neurosecretory vesicles.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190759}, pmid = {33550951}, issn = {1471-2970}, mesh = {*Biological Evolution ; Choanoflagellata/*physiology ; R-SNARE Proteins/*metabolism ; Synaptic Vesicles/*physiology ; }, abstract = {Neurosecretory vesicles are highly specialized trafficking organelles that store neurotransmitters that are released at presynaptic nerve endings and are, therefore, important for animal cell-cell signalling. Despite considerable anatomical and functional diversity of neurons in animals, the protein composition of neurosecretory vesicles in bilaterians appears to be similar. This similarity points towards a common evolutionary origin. Moreover, many putative homologues of key neurosecretory vesicle proteins predate the origin of the first neurons, and some even the origin of the first animals. However, little is known about the molecular toolkit of these vesicles in non-bilaterian animals and their closest unicellular relatives, making inferences about the evolutionary origin of neurosecretory vesicles extremely difficult. By comparing 28 proteins of the core neurosecretory vesicle proteome in 13 different species, we demonstrate that most of the proteins are present in unicellular organisms. Surprisingly, we find that the vesicular membrane-associated soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein synaptobrevin is localized to the vesicle-rich apical and basal pole in the choanoflagellate Salpingoeca rosetta. Our 3D vesicle reconstructions reveal that the choanoflagellates S. rosetta and Monosiga brevicollis exhibit a polarized and diverse vesicular landscape reminiscent of the polarized organization of chemical synapses that secrete the content of neurosecretory vesicles into the synaptic cleft. This study sheds light on the ancestral molecular machinery of neurosecretory vesicles and provides a framework to understand the origin and evolution of secretory cells, synapses and neurons. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550950, year = {2021}, author = {Levin, M and Keijzer, F and Lyon, P and Arendt, D}, title = {Uncovering cognitive similarities and differences, conservation and innovation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20200458}, pmid = {33550950}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Cognition/*physiology ; *Nervous System Physiological Phenomena ; }, abstract = {This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550949, year = {2021}, author = {Moroz, LL and Romanova, DY and Kohn, AB}, title = {Neural versus alternative integrative systems: molecular insights into origins of neurotransmitters.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20190762}, pmid = {33550949}, issn = {1471-2970}, support = {R01 NS114491/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Communication/*physiology ; *Evolution, Molecular ; Neurotransmitter Agents/*chemistry ; Placozoa/physiology ; *Signal Transduction ; }, abstract = {Transmitter signalling is the universal chemical language of any nervous system, but little is known about its early evolution. Here, we summarize data about the distribution and functions of neurotransmitter systems in basal metazoans as well as outline hypotheses of their origins. We explore the scenario that neurons arose from genetically different populations of secretory cells capable of volume chemical transmission and integration of behaviours without canonical synapses. The closest representation of this primordial organization is currently found in Placozoa, disk-like animals with the simplest known cell composition but complex behaviours. We propose that injury-related signalling was the evolutionary predecessor for integrative functions of early transmitters such as nitric oxide, ATP, protons, glutamate and small peptides. By contrast, acetylcholine, dopamine, noradrenaline, octopamine, serotonin and histamine were recruited as canonical neurotransmitters relatively later in animal evolution, only in bilaterians. Ligand-gated ion channels often preceded the establishment of novel neurotransmitter systems. Moreover, lineage-specific diversification of neurotransmitter receptors occurred in parallel within Cnidaria and several bilaterian lineages, including acoels. In summary, ancestral diversification of secretory signal molecules provides unique chemical microenvironments for behaviour-driven innovations that pave the way to complex brain functions and elementary cognition. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33550948, year = {2021}, author = {Arendt, D}, title = {Elementary nervous systems.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1821}, pages = {20200347}, pmid = {33550948}, issn = {1471-2970}, mesh = {Animals ; Behavior, Animal/*physiology ; *Biological Evolution ; *Body Size ; Cilia/*physiology ; Nerve Net/*physiology ; }, abstract = {The evolutionary origin of the nervous system has been a matter of long-standing debate. This is due to the different perspectives taken. Earlier studies addressed nervous system origins at the cellular level. They focused on the selective advantage of the first neuron in its local context, and considered vertical sensory-motor reflex arcs the first nervous system. Later studies emphasized the value of the nervous system at the tissue level. Rather than acting locally, early neurons were seen as part of an elementary nerve net that enabled the horizontal coordination of tissue movements. Opinions have also differed on the nature of effector cells. While most authors have favoured contractile systems, others see the key output of the incipient nervous system in the coordination of motile cilia, or the secretion of antimicrobial peptides. I will discuss these divergent views and explore how they can be validated by molecular and single-cell data. From this survey, possible consensus emerges: (i) the first manifestation of the nervous system likely was a nerve net, whereas specialized local circuits evolved later; (ii) different nerve nets may have evolved for the coordination of contractile or cilia-driven movements; (iii) all evolving nerve nets facilitated new forms of animal behaviour with increasing body size. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.}, } @article {pmid33542245, year = {2021}, author = {Grum-Grzhimaylo, AA and Bastiaans, E and van den Heuvel, J and Berenguer Millanes, C and Debets, AJM and Aanen, DK}, title = {Somatic deficiency causes reproductive parasitism in a fungus.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {783}, pmid = {33542245}, issn = {2041-1723}, mesh = {Cell Fusion ; DNA Mutational Analysis ; *Evolution, Molecular ; Fungal Proteins/*genetics/metabolism ; Gene Knockout Techniques ; Genes, Fungal/genetics ; Hyphae/*physiology ; Mutation ; Neurospora crassa/*physiology ; }, abstract = {Some multicellular organisms can fuse because mergers potentially provide mutual benefits. However, experimental evolution in the fungus Neurospora crassa has demonstrated that free fusion of mycelia favours cheater lineages, but the mechanism and evolutionary dynamics of this exploitation are unknown. Here we show, paradoxically, that all convergently evolved cheater lineages have similar fusion deficiencies. These mutants are unable to initiate fusion but retain access to wild-type mycelia that fuse with them. This asymmetry reduces cheater-mutant contributions to somatic substrate-bound hyphal networks, but increases representation of their nuclei in the aerial reproductive hyphae. Cheaters only benefit when relatively rare and likely impose genetic load reminiscent of germline senescence. We show that the consequences of somatic fusion can be unequally distributed among fusion partners, with the passive non-fusing partner profiting more. We discuss how our findings may relate to the extensive variation in fusion frequency of fungi found in nature.}, } @article {pmid33539025, year = {2021}, author = {Gostner, JM and Fuchs, D and Kurz, K}, title = {Metabolic Stress and Immunity: Nutrient-Sensing Kinases and Tryptophan Metabolism.}, journal = {Advances in experimental medicine and biology}, volume = {1275}, number = {}, pages = {395-405}, pmid = {33539025}, issn = {0065-2598}, mesh = {Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Kynurenine ; Nutrients ; *Protein Serine-Threonine Kinases ; Stress, Physiological ; *Tryptophan ; }, abstract = {The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO-1) has gained major attention due the immunoregulatory nature of this pathway. Both depletion of tryptophan concentrations as well as the accumulation of downstream metabolites are relevant for the mediation of the manifold consequences of increased tryptophan metabolism. Increased tryptophan catabolism is indicative for several chronic inflammatory disorders such as infections, autoimmune diseases or cancer. Low tryptophan availability is likely to be involved in the manifestation of a variety of comorbidities such as anemia, cachexia, depression and neurocognitive disturbances.Several nutrient sensing kinases are implicated in the downstream effects of dysregulated tryptophan metabolism. These include mechanisms that were conserved during evolution but have gained special features in multicellular eukaryotes, such as pathways regulated by eukaryotic translation initiation factor 2 (eIF-2)-alpha kinase (GCN2, also named general control nonderepressible 2 kinase), 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and target of rapamycin (TOR).The interplay between IDO-1 and above-mentioned pathway seems to be highly context dependent. A better understanding of the crosstalk is necessary to support the search for druggable targets for the treatment of inflammatory and autoimmune disorders.}, } @article {pmid33535413, year = {2021}, author = {Parker, GA}, title = {How Soon Hath Time… A History of Two "Seminal" Publications.}, journal = {Cells}, volume = {10}, number = {2}, pages = {}, pmid = {33535413}, issn = {2073-4409}, mesh = {Animals ; Female ; Insecta ; Male ; Sexual Selection/*physiology ; }, abstract = {This review documents the history of the two papers written half a century ago that relate to this special issue of Cells. The first, "Sperm competition and its evolutionary consequences in the insects" (Biological Reviews, 1970), stressed that sexual selection continues after ejaculation, resulting in many adaptations (e.g., postcopulatory guarding phases, copulatory plugs, seminal fluid components that modify female reproduction, and optimal ejaculation strategies), an aspect not considered by Darwin in his classic treatise of 1871. Sperm competition has subsequently been studied in many taxa, and post-copulatory sexual selection is now considered an important sequel to Darwinian pre-copulatory sexual selection. The second, "The origin and evolution of gamete dimorphism and the male-female phenomenon" (Journal of Theoretical Biology, 1972) showed how selection, based on gamete competition between individuals, can give rise to anisogamy in an isogamous broadcast spawning ancestor. This theory, which has subsequently been developed in various ways, is argued to form the most powerful explanation of why there are two sexes in most multicellular organisms. Together, the two papers have influenced our general understanding of the evolutionary differentiation of the two forms of gametic cells, and the divergence of sexual strategies between males and females under sexual selection.}, } @article {pmid33529558, year = {2021}, author = {Berger, D and Stångberg, J and Baur, J and Walters, RJ}, title = {Elevated temperature increases genome-wide selection on de novo mutations.}, journal = {Proceedings. Biological sciences}, volume = {288}, number = {1944}, pages = {20203094}, pmid = {33529558}, issn = {1471-2954}, mesh = {*Adaptation, Physiological ; Animals ; *Climate Change ; Coleoptera/*genetics ; DNA Mutational Analysis ; Mutation ; *Selection, Genetic ; *Temperature ; }, abstract = {Adaptation in new environments depends on the amount of genetic variation available for evolution, and the efficacy by which natural selection discriminates among this variation. However, whether some ecological factors reveal more genetic variation, or impose stronger selection pressures than others, is typically not known. Here, we apply the enzyme kinetic theory to show that rising global temperatures are predicted to intensify natural selection throughout the genome by increasing the effects of DNA sequence variation on protein stability. We test this prediction by (i) estimating temperature-dependent fitness effects of induced mutations in seed beetles adapted to ancestral or elevated temperature, and (ii) calculate 100 paired selection estimates on mutations in benign versus stressful environments from unicellular and multicellular organisms. Environmental stress per se did not increase mean selection on de novo mutation, suggesting that the cost of adaptation does not generally increase in new ecological settings to which the organism is maladapted. However, elevated temperature increased the mean strength of selection on genome-wide polymorphism, signified by increases in both mutation load and mutational variance in fitness. These results have important implications for genetic diversity gradients and the rate and repeatability of evolution under climate change.}, } @article {pmid33520185, year = {2021}, author = {Naimark, E and Kirpotin, D and Boeva, N and Gmoshinskiy, V and Kalinina, M and Lyupina, Y and Markov, A and Nikitin, M and Shokurov, A and Volkov, D}, title = {Taphonomic experiments imply a possible link between the evolution of multicellularity and the fossilization potential of soft-bodied organisms.}, journal = {Ecology and evolution}, volume = {11}, number = {2}, pages = {1037-1056}, pmid = {33520185}, issn = {2045-7758}, abstract = {The reliability of evolutionary reconstructions based on the fossil record critically depends on our knowledge of the factors affecting the fossilization of soft-bodied organisms. Despite considerable research effort, these factors are still poorly understood. In order to elucidate the main prerequisites for the preservation of soft-bodied organisms, we conducted long-term (1-5 years) taphonomic experiments with the model crustacean Artemia salina buried in five different sediments. The subsequent analysis of the carcasses and sediments revealed that, in our experimental settings, better preservation was associated with the fast deposition of aluminum and silicon on organic tissues. Other elements such as calcium, magnesium, and iron, which can also accumulate quickly on the carcasses, appear to be much less efficient in preventing decay. Next, we asked if the carcasses of uni- and multicellular organisms differ in their ability to accumulate aluminum ions on their surface. The experiments with the flagellate Euglena gracilis and the sponge Spongilla lacustris showed that aluminum ions are more readily deposited onto a multicellular body. This was further confirmed by the experiments with uni- and multicellular stages of the social ameba Dictyostelium discoideum. The results lead us to speculate that the evolution of cell adhesion molecules, which provide efficient cell-cell and cell-substrate binding, probably can explain the rich fossil record of soft-bodied animals, the comparatively poor fossil record of nonskeletal unicellular eukaryotes, and the explosive emergence of the Cambrian diversity of soft-bodied fossils.}, } @article {pmid33507545, year = {2021}, author = {Li, J and Meng, Q and Fu, Y and Yu, X and Ji, T and Chao, Y and Chen, Q and Li, Y and Bian, H}, title = {Novel insights: Dynamic foam cells derived from the macrophage in atherosclerosis.}, journal = {Journal of cellular physiology}, volume = {236}, number = {9}, pages = {6154-6167}, doi = {10.1002/jcp.30300}, pmid = {33507545}, issn = {1097-4652}, mesh = {Animals ; Atherosclerosis/*pathology ; Cell Communication ; Cholesterol/metabolism ; Esterification ; Foam Cells/metabolism/*pathology ; Humans ; Metabolome ; }, abstract = {Atherosclerosis can be regarded as a chronic disease derived from the interaction between disordered lipoproteins and an unsuitable immune response. The evolution of foam cells is not only a significant pathological change in the early stage of atherosclerosis but also a key stage in the occurrence and development of atherosclerosis. The formation of foam cells is mainly caused by the imbalance among lipids uptake, lipids treatment, and reverse cholesterol transport. Although a large number of studies have summarized the source of foam cells and the mechanism of foam cells formation, we propose a new idea about foam cells in atherosclerosis. Rather than an isolated microenvironment, the macrophage multiple lipid uptake pathways, lipid internalization, lysosome, mitochondria, endoplasmic reticulum, neutral cholesterol ester hydrolase (NCEH), acyl-coenzyme A-cholesterol acyltransferase (ACAT), and reverse cholesterol transport are mutually influential, and form a dynamic process under multi-factor regulation. The macrophage takes on different uptake lipid statuses depending on multiple uptake pathways and intracellular lipids, lipid metabolites versus pro-inflammatory factors. Except for NCEH and ACAT, the lipid internalization of macrophages also depends on multicellular organelles including the lysosome, mitochondria, and endoplasmic reticulum, which are associated with each other. A dynamic balance between esterification and hydrolysis of cholesterol for macrophages is essential for physiology and pathology. Therefore, we propose that the foam cell in the process of atherosclerosis may be dynamic under multi-factor regulation, and collate this study to provide a holistic and dynamic idea of the foam cell.}, } @article {pmid33487113, year = {2021}, author = {Schaap, P}, title = {From environmental sensing to developmental control: cognitive evolution in dictyostelid social amoebas.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1820}, pages = {20190756}, pmid = {33487113}, issn = {1471-2970}, mesh = {*Biological Evolution ; *Cognition ; Dictyosteliida/*physiology ; *Quorum Sensing ; *Signal Transduction ; }, abstract = {Dictyostelid social amoebas respond to starvation by self-organizing into multicellular slugs that migrate towards light to construct spore-bearing structures. These behaviours depend on excitable networks that enable amoebas to produce propagating waves of the chemoattractant cAMP, and to respond by directional movement. cAMP additionally regulates cell differentiation throughout development, with differentiation and cell movement being coordinated by interaction of the stalk inducer c-di-GMP with the adenylate cyclase that generates cAMP oscillations. Evolutionary studies indicate how the manifold roles of cAMP in multicellular development evolved from a role as intermediate for starvation-induced encystation in the unicellular ancestor. A merger of this stress response with the chemotaxis excitable networks yielded the developmental complexity and cognitive capabilities of extant Dictyostelia. This article is part of the theme issue 'Basal cognition: conceptual tools and the view from the single cell'.}, } @article {pmid33479850, year = {2021}, author = {Tourigny, DS}, title = {Cooperative metabolic resource allocation in spatially-structured systems.}, journal = {Journal of mathematical biology}, volume = {82}, number = {1-2}, pages = {5}, pmid = {33479850}, issn = {1432-1416}, mesh = {Biological Evolution ; Entropy ; Humans ; Models, Biological ; Quorum Sensing ; Resource Allocation ; *Selection, Genetic ; *Social Behavior ; }, abstract = {Natural selection has shaped the evolution of cells and multi-cellular organisms such that social cooperation can often be preferred over an individualistic approach to metabolic regulation. This paper extends a framework for dynamic metabolic resource allocation based on the maximum entropy principle to spatiotemporal models of metabolism with cooperation. Much like the maximum entropy principle encapsulates 'bet-hedging' behaviour displayed by organisms dealing with future uncertainty in a fluctuating environment, its cooperative extension describes how individuals adapt their metabolic resource allocation strategy to further accommodate limited knowledge about the welfare of others within a community. The resulting theory explains why local regulation of metabolic cross-feeding can fulfil a community-wide metabolic objective if individuals take into consideration an ensemble measure of total population performance as the only form of global information. The latter is likely supplied by quorum sensing in microbial systems or signalling molecules such as hormones in multi-cellular eukaryotic organisms.}, } @article {pmid33479022, year = {2021}, author = {Kjellin, J and Avesson, L and Reimegård, J and Liao, Z and Eichinger, L and Noegel, A and Glöckner, G and Schaap, P and Söderbom, F}, title = {Abundantly expressed class of noncoding RNAs conserved through the multicellular evolution of dictyostelid social amoebas.}, journal = {Genome research}, volume = {31}, number = {3}, pages = {436-447}, pmid = {33479022}, issn = {1549-5469}, support = {BB/D013453/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Dictyostelium/classification/*cytology/*genetics ; *Evolution, Molecular ; *Phylogeny ; RNA, Untranslated/*genetics ; }, abstract = {Aggregative multicellularity has evolved multiple times in diverse groups of eukaryotes, exemplified by the well-studied development of dictyostelid social amoebas, for example, Dictyostelium discoideum However, it is still poorly understood why multicellularity emerged in these amoebas while the majority of other members of Amoebozoa are unicellular. Previously, a novel type of noncoding RNA, Class I RNAs, was identified in D. discoideum and shown to be important for normal multicellular development. Here, we investigated Class I RNA evolution and its connection to multicellular development. We identified a large number of new Class I RNA genes by constructing a covariance model combined with a scoring system based on conserved upstream sequences. Multiple genes were predicted in representatives of each major group of Dictyostelia and expression analysis confirmed that our search approach identifies expressed Class I RNA genes with high accuracy and sensitivity and that the RNAs are developmentally regulated. Further studies showed that Class I RNAs are ubiquitous in Dictyostelia and share highly conserved structure and sequence motifs. In addition, Class I RNA genes appear to be unique to dictyostelid social amoebas because they could not be identified in outgroup genomes, including their closest known relatives. Our results show that Class I RNA is an ancient class of ncRNAs, likely to have been present in the last common ancestor of Dictyostelia dating back at least 600 million years. Based on previous functional analyses and the presented evolutionary investigation, we hypothesize that Class I RNAs were involved in evolution of multicellularity in Dictyostelia.}, } @article {pmid33471791, year = {2021}, author = {Miele, L and De Monte, S}, title = {Aggregative cycles evolve as a solution to conflicts in social investment.}, journal = {PLoS computational biology}, volume = {17}, number = {1}, pages = {e1008617}, pmid = {33471791}, issn = {1553-7358}, mesh = {*Biological Evolution ; Cell Aggregation/*physiology ; Cell Movement/*physiology ; Computational Biology ; Dictyostelium/cytology/physiology ; *Models, Biological ; }, abstract = {Multicellular organization is particularly vulnerable to conflicts between different cell types when the body forms from initially isolated cells, as in aggregative multicellular microbes. Like other functions of the multicellular phase, coordinated collective movement can be undermined by conflicts between cells that spend energy in fuelling motion and 'cheaters' that get carried along. The evolutionary stability of collective behaviours against such conflicts is typically addressed in populations that undergo extrinsically imposed phases of aggregation and dispersal. Here, via a shift in perspective, we propose that aggregative multicellular cycles may have emerged as a way to temporally compartmentalize social conflicts. Through an eco-evolutionary mathematical model that accounts for individual and collective strategies of resource acquisition, we address regimes where different motility types coexist. Particularly interesting is the oscillatory regime that, similarly to life cycles of aggregative multicellular organisms, alternates on the timescale of several cell generations phases of prevalent solitary living and starvation-triggered aggregation. Crucially, such self-organized oscillations emerge as a result of evolution of cell traits associated to conflict escalation within multicellular aggregates.}, } @article {pmid33460641, year = {2021}, author = {Schrankel, CS and Hamdoun, A}, title = {Early patterning of ABCB, ABCC, and ABCG transporters establishes unique territories of small molecule transport in embryonic mesoderm and endoderm.}, journal = {Developmental biology}, volume = {472}, number = {}, pages = {115-124}, pmid = {33460641}, issn = {1095-564X}, support = {F32 ES029843/ES/NIEHS NIH HHS/United States ; R01 ES027921/ES/NIEHS NIH HHS/United States ; R01 ES030318/ES/NIEHS NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/genetics/*metabolism ; Animals ; Biological Transport ; Endoderm/*metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Intestinal Mucosa/metabolism ; Intestines/embryology ; Mesoderm/*metabolism ; Sea Urchins/*embryology/genetics/metabolism ; Signal Transduction ; }, abstract = {Directed intercellular movement of diverse small molecules, including metabolites, signal molecules and xenobiotics, is a key feature of multicellularity. Networks of small molecule transporters (SMTs), including several ATP Binding Cassette (ABC) transporters, are central to this process. While small molecule transporters are well described in differentiated organs, little is known about their patterns of expression in early embryogenesis. Here we report the pattern of ABC-type SMT expression and activity during the early development of sea urchins. Of the six major ABCs in this embryo (ABCB1, -B4, -C1, -C4, -C5 and -G2), three expression patterns were observed: 1) ABCB1 and ABCC1 are first expressed ubiquitously, and then become enriched in endoderm and ectoderm-derived structures. 2) ABCC4 and ABCC5 are restricted to a ring of mesoderm in the blastula and ABCC4 is later expressed in the coelomic pouches, the embryonic niche of the primordial germ cells. 3) ABCB4 and ABCG2 are expressed exclusively in endoderm-fated cells. Assays with fluorescent substrates and inhibitors of transporters revealed a ring of ABCC4 efflux activity emanating from ABCC4[+] mesodermal cells. Similarly, ABCB1 and ABCB4 efflux activity was observed in the developing gut, prior to the onset of feeding. This study reveals the early establishment of unique territories of small molecule transport during embryogenesis. A pattern of ABCC4/C5 expression is consistent with signaling functions during gut invagination and germ line development, while a later pattern of ABCB1/B4 and ABCG2 is consistent with roles in the embryonic gut. This work provides a conceptual framework with which to examine the function and evolution of SMT networks and to define the specific developmental pathways that drive the expression of these genes.}, } @article {pmid33455859, year = {2021}, author = {Jana, SC}, title = {Centrosome structure and biogenesis: Variations on a theme?.}, journal = {Seminars in cell & developmental biology}, volume = {110}, number = {}, pages = {123-138}, doi = {10.1016/j.semcdb.2020.10.014}, pmid = {33455859}, issn = {1096-3634}, mesh = {Actins/genetics/metabolism ; Animals ; Biodiversity ; Biological Evolution ; Cell Cycle/genetics ; Centrioles/metabolism/*ultrastructure ; Chlorophyta/genetics/metabolism/ultrastructure ; Cilia/metabolism/*ultrastructure ; Eukaryotic Cells/metabolism/ultrastructure ; Gene Expression Regulation ; Humans ; Microtubule-Associated Proteins/classification/*genetics/metabolism ; Microtubules/metabolism/*ultrastructure ; *Organelle Biogenesis ; Species Specificity ; Tubulin/genetics/metabolism ; }, abstract = {Centrosomes are composed of two orthogonally arranged centrioles surrounded by an electron-dense matrix called the pericentriolar material (PCM). Centrioles are cylinders with diameters of ~250 nm, are several hundred nanometres in length and consist of 9-fold symmetrically arranged microtubules (MT). In dividing animal cells, centrosomes act as the principal MT-organising centres and they also organise actin, which tunes cytoplasmic MT nucleation. In some specialised cells, the centrosome acquires additional critical structures and converts into the base of a cilium with diverse functions including signalling and motility. These structures are found in most eukaryotes and are essential for development and homoeostasis at both cellular and organism levels. The ultrastructure of centrosomes and their derived organelles have been known for more than half a century. However, recent advances in a number of techniques have revealed the high-resolution structures (at Å-to-nm scale resolution) of centrioles and have begun to uncover the molecular principles underlying their properties, including: protein components; structural elements; and biogenesis in various model organisms. This review covers advances in our understanding of the features and processes that are critical for the biogenesis of the evolutionarily conserved structures of the centrosomes. Furthermore, it discusses how variations of these aspects can generate diversity in centrosome structure and function among different species and even between cell types within a multicellular organism.}, } @article {pmid33449147, year = {2021}, author = {Kruger, AN and Mueller, JL}, title = {Mechanisms of meiotic drive in symmetric and asymmetric meiosis.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {78}, number = {7}, pages = {3205-3218}, pmid = {33449147}, issn = {1420-9071}, support = {HD094736//National Institute of Child Health and Human Development/ ; R01 HD094736/HD/NICHD NIH HHS/United States ; 1256260//National Science Foundation/ ; T32 GM007544/GM/NIGMS NIH HHS/United States ; T32GM007544/GM/NIGMS NIH HHS/United States ; T32GM007544/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Chromosome Segregation ; Humans ; *Meiosis ; Spindle Apparatus/*physiology ; }, abstract = {Meiotic drive, the non-Mendelian transmission of chromosomes to the next generation, functions in asymmetric or symmetric meiosis across unicellular and multicellular organisms. In asymmetric meiosis, meiotic drivers act to alter a chromosome's spatial position in a single egg. In symmetric meiosis, meiotic drivers cause phenotypic differences between gametes with and without the driver. Here we discuss existing models of meiotic drive, highlighting the underlying mechanisms and regulation governing systems for which the most is known. We focus on outstanding questions surrounding these examples and speculate on how new meiotic drive systems evolve and how to detect them.}, } @article {pmid33446527, year = {2021}, author = {Stadler, T and Pybus, OG and Stumpf, MPH}, title = {Phylodynamics for cell biologists.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6526}, pages = {}, doi = {10.1126/science.aah6266}, pmid = {33446527}, issn = {1095-9203}, mesh = {Animals ; Caenorhabditis elegans/cytology/growth & development ; Cell Biology/trends ; *Cell Lineage ; Humans ; *Phylogeny ; *Single-Cell Analysis ; Stem Cells/cytology/physiology ; }, abstract = {Multicellular organisms are composed of cells connected by ancestry and descent from progenitor cells. The dynamics of cell birth, death, and inheritance within an organism give rise to the fundamental processes of development, differentiation, and cancer. Technical advances in molecular biology now allow us to study cellular composition, ancestry, and evolution at the resolution of individual cells within an organism or tissue. Here, we take a phylogenetic and phylodynamic approach to single-cell biology. We explain how "tree thinking" is important to the interpretation of the growing body of cell-level data and how ecological null models can benefit statistical hypothesis testing. Experimental progress in cell biology should be accompanied by theoretical developments if we are to exploit fully the dynamical information in single-cell data.}, } @article {pmid33440882, year = {2021}, author = {Takahashi, T}, title = {Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function.}, journal = {International journal of molecular sciences}, volume = {22}, number = {2}, pages = {}, pmid = {33440882}, issn = {1422-0067}, support = {JP17K07495 and JP20K06751//Japan Society for the Promotion of Science/ ; }, mesh = {Acetylcholine/*metabolism ; Age Factors ; Animals ; Biomarkers ; Brain/cytology/metabolism ; Cell Differentiation/genetics ; Homeostasis ; Humans ; Organ Specificity ; Receptors, Cholinergic/*metabolism ; *Signal Transduction ; Stem Cells/cytology/*metabolism ; }, abstract = {Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.}, } @article {pmid33421998, year = {2021}, author = {Mondal, M and Peter, J and Scarbrough, O and Flynt, A}, title = {Environmental RNAi pathways in the two-spotted spider mite.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {42}, pmid = {33421998}, issn = {1471-2164}, support = {P20 GM103476/GM/NIGMS NIH HHS/United States ; 1616725//Directorate for Biological Sciences/ ; P204M103476//Mississippi IDeA Network of Biomedical Research Excellence (US)/ ; }, mesh = {Animals ; Gene Expression ; Plants ; RNA Interference ; *Tetranychidae/genetics ; }, abstract = {BACKGROUND: RNA interference (RNAi) regulates gene expression in most multicellular organisms through binding of small RNA effectors to target transcripts. Exploiting this process is a popular strategy for genetic manipulation and has applications that includes arthropod pest control. RNAi technologies are dependent on delivery method with the most convenient likely being feeding, which is effective in some animals while others are insensitive. The two-spotted spider mite, Tetranychus urticae, is prime candidate for developing RNAi approaches due to frequent occurrence of conventional pesticide resistance. Using a sequencing-based approach, the fate of ingested RNAs was explored to identify features and conditions that affect small RNA biogenesis from external sources to better inform RNAi design.

RESULTS: Biochemical and sequencing approaches in conjunction with extensive computational assessment were used to evaluate metabolism of ingested RNAs in T. urticae. This chelicerae arthropod shows only modest response to oral RNAi and has biogenesis pathways distinct from model organisms. Processing of synthetic and plant host RNAs ingested during feeding were evaluated to identify active substrates for spider mite RNAi pathways. Through cataloging characteristics of biochemically purified RNA from these sources, trans-acting small RNAs could be distinguished from degradation fragments and their origins documented.

CONCLUSIONS: Using a strategy that delineates small RNA processing, we found many transcripts have the potential to enter spider mite RNAi pathways, however, trans-acting RNAs appear very unstable and rare. This suggests potential RNAi pathway substrates from ingested materials are mostly degraded and infrequently converted into regulators of gene expression. Spider mites infest a variety of plants, and it would be maladaptive to generate diverse gene regulators from dietary RNAs. This study provides a framework for assessing RNAi technology in organisms where genetic and biochemical tools are absent and benefit rationale design of RNAi triggers for T.urticae.}, } @article {pmid33418487, year = {2021}, author = {Sagova-Mareckova, M and Boenigk, J and Bouchez, A and Cermakova, K and Chonova, T and Cordier, T and Eisendle, U and Elersek, T and Fazi, S and Fleituch, T and Frühe, L and Gajdosova, M and Graupner, N and Haegerbaeumer, A and Kelly, AM and Kopecky, J and Leese, F and Nõges, P and Orlic, S and Panksep, K and Pawlowski, J and Petrusek, A and Piggott, JJ and Rusch, JC and Salis, R and Schenk, J and Simek, K and Stovicek, A and Strand, DA and Vasquez, MI and Vrålstad, T and Zlatkovic, S and Zupancic, M and Stoeck, T}, title = {Expanding ecological assessment by integrating microorganisms into routine freshwater biomonitoring.}, journal = {Water research}, volume = {191}, number = {}, pages = {116767}, doi = {10.1016/j.watres.2020.116767}, pmid = {33418487}, issn = {1879-2448}, mesh = {Archaea/genetics ; *Biological Monitoring ; *Ecosystem ; Environmental Biomarkers ; Environmental Monitoring ; Fresh Water ; }, abstract = {Bioindication has become an indispensable part of water quality monitoring in most countries of the world, with the presence and abundance of bioindicator taxa, mostly multicellular eukaryotes, used for biotic indices. In contrast, microbes (bacteria, archaea and protists) are seldom used as bioindicators in routine assessments, although they have been recognized for their importance in environmental processes. Recently, the use of molecular methods has revealed unexpected diversity within known functional groups and novel metabolic pathways that are particularly important in energy and nutrient cycling. In various habitats, microbial communities respond to eutrophication, metals, and natural or anthropogenic organic pollutants through changes in diversity and function. In this review, we evaluated the common trends in these changes, documenting that they have value as bioindicators and can be used not only for monitoring but also for improving our understanding of the major processes in lotic and lentic environments. Current knowledge provides a solid foundation for exploiting microbial taxa, community structures and diversity, as well as functional genes, in novel monitoring programs. These microbial community measures can also be combined into biotic indices, improving the resolution of individual bioindicators. Here, we assess particular molecular approaches complemented by advanced bioinformatic analysis, as these are the most promising with respect to detailed bioindication value. We conclude that microbial community dynamics are a missing link important for our understanding of rapid changes in the structure and function of aquatic ecosystems, and should be addressed in the future environmental monitoring of freshwater ecosystems.}, } @article {pmid33412387, year = {2021}, author = {Liu, Q and Piao, H and Wang, Y and Zheng, D and Wang, W}, title = {Circulating exosomes in cardiovascular disease: Novel carriers of biological information.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {135}, number = {}, pages = {111148}, doi = {10.1016/j.biopha.2020.111148}, pmid = {33412387}, issn = {1950-6007}, mesh = {Animals ; Biomarkers/metabolism ; Cardiovascular Diseases/blood/genetics/*metabolism/therapy ; Cardiovascular System/*metabolism ; *Cell Communication ; Drug Carriers ; Exosomes/genetics/*metabolism/transplantation ; Gene Transfer Techniques ; Genetic Therapy ; Humans ; Signal Transduction ; }, abstract = {Exosomes are a group of nanosized extracellular vesicles that include various bioactive nucleic acids, lipids, and proteins. They originate from membrane invagination and are released by exocytosis, which can transmit signals to target cells to achieve cell-to-cell communication and maintain homeostasis. The heart is a complex multicellular organ that contains resident cell types such as fibroblasts, endothelial cells, and smooth muscle cells. Communication between different cell types and immune systems is essential for the dynamic equilibrium of the cardiac internal environment. Intercellular communication is a universal phenomenon mediated by exosomes and their contents during several pathological processes in cardiovascular diseases, such as cardiomyocyte hypertrophy, apoptosis, and angiogenesis. Therefore, exosomes can be used as novel invasive diagnostic biomarkers in multiple diseases, including atherosclerosis, myocardial ischemia, cardiac fibrosis, and ischemia-reperfusion injury. In addition, the biocompatible nature and low immunogenicity of exosomes make them high-quality nanoparticle drug carriers with potential applications in translational medicine and therapeutic strategies. Here, we focus on the biogenesis, isolation, biological functions, and future application prospects of exosomes in cardiovascular disease.}, } @article {pmid33411582, year = {2021}, author = {Costa, M and Blaschke, TF and Amara, SG and Meyer, UA and Insel, PA}, title = {Introduction to the Theme "Old and New Toxicology: Interfaces with Pharmacology".}, journal = {Annual review of pharmacology and toxicology}, volume = {61}, number = {}, pages = {1-7}, doi = {10.1146/annurev-pharmtox-092220-033032}, pmid = {33411582}, issn = {1545-4304}, mesh = {Female ; Humans ; Male ; *Pharmacology ; *Toxicology ; }, abstract = {The theme of Volume 61 is "Old and New Toxicology: Interfaces with Pharmacology." Old toxicology is exemplified by the authors of the autobiographical articles: B.M. Olivera's work on toxins and venoms from cone snails and P. Taylor's studies of acetylcholinesterase and the nicotinic cholinergic receptor, which serve as sites of action for numerous pesticides and venoms. Other articles in this volume focus on new understanding and new types of toxicology, including (a) arsenic toxicity, which is an ancient poison that, through evolution, has caused most multicellular organisms to express an active arsenic methyltransferase to methylate arsenite, which accelerates the excretion of arsenic from the body; (b) small molecules that react with lipid dicarbonyls, which are now considered the most toxic oxidative stress end products; (c) immune checkpoint inhibitors (ICIs), which have revolutionized cancer therapy but have numerous immune-related adverse events, including cardiovascular complications; (d) autoimmunity caused by the environment; (e) idiosyncratic drug-induced liver disease, which together with the toxicity of ICIs represents new toxicology interfacing with pharmacology; and (f) sex differences in the development of cardiovascular disease, with men more susceptible than women to vascular inflammation that initiates and perpetuates disease. These articles and others in Volume 61 reflect the interface and close integration of pharmacology and toxicology that began long ago but continues today.}, } @article {pmid33397407, year = {2021}, author = {Bourdareau, S and Tirichine, L and Lombard, B and Loew, D and Scornet, D and Wu, Y and Coelho, SM and Cock, JM}, title = {Histone modifications during the life cycle of the brown alga Ectocarpus.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {12}, pmid = {33397407}, issn = {1474-760X}, mesh = {Chromatin/metabolism ; Epigenesis, Genetic ; Genome ; Germ Cells, Plant ; *Histone Code ; *Histones ; *Life Cycle Stages ; Phaeophyceae/*genetics/physiology ; Phylogeny ; Plants/genetics ; *Protein Processing, Post-Translational ; }, abstract = {BACKGROUND: Brown algae evolved complex multicellularity independently of the animal and land plant lineages and are the third most developmentally complex phylogenetic group on the planet. An understanding of developmental processes in this group is expected to provide important insights into the evolutionary events necessary for the emergence of complex multicellularity. Here, we focus on mechanisms of epigenetic regulation involving post-translational modifications of histone proteins.

RESULTS: A total of 47 histone post-translational modifications are identified, including a novel mark H2AZR38me1, but Ectocarpus lacks both H3K27me3 and the major polycomb complexes. ChIP-seq identifies modifications associated with transcription start sites and gene bodies of active genes and with transposons. H3K79me2 exhibits an unusual pattern, often marking large genomic regions spanning several genes. Transcription start sites of closely spaced, divergently transcribed gene pairs share a common nucleosome-depleted region and exhibit shared histone modification peaks. Overall, patterns of histone modifications are stable through the life cycle. Analysis of histone modifications at generation-biased genes identifies a correlation between the presence of specific chromatin marks and the level of gene expression.

CONCLUSIONS: The overview of histone post-translational modifications in the brown alga presented here will provide a foundation for future studies aimed at understanding the role of chromatin modifications in the regulation of brown algal genomes.}, } @article {pmid33389562, year = {2021}, author = {Furumizu, C and Sawa, S}, title = {Insight into early diversification of leucine-rich repeat receptor-like kinases provided by the sequenced moss and hornwort genomes.}, journal = {Plant molecular biology}, volume = {107}, number = {4-5}, pages = {337-353}, pmid = {33389562}, issn = {1573-5028}, support = {17H03967//Japan Society for the Promotion of Science/ ; 18H04841//Japan Society for the Promotion of Science/ ; 18H04625//Japan Society for the Promotion of Science/ ; 18H05487//Japan Society for the Promotion of Science/ ; 20H00422//Japan Society for the Promotion of Science/ ; 20K06770//Japan Society for the Promotion of Science/ ; }, mesh = {Amino Acid Sequence ; Anthocerotophyta/*genetics ; Computer Simulation ; Evolution, Molecular ; *Genetic Variation ; Genome, Plant/*genetics ; Genomics/methods ; Phylogeny ; Plant Proteins/chemistry/classification/*genetics ; Protein Domains ; Protein Kinases/chemistry/classification/*genetics ; Sequence Homology, Amino Acid ; Signal Transduction/genetics ; Sphagnopsida/*genetics ; }, abstract = {Identification of the subfamily X leucine-rich repeat receptor-like kinases in the recently sequenced moss and hornwort genomes points to their diversification into distinct groups during early evolution of land plants. Signal transduction mediated through receptor-ligand interactions plays key roles in controlling developmental and physiological processes of multicellular organisms, and plants employ diverse receptors in signaling. Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent one of the largest receptor classes in plants and are structurally classified into subfamilies. LRR-RLKs of the subfamily X are unique in the variety of their signaling roles; they include receptors for steroid or peptide hormones as well as negative regulators of signaling through binding to other LRR-RLKs, raising a question as to how they diversified. However, our understanding of diversification processes of LRR-RLKs has been hindered by the paucity of genomic data in non-seed plants and limited taxa sampling in previous phylogenetic analyses. Here we analyzed the phylogeny of LRR-RLK X sequences collected from all major land plant lineages and show that this subfamily diversified into six major clades before the divergence between bryophytes and vascular plants. Notably, we have identified homologues of the brassinosteroid receptor, BRASSINOSTEROID INSENSITIVE 1 (BRI1), in the genomes of Sphagnum mosses, hornworts, and ferns, contrary to earlier reports that postulate the origin of BRI1-like LRR-RLKs in the seed plant lineage. The phylogenetic distribution of major clades illustrates that the current receptor repertoire was shaped through lineage-specific gene family expansion and independent gene losses, highlighting dynamic changes in the evolution of LRR-RLKs.}, } @article {pmid33373044, year = {2021}, author = {Montoro, R and Heine, VM and Kemp, S and Engelen, M}, title = {Evolution of adrenoleukodystrophy model systems.}, journal = {Journal of inherited metabolic disease}, volume = {44}, number = {3}, pages = {544-553}, pmid = {33373044}, issn = {1573-2665}, mesh = {ATP Binding Cassette Transporter, Subfamily D, Member 1/*genetics ; Adrenoleukodystrophy/epidemiology/*genetics ; Adult ; Animals ; Biological Evolution ; Fatty Acids/metabolism ; Female ; Humans ; Male ; *Models, Animal ; *Models, Biological ; Mutation ; Sex Factors ; Spinal Cord Diseases/epidemiology ; }, abstract = {X-linked adrenoleukodystrophy (ALD) is a neurometabolic disorder affecting the adrenal glands, testes, spinal cord and brain. The disease is caused by mutations in the ABCD1 gene resulting in a defect in peroxisomal degradation of very long-chain fatty acids and their accumulation in plasma and tissues. Males with ALD have a near 100% life-time risk to develop myelopathy. The life-time prevalence to develop progressive cerebral white matter lesions (known as cerebral ALD) is about 60%. Adrenal insufficiency occurs in about 80% of male patients. In adulthood, 80% of women with ALD also develop myelopathy, but adrenal insufficiency or cerebral ALD are very rare. The complex clinical presentation and the absence of a genotype-phenotype correlation are complicating our understanding of the disease. In an attempt to understand the pathophysiology of ALD various model systems have been developed. While these model systems share the basic genetics and biochemistry of ALD they fail to fully recapitulate the complex neurodegenerative etiology of ALD. Each model system recapitulates certain aspects of the disorder. This exposes the complexity of ALD and therefore the challenge to create a comprehensive model system to fully understand ALD. In this review, we provide an overview of the different ALD modeling strategies from single-celled to multicellular organisms and from in vitro to in vivo approaches, and introduce how emerging iPSC-derived technologies could improve the understanding of this highly complex disorder.}, } @article {pmid33355212, year = {2021}, author = {Stresser, DM and Sun, J and Wilson, SS}, title = {Evaluation of Tissue Stem Cell-Derived Human Intestinal Organoids, a Physiologically Relevant Model to Evaluate Cytochrome P450 Induction in Gut.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {49}, number = {3}, pages = {245-253}, doi = {10.1124/dmd.120.000281}, pmid = {33355212}, issn = {1521-009X}, mesh = {Cell Line ; Cytochrome P-450 Enzyme Inducers/*pharmacology ; Cytochrome P-450 Enzyme System/*biosynthesis ; Dose-Response Relationship, Drug ; Enzyme Induction/drug effects/physiology ; Humans ; Intestines/cytology/drug effects/*enzymology ; Organoids/drug effects/*enzymology ; Rifampin/pharmacology ; Stem Cells/drug effects/*enzymology ; }, abstract = {Induction of cytochrome P450 can cause drug-drug interactions and efficacy failure. Induction risk in liver and gut is typically inferred from experiments with plated hepatocytes. Organoids are physiologically relevant, multicellular structures originating from stem cells. Intestinal stem cell-derived organoids retain traits of normal gut physiology, such as an epithelial barrier and cellular diversity. Matched human enteroid and colonoid lines, generated from ileal and colon biopsies from two donors, were cultured in extracellular matrix for 3 days, followed by a single 48-hour treatment with rifampin, omeprazole, CITCO, and phenytoin at concentrations that induce target genes in hepatocytes. After treatment, mRNA was analyzed for induction of target genes. Rifampin induced CYP3A4; estimated EC50 and maximal fold induction were 3.75 µM and 8.96-fold, respectively, for ileal organoids and 1.40 µM and 11.3-fold, respectively, for colon organoids. Ileal, but not colon, organoids exhibited nifedipine oxidase activity, which was induced by rifampin up to 14-fold. The test compounds did not increase mRNA expression of CYP1A2, CYP2B6, multidrug resistance transporter 1 (P-glycoprotein), breast cancer resistance protein, and UDP-glucuronosyltransferase 1A1 in ileal organoids. Whereas omeprazole induced CYP3A4 (up to 5.3-fold, geometric mean, n = 4 experiments), constitutive androstane receptor activators phenytoin and CITCO did not. Omeprazole failed to induce CYP1A2 mRNA but did induce CYP1A1 mRNA (up to 7.7-fold and 15-fold in ileal and colon organoids, respectively, n = 4 experiments). Despite relatively high intra- and interexperimental variability, data suggest that the model yields induction responses that are distinct from hepatocytes and holds promise to enable evaluation of CYP1A1 and CYP3A4 induction in gut. SIGNIFICANCE STATEMENT: An adult intestinal stem cell-derived organoid model to test P450 induction in gut was evaluated. Testing several prototypical inducers for mRNA induction of P450 isoforms, UDP-glucuronosyltransferase 1A1, P-glycoprotein, and breast cancer resistance protein with both human colon and ileal organoids resulted in a range of responses, often distinct from those found in hepatocytes, indicating the potential for further development of this model as a physiologically relevant gut induction test system.}, } @article {pmid33354870, year = {2021}, author = {Fritsche, E and Haarmann-Stemmann, T and Kapr, J and Galanjuk, S and Hartmann, J and Mertens, PR and Kämpfer, AAM and Schins, RPF and Tigges, J and Koch, K}, title = {Stem Cells for Next Level Toxicity Testing in the 21st Century.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {17}, number = {15}, pages = {e2006252}, doi = {10.1002/smll.202006252}, pmid = {33354870}, issn = {1613-6829}, mesh = {Humans ; In Vitro Techniques ; *Induced Pluripotent Stem Cells ; *Toxicity Tests ; United States ; }, abstract = {The call for a paradigm change in toxicology from the United States National Research Council in 2007 initiates awareness for the invention and use of human-relevant alternative methods for toxicological hazard assessment. Simple 2D in vitro systems may serve as first screening tools, however, recent developments infer the need for more complex, multicellular organotypic models, which are superior in mimicking the complexity of human organs. In this review article most critical organs for toxicity assessment, i.e., skin, brain, thyroid system, lung, heart, liver, kidney, and intestine are discussed with regards to their functions in health and disease. Embracing the manifold modes-of-action how xenobiotic compounds can interfere with physiological organ functions and cause toxicity, the need for translation of such multifaceted organ features into the dish seems obvious. Currently used in vitro methods for toxicological applications and ongoing developments not yet arrived in toxicity testing are discussed, especially highlighting the potential of models based on embryonic stem cells and induced pluripotent stem cells of human origin. Finally, the application of innovative technologies like organs-on-a-chip and genome editing point toward a toxicological paradigm change moves into action.}, } @article {pmid33305692, year = {2020}, author = {Giam, M and Wong, CK and Low, JS and Sinelli, M and Dreesen, O and Rancati, G}, title = {P53 induces senescence in the unstable progeny of aneuploid cells.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {19}, number = {24}, pages = {3508-3520}, pmid = {33305692}, issn = {1551-4005}, mesh = {*Aneuploidy ; Cell Cycle Checkpoints/genetics ; Cell Proliferation/genetics ; Cell Transformation, Neoplastic/genetics/metabolism ; Cellular Senescence/*genetics ; Chromosomal Instability/genetics ; Chromosome Segregation/genetics ; Epithelial Cells/*metabolism ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Karyotype ; Retinal Pigment Epithelium/*cytology ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Aneuploidy is the condition of having an imbalanced karyotype, which is associated with tumor initiation, evolution, and acquisition of drug-resistant features, possibly by generating heterogeneous populations of cells with distinct genotypes and phenotypes. Multicellular eukaryotes have therefore evolved a range of extrinsic and cell-autonomous mechanisms for restraining proliferation of aneuploid cells, including activation of the tumor suppressor protein p53. However, accumulating evidence indicates that a subset of aneuploid cells can escape p53-mediated growth restriction and continue proliferating in vitro. Here we show that such aneuploid cell lines display a robust modal karyotype and low frequency of chromosomal aberrations despite ongoing chromosome instability. Indeed, while these aneuploid cells are able to survive for extended periods in vitro, their chromosomally unstable progeny remain subject to p53-induced senescence and growth restriction, leading to subsequent elimination from the aneuploid pool. This mechanism helps maintain low levels of heterogeneity in aneuploid populations and may prevent detrimental evolutionary processes such as cancer progression and development of drug resistance.}, } @article {pmid33272929, year = {2020}, author = {Ruiz-Trillo, I and de Mendoza, A}, title = {Towards understanding the origin of animal development.}, journal = {Development (Cambridge, England)}, volume = {147}, number = {23}, pages = {}, doi = {10.1242/dev.192575}, pmid = {33272929}, issn = {1477-9129}, mesh = {Animals ; *Biological Evolution ; Choanoflagellata/genetics/*growth & development ; Embryonic Development/*genetics ; Gene Expression Regulation, Developmental/genetics ; Mammals/genetics ; Morphogenesis/*genetics ; Phylogeny ; Zygote/growth & development ; }, abstract = {Almost all animals undergo embryonic development, going from a single-celled zygote to a complex multicellular adult. We know that the patterning and morphogenetic processes involved in development are deeply conserved within the animal kingdom. However, the origins of these developmental processes are just beginning to be unveiled. Here, we focus on how the protist lineages sister to animals are reshaping our view of animal development. Most intriguingly, many of these protistan lineages display transient multicellular structures, which are governed by similar morphogenetic and gene regulatory processes as animal development. We discuss here two potential alternative scenarios to explain the origin of animal embryonic development: either it originated concomitantly at the onset of animals or it evolved from morphogenetic processes already present in their unicellular ancestors. We propose that an integrative study of several unicellular taxa closely related to animals will allow a more refined picture of how the last common ancestor of animals underwent embryonic development.}, } @article {pmid33266251, year = {2020}, author = {Lyall, R and Nikoloski, Z and Gechev, T}, title = {Comparative Analysis of ROS Network Genes in Extremophile Eukaryotes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {23}, pages = {}, pmid = {33266251}, issn = {1422-0067}, support = {SGA-CSA No. 739582//Project PlantaSYST, European Union's Horizon 2020 Research & Innovation Programme/ ; GA No. 823746//Project RESIST, European Union's Horizon 2020 Research & Innovation Programme/ ; BG05M2OP001-1.003-001-C01//European Regional Development Fund/ ; }, mesh = {Biomarkers ; Eukaryota/*genetics/*metabolism ; Extremophiles/*genetics/*metabolism ; Gene Expression Regulation ; Gene Expression Regulation, Enzymologic ; *Gene Regulatory Networks ; Oxidative Stress ; Plants/genetics/metabolism ; Reactive Oxygen Species/*metabolism ; }, abstract = {The reactive oxygen species (ROS) gene network, consisting of both ROS-generating and detoxifying enzymes, adjusts ROS levels in response to various stimuli. We performed a cross-kingdom comparison of ROS gene networks to investigate how they have evolved across all Eukaryotes, including protists, fungi, plants and animals. We included the genomes of 16 extremotolerant Eukaryotes to gain insight into ROS gene evolution in organisms that experience extreme stress conditions. Our analysis focused on ROS genes found in all Eukaryotes (such as catalases, superoxide dismutases, glutathione reductases, peroxidases and glutathione peroxidase/peroxiredoxins) as well as those specific to certain groups, such as ascorbate peroxidases, dehydroascorbate/monodehydroascorbate reductases in plants and other photosynthetic organisms. ROS-producing NADPH oxidases (NOX) were found in most multicellular organisms, although several NOX-like genes were identified in unicellular or filamentous species. However, despite the extreme conditions experienced by extremophile species, we found no evidence for expansion of ROS-related gene families in these species compared to other Eukaryotes. Tardigrades and rotifers do show ROS gene expansions that could be related to their extreme lifestyles, although a high rate of lineage-specific horizontal gene transfer events, coupled with recent tetraploidy in rotifers, could explain this observation. This suggests that the basal Eukaryotic ROS scavenging systems are sufficient to maintain ROS homeostasis even under the most extreme conditions.}, } @article {pmid33263876, year = {2020}, author = {Kaczanowski, S}, title = {Symbiotic Origin of Apoptosis.}, journal = {Results and problems in cell differentiation}, volume = {69}, number = {}, pages = {253-280}, pmid = {33263876}, issn = {0080-1844}, mesh = {Animals ; *Apoptosis ; *Biological Evolution ; *Eukaryota ; Mitochondria/*microbiology ; Phylogeny ; *Symbiosis ; }, abstract = {The progress of evolutionary biology has revealed that symbiosis played a basic role in the evolution of complex eukaryotic organisms, including humans. Mitochondria are actually simplified endosymbiotic bacteria currently playing the role of cellular organelles. Mitochondrial domestication occurred at the very beginning of eukaryotic evolution. Mitochondria have two different basic functions: they produce energy using oxidative respiration, and they initiate different forms of apoptotic programmed/regulated cell death. Apoptotic programmed cell death may have different cytological forms. Mechanisms of apoptotic programmed cell death exist even in the unicellular organisms, and they play a basic role in the development of complex multicellular organisms, such as fungi, green plants, and animals. Multicellularity was independently established many times among eukaryotes. There are indications that apoptotic programmed cell death is a trait required for the establishment of multicellularity. Regulated cell death is initiated by many different parallel biochemical pathways. It is generally accepted that apoptosis evolved during mitochondrial domestication. However, there are different hypothetical models of the origin of apoptosis. The phylogenetic studies of my group indicate that apoptosis probably evolved during an evolutionary arms race between host ancestral eukaryotic predators and ancestral prey mitochondria (named protomitochondria). Protomitochondrial prey produced many different toxins as a defense against predators. From these toxins evolved extant apoptotic factors. There are indications that aerobic respiration and apoptosis co-evolved and are functionally linked in extant organisms. Perturbations of apoptosis and oxidative respiration are frequently observed during neoplastic transition. Our group showed that perturbations of apoptosis in yeasts also cause perturbations of oxidative respiration.}, } @article {pmid33262337, year = {2020}, author = {McEvoy, E and Han, YL and Guo, M and Shenoy, VB}, title = {Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6148}, pmid = {33262337}, issn = {2041-1723}, support = {R01 CA232256/CA/NCI NIH HHS/United States ; R01 EB017753/EB/NIBIB NIH HHS/United States ; R01 EB030876/EB/NIBIB NIH HHS/United States ; }, mesh = {Breast Neoplasms/chemistry/pathology/*physiopathology ; Cell Line, Tumor ; *Cell Proliferation ; Cell Size ; Disease Progression ; Female ; Gap Junctions/*chemistry ; Humans ; Osmotic Pressure ; Spheroids, Cellular/chemistry/*cytology ; }, abstract = {Sustained proliferation is a significant driver of cancer progression. Cell-cycle advancement is coupled with cell size, but it remains unclear how multiple cells interact to control their volume in 3D clusters. In this study, we propose a mechano-osmotic model to investigate the evolution of volume dynamics within multicellular systems. Volume control depends on an interplay between multiple cellular constituents, including gap junctions, mechanosensitive ion channels, energy-consuming ion pumps, and the actomyosin cortex, that coordinate to manipulate cellular osmolarity. In connected cells, we show that mechanical loading leads to the emergence of osmotic pressure gradients between cells with consequent increases in cellular ion concentrations driving swelling. We identify how gap junctions can amplify spatial variations in cell volume within multicellular spheroids and, further, describe how the process depends on proliferation-induced solid stress. Our model may provide new insight into the role of gap junctions in breast cancer progression.}, } @article {pmid33259762, year = {2020}, author = {König, SG and Nedelcu, AM}, title = {The genetic basis for the evolution of soma: mechanistic evidence for the co-option of a stress-induced gene into a developmental master regulator.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1940}, pages = {20201414}, pmid = {33259762}, issn = {1471-2954}, mesh = {*Biological Evolution ; Chlorophyta/*genetics ; Clonal Evolution/*genetics ; Stress, Physiological/*genetics ; }, abstract = {In multicellular organisms with specialized cells, the most significant distinction among cell types is between reproductive (germ) cells and non-reproductive/somatic cells (soma). Although soma contributed to the marked increase in complexity of many multicellular lineages, little is known about its evolutionary origins. We have previously suggested that the evolution of genes responsible for the differentiation of somatic cells involved the co-option of life history trade-off genes that in unicellular organisms enhanced survival at a cost to immediate reproduction. In the multicellular green alga, Volvox carteri, cell fate is established early in development by the differential expression of a master regulatory gene known as regA. A closely related RegA-Like Sequence (RLS1) is present in its single-celled relative, Chlamydomonas reinhardtii. RLS1 is expressed in response to stress, and we proposed that an environmentally induced RLS1-like gene was co-opted into a developmental pathway in the lineage leading to V. carteri. However, the exact evolutionary scenario responsible for the postulated co-option event remains to be determined. Here, we show that in addition to being developmentally regulated, regA can also be induced by environmental cues, indicating that regA has maintained its ancestral regulation. We also found that the absence of a functional RegA protein confers increased sensitivity to stress, consistent with RegA having a direct or indirect role in stress responses. Overall, this study (i) provides mechanistic evidence for the co-option of an environmentally induced gene into a major developmental regulator, (ii) supports the view that major morphological innovations can evolve via regulatory changes and (iii) argues for the role of stress in the evolution of multicellular complexity.}, } @article {pmid33254563, year = {2020}, author = {Retzinger, AC and Retzinger, GS}, title = {Mites, ticks, anaphylaxis and allergy: The Acari hypothesis.}, journal = {Medical hypotheses}, volume = {144}, number = {}, pages = {110257}, doi = {10.1016/j.mehy.2020.110257}, pmid = {33254563}, issn = {1532-2777}, mesh = {Allergens ; *Anaphylaxis ; Animals ; *Food Hypersensitivity ; Humans ; Immunoglobulin E ; *Mites ; *Ticks ; }, abstract = {Anaphylaxis is a poorly understood immune process in which a Th2-/IgE-mediated adaptive response commandeers cellular machinery, typically reserved for defense against multicellular ectoparasites, to activate against otherwise benign molecules. Its clinical manifestations consist of rapid pathophysiological reflexes that target epithelial surfaces. The galactose-α-1,3-galactose hypersensitivity response is a compelling model of anaphylaxis for which causation has been demonstrated. At the core of the model, a tick bite sensitizes a recipient to a tick foodstuff. As proposed herein, the model likely informs on the origin of all allergic inflammation; namely, allergy is not intended to protect against seemingly harmless and irrelevant materials, but is, instead, intended to rid epithelial surfaces of pathogen-bearing Acari, i.e., mites and ticks. The demonstrated adjuvant activity of acarian gastrointestinal secretions, when paired with the polyphagous diet of mites, renders acarians eminently suited to accounting, mechanistically, for many, if not all, human allergies.}, } @article {pmid33248278, year = {2020}, author = {Chi, S and Wang, G and Liu, T and Wang, X and Liu, C and Jin, Y and Yin, H and Xu, X and Yu, J}, title = {Transcriptomic and Proteomic Analysis of Mannitol-metabolism-associated Genes in Saccharina japonica.}, journal = {Genomics, proteomics & bioinformatics}, volume = {18}, number = {4}, pages = {415-429}, pmid = {33248278}, issn = {2210-3244}, mesh = {*Laminaria ; Mannitol ; *Phaeophyceae/genetics ; Proteomics ; Transcriptome ; }, abstract = {As a carbon-storage compound and osmoprotectant in brown algae, mannitol is synthesized and then accumulated at high levels in Saccharina japonica (Sja); however, the underlying control mechanisms have not been studied. Our analysis of genomic and transcriptomic data from Sja shows that mannitol metabolism is a cyclic pathway composed of four distinct steps. A mannitol-1-phosphate dehydrogenase (M1PDH2) and two mannitol-1-phosphatases (M1Pase1 and MIPase2) work together or in combination to exhibit full enzymatic properties. Based on comprehensive transcriptomic data from different tissues, generations, and sexes as well as under different stress conditions, coupled with droplet digital PCR (ddPCR) and proteomic confirmation, we suggest that SjaM1Pase1 plays a major role in mannitol biosynthesis and that the basic mannitol anabolism and the carbohydrate pool dynamics are responsible for carbon storage and anti-stress mechanism. Our proteomic data indicate that mannitol metabolism remains constant during diurnal cycle in Sja. In addition, we discover that mannitol-metabolism-associated (MMA) genes show differential expression between the multicellular filamentous (gametophyte) and large parenchymal thallus (sporophyte) generations and respond differentially to environmental stresses, such as hyposaline and hyperthermia conditions. Our results indicate that the ecophysiological significance of such differentially expressed genes may be attributable to the evolution of heteromorphic generations (filamentous and thallus) and environmental adaptation of Laminariales.}, } @article {pmid33239636, year = {2020}, author = {Xu, Z and Wang, S and Zhao, C and Li, S and Liu, X and Wang, L and Li, M and Huang, X and Mann, S}, title = {Photosynthetic hydrogen production by droplet-based microbial micro-reactors under aerobic conditions.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5985}, pmid = {33239636}, issn = {2041-1723}, mesh = {Aerobiosis/physiology ; Bioreactors/*microbiology ; Cell Hypoxia/physiology ; Chlorella/metabolism ; Escherichia coli/metabolism ; Hydrogen/*metabolism ; Industrial Microbiology/*methods ; Microbiota/*physiology ; Oxygen/*metabolism ; Photosynthesis/physiology ; Renewable Energy ; }, abstract = {The spontaneous self-assembly of multicellular ensembles into living materials with synergistic structure and function remains a considerable challenge in biotechnology and synthetic biology. Here, we exploit the aqueous two-phase separation of dextran-in-PEG emulsion micro-droplets for the capture, spatial organization and immobilization of algal cells or algal/bacterial cell communities to produce discrete multicellular spheroids capable of both aerobic (oxygen producing) and hypoxic (hydrogen producing) photosynthesis in daylight under air. We show that localized oxygen depletion results in hydrogen production from the core of the algal microscale reactor, and demonstrate that enhanced levels of hydrogen evolution can be achieved synergistically by spontaneously enclosing the photosynthetic cells within a shell of bacterial cells undergoing aerobic respiration. Our results highlight a promising droplet-based environmentally benign approach to dispersible photosynthetic microbial micro-reactors comprising segregated cellular micro-niches with dual functionality, and provide a step towards photobiological hydrogen production under aerobic conditions.}, } @article {pmid33228413, year = {2020}, author = {Coelho, SM and Cock, JM}, title = {Brown Algal Model Organisms.}, journal = {Annual review of genetics}, volume = {54}, number = {}, pages = {71-92}, doi = {10.1146/annurev-genet-030620-093031}, pmid = {33228413}, issn = {1545-2948}, mesh = {Animals ; Genome/genetics ; Humans ; Models, Biological ; Phaeophyceae/*genetics ; Phylogeny ; }, abstract = {Model organisms are extensively used in research as accessible and convenient systems for studying a particular area or question in biology. Traditionally, only a limited number of organisms have been studied in detail, but modern genomic tools are enabling researchers to extend beyond the set of classical model organisms to include novel species from less-studied phylogenetic groups. This review focuses on model species for an important group of multicellular organisms, the brown algae. The development of genetic and genomic tools for the filamentous brown alga Ectocarpus has led to it emerging as a general model system for this group, but additional models, such as Fucus or Dictyota dichotoma, remain of interest for specific biological questions. In addition, Saccharina japonica has emerged as a model system to directly address applied questions related to algal aquaculture. We discuss the past, present, and future of brown algal model organisms in relation to the opportunities and challenges in brown algal research.}, } @article {pmid33228223, year = {2020}, author = {Anatskaya, OV and Vinogradov, AE and Vainshelbaum, NM and Giuliani, A and Erenpreisa, J}, title = {Phylostratic Shift of Whole-Genome Duplications in Normal Mammalian Tissues towards Unicellularity Is Driven by Developmental Bivalent Genes and Reveals a Link to Cancer.}, journal = {International journal of molecular sciences}, volume = {21}, number = {22}, pages = {}, pmid = {33228223}, issn = {1422-0067}, support = {1.1.1.1/18/A/099//European Regional Development Fund (ERDF)/ ; 12//Institute of Cytology Director's Fund/ ; XX//Natural Sciences PhD Student Scholarship from the University of Latvia Foundation/ ; }, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Carcinogenesis/*genetics/metabolism/pathology ; Circadian Rhythm Signaling Peptides and Proteins/genetics/metabolism ; Drug Resistance, Neoplasm/genetics ; Epigenesis, Genetic ; Gene Duplication ; *Gene Expression Regulation, Neoplastic ; *Genome ; Humans ; Metabolic Networks and Pathways/genetics ; Mice ; Neoplasm Proteins/*genetics/metabolism ; Neoplasms/drug therapy/*genetics/metabolism/pathology ; Oncogenes ; *Ploidies ; Protein Interaction Mapping ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; }, abstract = {Tumours were recently revealed to undergo a phylostratic and phenotypic shift to unicellularity. As well, aggressive tumours are characterized by an increased proportion of polyploid cells. In order to investigate a possible shared causation of these two features, we performed a comparative phylostratigraphic analysis of ploidy-related genes, obtained from transcriptomic data for polyploid and diploid human and mouse tissues using pairwise cross-species transcriptome comparison and principal component analysis. Our results indicate that polyploidy shifts the evolutionary age balance of the expressed genes from the late metazoan phylostrata towards the upregulation of unicellular and early metazoan phylostrata. The up-regulation of unicellular metabolic and drug-resistance pathways and the downregulation of pathways related to circadian clock were identified. This evolutionary shift was associated with the enrichment of ploidy with bivalent genes (p < 10[-16]). The protein interactome of activated bivalent genes revealed the increase of the connectivity of unicellulars and (early) multicellulars, while circadian regulators were depressed. The mutual polyploidy-c-MYC-bivalent genes-associated protein network was organized by gene-hubs engaged in both embryonic development and metastatic cancer including driver (proto)-oncogenes of viral origin. Our data suggest that, in cancer, the atavistic shift goes hand-in-hand with polyploidy and is driven by epigenetic mechanisms impinging on development-related bivalent genes.}, } @article {pmid33211684, year = {2020}, author = {Aubier, TG and Galipaud, M and Erten, EY and Kokko, H}, title = {Transmissible cancers and the evolution of sex under the Red Queen hypothesis.}, journal = {PLoS biology}, volume = {18}, number = {11}, pages = {e3000916}, pmid = {33211684}, issn = {1545-7885}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Genetics, Population/methods ; Host-Parasite Interactions/genetics ; Humans ; Models, Biological ; Models, Genetic ; Neoplasms/etiology/genetics ; Parasites ; Reproduction/*genetics/physiology ; Selection, Genetic/genetics/*physiology ; Sex ; }, abstract = {The predominance of sexual reproduction in eukaryotes remains paradoxical in evolutionary theory. Of the hypotheses proposed to resolve this paradox, the 'Red Queen hypothesis' emphasises the potential of antagonistic interactions to cause fluctuating selection, which favours the evolution and maintenance of sex. Whereas empirical and theoretical developments have focused on host-parasite interactions, the premises of the Red Queen theory apply equally well to any type of antagonistic interactions. Recently, it has been suggested that early multicellular organisms with basic anticancer defences were presumably plagued by antagonistic interactions with transmissible cancers and that this could have played a pivotal role in the evolution of sex. Here, we dissect this argument using a population genetic model. One fundamental aspect distinguishing transmissible cancers from other parasites is the continual production of cancerous cell lines from hosts' own tissues. We show that this influx dampens fluctuating selection and therefore makes the evolution of sex more difficult than in standard Red Queen models. Although coevolutionary cycling can remain sufficient to select for sex under some parameter regions of our model, we show that the size of those regions shrinks once we account for epidemiological constraints. Altogether, our results suggest that horizontal transmission of cancerous cells is unlikely to cause fluctuating selection favouring sexual reproduction. Nonetheless, we confirm that vertical transmission of cancerous cells can promote the evolution of sex through a separate mechanism, known as similarity selection, that does not depend on coevolutionary fluctuations.}, } @article {pmid33184914, year = {2021}, author = {Castillo, SP and Keymer, JE and Marquet, PA}, title = {Do microenvironmental changes disrupt multicellular organisation with ageing, enacting and favouring the cancer cell phenotype?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {2}, pages = {e2000126}, doi = {10.1002/bies.202000126}, pmid = {33184914}, issn = {1521-1878}, mesh = {Aging ; Animals ; *Biological Evolution ; Ecosystem ; Humans ; *Neoplasms/genetics ; Phenotype ; }, abstract = {Cancer is a singular cellular state, the emergence of which destabilises the homeostasis reached through the evolution to multicellularity. We present the idea that the onset of the cellular disobedience to the metazoan functional and structural architecture, known as the cancer phenotype, is triggered by changes in the cell's external environment that occur with ageing: what ensues is a breach of the social contract of multicellular life characteristic of metazoans. By integrating old ideas with new evidence, we propose that with ageing the environmental information that maintains a multicellular organisation is eroded, rewiring internal processes of the cell, and resulting in an internal shift towards an ancestral condition resulting in the pseudo-multicellular cancer phenotype. Once that phenotype emerges, a new local social contract is built, different from the homeostatic one, leading to tumour formation and the foundation of a novel local ecosystem.}, } @article {pmid33180181, year = {2020}, author = {Konarska, A and Łotocka, B}, title = {Glandular trichomes of Robinia viscosa Vent. var. hartwigii (Koehne) Ashe (Faboideae, Fabaceae)-morphology, histochemistry and ultrastructure.}, journal = {Planta}, volume = {252}, number = {6}, pages = {102}, pmid = {33180181}, issn = {1432-2048}, mesh = {Flowers ; *Histocytochemistry ; Microscopy, Electron ; Plant Leaves ; *Robinia/chemistry/ultrastructure ; *Trichomes/chemistry/ultrastructure ; }, abstract = {Permanent glandular trichomes of Robinia viscosa var. hartwigii produce viscous secretion containing several secondary metabolites, as lipids, mucilage, flavonoids, proteins and alkaloids. Robinia viscosa var. hartwigii (Hartweg's locust) is an ornamental tree with high apicultural value. It can be planted in urban greenery and in degraded areas. The shoots, leaves, and inflorescences of this plant are equipped with numerous persistent glandular trichomes producing sticky secretion. The distribution, origin, development, morphology, anatomy, and ultrastructure of glandular trichomes of Hartweg's locust flowers as well as the localisation and composition of their secretory products were investigated for the first time. To this end, light, scanning, and transmission electron microscopy combined with histochemical and fluorescence techniques were used. The massive glandular trichomes differing in the distribution, length, and stage of development were built of a multicellular and multiseriate stalk and a multicellular head. The secretory cells in the stalk and head had large nuclei with nucleoli, numerous chloroplasts with thylakoids and starch grains, mitochondria, endoplasmic reticulum profiles, Golgi apparatus, vesicles, and multivesicular bodies. Many vacuoles contained phenolic compounds dissolved or forming various condensed deposits. The secretion components were transported through symplast elements, and the granulocrine and eccrine modes of nectar secretion were observed. The secretion was accumulated in the subcuticular space at the trichome apex and released through a pore in the cuticle. Histochemical and fluorescence assays showed that the trichomes and secretion contained lipophilic and polyphenol compounds, polysaccharides, proteins, and alkaloids. We suggest that these metabolites may serve an important function in protection of plants against biotic stress conditions and may also be a source of phytopharmaceuticals in the future.}, } @article {pmid33177521, year = {2020}, author = {Du, K and Luo, Q and Yin, L and Wu, J and Liu, Y and Gan, J and Dong, A and Shen, WH}, title = {OsChz1 acts as a histone chaperone in modulating chromatin organization and genome function in rice.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5717}, pmid = {33177521}, issn = {2041-1723}, mesh = {CRISPR-Cas Systems ; Chromatin/genetics/*metabolism ; DNA Methylation ; Flowers/metabolism ; Gene Expression Regulation, Plant ; Genome, Plant ; Histones/genetics/*metabolism ; Molecular Chaperones/genetics/metabolism ; Mutation ; Nucleosomes/genetics ; Oryza/*genetics/growth & development/metabolism ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified ; Protein Multimerization ; }, abstract = {While the yeast Chz1 acts as a specific histone-chaperone for H2A.Z, functions of CHZ-domain proteins in multicellular eukaryotes remain obscure. Here, we report on the functional characterization of OsChz1, a sole CHZ-domain protein identified in rice. OsChz1 interacts with both the canonical H2A-H2B dimer and the variant H2A.Z-H2B dimer. Within crystal structure the C-terminal region of OsChz1 binds H2A-H2B via an acidic region, pointing to a previously unknown recognition mechanism. Knockout of OsChz1 leads to multiple plant developmental defects. At genome-wide level, loss of OsChz1 causes mis-regulations of thousands of genes and broad alterations of nucleosome occupancy as well as reductions of H2A.Z-enrichment. While OsChz1 associates with chromatin regions enriched of repressive histone marks (H3K27me3 and H3K4me2), its loss does not affect the genome landscape of DNA methylation. Taken together, it is emerging that OsChz1 functions as an important H2A/H2A.Z-H2B chaperone in dynamic regulation of chromatin for higher eukaryote development.}, } @article {pmid33169570, year = {2020}, author = {Ma, X and Li, K and Wang, Z and Wei, D and Tang, Q}, title = {[Research progress in regulation model in different types of plant trichome].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {36}, number = {10}, pages = {2051-2065}, doi = {10.13345/j.cjb.200114}, pmid = {33169570}, issn = {1872-2075}, mesh = {Arabidopsis/genetics ; *Gene Expression Regulation, Plant ; Gossypium/genetics ; Solanum lycopersicum ; Plant Growth Regulators/genetics/metabolism ; *Trichomes/genetics ; }, abstract = {Plant trichomes are special structures that originate from epidermal outgrowths. Trichomes play an important role in plant defense against pests and diseases, and possess economic and medicinal values. Study on molecular mechanism of plant trichomes will contribute to the molecular design breeding and genetic improvement of crops. In recent years, the regulation mechanism of trichome development has been basically clarified in the model plant Arabidopsis thaliana, while great progresses are also found in other plant species. In this review, we focus on the developmental regulation of trichome formation from gene and phytohormones levels in Arabidopsis and cotton (with unicellular trichomes), as well as in tomato and Artemisia annua (with multicellular trichomes). The research progress associated with trichomes is also introduced in other typical monocotyledons and dicotyledons. Finally, the research and application of plant trichomes are prospected.}, } @article {pmid33165962, year = {2021}, author = {Blackstone, NW and Gutterman, JU}, title = {Can natural selection and druggable targets synergize? Of nutrient scarcity, cancer, and the evolution of cooperation.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {2}, pages = {e2000160}, doi = {10.1002/bies.202000160}, pmid = {33165962}, issn = {1521-1878}, mesh = {Animals ; *Biological Evolution ; Humans ; *Neoplasms/drug therapy ; Nutrients ; Selection, Genetic ; Symbiosis ; }, abstract = {Since the dawn of molecular biology, cancer therapy has focused on druggable targets. Despite some remarkable successes, cell-level evolution remains a potent antagonist to this approach. We suggest that a deeper understanding of the breakdown of cooperation can synergize the evolutionary and druggable-targets approaches. Complexity requires cooperation, whether between cells of different species (symbiosis) or between cells of the same organism (multicellularity). Both forms of cooperation may be associated with nutrient scarcity, which in turn may be associated with a chemiosmotic metabolism. A variety of examples from modern organisms supports these generalities. Indeed, mammalian cancers-unicellular, glycolytic, and fast-replicating-parallel these examples. Nutrient scarcity, chemiosmosis, and associated signaling may favor cooperation, while under conditions of nutrient abundance a fermentative metabolism may signal the breakdown of cooperation. Manipulating this metabolic milieu may potentiate the effects of targeted therapeutics. Specific opportunities are discussed in this regard, including avicins, a novel plant product.}, } @article {pmid33159138, year = {2020}, author = {Willman, S and Peel, JS and Ineson, JR and Schovsbo, NH and Rugen, EJ and Frei, R}, title = {Ediacaran Doushantuo-type biota discovered in Laurentia.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {647}, pmid = {33159138}, issn = {2399-3642}, mesh = {Animals ; *Biological Evolution ; *Biota ; *Fossils ; Geologic Sediments ; Greenland ; }, abstract = {The Ediacaran period (635-541 Ma) was a time of major environmental change, accompanied by a transition from a microbial world to the animal world we know today. Multicellular, macroscopic organisms preserved as casts and molds in Ediacaran siliciclastic rocks are preserved worldwide and provide snapshots of early organismal, including animal, evolution. Remarkable evolutionary advances are also witnessed by diverse cellular and subcellular phosphatized microfossils described from the Doushantuo Formation in China, the only source showing a diversified assemblage of microfossils. Here, we greatly extend the known distribution of this Doushantuo-type biota in reporting an Ediacaran Lagerstätte from Laurentia (Portfjeld Formation, North Greenland), with phosphatized animal-like eggs, embryos, acritarchs, and cyanobacteria, the age of which is constrained by the Shuram-Wonoka anomaly (c. 570-560 Ma). The discovery of these Ediacaran phosphatized microfossils from outside East Asia extends the distribution of the remarkable biota to a second palaeocontinent in the other hemisphere of the Ediacaran world, considerably expanding our understanding of the temporal and environmental distribution of organisms immediately prior to the Cambrian explosion.}, } @article {pmid33148926, year = {2020}, author = {Katoh, T and Satoh, M}, title = {[Environment and immunity-Allergies and autoimmune diseases from epidemiological perspective].}, journal = {Nihon eiseigaku zasshi. Japanese journal of hygiene}, volume = {75}, number = {0}, pages = {}, doi = {10.1265/jjh.20005}, pmid = {33148926}, issn = {1882-6482}, mesh = {Adolescent ; Adult ; Aged ; Autoantibodies ; Autoimmune Diseases/epidemiology/*immunology ; *Autoimmunity ; Biological Evolution ; Celiac Disease/immunology ; Child ; Child, Preschool ; Environment ; Female ; Humans ; Hypersensitivity/epidemiology/*immunology ; Infant ; Male ; Middle Aged ; Young Adult ; }, abstract = {Immunity, which denotes the protection of multicellular organisms against various bacterial and viral infections, is an essential protective mechanism for living organisms. Allergy is a reaction to a foreign substance existing in the environment that is basically not a component of the self. Additionally, autoimmune diseases are associated with the dysfunction in the recognition of self and non-self, and are pathological conditions caused by immune cells attacking their own tissues and cells. In this paper, we outline the current status of immunity with respect to the environment from the epidemiological perspective with regard to the following: (1) evolution and immunity, (2) allergy, (3) autoantibodies, (4) autoimmune diseases, (5) relationships of immunity with the environment, allergy, autoantibodies, and autoimmune diseases, and (6) celiac disease.}, } @article {pmid33143227, year = {2020}, author = {Petrushin, I and Belikov, S and Chernogor, L}, title = {Cooperative Interaction of Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02 in the Diseased Sponge Lubomirskia baicalensis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {21}, pages = {}, pmid = {33143227}, issn = {1422-0067}, support = {19-14-00088//Russian Science Foundation/ ; 0345-2019-0002 (AAAA-A16-116122110066-1)//Siberian Branch, Russian Academy of Sciences/ ; }, mesh = {Animals ; Cooperative Behavior ; *Ecosystem ; Flavobacterium/*physiology ; Lakes ; Oxalobacteraceae/*physiology ; Phylogeny ; Porifera/*metabolism/*microbiology ; *Symbiosis ; }, abstract = {Endemic freshwater sponges (demosponges, Lubomirskiidae) dominate in Lake Baikal, Central Siberia, Russia. These sponges are multicellular filter-feeding animals that represent a complex consortium of many species of eukaryotes and prokaryotes. In recent years, mass disease and death of Lubomirskia baicalensis has been a significant problem in Lake Baikal. The etiology and ecology of these events remain unknown. Bacteria from the families Flavobacteriaceae and Oxalobacteraceae dominate the microbiomes of diseased sponges. Both species are opportunistic pathogens common in freshwater ecosystems. The aim of our study was to analyze the genomes of strains Janthinobacterium sp. SLB01 and Flavobacterium sp. SLB02, isolated from diseased sponges to identify the reasons for their joint dominance. Janthinobacterium sp. SLB01 attacks other cells using a type VI secretion system and suppresses gram-positive bacteria with violacein, and regulates its own activity via quorum sensing. It produces floc and strong biofilm by exopolysaccharide biosynthesis and PEP-CTERM/XrtA protein expression. Flavobacterium sp. SLB02 utilizes the fragments of cell walls produced by polysaccharides. These two strains have a marked difference in carbohydrate acquisition. We described a possible means of joint occupation of the ecological niche in the freshwater sponge microbial community. This study expands the understanding of the symbiotic relationship of microorganisms with freshwater Baikal sponges.}, } @article {pmid33138108, year = {2020}, author = {Ingargiola, C and Turqueto Duarte, G and Robaglia, C and Leprince, AS and Meyer, C}, title = {The Plant Target of Rapamycin: A Conduc TOR of Nutrition and Metabolism in Photosynthetic Organisms.}, journal = {Genes}, volume = {11}, number = {11}, pages = {}, pmid = {33138108}, issn = {2073-4425}, mesh = {Chlorophyta/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Metabolic Networks and Pathways ; Models, Biological ; Nitrogen/metabolism ; Phosphates/metabolism ; Photosynthesis ; Plant Development ; Plant Proteins/*metabolism ; Plants/*metabolism ; Potassium/metabolism ; Signal Transduction ; Stress, Physiological ; Sugars/metabolism ; Sulfur/metabolism ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Living organisms possess many mechanisms to sense nutrients and favorable conditions, which allow them to grow and develop. Photosynthetic organisms are very diverse, from green unicellular algae to multicellular flowering plants, but most of them are sessile and thus unable to escape from the biotic and abiotic stresses they experience. The Target of Rapamycin (TOR) signaling pathway is conserved in all eukaryotes and acts as a central regulatory hub between growth and extrinsic factors, such as nutrients or stress. However, relatively little is known about the regulations and roles of this pathway in plants and algae. Although some features of the TOR pathway seem to have been highly conserved throughout evolution, others clearly differ in plants, perhaps reflecting adaptations to different lifestyles and the rewiring of this primordial signaling module to adapt to specific requirements. Indeed, TOR is involved in plant responses to a vast array of signals including nutrients, hormones, light, stresses or pathogens. In this review, we will summarize recent studies that address the regulations of TOR by nutrients in photosynthetic organisms, and the roles of TOR in controlling important metabolic pathways, highlighting similarities and differences with the other eukaryotes.}, } @article {pmid33126770, year = {2020}, author = {Combarnous, Y and Nguyen, TMD}, title = {Cell Communications among Microorganisms, Plants, and Animals: Origin, Evolution, and Interplays.}, journal = {International journal of molecular sciences}, volume = {21}, number = {21}, pages = {}, pmid = {33126770}, issn = {1422-0067}, mesh = {Animals ; Bacteria/*metabolism ; *Biological Evolution ; *Cell Communication ; Fungi/*metabolism ; Phylogeny ; Plants/*metabolism ; Viruses/*metabolism ; }, abstract = {Cellular communications play pivotal roles in multi-cellular species, but they do so also in uni-cellular species. Moreover, cells communicate with each other not only within the same individual, but also with cells in other individuals belonging to the same or other species. These communications occur between two unicellular species, two multicellular species, or between unicellular and multicellular species. The molecular mechanisms involved exhibit diversity and specificity, but they share common basic features, which allow common pathways of communication between different species, often phylogenetically very distant. These interactions are possible by the high degree of conservation of the basic molecular mechanisms of interaction of many ligand-receptor pairs in evolutionary remote species. These inter-species cellular communications played crucial roles during Evolution and must have been positively selected, particularly when collectively beneficial in hostile environments. It is likely that communications between cells did not arise after their emergence, but were part of the very nature of the first cells. Synchronization of populations of non-living protocells through chemical communications may have been a mandatory step towards their emergence as populations of living cells and explain the large commonality of cell communication mechanisms among microorganisms, plants, and animals.}, } @article {pmid33126482, year = {2020}, author = {Kulkarni, P}, title = {Intrinsically Disordered Proteins: Insights from Poincaré, Waddington, and Lamarck.}, journal = {Biomolecules}, volume = {10}, number = {11}, pages = {}, pmid = {33126482}, issn = {2218-273X}, mesh = {*Biological Evolution ; Humans ; Intrinsically Disordered Proteins/chemistry/*genetics ; Phenotype ; *Protein Conformation ; }, abstract = {The past quarter-century may justly be referred to as a period analogous to the "Cambrian explosion" in the history of proteins. This period is marked by the appearance of the intrinsically disordered proteins (IDPs) on the scene since their discovery in the mid-1990s. Here, I first reflect on how we accidentally stumbled on these fascinating molecules. Next, I describe our research on the IDPs over the past decade and identify six areas as important for future research in this field. In addition, I draw on discoveries others in the field have made to present a more comprehensive essay. More specifically, I discuss the role of IDPs in two fundamental aspects of life: in phenotypic switching, and in multicellularity that marks one of the major evolutionary transitions. I highlight how serendipity, imagination, and an interdisciplinary approach embodying empirical evidence and theoretical insights from the works of Poincaré, Waddington, and Lamarck, shaped our thinking, and how this led us to propose the MRK hypothesis, a conceptual framework addressing phenotypic switching, the emergence of new traits, and adaptive evolution via nongenetic and IDP conformation-based mechanisms. Finally, I present a perspective on the evolutionary link between phenotypic switching and the origin of multicellularity.}, } @article {pmid33097400, year = {2021}, author = {Véron, E and Vernoux, T and Coudert, Y}, title = {Phyllotaxis from a Single Apical Cell.}, journal = {Trends in plant science}, volume = {26}, number = {2}, pages = {124-131}, doi = {10.1016/j.tplants.2020.09.014}, pmid = {33097400}, issn = {1878-4372}, mesh = {*Bryopsida ; *Meristem/genetics ; Plant Leaves ; Plant Shoots ; }, abstract = {Phyllotaxis, the geometry of leaf arrangement around stems, determines plant architecture. Molecular interactions coordinating the formation of phyllotactic patterns have mainly been studied in multicellular shoot apical meristems of flowering plants. Phyllotaxis evolved independently in the major land plant lineages. In mosses, it arises from a single apical cell, raising the question of how asymmetric divisions of a single-celled meristem create phyllotactic patterns and whether associated genetic processes are shared across lineages. We present an overview of the mechanisms governing shoot apical cell specification and activity in the model moss, Physcomitrium patens, and argue that similar molecular regulatory modules have been deployed repeatedly across evolution to operate at different scales and drive apical function in convergent shoot forms.}, } @article {pmid33093150, year = {2020}, author = {Soubigou, A and Ross, EG and Touhami, Y and Chrismas, N and Modepalli, V}, title = {Regeneration in the sponge Sycon ciliatum partly mimics postlarval development.}, journal = {Development (Cambridge, England)}, volume = {147}, number = {22}, pages = {}, doi = {10.1242/dev.193714}, pmid = {33093150}, issn = {1477-9129}, mesh = {Animals ; Embryonic Development/*physiology ; Larva ; Porifera/*embryology ; Regeneration/*physiology ; Transcriptome/*physiology ; }, abstract = {Somatic cells dissociated from an adult sponge can reorganize and develop into a juvenile-like sponge, a remarkable phenomenon of regeneration. However, the extent to which regeneration recapitulates embryonic developmental pathways has remained enigmatic. We have standardized and established a sponge Sycon ciliatum regeneration protocol from dissociated cells. Morphological analysis demonstrated that dissociated sponge cells follow a series of morphological events resembling postembryonic development. We performed high-throughput sequencing on regenerating samples and compared the data with that from regular postlarval development. Our comparative transcriptomic analysis revealed that sponge regeneration is as equally dynamic as embryogenesis. We found that sponge regeneration is orchestrated by recruiting pathways similar to those utilized in embryonic development. We also demonstrated that sponge regeneration is accompanied by cell death at early stages, revealing the importance of apoptosis in remodelling the primmorphs to initiate re-development. Because sponges are likely to be the first branch of extant multicellular animals, we suggest that this system can be explored to study the genetic features underlying the evolution of multicellularity and regeneration.}, } @article {pmid33093080, year = {2020}, author = {Hammarlund, EU and Flashman, E and Mohlin, S and Licausi, F}, title = {Oxygen-sensing mechanisms across eukaryotic kingdoms and their roles in complex multicellularity.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6515}, pages = {}, doi = {10.1126/science.aba3512}, pmid = {33093080}, issn = {1095-9203}, mesh = {Anaerobiosis ; Animals ; Biological Evolution ; Dioxygenases/genetics/*metabolism ; Eukaryota/*classification/*metabolism ; Fungi ; Oxygen/*metabolism ; Plants ; }, abstract = {Oxygen-sensing mechanisms of eukaryotic multicellular organisms coordinate hypoxic cellular responses in a spatiotemporal manner. Although this capacity partly allows animals and plants to acutely adapt to oxygen deprivation, its functional and historical roots in hypoxia emphasize a broader evolutionary role. For multicellular life-forms that persist in settings with variable oxygen concentrations, the capacity to perceive and modulate responses in and between cells is pivotal. Animals and higher plants represent the most complex life-forms that ever diversified on Earth, and their oxygen-sensing mechanisms demonstrate convergent evolution from a functional perspective. Exploring oxygen-sensing mechanisms across eukaryotic kingdoms can inform us on biological innovations to harness ever-changing oxygen availability at the dawn of complex life and its utilization for their organismal development.}, } @article {pmid33081011, year = {2020}, author = {Steinberg, E and Orehov, N and Tischenko, K and Schwob, O and Zamir, G and Hubert, A and Manevitch, Z and Benny, O}, title = {Rapid Clearing for High Resolution 3D Imaging of Ex Vivo Pancreatic Cancer Spheroids.}, journal = {International journal of molecular sciences}, volume = {21}, number = {20}, pages = {}, pmid = {33081011}, issn = {1422-0067}, support = {0305260//Israel Science Foundation/ ; 0394906//Ministry of Science and Technology, Israel/ ; 0305260//H2020 European Research Council/ ; 3011004240//Israel Science Foundation/ ; }, mesh = {Cell Line, Tumor ; Extracellular Matrix/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; *Imaging, Three-Dimensional ; Pancreatic Neoplasms/*diagnostic imaging/*pathology ; Spheroids, Cellular/*pathology ; Tumor Microenvironment ; }, abstract = {The currently accepted imaging methods have been a central hurdle to imaging the finer details of tumor behavior in three-dimensional (3D) ex vivo multicellular culture models. In our search for an improved way of imaging tumor behavior in its physiological-like niche, we developed a simple, efficient, and straightforward procedure using standard reagents and imaging equipment that significantly enhanced 3D imaging up to a ~200-micron depth. We tested its efficacy on pancreatic spheroids, prototypes of high-density tissues that are difficult to image. We found we could both save time with this method and extract information about pancreatic tumor spheroids that previously was difficult to obtain. We were able to discern clear differences in the organization of pancreatic tumor spheroids generated from different origins, suggesting cell-specific, inherent, bottom-up organization with a correlation to the level of malignancy. We also examined the dynamic changes in the spheroids at predetermined time points, providing important information related to tissue morphogenesis and its metabolic state. Lastly, this process enabled us to assess a drug vehicle's potential to penetrate dense tumor tissue by improving our view of the inert particles' diffusion in the 3D spheroid. This clearing method, a simple procedure, can open the door to more accurate imaging and reveal more about cancer behavior.}, } @article {pmid33072737, year = {2020}, author = {Teulière, J and Bernard, G and Bapteste, E}, title = {The Distribution of Genes Associated With Regulated Cell Death Is Decoupled From the Mitochondrial Phenotypes Within Unicellular Eukaryotic Hosts.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {536389}, pmid = {33072737}, issn = {2296-634X}, abstract = {Genetically regulated cell death (RCD) occurs in all domains of life. In eukaryotes, the evolutionary origin of the mitochondrion and of certain forms of RCD, in particular apoptosis, are thought to coincide, suggesting a central general role for mitochondria in cellular suicide. We tested this mitochondrial centrality hypothesis across a dataset of 67 species of protists, presenting 5 classes of mitochondrial phenotypes, including functional mitochondria, metabolically diversified mitochondria, functionally reduced mitochondria (Mitochondrion Related Organelle or MRO) and even complete absence of mitochondria. We investigated the distribution of genes associated with various forms of RCD. No homologs for described mammalian regulators of regulated necrosis could be identified in our set of 67 unicellular taxa. Protists with MRO and the secondarily a mitochondriate Monocercomonoides exilis display heterogeneous reductions of apoptosis gene sets with respect to typical mitochondriate protists. Remarkably, despite the total lack of mitochondria in M. exilis, apoptosis-associated genes could still be identified. These same species of protists with MRO and M. exilis harbored non-reduced autophagic cell death gene sets. Moreover, transiently multicellular protist taxa appeared enriched in apoptotic and autophagy associated genes compared to free-living protists. This analysis suggests that genes associated with apoptosis in animals and the presence of the mitochondria are significant yet non-essential biological components for RCD in protists. More generally, our results support the hypothesis of a selection for RCD, including both apoptosis and autophagy, as a developmental mechanism linked to multicellularity.}, } @article {pmid33068526, year = {2020}, author = {Palazzo, AF and Koonin, EV}, title = {Functional Long Non-coding RNAs Evolve from Junk Transcripts.}, journal = {Cell}, volume = {183}, number = {5}, pages = {1151-1161}, doi = {10.1016/j.cell.2020.09.047}, pmid = {33068526}, issn = {1097-4172}, support = {//CIHR/Canada ; }, mesh = {Animals ; DNA, Intergenic/genetics ; Enhancer Elements, Genetic/genetics ; Evolution, Molecular ; Humans ; RNA, Long Noncoding/*genetics/metabolism ; RNA, Messenger/*genetics/metabolism ; Transcription, Genetic ; }, abstract = {Transcriptome studies reveal pervasive transcription of complex genomes, such as those of mammals. Despite popular arguments for functionality of most, if not all, of these transcripts, genome-wide analysis of selective constraints indicates that most of the produced RNA are junk. However, junk is not garbage. On the contrary, junk transcripts provide the raw material for the evolution of diverse long non-coding (lnc) RNAs by non-adaptive mechanisms, such as constructive neutral evolution. The generation of many novel functional entities, such as lncRNAs, that fuels organismal complexity does not seem to be driven by strong positive selection. Rather, the weak selection regime that dominates the evolution of most multicellular eukaryotes provides ample material for functional innovation with relatively little adaptation involved.}, } @article {pmid33064719, year = {2020}, author = {Liu, XB and Xia, EH and Li, M and Cui, YY and Wang, PM and Zhang, JX and Xie, BG and Xu, JP and Yan, JJ and Li, J and Nagy, LG and Yang, ZL}, title = {Transcriptome data reveal conserved patterns of fruiting body development and response to heat stress in the mushroom-forming fungus Flammulina filiformis.}, journal = {PloS one}, volume = {15}, number = {10}, pages = {e0239890}, pmid = {33064719}, issn = {1932-6203}, mesh = {Agaricales/*genetics/growth & development/metabolism ; Conserved Sequence ; *Evolution, Molecular ; Fruiting Bodies, Fungal/genetics/*growth & development/metabolism ; Fungal Proteins/genetics/metabolism ; Heat-Shock Proteins/genetics/metabolism ; *Heat-Shock Response ; *Transcriptome ; }, abstract = {Mushroom-forming fungi are complex multicellular organisms that form the basis of a large industry, yet, our understanding of the mechanisms of mushroom development and its responses to various stresses remains limited. The winter mushroom (Flammulina filiformis) is cultivated at a large commercial scale in East Asia and is a species with a preference for low temperatures. This study investigated fruiting body development in F. filiformis by comparing transcriptomes of 4 developmental stages, and compared the developmental genes to a 200-genome dataset to identify conserved genes involved in fruiting body development, and examined the response of heat sensitive and -resistant strains to heat stress. Our data revealed widely conserved genes involved in primordium development of F. filiformis, many of which originated before the emergence of the Agaricomycetes, indicating co-option for complex multicellularity during evolution. We also revealed several notable fruiting-specific genes, including the genes with conserved stipe-specific expression patterns and the others which related to sexual development, water absorption, basidium formation and sporulation, among others. Comparative analysis revealed that heat stress induced more genes in the heat resistant strain (M1) than in the heat sensitive one (XR). Of particular importance are the hsp70, hsp90 and fes1 genes, which may facilitate the adjustment to heat stress in the early stages of fruiting body development. These data highlighted novel genes involved in complex multicellular development in fungi and aid further studies on gene function and efforts to improve the productivity and heat tolerance in mushroom-forming fungi.}, } @article {pmid33062243, year = {2020}, author = {Arias Del Angel, JA and Nanjundiah, V and Benítez, M and Newman, SA}, title = {Interplay of mesoscale physics and agent-like behaviors in the parallel evolution of aggregative multicellularity.}, journal = {EvoDevo}, volume = {11}, number = {}, pages = {21}, pmid = {33062243}, issn = {2041-9139}, abstract = {Myxobacteria and dictyostelids are prokaryotic and eukaryotic multicellular lineages, respectively, that after nutrient depletion aggregate and develop into structures called fruiting bodies. The developmental processes and resulting morphological outcomes resemble one another to a remarkable extent despite their independent origins, the evolutionary distance between them and the lack of traceable homology in molecular mechanisms. We hypothesize that the morphological parallelism between the two lineages arises as the consequence of the interplay within multicellular aggregates between generic processes, physical and physicochemical processes operating similarly in living and non-living matter at the mesoscale (~10[-3]-10[-1] m) and agent-like behaviors, unique to living systems and characteristic of the constituent cells, considered as autonomous entities acting according to internal rules in a shared environment. Here, we analyze the contributions of generic and agent-like determinants in myxobacteria and dictyostelid development and their roles in the generation of their common traits. Consequent to aggregation, collective cell-cell contacts mediate the emergence of liquid-like properties, making nascent multicellular masses subject to novel patterning and morphogenetic processes. In both lineages, this leads to behaviors such as streaming, rippling, and rounding-up, as seen in non-living fluids. Later the aggregates solidify, leading them to exhibit additional generic properties and motifs. Computational models suggest that the morphological phenotypes of the multicellular masses deviate from the predictions of generic physics due to the contribution of agent-like behaviors of cells such as directed migration, quiescence, and oscillatory signal transduction mediated by responses to external cues. These employ signaling mechanisms that reflect the evolutionary histories of the respective organisms. We propose that the similar developmental trajectories of myxobacteria and dictyostelids are more due to shared generic physical processes in coordination with analogous agent-type behaviors than to convergent evolution under parallel selection regimes. Insights from the biology of these aggregative forms may enable a unified understanding of developmental evolution, including that of animals and plants.}, } @article {pmid33060357, year = {2020}, author = {Toda, S and McKeithan, WL and Hakkinen, TJ and Lopez, P and Klein, OD and Lim, WA}, title = {Engineering synthetic morphogen systems that can program multicellular patterning.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6514}, pages = {327-331}, pmid = {33060357}, issn = {1095-9203}, support = {F32 DK123939/DK/NIDDK NIH HHS/United States ; R01 DE028496/DE/NIDCR NIH HHS/United States ; R35 DE026602/DE/NIDCR NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Body Patterning ; Drosophila melanogaster/growth & development ; Fibroblasts ; Green Fluorescent Proteins/genetics/*metabolism ; Protein Engineering ; Receptors, Notch/genetics/metabolism ; Tissue Engineering/*methods ; }, abstract = {In metazoan tissues, cells decide their fates by sensing positional information provided by specialized morphogen proteins. To explore what features are sufficient for positional encoding, we asked whether arbitrary molecules (e.g., green fluorescent protein or mCherry) could be converted into synthetic morphogens. Synthetic morphogens expressed from a localized source formed a gradient when trapped by surface-anchoring proteins, and they could be sensed by synthetic receptors. Despite their simplicity, these morphogen systems yielded patterns reminiscent of those observed in vivo. Gradients could be reshaped by altering anchor density or by providing a source of competing inhibitor. Gradient interpretation could be altered by adding feedback loops or morphogen cascades to receiver cell response circuits. Orthogonal cell-cell communication systems provide insight into morphogen evolution and a platform for engineering tissues.}, } @article {pmid33058872, year = {2020}, author = {Dyrka, W and Coustou, V and Daskalov, A and Lends, A and Bardin, T and Berbon, M and Kauffmann, B and Blancard, C and Salin, B and Loquet, A and Saupe, SJ}, title = {Identification of NLR-associated Amyloid Signaling Motifs in Bacterial Genomes.}, journal = {Journal of molecular biology}, volume = {432}, number = {23}, pages = {6005-6027}, doi = {10.1016/j.jmb.2020.10.004}, pmid = {33058872}, issn = {1089-8638}, mesh = {Amino Acid Motifs/genetics ; Amino Acid Sequence/genetics ; Amyloid/*genetics ; Amyloidogenic Proteins/genetics ; Animals ; Cyanobacteria/genetics ; Drosophila/genetics ; *Evolution, Molecular ; Fungi/genetics ; Genome, Bacterial/genetics ; Immunity, Innate/*genetics ; NLR Proteins/*genetics ; Prions/genetics ; Signal Transduction/genetics ; }, abstract = {In filamentous fungi, amyloid signaling sequences allow Nod-like receptors (NLRs) to activate downstream cell-death inducing proteins with HeLo and HeLo-like (HELL) domains and amyloid RHIM and RHIM-related motifs control immune defense pathways in mammals and flies. Herein, we show bioinformatically that analogous amyloid signaling motifs exist in bacteria. These short motifs are found at the N terminus of NLRs and at the C terminus of proteins with a domain we term BELL. The corresponding NLR and BELL proteins are encoded by adjacent genes. We identify 10 families of such bacterial amyloid signaling sequences (BASS), one of which (BASS3) is homologous to RHIM and a fungal amyloid motif termed PP. BASS motifs occur nearly exclusively in bacteria forming multicellular structures (mainly in Actinobacteria and Cyanobacteria). We analyze experimentally a subset of seven of these motifs (from the most common BASS1 family and the RHIM-related BASS3 family) and find that these sequences form fibrils in vitro. Using a fungal in vivo model, we show that all tested BASS-motifs form prions and that the NLR-side motifs seed prion-formation of the corresponding BELL-side motif. We find that BASS3 motifs show partial prion cross-seeding with mammalian RHIM and fungal PP-motifs and that proline mutations on key positions of the BASS3 core motif, conserved in RHIM and PP-motifs, abolish prion formation. This work expands the paradigm of prion amyloid signaling to multicellular prokaryotes and suggests a long-term evolutionary conservation of these motifs from bacteria, to fungi and animals.}, } @article {pmid33050851, year = {2020}, author = {Kurakin, GF and Samoukina, AM and Potapova, NA}, title = {Bacterial and Protozoan Lipoxygenases Could be Involved in Cell-to-Cell Signaling and Immune Response Suppression.}, journal = {Biochemistry. Biokhimiia}, volume = {85}, number = {9}, pages = {1048-1071}, doi = {10.1134/S0006297920090059}, pmid = {33050851}, issn = {1608-3040}, mesh = {Animals ; Bacteria/*enzymology ; *Biological Evolution ; *Cell Communication ; Humans ; Immunity/*immunology ; Lipoxygenases/*metabolism ; Protozoan Proteins/*metabolism ; }, abstract = {Lipoxygenases are found in animals, plants, and fungi, where they are involved in a wide range of cell-to-cell signaling processes. The presence of lipoxygenases in a number of bacteria and protozoa has been also established, but their biological significance remains poorly understood. Several hypothetical functions of lipoxygenases in bacteria and protozoa have been suggested without experimental validation. The objective of our study was evaluating the functions of bacterial and protozoan lipoxygenases by evolutionary and taxonomic analysis using bioinformatics tools. Lipoxygenase sequences were identified and examined using BLAST, followed by analysis of constructed phylogenetic trees and networks. Our results support the theory on the involvement of lipoxygenases in the formation of multicellular structures by microorganisms and their possible evolutionary significance in the emergence of multicellularity. Furthermore, we observed association of lipoxygenases with the suppression of host immune response by parasitic and symbiotic bacteria including dangerous opportunistic pathogens.}, } @article {pmid33035180, year = {2020}, author = {Essen, LO and Vogt, MS and Mösch, HU}, title = {Diversity of GPI-anchored fungal adhesins.}, journal = {Biological chemistry}, volume = {401}, number = {12}, pages = {1389-1405}, doi = {10.1515/hsz-2020-0199}, pmid = {33035180}, issn = {1437-4315}, mesh = {Cell Adhesion ; Glycosylphosphatidylinositols/*metabolism ; Saccharomyces cerevisiae/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {Selective adhesion of fungal cells to one another and to foreign surfaces is fundamental for the development of multicellular growth forms and the successful colonization of substrates and host organisms. Accordingly, fungi possess diverse cell wall-associated adhesins, mostly large glycoproteins, which present N-terminal adhesion domains at the cell surface for ligand recognition and binding. In order to function as robust adhesins, these glycoproteins must be covalently linkedto the cell wall via C-terminal glycosylphosphatidylinositol (GPI) anchors by transglycosylation. In this review, we summarize the current knowledge on the structural and functional diversity of so far characterized protein families of adhesion domains and set it into a broad context by an in-depth bioinformatics analysis using sequence similarity networks. In addition, we discuss possible mechanisms for the membrane-to-cell wall transfer of fungal adhesins by membrane-anchored Dfg5 transglycosidases.}, } @article {pmid33031891, year = {2021}, author = {Gao, JG}, title = {Tracking the evolutionary innovations of plant terrestrialization.}, journal = {Gene}, volume = {769}, number = {}, pages = {145203}, doi = {10.1016/j.gene.2020.145203}, pmid = {33031891}, issn = {1879-0038}, mesh = {*Biological Evolution ; Bryophyta/genetics/physiology ; Gene Transfer, Horizontal ; Genome, Plant ; *Plant Physiological Phenomena ; Plants/genetics ; }, abstract = {The gradual transition of the algal ancestor from the freshwater to land has always attracted evolutionary biologists. The recent report of high-quality reference genomes of five Charophyta algae (Spirogloea muscicola, Mesotaenium endlicherianum, Mesostigma viride, Chlorokybus atmophyticus and Penium margaritaceum) and one hornwort (Anthoceros angustus) species sheds light on this fascinating transition. These early diverging plants and algae could have gained new genes from soil bacteria and fungi through horizontal gene transfer (HGT), which was so common during plant terrestrialization and may outrun our expectations. Through reviewing and critical thinking about the advancements on these plant genomes, here, I propose three prospective research directions that need to address in the future: (i) due to the ubiquitous nature of viruses that is similar to soil bacteria and fungi, there is less attention to viruses that probably also play an important role in the genome evolution of plants via HGT; (ii) multicellularity has occurred many times independently, but we still know a little about the biological and ecological mechanisms leading to multi-cellularity in Streptophyta; (iii) and most importantly, the quantitative relationships between genetic innovations and environmental variables such as temperature, precipitation and solar radiation, need pioneering research collaborated by biological evolutionists, computer scientists, and ecologists, which are crucial for understanding the macroevolution of plants and could also be used to simulate the evolution of plants under future climate change.}, } @article {pmid33028229, year = {2020}, author = {Jiang, L and Lu, Y and Zheng, L and Li, G and Chen, L and Zhang, M and Ni, J and Liu, Q and Zhang, Y}, title = {The algal selenoproteomes.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {699}, pmid = {33028229}, issn = {1471-2164}, support = {31401129//National Natural Science Foundation of China/ ; }, mesh = {Codon, Terminator ; *Eukaryota/genetics/metabolism ; Evolution, Molecular ; Proteome ; *Selenium ; Selenocysteine ; *Selenoproteins/genetics/metabolism ; }, abstract = {BACKGROUND: Selenium is an essential trace element, and selenocysteine (Sec, U) is its predominant form in vivo. Proteins that contain Sec are selenoproteins, whose special structural features include not only the TGA codon encoding Sec but also the SECIS element in mRNA and the conservation of the Sec-flanking region. These unique features have led to the development of a series of bioinformatics methods to predict and research selenoprotein genes. There have been some studies and reports on the evolution and distribution of selenoprotein genes in prokaryotes and multicellular eukaryotes, but the systematic analysis of single-cell eukaryotes, especially algae, has been very limited.

RESULTS: In this study, we predicted selenoprotein genes in 137 species of algae by using a program we previously developed. More than 1000 selenoprotein genes were obtained. A database website was built to record these algae selenoprotein genes (www.selenoprotein.com). These genes belong to 42 selenoprotein families, including three novel selenoprotein gene families.

CONCLUSIONS: This study reveals the primordial state of the eukaryotic selenoproteome. It is an important clue to explore the significance of selenium for primordial eukaryotes and to determine the complete evolutionary spectrum of selenoproteins in all life forms.}, } @article {pmid33024265, year = {2021}, author = {Ibrahim-Hashim, A and Luddy, K and Abrahams, D and Enriquez-Navas, P and Damgaci, S and Yao, J and Chen, T and Bui, MM and Gillies, RJ and O'Farrelly, C and Richards, CL and Brown, JS and Gatenby, RA}, title = {Artificial selection for host resistance to tumour growth and subsequent cancer cell adaptations: an evolutionary arms race.}, journal = {British journal of cancer}, volume = {124}, number = {2}, pages = {455-465}, pmid = {33024265}, issn = {1532-1827}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; U01 CA232382/CA/NCI NIH HHS/United States ; U54 CA143970/CA/NCI NIH HHS/United States ; R01 CA077575/CA/NCI NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*physiology ; Animals ; *Biological Evolution ; *Carcinoma, Lewis Lung ; Cell Plasticity/*physiology ; Disease Resistance/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, SCID ; }, abstract = {BACKGROUND: Cancer progression is governed by evolutionary dynamics in both the tumour population and its host. Since cancers die with the host, each new population of cancer cells must reinvent strategies to overcome the host's heritable defences. In contrast, host species evolve defence strategies over generations if tumour development limits procreation.

METHODS: We investigate this "evolutionary arms race" through intentional breeding of immunodeficient SCID and immunocompetent Black/6 mice to evolve increased tumour suppression. Over 10 generations, we injected Lewis lung mouse carcinoma cells [LL/2-Luc-M38] and selectively bred the two individuals with the slowest tumour growth at day 11. Their male progeny were hosts in the subsequent round.

RESULTS: The evolved SCID mice suppressed tumour growth through biomechanical restriction from increased mesenchymal proliferation, and the evolved Black/6 mice suppressed tumour growth by increasing immune-mediated killing of cancer cells. However, transcriptomic changes of multicellular tissue organisation and function genes allowed LL/2-Luc-M38 cells to adapt through increased matrix remodelling in SCID mice, and reduced angiogenesis, increased energy utilisation and accelerated proliferation in Black/6 mice.

CONCLUSION: Host species can rapidly evolve both immunologic and non-immunologic tumour defences. However, cancer cell plasticity allows effective phenotypic and population-based counter strategies.}, } @article {pmid33009502, year = {2020}, author = {Rochman, ND and Wolf, YI and Koonin, EV}, title = {Deep phylogeny of cancer drivers and compensatory mutations.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {551}, pmid = {33009502}, issn = {2399-3642}, mesh = {Animals ; Evolution, Molecular ; Genes, Neoplasm/*genetics ; Genes, Tumor Suppressor ; Humans ; Mutation/*genetics ; Neoplasms/*genetics ; Oncogenes/genetics ; Phylogeny ; Sequence Alignment ; }, abstract = {Driver mutations (DM) are the genetic impetus for most cancers. The DM are assumed to be deleterious in species evolution, being eliminated by purifying selection unless compensated by other mutations. We present deep phylogenies for 84 cancer driver genes and investigate the prevalence of 434 DM across gene-species trees. The DM are rare in species evolution, and 181 are completely absent, validating their negative fitness effect. The DM are more common in unicellular than in multicellular eukaryotes, suggesting a link between these mutations and cell proliferation control. 18 DM appear as the ancestral state in one or more major clades, including 3 among mammals. We identify within-gene, compensatory mutations for 98 DM and infer likely interactions between the DM and compensatory sites in protein structures. These findings elucidate the evolutionary status of DM and are expected to advance the understanding of the functions and evolution of oncogenes and tumor suppressors.}, } @article {pmid32991271, year = {2020}, author = {Michalakis, Y and Blanc, S}, title = {The Curious Strategy of Multipartite Viruses.}, journal = {Annual review of virology}, volume = {7}, number = {1}, pages = {203-218}, doi = {10.1146/annurev-virology-010220-063346}, pmid = {32991271}, issn = {2327-0578}, mesh = {DNA Viruses/genetics ; *Genome, Viral ; Humans ; Virion/genetics ; Virus Replication ; Viruses/*genetics ; }, abstract = {Multipartite virus genomes are composed of several segments, each packaged in a distinct viral particle. Although this puzzling genome architecture is found in ∼17% of known viral species, its distribution among hosts or among distinct types of genome-composing nucleic acid remains poorly understood. No convincing advantage of multipartitism has been identified, yet the maintenance of genomic integrity appears problematic. Here we review recent studies shedding light on these issues. Multipartite viruses rapidly modify the copy number of each segment/gene from one host species to another, a putative benefit if host switches are common. One multipartite virus functions in a multicellular way: The segments do not all need to be present in the same cell and can functionally complement across cells, maintaining genome integrity within hosts. The genomic integrity maintenance during host-to-host transmission needs further elucidation. These features challenge several virology foundations and could apply to other multicomponent viral systems.}, } @article {pmid32973760, year = {2020}, author = {Petre, B}, title = {Toward the Discovery of Host-Defense Peptides in Plants.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1825}, pmid = {32973760}, issn = {1664-3224}, mesh = {Antimicrobial Cationic Peptides/*metabolism ; Bacterial Infections/immunology/*metabolism/microbiology ; Botany ; Host-Pathogen Interactions ; *Plant Diseases/immunology/microbiology/virology ; Plant Immunity ; Plant Proteins/*metabolism ; Plants/immunology/*metabolism/microbiology/virology ; Research ; Signal Transduction ; Virus Diseases/immunology/*metabolism/virology ; }, abstract = {Defense peptides protect multicellular eukaryotes from infections. In biomedical sciences, a dominant conceptual framework refers to defense peptides as host-defense peptides (HDPs), which are bifunctional peptides with both direct antimicrobial and immunomodulatory activities. No HDP has been reported in plants so far, and the very concept of HDP has not been captured yet by the plant science community. Plant science thus lacks the conceptual framework that would coordinate research efforts aimed at discovering plant HDPs. In this perspective article, I used bibliometric and literature survey approaches to raise awareness about the HDP concept among plant scientists, and to encourage research efforts aimed at discovering plant HDPs. Such discovery would enrich our comprehension of the function and evolution of the plant immune system, and provide us with novel molecular tools to develop innovative strategies to control crop diseases.}, } @article {pmid32934242, year = {2020}, author = {Kinsella, CM and Bart, A and Deijs, M and Broekhuizen, P and Kaczorowska, J and Jebbink, MF and van Gool, T and Cotten, M and van der Hoek, L}, title = {Entamoeba and Giardia parasites implicated as hosts of CRESS viruses.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4620}, pmid = {32934242}, issn = {2041-1723}, mesh = {Adult ; Cohort Studies ; Entamoeba/*virology ; Feces/parasitology/virology ; Female ; Genome, Viral ; Giardia/*virology ; Host Specificity ; Humans ; Male ; Middle Aged ; Phylogeny ; Virus Physiological Phenomena ; Viruses/classification/genetics ; Young Adult ; }, abstract = {Metagenomic techniques have enabled genome sequencing of unknown viruses without isolation in cell culture, but information on the virus host is often lacking, preventing viral characterisation. High-throughput methods capable of identifying virus hosts based on genomic data alone would aid evaluation of their medical or biological relevance. Here, we address this by linking metagenomic discovery of three virus families in human stool samples with determination of probable hosts. Recombination between viruses provides evidence of a shared host, in which genetic exchange occurs. We utilise networks of viral recombination to delimit virus-host clusters, which are then anchored to specific hosts using (1) statistical association to a host organism in clinical samples, (2) endogenous viral elements in host genomes, and (3) evidence of host small RNA responses to these elements. This analysis suggests two CRESS virus families (Naryaviridae and Nenyaviridae) infect Entamoeba parasites, while a third (Vilyaviridae) infects Giardia duodenalis. The trio supplements five CRESS virus families already known to infect eukaryotes, extending the CRESS virus host range to protozoa. Phylogenetic analysis implies CRESS viruses infecting multicellular life have evolved independently on at least three occasions.}, } @article {pmid32931463, year = {2020}, author = {Cai, Y and Huang, J and Xu, H and Zhang, T and Cao, C and Pan, Y}, title = {Synthesis, characterization and application of magnetoferritin nanoparticle by using human H chain ferritin expressed by Pichia pastoris.}, journal = {Nanotechnology}, volume = {31}, number = {48}, pages = {485709}, doi = {10.1088/1361-6528/abb15d}, pmid = {32931463}, issn = {1361-6528}, mesh = {Animals ; Apoferritins/*analysis/genetics/toxicity/ultrastructure ; Fluorescent Dyes/*analysis/toxicity ; Gene Expression ; Humans ; Iron/*analysis/toxicity ; Nanoparticles/*analysis/ultrastructure ; Optical Imaging/*methods ; Oxides/*analysis/toxicity ; Rats, Sprague-Dawley ; Recombinant Proteins/analysis/genetics/toxicity/ultrastructure ; Saccharomycetales/genetics ; }, abstract = {Protein-based nanoparticles have developed rapidly in areas such as drug delivery, biomedical imaging and biocatalysis. Ferritin possesses unique properties that make it attractive as a potential platform for a variety of nanobiotechnological applications. Here we synthesized magnetoferritin (P-MHFn) nanoparticles for the first time by using the human H chain of ferritin that was expressed by Pichia pastoris (P-HFn). Western blot results showed that recombinant P-HFn was successfully expressed after methanol induction. Transmission electron microscopy (TEM) showed the spherical cage-like shape and monodispersion of P-HFn. The synthesized magnetoferritin (P-MHFn) retained the properties of magnetoferritin nanoparticles synthesized using HFn expressed by E. coli (E-MHFn): superparamagnetism under ambient conditions and peroxidase-like activity. It is stable under a wider range of pH values (from 5.0 to 11.0), likely due to post-translational modifications such as N-glycosylation on P-HFn. In vivo near-infrared fluorescence imaging experiments revealed that P-MHFn nanoparticles can accumulate in tumors, which suggests that P-MHFn could be used in tumor imaging and therapy. An acute toxicity study of P-MHFn in Sprague Dawley rats showed no abnormalities at a dose up to 20 mg Fe Kg[-1] body weight. Therefore, this study shed light on the development of magnetoferritin nanoparticles using therapeutic HFn expressed by Pichia pastoris for biomedical applications.}, } @article {pmid32930360, year = {2021}, author = {Salas-Vidal, E and Méndez-Cruz, FJ and Ramírez-Corona, A and Reza-Medina, B}, title = {Oxygen, reactive oxygen species and developmental redox networks: Evo-Devo Evil-Devils?.}, journal = {The International journal of developmental biology}, volume = {65}, number = {4-5-6}, pages = {345-356}, doi = {10.1387/ijdb.200170es}, pmid = {32930360}, issn = {1696-3547}, mesh = {Animals ; *Biological Evolution ; *Developmental Biology ; Oxidation-Reduction ; *Oxygen ; *Reactive Oxygen Species ; }, abstract = {Molecular oxygen (O2), reactive oxygen species (ROS), and associated redox networks are cornerstones of aerobic life. These molecules and networks have gained recognition as fundamental players in mechanisms that regulate the development of multicellular organisms. First, we present a brief review in which we provide a historical description of some relevant discoveries that led to this recognition. We also discuss the fact that, despite its abundance in nature, oxygen is a limiting factor, and its high availability variation impacted the evolution of adaptive mechanisms to guarantee the proper development of diverse species under such extreme environments. Finally, some examples of when oxygen and ROS were identified as relevant for the control of developmental processes are discussed. We take into account not only the current knowledge on animal redox developmental biology, but also briefly discuss potential scenarios on the origin and evolution of redox developmental mechanisms and the importance of the ever-changing environment.}, } @article {pmid32929605, year = {2020}, author = {Cui, Y and Zhao, H and Wu, S and Li, X}, title = {Human Female Reproductive System Organoids: Applications in Developmental Biology, Disease Modelling, and Drug Discovery.}, journal = {Stem cell reviews and reports}, volume = {16}, number = {6}, pages = {1173-1184}, doi = {10.1007/s12015-020-10039-0}, pmid = {32929605}, issn = {2629-3277}, mesh = {Animals ; *Developmental Biology ; Disease Models, Animal ; *Drug Discovery ; Female ; Genitalia, Female/*pathology ; Humans ; Organoids/*pathology ; Trophoblasts/pathology ; }, abstract = {Organoid technique has achieved significant progress in recent years, owing to the rapid development of the three-dimensional (3D) culture techniques in adult stem cells (ASCs) and pluripotent stem cells (PSCs) that are capable of self-renewal and induced differentiation. However, our understanding of human female reproductive system organoids is in its infancy. Recently, scientists have established self-organizing 3D organoids for human endometrium, fallopian tubes, oocyte, and trophoblasts by culturing stem cells with a cocktail of cytokines in a 3D scaffold. These organoids express multicellular biomarkers and show functional characteristics similar to those of their origin organs, which provide potential avenues to explore reproductive system development, disease modelling, and patient-specific therapy. Nevertheless, advanced culture methods, such as co-culture system, 3D bioprinting and organoid-on-a-chip technology, remain to be explored, and more efforts should be made for further elucidation of cell-cell crosstalk. This review describes the development and applications of human female reproductive system organoids. Graphical abstract Figure: Applications in developmental biology, disease modelling, and drug discovery of human female reproductive system organoids. ASCs: adult stem cells; PSCs: pluripotent stem cells.}, } @article {pmid32929365, year = {2020}, author = {Mowday, AM and Copp, JN and Syddall, SP and Dubois, LJ and Wang, J and Lieuwes, NG and Biemans, R and Ashoorzadeh, A and Abbattista, MR and Williams, EM and Guise, CP and Lambin, P and Ackerley, DF and Smaill, JB and Theys, J and Patterson, AV}, title = {E. coli nitroreductase NfsA is a reporter gene for non-invasive PET imaging in cancer gene therapy applications.}, journal = {Theranostics}, volume = {10}, number = {23}, pages = {10548-10562}, pmid = {32929365}, issn = {1838-7640}, mesh = {Animals ; Antineoplastic Agents, Alkylating/*pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; Escherichia coli Proteins/*administration & dosage/genetics ; Etanidazole/administration & dosage/analogs & derivatives/pharmacokinetics ; *Genes, Reporter ; Genetic Therapy ; Genetic Vectors/administration & dosage/pharmacokinetics ; HCT116 Cells ; Humans ; Hydrocarbons, Fluorinated/administration & dosage/pharmacokinetics ; Imidazoles/administration & dosage ; Indicators and Reagents/administration & dosage/pharmacokinetics ; Mice ; Molecular Imaging/methods ; Neoplasms/*diagnostic imaging/drug therapy/genetics/pathology ; Nitrogen Mustard Compounds/pharmacology/therapeutic use ; Nitroreductases/*administration & dosage/genetics ; Positron-Emission Tomography/*methods ; Precision Medicine/methods ; Proof of Concept Study ; Radiopharmaceuticals/administration & dosage ; Recombinant Proteins/administration & dosage/genetics ; Triazoles/administration & dosage ; Tumor Hypoxia ; Xenograft Model Antitumor Assays ; }, abstract = {The use of reporter genes to non-invasively image molecular processes inside cells has significant translational potential, particularly in the context of systemically administered gene therapy vectors and adoptively administered cells such as immune or stem cell based therapies. Bacterial nitroreductase enzymes possess ideal properties for reporter gene imaging applications, being of non-human origin and possessing the ability to metabolize a range of clinically relevant nitro(hetero)cyclic substrates. Methods: A library of eleven Escherichia coli nitroreductase candidates were screened for the ability to efficiently metabolize 2-nitroimidazole based positron emission tomography (PET) probes originally developed as radiotracers for hypoxic cell imaging. Several complementary methods were utilized to detect formation of cell-entrapped metabolites, including various in vitro and in vivo models to establish the capacity of the 2-nitroimidazole PET agent EF5 to quantify expression of a nitroreductase candidate. Proof-of-principle PET imaging studies were successfully conducted using [18]F-HX4. Results: Recombinant enzyme kinetics, bacterial SOS reporter assays, anti-proliferative assays and flow cytometry approaches collectively identified the major oxygen-insensitive nitroreductase NfsA from E. coli (NfsA_Ec) as the most promising nitroreductase reporter gene. Cells expressing NfsA_Ec were demonstrably labelled with the imaging agent EF5 in a manner that was quantitatively superior to hypoxia, in monolayers (2D), multicellular layers (3D), and in human tumor xenograft models. EF5 retention correlated with NfsA_Ec positive cell density over a range of EF5 concentrations in 3D in vitro models and in xenografts in vivo and was predictive of in vivo anti-tumor activity of the cytotoxic prodrug PR-104. Following PET imaging with [18]F-HX4, a significantly higher tumor-to-blood ratio was observed in two xenograft models for NfsA_Ec expressing tumors compared to the parental tumors thereof, providing verification of this reporter gene imaging approach. Conclusion: This study establishes that the bacterial nitroreductase NfsA_Ec can be utilized as an imaging capable reporter gene, with the ability to metabolize and trap 2-nitroimidazole PET imaging agents for non-invasive imaging of gene expression.}, } @article {pmid32802320, year = {2020}, author = {Cohen, IR and Marron, A}, title = {The evolution of universal adaptations of life is driven by universal properties of matter: energy, entropy, and interaction.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {626}, pmid = {32802320}, issn = {2046-1402}, mesh = {*Adaptation, Biological ; Animals ; *Entropy ; Humans ; Metabolic Networks and Pathways ; Microbiota ; Phenotype ; *Reproduction ; }, abstract = {The evolution of multicellular eukaryotes expresses two sorts of adaptations: local adaptations like fur or feathers, which characterize species in particular environments, and universal adaptations like microbiomes or sexual reproduction, which characterize most multicellulars in any environment. We reason that the mechanisms driving the universal adaptations of multicellulars should themselves be universal, and propose a mechanism based on properties of matter and systems: energy, entropy, and interaction. Energy from the sun, earth and beyond creates new arrangements and interactions. Metabolic networks channel some of this energy to form cooperating, interactive arrangements. Entropy, used here as a term for all forces that dismantle ordered structures (rather than as a physical quantity), acts as a selective force. Entropy selects for arrangements that resist it long enough to replicate, and dismantles those that do not. Interactions, energy-charged and dynamic, restrain entropy and enable survival and propagation of integrated living systems. This fosters survival-of-the-fitted - those entities that resist entropic destruction - and not only of the fittest - the entities with the greatest reproductive success. The "unit" of evolution is not a discrete entity, such as a gene, individual, or species; what evolves are collections of related interactions at multiple scales. Survival-of-the-fitted explains universal adaptations, including resident microbiomes, sexual reproduction, continuous diversification, programmed turnover, seemingly wasteful phenotypes, altruism, co-evolving environmental niches, and advancing complexity. Indeed survival-of-the-fittest may be a particular case of the survival-of-the-fitted mechanism, promoting local adaptations that express reproductive advantages in addition to resisting entropy. Survival-of-the-fitted accounts for phenomena that have been attributed to neutral evolution: in the face of entropy, there is no neutrality; all variations are challenged by ubiquitous energy and entropy, retaining those that are "fit enough". We propose experiments to test predictions of the survival-of-the-fitted theory, and discuss implications for the wellbeing of humans and the biosphere.}, } @article {pmid32918875, year = {2020}, author = {Funato, Y and Yoshida, A and Hirata, Y and Hashizume, O and Yamazaki, D and Miki, H}, title = {The Oncogenic PRL Protein Causes Acid Addiction of Cells by Stimulating Lysosomal Exocytosis.}, journal = {Developmental cell}, volume = {55}, number = {4}, pages = {387-397.e8}, doi = {10.1016/j.devcel.2020.08.009}, pmid = {32918875}, issn = {1878-1551}, mesh = {Acids/*metabolism ; Animals ; CRISPR-Cas Systems/genetics ; Caenorhabditis elegans/metabolism ; Conserved Sequence ; Dogs ; Evolution, Molecular ; *Exocytosis ; HEK293 Cells ; Humans ; Immediate-Early Proteins/*metabolism ; Intracellular Membranes/metabolism ; Lysosomes/*metabolism ; Madin Darby Canine Kidney Cells ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Neoplasm Proteins/*metabolism ; Protein Tyrosine Phosphatases/*metabolism ; }, abstract = {Extracellular pH is usually maintained around 7.4 in multicellular organisms, and cells are optimized to proliferate under this condition. Here, we find cells can adapt to a more acidic pH of 6.5 and become addicted to this acidic microenvironment by expressing phosphatase of regenerating liver (PRL), a driver of cancer malignancy. Genome-scale CRISPR-Cas9 knockout screening and subsequent analyses revealed that PRL promotes H[+] extrusion and acid addiction by stimulating lysosomal exocytosis. Further experiments using cultured cells and Caenorhabditis elegans clarified the molecular link between PRL and lysosomal exocytosis across species, involving activation of lysosomal Ca[2+] channel TRPML by ROS. Indeed, disruption of TRPML in cancer cells abolished PRL-stimulated lysosomal exocytosis, acid addiction, and metastasis. Thus, PRL is the molecular switch turning cells addicted to an acidic condition, which should benefit cancer cells to thrive in an acidic tumor microenvironment.}, } @article {pmid32914530, year = {2020}, author = {Gao, M and Mackley, IGP and Mesbahi-Vasey, S and Bamonte, HA and Struyvenberg, SA and Landolt, L and Pederson, NJ and Williams, LI and Bahl, CD and Brooks, L and Amacher, JF}, title = {Structural characterization and computational analysis of PDZ domains in Monosiga brevicollis.}, journal = {Protein science : a publication of the Protein Society}, volume = {29}, number = {11}, pages = {2226-2244}, pmid = {32914530}, issn = {1469-896X}, support = {S10OD021832/NH/NIH HHS/United States ; S10 OD021832/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Algorithms ; Choanoflagellata/*chemistry/genetics ; Crystallography, X-Ray ; Databases, Protein ; *Models, Molecular ; *PDZ Domains ; Protozoan Proteins/*chemistry/genetics ; *Sequence Analysis, Protein ; }, abstract = {Identification of the molecular networks that facilitated the evolution of multicellular animals from their unicellular ancestors is a fundamental problem in evolutionary cellular biology. Choanoflagellates are recognized as the closest extant nonmetazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular-like "rosette" state. Therefore, they are compelling models for the study of early multicellularity. Comparative studies revealed that a number of putative human orthologs are present in choanoflagellate genomes, suggesting that a subset of these genes were necessary for the emergence of multicellularity. However, previous work is largely based on sequence alignments alone, which does not confirm structural nor functional similarity. Here, we focus on the PDZ domain, a peptide-binding domain which plays critical roles in myriad cellular signaling networks and which underwent a gene family expansion in metazoan lineages. Using a customized sequence similarity search algorithm, we identified 178 PDZ domains in the Monosiga brevicollis proteome. This includes 11 previously unidentified sequences, which we analyzed using Rosetta and homology modeling. To assess conservation of protein structure, we solved high-resolution crystal structures of representative M. brevicollis PDZ domains that are homologous to human Dlg1 PDZ2, Dlg1 PDZ3, GIPC, and SHANK1 PDZ domains. To assess functional conservation, we calculated binding affinities for mbGIPC, mbSHANK1, mbSNX27, and mbDLG-3 PDZ domains from M. brevicollis. Overall, we find that peptide selectivity is generally conserved between these two disparate organisms, with one possible exception, mbDLG-3. Overall, our results provide novel insight into signaling pathways in a choanoflagellate model of primitive multicellularity.}, } @article {pmid32900997, year = {2020}, author = {Fukushima, K and Pollock, DD}, title = {Amalgamated cross-species transcriptomes reveal organ-specific propensity in gene expression evolution.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4459}, pmid = {32900997}, issn = {2041-1723}, support = {R01 GM083127/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Databases, Nucleic Acid ; *Evolution, Molecular ; Female ; Gene Duplication ; Humans ; Male ; Models, Genetic ; Multigene Family ; Organ Specificity ; Phylogeny ; Proteins/genetics ; RNA-Seq ; Species Specificity ; *Transcriptome ; Vertebrates/classification/genetics ; }, abstract = {The origins of multicellular physiology are tied to evolution of gene expression. Genes can shift expression as organisms evolve, but how ancestral expression influences altered descendant expression is not well understood. To examine this, we amalgamate 1,903 RNA-seq datasets from 182 research projects, including 6 organs in 21 vertebrate species. Quality control eliminates project-specific biases, and expression shifts are reconstructed using gene-family-wise phylogenetic Ornstein-Uhlenbeck models. Expression shifts following gene duplication result in more drastic changes in expression properties than shifts without gene duplication. The expression properties are tightly coupled with protein evolutionary rate, depending on whether and how gene duplication occurred. Fluxes in expression patterns among organs are nonrandom, forming modular connections that are reshaped by gene duplication. Thus, if expression shifts, ancestral expression in some organs induces a strong propensity for expression in particular organs in descendants. Regardless of whether the shifts are adaptive or not, this supports a major role for what might be termed preadaptive pathways of gene expression evolution.}, } @article {pmid32889101, year = {2020}, author = {Sidorova, A and Tverdislov, V and Levashova, N and Garaeva, A}, title = {A model of autowave self-organization as a hierarchy of active media in the biological evolution.}, journal = {Bio Systems}, volume = {198}, number = {}, pages = {104234}, doi = {10.1016/j.biosystems.2020.104234}, pmid = {32889101}, issn = {1872-8324}, mesh = {*Algorithms ; *Biological Evolution ; Eukaryota/*classification/cytology/genetics ; *Genetic Speciation ; Genome/genetics ; *Models, Theoretical ; Mutation/genetics ; Prokaryotic Cells/*classification/metabolism ; Species Specificity ; Time Factors ; }, abstract = {Within the framework of the active media concept, we develop a biophysical model of autowave self-organization which is treated as a hierarchy of active media in the evolution of the biosphere. We also propose a mathematical model of the autowave process of speciation in a flow of mutations for the three main taxonometric groups (prokaryotes, unicellular and multicellular eukaryotes) with a naturally determined lower boundary of living matter (the appearance of prokaryotes) and an open upper boundary for the formation of new species. It is shown that the fluctuation-bifurcation description of the evolution for the formation of new taxonometric groups as a trajectory of transformation of small fluctuations into giant ones adequately reflects the process of self-organization during the formation of taxa. The major concepts of biological evolution, conditions of hierarchy formation as a fundamental manifestation of self-organization and complexity in the evolution of biological systems are considered.}, } @article {pmid32888478, year = {2020}, author = {Pentz, JT and Márquez-Zacarías, P and Bozdag, GO and Burnetti, A and Yunker, PJ and Libby, E and Ratcliff, WC}, title = {Ecological Advantages and Evolutionary Limitations of Aggregative Multicellular Development.}, journal = {Current biology : CB}, volume = {30}, number = {21}, pages = {4155-4164.e6}, doi = {10.1016/j.cub.2020.08.006}, pmid = {32888478}, issn = {1879-0445}, mesh = {*Biological Evolution ; Cell Adhesion/*physiology ; *Models, Biological ; Saccharomyces cerevisiae/*growth & development ; }, abstract = {All multicellular organisms develop through one of two basic routes: they either aggregate from free-living cells, creating potentially chimeric multicellular collectives, or they develop clonally via mother-daughter cellular adhesion. Although evolutionary theory makes clear predictions about trade-offs between these developmental modes, these have never been experimentally tested in otherwise genetically identical organisms. We engineered unicellular baker's yeast (Saccharomyces cerevisiae) to develop either clonally ("snowflake"; Δace2) or aggregatively ("floc"; GAL1p::FLO1) and examined their fitness in a fluctuating environment characterized by periods of growth and selection for rapid sedimentation. When cultured independently, aggregation was far superior to clonal development, providing a 35% advantage during growth and a 2.5-fold advantage during settling selection. Yet when competed directly, clonally developing snowflake yeast rapidly displaced aggregative floc. This was due to unexpected social exploitation: snowflake yeast, which do not produce adhesive FLO1, nonetheless become incorporated into flocs at a higher frequency than floc cells themselves. Populations of chimeric clusters settle much faster than floc alone, providing snowflake yeast with a fitness advantage during competition. Mathematical modeling suggests that such developmental cheating may be difficult to circumvent; hypothetical "choosy floc" that avoid exploitation by maintaining clonality pay an ecological cost when rare, often leading to their extinction. Our results highlight the conflict at the heart of aggregative development: non-specific cellular binding provides a strong ecological advantage-the ability to quickly form groups-but this very feature leads to its exploitation.}, } @article {pmid32882615, year = {2020}, author = {Ruiz-Arrebola, S and Tornero-López, AM and Guirado, D and Villalobos, M and Lallena, AM}, title = {An on-lattice agent-based Monte Carlo model simulating the growth kinetics of multicellular tumor spheroids.}, journal = {Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)}, volume = {77}, number = {}, pages = {194-203}, doi = {10.1016/j.ejmp.2020.07.026}, pmid = {32882615}, issn = {1724-191X}, mesh = {*Breast Neoplasms ; Female ; Humans ; Kinetics ; Monte Carlo Method ; Necrosis ; *Spheroids, Cellular ; }, abstract = {PURPOSE: To develop an on-lattice agent-based model describing the growth of multicellular tumor spheroids using simple Monte Carlo tools.

METHODS: Cells are situated on the vertices of a cubic grid. Different cell states (proliferative, hypoxic or dead) and cell evolution rules, driven by 10 parameters, and the effects of the culture medium are included. About twenty spheroids of MCF-7 human breast cancer were cultivated and the experimental data were used for tuning the model parameters.

RESULTS: Simulated spheroids showed adequate sizes of the necrotic nuclei and of the hypoxic and proliferative cell phases as a function of the growth time, mimicking the overall characteristics of the experimental spheroids. The relation between the radii of the necrotic nucleus and the whole spheroid obtained in the simulations was similar to the experimental one and the number of cells, as a function of the spheroid volume, was well reproduced. The statistical variability of the Monte Carlo model described the whole volume range observed for the experimental spheroids. Assuming that the model parameters vary within Gaussian distributions it was obtained a sample of spheroids that reproduced much better the experimental findings.

CONCLUSIONS: The model developed allows describing the growth of in vitro multicellular spheroids and the experimental variability can be well reproduced. Its flexibility permits to vary both the agents involved and the rules that govern the spheroid growth. More general situations, such as, e. g., tumor vascularization, radiotherapy effects on solid tumors, or the validity of the tumor growth mathematical models can be studied.}, } @article {pmid32873627, year = {2021}, author = {Saucedo, LJ and Triolo, RE and Segar, KE}, title = {How Drosophila Can Inform the Emerging Paradigm of the Role of Antioxidants in Cancer.}, journal = {Molecular cancer research : MCR}, volume = {19}, number = {1}, pages = {38-41}, doi = {10.1158/1541-7786.MCR-20-0172}, pmid = {32873627}, issn = {1557-3125}, mesh = {Animals ; Antioxidants/*metabolism ; Drosophila melanogaster/*genetics ; Humans ; Neoplasms/*genetics ; }, abstract = {Drosophila melanogaster has proven to be an effective model system in uncovering both genetic and cellular contributions to human cancer. Many elusive genes and signaling pathways that control oncogenic growth were first identified using flies. In many cases, these discoveries were not driven by a direct search for novel genes involved in cancer but rather stemmed from research programs to uncover mechanisms that control growth and development. However, the bounty of genetic tools and the shared evolution of multicellular organisms places Drosophila in a powerful position to purposefully elucidate observations seen in human cancers. In the past decade, the role of antioxidants in cancer progression has shifted dramatically. This review highlights major findings driving this change in perspective and underscores an array of existing work and resources in laboratories using Drosophila that can make significant contributions to how the redox environment affects cancer progression.}, } @article {pmid32871001, year = {2021}, author = {Futo, M and Opašić, L and Koska, S and Čorak, N and Široki, T and Ravikumar, V and Thorsell, A and Lenuzzi, M and Kifer, D and Domazet-Lošo, M and Vlahoviček, K and Mijakovic, I and Domazet-Lošo, T}, title = {Embryo-Like Features in Developing Bacillus subtilis Biofilms.}, journal = {Molecular biology and evolution}, volume = {38}, number = {1}, pages = {31-47}, pmid = {32871001}, issn = {1537-1719}, mesh = {Bacillus subtilis/cytology/*physiology ; *Biofilms ; *Biological Evolution ; }, abstract = {Correspondence between evolution and development has been discussed for more than two centuries. Recent work reveals that phylogeny-ontogeny correlations are indeed present in developmental transcriptomes of eukaryotic clades with complex multicellularity. Nevertheless, it has been largely ignored that the pervasive presence of phylogeny-ontogeny correlations is a hallmark of development in eukaryotes. This perspective opens a possibility to look for similar parallelisms in biological settings where developmental logic and multicellular complexity are more obscure. For instance, it has been increasingly recognized that multicellular behavior underlies biofilm formation in bacteria. However, it remains unclear whether bacterial biofilm growth shares some basic principles with development in complex eukaryotes. Here we show that the ontogeny of growing Bacillus subtilis biofilms recapitulates phylogeny at the expression level. Using time-resolved transcriptome and proteome profiles, we found that biofilm ontogeny correlates with the evolutionary measures, in a way that evolutionary younger and more diverged genes were increasingly expressed toward later timepoints of biofilm growth. Molecular and morphological signatures also revealed that biofilm growth is highly regulated and organized into discrete ontogenetic stages, analogous to those of eukaryotic embryos. Together, this suggests that biofilm formation in Bacillus is a bona fide developmental process comparable to organismal development in animals, plants, and fungi. Given that most cells on Earth reside in the form of biofilms and that biofilms represent the oldest known fossils, we anticipate that the widely adopted vision of the first life as a single-cell and free-living organism needs rethinking.}, } @article {pmid32861802, year = {2020}, author = {Stewart, JE}, title = {Towards a general theory of the major cooperative evolutionary transitions.}, journal = {Bio Systems}, volume = {198}, number = {}, pages = {104237}, doi = {10.1016/j.biosystems.2020.104237}, pmid = {32861802}, issn = {1872-8324}, mesh = {Adaptation, Physiological/*physiology ; *Biological Evolution ; *Communication ; *Cooperative Behavior ; Humans ; Political Systems ; Public Policy ; Social Behavior ; Socioeconomic Factors ; }, abstract = {Major Cooperative Evolutionary Transitions occur when smaller-scale entities cooperate together to give rise to larger-scale entities that evolve and adapt as coherent wholes. Key examples of cooperative transitions are the emergence of the complex eukaryote cell from communities of simpler cells, the transition from eukaryote cells to multicellular organisms, and the organization of humans into complex, modern societies. A number of attempts have been made to develop a general theory of the major cooperative transitions. This paper begins by critiquing key aspects of these previous attempts. Largely, these attempts comprise poorly-integrated collections of separate models that were each originally developed to explain particular transitions. In contrast, this paper sets out to identify processes that are common to all cooperative transitions. It develops an alternative theoretical framework known as Management Theory. This general framework suggests that all major cooperative transitions are the result of the emergence of powerful, evolvable 'managers' that derive benefit from using their power to organize smaller-scale entities into larger-scale cooperatives. Management Theory is a contribution to the development of a general, "all levels" understanding of major cooperative transitions that is capable of identifying those features that are level-specific, those that are common across levels and those that are involved in trends across levels.}, } @article {pmid32857975, year = {2020}, author = {Parra-Acero, H and Harcet, M and Sánchez-Pons, N and Casacuberta, E and Brown, NH and Dudin, O and Ruiz-Trillo, I}, title = {Integrin-Mediated Adhesion in the Unicellular Holozoan Capsaspora owczarzaki.}, journal = {Current biology : CB}, volume = {30}, number = {21}, pages = {4270-4275.e4}, doi = {10.1016/j.cub.2020.08.015}, pmid = {32857975}, issn = {1879-0445}, mesh = {CD18 Antigens/metabolism ; Cell Adhesion/*physiology ; Eukaryota/cytology/*physiology ; Fibronectins/metabolism ; Integrins/metabolism ; Pseudopodia/metabolism ; Vinculin/metabolism ; }, abstract = {In animals, cell-matrix adhesions are essential for cell migration, tissue organization, and differentiation, which have central roles in embryonic development [1-6]. Integrins are the major cell surface adhesion receptors mediating cell-matrix adhesion in animals. They are heterodimeric transmembrane proteins that bind extracellular matrix (ECM) molecules on one side and connect to the actin cytoskeleton on the other [7]. Given the importance of integrin-mediated cell-matrix adhesion in development of multicellular animals, it is of interest to discover when and how this machinery arose during evolution. Comparative genomic analyses have shown that core components of the integrin adhesome pre-date the emergence of animals [8-11]; however, whether it mediates cell adhesion in non-metazoan taxa remains unknown. Here, we investigate cell-substrate adhesion in Capsaspora owczarzaki, the closest unicellular relative of animals with the most complete integrin adhesome [11, 12]. Previous work described that the life cycle of C. owczarzaki (hereafter, Capsaspora) includes three distinct life stages: adherent; cystic; and aggregative [13]. Using an adhesion assay, we show that, during the adherent life stage, C. owczarzaki adheres to surfaces using actin-dependent filopodia. We show that integrin β2 and its associated protein vinculin localize as distinct patches in the filopodia. We also demonstrate that substrate adhesion and integrin localization are enhanced by mammalian fibronectin. Finally, using a specific antibody for integrin β2, we inhibited cell adhesion to a fibronectin-coated surface. Our results suggest that adhesion to the substrate in C. owczarzaki is mediated by integrins. We thus propose that integrin-mediated adhesion pre-dates the emergence of animals.}, } @article {pmid32849605, year = {2020}, author = {Pérez-Hernández, CA and Kern, CC and Butkeviciute, E and McCarthy, E and Dockrell, HM and Moreno-Altamirano, MMB and Aguilar-López, BA and Bhosale, G and Wang, H and Gems, D and Duchen, MR and Smith, SG and Sánchez-García, FJ}, title = {Mitochondrial Signature in Human Monocytes and Resistance to Infection in C. elegans During Fumarate-Induced Innate Immune Training.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1715}, pmid = {32849605}, issn = {1664-3224}, support = {215574/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; MR/R005850/1/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 098565/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Caenorhabditis elegans/*drug effects/immunology/metabolism/microbiology ; Calcium Signaling/drug effects ; Cells, Cultured ; Cytokines/metabolism ; Escherichia coli/immunology/*pathogenicity ; Escherichia coli Infections/immunology/metabolism/microbiology/*prevention & control ; Fumarates/*pharmacology ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/*drug effects ; Immunologic Memory/*drug effects ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/*drug effects/immunology/metabolism ; Mitochondrial Dynamics/drug effects ; Monocytes/*drug effects/immunology/metabolism ; }, abstract = {Monocytes can develop immunological memory, a functional characteristic widely recognized as innate immune training, to distinguish it from memory in adaptive immune cells. Upon a secondary immune challenge, either homologous or heterologous, trained monocytes/macrophages exhibit a more robust production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, than untrained monocytes. Candida albicans, β-glucan, and BCG are all inducers of monocyte training and recent metabolic profiling analyses have revealed that training induction is dependent on glycolysis, glutaminolysis, and the cholesterol synthesis pathway, along with fumarate accumulation; interestingly, fumarate itself can induce training. Since fumarate is produced by the tricarboxylic acid (TCA) cycle within mitochondria, we asked whether extra-mitochondrial fumarate has an effect on mitochondrial function. Results showed that the addition of fumarate to monocytes induces mitochondrial Ca[2+] uptake, fusion, and increased membrane potential (Δψm), while mitochondrial cristae became closer to each other, suggesting that immediate (from minutes to hours) mitochondrial activation plays a role in the induction phase of innate immune training of monocytes. To establish whether fumarate induces similar mitochondrial changes in vivo in a multicellular organism, effects of fumarate supplementation were tested in the nematode worm Caenorhabditis elegans. This induced mitochondrial fusion in both muscle and intestinal cells and also increased resistance to infection of the pharynx with E. coli. Together, these findings contribute to defining a mitochondrial signature associated with the induction of innate immune training by fumarate treatment, and to the understanding of whole organism infection resistance.}, } @article {pmid32839450, year = {2020}, author = {Du, P and Zhao, H and Zhang, H and Wang, R and Huang, J and Tian, Y and Luo, X and Luo, X and Wang, M and Xiang, Y and Qian, L and Chen, Y and Tao, Y and Lou, C}, title = {De novo design of an intercellular signaling toolbox for multi-channel cell-cell communication and biological computation.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4226}, pmid = {32839450}, issn = {2041-1723}, mesh = {Cell Communication/*genetics ; Computational Biology/*methods ; Escherichia coli/genetics/metabolism ; Green Fluorescent Proteins/genetics/metabolism ; HEK293 Cells ; Humans ; Microscopy, Fluorescence ; Mutation ; Reproducibility of Results ; Saccharomyces cerevisiae/genetics/metabolism ; Signal Transduction/*genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {Intercellular signaling is indispensable for single cells to form complex biological structures, such as biofilms, tissues and organs. The genetic tools available for engineering intercellular signaling, however, are quite limited. Here we exploit the chemical diversity of biological small molecules to de novo design a genetic toolbox for high-performance, multi-channel cell-cell communications and biological computations. By biosynthetic pathway design for signal molecules, rational engineering of sensing promoters and directed evolution of sensing transcription factors, we obtain six cell-cell signaling channels in bacteria with orthogonality far exceeding the conventional quorum sensing systems and successfully transfer some of them into yeast and human cells. For demonstration, they are applied in cell consortia to generate bacterial colony-patterns using up to four signaling channels simultaneously and to implement distributed bio-computation containing seven different strains as basic units. This intercellular signaling toolbox paves the way for engineering complex multicellularity including artificial ecosystems and smart tissues.}, } @article {pmid32822576, year = {2020}, author = {Maynard, A and McCoach, CE and Rotow, JK and Harris, L and Haderk, F and Kerr, DL and Yu, EA and Schenk, EL and Tan, W and Zee, A and Tan, M and Gui, P and Lea, T and Wu, W and Urisman, A and Jones, K and Sit, R and Kolli, PK and Seeley, E and Gesthalter, Y and Le, DD and Yamauchi, KA and Naeger, DM and Bandyopadhyay, S and Shah, K and Cech, L and Thomas, NJ and Gupta, A and Gonzalez, M and Do, H and Tan, L and Bacaltos, B and Gomez-Sjoberg, R and Gubens, M and Jahan, T and Kratz, JR and Jablons, D and Neff, N and Doebele, RC and Weissman, J and Blakely, CM and Darmanis, S and Bivona, TG}, title = {Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing.}, journal = {Cell}, volume = {182}, number = {5}, pages = {1232-1251.e22}, pmid = {32822576}, issn = {1097-4172}, support = {R01 CA227807/CA/NCI NIH HHS/United States ; T32 HL007185/HL/NHLBI NIH HHS/United States ; U54 CA224081/CA/NCI NIH HHS/United States ; R01 CA211052/CA/NCI NIH HHS/United States ; U01 CA217882/CA/NCI NIH HHS/United States ; 2018110/DDCF_/Doris Duke Charitable Foundation/United States ; R01 CA231300/CA/NCI NIH HHS/United States ; R01 CA169338/CA/NCI NIH HHS/United States ; R01 CA204302/CA/NCI NIH HHS/United States ; K12 CA086913/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Cell Line ; Ecosystem ; Humans ; Lung Neoplasms/*genetics/pathology ; Macrophages/pathology ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; T-Lymphocytes/pathology ; Tumor Microenvironment/genetics ; }, abstract = {Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.}, } @article {pmid32810421, year = {2020}, author = {Grassam-Rowe, A and Ou, X and Lei, M}, title = {Novel cardiac cell subpopulations: Pnmt-derived cardiomyocytes.}, journal = {Open biology}, volume = {10}, number = {8}, pages = {200095}, pmid = {32810421}, issn = {2046-2441}, support = {G1002082/MRC_/Medical Research Council/United Kingdom ; PG/14/80/31106/BHF_/British Heart Foundation/United Kingdom ; G10002647/MRC_/Medical Research Council/United Kingdom ; G1002647/MRC_/Medical Research Council/United Kingdom ; PG/11/59/29004/BHF_/British Heart Foundation/United Kingdom ; PG/16/67/32340/BHF_/British Heart Foundation/United Kingdom ; PG/12/21/29473/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Age Factors ; Animals ; Biomarkers ; Catecholamines/metabolism ; *Cell Plasticity ; Electrophysiological Phenomena ; Humans ; Myocardium/cytology/enzymology/metabolism ; Myocytes, Cardiac/*cytology/*metabolism ; Organogenesis/genetics ; Phenotype ; Phenylethanolamine N-Methyltransferase/genetics/*metabolism ; }, abstract = {Diversity among highly specialized cells underlies the fundamental biology of complex multi-cellular organisms. One of the essential scientific questions in cardiac biology has been to define subpopulations within the heart. The heart parenchyma comprises specialized cardiomyocytes (CMs). CMs have been canonically classified into a few phenotypically diverse subpopulations largely based on their function and anatomic localization. However, there is growing evidence that CM subpopulations are in fact numerous, with a diversity of genetic origin and putatively different roles in physiology and pathophysiology. In this chapter, we introduce a recently discovered CM subpopulation: phenylethanolamine-N-methyl transferase (Pnmt)-derived cardiomyocytes (PdCMs). We discuss: (i) canonical classifications of CM subpopulations; (ii) discovery of PdCMs; (iii) Pnmt and the role of catecholamines in the heart; similarities and dissimilarities of PdCMs and canonical CMs; and (iv) putative functions of PdCMs in both physiological and pathological states and future directions, such as in intra-cardiac adrenergic signalling.}, } @article {pmid32797190, year = {2021}, author = {Ho, AT and Hurst, LD}, title = {Effective Population Size Predicts Local Rates but Not Local Mitigation of Read-through Errors.}, journal = {Molecular biology and evolution}, volume = {38}, number = {1}, pages = {244-262}, pmid = {32797190}, issn = {1537-1719}, mesh = {Arabidopsis ; *Codon, Terminator ; Dictyostelium ; *Evolution, Molecular ; *Mutation Rate ; Population Density ; *Selection, Genetic ; }, abstract = {In correctly predicting that selection efficiency is positively correlated with the effective population size (Ne), the nearly neutral theory provides a coherent understanding of between-species variation in numerous genomic parameters, including heritable error (germline mutation) rates. Does the same theory also explain variation in phenotypic error rates and in abundance of error mitigation mechanisms? Translational read-through provides a model to investigate both issues as it is common, mostly nonadaptive, and has good proxy for rate (TAA being the least leaky stop codon) and potential error mitigation via "fail-safe" 3' additional stop codons (ASCs). Prior theory of translational read-through has suggested that when population sizes are high, weak selection for local mitigation can be effective thus predicting a positive correlation between ASC enrichment and Ne. Contra to prediction, we find that ASC enrichment is not correlated with Ne. ASC enrichment, although highly phylogenetically patchy, is, however, more common both in unicellular species and in genes expressed in unicellular modes in multicellular species. By contrast, Ne does positively correlate with TAA enrichment. These results imply that local phenotypic error rates, not local mitigation rates, are consistent with a drift barrier/nearly neutral model.}, } @article {pmid32778581, year = {2020}, author = {Xin, Y and Le Poul, Y and Ling, L and Museridze, M and Mühling, B and Jaenichen, R and Osipova, E and Gompel, N}, title = {Enhancer evolutionary co-option through shared chromatin accessibility input.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {34}, pages = {20636-20644}, pmid = {32778581}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Chromatin/genetics/metabolism ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/genetics ; Enhancer Elements, Genetic/*genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental/*genetics ; Regulatory Elements, Transcriptional/genetics ; Wings, Animal/metabolism ; }, abstract = {The diversity of forms in multicellular organisms originates largely from the spatial redeployment of developmental genes [S. B. Carroll, Cell 134, 25-36 (2008)]. Several scenarios can explain the emergence of cis-regulatory elements that govern novel aspects of a gene expression pattern [M. Rebeiz, M. Tsiantis, Curr. Opin. Genet. Dev. 45, 115-123 (2017)]. One scenario, enhancer co-option, holds that a DNA sequence producing an ancestral regulatory activity also becomes the template for a new regulatory activity, sharing regulatory information. While enhancer co-option might fuel morphological diversification, it has rarely been documented [W. J. Glassford et al., Dev. Cell 34, 520-531 (2015)]. Moreover, if two regulatory activities are borne from the same sequence, their modularity, considered a defining feature of enhancers [J. Banerji, L. Olson, W. Schaffner, Cell 33, 729-740 (1983)], might be affected by pleiotropy. Sequence overlap may thereby play a determinant role in enhancer function and evolution. Here, we investigated this problem with two regulatory activities of the Drosophila gene yellow, the novel spot enhancer and the ancestral wing blade enhancer. We used precise and comprehensive quantification of each activity in Drosophila wings to systematically map their sequences along the locus. We show that the spot enhancer has co-opted the sequences of the wing blade enhancer. We also identified a pleiotropic site necessary for DNA accessibility of a shared regulatory region. While the evolutionary steps leading to the derived activity are still unknown, such pleiotropy suggests that enhancer accessibility could be one of the molecular mechanisms seeding evolutionary co-option.}, } @article {pmid32767819, year = {2020}, author = {Kundu, R}, title = {Cationic Amphiphilic Peptides: Synthetic Antimicrobial Agents Inspired by Nature.}, journal = {ChemMedChem}, volume = {15}, number = {20}, pages = {1887-1896}, doi = {10.1002/cmdc.202000301}, pmid = {32767819}, issn = {1860-7187}, mesh = {Amino Acid Sequence ; Anti-Bacterial Agents/chemistry/*pharmacology/therapeutic use ; Antimicrobial Cationic Peptides/chemistry/*pharmacology/therapeutic use ; Bacteria/drug effects ; Clinical Trials as Topic ; Humans ; Lipopeptides/chemistry/pharmacology/therapeutic use ; Peptides, Cyclic/chemistry/pharmacology/therapeutic use ; Peptidomimetics/chemistry/pharmacology/therapeutic use ; Protein Conformation, alpha-Helical ; }, abstract = {Antimicrobial peptides are ubiquitous in multicellular organisms and have served as defense mechanisms for their successful evolution and throughout their life cycle. These peptides are short cationic amphiphilic polypeptides of fewer than 50 amino acids containing either a few disulfide-linked cysteine residues with a characteristic β-sheet-rich structure or linear α-helical conformations with hydrophilic side chains at one side of the helix and hydrophobic side chains on the other side. Antimicrobial peptides cause bacterial cell lysis either by direct cell-surface damage via electrostatic interactions between the cationic side chains of the peptide and the negatively charged cell surface, or by indirect modulation of the host defense systems. Electrostatic interactions lead to bacterial cell membrane disruption followed by leakage of cellular components and finally bacterial cell death. Because of their unusual mechanism of cell damage, antimicrobial peptides are effective against drug-resistant bacteria and may therefore prove more effective than classical antibiotics in certain cases. Currently, around 3000 natural antimicrobial peptides from six kingdoms (bacteria, archaea, protists, fungi, plants, and animals) have been isolated and sequenced. However, only a few of them are under clinical trials and/or in the commercial development stage for the treatment of bacterial infections caused by antibiotic-resistant bacteria. Moreover, high structural complexity, poor pharmacokinetic properties, and low antibacterial activity of natural antimicrobial peptides hinder their progress in drug development. To overcome these hurdles, researchers have become increasingly interested in modification and nature-inspired synthetic antimicrobial peptides. This review discusses some of the recent studies reported on antimicrobial peptides.}, } @article {pmid32762341, year = {2020}, author = {Whelan, CJ and Avdieiev, SS and Gatenby, RA}, title = {Insights From the Ecology of Information to Cancer Control.}, journal = {Cancer control : journal of the Moffitt Cancer Center}, volume = {27}, number = {3}, pages = {1073274820945980}, pmid = {32762341}, issn = {1526-2359}, support = {U54 CA193489/CA/NCI NIH HHS/United States ; }, mesh = {Cytoskeleton/physiology ; *Ecosystem ; Humans ; Integrins/physiology ; Models, Theoretical ; Neoplasms/pathology/*therapy ; Tumor Microenvironment ; }, abstract = {Uniquely in nature, living systems must acquire, store, and act upon information. The survival and replicative fate of each normal cell in a multicellular organism is determined solely by information obtained from its surrounding tissue. In contrast, cancer cells as single-cell eukaryotes live in a disrupted, heterogeneous environment with opportunities and hazards. Thus, cancer cells, unlike normal somatic cells, must constantly obtain information from their environment to ensure survival and proliferation. In this study, we build upon a simple mathematical modeling framework developed to predict (1) how information promotes population persistence in a highly heterogeneous environment and (2) how disruption of information resulting from habitat fragmentation increases the probability of population extinction. Because (1) tumors grow in a highly heterogeneous microenvironment and (2) many cancer therapies fragment tumors into isolated, small cancer cell populations, we identify parallels between these 2 systems and develop ideas for cancer cure based on lessons gleaned from Anthropocene extinctions. In many Anthropocene extinctions, such as that of the North American heath hen (Tympanuchus cupido cupido), a large and widespread population was initially reduced and fragmented owing to overexploitation by humans (a "first strike"). After this, the small surviving populations are vulnerable to extinction from environmental or demographic stochastic disturbances (a "second strike"). Following this analogy, after a tumor is fragmented into small populations of isolated cancer cells by an initial therapy, additional treatment can be applied with the intent of extinction (cure). Disrupting a cancer cell's ability to acquire and use information in a heterogeneous environment may be an important tactic for causing extinction following an effective initial therapy. Thus, information, from the scale of cells within tumors to that of species within ecosystems, can be used to identify vulnerabilities to extinction and opportunities for novel treatment strategies.}, } @article {pmid32738355, year = {2020}, author = {Miller, WB and Baluška, F and Torday, JS}, title = {Cellular senomic measurements in Cognition-Based Evolution.}, journal = {Progress in biophysics and molecular biology}, volume = {156}, number = {}, pages = {20-33}, doi = {10.1016/j.pbiomolbio.2020.07.002}, pmid = {32738355}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Biology/trends ; Cell Communication ; *Cognition ; Homeostasis ; Humans ; Models, Biological ; Thermodynamics ; }, abstract = {All living entities are cognitive and dependent on ambiguous information. Any assessment of that imprecision is necessarily a measuring function. Individual cells measure information to sustain self-referential homeostatic equipoise (self-identity) in juxtaposition to the external environment. The validity of that information is improved by its collective assessment. The reception of cellular information obliges thermodynamic reactions that initiate a self-reinforcing work channel. This expresses as natural cellular engineering and niche constructions which become the complex interrelated tissue ecologies of holobionts. Multicellularity is collaborative cellular information management directed towards the optimization of information quality through its collective measured assessment. Biology and its evolution can now be re-framed as the continuous process of self-referential cellular measurement in the perpetual defense of individual cellular self-identities through the collective form.}, } @article {pmid32731489, year = {2020}, author = {Pajkos, M and Zeke, A and Dosztányi, Z}, title = {Ancient Evolutionary Origin of Intrinsically Disordered Cancer Risk Regions.}, journal = {Biomolecules}, volume = {10}, number = {8}, pages = {}, pmid = {32731489}, issn = {2218-273X}, support = {FIEK16-1-2016-0005//FIEK Grant of the National Research, Development and Innovation Office/International ; ED-18-1-2019-003//ELTE Thematic Excellence Programme supported by the Hungarian Ministry for Innovation and Technology./International ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Evolution, Molecular ; Gene Duplication ; Humans ; Intrinsically Disordered Proteins/chemistry/*genetics ; Mutation ; Neoplasms/*genetics ; Protein Conformation ; Protein Domains ; }, abstract = {Cancer is a heterogeneous genetic disease that alters the proper functioning of proteins involved in key regulatory processes such as cell cycle, DNA repair, survival, or apoptosis. Mutations often accumulate in hot-spots regions, highlighting critical functional modules within these proteins that need to be altered, amplified, or abolished for tumor formation. Recent evidence suggests that these mutational hotspots can correspond not only to globular domains, but also to intrinsically disordered regions (IDRs), which play a significant role in a subset of cancer types. IDRs have distinct functional properties that originate from their inherent flexibility. Generally, they correspond to more recent evolutionary inventions and show larger sequence variations across species. In this work, we analyzed the evolutionary origin of disordered regions that are specifically targeted in cancer. Surprisingly, the majority of these disordered cancer risk regions showed remarkable conservation with ancient evolutionary origin, stemming from the earliest multicellular animals or even beyond. Nevertheless, we encountered several examples where the mutated region emerged at a later stage compared with the origin of the gene family. We also showed the cancer risk regions become quickly fixated after their emergence, but evolution continues to tinker with their genes with novel regulatory elements introduced even at the level of humans. Our concise analysis provides a much clearer picture of the emergence of key regulatory elements in proteins and highlights the importance of taking into account the modular organisation of proteins for the analyses of evolutionary origin.}, } @article {pmid32723540, year = {2020}, author = {Ovsepian, SV and O'Leary, VB and Vesselkin, NP}, title = {Evolutionary origins of chemical synapses.}, journal = {Vitamins and hormones}, volume = {114}, number = {}, pages = {1-21}, doi = {10.1016/bs.vh.2020.04.009}, pmid = {32723540}, issn = {0083-6729}, mesh = {Animals ; *Biological Evolution ; Neurons/*physiology ; Synapses/physiology ; Synaptic Transmission/*genetics/*physiology ; }, abstract = {Synaptic transmission is a fundamental neurobiological process by which neurons interact with each other and non-neuronal cells. It involves release of active substances from the presynaptic neuron onto receptive elements of postsynaptic cells, inducing waves of spreading electrochemical response. While much has been learned about the cellular and molecular mechanisms driving and governing transmitter release and sensing, the evolutionary origin of synaptic connections remains obscure. Herein, we review emerging evidence and concepts suggesting that key components of chemical synapse arose independently from neurons, in different functional and biological contexts, before the rise of multicellular living forms. We argue that throughout evolution, distinct synaptic constituents have been co-opted from ancestral forms for a new role in early metazoan, leading to the rise of chemical synapses and neurotransmission. Such a mosaic model of the origin of chemical synapses agrees with and supports the pluralistic hypothesis of evolutionary change.}, } @article {pmid32717856, year = {2020}, author = {Erber, L and Hoffmann, A and Fallmann, J and Hagedorn, M and Hammann, C and Stadler, PF and Betat, H and Prohaska, S and Mörl, M}, title = {Unusual Occurrence of Two Bona-Fide CCA-Adding Enzymes in Dictyostelium discoideum.}, journal = {International journal of molecular sciences}, volume = {21}, number = {15}, pages = {}, pmid = {32717856}, issn = {1422-0067}, support = {MO 634/8-2; PR 1288/6-2//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Dictyostelium/enzymology/genetics ; *Genome, Protozoan ; *Protozoan Proteins/genetics/metabolism ; *RNA Nucleotidyltransferases/genetics/metabolism ; RNA, Protozoan/genetics/metabolism ; RNA, Transfer/genetics/metabolism ; }, abstract = {Dictyostelium discoideum, the model organism for the evolutionary supergroup of Amoebozoa, is a social amoeba that, upon starvation, undergoes transition from a unicellular to a multicellular organism. In its genome, we identified two genes encoding for tRNA nucleotidyltransferases. Such pairs of tRNA nucleotidyltransferases usually represent collaborating partial activities catalyzing CC- and A-addition to the tRNA 3'-end, respectively. In D. discoideum, however, both enzymes exhibit identical activities, representing bona-fide CCA-adding enzymes. Detailed characterization of the corresponding activities revealed that both enzymes seem to be essential and are regulated inversely during different developmental stages of D. discoideum. Intriguingly, this is the first description of two functionally equivalent CCA-adding enzymes using the same set of tRNAs and showing a similar distribution within the cell. This situation seems to be a common feature in Dictyostelia, as other members of this phylum carry similar pairs of tRNA nucleotidyltransferase genes in their genome.}, } @article {pmid32707067, year = {2020}, author = {Preussger, D and Giri, S and Muhsal, LK and Oña, L and Kost, C}, title = {Reciprocal Fitness Feedbacks Promote the Evolution of Mutualistic Cooperation.}, journal = {Current biology : CB}, volume = {30}, number = {18}, pages = {3580-3590.e7}, doi = {10.1016/j.cub.2020.06.100}, pmid = {32707067}, issn = {1879-0445}, mesh = {*Biological Evolution ; Escherichia coli/*genetics/growth & development/*metabolism ; *Feedback, Physiological ; *Genetic Fitness ; Humans ; *Microbial Interactions ; *Symbiosis ; }, abstract = {Mutually beneficial interactions are ubiquitous in nature and have played a pivotal role for the evolution of life on earth. However, the factors facilitating their emergence remain poorly understood. Here, we address this issue both experimentally and by mathematical modeling using cocultures of auxotrophic strains of Escherichia coli, whose growth depends on a reciprocal exchange of amino acids. Coevolving auxotrophic pairs in a spatially heterogeneous environment for less than 150 generations transformed the initial interaction that was merely based on an exchange of metabolic byproducts into a costly metabolic cooperation, in which both partners increased the amounts of metabolites they produced to benefit their corresponding partner. The observed changes were afforded by the formation of multicellular clusters, within which increased cooperative investments were favored by positive fitness feedbacks among interacting genotypes. Under these conditions, non-cooperative individuals were less fit than cooperative mutants. Together, our results highlight the ease with which mutualistic cooperation can evolve, suggesting similar mechanisms likely operate in natural communities. VIDEO ABSTRACT.}, } @article {pmid32698133, year = {2020}, author = {Yan, JJ and Lee, YC and Tsou, YL and Tseng, YC and Hwang, PP}, title = {Insulin-like growth factor 1 triggers salt secretion machinery in fish under acute salinity stress.}, journal = {The Journal of endocrinology}, volume = {246}, number = {3}, pages = {277-288}, doi = {10.1530/JOE-20-0053}, pmid = {32698133}, issn = {1479-6805}, mesh = {Animals ; Fish Proteins/metabolism ; Insulin-Like Growth Factor I/antagonists & inhibitors/*metabolism ; Oryzias ; Salinity ; Salt Stress ; Signal Transduction/drug effects ; Sodium Chloride/*pharmacology ; }, abstract = {Timely adjustment of osmoregulation upon acute salinity stress is essential for the survival of euryhaline fish. This rapid response is thought to be tightly controlled by hormones; however, there are still questions unanswered. In this work, we tested the hypothesis that the endocrine hormone, insulin-like growth factor 1 (Igf1), a slow-acting hormone, is involved in the activation of salt secretion mechanisms in euryhaline medaka (Oryzias melastigma) during acclimation to acute salinity stress. In response to a 30-ppt seawater (SW) challenge, Na+/Cl- secretion was enhanced within 0.5 h, with concomitant organization of ionocyte multicellular complexes and without changes in expression of major transporters. Igf1 receptor inhibitors significantly impair the Na+/Cl- secretion and ionocyte multicellular complex responses without affecting transporter expression. Thus, Igf1 may activate salt secretion as part of the teleost response to acute salinity stress by exerting effects on transporter function and enhancing the formation of ionocyte multicellular complexes. These findings provide new insights into hormonal control of body fluid ionic/osmotic homeostasis during vertebrate evolution.}, } @article {pmid32693719, year = {2020}, author = {Fisher, RM and Shik, JZ and Boomsma, JJ}, title = {The evolution of multicellular complexity: the role of relatedness and environmental constraints.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1931}, pages = {20192963}, pmid = {32693719}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; Phylogeny ; }, abstract = {A major challenge in evolutionary biology has been to explain the variation in multicellularity across the many independently evolved multicellular lineages, from slime moulds to vertebrates. Social evolution theory has highlighted the key role of relatedness in determining multicellular complexity and obligateness; however, there is a need to extend this to a broader perspective incorporating the role of the environment. In this paper, we formally test Bonner's 1998 hypothesis that the environment is crucial in determining the course of multicellular evolution, with aggregative multicellularity evolving more frequently on land and clonal multicellularity more frequently in water. Using a combination of scaling theory and phylogenetic comparative analyses, we describe multicellular organizational complexity across 139 species spanning 14 independent transitions to multicellularity and investigate the role of the environment in determining multicellular group formation and in imposing constraints on multicellular evolution. Our results, showing that the physical environment has impacted the way in which multicellular groups form, highlight that environmental conditions might have affected the major evolutionary transition to obligate multicellularity.}, } @article {pmid32691527, year = {2020}, author = {Parmentier, T and De Laender, F and Bonte, D}, title = {The topology and drivers of ant-symbiont networks across Europe.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {95}, number = {6}, pages = {1664-1688}, doi = {10.1111/brv.12634}, pmid = {32691527}, issn = {1469-185X}, support = {BOF17/PDO/084//Bijzonder Onderzoeksfonds/International ; 1203020N//Fonds Wetenschappelijk Onderzoek/International ; W0.003.16N//Fonds Wetenschappelijk Onderzoek/International ; }, mesh = {Animals ; *Ants ; Biological Evolution ; Ecosystem ; Phylogeny ; Symbiosis ; }, abstract = {Intimate associations between different species drive community composition across ecosystems. Understanding the ecological and evolutionary drivers of these symbiotic associations is challenging because their structure eventually determines stability and resilience of the entire species network. Here, we compiled a detailed database on naturally occurring ant-symbiont networks in Europe to identify factors that affect symbiont network topology. These networks host an unrivalled diversity of macrosymbiotic associations, spanning the entire mutualism-antagonism continuum, including: (i) myrmecophiles - commensalistic and parasitic arthropods; (ii) trophobionts - mutualistic aphids, scale insects, planthoppers and caterpillars; (iii) social parasites - parasitic ant species; (iv) parasitic helminths; and (v) parasitic fungi. We dissected network topology to investigate what determines host specificity, symbiont species richness, and the capacity of different symbiont types to switch hosts. We found 722 macrosymbionts (multicellular symbionts) associated with European ants. Symbiont type explained host specificity and the average relatedness of the host species. Social parasites were associated with few hosts that were phylogenetically highly related, whereas the other symbiont types interacted with a larger number of hosts across a wider taxonomic distribution. The hosts of trophobionts were the least phylogenetically related across all symbiont types. Colony size, host range and habitat type predicted total symbiont richness: ant hosts with larger colony size, a larger distribution range or with a wider habitat range contained more symbiont species. However, we found that different sets of host factors affected diversity in the different types of symbionts. Ecological factors, such as colony size, host range and niche width predominantly determined myrmecophile species richness, whereas host phylogeny was the most important predictor of mutualistic trophobiont, social parasite and parasitic helminth species richness. Lastly, we found that hosts with a common biogeographic history support a more similar community of symbionts. Phylogenetically related hosts also shared more trophobionts, social parasites and helminths, but not myrmecophiles. Taken together, these results suggest that ecological and evolutionary processes structure host specificity and symbiont richness in large-scale ant-symbiont networks, but these drivers may shift in importance depending on the type of symbiosis. Our findings highlight the potential of well-characterized bipartite networks composed of different types of symbioses to identify candidate processes driving community composition.}, } @article {pmid32689913, year = {2020}, author = {Gonçalves, AP and Heller, J and Rico-Ramírez, AM and Daskalov, A and Rosenfield, G and Glass, NL}, title = {Conflict, Competition, and Cooperation Regulate Social Interactions in Filamentous Fungi.}, journal = {Annual review of microbiology}, volume = {74}, number = {}, pages = {693-712}, doi = {10.1146/annurev-micro-012420-080905}, pmid = {32689913}, issn = {1545-3251}, mesh = {Alleles ; Apoptosis ; Evolution, Molecular ; Fungal Proteins/*genetics/metabolism ; Fungi/classification/*genetics ; *Gene Expression Regulation, Fungal ; Haplotypes ; Microbial Interactions/*genetics/physiology ; Phylogeny ; }, abstract = {Social cooperation impacts the development and survival of species. In higher taxa, kin recognition occurs via visual, chemical, or tactile cues that dictate cooperative versus competitive interactions. In microbes, the outcome of cooperative versus competitive interactions is conferred by identity at allorecognition loci, so-called kind recognition. In syncytial filamentous fungi, the acquisition of multicellularity is associated with somatic cell fusion within and between colonies. However, such intraspecific cooperation entails risks, as fusion can transmit deleterious genotypes or infectious components that reduce fitness, or give rise to cheaters that can exploit communal goods without contributing to their production. Allorecognition mechanisms in syncytial fungi regulate somatic cell fusion by operating precontact during chemotropic interactions, during cell adherence, and postfusion by triggering programmed cell death reactions. Alleles at fungal allorecognition loci are highly polymorphic, fall into distinct haplogroups, and show evolutionary signatures of balancing selection, similar to allorecognition loci across the tree of life.}, } @article {pmid32687894, year = {2020}, author = {Wavreil, FDM and Yajima, M}, title = {Diversity of activator of G-protein signaling (AGS)-family proteins and their impact on asymmetric cell division across taxa.}, journal = {Developmental biology}, volume = {465}, number = {2}, pages = {89-99}, pmid = {32687894}, issn = {1095-564X}, support = {R01 GM126043/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Asymmetric Cell Division/*physiology ; Cell Cycle Proteins/genetics/*metabolism ; Humans ; *Multigene Family ; Signal Transduction/*physiology ; Species Specificity ; Spindle Apparatus/genetics/*metabolism ; }, abstract = {Asymmetric cell division (ACD) is a cellular process that forms two different cell types through a cell division and is thus critical for the development of all multicellular organisms. Not all but many of the ACD processes are mediated by proper orientation of the mitotic spindle, which segregates the fate determinants asymmetrically into daughter cells. In many cell types, the evolutionarily conserved protein complex of Gαi/AGS-family protein/NuMA-like protein appears to play critical roles in orienting the spindle and/or generating the polarized cortical forces to regulate ACD. Studies in various organisms reveal that this conserved protein complex is slightly modified in each phylum or even within species. In particular, AGS-family proteins appear to be modified with a variable number of motifs in their functional domains across taxa. This apparently creates different molecular interactions and mechanisms of ACD in each developmental program, ultimately contributing to developmental diversity across species. In this review, we discuss how a conserved ACD machinery has been modified in each phylum over the course of evolution with a major focus on the molecular evolution of AGS-family proteins and its impact on ACD regulation.}, } @article {pmid32681710, year = {2021}, author = {Rose, CJ}, title = {Germ lines and extended selection during the evolutionary transition to multicellularity.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {336}, number = {8}, pages = {680-686}, doi = {10.1002/jez.b.22985}, pmid = {32681710}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; *Germ Cells ; Life Cycle Stages ; Reproduction ; *Selection, Genetic ; }, abstract = {The major evolutionary transitions from unicellular organisms to multicellularity resulted in a profusion of complex life forms. During the transition from single cells to multicellular life, groups of cells acquired the capacity for reproduction as discrete units; however, the selective causes and underlying mechanisms remain debated. One perspective views the evolution of multicellularity as a shift in the timescale at which natural selection primarily operates-from that of individual cells to the timescale of reproducing groups of cells. Therefore, a distinguishing feature of multicellular reproduction, as opposed to simple growth of a multicellular collective, is that the capacity for reproduction must develop over a timescale that is greater than the reproductive timescale of a single cell. Here, I suggest that the emergence of specialized reproductive cells (the germ line) was an essential first stage of the evolutionary transition to multicellularity because it imposed the necessary "delay"-allowing natural selection to operate over the longer timescale of a multicellular life cycle, ultimately resulting in the evolution of complex multicellular organisms. This perspective highlights the possibility that the ubiquity of a germ-soma distinction among complex multicellular organisms reflects the fact that such life cycles, on first emergence, had the greatest propensity to participate in Darwinian evolution.}, } @article {pmid32677677, year = {2020}, author = {Nedelcu, AM}, title = {The evolution of multicellularity and cancer: views and paradigms.}, journal = {Biochemical Society transactions}, volume = {48}, number = {4}, pages = {1505-1518}, doi = {10.1042/BST20190992}, pmid = {32677677}, issn = {1470-8752}, mesh = {*Biological Evolution ; Humans ; Models, Biological ; Neoplasms/metabolism/*pathology ; Spheroids, Cellular/*metabolism ; Tumor Microenvironment ; }, abstract = {Conceptually and mechanistically, the evolution of multicellularity required the integration of single cells into new functionally, reproductively and evolutionary stable multicellular individuals. As part of this process, a change in levels of selection occurred, with selection at the multicellular level overriding selection at the cell level. The stability of multicellular individuals is dependent on a combination of mechanisms that supress within-group evolution, by both reducing the occurrence of somatic mutations as well as supressing somatic selection. Nevertheless, mutations that, in a particular microenvironment, confer mutant lineages a fitness advantage relative to normal somatic cells do occur, and can result in cancer. This minireview highlights several views and paradigms that relate the evolution of multicellularity to cancer. As a phenomenon, cancer is generally understood as a failure of multicellular systems to suppress somatic evolution. However, as a disease, cancer is interpreted in different frameworks: (i) a breakdown of cooperative behaviors underlying the evolution of multicellularity, (ii) a disruption of molecular networks established during the emergence of multicellularity to impose constraints on single-celled units, or (iii) an atavistic state resulting from reactivating primitive programs that originated in the earliest unicellular species. A number of assumptions are common in all the views relating cancer as a disease to the evolution of multicellularity. For instance, cancer is considered a reversal to unicellularity, and cancer cells are thought to both resemble unicellular organisms and benefit from ancestral-like traits. Nevertheless, potential limitations of current paradigms should be acknowledged as different perspectives can provide novel insights with potential therapeutic implications.}, } @article {pmid32664620, year = {2020}, author = {Bylino, OV and Ibragimov, AN and Shidlovskii, YV}, title = {Evolution of Regulated Transcription.}, journal = {Cells}, volume = {9}, number = {7}, pages = {}, pmid = {32664620}, issn = {2073-4409}, mesh = {Animals ; Enhancer Elements, Genetic ; *Evolution, Molecular ; *Gene Expression Regulation ; Genome Size ; Humans ; Models, Genetic ; *Transcription, Genetic ; }, abstract = {The genomes of all organisms abound with various cis-regulatory elements, which control gene activity. Transcriptional enhancers are a key group of such elements in eukaryotes and are DNA regions that form physical contacts with gene promoters and precisely orchestrate gene expression programs. Here, we follow gradual evolution of this regulatory system and discuss its features in different organisms. In eubacteria, an enhancer-like element is often a single regulatory element, is usually proximal to the core promoter, and is occupied by one or a few activators. Activation of gene expression in archaea is accompanied by the recruitment of an activator to several enhancer-like sites in the upstream promoter region. In eukaryotes, activation of expression is accompanied by the recruitment of activators to multiple enhancers, which may be distant from the core promoter, and the activators act through coactivators. The role of the general DNA architecture in transcription control increases in evolution. As a whole, it can be seen that enhancers of multicellular eukaryotes evolved from the corresponding prototypic enhancer-like regulatory elements with the gradually increasing genome size of organisms.}, } @article {pmid32659023, year = {2020}, author = {Begum, R and Saran, S}, title = {Glimpses of Dictyostelid research in India.}, journal = {The International journal of developmental biology}, volume = {64}, number = {1-2-3}, pages = {99-107}, doi = {10.1387/ijdb.190208ss}, pmid = {32659023}, issn = {1696-3547}, mesh = {Animals ; *Biological Evolution ; Biomedical Research/*trends ; Cell Differentiation ; Dictyostelium/*physiology ; *Gene Expression Regulation ; India ; Models, Biological ; *Morphogenesis ; }, abstract = {Simple organisms are preferred for understanding the molecular and cellular function(s) of complex processes. Dictyostelium discoideum is a lower eukaryote, a protist and a cellular slime mould, which has been in recent times used for various studies such as cell differentiation, development, cell death, stress responses etc. It is a soil amoeba (unicellular) that undertakes a remarkable, facultative shift to multicellularity when exposed to starvation and requires signal pathways that result in alteration of gene expression and finally show cell differentiation. The amoebae aggregate, differentiate and form fruiting bodies with two terminally differentiated cells: the dead stalk (non-viable) and dormant spores (viable). In India, starting from the isolation of Dictyostelium species to morphogenesis, cell signalling and social evolution has been studied with many more new research additions. Advances in molecular genetics make Dictyostelium an attractive model system to study cell biology, biochemistry, signal transduction and many more.}, } @article {pmid32658971, year = {2020}, author = {Helsen, J and Voordeckers, K and Vanderwaeren, L and Santermans, T and Tsontaki, M and Verstrepen, KJ and Jelier, R}, title = {Gene Loss Predictably Drives Evolutionary Adaptation.}, journal = {Molecular biology and evolution}, volume = {37}, number = {10}, pages = {2989-3002}, pmid = {32658971}, issn = {1537-1719}, mesh = {Adaptation, Biological/*genetics ; *Biological Evolution ; *Gene Deletion ; Gene Regulatory Networks ; *Genetic Fitness ; Oxidative Stress/genetics ; Saccharomyces cerevisiae ; }, abstract = {Loss of gene function is common throughout evolution, even though it often leads to reduced fitness. In this study, we systematically evaluated how an organism adapts after deleting genes that are important for growth under oxidative stress. By evolving, sequencing, and phenotyping over 200 yeast lineages, we found that gene loss can enhance an organism's capacity to evolve and adapt. Although gene loss often led to an immediate decrease in fitness, many mutants rapidly acquired suppressor mutations that restored fitness. Depending on the strain's genotype, some ultimately even attained higher fitness levels than similarly adapted wild-type cells. Further, cells with deletions in different modules of the genetic network followed distinct and predictable mutational trajectories. Finally, losing highly connected genes increased evolvability by facilitating the emergence of a more diverse array of phenotypes after adaptation. Together, our findings show that loss of specific parts of a genetic network can facilitate adaptation by opening alternative evolutionary paths.}, } @article {pmid32653903, year = {2020}, author = {Plachetzki, DC and Pankey, MS and MacManes, MD and Lesser, MP and Walker, CW}, title = {The Genome of the Softshell Clam Mya arenaria and the Evolution of Apoptosis.}, journal = {Genome biology and evolution}, volume = {12}, number = {10}, pages = {1681-1693}, pmid = {32653903}, issn = {1759-6653}, support = {R15 CA104112/CA/NCI NIH HHS/United States ; R35 GM128843/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/*genetics ; *Genes, p53 ; *Genome ; Mya/*genetics ; *Phylogeny ; }, abstract = {Apoptosis is a fundamental feature of multicellular animals and is best understood in mammals, flies, and nematodes, with the invertebrate models being thought to represent a condition of ancestral simplicity. However, the existence of a leukemia-like cancer in the softshell clam Mya arenaria provides an opportunity to re-evaluate the evolution of the genetic machinery of apoptosis. Here, we report the whole-genome sequence for M. arenaria which we leverage with existing data to test evolutionary hypotheses on the origins of apoptosis in animals. We show that the ancestral bilaterian p53 locus, a master regulator of apoptosis, possessed a complex domain structure, in contrast to that of extant ecdysozoan p53s. Further, ecdysozoan taxa, but not chordates or lophotrochozoans like M. arenaria, show a widespread reduction in apoptosis gene copy number. Finally, phylogenetic exploration of apoptosis gene copy number reveals a striking linkage with p53 domain complexity across species. Our results challenge the current understanding of the evolution of apoptosis and highlight the ancestral complexity of the bilaterian apoptotic tool kit and its subsequent dismantlement during the ecdysozoan radiation.}, } @article {pmid32651001, year = {2021}, author = {Picard, M and Sandi, C}, title = {The social nature of mitochondria: Implications for human health.}, journal = {Neuroscience and biobehavioral reviews}, volume = {120}, number = {}, pages = {595-610}, pmid = {32651001}, issn = {1873-7528}, support = {R01 MH119336/MH/NIMH NIH HHS/United States ; R01 MH122706/MH/NIMH NIH HHS/United States ; R35 GM119793/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Humans ; *Mitochondria ; Social Behavior ; }, abstract = {Sociality has profound evolutionary roots and is observed from unicellular organisms to multicellular animals. In line with the view that social principles apply across levels of biological complexity, a growing body of data highlights the remarkable social nature of mitochondria - life-sustaining endosymbiotic organelles with their own genome that populate the cell cytoplasm. Here, we draw from organizing principles of behavior in social organisms to reveal that similar to individuals among social networks, mitochondria communicate with each other and with the cell nucleus, exhibit group formation and interdependence, synchronize their behaviors, and functionally specialize to accomplish specific functions within the organism. Mitochondria are social organelles. The extension of social principles across levels of biological complexity is a theoretical shift that emphasizes the role of communication and interdependence in cell biology, physiology, and neuroscience. With the help of emerging computational methods capable of capturing complex dynamic behavioral patterns, the implementation of social concepts in mitochondrial biology may facilitate cross-talk across disciplines towards increasingly holistic and accurate models of human health.}, } @article {pmid32649861, year = {2020}, author = {Brunkard, JO}, title = {Exaptive Evolution of Target of Rapamycin Signaling in Multicellular Eukaryotes.}, journal = {Developmental cell}, volume = {54}, number = {2}, pages = {142-155}, pmid = {32649861}, issn = {1878-1551}, support = {DP5 OD023072/OD/NIH HHS/United States ; }, mesh = {Amino Acids/metabolism ; Animals ; Eukaryota/*drug effects/metabolism ; Signal Transduction/*drug effects/physiology ; Sirolimus/*pharmacology ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Target of rapamycin (TOR) is a protein kinase that coordinates metabolism with nutrient and energy availability in eukaryotes. TOR and its primary interactors, RAPTOR and LST8, have been remarkably evolutionarily static since they arose in the unicellular last common ancestor of plants, fungi, and animals, but the upstream regulatory mechanisms and downstream effectors of TOR signaling have evolved considerable diversity in these separate lineages. Here, I focus on the roles of exaptation and adaptation in the evolution of novel signaling axes in the TOR network in multicellular eukaryotes, concentrating especially on amino acid sensing, cell-cell signaling, and cell differentiation.}, } @article {pmid32643307, year = {2020}, author = {Rose, CJ and Hammerschmidt, K and Pichugin, Y and Rainey, PB}, title = {Meta-population structure and the evolutionary transition to multicellularity.}, journal = {Ecology letters}, volume = {23}, number = {9}, pages = {1380-1390}, doi = {10.1111/ele.13570}, pmid = {32643307}, issn = {1461-0248}, support = {//Marsden Fund Council from government funding administered by the Royal Society of New Zealand/ ; //Marsden Fund/ ; //Royal Society/ ; }, mesh = {Animals ; *Biological Evolution ; Life Cycle Stages ; Phenotype ; *Reproduction ; }, abstract = {The evolutionary transition to multicellularity has occurred on numerous occasions, but transitions to complex life forms are rare. Here, using experimental bacterial populations as proxies for nascent multicellular organisms, we manipulate ecological factors shaping the evolution of groups. Groups were propagated under regimes requiring reproduction via a life cycle replete with developmental and dispersal (propagule) phases, but in one treatment lineages never mixed, whereas in a second treatment, cells from different lineages experienced intense competition during the dispersal phase. The latter treatment favoured traits promoting cell growth at the expense of traits underlying group fitness - a finding that is supported by results from a mathematical model. Our results show that the transition to multicellularity benefits from ecological conditions that maintain discreteness not just of the group (soma) phase, but also of the dispersal (germline) phase.}, } @article {pmid32626570, year = {2020}, author = {Umen, JG}, title = {Volvox and volvocine green algae.}, journal = {EvoDevo}, volume = {11}, number = {}, pages = {13}, pmid = {32626570}, issn = {2041-9139}, abstract = {The transition of life from single cells to more complex multicellular forms has occurred at least two dozen times among eukaryotes and is one of the major evolutionary transitions, but the early steps that enabled multicellular life to evolve and thrive remain poorly understood. Volvocine green algae are a taxonomic group that is uniquely suited to investigating the step-wise acquisition of multicellular organization. The multicellular volvocine species Volvox carteri exhibits many hallmarks of complex multicellularity including complete germ-soma division of labor, asymmetric cell divisions, coordinated tissue-level morphogenesis, and dimorphic sexes-none of which have obvious analogs in its closest unicellular relative, the model alga Chlamydomonas reinhardtii. Here, I summarize some of the key questions and areas of study that are being addressed with Volvox carteri and how increasing genomic information and methodologies for volvocine algae are opening up the entire group as an integrated experimental system for exploring the evolution of multicellularity and more.}, } @article {pmid32617614, year = {2020}, author = {Seoighe, C and Kiniry, SJ and Peters, A and Baranov, PV and Yang, H}, title = {Selection Shapes Synonymous Stop Codon Use in Mammals.}, journal = {Journal of molecular evolution}, volume = {88}, number = {7}, pages = {549-561}, doi = {10.1007/s00239-020-09957-x}, pmid = {32617614}, issn = {1432-1432}, support = {210692/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Codon, Terminator ; *Evolution, Molecular ; Humans ; Mammals/*genetics ; *Models, Genetic ; Phylogeny ; }, abstract = {Phylogenetic models of the evolution of protein-coding sequences can provide insights into the selection pressures that have shaped them. In the application of these models synonymous nucleotide substitutions, which do not alter the encoded amino acid, are often assumed to have limited functional consequences and used as a proxy for the neutral rate of evolution. The ratio of nonsynonymous to synonymous substitution rates is then used to categorize the selective regime that applies to the protein (e.g., purifying selection, neutral evolution, diversifying selection). Here, we extend the Muse and Gaut model of codon evolution to explore the extent of purifying selection acting on substitutions between synonymous stop codons. Using a large collection of coding sequence alignments, we estimate that a high proportion (approximately 57%) of mammalian genes are affected by selection acting on stop codon preference. This proportion varies substantially by codon, with UGA stop codons far more likely to be conserved. Genes with evidence of selection acting on synonymous stop codons have distinctive characteristics, compared to unconserved genes with the same stop codon, including longer [Formula: see text] untranslated regions (UTRs) and shorter mRNA half-life. The coding regions of these genes are also much more likely to be under strong purifying selection pressure. Our results suggest that the preference for UGA stop codons found in many multicellular eukaryotes is selective rather than mutational in origin.}, } @article {pmid32603492, year = {2020}, author = {Liao, X and Wang, J and Zhu, S and Xie, Q and Wang, L and Yu, H and Ye, Z and Yang, C}, title = {Transcriptomic and functional analyses uncover the regulatory role of lncRNA000170 in tomato multicellular trichome formation.}, journal = {The Plant journal : for cell and molecular biology}, volume = {104}, number = {1}, pages = {18-29}, doi = {10.1111/tpj.14902}, pmid = {32603492}, issn = {1365-313X}, mesh = {Gene Expression Profiling ; Solanum lycopersicum/growth & development/*metabolism ; MicroRNAs/metabolism/physiology ; RNA, Long Noncoding/metabolism/*physiology ; RNA, Plant/metabolism/*physiology ; Trichomes/*genetics/metabolism ; }, abstract = {Trichomes are universal specific structures originating from nearly all terrestrial plants. Although quantities of long non-coding RNAs (lncRNAs) have been identified in many plant species, the role of lncRNAs in trichome formation still remains unknown. Here, we identified a total of 1303 lncRNAs in the young stems of woolly mutant LA3560 (Wo) and its non-woolly segregants (WT). Out of these lncRNAs, 86 lncRNAs were obviously upregulated in Wo and 110 lncRNAs were downregulated. We determined that seven lncRNAs were highly expressed in stem trichomes compared to trichome-free stems and several other tissues of LA3560 by a quantitative reverse transcriptase-polymerase chain reaction, including lncRNA000746, lncRNA000170, lncRNA000277, lncRNA000774, lncRNA000756, lncRNA000100, and lncRNA000898. Transgenic experiments revealed that overexpression of lncRNA000170 inhibited type I trichome formation on the lower stems of the adult transgenic plants. We further determined that lncRNA000170 was transcribed from the complementary strand of Solyc10g006360, for which expression can be induced by lncRNA000170 in its overexpression lines and woolly mutants. Solyc10g006360 overexpression also caused type I trichome decrease. In addition, several trichome regulators, such as Wo, H, SlCycB2, and SlCycB3, were markedly downregulated in lncRNA000170 overexpression lines. These findings demonstrate that lncRNA000170 may be involved in the regulatory pathway mediated by these trichome regulators.}, } @article {pmid32602227, year = {2020}, author = {Ryu, C and Walia, A and Ortiz, V and Perry, C and Woo, S and Reeves, BC and Sun, H and Winkler, J and Kanyo, JE and Wang, W and Vukmirovic, M and Ristic, N and Stratton, EA and Meena, SR and Minasyan, M and Kurbanov, D and Liu, X and Lam, TT and Farina, G and Gomez, JL and Gulati, M and Herzog, EL}, title = {Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma-Associated Interstitial Lung Disease.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {72}, number = {11}, pages = {1905-1915}, pmid = {32602227}, issn = {2326-5205}, support = {U01HL112702/HL/NHLBI NIH HHS/United States ; S10-OD-018034-01/HL/NHLBI NIH HHS/United States ; R01 HL152677/HL/NHLBI NIH HHS/United States ; K01-HL1-25474-03/HL/NHLBI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; R01 HL109233/HL/NHLBI NIH HHS/United States ; U01 HL112702/HL/NHLBI NIH HHS/United States ; R01-HL-109233/HL/NHLBI NIH HHS/United States ; R01-HL-125850/HL/NHLBI NIH HHS/United States ; K08 HL151970/HL/NHLBI NIH HHS/United States ; R01 HL153604/HL/NHLBI NIH HHS/United States ; R03 HL154275/HL/NHLBI NIH HHS/United States ; K01 HL125474/HL/NHLBI NIH HHS/United States ; R01 HL125850/HL/NHLBI NIH HHS/United States ; U01-HL-112702/HL/NHLBI NIH HHS/United States ; }, mesh = {Actins/metabolism ; Cytokines/metabolism ; DNA, Mitochondrial/*blood ; Disease Progression ; Female ; Fibroblasts/metabolism ; HEK293 Cells ; Humans ; Lung Diseases, Interstitial/*blood/etiology ; Male ; Scleroderma, Systemic/*blood/complications ; }, abstract = {OBJECTIVE: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterized by variable clinical outcomes, activation of innate immune pattern-recognition receptors (PRRs), and accumulation of α-smooth muscle actin (α-SMA)-expressing myofibroblasts. The aim of this study was to identify an association between these entities and mitochondrial DNA (mtDNA), an endogenous ligand for the intracellular DNA-sensing PRRs Toll-like receptor 9 (TLR-9) and cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING), which has yet to be determined.

METHODS: Human lung fibroblasts (HLFs) from normal donors and SSc-ILD explants were treated with synthetic CpG DNA and assayed for α-SMA expression and extracellular mtDNA using quantitative polymerase chain reaction for the human MT-ATP6 gene. Plasma MT-ATP6 concentrations were evaluated in 2 independent SSc-ILD cohorts and demographically matched controls. The ability of SSc-ILD and control plasma to induce TLR-9 and cGAS/STING activation was evaluated with commercially available HEK 293 reporter cells. Plasma concentrations of type I interferons (IFNs), interleukin-6 (IL-6), and oxidized DNA were measured using electrochemiluminescence and enzyme-linked immunosorbent assay-based methods. Extracellular vesicles (EVs) precipitated from plasma were evaluated for MT-ATP6 concentrations and proteomics via liquid chromatography mass spectrometry.

RESULTS: Normal HLFs and SSc-ILD fibroblasts developed increased α-SMA expression and MT-ATP6 release following CpG stimulation. Plasma mtDNA concentrations were increased in the 2 SSc-ILD cohorts, reflective of ventilatory decline, and were positively associated with both TLR-9 and cGAS/STING activation as well as type I IFN and IL-6 expression. Plasma mtDNA was not oxidized and was conveyed by EVs displaying a proteomics profile consistent with a multicellular origin.

CONCLUSION: These findings demonstrate a previously unrecognized connection between EV-encapsulated mtDNA, clinical outcomes, and intracellular DNA-sensing PRR activation in SSc-ILD. Further study of these interactions could catalyze novel mechanistic and therapeutic insights into SSc-ILD and related disorders.}, } @article {pmid32599749, year = {2020}, author = {Opalek, M and Wloch-Salamon, D}, title = {Aspects of Multicellularity in Saccharomyces cerevisiae Yeast: A Review of Evolutionary and Physiological Mechanisms.}, journal = {Genes}, volume = {11}, number = {6}, pages = {}, pmid = {32599749}, issn = {2073-4425}, mesh = {*Biological Evolution ; Phenotype ; Saccharomyces cerevisiae/*genetics ; }, abstract = {The evolutionary transition from single-celled to multicellular growth is a classic and intriguing problem in biology. Saccharomyces cerevisiae is a useful model to study questions regarding cell aggregation, heterogeneity and cooperation. In this review, we discuss scenarios of group formation and how this promotes facultative multicellularity in S. cerevisiae. We first describe proximate mechanisms leading to aggregation. These mechanisms include staying together and coming together, and can lead to group heterogeneity. Heterogeneity is promoted by nutrient limitation, structured environments and aging. We then characterize the evolutionary benefits and costs of facultative multicellularity in yeast. We summarize current knowledge and focus on the newest state-of-the-art discoveries that will fuel future research programmes aiming to understand facultative microbial multicellularity.}, } @article {pmid32592586, year = {2020}, author = {Lustofin, K and Świątek, P and Stolarczyk, P and Miranda, VFO and Płachno, BJ}, title = {Do food trichomes occur in Pinguicula (Lentibulariaceae) flowers?.}, journal = {Annals of botany}, volume = {126}, number = {6}, pages = {1039-1048}, pmid = {32592586}, issn = {1095-8290}, mesh = {Animals ; Bees ; *Flowers ; Phylogeny ; Pollination ; South America ; *Trichomes ; }, abstract = {BACKGROUND AND AIMS: Floral food bodies (including edible trichomes) are a form of floral reward for pollinators. This type of nutritive reward has been recorded in several angiosperm families: Annonaceae, Araceae, Calycanthaceae, Eupomatiaceae, Himantandraceae, Nymphaeaceae, Orchidaceae, Pandanaceae and Winteraceae. Although these bodies are very diverse in their structure, their cells contain food material: starch grains, protein bodies or lipid droplets. In Pinguicula flowers, there are numerous multicellular clavate trichomes. Previous authors have proposed that these trichomes in the Pinguicula flower play the role of 'futterhaare' ('feeding hairs') and are eaten by pollinators. The main aim of this study was to investigate whether the floral non-glandular trichomes of Pinguicula contain food reserves and thus are a reward for pollinators. The trichomes from the Pinguicula groups, which differ in their taxonomy (species from the subgenera: Temnoceras, Pinguicula and Isoloba) as well as the types of their pollinators (butterflies/flies and bees/hummingbirds), were examined. Thus, it was determined whether there are any connections between the occurrence of food trichomes and phylogeny position or pollination biology. Additionally, we determined the phylogenetic history of edible trichomes and pollinator evolution in the Pinguicula species.

METHODS: The species that were sampled were: Pinguicula moctezumae, P. esseriana, P. moranensis, P. emarginata, P. rectifolia, P. mesophytica, P. hemiepiphytica, P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia, P. gigantea, P. lusitanica, P. alpina and P. vulgaris. Light microscopy, histochemistry, and scanning and transmission electron microscopy were used to address our aims with a phylogenetic perspective based on matK/trnK DNA sequences.

KEY RESULTS: No accumulation of protein bodies or lipid droplets was recorded in the floral non-glandular trichomes of any of the analysed species. Starch grains occurred in the cells of the trichomes of the bee-/fly-pollinated species: P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia and P. gigantea, but not in P. alpina or P. vulgaris. Moreover, starch grains were not recorded in the cells of the trichomes of the Pinguicula species that have long spurs, which are pollinated by Lepidoptera (P. moctezumae, P. esseriana, P. moranensis, P. emarginata and P. rectifolia) or birds (P. mesophytica and P. hemiepihytica), or in species with a small and whitish corolla that self-pollinate (P. lusitanica). The results on the occurrence of edible trichomes and pollinator syndromes were mapped onto a phylogenetic reconstruction of the genus.

CONCLUSION: Floral non-glandular trichomes play the role of edible trichomes in some Pinguicula species (P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia and P. gigantea), which are mainly classified as bee-pollinated species that had originated from Central and South America. It seems that in the Pinguicula that are pollinated by other pollinator groups (Lepidoptera and hummingbirds), the non-glandular trichomes in the flowers play a role other than that of a floral reward for their pollinators. Edible trichomes are symplesiomorphic for the Pinguicula species, and thus do not support a monophyletic group such as a synapomorphy. Nevertheless, edible trichomes are derived and are possibly a specialization for fly and bee pollinators by acting as a food reward for these visitors.}, } @article {pmid32572049, year = {2020}, author = {Jacqueline, C and Parvy, JP and Rollin, ML and Faugère, D and Renaud, F and Missé, D and Thomas, F and Roche, B}, title = {The role of innate immunity in the protection conferred by a bacterial infection against cancer: study of an invertebrate model.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {10106}, pmid = {32572049}, issn = {2045-2322}, support = {C596/A17196/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Anti-Bacterial Agents/metabolism ; Antimicrobial Cationic Peptides/*metabolism ; Bacteria/genetics ; Bacterial Infections/metabolism ; Drosophila Proteins/metabolism/pharmacology ; Drosophila melanogaster ; Fungi/genetics ; Gene Expression/genetics ; Immunity, Innate/*physiology ; Invertebrates/genetics ; Larva/metabolism/microbiology ; Neoplasms/*immunology/prevention & control ; }, abstract = {All multicellular organisms are exposed to a diversity of infectious agents and to the emergence and proliferation of malignant cells. The protection conferred by some infections against cancer has been recently linked to the production of acquired immunity effectors such as antibodies. However, the evolution of innate immunity as a mechanism to prevent cancer and how it is jeopardized by infections remain poorly investigated. Here, we explored this question by performing experimental infections in two genetically modified invertebrate models (Drosophila melanogaster) that develop invasive or non-invasive neoplastic brain tumors. After quantifying tumor size and antimicrobial peptide gene expression, we found that Drosophila larvae infected with a naturally occurring bacterium had smaller tumors compared to controls and to fungus-infected larvae. This was associated with the upregulation of genes encoding two antimicrobial peptides-diptericin and drosomycin-that are known to be important mediators of tumor cell death. We further confirmed that tumor regression upon infection was associated with an increase in tumor cell death. Thus, our study suggests that infection could have a protective role through the production of antimicrobial peptides that increase tumor cell death. Finally, our study highlights the need to understand the role of innate immune effectors in the complex interactions between infections and cancer cell communities in order to develop innovative cancer treatment strategies.}, } @article {pmid32562277, year = {2021}, author = {Merle, NS and Singh, P and Rahman, J and Kemper, C}, title = {Integrins meet complement: The evolutionary tip of an iceberg orchestrating metabolism and immunity.}, journal = {British journal of pharmacology}, volume = {178}, number = {14}, pages = {2754-2770}, pmid = {32562277}, issn = {1476-5381}, support = {zia/hl006223//National Institutes of Health (NIH)/ ; }, mesh = {*Complement System Proteins ; Humans ; Immune System ; *Integrins ; }, abstract = {Immunologists have recently realized that there is more to the classic innate immune sensor systems than just mere protection against invading pathogens. It is becoming increasingly clear that such sensors, including the inflammasomes, toll-like receptors, and the complement system, are heavily involved in the regulation of basic cell physiological processes and particularly those of metabolic nature. In fact, their "non-canonical" activities make sense as no system directing immune cell activity can perform such task without the need for energy. Further, many of these ancient immune sensors appeared early and concurrently during evolution, particularly during the developmental leap from the single-cell organisms to multicellularity, and therefore crosstalk heavily with each other. Here, we will review the current knowledge about the emerging cooperation between the major inter-cell communicators, integrins, and the cell-autonomous intracellularly and autocrine-active complement, the complosome, during the regulation of single-cell metabolism. LINKED ARTICLES: This article is part of a themed issue on Canonical and non-canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc.}, } @article {pmid32535731, year = {2020}, author = {Hammarlund, EU and Amend, SR and Pienta, KJ}, title = {The issues with tissues: the wide range of cell fate separation enables the evolution of multicellularity and cancer.}, journal = {Medical oncology (Northwood, London, England)}, volume = {37}, number = {7}, pages = {62}, pmid = {32535731}, issn = {1559-131X}, support = {CA163124/CA/NCI NIH HHS/United States ; CA143055/CA/NCI NIH HHS/United States ; CA093900/CA/NCI NIH HHS/United States ; U54CA143803/CA/NCI NIH HHS/United States ; U01 CA143055/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Cell Differentiation/physiology ; Cell Plasticity/physiology ; Cell Survival/physiology ; Ecosystem ; Humans ; Neoplasms/genetics/metabolism/*pathology ; Selection, Genetic ; }, abstract = {Our understanding of the rises of animal and cancer multicellularity face the same conceptual hurdles: what makes the clade originate and what makes it diversify. Between the events of origination and diversification lies complex tissue organization that gave rise to novel functionality for organisms and, unfortunately, for malignant transformation in cells. Tissue specialization with distinctly separated cell fates allowed novel functionality at organism level, such as for vertebrate animals, but also involved trade-offs at the cellular level that are potentially disruptive. These trade-offs are under-appreciated and here we discuss how the wide separation of cell phenotypes may contribute to cancer evolution by (a) how factors can reverse differentiated cells into a window of phenotypic plasticity, (b) the reversal to phenotypic plasticity coupled with asexual reproduction occurs in a way that the host cannot adapt, and (c) the power of the transformation factor correlates to the power needed to reverse tissue specialization. The role of reversed cell fate separation for cancer evolution is strengthened by how some tissues and organisms maintain high cell proliferation and plasticity without developing tumours at a corresponding rate. This demonstrates a potential proliferation paradox that requires further explanation. These insights from the cancer field, which observes tissue evolution in real time and closer than any other field, allow inferences to be made on evolutionary events in animal history. If a sweet spot of phenotypic and reproductive versatility is key to transformation, factors stimulating cell fate separation may have promoted also animal diversification on Earth.}, } @article {pmid32529251, year = {2020}, author = {Buschmann, H and Holzinger, A}, title = {Understanding the algae to land plant transition.}, journal = {Journal of experimental botany}, volume = {71}, number = {11}, pages = {3241-3246}, doi = {10.1093/jxb/eraa196}, pmid = {32529251}, issn = {1460-2431}, mesh = {*Embryophyta ; Evolution, Molecular ; Phylogeny ; *Plants ; }, } @article {pmid32523039, year = {2020}, author = {Duraivelan, K and Samanta, D}, title = {Tracing the evolution of nectin and nectin-like cell adhesion molecules.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9434}, pmid = {32523039}, issn = {2045-2322}, mesh = {Animals ; Cell Adhesion/*genetics/physiology ; Cell Adhesion Molecules/*genetics/metabolism ; Cell Adhesion Molecules, Neuronal/genetics/metabolism ; Cell Line ; Computational Biology/methods ; Evolution, Molecular ; Humans ; Nectins/*genetics/metabolism ; }, abstract = {Nectin and nectin-like cell adhesion molecules (collectively referred as nectin family henceforth) are known to mediate cell-cell adhesion and related functions. While current literature suggests that nectins are prevalent in vertebrates, there are no in-depth analyses regarding the evolution of nectin family as a whole. In this work, we examine the evolutionary origin of the nectin family, using selected multicellular metazoans representing diverse clades whose whole genome sequencing data is available. Our results show that this family may have appeared earlier during metazoan evolution than previously believed. Systematic analyses indicate the order in which various members of nectin family seem to have evolved, with some nectin-like molecules appearing first, followed by the evolution of other members. Furthermore, we also found a few possible ancient homologues of nectins. While our study confirms the previous grouping of the nectin family into nectins and nectin-like molecules, it also shows poliovirus receptor (PVR/nectin-like-5) to possess characteristics that are intermediate between these two groups. Interestingly, except for PVR, the other nectins show surprising sequence conservations across species, suggesting evolutionary constraints due to critical roles played by these proteins.}, } @article {pmid32521019, year = {2020}, author = {Phansopa, C and Dunning, LT and Reid, JD and Christin, PA}, title = {Lateral Gene Transfer Acts As an Evolutionary Shortcut to Efficient C4 Biochemistry.}, journal = {Molecular biology and evolution}, volume = {37}, number = {11}, pages = {3094-3104}, pmid = {32521019}, issn = {1537-1719}, mesh = {Amino Acid Substitution ; *Biological Evolution ; *Gene Transfer, Horizontal ; Phosphoenolpyruvate Carboxylase/*genetics ; Photosynthesis/*genetics ; Poaceae/enzymology/*genetics ; }, abstract = {The adaptation of proteins for novel functions often requires changes in their kinetics via amino acid replacement. This process can require multiple mutations, and therefore extended periods of selection. The transfer of genes among distinct species might speed up the process, by providing proteins already adapted for the novel function. However, this hypothesis remains untested in multicellular eukaryotes. The grass Alloteropsis is an ideal system to test this hypothesis due to its diversity of genes encoding phosphoenolpyruvate carboxylase, an enzyme that catalyzes one of the key reactions in the C4 pathway. Different accessions of Alloteropsis either use native isoforms relatively recently co-opted from other functions or isoforms that were laterally acquired from distantly related species that evolved the C4 trait much earlier. By comparing the enzyme kinetics, we show that native isoforms with few amino acid replacements have substrate KM values similar to the non-C4 ancestral form, but exhibit marked increases in catalytic efficiency. The co-option of native isoforms was therefore followed by rapid catalytic improvements, which appear to rely on standing genetic variation observed within one species. Native C4 isoforms with more amino acid replacements exhibit additional changes in affinities, suggesting that the initial catalytic improvements are followed by gradual modifications. Finally, laterally acquired genes show both strong increases in catalytic efficiency and important changes in substrate handling. We conclude that the transfer of genes among distant species sharing the same physiological novelty creates an evolutionary shortcut toward more efficient enzymes, effectively accelerating evolution.}, } @article {pmid32517626, year = {2020}, author = {Laundon, D and Chrismas, N and Wheeler, G and Cunliffe, M}, title = {Chytrid rhizoid morphogenesis resembles hyphal development in multicellular fungi and is adaptive to resource availability.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1928}, pages = {20200433}, pmid = {32517626}, issn = {1471-2954}, mesh = {Chytridiomycota/*physiology ; Fungi ; Hyphae/*growth & development ; Morphogenesis ; }, abstract = {Key to the ecological prominence of fungi is their distinctive cell biology, our understanding of which has been principally based on dikaryan hyphal and yeast forms. The early-diverging Chytridiomycota (chytrids) are ecologically important and a significant component of fungal diversity, yet their cell biology remains poorly understood. Unlike dikaryan hyphae, chytrids typically attach to substrates and feed osmotrophically via anucleate rhizoids. The evolution of fungal hyphae appears to have occurred from rhizoid-bearing lineages and it has been hypothesized that a rhizoid-like structure was the precursor to multicellular hyphae. Here, we show in a unicellular chytrid, Rhizoclosmatium globosum, that rhizoid development exhibits striking similarities with dikaryan hyphae and is adaptive to resource availability. Rhizoid morphogenesis exhibits analogous patterns to hyphal growth and is controlled by β-glucan-dependent cell wall synthesis and actin polymerization. Chytrid rhizoids growing from individual cells also demonstrate adaptive morphological plasticity in response to resource availability, developing a searching phenotype when carbon starved and spatial differentiation when interacting with particulate organic matter. We demonstrate that the adaptive cell biology and associated developmental plasticity considered characteristic of hyphal fungi are shared more widely across the Kingdom Fungi and therefore could be conserved from their most recent common ancestor.}, } @article {pmid32514997, year = {2020}, author = {Villagra, C and Frías-Lasserre, D}, title = {Epigenetic Molecular Mechanisms in Insects.}, journal = {Neotropical entomology}, volume = {49}, number = {5}, pages = {615-642}, doi = {10.1007/s13744-020-00777-8}, pmid = {32514997}, issn = {1678-8052}, mesh = {*Adaptation, Physiological ; Animals ; *Epigenesis, Genetic ; Insecta/*genetics ; Life Cycle Stages ; Phenotype ; Social Behavior ; }, abstract = {Insects are the largest animal group on Earth both in biomass and diversity. Their outstanding success has inspired genetics and developmental research, allowing the discovery of dynamic process explaining extreme phenotypic plasticity and canalization. Epigenetic molecular mechanisms (EMMs) are vital for several housekeeping functions in multicellular organisms, regulating developmental, ontogenetic trajectories and environmental adaptations. In Insecta, EMMs are involved in the development of extreme phenotypic divergences such as polyphenisms and eusocial castes. Here, we review the history of this research field and how the main EMMs found in insects help to understand their biological processes and diversity. EMMs in insects confer them rapid response capacity allowing insect either to change with plastic divergence or to keep constant when facing different stressors or stimuli. EMMs function both at intra as well as transgenerational scales, playing important roles in insect ecology and evolution. We discuss on how EMMs pervasive influences in Insecta require not only the control of gene expression but also the dynamic interplay of EMMs with further regulatory levels, including genetic, physiological, behavioral, and environmental among others, as was earlier proposed by the Probabilistic Epigenesis model and Developmental System Theory.}, } @article {pmid32510705, year = {2020}, author = {Palmer, MA and Nelson, CM}, title = {Fusion of airways during avian lung development constitutes a novel mechanism for the formation of continuous lumena in multicellular epithelia.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {249}, number = {11}, pages = {1318-1333}, doi = {10.1002/dvdy.215}, pmid = {32510705}, issn = {1097-0177}, support = {CA187692/CA/NCI NIH HHS/United States ; HL110335/HL/NHLBI NIH HHS/United States ; HL118532/HL/NHLBI NIH HHS/United States ; HL120142/HL/NHLBI NIH HHS/United States ; CMMI-1435853//National Science Foundation/International ; //Camille & Henry Dreyfus Foundation/International ; //David & Lucile Packard Foundation/International ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Basement Membrane/cytology/*embryology ; Chick Embryo ; *Chickens ; Lung/cytology/*embryology ; Respiratory Mucosa/cytology/*embryology ; }, abstract = {BACKGROUND: During development of the avian lung, the initially terminally branched epithelial tree later forms a continuous network of airways. This occurs via a large-scale epithelial fusion event, wherein airways that originate proximally collide with those that originate distally to form one continuous lumen.

RESULTS: Here, we found that prior to fusion, the epithelium of the embryonic chicken lung undergoes a shape change to permit the initiation and extension of new branches which contain the cells that initiate contact. These changes in epithelial shape coincide with the differentiation of smooth muscle cells that wrap the airways. From these nascent epithelial branches, individual cells form cytoskeletal protrusions that extend toward and form a bridge with their target airway. Additional cells then join the fusion site, forming a bilayered epithelium. During this process, the basement membrane around the prefusion epithelium degrades and then reforms after fusion. The epithelial bilayer then undergoes apoptosis, clearing the path between the two lumens.

CONCLUSIONS: The process of airway epithelial fusion in the developing chicken lung constitutes a novel mechanism for the generation of complex multicellular tubes and suggests a conserved role for smooth muscle in the shaping of airway epithelia.}, } @article {pmid32505051, year = {2020}, author = {Oates, AC}, title = {Waiting on the Fringe: cell autonomy and signaling delays in segmentation clocks.}, journal = {Current opinion in genetics & development}, volume = {63}, number = {}, pages = {61-70}, doi = {10.1016/j.gde.2020.04.008}, pmid = {32505051}, issn = {1879-0380}, mesh = {Animals ; *Body Patterning ; *Embryonic Development ; Membrane Proteins/*metabolism ; *Models, Biological ; Signal Transduction ; Vertebrates/*physiology ; }, abstract = {The rhythmic and sequential segmentation of the vertebrate body axis into somites during embryogenesis is governed by a multicellular, oscillatory patterning system called the segmentation clock. Despite many overt similarities between vertebrates, differences in genetic and dynamic regulation have been reported, raising intriguing questions about the evolution and conservation of this fundamental patterning process. Recent studies have brought insights into two important and related issues: (1) whether individual cells of segmentation clocks are autonomous oscillators or require cell-cell communication for their rhythm; and (2) the role of delays in the cell-cell communication that synchronizes the population of genetic oscillators. Although molecular details differ between species, conservation may exist at the level of the dynamics, hinting at rules for evolutionary trajectories in the system.}, } @article {pmid32499560, year = {2020}, author = {Tang, M and Xie, Q and Gimple, RC and Zhong, Z and Tam, T and Tian, J and Kidwell, RL and Wu, Q and Prager, BC and Qiu, Z and Yu, A and Zhu, Z and Mesci, P and Jing, H and Schimelman, J and Wang, P and Lee, D and Lorenzini, MH and Dixit, D and Zhao, L and Bhargava, S and Miller, TE and Wan, X and Tang, J and Sun, B and Cravatt, BF and Muotri, AR and Chen, S and Rich, JN}, title = {Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions.}, journal = {Cell research}, volume = {30}, number = {10}, pages = {833-853}, pmid = {32499560}, issn = {1748-7838}, support = {R01 CA169117/CA/NCI NIH HHS/United States ; P30 NS047101/NS/NINDS NIH HHS/United States ; F30 CA217065/CA/NCI NIH HHS/United States ; R21 AR074763/AR/NIAMS NIH HHS/United States ; RC2 DK114785/DK/NIDDK NIH HHS/United States ; R01 CA238662/CA/NCI NIH HHS/United States ; F30 CA217066/CA/NCI NIH HHS/United States ; R01 CA171652/CA/NCI NIH HHS/United States ; R01 NS089272/NS/NINDS NIH HHS/United States ; R01 NS087913/NS/NINDS NIH HHS/United States ; U19 MH107367/MH/NIMH NIH HHS/United States ; R01 NS103434/NS/NINDS NIH HHS/United States ; R24 DK099810/DK/NIDDK NIH HHS/United States ; F31 CA243296/CA/NCI NIH HHS/United States ; R35 CA197718/CA/NCI NIH HHS/United States ; R33 HD090662/HD/NICHD NIH HHS/United States ; R01 EB021857/EB/NIBIB NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; R01 CA154130/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bioprinting ; Cell Line, Tumor ; Cell Proliferation ; Glioblastoma/*immunology ; Humans ; Mice ; Neural Stem Cells ; Tissue Scaffolds ; Tumor Microenvironment/*immunology ; }, abstract = {Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.}, } @article {pmid32496191, year = {2020}, author = {Booth, DS and King, N}, title = {Genome editing enables reverse genetics of multicellular development in the choanoflagellate Salpingoeca rosetta.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32496191}, issn = {2050-084X}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {CRISPR-Cas Systems ; Choanoflagellata/*genetics/*growth & development ; Gene Editing ; Genome, Protozoan ; Lectins, C-Type/genetics ; Protozoan Proteins/genetics ; Reverse Genetics/*methods ; }, abstract = {In a previous study, we established a forward genetic screen to identify genes required for multicellular development in the choanoflagellate, Salpingoeca rosetta (Levin et al., 2014). Yet, the paucity of reverse genetic tools for choanoflagellates has hampered direct tests of gene function and impeded the establishment of choanoflagellates as a model for reconstructing the origin of their closest living relatives, the animals. Here we establish CRISPR/Cas9-mediated genome editing in S. rosetta by engineering a selectable marker to enrich for edited cells. We then use genome editing to disrupt the coding sequence of a S. rosetta C-type lectin gene, rosetteless, and thereby demonstrate its necessity for multicellular rosette development. This work advances S. rosetta as a model system in which to investigate how genes identified from genetic screens and genomic surveys function in choanoflagellates and evolved as critical regulators of animal biology.}, } @article {pmid32491889, year = {2020}, author = {Nguyen, M and Shiferaw, Y}, title = {Feedback control of calcium driven alternans in cardiac myocytes.}, journal = {Chaos (Woodbury, N.Y.)}, volume = {30}, number = {5}, pages = {053106}, pmid = {32491889}, issn = {1089-7682}, support = {R01 HL119095/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Calcium Signaling/*physiology ; Feedback ; Glucans/antagonists & inhibitors ; Myocytes, Cardiac/*physiology ; Ventricular Fibrillation ; }, abstract = {Cardiac alternans is a beat-to-beat alternation of the action potential duration (APD), which has been implicated as a possible cause of ventricular fibrillation. Previous studies have shown that alternans can originate via a period doubling bifurcation caused by the nonlinear dependence of the APD on the previous diastolic interval. In this case, it has been demonstrated that alternans can be eliminated by applying feedback control on the pacing cycle length. However, studies have shown that alternans can also originate due to unstable calcium (Ca) cycling in cardiac myocytes. In this study, we explore the effectiveness of APD feedback control to suppress alternans when the underlying instability is due to unstable Ca cycling. In particular, we explore the role of the bi-directional coupling between Ca and voltage and determine the effectiveness of feedback control under a wide range of conditions. We also analyze the applicability of feedback control on a coupled two cell system and show that APD control induces spatially out-of-phase alternans. We analyze the onset and the necessary conditions for the emergence of these out-of-phase patterns and assess the effectiveness of feedback control to suppress Ca driven alternans in a multi-cellular system.}, } @article {pmid32472019, year = {2020}, author = {Lawal, HM and Schilde, C and Kin, K and Brown, MW and James, J and Prescott, AR and Schaap, P}, title = {Cold climate adaptation is a plausible cause for evolution of multicellular sporulation in Dictyostelia.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {8797}, pmid = {32472019}, issn = {2045-2322}, support = {100293/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; BB/K000799/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Acclimatization ; Biological Evolution ; Cold Climate ; Dictyostelium/*classification/*physiology ; Fossils/*parasitology ; Phylogeny ; Spores/physiology ; }, abstract = {Unicellular protozoa that encyst individually upon starvation evolved at least eight times into organisms that instead form multicellular fruiting bodies with spores. The Dictyostelia are the largest and most complex group of such organisms. They can be subdivided into 4 major groups, with many species in groups 1-3 having additionally retained encystment. To understand fitness differences between spores and cysts, we measured long-term survival of spores and cysts under climate-mimicking conditions, investigated spore and cyst ultrastructure, and related fitness characteristics to species ecology. We found that spores and cysts survived 22 °C equally well, but that spores survived wet and dry frost better than cysts, with group 4 spores being most resilient. Spore walls consist of three layers and those of cysts of maximally two, while spores were also more compacted than cysts, with group 4 spores being the most compacted. Group 4 species were frequently isolated from arctic and alpine zones, which was rarely the case for group 1-3 species. We inferred a fossil-calibrated phylogeny of Dictyostelia, which showed that its two major branches diverged 0.52 billion years ago, following several global glaciations. Our results suggest that Dictyostelium multicellular sporulation was a likely adaptation to a cold climate.}, } @article {pmid32471172, year = {2020}, author = {Demin, SI and Bogolyubov, DS and Granovitch, AI and Mikhailova, NA}, title = {New data on spermatogenic cyst formation and cellular composition of the testis in a marine gastropod, Littorina saxatilis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {11}, pages = {}, pmid = {32471172}, issn = {1422-0067}, support = {АААА-А17-117122790092-9//Russian Academy of Sciences/ ; 19-14-00321//Russian Science Support Foundation/ ; 0.40.491.2017//St. Petersburg State University/ ; }, mesh = {Animals ; Gastropoda/*cytology ; Male ; Spermatogonia/ultrastructure ; Testis/*cytology ; }, abstract = {Knowledge of the testis structure is important for gastropod taxonomy and phylogeny, particularly for the comparative analysis of sympatric Littorina species. Observing fresh tissue and squashing fixed tissue with gradually increasing pressure, we have recently described a peculiar type of cystic spermatogenesis, rare in mollusks. It has not been documented in most mollusks until now. The testis of adult males consists of numerous lobules filled with multicellular cysts containing germline cells at different stages of differentiation. Each cyst is formed by one cyst cell of somatic origin. Here, we provide evidence for the existence of two ways of cyst formation in Littorina saxatilis. One of them begins with a goniablast cyst formation; it somewhat resembles cyst formation in Drosophila testes. The second way begins with capture of a free spermatogonium by the polyploid cyst cell which is capable to move along the gonad tissues. This way of cyst formation has not been described previously. Our data expand the understanding of the diversity of spermatogenesis types in invertebrates.}, } @article {pmid32471018, year = {2020}, author = {Kuroiwa, A}, title = {Enhancers, development, and evolution.}, journal = {Development, growth & differentiation}, volume = {62}, number = {5}, pages = {265-268}, doi = {10.1111/dgd.12683}, pmid = {32471018}, issn = {1440-169X}, mesh = {Animals ; *Biological Evolution ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Germ Layers ; }, abstract = {A single-celled fertilized egg develops into a complex, multicellular animal through a series of selection processes of developmental pathways. During these processes, regulatory genes exhibit spatiotemporally restricted expression under the control of the species-specific genetic program, and dictate developmental processes from germ layer formation to cellular differentiation. Elucidation of molecular mechanisms underlying developmental processes and also of mechanistic bases for morphological diversification during evolution is one of the central issues in contemporary developmental biology. Progress has been made due to recent technological innovations, such as high-throughput nucleotide sequencing, live-cell imaging, efficient genetic manipulation, and establishment of the organoid system, opening new avenues to the above issues.}, } @article {pmid32463355, year = {2020}, author = {Kuncha, SK and Venkadasamy, VL and Amudhan, G and Dahate, P and Kola, SR and Pottabathini, S and Kruparani, SP and Shekar, PC and Sankaranarayanan, R}, title = {Genomic innovation of ATD alleviates mistranslation associated with multicellularity in Animalia.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32463355}, issn = {2050-084X}, support = {DST-INSPIRE//Department of Science and Technology, Ministry of Science and Technology/International ; J. C. Bose Fellowship//Science and Engineering Research Board/International ; Centre of Excellence//Department of Biotechnology , Ministry of Science and Technology/International ; Healthcare Theme project//Council of Scientific and Industrial Research/International ; Centre of Excellence//Department of Biotechnology, Ministry of Science and Technology/International ; }, mesh = {Amino Acyl-tRNA Synthetases/genetics/metabolism ; Animals ; Biological Evolution ; Cell Line ; Choanoflagellata/enzymology/genetics/metabolism ; Eukaryota/*enzymology/*genetics/metabolism ; Genome ; Genomics ; Humans ; Hydrolases/genetics/*metabolism ; Mice ; Oxidative Stress ; *Protein Biosynthesis ; RNA, Transfer/genetics/metabolism ; Threonine/metabolism ; }, abstract = {The emergence of multicellularity in Animalia is associated with increase in ROS and expansion of tRNA-isodecoders. tRNA expansion leads to misselection resulting in a critical error of L-Ala mischarged onto tRNA[Thr], which is proofread by Animalia-specific-tRNA Deacylase (ATD) in vitro. Here we show that in addition to ATD, threonyl-tRNA synthetase (ThrRS) can clear the error in cellular scenario. This two-tier functional redundancy for translation quality control breaks down during oxidative stress, wherein ThrRS is rendered inactive. Therefore, ATD knockout cells display pronounced sensitivity through increased mistranslation of threonine codons leading to cell death. Strikingly, we identify the emergence of ATD along with the error inducing tRNA species starting from Choanoflagellates thus uncovering an important genomic innovation required for multicellularity that occurred in unicellular ancestors of animals. The study further provides a plausible regulatory mechanism wherein the cellular fate of tRNAs can be switched from protein biosynthesis to non-canonical functions.}, } @article {pmid32462426, year = {2020}, author = {Casanova, JL and Abel, L}, title = {The human genetic determinism of life-threatening infectious diseases: genetic heterogeneity and physiological homogeneity?.}, journal = {Human genetics}, volume = {139}, number = {6-7}, pages = {681-694}, pmid = {32462426}, issn = {1432-1203}, support = {UL1 TR001866/TR/NCATS NIH HHS/United States ; R21 AI137371/AI/NIAID NIH HHS/United States ; R37 AI095983/AI/NIAID NIH HHS/United States ; R01 AI127564/AI/NIAID NIH HHS/United States ; R01 NS072381/NS/NINDS NIH HHS/United States ; U19 AI111143/AI/NIAID NIH HHS/United States ; R01 AI088364/AI/NIAID NIH HHS/United States ; P01 AI061093/AI/NIAID NIH HHS/United States ; }, mesh = {Communicable Diseases/*genetics/immunology/*pathology ; *Genetic Heterogeneity ; *Genetic Predisposition to Disease ; Humans ; Models, Genetic ; }, abstract = {Multicellular eukaryotes emerged late in evolution from an ocean of viruses, bacteria, archaea, and unicellular eukaryotes. These macroorganisms are exposed to and infected by a tremendous diversity of microorganisms. Those that are large enough can even be infected by multicellular fungi and parasites. Each interaction is unique, if only because it operates between two unique living organisms, in an infinite diversity of circumstances. This is neatly illustrated by the extraordinarily high level of interindividual clinical variability in human infections, even for a given pathogen, ranging from a total absence of clinical manifestations to death. We discuss here the idea that the determinism of human life-threatening infectious diseases can be governed by single-gene inborn errors of immunity, which are rarely Mendelian and frequently display incomplete penetrance. We briefly review the evidence in support of this notion obtained over the last two decades, referring to a number of focused and thorough reviews published by eminent colleagues in this issue of Human Genetics. It seems that almost any life-threatening infectious disease can be driven by at least one, and, perhaps, a great many diverse monogenic inborn errors, which may nonetheless be immunologically related. While the proportions of monogenic cases remain unknown, a picture in which genetic heterogeneity is combined with physiological homogeneity is emerging from these studies. A preliminary sketch of the human genetic architecture of severe infectious diseases is perhaps in sight.}, } @article {pmid32455487, year = {2020}, author = {Kumler, WE and Jorge, J and Kim, PM and Iftekhar, N and Koehl, MAR}, title = {Does Formation of Multicellular Colonies by Choanoflagellates Affect Their Susceptibility to Capture by Passive Protozoan Predators?.}, journal = {The Journal of eukaryotic microbiology}, volume = {67}, number = {5}, pages = {555-565}, doi = {10.1111/jeu.12808}, pmid = {32455487}, issn = {1550-7408}, mesh = {Choanoflagellata/*cytology ; *Food Chain ; Stramenopiles/*physiology ; }, abstract = {Microbial eukaryotes, critical links in aquatic food webs, are unicellular, but some, such as choanoflagellates, form multicellular colonies. Are there consequences to predator avoidance of being unicellular vs. forming larger colonies? Choanoflagellates share a common ancestor with animals and are used as model organisms to study the evolution of multicellularity. Escape in size from protozoan predators is suggested as a selective factor favoring evolution of multicellularity. Heterotrophic protozoans are categorized as suspension feeders, motile raptors, or passive predators that eat swimming prey which bump into them. We focused on passive predation and measured the mechanisms responsible for the susceptibility of unicellular vs. multicellular choanoflagellates, Salpingoeca helianthica, to capture by passive heliozoan predators, Actinosphaerium nucleofilum, which trap prey on axopodia radiating from the cell body. Microvideography showed that unicellular and colonial choanoflagellates entered the predator's capture zone at similar frequencies, but a greater proportion of colonies contacted axopodia. However, more colonies than single cells were lost during transport by axopodia to the cell body. Thus, feeding efficiency (proportion of prey entering the capture zone that were engulfed in phagosomes) was the same for unicellular and multicellular prey, suggesting that colony formation is not an effective defense against such passive predators.}, } @article {pmid32450967, year = {2020}, author = {McQueen, E and Rebeiz, M}, title = {On the specificity of gene regulatory networks: How does network co-option affect subsequent evolution?.}, journal = {Current topics in developmental biology}, volume = {139}, number = {}, pages = {375-405}, pmid = {32450967}, issn = {1557-8933}, support = {R01 GM112758/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Body Patterning/*genetics ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Humans ; Models, Genetic ; Organ Specificity/*genetics ; Regulatory Elements, Transcriptional/*genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {The process of multicellular organismal development hinges upon the specificity of developmental programs: for different parts of the organism to form unique features, processes must exist to specify each part. This specificity is thought to be hardwired into gene regulatory networks, which activate cohorts of genes in particular tissues at particular times during development. However, the evolution of gene regulatory networks sometimes occurs by mechanisms that sacrifice specificity. One such mechanism is network co-option, in which existing gene networks are redeployed in new developmental contexts. While network co-option may offer an efficient mechanism for generating novel phenotypes, losses of tissue specificity at redeployed network genes could restrict the ability of the affected traits to evolve independently. At present, there has not been a detailed discussion regarding how tissue specificity of network genes might be altered due to gene network co-option at its initiation, as well as how trait independence can be retained or restored after network co-option. A lack of clarity about network co-option makes it more difficult to speculate on the long-term evolutionary implications of this mechanism. In this review, we will discuss the possible initial outcomes of network co-option, outline the mechanisms by which networks may retain or subsequently regain specificity after network co-option, and comment on some of the possible evolutionary consequences of network co-option. We place special emphasis on the need to consider selectively-neutral outcomes of network co-option to improve our understanding of the role of this mechanism in trait evolution.}, } @article {pmid32444651, year = {2020}, author = {Heaton, LLM and Jones, NS and Fricker, MD}, title = {A mechanistic explanation of the transition to simple multicellularity in fungi.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {2594}, pmid = {32444651}, issn = {2041-1723}, mesh = {Carbon/metabolism ; Cytoplasm/metabolism ; Fungi/*cytology/growth & development/*physiology ; Hyphae/cytology/growth & development ; *Models, Biological ; Nitrogen/metabolism ; Phosphorus/metabolism ; }, abstract = {Development of multicellularity was one of the major transitions in evolution and occurred independently multiple times in algae, plants, animals, and fungi. However recent comparative genome analyses suggest that fungi followed a different route to other eukaryotic lineages. To understand the driving forces behind the transition from unicellular fungi to hyphal forms of growth, we develop a comparative model of osmotrophic resource acquisition. This predicts that whenever the local resource is immobile, hard-to-digest, and nutrient poor, hyphal osmotrophs outcompete motile or autolytic unicellular osmotrophs. This hyphal advantage arises because transporting nutrients via a contiguous cytoplasm enables continued exploitation of remaining resources after local depletion of essential nutrients, and more efficient use of costly exoenzymes. The model provides a mechanistic explanation for the origins of multicellular hyphal organisms, and explains why fungi, rather than unicellular bacteria, evolved to dominate decay of recalcitrant, nutrient poor substrates such as leaf litter or wood.}, } @article {pmid32438974, year = {2020}, author = {Yang, S and Qu, G and Fu, B and Yang, F and Zeng, W and Cai, Y and Ye, T and Yang, Y and Deng, X and Xiang, W and Peng, D and Zhou, B}, title = {The function of KptA/Tpt1 gene - a minor review.}, journal = {Functional plant biology : FPB}, volume = {47}, number = {7}, pages = {577-591}, doi = {10.1071/FP19159}, pmid = {32438974}, issn = {1445-4416}, mesh = {NAD ; Phosphotransferases (Alcohol Group Acceptor) ; RNA, Transfer ; Saccharomyces cerevisiae/genetics ; *Saccharomyces cerevisiae Proteins ; }, abstract = {Rapid response of uni- and multicellular organisms to environmental changes and their own growth is achieved through a series of molecular mechanisms, often involving modification of macromolecules, including nucleic acids, proteins and lipids. The ADP-ribosylation process has ability to modify these different macromolecules in cells, and is closely related to the biological processes, such as DNA replication, transcription, signal transduction, cell division, stress, microbial aging and pathogenesis. In addition, tRNA plays an essential role in the regulation of gene expression, as effector molecules, no-load tRNA affects the overall gene expression level of cells under some nutritional stress. KptA/Tpt1 is an essential phosphotransferase in the process of pre-tRNA splicing, releasing mature tRNA and participating in ADP-ribose. The objective of this review is concluding the gene structure, the evolution history and the function of KptA/Tpt1 from prokaryote to eukaryote organisms. At the same time, the results of promoter elements analysis were also shown in the present study. Moreover, the problems in the function of KptA/Tpt1 that have not been clarified at the present time are summarised, and some suggestions to solve those problems are given. This review presents no only a summary of clear function of KptA/Tpt1 in the process of tRNA splicing and ADP-ribosylation of organisms, but also gives some proposals to clarify unclear problems of it in the future.}, } @article {pmid32428501, year = {2020}, author = {Arendt, D}, title = {The Evolutionary Assembly of Neuronal Machinery.}, journal = {Current biology : CB}, volume = {30}, number = {10}, pages = {R603-R616}, doi = {10.1016/j.cub.2020.04.008}, pmid = {32428501}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; Neurons/*physiology ; Synapses/physiology ; Synaptic Transmission/*physiology ; }, abstract = {Neurons are highly specialized cells equipped with a sophisticated molecular machinery for the reception, integration, conduction and distribution of information. The evolutionary origin of neurons remains unsolved. How did novel and pre-existing proteins assemble into the complex machinery of the synapse and of the apparatus conducting current along the neuron? In this review, the step-wise assembly of functional modules in neuron evolution serves as a paradigm for the emergence and modification of molecular machinery in the evolution of cell types in multicellular organisms. The pre-synaptic machinery emerged through modification of calcium-regulated large vesicle release, while the postsynaptic machinery has different origins: the glutamatergic postsynapse originated through the fusion of a sensory signaling module and a module for filopodial outgrowth, while the GABAergic postsynapse incorporated an ancient actin regulatory module. The synaptic junction, in turn, is built around two adhesion modules controlled by phosphorylation, which resemble septate and adherens junctions. Finally, neuronal action potentials emerged via a series of duplications and modifications of voltage-gated ion channels. Based on these origins, key molecular innovations are identified that led to the birth of the first neuron in animal evolution.}, } @article {pmid32421773, year = {2020}, author = {Tollis, M and Schneider-Utaka, AK and Maley, CC}, title = {The Evolution of Human Cancer Gene Duplications across Mammals.}, journal = {Molecular biology and evolution}, volume = {37}, number = {10}, pages = {2875-2886}, pmid = {32421773}, issn = {1537-1719}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; U2C CA233254/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA149566/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Dosage ; *Gene Duplication ; *Genes, Neoplasm ; Humans ; *Life History Traits ; Longevity ; Mammals/*genetics ; Mole Rats/genetics ; }, abstract = {Cancer is caused by genetic alterations that affect cellular fitness, and multicellular organisms have evolved mechanisms to suppress cancer such as cell cycle checkpoints and apoptosis. These pathways may be enhanced by the addition of tumor suppressor gene paralogs or deletion of oncogenes. To provide insights to the evolution of cancer suppression across the mammalian radiation, we estimated copy numbers for 548 human tumor suppressor gene and oncogene homologs in 63 mammalian genome assemblies. The naked mole rat contained the most cancer gene copies, consistent with the extremely low rates of cancer found in this species. We found a positive correlation between a species' cancer gene copy number and its longevity, but not body size, contrary to predictions from Peto's Paradox. Extremely long-lived mammals also contained more copies of caretaker genes in their genomes, suggesting that the maintenance of genome integrity is an essential form of cancer prevention in long-lived species. We found the strongest association between longevity and copy numbers of genes that are both germline and somatic tumor suppressor genes, suggesting that selection has acted to suppress both hereditary and sporadic cancers. We also found a strong relationship between the number of tumor suppressor genes and the number of oncogenes in mammalian genomes, suggesting that complex regulatory networks mediate the balance between cell proliferation and checks on tumor progression. This study is the first to investigate cancer gene expansions across the mammalian radiation and provides a springboard for potential human therapies based on evolutionary medicine.}, } @article {pmid32415185, year = {2020}, author = {Hörandl, E and Hadacek, F}, title = {Oxygen, life forms, and the evolution of sexes in multicellular eukaryotes.}, journal = {Heredity}, volume = {125}, number = {1-2}, pages = {1-14}, pmid = {32415185}, issn = {1365-2540}, mesh = {Animals ; *Biological Evolution ; *Eukaryota ; Female ; Fungi/genetics ; Male ; Oxidative Stress ; *Oxygen ; Reproduction ; Sex Chromosomes ; Sexual Behavior, Animal ; }, abstract = {The evolutionary advantage of different sexual systems in multicellular eukaryotes is still not well understood, because the differentiation into male and female individuals halves offspring production compared with asexuality. Here we propose that various physiological adaptations to oxidative stress could have forged sessility versus motility, and consequently the evolution of sexual systems in multicellular animals, plants, and fungi. Photosynthesis causes substantial amounts of oxidative stress in photoautotrophic plants and, likewise, oxidative chemistry of polymer breakdown, cellulose and lignin, for saprotrophic fungi. In both cases, its extent precludes motility, an additional source of oxidative stress. Sessile life form and the lack of neuronal systems, however, limit options for mate recognition and adult sexual selection, resulting in inefficient mate-searching systems. Hence, sessility requires that all individuals can produce offspring, which is achieved by hermaphroditism in plants and/or by multiple mating types in fungi. In animals, motility requires neuronal systems, and muscle activity, both of which are highly sensitive to oxidative damage. As a consequence, motility has evolved in animals as heterotrophic organisms that (1) are not photosynthetically active, and (2) are not primary decomposers. Adaptations to motility provide prerequisites for an active mating behavior and efficient mate-searching systems. These benefits compensate for the "cost of males", and may explain the early evolution of sex chromosomes in metazoans. We conclude that different sexual systems evolved under the indirect physiological constraints of lifestyles.}, } @article {pmid32399193, year = {2020}, author = {Zardoya, R}, title = {Recent advances in understanding mitochondrial genome diversity.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {}, pmid = {32399193}, issn = {2046-1402}, mesh = {Animals ; *Evolution, Molecular ; Fungi/genetics ; *Genome, Mitochondrial ; Introns ; Mitochondria ; Plants/genetics ; RNA Editing ; }, abstract = {Ever since its discovery, the double-stranded DNA contained in the mitochondria of eukaryotes has fascinated researchers because of its bacterial endosymbiotic origin, crucial role in encoding subunits of the respiratory complexes, compact nature, and specific inheritance mechanisms. In the last few years, high-throughput sequencing techniques have accelerated the sequencing of mitochondrial genomes (mitogenomes) and uncovered the great diversity of organizations, gene contents, and modes of replication and transcription found in living eukaryotes. Some early divergent lineages of unicellular eukaryotes retain certain synteny and gene content resembling those observed in the genomes of alphaproteobacteria (the inferred closest living group of mitochondria), whereas others adapted to anaerobic environments have drastically reduced or even lost the mitogenome. In the three main multicellular lineages of eukaryotes, mitogenomes have pursued diverse evolutionary trajectories in which different types of molecules (circular versus linear and single versus multipartite), gene structures (with or without self-splicing introns), gene contents, gene orders, genetic codes, and transfer RNA editing mechanisms have been selected. Whereas animals have evolved a rather compact mitochondrial genome between 11 and 50 Kb in length with a highly conserved gene content in bilaterians, plants exhibit large mitochondrial genomes of 66 Kb to 11.3 Mb with large intergenic repetitions prone to recombination, and fungal mitogenomes have intermediate sizes of 12 to 236 Kb.}, } @article {pmid32355003, year = {2020}, author = {Lazzaro, BP and Zasloff, M and Rolff, J}, title = {Antimicrobial peptides: Application informed by evolution.}, journal = {Science (New York, N.Y.)}, volume = {368}, number = {6490}, pages = {}, pmid = {32355003}, issn = {1095-9203}, support = {R01 AI141385/AI/NIAID NIH HHS/United States ; /ERC_/European Research Council/International ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Antimicrobial Cationic Peptides/chemistry/*genetics/*pharmacology ; Drosophila Proteins/genetics/pharmacology ; *Drug Resistance, Bacterial ; Drug Synergism ; *Evolution, Molecular ; Humans ; Polymorphism, Genetic ; Translational Research, Biomedical ; }, abstract = {Antimicrobial peptides (AMPs) are essential components of immune defenses of multicellular organisms and are currently in development as anti-infective drugs. AMPs have been classically assumed to have broad-spectrum activity and simple kinetics, but recent evidence suggests an unexpected degree of specificity and a high capacity for synergies. Deeper evaluation of the molecular evolution and population genetics of AMP genes reveals more evidence for adaptive maintenance of polymorphism in AMP genes than has previously been appreciated, as well as adaptive loss of AMP activity. AMPs exhibit pharmacodynamic properties that reduce the evolution of resistance in target microbes, and AMPs may synergize with one another and with conventional antibiotics. Both of these properties make AMPs attractive for translational applications. However, if AMPs are to be used clinically, it is crucial to understand their natural biology in order to lessen the risk of collateral harm and avoid the crisis of resistance now facing conventional antibiotics.}, } @article {pmid32353148, year = {2020}, author = {Hoffman, SK and Seitz, KW and Havird, JC and Weese, DA and Santos, SR}, title = {Phenotypic Comparability from Genotypic Variability among Physically Structured Microbial Consortia.}, journal = {Integrative and comparative biology}, volume = {60}, number = {2}, pages = {288-303}, doi = {10.1093/icb/icaa022}, pmid = {32353148}, issn = {1557-7023}, mesh = {Bacteria/*genetics ; Cyanobacteria/genetics ; *Genotype ; Hawaii ; Microbial Consortia/*genetics ; *Phenotype ; }, abstract = {Microbiomes represent the collective bacteria, archaea, protist, fungi, and virus communities living in or on individual organisms that are typically multicellular eukaryotes. Such consortia have become recognized as having significant impacts on the development, health, and disease status of their hosts. Since understanding the mechanistic connections between an individual's genetic makeup and their complete set of traits (i.e., genome to phenome) requires consideration at different levels of biological organization, this should include interactions with, and the organization of, microbial consortia. To understand microbial consortia organization, we elucidated the genetic constituents among phenotypically similar (and hypothesized functionally-analogous) layers (i.e., top orange, second orange, pink, and green layers) in the unique laminated orange cyanobacterial-bacterial crusts endemic to Hawaii's anchialine ecosystem. High-throughput amplicon sequencing of ribosomal RNA hypervariable regions (i.e., Bacteria-specific V6 and Eukarya-biased V9) revealed microbial richness increasing by crust layer depth, with samples of a given layer more similar to different layers from the same geographic site than to their phenotypically-analogous layer from different sites. Furthermore, samples from sites on the same island were more similar to each other, regardless of which layer they originated from, than to analogous layers from another island. However, cyanobacterial and algal taxa were abundant in all surface and bottom layers, with anaerobic and chemoautotrophic taxa concentrated in the middle two layers, suggesting crust oxygenation from both above and below. Thus, the arrangement of oxygenated vs. anoxygenated niches in these orange crusts is functionally distinct relative to other laminated cyanobacterial-bacterial communities examined to date, with convergent evolution due to similar environmental conditions a likely driver for these phenotypically comparable but genetically distinct microbial consortia.}, } @article {pmid32330159, year = {2020}, author = {Safdari, H and Kalirad, A and Picioreanu, C and Tusserkani, R and Goliaei, B and Sadeghi, M}, title = {Noise-driven cell differentiation and the emergence of spatiotemporal patterns.}, journal = {PloS one}, volume = {15}, number = {4}, pages = {e0232060}, pmid = {32330159}, issn = {1932-6203}, mesh = {Adaptation, Biological/*physiology ; Animals ; Artifacts ; *Biodiversity ; *Biological Evolution ; Cell Differentiation/physiology ; Cell Lineage/physiology ; Humans ; Models, Biological ; Models, Theoretical ; Phenotype ; Spatio-Temporal Analysis ; }, abstract = {The emergence of phenotypic diversity in a population of cells and their arrangement in space and time is one of the most fascinating features of living systems. In fact, understanding multicellularity is unthinkable without explaining the proximate and the ultimate causes of cell differentiation in time and space. Simpler forms of cell differentiation can be found in unicellular organisms, such as bacterial biofilm, where reversible cell differentiation results in phenotypically diverse populations. In this manuscript, we attempt to start with the simple case of reversible nongenetic phenotypic to construct a model of differentiation and pattern formation. Our model, which we refer to as noise-driven differentiation (NDD) model, is an attempt to consider the prevalence of noise in biological systems, alongside what is known about genetic switches and signaling, to create a simple model which generates spatiotemporal patterns from bottom-up. Our simulations indicate that the presence of noise in cells can lead to reversible differentiation and the addition of signaling can create spatiotemporal pattern.}, } @article {pmid32315081, year = {2020}, author = {Rainey, L and Deevi, RK and McClements, J and Khawaja, H and Watson, CJ and Roudier, M and Van Schaeybroeck, S and Campbell, FC}, title = {Fundamental control of grade-specific colorectal cancer morphology by Src regulation of ezrin-centrosome engagement.}, journal = {The Journal of pathology}, volume = {251}, number = {3}, pages = {310-322}, doi = {10.1002/path.5452}, pmid = {32315081}, issn = {1096-9896}, support = {MR/L015110/1/MRC_/Medical Research Council/United Kingdom ; L015110/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Caco-2 Cells ; Centrosome/*enzymology/pathology ; Colorectal Neoplasms/*enzymology/genetics/pathology ; Cytoskeletal Proteins/genetics/*metabolism ; Focal Adhesion Kinase 1/genetics/metabolism ; HCT116 Cells ; Humans ; *Mitosis ; Neoplasm Grading ; PTEN Phosphohydrolase/genetics/metabolism ; Signal Transduction ; src-Family Kinases/genetics/*metabolism ; }, abstract = {The phenotypic spectrum of colorectal cancer (CRC) is remarkably diverse, with seemingly endless variations in cell shape, mitotic figures and multicellular configurations. Despite this morphological complexity, histological grading of collective phenotype patterns provides robust prognostic stratification in CRC. Although mechanistic understanding is incomplete, previous studies have shown that the cortical protein ezrin controls diversification of cell shape, mitotic figure geometry and multicellular architecture, in 3D organotypic CRC cultures. Because ezrin is a substrate of Src tyrosine kinase that is frequently overexpressed in CRC, we investigated Src regulation of ezrin and morphogenic growth in 3D CRC cultures. Here we show that Src perturbations disrupt CRC epithelial spatial organisation. Aberrant Src activity suppresses formation of the cortical ezrin cap that anchors interphase centrosomes. In CRC cells with a normal centrosome number, these events lead to mitotic spindle misorientation, perturbation of cell cleavage, abnormal epithelial stratification, apical membrane misalignment, multilumen formation and evolution of cribriform multicellular morphology, a feature of low-grade cancer. In isogenic CRC cells with centrosome amplification, aberrant Src signalling promotes multipolar mitotic spindle formation, pleomorphism and morphological features of high-grade cancer. Translational studies in archival human CRC revealed associations between Src intensity, multipolar mitotic spindle frequency and high-grade cancer morphology. Collectively, our study reveals Src regulation of CRC morphogenic growth via ezrin-centrosome engagement and uncovers combined perturbations underlying transition to high-grade CRC morphology. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.}, } @article {pmid32305342, year = {2020}, author = {Friedman, DA and Johnson, BR and Linksvayer, TA}, title = {Distributed physiology and the molecular basis of social life in eusocial insects.}, journal = {Hormones and behavior}, volume = {122}, number = {}, pages = {104757}, doi = {10.1016/j.yhbeh.2020.104757}, pmid = {32305342}, issn = {1095-6867}, mesh = {Animals ; Ants/genetics/physiology ; Bees/genetics/physiology ; Behavior, Animal/*physiology ; Biological Evolution ; Cooperative Behavior ; Genome, Insect/*physiology ; Insecta/*genetics/*physiology ; Isoptera/genetics/physiology ; Nesting Behavior/physiology ; Phenotype ; *Social Behavior ; }, abstract = {The traditional focus of physiological and functional genomic research is on molecular processes that play out within a single multicellular organism. In the colonial (eusocial) insects such as ants, bees, and termites, molecular and behavioral responses of interacting nestmates are tightly linked, and key physiological processes are regulated at the scale of the colony. Such colony-level physiological processes regulate nestmate physiology in a distributed fashion, through various social communication mechanisms. As a result of physiological decentralization over evolutionary time, organismal mechanisms, for example related to pheromone detection, hormone signaling, and neural signaling pathways, are deployed in novel contexts to influence nestmate and colony traits. Here we explore how functional genomic, physiological, and behavioral studies can benefit from considering the traits of eusocial insects in this light. We highlight functional genomic work exploring how nestmate-level and colony-level traits arise and are influenced by interactions among physiologically-specialized nestmates of various developmental stages. We also consider similarities and differences between nestmate-level (organismal) and colony-level (superorganismal) physiological processes, and make specific hypotheses regarding the physiology of eusocial taxa. Integrating theoretical models of distributed systems with empirical functional genomics approaches will be useful in addressing fundamental questions related to the evolution of eusociality and collective behavior in natural systems.}, } @article {pmid32301582, year = {2020}, author = {Naranjo-Ortiz, MA and Gabaldón, T}, title = {Fungal evolution: cellular, genomic and metabolic complexity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {95}, number = {5}, pages = {1198-1232}, pmid = {32301582}, issn = {1469-185X}, support = {PT17/0009/0023 - ISCIII-SGEFI/ERDF//INB Grant/International ; H2020-MSCA-IF-2017-793699//Marie Sklodowska-Curie/International ; ERC-2016-724173//European Union's Horizon 2020/International ; SGR423//Catalan Research Agency (AGAUR)/International ; //CERCA Programme/Generalitat de Catalunya/International ; //European Regional Development Fund/International ; //Spanish Ministry of Science and Innovation/International ; }, mesh = {Adaptation, Physiological ; Animals ; *Fungi/genetics ; *Genome, Fungal ; Genomics ; Plants/genetics ; }, abstract = {The question of how phenotypic and genomic complexity are inter-related and how they are shaped through evolution is a central question in biology that historically has been approached from the perspective of animals and plants. In recent years, however, fungi have emerged as a promising alternative system to address such questions. Key to their ecological success, fungi present a broad and diverse range of phenotypic traits. Fungal cells can adopt many different shapes, often within a single species, providing them with great adaptive potential. Fungal cellular organizations span from unicellular forms to complex, macroscopic multicellularity, with multiple transitions to higher or lower levels of cellular complexity occurring throughout the evolutionary history of fungi. Similarly, fungal genomes are very diverse in their architecture. Deep changes in genome organization can occur very quickly, and these phenomena are known to mediate rapid adaptations to environmental changes. Finally, the biochemical complexity of fungi is huge, particularly with regard to their secondary metabolites, chemical products that mediate many aspects of fungal biology, including ecological interactions. Herein, we explore how the interplay of these cellular, genomic and metabolic traits mediates the emergence of complex phenotypes, and how this complexity is shaped throughout the evolutionary history of Fungi.}, } @article {pmid32290841, year = {2020}, author = {Gao, F and Cai, Y and Kapranov, P and Xu, D}, title = {Reverse-genetics studies of lncRNAs-what we have learnt and paths forward.}, journal = {Genome biology}, volume = {21}, number = {1}, pages = {93}, pmid = {32290841}, issn = {1474-760X}, mesh = {Animals ; Evolution, Molecular ; Phenotype ; RNA, Long Noncoding/*physiology ; Reverse Genetics ; Vertebrates/genetics ; }, abstract = {Long non-coding RNAs (lncRNAs) represent a major fraction of the transcriptome in multicellular organisms. Although a handful of well-studied lncRNAs are broadly recognized as biologically meaningful, the fraction of such transcripts out of the entire collection of lncRNAs remains a subject of vigorous debate. Here we review the evidence for and against biological functionalities of lncRNAs and attempt to arrive at potential modes of lncRNA functionality that would reconcile the contradictory conclusions. Finally, we discuss different strategies of phenotypic analyses that could be used to investigate such modes of lncRNA functionality.}, } @article {pmid32285363, year = {2020}, author = {Low, LA and Sutherland, M and Lumelsky, N and Selimovic, S and Lundberg, MS and Tagle, DA}, title = {Organs-on-a-Chip.}, journal = {Advances in experimental medicine and biology}, volume = {1230}, number = {}, pages = {27-42}, doi = {10.1007/978-3-030-36588-2_3}, pmid = {32285363}, issn = {0065-2598}, mesh = {Animals ; Drug Development ; Drug Discovery ; Humans ; *Lab-On-A-Chip Devices ; *Tissue Array Analysis ; }, abstract = {Organs-on-chips, also known as "tissue chips" or microphysiological systems (MPS), are bioengineered microsystems capable of recreating aspects of human organ physiology and function and are in vitro tools with multiple applications in drug discovery and development. The ability to recapitulate human and animal tissues in physiologically relevant three-dimensional, multi-cellular environments allows applications in the drug development field, including; (1) use in assessing the safety and toxicity testing of potential therapeutics during early-stage preclinical drug development; (2) confirmation of drug/therapeutic efficacy in vitro; and (3) disease modeling of human tissues to recapitulate pathophysiology within specific subpopulations and even individuals, thereby advancing precision medicine efforts. This chapter will discuss the development and evolution of three-dimensional organ models over the past decade, and some of the opportunities offered by MPS technology that are not available through current standard two-dimensional cell cultures, or three-dimensional organoid systems. This chapter will outline future avenues of research in the MPS field, how cutting-edge biotechnology advances are expanding the applications for these systems, and discuss the current and future potential and challenges remaining for the field to address.}, } @article {pmid32284424, year = {2020}, author = {Fouchard, J and Wyatt, TPJ and Proag, A and Lisica, A and Khalilgharibi, N and Recho, P and Suzanne, M and Kabla, A and Charras, G}, title = {Curling of epithelial monolayers reveals coupling between active bending and tissue tension.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {17}, pages = {9377-9383}, pmid = {32284424}, issn = {1091-6490}, support = {BB/M003280/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M002578/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Biomechanical Phenomena ; Cell Adhesion ; Cell Line ; Dogs ; Elasticity ; Epithelium/*physiology ; Stress, Mechanical ; }, abstract = {Epithelial monolayers are two-dimensional cell sheets which compartmentalize the body and organs of multicellular organisms. Their morphogenesis during development or pathology results from patterned endogenous and exogenous forces and their interplay with tissue mechanical properties. In particular, bending of epithelia is thought to result from active torques generated by the polarization of myosin motors along their apicobasal axis. However, the contribution of these out-of-plane forces to morphogenesis remains challenging to evaluate because of the lack of direct mechanical measurement. Here we use epithelial curling to characterize the out-of-plane mechanics of epithelial monolayers. We find that curls of high curvature form spontaneously at the free edge of epithelial monolayers devoid of substrate in vivo and in vitro. Curling originates from an enrichment of myosin in the basal domain that generates an active spontaneous curvature. By measuring the force necessary to flatten curls, we can then estimate the active torques and the bending modulus of the tissue. Finally, we show that the extent of curling is controlled by the interplay between in-plane and out-of-plane stresses in the monolayer. Such mechanical coupling emphasizes a possible role for in-plane stresses in shaping epithelia during morphogenesis.}, } @article {pmid32283732, year = {2020}, author = {Annenkova, NV and Giner, CR and Logares, R}, title = {Tracing the Origin of Planktonic Protists in an Ancient Lake.}, journal = {Microorganisms}, volume = {8}, number = {4}, pages = {}, pmid = {32283732}, issn = {2076-2607}, support = {18-74-00054//Russian Science Foundation/ ; 0345-2016-0009//Russian state assignment/ ; RYC-2013-12554//Ministerio de Economía y Competitividad/ ; }, abstract = {Ancient lakes are among the most interesting models for evolution studies because their biodiversity is the result of a complex combination of migration and speciation. Here, we investigate the origin of single celled planktonic eukaryotes from the oldest lake in the world-Lake Baikal (Russia). By using 18S rDNA metabarcoding, we recovered 1414 Operational Taxonomic Units (OTUs) belonging to protists populating surface waters (1-50 m) and representing pico/nano-sized cells. The recovered communities resembled other lacustrine freshwater assemblages found elsewhere, especially the taxonomically unclassified protists. However, our results suggest that a fraction of Baikal protists could belong to glacial relicts and have close relationships with marine/brackish species. Moreover, our results suggest that rapid radiation may have occurred among some protist taxa, partially mirroring what was already shown for multicellular organisms in Lake Baikal. We found 16% of the OTUs belonging to potential species flocks in Stramenopiles, Alveolata, Opisthokonta, Archaeplastida, Rhizaria, and Hacrobia. Putative flocks predominated in Chrysophytes, which are highly diverse in Lake Baikal. Also, the 18S rDNA of a number of species (7% of the total) differed >10% from other known sequences. These taxa as well as those belonging to the flocks may be endemic to Lake Baikal. Overall, our study points to novel diversity of planktonic protists in Lake Baikal, some of which may have emerged in situ after evolutionary diversification.}, } @article {pmid32282832, year = {2020}, author = {Brun-Usan, M and Thies, C and Watson, RA}, title = {How to fit in: The learning principles of cell differentiation.}, journal = {PLoS computational biology}, volume = {16}, number = {4}, pages = {e1006811}, pmid = {32282832}, issn = {1553-7358}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Biological Evolution ; *Cell Differentiation ; Computer Simulation ; Developmental Biology/*methods ; Environment ; Gene Regulatory Networks ; Genetic Variation ; Learning ; Models, Biological ; Phenotype ; Selection, Genetic ; }, abstract = {Cell differentiation in multicellular organisms requires cells to respond to complex combinations of extracellular cues, such as morphogen concentrations. Some models of phenotypic plasticity conceptualise the response as a relatively simple function of a single environmental cues (e.g. a linear function of one cue), which facilitates rigorous analysis. Conversely, more mechanistic models such those implementing GRNs allows for a more general class of response functions but makes analysis more difficult. Therefore, a general theory describing how cells integrate multi-dimensional signals is lacking. In this work, we propose a theoretical framework for understanding the relationships between environmental cues (inputs) and phenotypic responses (outputs) underlying cell plasticity. We describe the relationship between environment and cell phenotype using logical functions, making the evolution of cell plasticity equivalent to a simple categorisation learning task. This abstraction allows us to apply principles derived from learning theory to understand the evolution of multi-dimensional plasticity. Our results show that natural selection is capable of discovering adaptive forms of cell plasticity associated with complex logical functions. However, developmental dynamics cause simpler functions to evolve more readily than complex ones. By using conceptual tools derived from learning theory we show that this developmental bias can be interpreted as a learning bias in the acquisition of plasticity functions. Because of that bias, the evolution of plasticity enables cells, under some circumstances, to display appropriate plastic responses to environmental conditions that they have not experienced in their evolutionary past. This is possible when the selective environment mirrors the bias of the developmental dynamics favouring the acquisition of simple plasticity functions-an example of the necessary conditions for generalisation in learning systems. These results illustrate the functional parallelisms between learning in neural networks and the action of natural selection on environmentally sensitive gene regulatory networks. This offers a theoretical framework for the evolution of plastic responses that integrate information from multiple cues, a phenomenon that underpins the evolution of multicellularity and developmental robustness.}, } @article {pmid32278076, year = {2020}, author = {Hehenberger, E and Eitel, M and Fortunato, SAV and Miller, DJ and Keeling, PJ and Cahill, MA}, title = {Early eukaryotic origins and metazoan elaboration of MAPR family proteins.}, journal = {Molecular phylogenetics and evolution}, volume = {148}, number = {}, pages = {106814}, doi = {10.1016/j.ympev.2020.106814}, pmid = {32278076}, issn = {1095-9513}, mesh = {Amino Acid Sequence ; Animals ; Eukaryota/*metabolism ; Evolution, Molecular ; Membrane Proteins/chemistry/*metabolism ; Phylogeny ; Protein Binding ; Protein Domains ; Receptors, Progesterone/chemistry/genetics/*metabolism ; }, abstract = {The membrane-associated progesterone receptor (MAPR) family consists of heme-binding proteins containing a cytochrome b5 (cytb5) domain characterized by the presence of a MAPR-specific interhelical insert region (MIHIR) between helices 3 and 4 of the canonical cytb5-domain fold. Animals possess three MAPR genes (PGRMC-like, Neuferricin and Neudesin). Here we show that all three animal MAPR genes were already present in the common ancestor of the opisthokonts (comprising animals and fungi as well as related single-celled taxa). All three MAPR genes acquired extensions C-terminal to the cytb5 domain, either before or with the evolution of animals. The archetypical MAPR protein, progesterone receptor membrane component 1 (PGRMC1), contains phosphorylated tyrosines Y139 and Y180. The combination of Y139/Y180 appeared in the common ancestor of cnidarians and bilaterians, along with an early embryological organizer and synapsed neurons, and is strongly conserved in all bilaterian animals. A predicted protein interaction motif in the PGRMC1 MIHIR is potentially regulated by Y139 phosphorylation. A multilayered model of animal MAPR function acquisition includes some pre-metazoan functions (e.g., heme binding and cytochrome P450 interactions) and some acquired animal-specific functions that involve regulation of strongly conserved protein interaction motifs acquired by animals (Metazoa). This study provides a conceptual framework for future studies, against which especially PGRMC1's multiple functions can perhaps be stratified and functionally dissected.}, } @article {pmid32272915, year = {2020}, author = {Tikhonenkov, DV and Hehenberger, E and Esaulov, AS and Belyakova, OI and Mazei, YA and Mylnikov, AP and Keeling, PJ}, title = {Insights into the origin of metazoan multicellularity from predatory unicellular relatives of animals.}, journal = {BMC biology}, volume = {18}, number = {1}, pages = {39}, pmid = {32272915}, issn = {1741-7007}, support = {18-14-00239//Russian Science Foundation/International ; 227301//Natural Sciences and Engineering Research Council of Canada (CA)/International ; }, mesh = {Animals ; *Biological Evolution ; Eukaryota/*physiology ; Evolution, Molecular ; Invertebrates/*physiology ; Phylogeny ; Predatory Behavior ; }, abstract = {BACKGROUND: The origin of animals from their unicellular ancestor was one of the most important events in evolutionary history, but the nature and the order of events leading up to the emergence of multicellular animals are still highly uncertain. The diversity and biology of unicellular relatives of animals have strongly informed our understanding of the transition from single-celled organisms to the multicellular Metazoa. Here, we analyze the cellular structures and complex life cycles of the novel unicellular holozoans Pigoraptor and Syssomonas (Opisthokonta), and their implications for the origin of animals.

RESULTS: Syssomonas and Pigoraptor are characterized by complex life cycles with a variety of cell types including flagellates, amoeboflagellates, amoeboid non-flagellar cells, and spherical cysts. The life cycles also include the formation of multicellular aggregations and syncytium-like structures, and an unusual diet for single-celled opisthokonts (partial cell fusion and joint sucking of a large eukaryotic prey), all of which provide new insights into the origin of multicellularity in Metazoa. Several existing models explaining the origin of multicellular animals have been put forward, but these data are interestingly consistent with one, the "synzoospore hypothesis."

CONCLUSIONS: The feeding modes of the ancestral metazoan may have been more complex than previously thought, including not only bacterial prey, but also larger eukaryotic cells and organic structures. The ability to feed on large eukaryotic prey could have been a powerful trigger in the formation and development of both aggregative (e.g., joint feeding, which also implies signaling) and clonal (e.g., hypertrophic growth followed by palintomy) multicellular stages that played important roles in the emergence of multicellular animals.}, } @article {pmid32260425, year = {2020}, author = {Simeone, P and Bologna, G and Lanuti, P and Pierdomenico, L and Guagnano, MT and Pieragostino, D and Del Boccio, P and Vergara, D and Marchisio, M and Miscia, S and Mariani-Costantini, R}, title = {Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers.}, journal = {International journal of molecular sciences}, volume = {21}, number = {7}, pages = {}, pmid = {32260425}, issn = {1422-0067}, mesh = {Biomarkers/*metabolism ; Cell Communication ; Disease/*genetics ; Extracellular Vesicles/genetics/*metabolism ; Genetic Predisposition to Disease ; Humans ; Immunity ; Signal Transduction ; }, abstract = {Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.}, } @article {pmid32253306, year = {2020}, author = {Shao, S and Koh, M and Schultz, PG}, title = {Expanding the genetic code of the human hematopoietic system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {16}, pages = {8845-8849}, pmid = {32253306}, issn = {1091-6490}, support = {R01 GM132071/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acids/*genetics ; Animals ; Cell Differentiation/*genetics ; Fetal Blood/cytology ; Gene Transfer Techniques ; Genetic Code ; Genetic Vectors/*genetics ; HEK293 Cells ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*physiology ; Herpesvirus 4, Human/genetics ; Humans ; Mice ; Mice, Inbred NOD ; Plasmids/genetics ; Primary Cell Culture/methods ; Protein Engineering/*methods ; Transfection/methods ; Transplantation Chimera ; Transplantation, Heterologous/methods ; }, abstract = {The genetic incorporation of noncanonical amino acids (ncAAs) into proteins has been realized in bacteria, yeast, and mammalian cells, and recently, in multicellular organisms including plants and animals. However, the addition of new building blocks to the genetic code of tissues from human origin has not yet been achieved. To this end, we report a self-replicating Epstein-Barr virus-based episomal vector for the long-term encoding of ncAAs in human hematopoietic stem cells and reconstitution of this genetically engineered hematopoietic system in mice.}, } @article {pmid32251406, year = {2020}, author = {Kazer, SW and Aicher, TP and Muema, DM and Carroll, SL and Ordovas-Montanes, J and Miao, VN and Tu, AA and Ziegler, CGK and Nyquist, SK and Wong, EB and Ismail, N and Dong, M and Moodley, A and Berger, B and Love, JC and Dong, KL and Leslie, A and Ndhlovu, ZM and Ndung'u, T and Walker, BD and Shalek, AK}, title = {Integrated single-cell analysis of multicellular immune dynamics during hyperacute HIV-1 infection.}, journal = {Nature medicine}, volume = {26}, number = {4}, pages = {511-518}, pmid = {32251406}, issn = {1546-170X}, support = {UM1 AI100663/AI/NIAID NIH HHS/United States ; 107752/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; R01 AI138546/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; P01 AI039671/AI/NIAID NIH HHS/United States ; R01 AI145305/AI/NIAID NIH HHS/United States ; T32 GM008313/GM/NIGMS NIH HHS/United States ; U19 AI089992/AI/NIAID NIH HHS/United States ; P30 AI060354/AI/NIAID NIH HHS/United States ; RM1 HG006193/HG/NHGRI NIH HHS/United States ; R01 HL095791/HL/NHLBI NIH HHS/United States ; 210662/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; UM1 AI144462/AI/NIAID NIH HHS/United States ; R01 AI118544/AI/NIAID NIH HHS/United States ; R01 HL134539/HL/NHLBI NIH HHS/United States ; K08 AI118538/AI/NIAID NIH HHS/United States ; R37 AI067073/AI/NIAID NIH HHS/United States ; U24 AI118672/AI/NIAID NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; U54 CA217377/CA/NCI NIH HHS/United States ; R01 DA046277/DA/NIDA NIH HHS/United States ; }, mesh = {Acute Disease ; Acute-Phase Reaction/genetics/immunology/pathology ; Adolescent ; Adult ; *Cell Communication/genetics/immunology ; Female ; Gene Expression Profiling ; Gene Regulatory Networks/immunology ; HIV Infections/*genetics/*immunology/pathology ; HIV-1/genetics/pathogenicity ; Humans ; Immunity, Cellular/*physiology ; Killer Cells, Natural/immunology/metabolism ; Leukocytes, Mononuclear/metabolism/pathology ; Longitudinal Studies ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/*methods ; Systems Integration ; T-Lymphocytes, Cytotoxic/immunology/metabolism ; Viral Load/genetics/immunology ; Young Adult ; }, abstract = {Cellular immunity is critical for controlling intracellular pathogens, but individual cellular dynamics and cell-cell cooperativity in evolving human immune responses remain poorly understood. Single-cell RNA-sequencing (scRNA-seq) represents a powerful tool for dissecting complex multicellular behaviors in health and disease[1,2] and nominating testable therapeutic targets[3]. Its application to longitudinal samples could afford an opportunity to uncover cellular factors associated with the evolution of disease progression without potentially confounding inter-individual variability[4]. Here, we present an experimental and computational methodology that uses scRNA-seq to characterize dynamic cellular programs and their molecular drivers, and apply it to HIV infection. By performing scRNA-seq on peripheral blood mononuclear cells from four untreated individuals before and longitudinally during acute infection[5], we were powered within each to discover gene response modules that vary by time and cell subset. Beyond previously unappreciated individual- and cell-type-specific interferon-stimulated gene upregulation, we describe temporally aligned gene expression responses obscured in bulk analyses, including those involved in proinflammatory T cell differentiation, prolonged monocyte major histocompatibility complex II upregulation and persistent natural killer (NK) cell cytolytic killing. We further identify response features arising in the first weeks of infection, for example proliferating natural killer cells, which potentially may associate with future viral control. Overall, our approach provides a unified framework for characterizing multiple dynamic cellular responses and their coordination.}, } @article {pmid32234827, year = {2020}, author = {Pienta, KJ and Hammarlund, EU and Axelrod, R and Amend, SR and Brown, JS}, title = {Convergent Evolution, Evolving Evolvability, and the Origins of Lethal Cancer.}, journal = {Molecular cancer research : MCR}, volume = {18}, number = {6}, pages = {801-810}, pmid = {32234827}, issn = {1557-3125}, support = {U01 CA196390/CA/NCI NIH HHS/United States ; U54 CA143803/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; U54 CA143970/CA/NCI NIH HHS/United States ; U54 CA163124/CA/NCI NIH HHS/United States ; P01 CA093900/CA/NCI NIH HHS/United States ; U01 CA143055/CA/NCI NIH HHS/United States ; U54 CA210173/CA/NCI NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; *Genetic Variation ; Humans ; *Mutation ; Neoplasms/*genetics/*pathology ; *Selection, Genetic ; }, abstract = {Advances in curative treatment to remove the primary tumor have increased survival of localized cancers for most solid tumor types, yet cancers that have spread are typically incurable and account for >90% of cancer-related deaths. Metastatic disease remains incurable because, somehow, tumors evolve resistance to all known compounds, including therapies. In all of these incurable patients, de novo lethal cancer evolves capacities for both metastasis and resistance. Therefore, cancers in different patients appear to follow the same eco-evolutionary path that independently manifests in affected patients. This convergent outcome, that always includes the ability to metastasize and exhibit resistance, demands an explanation beyond the slow and steady accrual of stochastic mutations. The common denominator may be that cancer starts as a speciation event when a unicellular protist breaks away from its multicellular host and initiates a cancer clade within the patient. As the cancer cells speciate and diversify further, some evolve the capacity to evolve: evolvability. Evolvability becomes a heritable trait that influences the available variation of other phenotypes that can then be acted upon by natural selection. Evolving evolvability may be an adaptation for cancer cells. By generating and maintaining considerable heritable variation, the cancer clade can, with high certainty, serendipitously produce cells resistant to therapy and cells capable of metastasizing. Understanding that cancer cells can swiftly evolve responses to novel and varied stressors create opportunities for adaptive therapy, double-bind therapies, and extinction therapies; all involving strategic decision making that steers and anticipates the convergent coevolutionary responses of the cancers.}, } @article {pmid32234519, year = {2020}, author = {Nelson, WJ}, title = {The Glue that Binds Us: The Hunt for the Molecular Basis for Multicellularity.}, journal = {Cell}, volume = {181}, number = {3}, pages = {495-497}, doi = {10.1016/j.cell.2020.03.017}, pmid = {32234519}, issn = {1097-4172}, mesh = {Animals ; Awards and Prizes ; Biophysical Phenomena ; Cadherins/*metabolism/*physiology ; Canada ; Cell Adhesion/physiology ; Cell Communication/*physiology ; History, 20th Century ; History, 21st Century ; Homeostasis/physiology ; Humans ; Male ; }, abstract = {This year's Canada Gairdner International Prize is shared by Rolf Kemler and Masatoshi Takeichi for the discovery of the cadherin family of Ca[2+]-dependent cell-cell adhesion proteins, which play essential roles in animal evolution, tissue development, and homeostasis, and are disrupted in human cancers.}, } @article {pmid32224105, year = {2020}, author = {Mikhailovsky, G and Gordon, R}, title = {Shuffling type of biological evolution based on horizontal gene transfer and the biosphere gene pool hypothesis.}, journal = {Bio Systems}, volume = {193-194}, number = {}, pages = {104131}, doi = {10.1016/j.biosystems.2020.104131}, pmid = {32224105}, issn = {1872-8324}, mesh = {*Biological Evolution ; DNA Shuffling/*methods ; Eukaryota/genetics ; *Evolution, Molecular ; *Gene Pool ; Gene Transfer, Horizontal/*genetics ; Prokaryotic Cells/physiology ; }, abstract = {Widespread horizontal gene transfer (HGT) may appear a significant factor that accelerates biological evolution. Here we look at HGT primarily from the point of view of prokaryote clones, which we take as the descendants of a single cell, all of whom have exactly the same nucleotide sequence. Any novelty that emerges as a random mutation, creating a new clone, could either disappear before its first HGT, or survive for a period and be transferred to another clone. Due to the chain character of HGT, each gene with an adaptive mutation is thus spread among numerous existing clones, creating further new clones in the process. This makes propagation far faster than elimination, and such genes become practically immortal and form a kind of "biosphere gene pool" (BGP). Not all of these genes exist in every clone, and moreover not all of them are expressed. A significant fraction of the BGP includes of genes repressed by regulatory genes. However, these genes express often enough to be subject to natural selection. In a changing environment, both repressed and expressed genes, after transferring to another clone, may prove useful in an alternative environment, and this will give rise to new clones. This mechanism for testing repressed genes for adaptability can be thought as a "shuffle of a deck of genes" by analogy with shuffling a deck of cards. In the Archean and Proterozoic eons, both BGP and the operational part of each genome were rather poor, and the probability of incorporation of randomly expressed genes into the operational part of each genome was very small. Accordingly, biological evolution during these eons was slow due to rare adaptive mutations. This explains why the realm of prokaryotes as the sole organisms on Earth lasted so long. However, over about 3.5 billion years before the Phanerozoic eon, the BGP gradually accumulated a huge number of genes. Each of them was useful in a certain environment of past eras. We suggest that multicellular eukaryotes that appeared at the end of the Proterozoic eon could shuffle these genes accumulated in BGP via HGT from prokaryotes that live in these multicellular organisms. Perhaps this was the cause of the "Cambrian explosion" and the high (and increasing) rate of evolution in the Phanerozoic eon compared with the Archean and Proterozoic.}, } @article {pmid32220299, year = {2020}, author = {Aich, M and Chakraborty, D}, title = {Role of lncRNAs in stem cell maintenance and differentiation.}, journal = {Current topics in developmental biology}, volume = {138}, number = {}, pages = {73-112}, doi = {10.1016/bs.ctdb.2019.11.003}, pmid = {32220299}, issn = {1557-8933}, mesh = {Animals ; Cell Differentiation ; Cell Proliferation ; Embryonic Stem Cells/cytology/*physiology ; *Gene Expression Regulation, Developmental ; Humans ; Pluripotent Stem Cells/cytology/*physiology ; Promoter Regions, Genetic ; RNA, Long Noncoding/genetics/*metabolism ; Regulatory Sequences, Nucleic Acid ; }, abstract = {Embryonic Stem cells are widely studied to elucidate the disease and developmental processes because of their capability to differentiate into cells of any lineage, Pervasive transcription is a distinct feature of all multicellular organisms and genomic elements such as enhancers and bidirectional or unidirectional promoters regulate these processes. Thousands of loci in each species produce a class of transcripts called noncoding RNAs (ncRNAs), that are well known for their influential regulatory roles in multiple biological processes including stem cell pluripotency and differentiation. The number of lncRNA species increases in more complex organisms highlighting the importance of RNA-based control in the evolution of multicellular organisms. Over the past decade, numerous studies have shed light on lncRNA biogenesis and functional significance in the cell and the organism. In this review, we focus primarily on lncRNAs affecting the stem cell state and developmental pathways.}, } @article {pmid32198827, year = {2021}, author = {Koehl, MAR}, title = {Selective factors in the evolution of multicellularity in choanoflagellates.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {336}, number = {3}, pages = {315-326}, doi = {10.1002/jez.b.22941}, pmid = {32198827}, issn = {1552-5015}, mesh = {Animals ; Bacteria ; Behavior, Animal ; *Biological Evolution ; Choanoflagellata/*growth & development/*physiology ; Predatory Behavior ; }, abstract = {Choanoflagellates, unicellular eukaryotes that can form multicellular colonies by cell division and that share a common ancestor with animals, are used as a model system to study functional consequences of being unicellular versus colonial. This review examines performance differences between unicellular and multicellular choanoflagellates in swimming, feeding, and avoiding predation, to provide insights about possible selective advantages of being multicellular for the protozoan ancestors of animals. Each choanoflagellate cell propels water by beating a single flagellum and captures bacterial prey on a collar of microvilli around the flagellum. Formation of multicellular colonies does not improve the swimming performance, but the flux of prey-bearing water to the collars of some of the cells in colonies of certain configurations can be greater than for single cells. Colony geometry appears to affect whether cells in colonies catch more prey per cell per time than do unicellular choanoflagellates. Although multicellular choanoflagellates show chemokinetic behavior in response to oxygen, only the unicellular dispersal stage (fast swimmers without collars) use pH signals to aggregate in locations where bacterial prey might be abundant. Colonies produce larger hydrodynamic signals than do single cells, and raptorial protozoan predators capture colonies while ignoring single cells. In contrast, ciliate predators entrain both single cells and colonies in their feeding currents, but reject larger colonies, whereas passive heliozoan predators show no preference. Thus, the ability of choanoflagellate cells to differentiate into different morphotypes, including multicellular forms, in response to variable aquatic environments might have provided a selective advantage to the ancestors of animals.}, } @article {pmid32191693, year = {2020}, author = {Rossine, FW and Martinez-Garcia, R and Sgro, AE and Gregor, T and Tarnita, CE}, title = {Eco-evolutionary significance of "loners".}, journal = {PLoS biology}, volume = {18}, number = {3}, pages = {e3000642}, pmid = {32191693}, issn = {1545-7885}, support = {F32 GM103062/GM/NIGMS NIH HHS/United States ; K25 GM098875/GM/NIGMS NIH HHS/United States ; P50 GM071508/GM/NIGMS NIH HHS/United States ; R01 GM098407/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Dictyostelium/growth & development/*physiology ; Models, Biological ; Quorum Sensing ; Spatio-Temporal Analysis ; Stochastic Processes ; }, abstract = {Loners-individuals out of sync with a coordinated majority-occur frequently in nature. Are loners incidental byproducts of large-scale coordination attempts, or are they part of a mosaic of life-history strategies? Here, we provide empirical evidence of naturally occurring heritable variation in loner behavior in the model social amoeba Dictyostelium discoideum. We propose that Dictyostelium loners-cells that do not join the multicellular life stage-arise from a dynamic population-partitioning process, the result of each cell making a stochastic, signal-based decision. We find evidence that this imperfectly synchronized multicellular development is affected by both abiotic (environmental porosity) and biotic (signaling) factors. Finally, we predict theoretically that when a pair of strains differing in their partitioning behavior coaggregate, cross-signaling impacts slime-mold diversity across spatiotemporal scales. Our findings suggest that loners could be critical to understanding collective and social behaviors, multicellular development, and ecological dynamics in D. discoideum. More broadly, across taxa, imperfect coordination of collective behaviors might be adaptive by enabling diversification of life-history strategies.}, } @article {pmid32191325, year = {2020}, author = {Merényi, Z and Prasanna, AN and Wang, Z and Kovács, K and Hegedüs, B and Bálint, B and Papp, B and Townsend, JP and Nagy, LG}, title = {Unmatched Level of Molecular Convergence among Deeply Divergent Complex Multicellular Fungi.}, journal = {Molecular biology and evolution}, volume = {37}, number = {8}, pages = {2228-2240}, pmid = {32191325}, issn = {1537-1719}, support = {758161/ERC_/European Research Council/International ; }, mesh = {Ascomycota/*genetics ; Basidiomycota/*genetics ; *Biological Evolution ; Fruiting Bodies, Fungal/*genetics ; Gene Expression Regulation, Developmental ; Multigene Family ; }, abstract = {Convergent evolution is pervasive in nature, but it is poorly understood how various constraints and natural selection limit the diversity of evolvable phenotypes. Here, we analyze the transcriptome across fruiting body development to understand the independent evolution of complex multicellularity in the two largest clades of fungi-the Agarico- and Pezizomycotina. Despite >650 My of divergence between these clades, we find that very similar sets of genes have convergently been co-opted for complex multicellularity, followed by expansions of their gene families by duplications. Over 82% of shared multicellularity-related gene families were expanding in both clades, indicating a high prevalence of convergence also at the gene family level. This convergence is coupled with a rich inferred repertoire of multicellularity-related genes in the most recent common ancestor of the Agarico- and Pezizomycotina, consistent with the hypothesis that the coding capacity of ancestral fungal genomes might have promoted the repeated evolution of complex multicellularity. We interpret this repertoire as an indication of evolutionary predisposition of fungal ancestors for evolving complex multicellular fruiting bodies. Our work suggests that evolutionary convergence may happen not only when organisms are closely related or are under similar selection pressures, but also when ancestral genomic repertoires render certain evolutionary trajectories more likely than others, even across large phylogenetic distances.}, } @article {pmid32188079, year = {2020}, author = {Gura, C and Rogers, SO}, title = {Metatranscriptomic and Metagenomic Analysis of Biological Diversity in Subglacial Lake Vostok (Antarctica).}, journal = {Biology}, volume = {9}, number = {3}, pages = {}, pmid = {32188079}, issn = {2079-7737}, support = {ANT-0536870//National Science Foundation/ ; }, abstract = {A combined metatranscriptomic and metagenomic study of Vostok (Antarctica) ice core sections from glacial, basal, and lake water accretion ice yielded sequences that indicated a wide variety of species and possible conditions at the base of the glacier and in subglacial Lake Vostok. Few organisms were in common among the basal ice and accretion ice samples, suggesting little transmission of viable organisms from the basal ice meltwater into the lake water. Additionally, samples of accretion ice, each of which originated from water in several locations of the shallow embayment, exhibit only small amounts of mixing of species. The western-most portion of the embayment had very low numbers of organisms, likely due to biologically challenging conditions. Increasing numbers of organisms were found progressing from west to east, up to approximately 7 km into the embayment. At that point, the numbers of unique sequences and sequence reads from thermophilic, thermotolerant, psychrophilic, and psychrotolerant organisms increased dramatically, as did sequences from alkaliphilic, alkalitolerant, acidophilic, and acidotolerant sequences. The number of unique and total sequences were positively associated with increases in concentrations of Na[+], Ca[2+], Mg[2+], SO4[2-], Cl[-], total amino acids, and non-purgeable organic carbon. The numbers of unique sequences from organisms reported from soil, sediment, ice, aquatic, marine, animal, and plant (probably pollen) sources also peaked in this region, suggesting that this was the most biologically active region. The confluence of the high numbers of organisms, physiologies, and metabolic capabilities suggests the presence of energy and nutrient sources in the eastern half of the embayment. Data from the main basin suggested a cold oligotrophic environment containing fewer organisms. In addition to bacteria, both the basal ice and accretion ice contained sequences from a diverse assemblage of eukaryotes, as well as from bacteria that are known to be associated with multicellular eukaryotes.}, } @article {pmid32168362, year = {2020}, author = {Morgan, MD and Patin, E and Jagla, B and Hasan, M and Quintana-Murci, L and Marioni, JC}, title = {Quantitative genetic analysis deciphers the impact of cis and trans regulation on cell-to-cell variability in protein expression levels.}, journal = {PLoS genetics}, volume = {16}, number = {3}, pages = {e1008686}, pmid = {32168362}, issn = {1553-7404}, support = {17197/CRUK_/Cancer Research UK/United Kingdom ; /DH_/Department of Health/United Kingdom ; MR/M008975/1/MRC_/Medical Research Council/United Kingdom ; 105045/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; 22231/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Alleles ; Databases, Genetic ; Female ; Gene Expression/*genetics ; Gene Expression Profiling/methods ; Gene Expression Regulation/*genetics ; Genetic Testing/methods ; Genome-Wide Association Study/methods ; Humans ; Immune System/metabolism ; Immunity/genetics ; Male ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci/genetics ; Selection, Genetic/genetics ; }, abstract = {Identifying the factors that shape protein expression variability in complex multi-cellular organisms has primarily focused on promoter architecture and regulation of single-cell expression in cis. However, this targeted approach has to date been unable to identify major regulators of cell-to-cell gene expression variability in humans. To address this, we have combined single-cell protein expression measurements in the human immune system using flow cytometry with a quantitative genetics analysis. For the majority of proteins whose variability in expression has a heritable component, we find that genetic variants act in trans, with notably fewer variants acting in cis. Furthermore, we highlight using Mendelian Randomization that these variability-Quantitative Trait Loci might be driven by the cis regulation of upstream genes. This indicates that natural selection may balance the impact of gene regulation in cis with downstream impacts on expression variability in trans.}, } @article {pmid32163611, year = {2020}, author = {Nedelcu, AM and Michod, RE}, title = {Stress Responses Co-Opted for Specialized Cell Types During the Early Evolution of Multicellularity: The Role of Stress in the Evolution of Cell Types Can Be Traced Back to the Early Evolution of Multicellularity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {42}, number = {5}, pages = {e2000029}, doi = {10.1002/bies.202000029}, pmid = {32163611}, issn = {1521-1878}, support = {//Natural Sciences and Engineering Research Council (NSERC) of Canada and Harrison McCain Foundation/International ; NNX13AH41G/NASA/NASA/United States ; MCB-1412395//National Science Foundation/International ; //Natural Sciences and Engineering Research Council of Canada/International ; NNX13AH41G/NASA/NASA/United States ; }, mesh = {*Biological Evolution ; Humans ; Phylogeny ; }, } @article {pmid32146616, year = {2020}, author = {Fuchs, M and Lohmann, JU}, title = {Aiming for the top: non-cell autonomous control of shoot stem cells in Arabidopsis.}, journal = {Journal of plant research}, volume = {133}, number = {3}, pages = {297-309}, pmid = {32146616}, issn = {1618-0860}, support = {SFB873//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Arabidopsis/*growth & development ; Arabidopsis Proteins ; Gene Expression Regulation, Plant ; Homeodomain Proteins ; Meristem/*cytology ; Plant Shoots/*cytology ; Stem Cells/*cytology ; }, abstract = {In multicellular organisms, not all cells are created equal. Instead, organismal complexity is achieved by specialisation and division of labour between distinct cell types. Therefore, the organism depends on the presence, correct proportion and function of all cell types. It follows that early development is geared towards setting up the basic body plan and to specify cell lineages. Since plants employ a post-embryonic mode of development, the continuous growth and addition of new organs require a source of new cells, as well as a strict regulation of cellular composition throughout the entire life-cycle. To meet these demands, evolution has brought about complex regulatory systems to maintain and control continuously active stem cell systems. Here, we review recent work on the mechanisms of non cell-autonomous control of shoot stem cells in the model plant Arabidopsis thaliana with a strong focus on the cell-to-cell mobility and function of the WUSCHEL homeodomain transcription factor.}, } @article {pmid32143753, year = {2020}, author = {Klesen, S and Hill, K and Timmermans, MCP}, title = {Small RNAs as plant morphogens.}, journal = {Current topics in developmental biology}, volume = {137}, number = {}, pages = {455-480}, doi = {10.1016/bs.ctdb.2019.11.001}, pmid = {32143753}, issn = {1557-8933}, mesh = {Cell Communication ; *Gene Expression Regulation, Developmental ; MicroRNAs/genetics ; *Plant Development ; *Plant Physiological Phenomena ; Plant Proteins/genetics/*metabolism ; Plants/*genetics ; RNA/*genetics ; RNA, Small Interfering/genetics ; Signal Transduction ; }, abstract = {The coordination of cell fate decisions within complex multicellular structures rests on intercellular communication. To generate ordered patterns, cells need to know their relative positions within the growing structure. This is commonly achieved via the production and perception of mobile signaling molecules. In animal systems, such positional signals often act as morphogens and subdivide a field of cells into domains of discrete cell identities using a threshold-based readout of their mobility gradient. Reflecting the independent origin of multicellularity, plants evolved distinct signaling mechanisms to drive cell fate decisions. Many of the basic principles underlying developmental patterning are, however, shared between animals and plants, including the use of signaling gradients to provide positional information. In plant development, small RNAs can act as mobile instructive signals, and similar to classical morphogens in animals, employ a threshold-based readout of their mobility gradient to generate precisely defined cell fate boundaries. Given the distinctive nature of peptide morphogens and small RNAs, how might mechanisms underlying the function of traditionally morphogens be adapted to create morphogen-like behavior using small RNAs? In this review, we highlight the contributions of mobile small RNAs to pattern formation in plants and summarize recent studies that have advanced our understanding regarding the formation, stability, and interpretation of small RNA gradients.}, } @article {pmid32139673, year = {2020}, author = {Han, H and Yan, A and Li, L and Zhu, Y and Feng, B and Liu, X and Zhou, Y}, title = {A signal cascade originated from epidermis defines apical-basal patterning of Arabidopsis shoot apical meristems.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {1214}, pmid = {32139673}, issn = {2041-1723}, mesh = {Arabidopsis/*embryology/genetics/*metabolism ; Arabidopsis Proteins/metabolism ; Base Sequence ; *Body Patterning ; Gene Expression Regulation, Plant ; Green Fluorescent Proteins/metabolism ; Homeodomain Proteins/metabolism ; Meristem/*embryology/*metabolism ; MicroRNAs/genetics/metabolism ; Plant Epidermis/*metabolism ; Promoter Regions, Genetic/genetics ; Protein Binding ; *Signal Transduction ; Stem Cell Niche ; Up-Regulation/genetics ; }, abstract = {In multicellular organisms, a long-standing question is how spatial patterns of distinct cell types are initiated and maintained during continuous cell division and proliferation. Along the vertical axis of plant shoot apical meristems (SAMs), stem cells are located at the top while cells specifying the stem cells are located more basally, forming a robust apical-basal pattern. We previously found that in Arabidopsis SAMs, the HAIRY MERISTEM (HAM) family transcription factors form a concentration gradient from the epidermis to the interior cell layers, and this gradient is essential for the stem cell specification and the apical-basal patterning of the SAMs. Here, we uncover that epidermis specific transcription factors, ARABIDOPSIS THALIANA MERISTEM LAYER 1 (ATML1) and its close homolog, define the concentration gradient of HAM in the SAM through activating a group of microRNAs. This study provides a molecular framework linking the epidermis-derived signal to the stem cell homeostasis in plants.}, } @article {pmid32133683, year = {2020}, author = {Horton, MB and Hawkins, ED and Heinzel, S and Hodgkin, PD}, title = {Speculations on the evolution of humoral adaptive immunity.}, journal = {Immunology and cell biology}, volume = {98}, number = {6}, pages = {439-448}, pmid = {32133683}, issn = {1440-1711}, mesh = {*Adaptive Immunity ; *Biological Evolution ; Cell Differentiation ; Humans ; *Immunity, Humoral ; }, abstract = {The protection of a multicellular organism from infection, at both cell and humoral levels, has been a tremendous driver of gene selection and cellular response strategies. Here we focus on a critical event in the development of humoral immunity: The transition from principally innate responses to a system of adaptive cell selection, with all the attendant mechanical problems that must be solved in order for it to work effectively. Here we review recent advances, but our major goal is to highlight that the development of adaptive immunity resulted from the adoption, reuse and repurposing of an ancient, autonomous cellular program that combines and exploits three titratable cellular fate timers. We illustrate how this common cell machinery recurs and appears throughout biology, and has been essential for the evolution of complex organisms, at many levels of scale.}, } @article {pmid32130880, year = {2020}, author = {González, A and Hall, MN and Lin, SC and Hardie, DG}, title = {AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control.}, journal = {Cell metabolism}, volume = {31}, number = {3}, pages = {472-492}, doi = {10.1016/j.cmet.2020.01.015}, pmid = {32130880}, issn = {1932-7420}, support = {204766/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204766/WT_/Wellcome Trust/United Kingdom ; }, mesh = {AMP-Activated Protein Kinases/chemistry/genetics/*metabolism ; Animals ; Cell Proliferation ; Cells/*metabolism ; DNA Damage ; Humans ; Nutrients/*metabolism ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {The AMPK (AMP-activated protein kinase) and TOR (target-of-rapamycin) pathways are interlinked, opposing signaling pathways involved in sensing availability of nutrients and energy and regulation of cell growth. AMPK (Yin, or the "dark side") is switched on by lack of energy or nutrients and inhibits cell growth, while TOR (Yang, or the "bright side") is switched on by nutrient availability and promotes cell growth. Genes encoding the AMPK and TOR complexes are found in almost all eukaryotes, suggesting that these pathways arose very early during eukaryotic evolution. During the development of multicellularity, an additional tier of cell-extrinsic growth control arose that is mediated by growth factors, but these often act by modulating nutrient uptake so that AMPK and TOR remain the underlying regulators of cellular growth control. In this review, we discuss the evolution, structure, and regulation of the AMPK and TOR pathways and the complex mechanisms by which they interact.}, } @article {pmid32130562, year = {2020}, author = {Lashkarinia, SS and Çoban, G and Ermek, E and Çelik, M and Pekkan, K}, title = {Spatiotemporal remodeling of embryonic aortic arch: stress distribution, microstructure, and vascular growth in silico.}, journal = {Biomechanics and modeling in mechanobiology}, volume = {19}, number = {5}, pages = {1897-1915}, doi = {10.1007/s10237-020-01315-6}, pmid = {32130562}, issn = {1617-7940}, support = {307460/ERC_/European Research Council/International ; }, mesh = {Animals ; Aorta, Thoracic/*anatomy & histology/*embryology ; Chickens ; Collagen Type I/metabolism ; *Computer Simulation ; Finite Element Analysis ; Imaging, Three-Dimensional ; *Models, Anatomic ; Pressure ; Reproducibility of Results ; Stress, Mechanical ; }, abstract = {The microstructure for mature vessels has been investigated in detail, while there is limited information about the embryonic stages, in spite of their importance in the prognosis of congenital heart defects. It is hypothesized that the embryonic vasculature represents a disorganized but dynamic soft tissue, which rapidly evolves toward a specialized multi-cellular vascular structure under mechanical loading. Here the microstructural evolution process of the embryonic pharyngeal aortic arch structure was simulated using an in ovo validated long-term growth and remodeling computational model, implemented as an in-house FEBio plug-in. Optical coherence tomography-guided servo-null pressure measurements are assigned as boundary conditions through the critical embryonic stages. The accumulation of key microstructural constituents was recorded through zoom confocal microscopy for all six embryonic arch arteries simultaneously. The total amount and the radial variation slope of the collagen along the arch wall thickness in different arch types and for different embryonic times, with different dimension scales, were normalized and compared statistically. The arch growth model shows that the stress levels around the lumen boundary increase from [Formula: see text] (Stage 18) to a level higher than [Formula: see text] (Stage 24), depending on matrix constituent production rates, while the homeostatic strain level is kept constant. The statistical tests show that although the total collagen levels differentiate among bilateral positions of the same arch, the shape coefficient of the matrix microstructural gradient changes with embryonic time, proving radial localization, in accordance with numerical model results. In vivo cell number (DAPI) and vascular endothelial growth factor distributions followed similar trends.}, } @article {pmid32130216, year = {2020}, author = {Ronquist, F and Forshage, M and Häggqvist, S and Karlsson, D and Hovmöller, R and Bergsten, J and Holston, K and Britton, T and Abenius, J and Andersson, B and Buhl, PN and Coulianos, CC and Fjellberg, A and Gertsson, CA and Hellqvist, S and Jaschhof, M and Kjærandsen, J and Klopfstein, S and Kobro, S and Liston, A and Meier, R and Pollet, M and Riedel, M and Roháček, J and Schuppenhauer, M and Stigenberg, J and Struwe, I and Taeger, A and Ulefors, SO and Varga, O and Withers, P and Gärdenfors, U}, title = {Completing Linnaeus's inventory of the Swedish insect fauna: Only 5,000 species left?.}, journal = {PloS one}, volume = {15}, number = {3}, pages = {e0228561}, pmid = {32130216}, issn = {1932-6203}, mesh = {Animals ; *Biodiversity ; *Censuses ; Diptera/classification ; Ecosystem ; Europe ; *Extinction, Biological ; Insecta/*classification ; Phylogeny ; Records ; Sweden ; }, abstract = {Despite more than 250 years of taxonomic research, we still have only a vague idea about the true size and composition of the faunas and floras of the planet. Many biodiversity inventories provide limited insight because they focus on a small taxonomic subsample or a tiny geographic area. Here, we report on the size and composition of the Swedish insect fauna, thought to represent roughly half of the diversity of multicellular life in one of the largest European countries. Our results are based on more than a decade of data from the Swedish Taxonomy Initiative and its massive inventory of the country's insect fauna, the Swedish Malaise Trap Project The fauna is considered one of the best known in the world, but the initiative has nevertheless revealed a surprising amount of hidden diversity: more than 3,000 new species (301 new to science) have been documented so far. Here, we use three independent methods to analyze the true size and composition of the fauna at the family or subfamily level: (1) assessments by experts who have been working on the most poorly known groups in the fauna; (2) estimates based on the proportion of new species discovered in the Malaise trap inventory; and (3) extrapolations based on species abundance and incidence data from the inventory. For the last method, we develop a new estimator, the combined non-parametric estimator, which we show is less sensitive to poor coverage of the species pool than other popular estimators. The three methods converge on similar estimates of the size and composition of the fauna, suggesting that it comprises around 33,000 species. Of those, 8,600 (26%) were unknown at the start of the inventory and 5,000 (15%) still await discovery. We analyze the taxonomic and ecological composition of the estimated fauna, and show that most of the new species belong to Hymenoptera and Diptera groups that are decomposers or parasitoids. Thus, current knowledge of the Swedish insect fauna is strongly biased taxonomically and ecologically, and we show that similar but even stronger biases have distorted our understanding of the fauna in the past. We analyze latitudinal gradients in the size and composition of known European insect faunas and show that several of the patterns contradict the Swedish data, presumably due to similar knowledge biases. Addressing these biases is critical in understanding insect biomes and the ecosystem services they provide. Our results emphasize the need to broaden the taxonomic scope of current insect monitoring efforts, a task that is all the more urgent as recent studies indicate a possible worldwide decline in insect faunas.}, } @article {pmid32122349, year = {2020}, author = {Gray, MW and Burger, G and Derelle, R and Klimeš, V and Leger, MM and Sarrasin, M and Vlček, Č and Roger, AJ and Eliáš, M and Lang, BF}, title = {The draft nuclear genome sequence and predicted mitochondrial proteome of Andalucia godoyi, a protist with the most gene-rich and bacteria-like mitochondrial genome.}, journal = {BMC biology}, volume = {18}, number = {1}, pages = {22}, pmid = {32122349}, issn = {1741-7007}, support = {MOP-4124//CIHR/Canada ; MOP-11212//CIHR/Canada ; }, mesh = {Cell Nucleus/genetics ; Eukaryota/*genetics ; *Genome, Mitochondrial ; Mitochondrial Proteins/*genetics/metabolism ; *Proteome ; }, abstract = {BACKGROUND: Comparative analyses have indicated that the mitochondrion of the last eukaryotic common ancestor likely possessed all the key core structures and functions that are widely conserved throughout the domain Eucarya. To date, such studies have largely focused on animals, fungi, and land plants (primarily multicellular eukaryotes); relatively few mitochondrial proteomes from protists (primarily unicellular eukaryotic microbes) have been examined. To gauge the full extent of mitochondrial structural and functional complexity and to identify potential evolutionary trends in mitochondrial proteomes, more comprehensive explorations of phylogenetically diverse mitochondrial proteomes are required. In this regard, a key group is the jakobids, a clade of protists belonging to the eukaryotic supergroup Discoba, distinguished by having the most gene-rich and most bacteria-like mitochondrial genomes discovered to date.

RESULTS: In this study, we assembled the draft nuclear genome sequence for the jakobid Andalucia godoyi and used a comprehensive in silico approach to infer the nucleus-encoded portion of the mitochondrial proteome of this protist, identifying 864 candidate mitochondrial proteins. The A. godoyi mitochondrial proteome has a complexity that parallels that of other eukaryotes, while exhibiting an unusually large number of ancestral features that have been lost particularly in opisthokont (animal and fungal) mitochondria. Notably, we find no evidence that the A. godoyi nuclear genome has or had a gene encoding a single-subunit, T3/T7 bacteriophage-like RNA polymerase, which functions as the mitochondrial transcriptase in all eukaryotes except the jakobids.

CONCLUSIONS: As genome and mitochondrial proteome data have become more widely available, a strikingly punctuate phylogenetic distribution of different mitochondrial components has been revealed, emphasizing that the pathways of mitochondrial proteome evolution are likely complex and lineage-specific. Unraveling this complexity will require comprehensive comparative analyses of mitochondrial proteomes from a phylogenetically broad range of eukaryotes, especially protists. The systematic in silico approach described here offers a valuable adjunct to direct proteomic analysis (e.g., via mass spectrometry), particularly in cases where the latter approach is constrained by sample limitation or other practical considerations.}, } @article {pmid32118486, year = {2020}, author = {Chen, CY and Nguyen, LT and Paoli, GC and Irwin, PL}, title = {The complex multicellular morphology of the food spoilage bacteria Brochothrix thermosphacta strains isolated from ground chicken.}, journal = {Canadian journal of microbiology}, volume = {66}, number = {4}, pages = {303-312}, doi = {10.1139/cjm-2019-0502}, pmid = {32118486}, issn = {1480-3275}, mesh = {Animals ; Brochothrix/classification/*growth & development/isolation & purification/metabolism ; Chickens/*microbiology ; Culture Media/chemistry/metabolism ; Food Contamination/analysis ; Meat/microbiology ; Temperature ; }, abstract = {Herein we describe a highly structured, filamentous growth phenotype displayed by an isolate of the food spoilage microorganism Brochothrix thermosphacta. The growth morphology of this B. thermosphacta strain (strain BII) was dependent on environmental factors such as the growth media, incubation temperatures, and the inoculum concentration. Inoculation of cultures in highly dilute suspensions resulted in the formation of isolated, tight aggregates resembling fungal growth in liquid media. This same strain also formed stable, mesh-like structures in 6-well tissue culture plates under specific growth conditions. The complex growth phenotype does not appear to be unique to strain BII but was common among B. thermosphacta strains isolated from chicken. Light and electron micrographs showed that the filaments of multiple BII cells can organize into complex, tertiary structures resembling multistranded cables. Time-lapse microscopy was employed to monitor the development of such aggregates over 18 h and revealed growth originating from short filaments into compact ball-like clusters that appeared fuzzy due to protruding filaments or cables. This report is the first to document this complex filamentous growth phenotype in a wild-type bacterial isolate of B. thermosphacta.}, } @article {pmid32117212, year = {2019}, author = {Bonsignore, P and Kuiper, JWP and Adrian, J and Goob, G and Hauck, CR}, title = {CEACAM3-A Prim(at)e Invention for Opsonin-Independent Phagocytosis of Bacteria.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {3160}, pmid = {32117212}, issn = {1664-3224}, mesh = {Animals ; Bacteria/*immunology ; Biological Evolution ; Carcinoembryonic Antigen/*genetics/*immunology ; Humans ; Immunity, Innate/genetics/immunology ; Phagocytosis/*genetics/*immunology ; Primates ; }, abstract = {Phagocytosis is one of the key innate defense mechanisms executed by specialized cells in multicellular animals. Recent evidence suggests that a particular phagocytic receptor expressed by human polymorphonuclear granulocytes, the carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3), is one of the fastest-evolving human proteins. In this focused review, we will try to resolve the conundrum why a conserved process such as phagocytosis is conducted by a rapidly changing receptor. Therefore, we will first summarize the biochemical and structural details of this immunoglobulin-related glycoprotein in the context of the human CEACAM family. The function of CEACAM3 for the efficient, opsonin-independent detection and phagocytosis of highly specialized, host-restricted bacteria will be further elaborated. Taking into account the decisive role of CEACAM3 in the interaction with pathogenic bacteria, we will discuss the evolutionary trajectory of the CEACAM3 gene within the primate lineage and highlight the consequences of CEACAM3 polymorphisms in human populations. From a synopsis of these studies, CEACAM3 emerges as an important component of human innate immunity and a prominent example of a dedicated receptor for professional phagocytosis.}, } @article {pmid32115438, year = {2020}, author = {Urayama, SI and Takaki, Y and Hagiwara, D and Nunoura, T}, title = {dsRNA-seq Reveals Novel RNA Virus and Virus-Like Putative Complete Genome Sequences from Hymeniacidon sp. Sponge.}, journal = {Microbes and environments}, volume = {35}, number = {2}, pages = {}, pmid = {32115438}, issn = {1347-4405}, mesh = {Animals ; Aquatic Organisms/virology ; *Genome, Viral ; Phylogeny ; Porifera/*virology ; RNA Viruses/*classification/isolation & purification ; RNA, Double-Stranded/*genetics ; RNA, Viral/genetics ; RNA-Seq ; Sequence Analysis, DNA ; }, abstract = {Invertebrates are a source of previously unknown RNA viruses that fill gaps in the viral phylogenetic tree. Although limited information is currently available on RNA viral diversity in the marine sponge, a primordial multicellular animal that belongs to the phylum Porifera, the marine sponge is one of the well-studied holobiont systems. In the present study, we elucidated the putative complete genome sequences of five novel RNA viruses from Hymeniacidon sponge using a combination of double-stranded RNA sequencing, called fragmented and primer ligated dsRNA sequencing, and a conventional transcriptome method targeting single-stranded RNA. We identified highly diverged RNA-dependent RNA polymerase sequences, including a potential novel RNA viral lineage, in the sponge and three viruses presumed to infect sponge cells.}, } @article {pmid32109395, year = {2020}, author = {Tan, Y and Barnbrook, M and Wilson, Y and Molnár, A and Bukys, A and Hudson, A}, title = {Shared Mutations in a Novel Glutaredoxin Repressor of Multicellular Trichome Fate Underlie Parallel Evolution of Antirrhinum Species.}, journal = {Current biology : CB}, volume = {30}, number = {8}, pages = {1357-1366.e4}, doi = {10.1016/j.cub.2020.01.060}, pmid = {32109395}, issn = {1879-0445}, support = {BB/J01446X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Antirrhinum/*genetics/growth & development ; *Biological Evolution ; Glutaredoxins/antagonists & inhibitors/*genetics ; Mutation ; Plant Proteins/antagonists & inhibitors/*genetics ; Trichomes/genetics/*growth & development ; }, abstract = {Most angiosperms produce trichomes-epidermal hairs that have protective or more specialized roles. Trichomes are multicellular in almost all species and, in the majority, secretory. Despite the importance of multicellular trichomes for plant protection and as a source of high-value products, the mechanisms that control their development are only poorly understood. Here, we investigate the control of multicellular trichome patterns using natural variation within the genus Antirrhinum (snapdragons), which has evolved hairy alpine-adapted species or lowland species with a restricted trichome pattern multiple times in parallel. We find that a single gene, Hairy (H), which is needed to repress trichome fate, underlies variation in trichome patterns between all Antirrhinum species except one. We show that H encodes a novel epidermis-specific glutaredoxin and that the pattern of trichome distribution within individuals reflects the location of H expression. Phylogenetic and functional tests suggest that H gained its trichome-repressing role late in the history of eudicots and that the ancestral Antirrhinum had an active H gene and restricted trichome distribution. Loss of H function was involved in an early divergence of alpine and lowland Antirrhinum lineages, and the alleles underlying this split were later reused in parallel evolution of alpines from lowland ancestors, and vice versa. We also find evidence for an evolutionary reversal from a widespread to restricted trichome distribution involving a suppressor mutation and for a pleiotropic effect of H on plant growth that might constrain the evolution of trichome pattern.}, } @article {pmid32102937, year = {2020}, author = {Elliott, L and Moore, I and Kirchhelle, C}, title = {Spatio-temporal control of post-Golgi exocytic trafficking in plants.}, journal = {Journal of cell science}, volume = {133}, number = {4}, pages = {}, doi = {10.1242/jcs.237065}, pmid = {32102937}, issn = {1477-9137}, support = {BB/P01979X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Eukaryotic Cells/metabolism ; *Golgi Apparatus/metabolism ; *Plants/metabolism ; Protein Transport ; rab GTP-Binding Proteins/metabolism ; }, abstract = {A complex and dynamic endomembrane system is a hallmark of eukaryotic cells and underpins the evolution of specialised cell types in multicellular organisms. Endomembrane system function critically depends on the ability of the cell to (1) define compartment and pathway identity, and (2) organise compartments and pathways dynamically in space and time. Eukaryotes possess a complex molecular machinery to control these processes, including small GTPases and their regulators, SNAREs, tethering factors, motor proteins, and cytoskeletal elements. Whereas many of the core components of the eukaryotic endomembrane system are broadly conserved, there have been substantial diversifications within different lineages, possibly reflecting lineage-specific requirements of endomembrane trafficking. This Review focusses on the spatio-temporal regulation of post-Golgi exocytic transport in plants. It highlights recent advances in our understanding of the elaborate network of pathways transporting different cargoes to different domains of the cell surface, and the molecular machinery underpinning them (with a focus on Rab GTPases, their interactors and the cytoskeleton). We primarily focus on transport in the context of growth, but also highlight how these pathways are co-opted during plant immunity responses and at the plant-pathogen interface.}, } @article {pmid32095969, year = {2020}, author = {Moody, LA}, title = {Three-dimensional growth: a developmental innovation that facilitated plant terrestrialization.}, journal = {Journal of plant research}, volume = {133}, number = {3}, pages = {283-290}, pmid = {32095969}, issn = {1618-0860}, support = {University Research Fellowship//Royal Society/ ; BB/M020517/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Chlorophyta/classification/*growth & development ; Embryophyta/classification/*growth & development ; Flowers ; Phaeophyceae/classification/growth & development ; *Phylogeny ; Plant Roots ; }, abstract = {One of the most transformative events in the history of life on earth was the transition of plants from water to land approximately 470 million years ago. Within the Charophyte green algae, the closest living relatives of land plants, body plans have evolved from those that comprise simple unicells to those that are morphologically complex, large and multicellular. The Charophytes developed these broad ranging body plans by exploiting a range of one-dimensional and two-dimensional growth strategies to produce filaments, mats and branches. When plants were confronted with harsh conditions on land, they were required to make significant changes to the way they shaped their body plans. One of the fundamental developmental transitions that occurred was the evolution of three-dimensional growth and the acquisition of apical cells with three or more cutting faces. Plants subsequently developed a range of morphological adaptations (e.g. vasculature, roots, flowers, seeds) that enabled them to colonise progressively drier environments. 3D apical growth also evolved convergently in the brown algae, completely independently of the green lineage. This review summarises the evolving developmental complexities observed in the early divergent Charophytes all the way through to the earliest conquerors of land, and investigates 3D apical growth in the brown algae.}, } @article {pmid32094536, year = {2020}, author = {Tang, Q and Pang, K and Yuan, X and Xiao, S}, title = {A one-billion-year-old multicellular chlorophyte.}, journal = {Nature ecology & evolution}, volume = {4}, number = {4}, pages = {543-549}, pmid = {32094536}, issn = {2397-334X}, support = {80NSSC18K1086/ImNASA/Intramural NASA/United States ; }, mesh = {*Diatoms ; *Ecosystem ; Fossils ; Phylogeny ; }, abstract = {Chlorophytes (representing a clade within the Viridiplantae and a sister group of the Streptophyta) probably dominated marine export bioproductivity and played a key role in facilitating ecosystem complexity before the Mesozoic diversification of phototrophic eukaryotes such as diatoms, coccolithophorans and dinoflagellates. Molecular clock and biomarker data indicate that chlorophytes diverged in the Mesoproterozoic or early Neoproterozoic, followed by their subsequent phylogenetic diversification, multicellular evolution and ecological expansion in the late Neoproterozoic and Palaeozoic. This model, however, has not been rigorously tested with palaeontological data because of the scarcity of Proterozoic chlorophyte fossils. Here we report abundant millimetre-sized, multicellular and morphologically differentiated macrofossils from rocks approximately 1,000 million years ago. These fossils are described as Proterocladus antiquus new species and are interpreted as benthic siphonocladalean chlorophytes, suggesting that chlorophytes acquired macroscopic size, multicellularity and cellular differentiation nearly a billion years ago, much earlier than previously thought.}, } @article {pmid32094163, year = {2020}, author = {Yahalomi, D and Atkinson, SD and Neuhof, M and Chang, ES and Philippe, H and Cartwright, P and Bartholomew, JL and Huchon, D}, title = {A cnidarian parasite of salmon (Myxozoa: Henneguya) lacks a mitochondrial genome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {10}, pages = {5358-5363}, pmid = {32094163}, issn = {1091-6490}, mesh = {Animals ; *Genome, Mitochondrial ; *Host-Parasite Interactions ; Myxozoa/*classification/*genetics ; Phylogeny ; Salmon/*parasitology ; }, abstract = {Although aerobic respiration is a hallmark of eukaryotes, a few unicellular lineages, growing in hypoxic environments, have secondarily lost this ability. In the absence of oxygen, the mitochondria of these organisms have lost all or parts of their genomes and evolved into mitochondria-related organelles (MROs). There has been debate regarding the presence of MROs in animals. Using deep sequencing approaches, we discovered that a member of the Cnidaria, the myxozoan Henneguya salminicola, has no mitochondrial genome, and thus has lost the ability to perform aerobic cellular respiration. This indicates that these core eukaryotic features are not ubiquitous among animals. Our analyses suggest that H. salminicola lost not only its mitochondrial genome but also nearly all nuclear genes involved in transcription and replication of the mitochondrial genome. In contrast, we identified many genes that encode proteins involved in other mitochondrial pathways and determined that genes involved in aerobic respiration or mitochondrial DNA replication were either absent or present only as pseudogenes. As a control, we used the same sequencing and annotation methods to show that a closely related myxozoan, Myxobolus squamalis, has a mitochondrial genome. The molecular results are supported by fluorescence micrographs, which show the presence of mitochondrial DNA in M. squamalis, but not in H. salminicola. Our discovery confirms that adaptation to an anaerobic environment is not unique to single-celled eukaryotes, but has also evolved in a multicellular, parasitic animal. Hence, H. salminicola provides an opportunity for understanding the evolutionary transition from an aerobic to an exclusive anaerobic metabolism.}, } @article {pmid32084159, year = {2020}, author = {Finoshin, AD and Adameyko, KI and Mikhailov, KV and Kravchuk, OI and Georgiev, AA and Gornostaev, NG and Kosevich, IA and Mikhailov, VS and Gazizova, GR and Shagimardanova, EI and Gusev, OA and Lyupina, YV}, title = {Iron metabolic pathways in the processes of sponge plasticity.}, journal = {PloS one}, volume = {15}, number = {2}, pages = {e0228722}, pmid = {32084159}, issn = {1932-6203}, mesh = {Animals ; Computational Biology ; Gene Expression Profiling ; Iron/*metabolism ; Iron-Regulatory Proteins/genetics/metabolism ; Molecular Sequence Annotation ; Phylogeny ; Porifera/genetics/*metabolism ; RNA-Seq ; }, abstract = {The ability to regulate oxygen consumption evolved in ancestral animals and is intrinsically linked to iron metabolism. The iron pathways have been intensively studied in mammals, whereas data on distant invertebrates are limited. Sea sponges represent the oldest animal phylum and have unique structural plasticity and capacity to reaggregate after complete dissociation. We studied iron metabolic factors and their expression during reaggregation in the White Sea cold-water sponges Halichondria panicea and Halisarca dujardini. De novo transcriptomes were assembled using RNA-Seq data, and evolutionary trends were analyzed with bioinformatic tools. Differential expression during reaggregation was studied for H. dujardini. Enzymes of the heme biosynthesis pathway and transport globins, neuroglobin (NGB) and androglobin (ADGB), were identified in sponges. The globins mutate at higher evolutionary rates than the heme synthesis enzymes. Highly conserved iron-regulatory protein 1 (IRP1) presumably interacts with the iron-responsive elements (IREs) found in mRNAs of ferritin (FTH1) and a putative transferrin receptor NAALAD2. The reaggregation process is accompanied by increased expression of IRP1, the antiapoptotic factor BCL2, the inflammation factor NFκB (p65), FTH1 and NGB, as well as by an increase in mitochondrial density. Our data indicate a complex mechanism of iron regulation in sponge structural plasticity and help to better understand general mechanisms of morphogenetic processes in multicellular species.}, } @article {pmid32079678, year = {2020}, author = {Erwin, DH}, title = {The origin of animal body plans: a view from fossil evidence and the regulatory genome.}, journal = {Development (Cambridge, England)}, volume = {147}, number = {4}, pages = {}, doi = {10.1242/dev.182899}, pmid = {32079678}, issn = {1477-9129}, mesh = {Animals ; Biological Evolution ; *Body Patterning ; Cell Differentiation ; Embryo, Nonmammalian ; *Fossils ; Gene Regulatory Networks ; *Genome ; Genomics ; Invertebrates/classification ; Paleontology ; Phylogeny ; *Regulatory Sequences, Nucleic Acid ; Sequence Analysis, RNA ; }, abstract = {The origins and the early evolution of multicellular animals required the exploitation of holozoan genomic regulatory elements and the acquisition of new regulatory tools. Comparative studies of metazoans and their relatives now allow reconstruction of the evolution of the metazoan regulatory genome, but the deep conservation of many genes has led to varied hypotheses about the morphology of early animals and the extent of developmental co-option. In this Review, I assess the emerging view that the early diversification of animals involved small organisms with diverse cell types, but largely lacking complex developmental patterning, which evolved independently in different bilaterian clades during the Cambrian Explosion.}, } @article {pmid32078984, year = {2020}, author = {Moreau, CS}, title = {Symbioses among ants and microbes.}, journal = {Current opinion in insect science}, volume = {39}, number = {}, pages = {1-5}, doi = {10.1016/j.cois.2020.01.002}, pmid = {32078984}, issn = {2214-5753}, mesh = {Animals ; *Ants/microbiology/parasitology ; Bacteria ; Behavior ; Diet ; Fungi ; Gastrointestinal Microbiome ; Host-Parasite Interactions ; Microbiota ; Nematoda ; *Symbiosis ; Trematoda ; Viruses ; }, abstract = {Ants have been shown to engage in symbiosis across the tree of life, although our knowledge is far from complete. These interactions range from mutualistic to parasitic with several instances of manipulation of host behavior. Nutrient contributions in these symbioses include both farming for food and nitrogen recycling by gut-associated microbes. Interestingly, the ants that are mostly likely to host diverse and likely functional gut microbial communities are those that feed on extreme diets. Although we do see many instances of symbiosis between ants and microbes, there are also examples of species without a functional gut microbiome. Symbiosis among microbes and eukaryotic hosts is common and often considered a hallmark of multicellular evolution [1]. This is true among many of the over 13000 species of ants, although symbiosis between ants and microbes are not ubiquitous. These microbial-ant symbiotic interactions span the tree of life and include microbial eukaryotes, fungi, viruses, and bacteria. These interactions range from pathogenic to mutualistic, with many relationships still not well understood. Although our knowledge of the diversity of these microbes in ants is growing rapidly, and in some cases we know the function and interaction with the host, we still have much to learn about - the little things that run the little things that run the world!}, } @article {pmid32075388, year = {2020}, author = {Raudenská, M and Svobodová, M and Gumulec, J and Falk, M and Masařík, M}, title = {The Importance of Cancer-Associated Fibroblasts in the Pathogenesis of Head and Neck Cancers.}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {33}, number = {1}, pages = {39-48}, doi = {10.14735/amko202039}, pmid = {32075388}, issn = {1802-5307}, mesh = {*Cancer-Associated Fibroblasts ; Head and Neck Neoplasms/*pathology ; Humans ; Phenotype ; }, abstract = {BACKGROUND: Despite progress in anticancer therapies, head and neck squamous cell carcinoma (HNSCC) has still a low survival rate. Recent studies have shown that tumour stroma may play an important role in the pathogenesis of this malignant disease. Fibroblasts are a major component of the tumour microenvironment and may significantly influence HNSCC progression as indicated by the contribution they make to important hallmarks of cancer, such as inflammation, non-restricted growth, angiogenesis, invasion, metastasis, and therapy resistance. It is well known that tumour cells can confer a cancer-associated fibroblast (CAF) phenotype that supports the growth and dissemination of cancer cells. CAFs can stimulate cancer progression through cell-cell contacts and communication, remodelling of extracellular matrix, and production of many signal molecules and matrix metalloproteinases. Consequently, genetic changes in epithelial cells are probably not the only factor that drives HNSCC carcinogenesis. Non-genetic changes in the tumour stroma can also be significantly involved. Stress-induced signals can induce a multicellular program, creating a field of tissue that is predisposed to malignant transformation. The “field cancerization” concept represents a process of active evolution of intercellular interactions and feedback loops between tumour and stromal cells. This model paves the way to study cancer from a new perspective and identify new therapeutic targets.

PURPOSE: In this review, we discuss current knowledge about CAFs, such as their cellular origin, phenotypical plasticity and functional heterogeneity, and stress their contribution to HNSCC progression. This article was supported by the project AZV 16-29835A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 18. 6. 2019 Accepted: 9. 9. 2019.}, } @article {pmid32072723, year = {2020}, author = {Kulanthaivelu, K and Bhat, MD and Prasad, C and Srinivas, D and Mhatre, R and Nandeesh, BN}, title = {Brain MRI Findings in Coenurosis: A Helminth Infection.}, journal = {Journal of neuroimaging : official journal of the American Society of Neuroimaging}, volume = {30}, number = {3}, pages = {359-369}, doi = {10.1111/jon.12696}, pmid = {32072723}, issn = {1552-6569}, mesh = {Adult ; Aged ; Brain/*diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neurocysticercosis/complications/*diagnostic imaging ; Neuroimaging ; Retrospective Studies ; Seizures/*diagnostic imaging/etiology ; }, abstract = {BACKGROUND AND PURPOSE: Parasitic neuroinfections in humans have etiological agents spanning a broad spectrum from unicellular (protozoan) to multicellular helminthic (metazoan) organisms. Cerebral coenurosis is a rare cestodal helminthic infection caused by Taenia multiceps. The neuroimaging features of this entity were reviewed to discern an imaging phenotype.

METHODS: Retrospective analysis was performed on 6 cases of cerebral coenurosis, whose diagnoses were confirmed by histopathology. The clinical, imaging, and histopathological features were recorded for analysis.

RESULTS: Clinical expressions included focal neurological deficit due to mass effect (n = 4), intraventricular obstruction with features of raised intracranial tension (n = 1), headache (n = 3), seizures (n = 3), and incidental lesions (n = 1). One patient presented with recurrence 1 year after surgical excision. Neuroimaging revealed cystic thin-walled lesions with clustered eccentric internal nodules corresponding to the plenitude of protoscolices of the tapeworm. Three of the lesions showed a multilocular cystic morphology. Spectroscopic metabolite signature of alanine and succinate commensurate with the parasitic etiology was remarkable in the lesions. Enhancement and edema inversely correlated with the signal suppression on fluid-attenuated inversion recovery (FLAIR) imaging. The lesions had a predominantly juxtacortical distribution.

CONCLUSIONS: In an appropriate clinical setting, a cystic lesion with clustered eccentric internal nodular foci ought to raise the suspicion of this rare infection. Magnetic resonance spectroscopic signature of succinate and alanine, if present, further strengthens the likelihood of coenurosis. Signal characteristics, wall enhancement, and perilesional edema may vary, possibly determined by the stage in the evolution of the parasite.}, } @article {pmid32067938, year = {2020}, author = {Agosti, A and Marchesi, S and Scita, G and Ciarletta, P}, title = {Modelling cancer cell budding in-vitro as a self-organised, non-equilibrium growth process.}, journal = {Journal of theoretical biology}, volume = {492}, number = {}, pages = {110203}, doi = {10.1016/j.jtbi.2020.110203}, pmid = {32067938}, issn = {1095-8541}, mesh = {Cell Adhesion ; Cell Division ; Humans ; Mechanical Phenomena ; Models, Theoretical ; *Neoplasms ; }, abstract = {Tissue self-organization into defined and well-controlled three-dimensional structures is essential during development for the generation of organs. A similar, but highly deranged process might also occur during the aberrant growth of cancers, which frequently display a loss of the orderly structures of the tissue of origin, but retain a multicellular organization in the form of spheroids, strands, and buds. The latter structures are often seen when tumors masses switch to an invasive behavior into surrounding tissues. However, the general physical principles governing the self-organized architectures of tumor cell populations remain by and large unclear. In this work, we perform in-vitro experiments to characterize the growth properties of glioblastoma budding emerging from monolayers. We further propose a theoretical model and its finite element implementation to characterize such a topological transition, that is modelled as a self-organised, non-equilibrium phenomenon driven by the trade-off of mechanical forces and physical interactions exerted at cell-cell and cell-substrate adhesions. Notably, the unstable disorder states of uncontrolled cellular proliferation macroscopically emerge as complex spatio-temporal patterns that evolve statistically correlated by a universal law.}, } @article {pmid32061941, year = {2020}, author = {Lamrabet, O and Jauslin, T and Lima, WC and Leippe, M and Cosson, P}, title = {The multifarious lysozyme arsenal of Dictyostelium discoideum.}, journal = {Developmental and comparative immunology}, volume = {107}, number = {}, pages = {103645}, doi = {10.1016/j.dci.2020.103645}, pmid = {32061941}, issn = {1879-0089}, mesh = {Animals ; Bacteria ; Dictyostelium/*physiology ; Ion Channels/genetics/metabolism ; Muramidase/genetics/*metabolism ; Phagocytes/*immunology ; Phylogeny ; Pore Forming Cytotoxic Proteins/genetics/metabolism ; Protozoan Proteins/genetics/metabolism ; }, abstract = {Dictyostelium discoideum is a free-living soil amoeba which feeds upon bacteria. To bind, ingest, and kill bacteria, D. discoideum uses molecular mechanisms analogous to those found in professional phagocytic cells of multicellular organisms. D. discoideum is equipped with a large arsenal of antimicrobial peptides and proteins including amoebapore-like peptides and lysozymes. This review describes the family of lysozymes in D. discoideum. We identified 22 genes potentially encoding four different types of lysozymes in the D. discoideum genome. Although most of these genes are also present in the genomes of other amoebal species, no other organism is as well-equipped with lysozyme genes as D. discoideum.}, } @article {pmid32061337, year = {2020}, author = {Ishibashi, K and Tanaka, Y and Morishita, Y}, title = {Perspectives on the evolution of aquaporin superfamily.}, journal = {Vitamins and hormones}, volume = {112}, number = {}, pages = {1-27}, doi = {10.1016/bs.vh.2019.08.001}, pmid = {32061337}, issn = {0083-6729}, mesh = {Amino Acid Sequence ; *Aquaporins/genetics/metabolism ; *Phylogeny ; Water ; }, abstract = {Aquaporins (AQPs) belong to a transmembrane protein superfamily composed of an internal repeat of a three membrane-spanning domain and each has a highly conserved NPA box. Based on the more variable carboxyl-terminal NPA box, AQPs can be divided into three subfamilies: (1) glycerol-channel aquaglyceroporin (gAQP) (2) water-selective AQP (wAQP), and (3) deviated superaquaporin (sAQP) in the order of passible evolution. This classification has functional and localization relevance: most wAQPs transports water selectively whereas gAQPs and sAQPs also transport small molecules with sAQPs mostly localized inside the cell. As this classification is not based on the function, some wAQPs functioning as glycerol channels will not be included in gAQPs. AQP ancestors may have first originated in eubacteria as gAQPs to transport small molecules such as glycerol. Later some of them may have acquired a water-selective filter to become wAQPs. Although AQPs are absent in many bacteria, especially in archaea, both gAQPs and wAQPs may have been carried over to eukaryotes or horizontally transferred. Finally, multicellular organisms have obtained new sAQPs, which are curiously absent in fungi and plants. Interestingly, both plants and higher insects independently have lost gAQPs, whose functions, however, have been taken over by functionally modified wAQPs partly obtained by horizontal gene transfers from bacteria. This evolutionary viewpoints on AQPs will facilitate further functional analysis of AQP-like sequences and expand our viewpoints on AQP superfamily.}, } @article {pmid32053788, year = {2020}, author = {Prior, KF and Rijo-Ferreira, F and Assis, PA and Hirako, IC and Weaver, DR and Gazzinelli, RT and Reece, SE}, title = {Periodic Parasites and Daily Host Rhythms.}, journal = {Cell host & microbe}, volume = {27}, number = {2}, pages = {176-187}, pmid = {32053788}, issn = {1934-6069}, support = {202769/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; R21 AI131632/AI/NIAID NIH HHS/United States ; U19 AI089681/AI/NIAID NIH HHS/United States ; R21 AI150546/AI/NIAID NIH HHS/United States ; R21 NS103180/NS/NINDS NIH HHS/United States ; R01 AI079293/AI/NIAID NIH HHS/United States ; R01 NS098747/NS/NINDS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biological Evolution ; Circadian Clocks/physiology ; Circadian Rhythm/*physiology ; Erythrocytes/parasitology ; Host-Parasite Interactions/*physiology ; Humans ; Immunity/physiology ; Inflammation/parasitology ; Malaria ; Mice ; Mosquito Vectors/parasitology/physiology ; Parasites/physiology ; Plasmodium/*physiology ; }, abstract = {Biological rhythms appear to be an elegant solution to the challenge of coordinating activities with the consequences of the Earth's daily and seasonal rotation. The genes and molecular mechanisms underpinning circadian clocks in multicellular organisms are well understood. In contrast, the regulatory mechanisms and fitness consequences of biological rhythms exhibited by parasites remain mysterious. Here, we explore how periodicity in parasite traits is generated and why daily rhythms matter for parasite fitness. We focus on malaria (Plasmodium) parasites which exhibit developmental rhythms during replication in the mammalian host's blood and in transmission to vectors. Rhythmic in-host parasite replication is responsible for eliciting inflammatory responses, the severity of disease symptoms, and fueling transmission, as well as conferring tolerance to anti-parasite drugs. Thus, understanding both how and why the timing and synchrony of parasites are connected to the daily rhythms of hosts and vectors may make treatment more effective and less toxic to hosts.}, } @article {pmid32045589, year = {2020}, author = {Duan, H and Ni, S and Yang, S and Zhou, Y and Zhang, Y and Zhang, S}, title = {Conservation of eATP perception throughout multicellular animal evolution: Identification and functional characterization of coral and amphioxus P2X7-like receptors and flounder P2X7 receptor.}, journal = {Developmental and comparative immunology}, volume = {106}, number = {}, pages = {103641}, doi = {10.1016/j.dci.2020.103641}, pmid = {32045589}, issn = {1879-0089}, mesh = {Adenosine Triphosphate/*metabolism ; Alarmins/immunology ; Animals ; Anthozoa/*physiology ; Biological Evolution ; Conserved Sequence/*genetics ; Cytokines/metabolism ; Extracellular Space/*metabolism ; Flounder/*physiology ; Humans ; Inflammation Mediators/metabolism ; Lancelets/*physiology ; Mammals ; Phagocytosis ; Receptors, Purinergic P2X7/*genetics/metabolism ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; Signal Transduction ; }, abstract = {Perception of extracellular ATP (eATP), a common endogenous damage-associated molecular pattern, is through its receptor P2X7R. If eATP/P2X7R signaling is conserved throughout animal evolution is unknown. Moreover, little information is currently available regarding P2X7R in invertebrates. Here we demonstrated that the coral P2X7-like receptor, AdP2X7RL, the amphioxus P2X7-like receptor, BjP2X7RL and the flounder P2X7 receptor, PoP2X7R, shared common features characteristic of mammalian P2X7R, and their 3D structures displayed high resemblance to that of human P2X7R. Expression of Adp2x7rl, Bjp2x7rl and Pop2x7r was all subjected to the regulation by LPS and ATP. We also showed that AdP2X7RL, BjP2X7RL and PoP2X7R were distributed on the plasma membrane in AdP2X7RL-, BjP2X7RL- and PoP2X7R-expressing HEK cells, and had strong affinity to eATP. Importantly, the binding of AdP2X7RL, BjP2X7RL and PoP2X7R to eATP all induced similar downstream responses, including induction of cytokines (IL-1β, IL-6, IL-8 and CCL-2), enhancement of phagocytosis and activation of AKT/ERK-associated signaling pathway observed for mammalian P2X7R. Collectively, our results indicate for the first time that both coral and amphioxus P2X7RL as well as flounder P2X7R can interact with eATP, and induce events that trigger mammalian mechanisms, suggesting the high conservation of eATP perception throughout multicellular animal evolution.}, } @article {pmid32044287, year = {2020}, author = {Kuwabara, T and Igarashi, K}, title = {Thermotogales origin scenario of eukaryogenesis.}, journal = {Journal of theoretical biology}, volume = {492}, number = {}, pages = {110192}, doi = {10.1016/j.jtbi.2020.110192}, pmid = {32044287}, issn = {1095-8541}, mesh = {*Archaea/genetics ; Bacteria/genetics ; Biological Evolution ; *Eukaryota/genetics ; Eukaryotic Cells ; Evolution, Molecular ; Phylogeny ; }, abstract = {How eukaryotes were generated is an enigma of evolutionary biology. Widely accepted archaeal-origin eukaryogenesis scenarios, based on similarities of genes and related characteristics between archaea and eukaryotes, cannot explain several eukaryote-specific features of the last eukaryotic common ancestor, such as glycerol-3-phosphate-type membrane lipids, large cells and genomes, and endomembrane formation. Thermotogales spheroids, having multicopy-integrated large nucleoids and producing progeny in periplasm, may explain all of these features as well as endoplasmic reticulum-type signal cleavage sites, although they cannot divide. We hypothesize that the progeny chromosome is formed by random joining small DNAs in immature progeny, followed by reorganization by mechanisms including homologous recombination enabled with multicopy-integrated large genome (MILG). We propose that Thermotogales ancestor spheroids came to divide owing to the archaeal cell division genes horizontally transferred via virus-related particles, forming the first eukaryotic common ancestor (FECA). Referring to the hypothesis, the archaeal information-processing system would have been established in FECA by random joining DNAs excised from the MILG, which contained horizontally transferred archaeal and bacterial DNAs, followed by reorganization by the MILG-enabled homologous recombination. Thus, the large genome may have been a prerequisite, but not a consequence, of eukaryogenesis. The random joining of DNAs likely provided the basic mechanisms for eukaryotic evolution: producing the diversity by the formations of supergroups, novel genes, and introns that are involved in exon shuffling.}, } @article {pmid32032743, year = {2020}, author = {Dokanehiifard, S and Soltani, BM and Ghiasi, P and Baharvand, H and Reza Ganjali, M and Hosseinkhani, S}, title = {hsa-miR-766-5p as a new regulator of mitochondrial apoptosis pathway for discriminating of cell death from cardiac differentiation.}, journal = {Gene}, volume = {736}, number = {}, pages = {144448}, doi = {10.1016/j.gene.2020.144448}, pmid = {32032743}, issn = {1879-0038}, mesh = {Apoptosis/*genetics ; Cell Death/*genetics ; Cell Differentiation/*genetics ; Cell Line ; Computational Biology/methods ; Down-Regulation/genetics ; HEK293 Cells ; Human Embryonic Stem Cells/physiology ; Humans ; MicroRNAs/*genetics ; Mitochondria/*genetics ; Myocytes, Cardiac/*physiology ; }, abstract = {Dispose of unnecessary cells in multicellular organism take place through apoptosis as a mode of programmed cell death (PCD). This process is triggered through two main pathway including extrinsic pathway or death receptor pathway and intrinsic or mitochondrial pathway. An alternative role for mitochondrial pathway of cell death is its involvement in cell differentiation. Biochemistry of cell differentiation indicates a common origin for differentiation and apoptosis. miRNAs are a group of small non coding mediator RNAs in regulation of many routes such as apoptosis and differentiation. By using bioinformatics tools hsa-miR-766-5p was predicted to target the BAX, BAK and BOK genes involved in mitochondrial apoptosis pathway. RT-qPCR and dual luciferase assay showed targeting of BAX, BAK and BOK 3'UTRs via hsa-miR-766, detected in SW480 and HEK293T cell lines. Caspases 3/7 and 9 activity assay revealed the involvement of hsa-miR-766-5p in mitochondrial apoptosis pathway regulation detected following overexpression and downregulation of this miRNA, detected in SW480 cells treated with 1 μM doxorubicin. Flow cytometry and MTT assay indicated cell death reduction and viability elevation effect of hsa-miR-766 in SW480 cells after its overexpression. Endogenous expression of hsa-miR-766 during the course of human embryonic stem cells (hESCs) differentiation into cardiomyocytes revealed an inverse expression status of this miRNA with BOK. However, the expression of this miRNA was inversely related to BAX and BAK for some time points of differentiation. Overall this results show the involvement of hsa-miR-766 in regulation of mitochondrial apoptosis pathway.}, } @article {pmid32024776, year = {2020}, author = {Munke, A and Kimura, K and Tomaru, Y and Okamoto, K}, title = {Capsid Structure of a Marine Algal Virus of the Order Picornavirales.}, journal = {Journal of virology}, volume = {94}, number = {9}, pages = {}, pmid = {32024776}, issn = {1098-5514}, mesh = {Capsid/chemistry ; Capsid Proteins/*genetics/metabolism/*ultrastructure ; Cryoelectron Microscopy/methods ; Diatoms/metabolism/*virology ; Genome, Viral/genetics ; Phycodnaviridae/genetics ; Picornaviridae/metabolism/ultrastructure ; RNA Viruses/genetics ; Virion/genetics ; }, abstract = {The order Picornavirales includes viruses that infect different kinds of eukaryotes and that share similar properties. The capsid proteins (CPs) of viruses in the order that infect unicellular organisms, such as algae, presumably possess certain characteristics that have changed little over the course of evolution, and thus these viruses may resemble the Picornavirales ancestor in some respects. Herein, we present the capsid structure of Chaetoceros tenuissimus RNA virus type II (CtenRNAV-II) determined using cryo-electron microscopy at a resolution of 3.1 Å, the first alga virus belonging to the family Marnaviridae of the order Picornavirales A structural comparison to related invertebrate and vertebrate viruses revealed a unique surface loop of the major CP VP1 that had not been observed previously, and further, revealed that another VP1 loop obscures the so-called canyon, which is a host-receptor binding site for many of the mammalian Picornavirales viruses. VP2 has an N-terminal tail, which has previously been reported as a primordial feature of Picornavirales viruses. The above-mentioned and other critical structural features provide new insights on three long-standing theories about Picornavirales: (i) the canyon hypothesis, (ii) the primordial VP2 domain swap, and (iii) the hypothesis that alga Picornavirales viruses could share characteristics with the Picornavirales ancestor.IMPORTANCE Identifying the acquired structural traits in virus capsids is important for elucidating what functions are essential among viruses that infect different hosts. The Picornavirales viruses infect a broad spectrum of hosts, ranging from unicellular algae to insects and mammals and include many human pathogens. Those viruses that infect unicellular protists, such as algae, are likely to have undergone fewer structural changes during the course of evolution compared to those viruses that infect multicellular eukaryotes and thus still share some characteristics with the Picornavirales ancestor. This article describes the first atomic capsid structure of an alga Marnavirus, CtenRNAV-II. A comparison to capsid structures of the related invertebrate and vertebrate viruses identified a number of structural traits that have been functionally acquired or lost during the course of evolution. These observations provide new insights on past theories on the viability and evolution of Picornavirales viruses.}, } @article {pmid32020592, year = {2020}, author = {Nishino, J and Watanabe, S and Miya, F and Kamatani, T and Sugawara, T and Boroevich, KA and Tsunoda, T}, title = {Quantification of multicellular colonization in tumor metastasis using exome-sequencing data.}, journal = {International journal of cancer}, volume = {146}, number = {9}, pages = {2488-2497}, pmid = {32020592}, issn = {1097-0215}, mesh = {Biomarkers, Tumor/*genetics ; Cohort Studies ; Colorectal Neoplasms/*genetics/*pathology ; *DNA Copy Number Variations ; Exome/*genetics ; Gene Expression Regulation, Neoplastic ; Humans ; *Mutation ; Neoplasm Metastasis ; Prognosis ; Exome Sequencing/*methods ; }, abstract = {Metastasis is a major cause of cancer-related mortality, and it is essential to understand how metastasis occurs in order to overcome it. One relevant question is the origin of a metastatic tumor cell population. Although the hypothesis of a single-cell origin for metastasis from a primary tumor has long been prevalent, several recent studies using mouse models have supported a multicellular origin of metastasis. Human bulk whole-exome sequencing (WES) studies also have demonstrated a multiple "clonal" origin of metastasis, with different mutational compositions. Specifically, there has not yet been strong research to determine how many founder cells colonize a metastatic tumor. To address this question, under the metastatic model of "single bottleneck followed by rapid growth," we developed a method to quantify the "founder cell population size" in a metastasis using paired WES data from primary and metachronous metastatic tumors. Simulation studies demonstrated the proposed method gives unbiased results with sufficient accuracy in the range of realistic settings. Applying the proposed method to real WES data from four colorectal cancer patients, all samples supported a multicellular origin of metastasis and the founder size was quantified, ranging from 3 to 17 cells. Such a wide-range of founder sizes estimated by the proposed method suggests that there are large variations in genetic similarity between primary and metastatic tumors in the same subjects, which may explain the observed (dis)similarity of drug responses between tumors.}, } @article {pmid32019441, year = {2020}, author = {Carmel, Y and Shavit, A}, title = {Operationalizing evolutionary transitions in individuality.}, journal = {Proceedings. Biological sciences}, volume = {287}, number = {1920}, pages = {20192805}, pmid = {32019441}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; *Individuality ; Reproduction ; }, abstract = {Evolutionary transitions in individuality (hereafter, ETIs), such as the transition to multi-cellularity and the transition to social colonies, have been at the centre of evolutionary research, but only few attempts were made to systematically operationalize this concept. Here, we devise a set of four indicators intended to assess the change in complexity during ETIs: system size, inseparability, reproductive specialization and non-reproductive specialization. We then conduct a quantitative comparison across multiple taxa and ETIs. Our analysis reveals that inseparability has a crucial role in the process; it seems irreversible and may mark the point where a group of individuals becomes a new individual at a higher hierarchical level. Interestingly, we find that disparate groups demonstrate a similar pattern of progression along ETIs.}, } @article {pmid32016363, year = {2020}, author = {Alsufyani, T and Califano, G and Deicke, M and Grueneberg, J and Weiss, A and Engelen, AH and Kwantes, M and Mohr, JF and Ulrich, JF and Wichard, T}, title = {Macroalgal-bacterial interactions: identification and role of thallusin in morphogenesis of the seaweed Ulva (Chlorophyta).}, journal = {Journal of experimental botany}, volume = {71}, number = {11}, pages = {3340-3349}, pmid = {32016363}, issn = {1460-2431}, mesh = {Bacteria ; *Chlorophyta ; Morphogenesis ; Pyridines ; *Seaweed ; *Ulva ; }, abstract = {Macroalgal microbiomes have core functions related to biofilm formation, growth, and morphogenesis of seaweeds. In particular, the growth and development of the sea lettuce Ulva spp. (Chlorophyta) depend on bacteria releasing morphogenetic compounds. Under axenic conditions, the macroalga Ulva mutabilis develops a callus-like phenotype with cell wall protrusions. However, co-culturing with Roseovarius sp. (MS2) and Maribacter sp. (MS6), which produce various stimulatory chemical mediators, completely recovers morphogenesis. This ecological reconstruction forms a tripartite community which can be further studied for its role in cross-kingdom interactions. Hence, our study sought to identify algal growth- and morphogenesis-promoting factors (AGMPFs) capable of phenocopying the activity of Maribacter spp. We performed bioassay-guided solid-phase extraction in water samples collected from U. mutabilis aquaculture systems. We uncovered novel ecophysiological functions of thallusin, a sesquiterpenoid morphogen, identified for the first time in algal aquaculture. Thallusin, released by Maribacter sp., induced rhizoid and cell wall formation at a concentration of 11 pmol l-1. We demonstrated that gametes acquired the iron complex of thallusin, thereby linking morphogenetic processes with intracellular iron homeostasis. Understanding macroalgae-bacteria interactions permits further elucidation of the evolution of multicellularity and cellular differentiation, and development of new applications in microbiome-mediated aquaculture systems.}, } @article {pmid32003151, year = {2020}, author = {Rimskaya-Korsakova, N and Dyachuk, V and Temereva, E}, title = {Parapodial glandular organs in Owenia borealis (Annelida: Oweniidae) and their possible relationship with nephridia.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {334}, number = {2}, pages = {88-99}, doi = {10.1002/jez.b.22928}, pmid = {32003151}, issn = {1552-5015}, mesh = {Animals ; Annelida/*anatomy & histology/physiology ; Microscopy, Electron, Transmission ; Urinary Tract/anatomy & histology/ultrastructure ; }, abstract = {Oweniidae is a basal group of recent annelids and nowadays it attracts the attention of researchers of many biological fields. Surprisingly, details of their anatomy, like the adult excretory system, remain obscure. Researchers recently suggested that the paired organs of tubeworms in the family Oweniidae are related to nephridia. In the current study of Owenia borealis adults, we determined that these structures are parapodial glandular organs (PGOs) and are located in the first two segments of adults. The PGOs are complex subepidermal multicellular glands that contain secretory cells, that is, goblet cells, which are differentiated by the type of the producing tube matter. The goblet cells are surrounded by muscles that are used to extrude material stored in the PGO's lumen into the external environment. The anterior pair of PGOs have very well-developed rough endoplasmatic reticulum in the proximal cells, spacious Golgi complexes, numerous nail-shaped microvilli, and apocrine secretory processes in the goblet cells of the distal parts. The posterior pair of PGOs only consists of cells, which probably produce proteinaceous fibrils. We discuss the homology of goblet cells with specific nail-shaped microvilli that produce β-chitin within annelids. We also discuss the possibility that PGOs and nephridia have a common origin. This study provides new information on the ultrastructure of cells that secrete the organic material used to form the tubes inhabited by tube-dwelling annelids.}, } @article {pmid31983537, year = {2020}, author = {Yao, M and Ventura, PB and Jiang, Y and Rodriguez, FJ and Wang, L and Perry, JSA and Yang, Y and Wahl, K and Crittenden, RB and Bennett, ML and Qi, L and Gong, CC and Li, XN and Barres, BA and Bender, TP and Ravichandran, KS and Janes, KA and Eberhart, CG and Zong, H}, title = {Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth.}, journal = {Cell}, volume = {180}, number = {3}, pages = {502-520.e19}, pmid = {31983537}, issn = {1097-4172}, support = {R00 CA237728/CA/NCI NIH HHS/United States ; R01 NS055089/NS/NINDS NIH HHS/United States ; P30 CA044579/CA/NCI NIH HHS/United States ; U01 CA215794/CA/NCI NIH HHS/United States ; K99 CA237728/CA/NCI NIH HHS/United States ; T32 HD007348/HD/NICHD NIH HHS/United States ; R21 HL143025/HL/NHLBI NIH HHS/United States ; F31 NS076313/NS/NINDS NIH HHS/United States ; R01 NS097271/NS/NINDS NIH HHS/United States ; T32 GM145443/GM/NIGMS NIH HHS/United States ; T32 CA009109/CA/NCI NIH HHS/United States ; R01 CA194470/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/*metabolism ; Carcinogenesis/*metabolism ; Cell Lineage ; *Cell Transdifferentiation ; Cerebellar Neoplasms/*metabolism/pathology ; Disease Models, Animal ; Female ; Hedgehog Proteins/metabolism ; Heterografts ; Humans ; Insulin-Like Growth Factor I/genetics/metabolism ; Interleukin-4/genetics/metabolism ; Male ; Medulloblastoma/*metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/metabolism ; *Paracrine Communication ; Tumor Microenvironment ; }, abstract = {The tumor microenvironment (TME) is critical for tumor progression. However, the establishment and function of the TME remain obscure because of its complex cellular composition. Using a mouse genetic system called mosaic analysis with double markers (MADMs), we delineated TME evolution at single-cell resolution in sonic hedgehog (SHH)-activated medulloblastomas that originate from unipotent granule neuron progenitors in the brain. First, we found that astrocytes within the TME (TuAstrocytes) were trans-differentiated from tumor granule neuron precursors (GNPs), which normally never differentiate into astrocytes. Second, we identified that TME-derived IGF1 promotes tumor progression. Third, we uncovered that insulin-like growth factor 1 (IGF1) is produced by tumor-associated microglia in response to interleukin-4 (IL-4) stimulation. Finally, we found that IL-4 is secreted by TuAstrocytes. Collectively, our studies reveal an evolutionary process that produces a multi-lateral network within the TME of medulloblastoma: a fraction of tumor cells trans-differentiate into TuAstrocytes, which, in turn, produce IL-4 that stimulates microglia to produce IGF1 to promote tumor progression.}, } @article {pmid31982725, year = {2020}, author = {Bissoli, I and Muscari, C}, title = {Doxorubicin and α-Mangostin oppositely affect luminal breast cancer cell stemness evaluated by a new retinaldehyde-dependent ALDH assay in MCF-7 tumor spheroids.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {124}, number = {}, pages = {109927}, doi = {10.1016/j.biopha.2020.109927}, pmid = {31982725}, issn = {1950-6007}, mesh = {Aldehyde Dehydrogenase/metabolism ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/pharmacology ; Breast Neoplasms/*drug therapy/pathology ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Doxorubicin/administration & dosage/*pharmacology ; Female ; Humans ; Inhibitory Concentration 50 ; MCF-7 Cells ; Neoplastic Stem Cells/*drug effects ; Retinaldehyde/metabolism ; Spheroids, Cellular/drug effects/metabolism ; Xanthones/administration & dosage/*pharmacology ; }, abstract = {According to cancer stem cell theory, only a limited number of self-renewing and cloning cells are responsible for tumor relapse after a period of remittance. The aim of the present study was to investigate the effects of Doxorubicin and α-Mangostin, two antiproliferative drugs, on both tumor bulk and stem cells in multicellular tumor spheroids originated from the luminal MCF-7 breast cancer cell line. A new and original fluorimetric assay was used to selectively measure the activity of the retinaldehyde-dependent isoenzymes of aldehyde dehydrogenase (RALDH), which are markers of a subpopulation of breast cancer stem cells. The administration of 5 μg/ml (12.2 μM) α-Mangostin for 48 h provoked: i) a marked disaggregation of the spheroids, leading to a doubling of their volume (p < 0.01), ii) a 40 % decrease in cell viability (p < 0.01), evaluated by the acid phosphatase assay, and iii) a reduction by more than 90 % of RALDH activity. By contrast, Doxorubicin given for 48 h in the range of 0.1-40 μM did not significantly reduce cell viability and caused only a modest modification of the spheroid morphology. Moreover, 40 μM Doxorubicin increased RALDH activity 2.5-fold compared to the untreated sample. When the two drugs were administered together using 5 μg/ml α-Mangostin, the IC50 of Doxorubicin referred to cell viability decreased six-fold and the RALDH activity was further reduced. In conclusion, the combined administration of Doxorubicin and α-Mangostin provoked a significant cytotoxicity and a remarkable inhibition of RALDH activity in MCF-7 tumor spheroids, suggesting that these drugs could be effective in reducing cell stemness in luminal breast cancer.}, } @article {pmid31975241, year = {2020}, author = {Puzakov, MV and Puzakova, LV and Cheresiz, SV}, title = {The Tc1-like elements with the spliceosomal introns in mollusk genomes.}, journal = {Molecular genetics and genomics : MGG}, volume = {295}, number = {3}, pages = {621-633}, doi = {10.1007/s00438-020-01645-1}, pmid = {31975241}, issn = {1617-4623}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; *DNA Transposable Elements ; Evolution, Molecular ; *Genome ; *Introns ; Mollusca/*genetics ; *Phylogeny ; RNA Splicing/*genetics ; Sequence Homology ; Transposases/*genetics ; }, abstract = {Transposable elements (TEs) are DNA sequences capable of transpositions within the genome and thus exerting a considerable influence on the genome functioning and structure and serving as a source of new genes. TE biodiversity studies in previously unexplored species are important for the fundamental understanding of the TE influence on eukaryotic genomes. TEs are classified into retrotransposons and DNA transposons. IS630/Tc1/mariner (ITm) superfamily of DNA transposons is one of the most diverse groups broadly represented among the eukaryotes. The study of 19 mollusk genomes revealed a new group of ITm superfamily elements, which we henceforth refer to as TLEWI. These TEs are characterized by the low copy number, the lack of terminal inverted repeats, the catalytic domain with DD36E signature and the presence of spliceosomal introns in transposase coding sequence. Their prevalence among the mollusks is limited to the class Bivalvia. Since TLEWI possess the features of domesticated TE and structures similar to the eukaryotic genes which are not typical for the DNA transposons, we consider the hypothesis of co-optation of TLEWI gene by the bivalves. The results of our study will fill the gap of knowledge about the prevalence, activity, and evolution of the ITm DNA transposons in multicellular genomes and will facilitate our understanding of the mechanisms of TE domestication by the host genome.}, } @article {pmid31971511, year = {2020}, author = {Narasimhan, M and Johnson, A and Prizak, R and Kaufmann, WA and Tan, S and Casillas-Pérez, B and Friml, J}, title = {Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {31971511}, issn = {2050-084X}, support = {I 3630/FWF_/Austrian Science Fund FWF/Austria ; ALTF 723-2015//European Molecular Biology Organization/ ; 742985//H2020 European Research Council/ ; I3630B25//Austrian Science Fund/ ; }, mesh = {*Arabidopsis/genetics/metabolism/physiology ; Biological Evolution ; *Clathrin/chemistry/metabolism/ultrastructure ; Clathrin-Coated Vesicles/chemistry/metabolism/ultrastructure ; *Coated Pits, Cell-Membrane/chemistry/metabolism/ultrastructure ; Endocytosis/*physiology ; Microscopy, Electron ; Models, Biological ; }, abstract = {In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes.}, } @article {pmid31965986, year = {2020}, author = {Reddy, PC and Pradhan, SJ and Karmodiya, K and Galande, S}, title = {Origin of RNA Polymerase II pause in eumetazoans: Insights from Hydra.}, journal = {Journal of biosciences}, volume = {45}, number = {}, pages = {}, pmid = {31965986}, issn = {0973-7138}, support = {//Wellcome Trust/United Kingdom ; IA/E/16/1/503057/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, mesh = {Animals ; Chromatin/*genetics/ultrastructure ; *Evolution, Molecular ; Gene Expression Regulation/genetics ; High-Throughput Nucleotide Sequencing ; Histones/genetics ; Humans ; Hydra/*genetics ; Mice ; Promoter Regions, Genetic ; RNA Polymerase II/*genetics ; Transcriptome/genetics ; }, abstract = {Multicellular organisms have evolved sophisticated mechanisms for responding to various developmental, environmental and physical stimuli by regulating transcription. The correlation of distribution of RNA Polymerase II (RNA Pol II) with transcription is well established in higher metazoans, however genome-wide information about its distribution in early metazoans, such as Hydra, is virtually absent. To gain insights into RNA Pol II-mediated transcription and chromatin organization in Hydra, we performed chromatin immunoprecipitation (ChIP)-coupled high-throughput sequencing (ChIP-seq) for RNA Pol II and Histone H3. Strikingly, we found that Hydra RNA Pol II is uniformly distributed across the entire gene body, as opposed to its counterparts in bilaterians such as human and mouse. Furthermore, correlation with transcriptome data revealed that the levels of RNA Pol II correlate with the magnitude of gene expression. Strikingly, the characteristic peak of RNA Pol II pause typically observed in bilaterians at the transcription start sites (TSSs) was not observed in Hydra. The RNA Pol II traversing ratio in Hydra was found to be intermediate to yeast and bilaterians. The search for factors involved in RNA Pol II pause revealed that RNA Pol II pausing machinery was most likely acquired first in Cnidaria. However, only a small subset of genes exhibited the promoter proximal RNP Pol II pause. Interestingly, the nucleosome occupancy is highest over the subset of paused genes as compared to total Hydra genes, which is another indication of paused RNA Pol II at these genes. Thus, this study provides evidence for the molecular basis of RNA Pol II pause early during the evolution of multicellular organisms.}, } @article {pmid31959809, year = {2020}, author = {Oña, L and Lachmann, M}, title = {Signalling architectures can prevent cancer evolution.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {674}, pmid = {31959809}, issn = {2045-2322}, mesh = {Animals ; *Biological Evolution ; Cell Division ; Humans ; Models, Theoretical ; Mutation ; Neoplasms/*genetics/*pathology ; Signal Transduction/*physiology ; }, abstract = {Cooperation between cells in multicellular organisms is preserved by an active regulation of growth through the control of cell division. Molecular signals used by cells for tissue growth are usually present during developmental stages, angiogenesis, wound healing and other processes. In this context, the use of molecular signals triggering cell division is a puzzle, because any molecule inducing and aiding growth can be exploited by a cancer cell, disrupting cellular cooperation. A significant difference is that normal cells in a multicellular organism have evolved in competition between high-level organisms to be altruistic, being able to send signals even if it is to their detriment. Conversely, cancer cells evolve their abuse over the cancer's lifespan by out-competing their neighbours. A successful mutation leading to cancer must evolve to be adaptive, enabling a cancer cell to send a signal that results in higher chances to be selected. Using a mathematical model of such molecular signalling mechanism, this paper argues that a signal mechanism would be effective against abuse by cancer if it affects the cell that generates the signal as well as neighbouring cells that would receive a benefit without any cost, resulting in a selective disadvantage for a cancer signalling cell. We find that such molecular signalling mechanisms normally operate in cells as exemplified by growth factors. In scenarios of global and local competition between cells, we calculate how this process affects the fixation probability of a mutant cell generating such a signal, and find that this process can play a key role in limiting the emergence of cancer.}, } @article {pmid31956023, year = {2020}, author = {Bowles, AMC and Bechtold, U and Paps, J}, title = {The Origin of Land Plants Is Rooted in Two Bursts of Genomic Novelty.}, journal = {Current biology : CB}, volume = {30}, number = {3}, pages = {530-536.e2}, doi = {10.1016/j.cub.2019.11.090}, pmid = {31956023}, issn = {1879-0445}, support = {BB/N016831/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Biological Evolution ; Embryophyta/*genetics ; *Evolution, Molecular ; *Genome, Plant ; Phylogeny ; }, abstract = {Over the last 470 Ma, plant evolution has seen major evolutionary transitions, such as the move from water to land and the origins of vascular tissues, seeds, and flowers [1]. These have resulted in the evolution of terrestrial flora that has shaped modern ecosystems and the diversification of the Plant Kingdom, Viridiplantae, into over 374,000 described species [2]. Each of these transitions was accompanied by the gain and loss of genes in plant genomes. For example, whole-genome duplications are known to be fundamental to the origins of both seed and flowering plants [3, 4]. With the ever-increasing quality and quantity of whole-genome data, evolutionary insight into origins of distinct plant groups using comparative genomic techniques is now feasible. Here, using an evolutionary genomics pipeline to compare 208 complete genomes, we analyze the gene content of the ancestral genomes of the last common ancestor of land plants and all other major groups of plant. This approach reveals an unprecedented level of fundamental genomic novelties in two nodes related to the origin of land plants: the first in the origin of streptophytes during the Ediacaran and another in the ancestor of land plants in the Ordovician. Our findings highlight the biological processes that evolved with the origin of land plants and emphasize the importance of conserved gene novelties in plant diversification. Comparisons to other eukaryotic studies suggest a separation of the genomic origins of multicellularity and terrestrialization in plants.}, } @article {pmid31952837, year = {2020}, author = {Rowe, M and Veerus, L and Trosvik, P and Buckling, A and Pizzari, T}, title = {The Reproductive Microbiome: An Emerging Driver of Sexual Selection, Sexual Conflict, Mating Systems, and Reproductive Isolation.}, journal = {Trends in ecology & evolution}, volume = {35}, number = {3}, pages = {220-234}, doi = {10.1016/j.tree.2019.11.004}, pmid = {31952837}, issn = {1872-8383}, mesh = {Animals ; Biological Evolution ; Female ; Male ; *Microbiota ; Reproduction ; *Reproductive Isolation ; Sexual Behavior, Animal ; }, abstract = {All multicellular organisms host microbial communities in and on their bodies, and these microbiomes can have major influences on host biology. Most research has focussed on the oral, skin, and gut microbiomes, whereas relatively little is known about the reproductive microbiome. Here, we review empirical evidence to show that reproductive microbiomes can have significant effects on the reproductive function and performance of males and females. We then discuss the likely repercussions of these effects for evolutionary processes related to sexual selection and sexual conflict, as well as mating systems and reproductive isolation. We argue that knowledge of the reproductive microbiome is fundamental to our understanding of the evolutionary ecology of reproductive strategies and sexual dynamics of host organisms.}, } @article {pmid31943343, year = {2020}, author = {Wang, Y and Wang, F and Hong, DK and Gao, SJ and Wang, R and Wang, JD}, title = {Molecular characterization of DNA methyltransferase 1 and its role in temperature change of armyworm Mythimna separata Walker.}, journal = {Archives of insect biochemistry and physiology}, volume = {103}, number = {4}, pages = {e21651}, doi = {10.1002/arch.21651}, pmid = {31943343}, issn = {1520-6327}, support = {2017J01422//National Key R&D Program of China/ ; CARS-17//Sugar Crop Research System/ ; 31601363//National Natural Science Foundation of China/ ; 2017J01422//Nature Science Foundation of Fujian/ ; }, mesh = {Amino Acid Sequence ; Animals ; Body Temperature ; DNA (Cytosine-5-)-Methyltransferase 1/chemistry/*genetics/metabolism ; Insect Proteins/chemistry/*genetics/metabolism ; Larva/genetics/growth & development/physiology ; Moths/genetics/growth & development/*physiology ; Ovum/growth & development/physiology ; Phylogeny ; Pupa/genetics/growth & development/physiology ; Sequence Alignment ; }, abstract = {DNA methylation refers to the addition of cytosine residues in a CpG context (5'-cytosine-phosphate-guanine-3'). As one of the most common mechanisms of epigenetic modification, it plays a crucial role in regulating gene expression and in a diverse range of biological processes across all multicellular organisms. The relationship between temperature and DNA methylation and how it acts on the adaptability of migratory insects remain unknown. In the present work, a 5,496 bp full-length complementary DNA encoding 1,436 amino acids (named MsDnmt1) was cloned from the devastating migratory pest oriental armyworm, Mythimna separata Walker. The protein shares 36.8-84.4% identity with other insect Dnmt1 isoforms. Spatial and temporal expression analysis revealed that MsDnmt1 was highly expressed in adult stages and head tissue. The changing temperature decreased the expression of MsDnmt1 in both high and low temperature condition. Besides, we found that M. separata exhibited the shortest duration time from the last instar to pupae under 36°C environment when injected with DNA methylation inhibitor. Therefore, our data highlight a potential role for DNA methylation in thermal resistance, which help us to understand the biological role adaptability and colonization of migratory pest in various environments.}, } @article {pmid31942240, year = {2019}, author = {Green, KJ and Jaiganesh, A and Broussard, JA}, title = {Desmosomes: Essential contributors to an integrated intercellular junction network.}, journal = {F1000Research}, volume = {8}, number = {}, pages = {}, pmid = {31942240}, issn = {2046-1402}, support = {K01 AR075087/AR/NIAMS NIH HHS/United States ; R01 AR041836/AR/NIAMS NIH HHS/United States ; R01 CA228196/CA/NCI NIH HHS/United States ; R37 AR043380/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Cytoskeleton/*physiology ; Desmosomes/*physiology ; Intercellular Junctions/*physiology ; Signal Transduction ; }, abstract = {The development of adhesive connections between cells was critical for the evolution of multicellularity and for organizing cells into complex organs with discrete compartments. Four types of intercellular junction are present in vertebrates: desmosomes, adherens junctions, tight junctions, and gap junctions. All are essential for the development of the embryonic layers and organs as well as adult tissue homeostasis. While each junction type is defined as a distinct entity, it is now clear that they cooperate physically and functionally to create a robust and functionally diverse system. During evolution, desmosomes first appeared in vertebrates as highly specialized regions at the plasma membrane that couple the intermediate filament cytoskeleton at points of strong cell-cell adhesion. Here, we review how desmosomes conferred new mechanical and signaling properties to vertebrate cells and tissues through their interactions with the existing junctional and cytoskeletal network.}, } @article {pmid31935413, year = {2020}, author = {Bodmer, WF and Crouch, DJM}, title = {Somatic selection of poorly differentiating variant stem cell clones could be a key to human ageing.}, journal = {Journal of theoretical biology}, volume = {489}, number = {}, pages = {110153}, doi = {10.1016/j.jtbi.2020.110153}, pmid = {31935413}, issn = {1095-8541}, support = {107212/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; 203131/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Aging/genetics ; Biological Evolution ; Cell Differentiation ; Clone Cells ; Humans ; *Stem Cells ; }, abstract = {Any replicating system in which heritable variants with differing replicative potentials can arise is subject to a Darwinian evolutionary process. The continually replicating adult tissue stem cells that control the integrity of many tissues of long-lived, multicellular, complex vertebrate organisms, including humans, constitute such a replicating system. Our suggestion is that somatic selection for mutations (or stable epigenetic changes) that cause an increased rate of adult tissue stem cell proliferation, and their long-term persistence, at the expense of normal differentiation, is a major key to the ageing process. Once an organism has passed the reproductive age, there is no longer any significant counterselection at the organismal level to this inevitable cellular level Darwinian process.}, } @article {pmid31911467, year = {2020}, author = {Del Cortona, A and Jackson, CJ and Bucchini, F and Van Bel, M and D'hondt, S and Škaloud, P and Delwiche, CF and Knoll, AH and Raven, JA and Verbruggen, H and Vandepoele, K and De Clerck, O and Leliaert, F}, title = {Neoproterozoic origin and multiple transitions to macroscopic growth in green seaweeds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {5}, pages = {2551-2559}, pmid = {31911467}, issn = {1091-6490}, mesh = {Chlorophyta/classification/*growth & development ; Ecosystem ; *Evolution, Molecular ; Phylogeny ; Seaweed/classification/*growth & development ; }, abstract = {The Neoproterozoic Era records the transition from a largely bacterial to a predominantly eukaryotic phototrophic world, creating the foundation for the complex benthic ecosystems that have sustained Metazoa from the Ediacaran Period onward. This study focuses on the evolutionary origins of green seaweeds, which play an important ecological role in the benthos of modern sunlit oceans and likely played a crucial part in the evolution of early animals by structuring benthic habitats and providing novel niches. By applying a phylogenomic approach, we resolve deep relationships of the core Chlorophyta (Ulvophyceae or green seaweeds, and freshwater or terrestrial Chlorophyceae and Trebouxiophyceae) and unveil a rapid radiation of Chlorophyceae and the principal lineages of the Ulvophyceae late in the Neoproterozoic Era. Our time-calibrated tree points to an origin and early diversification of green seaweeds in the late Tonian and Cryogenian periods, an interval marked by two global glaciations with strong consequent changes in the amount of available marine benthic habitat. We hypothesize that unicellular and simple multicellular ancestors of green seaweeds survived these extreme climate events in isolated refugia, and diversified in benthic environments that became increasingly available as ice retreated. An increased supply of nutrients and biotic interactions, such as grazing pressure, likely triggered the independent evolution of macroscopic growth via different strategies, including true multicellularity, and multiple types of giant-celled forms.}, } @article {pmid31880593, year = {2020}, author = {Wang, DG and Huang, FR and Chen, W and Zhou, Y and Wang, CY and Zhu, F and Shao, BJ and Luo, D}, title = {Clinicopathological Analysis of Acquired Melanocytic Nevi and a Preliminary Study on the Possible Origin of Nevus Cells.}, journal = {The American Journal of dermatopathology}, volume = {42}, number = {6}, pages = {414-422}, doi = {10.1097/DAD.0000000000001599}, pmid = {31880593}, issn = {1533-0311}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers/analysis ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Nevus, Pigmented/*pathology ; Retrospective Studies ; Skin Neoplasms/*pathology ; Stem Cells/*pathology ; Young Adult ; }, abstract = {BACKGROUND: The pathogenesis of acquired melanocytic nevi (AMN) is still unclear, and the origin of nevus cells has not been clarified.

OBJECTIVE: To analyze the clinical features and pathological types of AMN and identify the possible origin of nevus cells.

METHODS: A retrospective study of 2929 cases of AMN was conducted, and 96 specimens of intradermal and junctional nevi were selected. Immunohistochemical assays were performed to detect the expression of basement membrane component receptor DDR-1 and the molecular markers on epidermal melanocytes, dermal stem cells (DSCs), and hair follicle stem cells.

RESULTS: Junctional nevi and compound nevi were prone to occur on glabrous skin, such as the palms, soles, and vulva, and on the extremities in children, whereas intradermal nevi tended to develop on the trunk, head, and face of adults. The immunohistochemical data revealed that both junctional nevi and intradermal nevi expressed the epidermal melanocyte surface markers E-cadherin, DDR-1, and integrin α6 and the DSC molecular markers NGFRp-75 and nestin. CD34 was expressed only in junctional nevi, whereas K19 was not expressed in any type of melanocytic nevi. There was no significant difference in molecular expression at different sites or in different ages of onset. Nestin expression was markedly stronger in the intradermal nevi than in the junctional nevi, but there was no difference between the superficial and deep nevus cell nests of intradermal nevi.

CONCLUSION: AMN may have a multicellular origin that commonly follows the mode of Abtropfung. Furthermore, DSCs may partly or independently participate in the formation of nevus cells.}, } @article {pmid31879283, year = {2020}, author = {Erives, A and Fritzsch, B}, title = {A Screen for Gene Paralogies Delineating Evolutionary Branching Order of Early Metazoa.}, journal = {G3 (Bethesda, Md.)}, volume = {10}, number = {2}, pages = {811-826}, pmid = {31879283}, issn = {2160-1836}, support = {R01 AG060504/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Duplication/radiation effects ; *Genes ; *Genetic Testing/methods ; *Genomics/methods ; Genotype ; Phylogeny ; Plant Proteins ; }, abstract = {The evolutionary diversification of animals is one of Earth's greatest marvels, yet its earliest steps are shrouded in mystery. Animals, the monophyletic clade known as Metazoa, evolved wildly divergent multicellular life strategies featuring ciliated sensory epithelia. In many lineages epithelial sensoria became coupled to increasingly complex nervous systems. Currently, different phylogenetic analyses of single-copy genes support mutually-exclusive possibilities that either Porifera or Ctenophora is sister to all other animals. Resolving this dilemma would advance the ecological and evolutionary understanding of the first animals and the evolution of nervous systems. Here we describe a comparative phylogenetic approach based on gene duplications. We computationally identify and analyze gene families with early metazoan duplications using an approach that mitigates apparent gene loss resulting from the miscalling of paralogs. In the transmembrane channel-like (TMC) family of mechano-transducing channels, we find ancient duplications that define separate clades for Eumetazoa (Placozoa + Cnidaria + Bilateria) vs. Ctenophora, and one duplication that is shared only by Eumetazoa and Porifera. In the Max-like protein X (MLX and MLXIP) family of bHLH-ZIP regulators of metabolism, we find that all major lineages from Eumetazoa and Porifera (sponges) share a duplicated gene pair that is sister to the single-copy gene maintained in Ctenophora. These results suggest a new avenue for deducing deep phylogeny by choosing rather than avoiding ancient gene paralogies.}, } @article {pmid31866780, year = {2019}, author = {Durand, PM and Barreto Filho, MM and Michod, RE}, title = {Cell Death in Evolutionary Transitions in Individuality.}, journal = {The Yale journal of biology and medicine}, volume = {92}, number = {4}, pages = {651-662}, pmid = {31866780}, issn = {1551-4056}, mesh = {Animals ; *Apoptosis ; *Biological Evolution ; Ecological and Environmental Phenomena ; Eukaryotic Cells/cytology/metabolism ; Humans ; Insecta/physiology ; Signal Transduction ; }, abstract = {Programmed cell death (PCD) in cell groups and microbial communities affects population structures, nutrient recycling, and sociobiological interactions. A less explored area is the role played by PCD in the emergence of higher-level individuals. Here, we examine how cell death impacted evolutionary transitions in individuality (ETIs). The focus is on three specific ETIs - the emergence of the eukaryote cell, multicellularity, and social insects - and we review the theoretical and empirical evidence for the role of PCD in these three transitions. We find that PCD likely contributed to many of the processes involved in eukaryogenesis and the transition to multicellularity. PCD is important for the formation of cooperative groups and is a mechanism by which mutual dependencies between individuals evolve. PCD is also a conflict mediator and involved in division of labor in social groups and in the origin of new cell types. In multicellularity, PCD facilitates the transfer of fitness to the higher-level individual. In eusocial insects, PCD of the gonadal cells in workers is the basis for conflict mediation and the division of labor in the colony. In the three ETIs discussed here, PCD likely played an essential role, without which alternate mechanisms would have been necessary for these increases in complexity to occur.}, } @article {pmid31854473, year = {2020}, author = {Costa, ML and de Andrade Rosa, I and Andrade, L and Mermelstein, C and C Coutinho, C}, title = {Distinct interactions between epithelial and mesenchymal cells control cell morphology and collective migration during sponge epithelial to mesenchymal transition.}, journal = {Journal of morphology}, volume = {281}, number = {2}, pages = {183-195}, doi = {10.1002/jmor.21090}, pmid = {31854473}, issn = {1097-4687}, mesh = {Animals ; Cell Aggregation ; *Cell Movement ; *Cell Shape ; Epithelial Cells/*cytology/ultrastructure ; *Epithelial-Mesenchymal Transition ; Mesoderm/*cytology/ultrastructure ; Porifera/*cytology/ultrastructure ; }, abstract = {Epithelial and mesenchymal cell types are basic for animal multicellularity and they have complementary functions coordinated by cellular interactions. Sponges are especially important model organisms to address the evolutionary basis of morphogenetic programs for epithelial and mesenchymal organization in animals. Evolutionary studies in sponges can contribute to the understanding of the mechanisms that control tissue maintenance and tumor progression in humans. In the present study, sponge mesenchymal and epithelial cells were isolated from the demosponge Hymeniacidon heliophila, and aggregate formation was observed by video microscopy. Epithelial-mesenchymal interaction, epithelial transition, and cell migration led to sponge cell aggregation after drastic stress. Based on their different morphologies, adhesion specificities, and motilities, we suggest a role for different sponge cell types as well as complementary functions in cell aggregation. Micromanipulation under the microscope and cell tracking were also used to promote specific grafting-host interaction, to further test the effects of cell type interaction. The loss of cell polarity and flattened shape during the epithelial to mesenchymal cell transition generated small immobile aggregates of round/amoeboid cells. The motility of these transited epithelial-cell aggregates was observed by cell tracking using fluorescent dye, but only after interaction with streams of migratory mesenchymal cells. Cell motility occurred independently of morphological changes, indicating a progressive step in the transition toward a migratory mesenchymal state. Our data suggest a two-step signaling process: (a) the lack of interaction between mesenchymal and epithelial cells triggers morphological changes; and (b) migratory mesenchymal cells instruct epithelial cells for directional cell motility. These results could have an impact on the understanding of evolutionary aspects of metastatic cancer cells. HIGHLIGHTS: Morphogenetic movements observed in modern sponges could have a common evolutionary origin with collective cell migration of human metastatic cells. A sponge regenerative model was used here to characterize epithelial and mesenchymal cells, and for the promotion of grafting/host interactions with subsequent cell tracking. The transition from epithelial to mesenchymal cell type can be observed in sponges in two steps: (a) withdrawal of epithelial/mesenchymal cell interactions to trigger morphological changes; (b) migratory mesenchymal cells to induce epithelial cells to a collective migratory state.}, } @article {pmid31847093, year = {2019}, author = {Nakamura, T and Fahmi, M and Tanaka, J and Seki, K and Kubota, Y and Ito, M}, title = {Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.}, journal = {International journal of molecular sciences}, volume = {20}, number = {24}, pages = {}, pmid = {31847093}, issn = {1422-0067}, support = {NA//MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2015-2019)/ ; NA//Takeda Science Foundation/ ; }, mesh = {*Computer Simulation ; *Databases, Genetic ; Genome-Wide Association Study ; Glycoside Hydrolases/classification/*genetics ; Humans ; }, abstract = {Glycans are involved in various metabolic processes via the functions of glycosyltransferases and glycoside hydrolases. Analysing the evolution of these enzymes is essential for improving the understanding of glycan metabolism and function. Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases. Using cluster analysis, 319 human glycoside hydrolases were classified into four clusters based on their similarity to enzymes conserved in chordates or metazoans (Class 1), metazoans (Class 2), metazoans and plants (Class 3) and eukaryotes (Class 4). The eukaryote and metazoan clusters included N- and O-glycoside hydrolases, respectively. The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases. These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.}, } @article {pmid31845961, year = {2020}, author = {Majic, P and Payne, JL}, title = {Enhancers Facilitate the Birth of De Novo Genes and Gene Integration into Regulatory Networks.}, journal = {Molecular biology and evolution}, volume = {37}, number = {4}, pages = {1165-1178}, pmid = {31845961}, issn = {1537-1719}, mesh = {Animals ; DNA, Intergenic ; *Enhancer Elements, Genetic ; *Evolution, Molecular ; *Gene Regulatory Networks ; Mice ; Open Reading Frames ; Promoter Regions, Genetic ; Transcription, Genetic ; }, abstract = {Regulatory networks control the spatiotemporal gene expression patterns that give rise to and define the individual cell types of multicellular organisms. In eumetazoa, distal regulatory elements called enhancers play a key role in determining the structure of such networks, particularly the wiring diagram of "who regulates whom." Mutations that affect enhancer activity can therefore rewire regulatory networks, potentially causing adaptive changes in gene expression. Here, we use whole-tissue and single-cell transcriptomic and chromatin accessibility data from mouse to show that enhancers play an additional role in the evolution of regulatory networks: They facilitate network growth by creating transcriptionally active regions of open chromatin that are conducive to de novo gene evolution. Specifically, our comparative transcriptomic analysis with three other mammalian species shows that young, mouse-specific intergenic open reading frames are preferentially located near enhancers, whereas older open reading frames are not. Mouse-specific intergenic open reading frames that are proximal to enhancers are more highly and stably transcribed than those that are not proximal to enhancers or promoters, and they are transcribed in a limited diversity of cellular contexts. Furthermore, we report several instances of mouse-specific intergenic open reading frames proximal to promoters showing evidence of being repurposed enhancers. We also show that open reading frames gradually acquire interactions with enhancers over macroevolutionary timescales, helping integrate genes-those that have arisen de novo or by other means-into existing regulatory networks. Taken together, our results highlight a dual role of enhancers in expanding and rewiring gene regulatory networks.}, } @article {pmid31841515, year = {2019}, author = {Lamelza, P and Young, JM and Noble, LM and Caro, L and Isakharov, A and Palanisamy, M and Rockman, MV and Malik, HS and Ailion, M}, title = {Hybridization promotes asexual reproduction in Caenorhabditis nematodes.}, journal = {PLoS genetics}, volume = {15}, number = {12}, pages = {e1008520}, pmid = {31841515}, issn = {1553-7404}, support = {R01 GM074108/GM/NIGMS NIH HHS/United States ; R01 GM121828/GM/NIGMS NIH HHS/United States ; T32 GM007270/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis/genetics/*physiology ; Female ; Fertility ; *Hybridization, Genetic ; Male ; Maternal Inheritance ; Parthenogenesis ; Paternal Inheritance ; *Reproduction, Asexual ; Whole Genome Sequencing ; }, abstract = {Although most unicellular organisms reproduce asexually, most multicellular eukaryotes are obligately sexual. This implies that there are strong barriers that prevent the origin or maintenance of asexuality arising from an obligately sexual ancestor. By studying rare asexual animal species we can gain a better understanding of the circumstances that facilitate their evolution from a sexual ancestor. Of the known asexual animal species, many originated by hybridization between two ancestral sexual species. The balance hypothesis predicts that genetic incompatibilities between the divergent genomes in hybrids can modify meiosis and facilitate asexual reproduction, but there are few instances where this has been shown. Here we report that hybridizing two sexual Caenorhabditis nematode species (C. nouraguensis females and C. becei males) alters the normal inheritance of the maternal and paternal genomes during the formation of hybrid zygotes. Most offspring of this interspecies cross die during embryogenesis, exhibiting inheritance of a diploid C. nouraguensis maternal genome and incomplete inheritance of C. becei paternal DNA. However, a small fraction of offspring develop into viable adults that can be either fertile or sterile. Fertile offspring are produced asexually by sperm-dependent parthenogenesis (also called gynogenesis or pseudogamy); these progeny inherit a diploid maternal genome but fail to inherit a paternal genome. Sterile offspring are hybrids that inherit both a diploid maternal genome and a haploid paternal genome. Whole-genome sequencing of individual viable worms shows that diploid maternal inheritance in both fertile and sterile offspring results from an altered meiosis in C. nouraguensis oocytes and the inheritance of two randomly selected homologous chromatids. We hypothesize that hybrid incompatibility between C. nouraguensis and C. becei modifies maternal and paternal genome inheritance and indirectly induces gynogenetic reproduction. This system can be used to dissect the molecular mechanisms by which hybrid incompatibilities can facilitate the emergence of asexual reproduction.}, } @article {pmid31841132, year = {2020}, author = {Karimi, E and Geslain, E and KleinJan, H and Tanguy, G and Legeay, E and Corre, E and Dittami, SM}, title = {Genome Sequences of 72 Bacterial Strains Isolated from Ectocarpus subulatus: A Resource for Algal Microbiology.}, journal = {Genome biology and evolution}, volume = {12}, number = {1}, pages = {3647-3655}, pmid = {31841132}, issn = {1759-6653}, mesh = {Bacteria/genetics/isolation & purification/metabolism ; *Genome, Bacterial ; Phaeophyceae/*microbiology ; Phylogeny ; Secondary Metabolism/genetics ; Symbiosis ; Vitamins/biosynthesis ; }, abstract = {Brown algae are important primary producers and ecosystem engineers in the ocean, and Ectocarpus has been established as a laboratory model for this lineage. Like most multicellular organisms, Ectocarpus is associated with a community of microorganisms, a partnership frequently referred to as holobiont due to the tight interconnections between the components. Although genomic resources for the algal host are well established, its associated microbiome is poorly characterized from a genomic point of view, limiting the possibilities of using these types of data to study host-microbe interactions. To address this gap in knowledge, we present the annotated draft genome sequences of seventy-two cultivable Ectocarpus-associated bacteria. A screening of gene clusters related to the production of secondary metabolites revealed terpene, bacteriocin, NRPS, PKS-t3, siderophore, PKS-t1, and homoserine lactone clusters to be abundant among the sequenced genomes. These compounds may be used by the bacteria to communicate with the host and other microbes. Moreover, detoxification and provision of vitamin B pathways have been observed in most sequenced genomes, highlighting potential contributions of the bacterial metabolism toward host fitness and survival. The genomes sequenced in this study form a valuable resource for comparative genomic analyses and evolutionary surveys of alga-associated bacteria. They help establish Ectocarpus as a model for brown algal holobionts and will enable the research community to produce testable hypotheses about the molecular interactions within this complex system.}, } @article {pmid31840777, year = {2019}, author = {Kundert, P and Shaulsky, G}, title = {Cellular allorecognition and its roles in Dictyostelium development and social evolution.}, journal = {The International journal of developmental biology}, volume = {63}, number = {8-9-10}, pages = {383-393}, pmid = {31840777}, issn = {1696-3547}, support = {R35 GM118016/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Cell Adhesion ; Chemotaxis ; Dictyostelium/genetics/*immunology/*physiology ; Glycoproteins/genetics ; Glycosylation ; Ligands ; Models, Biological ; Phenotype ; Protozoan Proteins/genetics ; }, abstract = {The social amoeba Dictyostelium discoideum is a tractable model organism to study cellular allorecognition, which is the ability of a cell to distinguish itself and its genetically similar relatives from more distantly related organisms. Cellular allorecognition is ubiquitous across the tree of life and affects many biological processes. Depending on the biological context, these versatile systems operate both within and between individual organisms, and both promote and constrain functional heterogeneity. Some of the most notable allorecognition systems mediate neural self-avoidance in flies and adaptive immunity in vertebrates. D. discoideum's allorecognition system shares several structures and functions with other allorecognition systems. Structurally, its key regulators reside at a single genomic locus that encodes two highly polymorphic proteins, a transmembrane ligand called TgrC1 and its receptor TgrB1. These proteins exhibit isoform-specific, heterophilic binding across cells. Functionally, this interaction determines the extent to which co-developing D. discoideum strains co-aggregate or segregate during the aggregation phase of multicellular development. The allorecognition system thus affects both development and social evolution, as available evidence suggests that the threat of developmental cheating represents a primary selective force acting on it. Other significant characteristics that may inform the study of allorecognition in general include that D. discoideum's allorecognition system is a continuous and inclusive trait, it is pleiotropic, and it is temporally regulated.}, } @article {pmid31840776, year = {2019}, author = {Medina, JM and Shreenidhi, PM and Larsen, TJ and Queller, DC and Strassmann, JE}, title = {Cooperation and conflict in the social amoeba Dictyostelium discoideum.}, journal = {The International journal of developmental biology}, volume = {63}, number = {8-9-10}, pages = {371-382}, doi = {10.1387/ijdb.190158jm}, pmid = {31840776}, issn = {1696-3547}, mesh = {Altruism ; Biological Evolution ; Dictyostelium/genetics/*physiology ; Genetic Variation ; Genetics, Population ; Genotype ; Models, Biological ; Reproduction ; Selection, Genetic ; Spores, Protozoan/*physiology ; }, abstract = {The social amoeba Dictyostelium discoideum has provided considerable insight into the evolution of cooperation and conflict. Under starvation, D. discoideum amoebas cooperate to form a fruiting body comprised of hardy spores atop a stalk. The stalk development is altruistic because stalk cells die to aid spore dispersal. The high relatedness of cells in fruiting bodies in nature implies that this altruism often benefits relatives. However, since the fruiting body forms through aggregation there is potential for non-relatives to join the aggregate and create conflict over spore and stalk fates. Cheating is common in chimeras of social amoebas, where one genotype often takes advantage of the other and makes more spores. This social conflict is a significant force in nature as indicated by rapid rates of adaptive evolution in genes involved in cheating and its resistance. However, cheating can be prevented by high relatedness, allorecognition via tgr genes, pleiotropy and evolved resistance. Future avenues for the study of cooperation and conflict in D. discoideum include the sexual cycle as well as the relationship between D. discoideum and its bacterial symbionts. D. discoideum's tractability in the laboratory as well as its uncommon mode of aggregative multicellularity have established it as a promising model for future studies of cooperation and conflict.}, } @article {pmid31840775, year = {2019}, author = {Kawabe, Y and Du, Q and Schilde, C and Schaap, P}, title = {Evolution of multicellularity in Dictyostelia.}, journal = {The International journal of developmental biology}, volume = {63}, number = {8-9-10}, pages = {359-369}, pmid = {31840775}, issn = {1696-3547}, mesh = {*Biological Evolution ; Cell Differentiation ; Cyclic AMP/metabolism ; Dictyostelium/*genetics/*physiology ; Gene Expression Regulation ; Genome ; Genomics ; Phenotype ; Phylogeny ; Protein Domains ; Signal Transduction ; }, abstract = {The well-orchestrated multicellular life cycle of Dictyostelium discoideum has fascinated biologists for over a century. Self-organisation of its amoebas into aggregates, migrating slugs and fruiting structures by pulsatile cAMP signalling and their ability to follow separate differentiation pathways in well-regulated proportions continue to be topics under investigation. A striking aspect of D. discoideum development is the recurrent use of cAMP as chemoattractant, differentiation inducing signal and second messenger for other signals that control the developmental programme. D. discoideum is one of >150 species of Dictyostelia and aggregative life styles similar to those of Dictyostelia evolved many times in eukaryotes. Here we review experimental studies investigating how phenotypic complexity and cAMP signalling co-evolved in Dictyostelia. In addition, we summarize comparative genomic studies of multicellular Dictyostelia and unicellular Amoebozoa aimed to identify evolutionary conservation and change in all genes known to be essential for D. discoideum development.}, } @article {pmid31840773, year = {2019}, author = {Nanjundiah, V}, title = {Individual and collective behaviour in cellular slime mould development: contributions of John Bonner (1920-2019).}, journal = {The International journal of developmental biology}, volume = {63}, number = {8-9-10}, pages = {333-342}, doi = {10.1387/ijdb.190272vn}, pmid = {31840773}, issn = {1696-3547}, mesh = {Animals ; Biological Evolution ; Body Patterning ; Cell Biology/history ; Chemotaxis ; Developmental Biology/history ; Dictyostelium/*genetics/*physiology ; History, 20th Century ; History, 21st Century ; Humans ; Models, Biological ; Selection, Genetic ; }, abstract = {John Bonner used the cellular slime moulds to address issues that lie at the heart of evolutionary and developmental biology. He did so mostly by combining acute observation and a knack for asking the right questions with the methods of classical embryology. The present paper focusses on his contributions to understanding two phenomena that are characteristic of development in general: chemotaxis of single cells to an external attractant, and spatial patterning and proportioning of cell types in the multicellular aggregate. Brief mention is also made of other areas of slime mould biology where he made significant inputs. He saw cellular slime moulds as exemplars of development and worthy of study in their own right. His ideas continue to inspire researchers.}, } @article {pmid31830880, year = {2020}, author = {Heredia-Soto, V and Redondo, A and Kreilinger, JJP and Martínez-Marín, V and Berjón, A and Mendiola, M}, title = {3D Culture Modelling: An Emerging Approach for Translational Cancer Research in Sarcomas.}, journal = {Current medicinal chemistry}, volume = {27}, number = {29}, pages = {4778-4788}, doi = {10.2174/0929867326666191212162102}, pmid = {31830880}, issn = {1875-533X}, mesh = {Humans ; *Neoplasm Recurrence, Local ; *Sarcoma/therapy ; Spheroids, Cellular ; *Translational Research, Biomedical ; }, abstract = {Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.}, } @article {pmid31820036, year = {2020}, author = {Arasu, UT and Deen, AJ and Pasonen-Seppänen, S and Heikkinen, S and Lalowski, M and Kärnä, R and Härkönen, K and Mäkinen, P and Lázaro-Ibáñez, E and Siljander, PR and Oikari, S and Levonen, AL and Rilla, K}, title = {HAS3-induced extracellular vesicles from melanoma cells stimulate IHH mediated c-Myc upregulation via the hedgehog signaling pathway in target cells.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {77}, number = {20}, pages = {4093-4115}, pmid = {31820036}, issn = {1420-9071}, support = {276426, 284520//Academy of Finland/ ; 312519//Academy of Finland/ ; }, mesh = {Cell Line ; Cell Line, Tumor ; Cell Proliferation/genetics ; Epithelial-Mesenchymal Transition/genetics ; Extracellular Vesicles/*genetics ; Hedgehog Proteins/*genetics ; Humans ; Hyaluronan Receptors/genetics ; Hyaluronan Synthases/*genetics ; Melanoma/*genetics ; Proto-Oncogene Proteins c-myc/*genetics ; Signal Transduction/genetics ; Up-Regulation/*genetics ; }, abstract = {Intercellular communication is fundamental to the survival and maintenance of all multicellular systems, whereas dysregulation of communication pathways can drive cancer progression. Extracellular vesicles (EVs) are mediators of cell-to-cell communication that regulate a variety of cellular processes involved in tumor progression. Overexpression of a specific plasma membrane enzyme, hyaluronan synthase 3 (HAS3), is one of the factors that can induce EV shedding. HAS3, and particularly its product hyaluronan (HA), are carried by EVs and are known to be associated with the tumorigenic properties of cancer cells. To elucidate the specific effects of cancerous, HAS3-induced EVs on target cells, normal human keratinocytes and melanoma cells were treated with EVs derived from GFP-HAS3 expressing metastatic melanoma cells. We found that the HA receptor CD44 participated in the regulation of EV binding to target cells. Furthermore, GFP-HAS3-positive EVs induced HA secretion, proliferation and invasion of target cells. Our results suggest that HAS3-EVs contains increased quantities of IHH, which activates the target cell hedgehog signaling cascade and leads to the activation of c-Myc and regulation of claspin expression. This signaling of IHH in HAS3-EVs resulted in increased cell proliferation. Claspin immunostaining correlated with HA content in human cutaneous melanocytic lesions, supporting our in vitro findings and suggesting a reciprocal regulation between claspin expression and HA synthesis. This study shows for the first time that EVs originating from HAS3 overexpressing cells carry mitogenic signals that induce proliferation and epithelial-to-mesenchymal transition in target cells. The study also identifies a novel feedback regulation between the hedgehog signaling pathway and HA metabolism in melanoma, mediated by EVs carrying HA and IHH.}, } @article {pmid31819969, year = {2020}, author = {Niklas, KJ and Newman, SA}, title = {The many roads to and from multicellularity.}, journal = {Journal of experimental botany}, volume = {71}, number = {11}, pages = {3247-3253}, pmid = {31819969}, issn = {1460-2431}, mesh = {Animals ; *Biological Evolution ; *Ecosystem ; Fungi/genetics ; Genome ; Plants ; }, abstract = {The multiple origins of multicellularity had far-reaching consequences ranging from the appearance of phenotypically complex life-forms to their effects on Earth's aquatic and terrestrial ecosystems. Yet, many important questions remain. For example, do all lineages and clades share an ancestral developmental predisposition for multicellularity emerging from genomic and biophysical motifs shared from a last common ancestor, or are the multiple origins of multicellularity truly independent evolutionary events? In this review, we highlight recent developments and pitfalls in understanding the evolution of multicellularity with an emphasis on plants (here defined broadly to include the polyphyletic algae), but also draw upon insights from animals and their holozoan relatives, fungi and amoebozoans. Based on our review, we conclude that the evolution of multicellular organisms requires three phases (origination by disparate cell-cell attachment modalities, followed by integration by lineage-specific physiological mechanisms, and autonomization by natural selection) that have been achieved differently in different lineages.}, } @article {pmid31818855, year = {2020}, author = {Hofmann, K}, title = {The Evolutionary Origins of Programmed Cell Death Signaling.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {12}, number = {9}, pages = {}, pmid = {31818855}, issn = {1943-0264}, mesh = {Animals ; *Apoptosis ; Apoptosis Regulatory Proteins/*metabolism ; *Biological Evolution ; Humans ; *Signal Transduction ; }, abstract = {Programmed cell death (PCD) pathways are found in many phyla, ranging from developmentally programmed apoptosis in animals to cell-autonomous programmed necrosis pathways that limit the spread of biotrophic pathogens in multicellular assemblies. Prominent examples for the latter include animal necroptosis and pyroptosis, plant hypersensitive response (HR), and fungal heterokaryon incompatibility (HI) pathways. PCD pathways in the different kingdoms show fundamental differences in execution mechanism, morphology of the dying cells, and in the biological sequelae. Nevertheless, recent studies have revealed remarkable evolutionary parallels, including a striking sequence relationship between the "HeLo" domains found in the pore-forming components of necroptosis and some types of plant HR and fungal HI pathways. Other PCD execution components show cross-kingdom conservation as well, or are derived from prokaryotic ancestors. The currently available data suggest a model, wherein the primordial eukaryotic PCD pathway used proteins similar to present-day plant R-proteins and caused necrotic cell death by direct action of Toll and IL-1 receptor (TIR) and HeLo-like domains.}, } @article {pmid31818848, year = {2020}, author = {Lee, MF and Trotman, LC}, title = {PTEN: Bridging Endocytosis and Signaling.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {10}, number = {10}, pages = {}, pmid = {31818848}, issn = {2157-1422}, support = {P30 CA045508/CA/NCI NIH HHS/United States ; R01 CA137050/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Endocytosis ; Humans ; PTEN Phosphohydrolase/*metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Proto-Oncogene Proteins c-akt/*metabolism ; *Signal Transduction ; }, abstract = {The transduction of signals in the PTEN/PI3-kinase (PI3K) pathway is built around a phosphoinositide (PIP) lipid messenger, phosphatidylinositol trisphosphate, PI(3,4,5)P3 or PIP3 Another, more ancient role of this family of messengers is the control of endocytosis, where a handful of separate PIPs act like postal codes. Prominent among them is PI(3)P, which helps to ensure that endocytic vesicles, their cargo, and membranes themselves reach their correct destinations. Traditionally, the cancer and the endocytic functions of the PI3K signaling pathway have been studied by cancer and membrane biologists, respectively, with some notable but overall minimal overlap. Modern microscopy has enabled monitoring of the PTEN/PI3K pathway in action. Here, we explore the flurry of groundbreaking concepts emerging from those efforts. The discovery that PTEN contains an autonomous PI(3)P reader domain, fused to the catalytic PIP3 eraser domain has prompted us to explore the relationship between PI3K signaling and endocytosis. This revealed how PTEN can achieve signal termination in a precisely controlled fashion, because endocytosis can package the PIP3 signal into discrete units that PTEN will erase. We explore how PTEN can bridge the worlds of endocytosis and PI3K signaling and discuss progress on how PI3K/AKT signaling can be acting from internal membranes. We discuss how the PTEN/PI3K system for growth control may have emerged from principles of endocytosis, and how this development could have affected the evolution of multicellular organisms.}, } @article {pmid31818732, year = {2020}, author = {Shuryak, I}, title = {Review of resistance to chronic ionizing radiation exposure under environmental conditions in multicellular organisms.}, journal = {Journal of environmental radioactivity}, volume = {212}, number = {}, pages = {106128}, doi = {10.1016/j.jenvrad.2019.106128}, pmid = {31818732}, issn = {1879-1700}, mesh = {Animals ; Humans ; Phylogeny ; *Radiation Exposure ; *Radiation Monitoring ; Radiation, Ionizing ; Radioisotopes ; }, abstract = {Ionizing radiation resistance occurs among many phylogenetic groups and its mechanisms remain incompletely understood. Tolerances to acute and chronic irradiation do not always correlate because different mechanisms may be involved. The radioresistance phenomenon becomes even more complex in the field than in the laboratory because the effects of radioactive contamination on natural populations are intertwined with those of other factors, such as bioaccumulation of radionuclides, interspecific competition, seasonal variations in environmental conditions, and land use changes due to evacuation of humans from contaminated areas. Previous reviews of studies performed in radioactive sites like the Kyshtym, Chernobyl, and Fukushima accident regions, and of protracted irradiation experiments, often focused on detecting radiation effects at low doses in radiosensitive organisms. Here we review the literature with a different purpose: to identify organisms with high tolerance to chronic irradiation under environmental conditions, which maintained abundant populations and/or outcompeted more radiosensitive species at high dose rates. Taxa for which consistent evidence for radioresistance came from multiple studies conducted in different locations and at different times were found among plants (e.g. willow and birch trees, sedges), invertebrate and vertebrate animals (e.g. rotifers, some insects, crustaceans and freshwater fish). These organisms are not specialized "extremophiles", but tend to tolerate broad ranges of environmental conditions and stresses, have small genomes, reproduce quickly and/or disperse effectively over long distances. Based on these findings, resistance to radioactive contamination can be examined in a more broad context of chronic stress responses.}, } @article {pmid31814500, year = {2020}, author = {Nguyen, H and Das, U and Xie, J}, title = {Genome-wide evolution of wobble base-pairing nucleotides of branchpoint motifs with increasing organismal complexity.}, journal = {RNA biology}, volume = {17}, number = {3}, pages = {311-324}, pmid = {31814500}, issn = {1555-8584}, mesh = {Alternative Splicing ; Ascomycota/cytology/*genetics ; *Base Pairing ; Basidiomycota/genetics ; Cytidine/genetics ; Evolution, Molecular ; Fungal Proteins/genetics ; *Genome, Fungal ; *Nucleotide Motifs ; *RNA Splice Sites ; RNA, Small Nuclear ; }, abstract = {How have the branchpoint motifs evolved in organisms of different complexity? Here we identified and examined the consensus motifs (R1C2T3R4A5Y6, R: A or G, Y: C or T) of 898 fungal genomes. In Ascomycota unicellular yeasts, the G4/A4 ratio is mostly (98%) below 0.125 but increases sharply in multicellular species by about 40 times on average, and in the more complex Basidiomycota, it increases further by about 7 times. The global G4 increase is consistent with A4 to G4 transitions in evolution. Of the G4/A4-interacting amino acids of the branchpoint binding protein MSL5 (SF1) and the HSH155 (SF3B1), as well as the 5' splice sites (SS) and U2 snRNA genes, the 5' SS G[3]/A[3] co-vary with the G4 to some extent. However, corresponding increase of the G4-complementary GCAGTA-U2 gene is rare, suggesting wobble-base pairing between the G4-containing branchpoint motif and GTAGTA-U2 in most of these species. Interestingly, the G4/A4 ratio correlates well with the abundance of alternative splicing in the two phyla, and G4 enriched significantly at the alternative 3' SS of genes in RNA metabolism, kinases and membrane proteins. Similar wobble nucleotides also enriched at the 3' SS of multicellular fungi with only thousands of protein-coding genes. Thus, branchpoint motifs have evolved U2-complementarity in unicellular Ascomycota yeasts, but have gradually gained more wobble base-pairing nucleotides in fungi of higher complexity, likely to destabilize branchpoint motif-U2 interaction and/or branchpoint A protrusion for alternative splicing. This implies an important role of relaxing the branchpoint signals in the multicellularity and further complexity of fungi.}, } @article {pmid31805037, year = {2019}, author = {Thomas, F and Giraudeau, M and Renaud, F and Ujvari, B and Roche, B and Pujol, P and Raymond, M and Lemaitre, JF and Alvergne, A}, title = {Can postfertile life stages evolve as an anticancer mechanism?.}, journal = {PLoS biology}, volume = {17}, number = {12}, pages = {e3000565}, pmid = {31805037}, issn = {1545-7885}, mesh = {Adaptation, Physiological/*physiology ; Animals ; Biological Evolution ; Female ; Humans ; Menopause/metabolism/*physiology ; Neoplasms/physiopathology/*prevention & control ; Reproduction/physiology ; }, abstract = {Why a postfertile stage has evolved in females of some species has puzzled evolutionary biologists for over 50 years. We propose that existing adaptive explanations have underestimated in their formulation an important parameter operating both at the specific and the individual levels: the balance between cancer risks and cancer defenses. During their life, most multicellular organisms naturally accumulate oncogenic processes in their body. In parallel, reproduction, notably the pregnancy process in mammals, exacerbates the progression of existing tumors in females. When, for various ecological or evolutionary reasons, anticancer defenses are too weak, given cancer risk, older females could not pursue their reproduction without triggering fatal metastatic cancers, nor even maintain a normal reproductive physiology if the latter also promotes the growth of existing oncogenic processes, e.g., hormone-dependent malignancies. At least until stronger anticancer defenses are selected for in these species, females could achieve higher inclusive fitness by ceasing their reproduction and/or going through menopause (assuming that these traits are easier to select than anticancer defenses), thereby limiting the risk of premature death due to metastatic cancers. Because relatively few species experience such an evolutionary mismatch between anticancer defenses and cancer risks, the evolution of prolonged life after reproduction could also be a rare, potentially transient, anticancer adaptation in the animal kingdom.}, } @article {pmid31802185, year = {2020}, author = {Walker, DM and Hill, AJ and Albecker, MA and McCoy, MW and Grisnik, M and Romer, A and Grajal-Puche, A and Camp, C and Kelehear, C and Wooten, J and Rheubert, J and Graham, SP}, title = {Variation in the Slimy Salamander (Plethodon spp.) Skin and Gut-Microbial Assemblages Is Explained by Geographic Distance and Host Affinity.}, journal = {Microbial ecology}, volume = {79}, number = {4}, pages = {985-997}, doi = {10.1007/s00248-019-01456-x}, pmid = {31802185}, issn = {1432-184X}, mesh = {Animal Distribution ; Animals ; Bacteria/isolation & purification ; *Bacterial Physiological Phenomena ; Fungi/isolation & purification/*physiology ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; *Microbiota ; Mycobiome ; Skin/*microbiology ; Southeastern United States ; Spatial Analysis ; Tennessee ; Caudata/*microbiology ; }, abstract = {A multicellular host and its microbial communities are recognized as a metaorganism-a composite unit of evolution. Microbial communities have a variety of positive and negative effects on the host life history, ecology, and evolution. This study used high-throughput amplicon sequencing to characterize the complete skin and gut microbial communities, including both bacteria and fungi, of a terrestrial salamander, Plethodon glutinosus (Family Plethodontidae). We assessed salamander populations, representing nine mitochondrial haplotypes ('clades'), for differences in microbial assemblages across 13 geographic locations in the Southeastern United States. We hypothesized that microbial assemblages were structured by both host factors and geographic distance. We found a strong correlation between all microbial assemblages at close geographic distances, whereas, as spatial distance increases, the patterns became increasingly discriminate. Network analyses revealed that gut-bacterial communities have the highest degree of connectedness across geographic space. Host salamander clade was explanatory of skin-bacterial and gut-fungal assemblages but not gut-bacterial assemblages, unless the latter were analyzed within a phylogenetic context. We also inferred the function of gut-fungal assemblages to understand how an understudied component of the gut microbiome may influence salamander life history. We concluded that dispersal limitation may in part describe patterns in microbial assemblages across space and also that the salamander host may select for skin and gut communities that are maintained over time in closely related salamander populations.}, } @article {pmid31799909, year = {2020}, author = {Fields, C and Bischof, J and Levin, M}, title = {Morphological Coordination: A Common Ancestral Function Unifying Neural and Non-Neural Signaling.}, journal = {Physiology (Bethesda, Md.)}, volume = {35}, number = {1}, pages = {16-30}, doi = {10.1152/physiol.00027.2019}, pmid = {31799909}, issn = {1548-9221}, mesh = {Animals ; *Biological Evolution ; Humans ; Models, Biological ; Nervous System/*pathology ; Neurons/*physiology ; Regenerative Medicine/methods ; Signal Transduction/*physiology ; }, abstract = {Nervous systems are traditionally thought of as providing sensing and behavioral coordination functions at the level of the whole organism. What is the evolutionary origin of the mechanisms enabling the nervous systems' information processing ability? Here, we review evidence from evolutionary, developmental, and regenerative biology suggesting a deeper, ancestral function of both pre-neural and neural cell-cell communication systems: the long-distance coordination of cell division and differentiation required to create and maintain body-axis symmetries. This conceptualization of the function of nervous system activity sheds new light on the evolutionary transition from the morphologically rudimentary, non-neural Porifera and Placazoa to the complex morphologies of Ctenophores, Cnidarians, and Bilaterians. It further allows a sharp formulation of the distinction between long-distance axis-symmetry coordination based on external coordinates, e.g., by whole-organism scale trophisms as employed by plants and sessile animals, and coordination based on body-centered coordinates as employed by motile animals. Thus we suggest that the systems that control animal behavior evolved from ancient mechanisms adapting preexisting ionic and neurotransmitter mechanisms to regulate individual cell behaviors during morphogenesis. An appreciation of the ancient, non-neural origins of bioelectrically mediated computation suggests new approaches to the study of embryological development, including embryological dysregulation, cancer, regenerative medicine, and synthetic bioengineering.}, } @article {pmid31798628, year = {2019}, author = {Baumgartner, M and Drake, K and Kanadia, RN}, title = {An Integrated Model of Minor Intron Emergence and Conservation.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {1113}, pmid = {31798628}, issn = {1664-8021}, support = {R01 NS102538/NS/NINDS NIH HHS/United States ; }, abstract = {Minor introns constitute <0.5% of the introns in the human genome and have remained an enigma since their discovery. These introns are removed by a distinct splicing complex, the minor spliceosome. Both are ancient, tracing back to the last eukaryotic common ancestor (LECA), which is reflected by minor intron enrichment in specific gene families, such as the mitogen activated-protein kinase kinases, voltage-gated sodium and calcium ion channels, and E2F transcription factors. Most minor introns occur as single introns in genes with predominantly major introns. Due to this organization, minor intron-containing gene (MIG) expression requires the coordinated action of two spliceosomes, which increases the probability of missplicing. Thus, one would expect loss of minor introns via purifying selection. This has resulted in complete minor intron loss in at least nine eukaryotic lineages. However, minor introns are highly conserved in land plants and metazoans, where their importance is underscored by embryonic lethality when the minor spliceosome is inactivated. Conditional inactivation of the minor spliceosome has shown that rapidly dividing progenitor cells are highly sensitive to minor spliceosome loss. Indeed, we found that MIGs were significantly enriched in a screen for genes essential for survival in 341 cycling cell lines. Here, we propose that minor introns inserted randomly into genes in LECA or earlier and were subsequently conserved in genes crucial for cycling cell survival. We hypothesize that the essentiality of MIGs allowed minor introns to endure through the unicellularity of early eukaryotic evolution. Moreover, we identified 59 MIGs that emerged after LECA, and that many of these are essential for cycling cell survival, reinforcing our essentiality model for MIG conservation. This suggests that minor intron emergence is dynamic across eukaryotic evolution, and that minor introns should not be viewed as molecular fossils. We also posit that minor intron splicing was co-opted in multicellular evolution as a regulatory switch for en masse control of MIG expression and the biological processes they regulate. Specifically, this mode of regulation could control cell proliferation and thus body size, an idea supported by domestication syndrome, wherein MIGs are enriched in common candidate animal domestication genes.}, } @article {pmid31794757, year = {2019}, author = {Jékely, G}, title = {Evolution: How Not to Become an Animal.}, journal = {Current biology : CB}, volume = {29}, number = {23}, pages = {R1240-R1242}, doi = {10.1016/j.cub.2019.10.014}, pmid = {31794757}, issn = {1879-0445}, mesh = {Animals ; *Choanoflagellata ; }, abstract = {The origin of animals has always fascinated biologists. Studies on choanoflagellates, the closest living relatives of animals, have contributed major insights. The discovery of a multicellular choanoflagellate with light-regulated collective behaviour now provides a new perspective.}, } @article {pmid31788034, year = {2019}, author = {Southworth, J and Grace, CA and Marron, AO and Fatima, N and Carr, M}, title = {A genomic survey of transposable elements in the choanoflagellate Salpingoeca rosetta reveals selection on codon usage.}, journal = {Mobile DNA}, volume = {10}, number = {}, pages = {44}, pmid = {31788034}, issn = {1759-8753}, abstract = {BACKGROUND: Unicellular species make up the majority of eukaryotic diversity, however most studies on transposable elements (TEs) have centred on multicellular host species. Such studies may have therefore provided a limited picture of how transposable elements evolve across eukaryotes. The choanoflagellates, as the sister group to Metazoa, are an important study group for investigating unicellular to multicellular transitions. A previous survey of the choanoflagellate Monosiga brevicollis revealed the presence of only three families of LTR retrotransposons, all of which appeared to be active. Salpingoeca rosetta is the second choanoflagellate to have its whole genome sequenced and provides further insight into the evolution and population biology of transposable elements in the closest relative of metazoans.

RESULTS: Screening the genome revealed the presence of a minimum of 20 TE families. Seven of the annotated families are DNA transposons and the remaining 13 families are LTR retrotransposons. Evidence for two putative non-LTR retrotransposons was also uncovered, but full-length sequences could not be determined. Superfamily phylogenetic trees indicate that vertical inheritance and, in the case of one family, horizontal transfer have been involved in the evolution of the choanoflagellates TEs. Phylogenetic analyses of individual families highlight recent element activity in the genome, however six families did not show evidence of current transposition. The majority of families possess young insertions and the expression levels of TE genes vary by four orders of magnitude across families. In contrast to previous studies on TEs, the families present in S. rosetta show the signature of selection on codon usage, with families favouring codons that are adapted to the host translational machinery. Selection is stronger in LTR retrotransposons than DNA transposons, with highly expressed families showing stronger codon usage bias. Mutation pressure towards guanosine and cytosine also appears to contribute to TE codon usage.

CONCLUSIONS: S. rosetta increases the known diversity of choanoflagellate TEs and the complement further highlights the role of horizontal gene transfer from prey species in choanoflagellate genome evolution. Unlike previously studied TEs, the S. rosetta families show evidence for selection on their codon usage, which is shown to act via translational efficiency and translational accuracy.}, } @article {pmid31766724, year = {2019}, author = {Kar, R and Jha, NK and Jha, SK and Sharma, A and Dholpuria, S and Asthana, N and Chaurasiya, K and Singh, VK and Burgee, S and Nand, P}, title = {A "NOTCH" Deeper into the Epithelial-To-Mesenchymal Transition (EMT) Program in Breast Cancer.}, journal = {Genes}, volume = {10}, number = {12}, pages = {}, pmid = {31766724}, issn = {2073-4425}, mesh = {Animals ; Breast Neoplasms/*genetics ; *Epithelial-Mesenchymal Transition ; Female ; Humans ; Receptors, Notch/*genetics ; Signal Transduction ; }, abstract = {Notch signaling is a primitive signaling pathway having various roles in the normal origin and development of each multicellular organisms. Therefore, any aberration in the pathway will inevitably lead to deadly outcomes such as cancer. It has now been more than two decades since Notch was acknowledged as an oncogene in mouse mammary tumor virus-infected mice. Since that discovery, activated Notch signaling and consequent up-regulation of tumor-promoting Notch target genes have been observed in human breast cancer. Moreover, consistent over-expression of Notch ligands and receptors has been shown to correlate with poor prognosis in human breast cancer. Notch regulates a number of key processes during breast carcinogenesis, of which, one key phenomenon is epithelial-mesenchymal transition (EMT). EMT is a key process for large-scale cell movement during morphogenesis at the time of embryonic development. Cancer cells aided by transcription factors usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. In this review, we recapitulate recent progress in breast cancer research that has provided new perceptions into the molecular mechanisms behind Notch-mediated EMT regulation during breast tumorigenesis.}, } @article {pmid31752673, year = {2019}, author = {Forbes, G and Chen, ZH and Kin, K and Lawal, HM and Schilde, C and Yamada, Y and Schaap, P}, title = {Phylogeny-wide conservation and change in developmental expression, cell-type specificity and functional domains of the transcriptional regulators of social amoebas.}, journal = {BMC genomics}, volume = {20}, number = {1}, pages = {890}, pmid = {31752673}, issn = {1471-2164}, support = {100293/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; 742288//H2020 European Research Council/ ; RPG-2016-220//Leverhulme Trust/ ; ALTF 295-2015//European Molecular Biology Organization/ ; H28-1002//Japan Society for the Promotion of Science/ ; }, mesh = {Amoebozoa/classification/*genetics/growth & development/metabolism ; Dictyostelium/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Phenotype ; Phylogeny ; Protein Domains ; Transcription Factors/chemistry/*genetics/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Dictyostelid social amoebas self-organize into fruiting bodies, consisting of spores and up to four supporting cell types in the phenotypically most complex taxon group 4. High quality genomes and stage- and cell-type specific transcriptomes are available for representative species of each of the four taxon groups. To understand how evolution of gene regulation in Dictyostelia contributed to evolution of phenotypic complexity, we analysed conservation and change in abundance, functional domain architecture and developmental regulation of their transcription factors (TFs).

RESULTS: We detected 440 sequence-specific TFs across 33 families, of which 68% were upregulated in multicellular development and about half conserved throughout Dictyostelia. Prespore cells expressed two times more TFs than prestalk cells, but stalk cells expressed more TFs than spores, suggesting that gene expression events that define spores occur earlier than those that define stalk cells. Changes in TF developmental expression, but not in TF abundance or functional domains occurred more frequently between group 4 and groups 1-3, than between the more distant branches formed by groups 1 + 2 and 3 + 4.

CONCLUSIONS: Phenotypic innovation is correlated with changes in TF regulation, rather than functional domain- or TF acquisition. The function of only 34 TFs is known. Of 12 TFs essential for cell differentiation, 9 are expressed in the cell type for which they are required. The information acquired here on conserved cell type specifity of 120 additional TFs can effectively guide further functional analysis, while observed evolutionary change in TF developmental expression may highlight how genotypic change caused phenotypic innovation.}, } @article {pmid31751628, year = {2020}, author = {Williams, LM and Inge, MM and Mansfield, KM and Rasmussen, A and Afghani, J and Agrba, M and Albert, C and Andersson, C and Babaei, M and Babaei, M and Bagdasaryants, A and Bonilla, A and Browne, A and Carpenter, S and Chen, T and Christie, B and Cyr, A and Dam, K and Dulock, N and Erdene, G and Esau, L and Esonwune, S and Hanchate, A and Huang, X and Jennings, T and Kasabwala, A and Kehoe, L and Kobayashi, R and Lee, M and LeVan, A and Liu, Y and Murphy, E and Nambiar, A and Olive, M and Patel, D and Pavesi, F and Petty, CA and Samofalova, Y and Sanchez, S and Stejskal, C and Tang, Y and Yapo, A and Cleary, JP and Yunes, SA and Siggers, T and Gilmore, TD}, title = {Transcription factor NF-κB in a basal metazoan, the sponge, has conserved and unique sequences, activities, and regulation.}, journal = {Developmental and comparative immunology}, volume = {104}, number = {}, pages = {103559}, doi = {10.1016/j.dci.2019.103559}, pmid = {31751628}, issn = {1879-0089}, support = {R01 AI116829/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Conserved Sequence/*genetics ; DNA-Binding Proteins/*genetics/metabolism ; Evolution, Molecular ; Gene Expression Regulation ; NF-kappa B/*genetics/metabolism ; Porifera/*immunology ; Protein Domains/*genetics ; Signal Transduction ; Transcription, Genetic ; }, abstract = {Herein, we characterize transcription factor NF-κB from the demosponge Amphimedon queenslandica (Aq). Aq-NF-κB is most similar to NF-κB p100/p105 among vertebrate proteins, with an N-terminal DNA-binding domain, a C-terminal Ankyrin (ANK) repeat domain, and a DNA binding-site profile akin to human NF-κB proteins. Like mammalian NF-κB p100, C-terminal truncation allows nuclear translocation of Aq-NF-κB and increases its transcriptional activation activity. Expression of IκB kinases (IKKs) induces proteasome-dependent C-terminal processing of Aq-NF-κB in human cells, and processing requires C-terminal serines in Aq-NF-κB. Unlike NF-κB p100, C-terminal sequences of Aq-NF-κB do not inhibit its DNA-binding activity. Tissue of a black encrusting demosponge contains NF-κB site DNA-binding activity, as well as nuclear and processed NF-κB. Treatment of sponge tissue with LPS increases both DNA-binding activity and processing of NF-κB. A. queenslandica transcriptomes contain homologs to upstream NF-κB pathway components. This is first functional characterization of NF-κB in sponge, the most basal multicellular animal.}, } @article {pmid31743442, year = {2020}, author = {Brenneis, G and Beltz, BS}, title = {Adult neurogenesis in crayfish: Origin, expansion, and migration of neural progenitor lineages in a pseudostratified neuroepithelium.}, journal = {The Journal of comparative neurology}, volume = {528}, number = {9}, pages = {1459-1485}, doi = {10.1002/cne.24820}, pmid = {31743442}, issn = {1096-9861}, mesh = {Animals ; Astacoidea/*cytology/physiology ; Brain/*cytology ; Cell Differentiation/physiology ; Cell Lineage/physiology ; Cell Movement/physiology ; Hemocytes/cytology ; Neural Stem Cells/*cytology ; Neurogenesis/*physiology ; }, abstract = {Two decades after the discovery of adult-born neurons in the brains of decapod crustaceans, the deutocerebral proliferative system (DPS) producing these neural lineages has become a model of adult neurogenesis in invertebrates. Studies on crayfish have provided substantial insights into the anatomy, cellular dynamics, and regulation of the DPS. Contrary to traditional thinking, recent evidence suggests that the neurogenic niche in the crayfish DPS lacks self-renewing stem cells, its cell pool being instead sustained via integration of hemocytes generated by the innate immune system. Here, we investigated the origin, division and migration patterns of the adult-born neural progenitor (NP) lineages in detail. We show that the niche cell pool is not only replenished by hemocyte integration but also by limited numbers of symmetric cell divisions with some characteristics reminiscent of interkinetic nuclear migration. Once specified in the niche, first generation NPs act as transit-amplifying intermediate NPs that eventually exit and produce multicellular clones as they move along migratory streams toward target brain areas. Different clones may migrate simultaneously in the streams but occupy separate tracks and show spatio-temporally flexible division patterns. Based on this, we propose an extended DPS model that emphasizes structural similarities to pseudostratified neuroepithelia in other arthropods and vertebrates. This model includes hemocyte integration and intrinsic cell proliferation to synergistically counteract niche cell pool depletion during the animal's lifespan. Further, we discuss parallels to recent findings on mammalian adult neurogenesis, as both systems seem to exhibit a similar decoupling of proliferative replenishment divisions and consuming neurogenic divisions.}, } @article {pmid31736534, year = {2019}, author = {Chen, J and Wang, N}, title = {Tissue cell differentiation and multicellular evolution via cytoskeletal stiffening in mechanically stressed microenvironments.}, journal = {Acta mechanica Sinica = Li xue xue bao}, volume = {35}, number = {2}, pages = {270-274}, pmid = {31736534}, issn = {0567-7718}, support = {R01 GM072744/GM/NIGMS NIH HHS/United States ; }, abstract = {Evolution of eukaryotes from simple cells to complex multicellular organisms remains a mystery. Our postulate is that cytoskeletal stiffening is a necessary condition for evolution of complex multicellular organisms from early simple eukaryotes. Recent findings show that embryonic stem cells are as soft as primitive eukaryotes-amoebae and that differentiated tissue cells can be two orders of magnitude stiffer than embryonic stem cells. Soft embryonic stem cells become stiff as they differentiate into tissue cells of the complex multicellular organisms to match their microenvironment stiffness. We perhaps see in differentiation of embryonic stem cells (derived from inner cell mass cells) the echo of those early evolutionary events. Early soft unicellular organisms might have evolved to stiffen their cytoskeleton to protect their structural integrity from external mechanical stresses while being able to maintain form, to change shape, and to move.}, } @article {pmid32412616, year = {2018}, author = {Xiao, S and Tang, Q}, title = {After the boring billion and before the freezing millions: evolutionary patterns and innovations in the Tonian Period.}, journal = {Emerging topics in life sciences}, volume = {2}, number = {2}, pages = {161-171}, doi = {10.1042/ETLS20170165}, pmid = {32412616}, issn = {2397-8554}, abstract = {The Tonian Period (ca. 1000-720 Ma) follows the 'boring billion' in the Mesoproterozoic Era and precedes 'snowball Earth' glaciations in the Cryogenian Period. It represents a critical transition in Earth history. Geochemical data indicate that the Tonian Period may have witnessed a significant increase in atmospheric pO2 levels and a major transition from predominantly sulfidic to ferruginous mid-depth seawaters. Molecular clock estimates suggest that early animals may have diverged in the Tonian Period, raising the intriguing possibility of coupled environmental changes and evolutionary innovations. The co-evolution of life and its environment during the Tonian Period can be tested against the fossil record by examining diversity trends in the Proterozoic and evolutionary innovations in the Tonian. Compilations of Proterozoic microfossils and macrofossils apparently support a Tonian increase in global taxonomic diversity and morphological range relative to the Mesoproterozoic Era, although this is not reflected in assemblage-level diversity patterns. The fossil record suggests that major eukaryote groups (including Opisthokonta, Amoebozoa, Plantae, and SAR) may have diverged and important evolutionary innovations (e.g. multicellularity and cell differentiation in several groups, eukaryovory, eukaryote biomineralization, and heterocystous cyanobacteria) may have arisen by the Tonian Period, but thus far no convincing animal fossils have been found in the Tonian. Tonian paleontology is still in its nascent stage, and it offers many opportunities to explore Earth-life evolution in this critical geological period.}, } @article {pmid32412615, year = {2018}, author = {Mills, DB and Francis, WR and Canfield, DE}, title = {Animal origins and the Tonian Earth system.}, journal = {Emerging topics in life sciences}, volume = {2}, number = {2}, pages = {289-298}, doi = {10.1042/ETLS20170160}, pmid = {32412615}, issn = {2397-8554}, abstract = {The Neoproterozoic Era (1000-541 million years ago, Ma) was characterized by dramatic environmental and evolutionary change, including at least two episodes of extensive, low-latitude glaciation, potential changes in the redox structure of the global ocean, and the origin and diversification of animal life. How these different events related to one another remains an active area of research, particularly how these environmental changes influenced, and were influenced by, the earliest evolution of animals. Animal multicellularity is estimated to have evolved in the Tonian Period (1000-720 Ma) and represents one of at least six independent acquisitions of complex multicellularity, characterized by cellular differentiation, three-dimensional body plans, and active nutrient transport. Compared with the other instances of complex multicellularity, animals represent the only clade to have evolved from wall-less, phagotrophic flagellates, which likely placed unique cytological and trophic constraints on the evolution of animal multicellularity. Here, we compare recent molecular clock estimates with compilations of the chromium isotope, micropaleontological, and organic biomarker records, suggesting that, as of now, the origin of animals was not obviously correlated to any environmental-ecological change in the Tonian Period. This lack of correlation is consistent with the idea that the evolution of animal multicellularity was primarily dictated by internal, developmental constraints and occurred independently of the known environmental-ecological changes that characterized the Neoproterozoic Era.}, } @article {pmid31724951, year = {2019}, author = {Thattai, M}, title = {How contraction has shaped evolution.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {31724951}, issn = {2050-084X}, mesh = {*Actin Cytoskeleton ; *Actomyosin ; Animals ; }, abstract = {Two unicellular relatives of animals reveal that coordinated contractions of groups of cells using actomyosin predated animal multicellularity during evolution.}, } @article {pmid31722397, year = {2020}, author = {López, EH and Palumbi, SR}, title = {Somatic Mutations and Genome Stability Maintenance in Clonal Coral Colonies.}, journal = {Molecular biology and evolution}, volume = {37}, number = {3}, pages = {828-838}, doi = {10.1093/molbev/msz270}, pmid = {31722397}, issn = {1537-1719}, mesh = {Animals ; Anthozoa/*genetics ; Clonal Evolution ; Coral Reefs ; Gene Expression Profiling/*methods ; Genomic Instability ; Loss of Heterozygosity ; *Mutation ; Mutation Rate ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/*methods ; }, abstract = {One challenge for multicellular organisms is maintaining genome stability in the face of mutagens across long life spans. Imperfect genome maintenance leads to mutation accumulation in somatic cells, which is associated with tumors and senescence in vertebrates. Colonial reef-building corals are often large, can live for hundreds of years, rarely develop recognizable tumors, and are thought to convert somatic cells into gamete producers, so they are a pivotal group in which to understand long-term genome maintenance. To measure rates and patterns of somatic mutations, we analyzed transcriptomes from 17 to 22 branches from each of four Acropora hyacinthus colonies, determined putative single nucleotide variants, and verified them with Sanger resequencing. Unlike for human skin carcinomas, there is no signature of mutations caused by UV damage, indicating either higher efficiency of repair than in vertebrates, or strong sunscreen protection in these shallow water tropical animals. The somatic mutation frequency per nucleotide in A. hyacinthus is on the same order of magnitude (10-7) as noncancerous human somatic cells, and accumulation of mutations with age is similar. Loss of heterozygosity variants outnumber gain of heterozygosity mutations ∼2:1. Although the mutation frequency is similar in mammals and corals, the preponderance of loss of heterozygosity changes and potential selection may reduce the frequency of deleterious mutations in colonial animals like corals. This may limit the deleterious effects of somatic mutations on the coral organism as well as potential offspring.}, } @article {pmid31721091, year = {2020}, author = {Martínez-Soto, D and Velez-Haro, JM and León-Ramírez, CG and Galán-Vásquez, E and Chávez-Munguía, B and Ruiz-Herrera, J}, title = {Multicellular growth of the Basidiomycota phytopathogen fungus Sporisorium reilianum induced by acid conditions.}, journal = {Folia microbiologica}, volume = {65}, number = {3}, pages = {511-521}, doi = {10.1007/s12223-019-00755-7}, pmid = {31721091}, issn = {1874-9356}, mesh = {Acids/*pharmacology ; Basidiomycota/drug effects/*genetics/*growth & development ; Cell Cycle/drug effects ; Cell Division/drug effects ; Fungal Proteins/*genetics ; Hydrogen-Ion Concentration ; Phylogeny ; Signal Transduction/drug effects ; }, abstract = {Fungi are considered model organisms for the analysis of important phenomena of eukaryotes. For example, some of them have been described as models to understand the phenomenon of multicellularity acquisition by different unicellular organisms phylogenetically distant. Interestingly, in this work, we describe the multicellular development in the model fungus S. reilianum. We observed that Sporisorium reilianum, a Basidiomycota cereal pathogen that at neutral pH grows with a yeast-like morphology during its saprophytic haploid stage, when incubated at acid pH grew in the form of multicellular clusters. The multicellularity observed in S. reilianum was of clonal type, where buds of "stem" cells growing as yeasts remain joined by their cell wall septa, after cytokinesis. The elaboration and analysis of a regulatory network of S. reilianum showed that the putative zinc finger transcription factor CBQ73544.1 regulates a number of genes involved in cell cycle, cellular division, signal transduction pathways, and biogenesis of cell wall. Interestingly, homologous of these genes have been found to be regulated during Saccharomyces cerevisiae multicellular growth. In adddition, some of these genes were found to be negatively regulated during multicellularity of S. reilianum. With these data, we suggest that S. reilianum is an interesting model for the study of multicellular development.}, } @article {pmid31714927, year = {2019}, author = {Hammond, MJ and Wang, T and Cummins, SF}, title = {Characterisation of early metazoan secretion through associated signal peptidase complex subunits, prohormone convertases and carboxypeptidases of the marine sponge (Amphimedon queenslandica).}, journal = {PloS one}, volume = {14}, number = {11}, pages = {e0225227}, pmid = {31714927}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Carboxypeptidases/chemistry/genetics/*metabolism ; Phylogeny ; Porifera/classification/genetics/*metabolism ; Proprotein Convertases/chemistry/genetics/*metabolism ; Protein Subunits/chemistry/*metabolism ; *Signal Transduction ; }, abstract = {Efficient communication between cells requires the ability to process precursor proteins into their mature and biologically active forms, prior to secretion into the extracellular space. Eukaryotic cells achieve this via a suite of enzymes that involve a signal peptidase complex, prohormone convertases and carboxypeptidases. Using genome and transcriptome data of the demosponge Amphimedon queenslandica, a universal ancestor to metazoan multicellularity, we endeavour to bridge the evolution of precursor processing machinery from single-celled eukaryotic ancestors through to the complex multicellular organisms that compromise Metazoa. The precursor processing repertoire as defined in this study of A. queenslandica consists of 3 defined signal peptidase subunits, 6 prohormone convertases and 1 carboxypeptidase, with 2 putative duplicates identified for signal peptidase complex subunits. Analysis of their gene expression levels throughout the sponge development enabled us to predict levels of activity. Some A. queenslandica precursor processing components belong to established functional clades while others were identified as having novel, yet to be discovered roles. These findings have clarified the presence of precursor processing machinery in the poriferans, showing the necessary machinery for the removal of precursor sequences, a critical post-translational modification required by multicellular organisms, and further sets a foundation towards understanding the molecular mechanism for ancient protein processing.}, } @article {pmid31707219, year = {2019}, author = {Stubbendieck, RM and Li, H and Currie, CR}, title = {Convergent evolution of signal-structure interfaces for maintaining symbioses.}, journal = {Current opinion in microbiology}, volume = {50}, number = {}, pages = {71-78}, pmid = {31707219}, issn = {1879-0364}, support = {T15 LM007359/LM/NLM NIH HHS/United States ; U19 AI109673/AI/NIAID NIH HHS/United States ; U19 TW009872/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; Ants/microbiology ; Decapodiformes/microbiology ; *Evolution, Molecular ; Fabaceae/microbiology ; *Host Microbial Interactions ; Humans ; *Microbiota ; *Symbiosis ; }, abstract = {Symbiotic microbes are essential to the ecological success and evolutionary diversification of multicellular organisms. The establishment and stability of bipartite symbioses are shaped by mechanisms ensuring partner fidelity between host and symbiont. In this minireview, we demonstrate how the interface of chemical signals and host structures influences fidelity between legume root nodules and rhizobia, Hawaiian bobtail squid light organs and Allivibrio fischeri, and fungus-growing ant crypts and Pseudonocardia. Subsequently, we illustrate the morphological diversity and widespread phylogenetic distribution of specialized structures used by hosts to house microbial symbionts, indicating the importance of signal-structure interfaces across the history of multicellular life. These observations, and the insights garnered from well-studied bipartite associations, demonstrate the need to concentrate on the signal-structure interface in complex and multipartite systems, including the human microbiome.}, } @article {pmid31702845, year = {2020}, author = {Grall, E and Tschopp, P}, title = {A sense of place, many times over - pattern formation and evolution of repetitive morphological structures.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {249}, number = {3}, pages = {313-327}, doi = {10.1002/dvdy.131}, pmid = {31702845}, issn = {1097-0177}, mesh = {Animals ; Body Patterning/genetics/*physiology ; Gene Expression Regulation, Developmental/genetics/*physiology ; Humans ; Morphogenesis/genetics/*physiology ; Signal Transduction/genetics/*physiology ; }, abstract = {Fifty years ago, Lewis Wolpert introduced the concept of "positional information" to explain how patterns form in a multicellular embryonic field. Using morphogen gradients, whose continuous distributions of positional values are discretized via thresholds into distinct cellular states, he provided, at the theoretical level, an elegant solution to the "French Flag problem." In the intervening years, many experimental studies have lent support to Wolpert's ideas. However, the embryonic patterning of highly repetitive morphological structures, as often occurring in nature, can reveal limitations in the strict implementation of his initial theory, given the number of distinct threshold values that would have to be specified. Here, we review how positional information is complemented to circumvent these inadequacies, to accommodate tissue growth and pattern periodicity. In particular, we focus on functional anatomical assemblies composed of such structures, like the vertebrate spine or tetrapod digits, where the resulting segmented architecture is intrinsically linked to periodic pattern formation and unidirectional growth. These systems integrate positional information and growth with additional patterning cues that, we suggest, increase robustness and evolvability. We discuss different experimental and theoretical models to study such patterning systems, and how the underlying processes are modulated over evolutionary timescales to enable morphological diversification.}, } @article {pmid31689405, year = {2019}, author = {Coudert, Y and Harris, S and Charrier, B}, title = {Design Principles of Branching Morphogenesis in Filamentous Organisms.}, journal = {Current biology : CB}, volume = {29}, number = {21}, pages = {R1149-R1162}, doi = {10.1016/j.cub.2019.09.021}, pmid = {31689405}, issn = {1879-0445}, mesh = {Ascomycota/*growth & development ; *Body Patterning ; Bryopsida/*growth & development ; Phaeophyceae/*growth & development ; }, abstract = {The radiation of life on Earth was accompanied by the diversification of multicellular body plans in the eukaryotic kingdoms Animalia, Plantae, Fungi and Chromista. Branching forms are ubiquitous in nature and evolved repeatedly in the above lineages. The developmental and genetic basis of branch formation is well studied in the three-dimensional shoot and root systems of land plants, and in animal organs such as the lung, kidney, mammary gland, vasculature, etc. Notably, recent thought-provoking studies combining experimental analysis and computational modeling of branching patterns in whole animal organs have identified global patterning rules and proposed unifying principles of branching morphogenesis. Filamentous branching forms represent one of the simplest expressions of the multicellular body plan and constitute a key step in the evolution of morphological complexity. Similarities between simple and complex branching forms distantly related in evolution are compelling, raising the question whether shared mechanisms underlie their development. Here, we focus on filamentous branching organisms that represent major study models from three distinct eukaryotic kingdoms, including the moss Physcomitrella patens (Plantae), the brown alga Ectocarpus sp. (Chromista), and the ascomycetes Neurospora crassa and Aspergillus nidulans (Fungi), and bring to light developmental regulatory mechanisms and design principles common to these lineages. Throughout the review we explore how the regulatory mechanisms of branching morphogenesis identified in other models, and in particular animal organs, may inform our thinking on filamentous systems and thereby advance our understanding of the diverse strategies deployed across the eukaryotic tree of life to evolve similar forms.}, } @article {pmid31687086, year = {2019}, author = {Poljsak, B and Kovac, V and Dahmane, R and Levec, T and Starc, A}, title = {Cancer Etiology: A Metabolic Disease Originating from Life's Major Evolutionary Transition?.}, journal = {Oxidative medicine and cellular longevity}, volume = {2019}, number = {}, pages = {7831952}, pmid = {31687086}, issn = {1942-0994}, mesh = {Animals ; *Biological Evolution ; Drug Resistance, Neoplasm ; Energy Metabolism ; Humans ; Metabolic Diseases/*etiology ; Mitochondria/metabolism ; Neoplasms/*etiology ; }, abstract = {A clear understanding of the origins of cancer is the basis of successful strategies for effective cancer prevention and management. The origin of cancer at the molecular and cellular levels is not well understood. Is the primary cause of the origin of cancer the genomic instability or impaired energy metabolism? An attempt was made to present cancer etiology originating from life's major evolutionary transition. The first evolutionary transition went from simple to complex cells when eukaryotic cells with glycolytic energy production merged with the oxidative mitochondrion (The Endosymbiosis Theory first proposed by Lynn Margulis in the 1960s). The second transition went from single-celled to multicellular organisms once the cells obtained mitochondria, which enabled them to obtain a higher amount of energy. Evidence will be presented that these two transitions, as well as the decline of NAD+ and ATP levels, are the root of cancer diseases. Restoring redox homeostasis and reactivation of mitochondrial oxidative metabolism are important factors in cancer prevention.}, } @article {pmid31673005, year = {2019}, author = {Brown, JL and Johnston, W and Delaney, C and Rajendran, R and Butcher, J and Khan, S and Bradshaw, D and Ramage, G and Culshaw, S}, title = {Biofilm-stimulated epithelium modulates the inflammatory responses in co-cultured immune cells.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {15779}, pmid = {31673005}, issn = {2045-2322}, support = {BB/P504567/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacteria/*immunology ; *Bacterial Physiological Phenomena ; Biofilms/*growth & development ; Coculture Techniques ; *Gingiva/immunology/microbiology/pathology ; Humans ; Inflammation/immunology/microbiology/pathology ; Inflammation Mediators/*immunology ; *Monocytes/immunology/microbiology/pathology ; *Mouth Mucosa/immunology/microbiology/pathology ; }, abstract = {The gingival epithelium is a physical and immunological barrier to the microbiota of the oral cavity, which interact through soluble mediators with the immune cells that patrol the tissue at the gingival epithelium. We sought to develop a three-dimensional gingivae-biofilm interface model using a commercially available gingival epithelium to study the tissue inflammatory response to oral biofilms associated with "health", "gingivitis" and "periodontitis". These biofilms were developed by sequential addition of microorganisms to mimic the formation of supra- and sub-gingival plaque in vivo. Secondly, to mimic the interactions between gingival epithelium and immune cells in vivo, we integrated peripheral blood mononuclear cells and CD14[+] monocytes into our three-dimensional model and were able to assess the inflammatory response in the immune cells cultured with and without gingival epithelium. We describe a differential inflammatory response in immune cells cultured with epithelial tissue, and more so following incubation with epithelium stimulated by "gingivitis-associated" biofilm. These results suggest that gingival epithelium-derived soluble mediators may control the inflammatory status of immune cells in vitro, and therefore targeting of the epithelial response may offer novel therapies. This multi-cellular interface model, both of microbial and host origin, offers a robust in vitro platform to investigate host-pathogens at the epithelial surface.}, } @article {pmid31649660, year = {2019}, author = {Smith, NC and Rise, ML and Christian, SL}, title = {A Comparison of the Innate and Adaptive Immune Systems in Cartilaginous Fish, Ray-Finned Fish, and Lobe-Finned Fish.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2292}, pmid = {31649660}, issn = {1664-3224}, mesh = {*Adaptive Immunity ; Animals ; *Evolution, Molecular ; Fish Proteins/genetics/immunology ; *Immunity, Innate ; Immunoglobulins/genetics/immunology ; Leukocytes/*immunology ; Major Histocompatibility Complex/genetics/immunology ; Skates, Fish/genetics/*immunology ; Species Specificity ; }, abstract = {The immune system is composed of two subsystems-the innate immune system and the adaptive immune system. The innate immune system is the first to respond to pathogens and does not retain memory of previous responses. Innate immune responses are evolutionarily older than adaptive responses and elements of innate immunity can be found in all multicellular organisms. If a pathogen persists, the adaptive immune system will engage the pathogen with specificity and memory. Several components of the adaptive system including immunoglobulins (Igs), T cell receptors (TCR), and major histocompatibility complex (MHC), are assumed to have arisen in the first jawed vertebrates-the Gnathostomata. This review will discuss and compare components of both the innate and adaptive immune systems in Gnathostomes, particularly in Chondrichthyes (cartilaginous fish) and in Osteichthyes [bony fish: the Actinopterygii (ray-finned fish) and the Sarcopterygii (lobe-finned fish)]. While many elements of both the innate and adaptive immune systems are conserved within these species and with higher level vertebrates, some elements have marked differences. Components of the innate immune system covered here include physical barriers, such as the skin and gastrointestinal tract, cellular components, such as pattern recognition receptors and immune cells including macrophages and neutrophils, and humoral components, such as the complement system. Components of the adaptive system covered include the fundamental cells and molecules of adaptive immunity: B lymphocytes (B cells), T lymphocytes (T cells), immunoglobulins (Igs), and major histocompatibility complex (MHC). Comparative studies in fish such as those discussed here are essential for developing a comprehensive understanding of the evolution of the immune system.}, } @article {pmid31649059, year = {2019}, author = {Duttke, SH and Chang, MW and Heinz, S and Benner, C}, title = {Identification and dynamic quantification of regulatory elements using total RNA.}, journal = {Genome research}, volume = {29}, number = {11}, pages = {1836-1846}, pmid = {31649059}, issn = {1549-5469}, support = {U19 AI106754/AI/NIAID NIH HHS/United States ; U19 AI135972/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Gene Regulatory Networks ; Histones/metabolism ; Mice ; Mice, Inbred C57BL ; RNA/*genetics ; RNA Caps ; Transcription Factors/metabolism ; Transcription, Genetic ; }, abstract = {The spatial and temporal regulation of transcription initiation is pivotal for controlling gene expression. Here, we introduce capped-small RNA-seq (csRNA-seq), which uses total RNA as starting material to detect transcription start sites (TSSs) of both stable and unstable RNAs at single-nucleotide resolution. csRNA-seq is highly sensitive to acute changes in transcription and identifies an order of magnitude more regulated transcripts than does RNA-seq. Interrogating tissues from species across the eukaryotic kingdoms identified unstable transcripts resembling enhancer RNAs, pri-miRNAs, antisense transcripts, and promoter upstream transcripts in multicellular animals, plants, and fungi spanning 1.6 billion years of evolution. Integration of epigenomic data from these organisms revealed that histone H3 trimethylation (H3K4me3) was largely confined to TSSs of stable transcripts, whereas H3K27ac marked nucleosomes downstream from all active TSSs, suggesting an ancient role for posttranslational histone modifications in transcription. Our findings show that total RNA is sufficient to identify transcribed regulatory elements and capture the dynamics of initiated stable and unstable transcripts at single-nucleotide resolution in eukaryotes.}, } @article {pmid31647412, year = {2019}, author = {Dudin, O and Ondracka, A and Grau-Bové, X and Haraldsen, AA and Toyoda, A and Suga, H and Bråte, J and Ruiz-Trillo, I}, title = {A unicellular relative of animals generates a layer of polarized cells by actomyosin-dependent cellularization.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {31647412}, issn = {2050-084X}, support = {Consolidator Grant ERC-2012-Co-616960/ERC_/European Research Council/International ; MEXT KAKENHI 221S0002//Ministry of Education, Culture, Sports, Science and Technology/International ; MEXT KAKENHI 26891021//Ministry of Education, Culture, Sports, Science and Technology/International ; Young Research Talents grant 240284//Research Council of Norway/International ; P2LAP3_171815/SNSF_/Swiss National Science Foundation/Switzerland ; Individual fellowship MSCA-IF 746044//H2020 Marie Skłodowska-Curie Actions/International ; Individual fellowship MSCA-IF 747086//H2020 Marie Skłodowska-Curie Actions/International ; ERC-2012-Co -616960//European Research Council Consolidator Grant/International ; 221S0002//MEXT KAKENHI/International ; 26891021//MEXT KAKENHI/International ; 240284//Young Research Talents grant from the Research Council of Norway/International ; MSCA-IF 746044//Marie Sklodowska-Curie individual fellowship/International ; MSCA-IF 747086//Marie Sklodowska-Curie individual fellowship/International ; }, mesh = {Actomyosin/*metabolism ; Animals ; Cell Membrane/*metabolism ; *Cell Polarity ; Gene Expression Regulation ; Mesomycetozoea/*physiology ; }, abstract = {In animals, cellularization of a coenocyte is a specialized form of cytokinesis that results in the formation of a polarized epithelium during early embryonic development. It is characterized by coordinated assembly of an actomyosin network, which drives inward membrane invaginations. However, whether coordinated cellularization driven by membrane invagination exists outside animals is not known. To that end, we investigate cellularization in the ichthyosporean Sphaeroforma arctica, a close unicellular relative of animals. We show that the process of cellularization involves coordinated inward plasma membrane invaginations dependent on an actomyosin network and reveal the temporal order of its assembly. This leads to the formation of a polarized layer of cells resembling an epithelium. We show that this stage is associated with tightly regulated transcriptional activation of genes involved in cell adhesion. Hereby we demonstrate the presence of a self-organized, clonally-generated, polarized layer of cells in a unicellular relative of animals.}, } @article {pmid31633482, year = {2019}, author = {Murphy, DP and Hughes, AE and Lawrence, KA and Myers, CA and Corbo, JC}, title = {Cis-regulatory basis of sister cell type divergence in the vertebrate retina.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {31633482}, issn = {2050-084X}, support = {T32 EY013360/EY/NEI NIH HHS/United States ; T32EY013360/EY/NEI NIH HHS/United States ; R01EY024958/EY/NEI NIH HHS/United States ; R01EY026672/EY/NEI NIH HHS/United States ; R01 EY024958/EY/NEI NIH HHS/United States ; R01 EY026672/EY/NEI NIH HHS/United States ; F32EY029571/EY/NEI NIH HHS/United States ; F32 EY029571/EY/NEI NIH HHS/United States ; R01EY025196/EY/NEI NIH HHS/United States ; R01 EY025196/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; Chromatin/metabolism ; *Evolution, Molecular ; Gene Expression Profiling ; *Gene Regulatory Networks ; Mice ; Photoreceptor Cells/*physiology ; Regulatory Sequences, Nucleic Acid/*genetics ; Retinal Bipolar Cells/*physiology ; }, abstract = {Multicellular organisms evolved via repeated functional divergence of transcriptionally related sister cell types, but the mechanisms underlying sister cell type divergence are not well understood. Here, we study a canonical pair of sister cell types, retinal photoreceptors and bipolar cells, to identify the key cis-regulatory features that distinguish them. By comparing open chromatin maps and transcriptomic profiles, we found that while photoreceptor and bipolar cells have divergent transcriptomes, they share remarkably similar cis-regulatory grammars, marked by enrichment of K50 homeodomain binding sites. However, cell class-specific enhancers are distinguished by enrichment of E-box motifs in bipolar cells, and Q50 homeodomain motifs in photoreceptors. We show that converting K50 motifs to Q50 motifs represses reporter expression in bipolar cells, while photoreceptor expression is maintained. These findings suggest that partitioning of Q50 motifs within cell type-specific cis-regulatory elements was a critical step in the evolutionary divergence of the bipolar transcriptome from that of photoreceptors.}, } @article {pmid31624206, year = {2019}, author = {Brunet, T and Larson, BT and Linden, TA and Vermeij, MJA and McDonald, K and King, N}, title = {Light-regulated collective contractility in a multicellular choanoflagellate.}, journal = {Science (New York, N.Y.)}, volume = {366}, number = {6463}, pages = {326-334}, doi = {10.1126/science.aay2346}, pmid = {31624206}, issn = {1095-9203}, mesh = {Actomyosin/metabolism ; Animals ; Biological Evolution ; Choanoflagellata/cytology/*physiology ; Cyclic GMP/metabolism ; *Light ; Microvilli/physiology ; Movement ; Phosphoric Diester Hydrolases/metabolism ; Protozoan Proteins/metabolism ; Sensory Rhodopsins/metabolism ; }, abstract = {Collective cell contractions that generate global tissue deformations are a signature feature of animal movement and morphogenesis. However, the origin of collective contractility in animals remains unclear. While surveying the Caribbean island of Curaçao for choanoflagellates, the closest living relatives of animals, we isolated a previously undescribed species (here named Choanoeca flexa sp. nov.) that forms multicellular cup-shaped colonies. The colonies rapidly invert their curvature in response to changing light levels, which they detect through a rhodopsin-cyclic guanosine monophosphate pathway. Inversion requires actomyosin-mediated apical contractility and allows alternation between feeding and swimming behavior. C. flexa thus rapidly converts sensory inputs directly into multicellular contractions. These findings may inform reconstructions of hypothesized animal ancestors that existed before the evolution of specialized sensory and contractile cells.}, } @article {pmid31617664, year = {2019}, author = {Nanjundiah, V}, title = {Many roads lead to Rome: Neutral phenotypes in microorganisms.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {339-348}, doi = {10.1002/jez.b.22909}, pmid = {31617664}, issn = {1552-5015}, mesh = {3',5'-Cyclic-AMP Phosphodiesterases ; Adaptation, Biological ; *Biological Evolution ; Dictyostelium/enzymology/*physiology ; *Phenotype ; }, abstract = {John Bonner pointed out that microorganisms differ in several ways, some of which may reflect neutral phenotypic evolution. For making his case, Bonner referred to interspecies differences and morphological traits. Here we consider intraspecies differences and physiological traits. As a case-study, we examine the production of an extracellular cyclic 3 ' ,5 ' monophosphate phosphodiesterase in the cellular slime mold Dictyostelium discoideum. Temporal profiles of phosphodiesterase activity differ significantly between wild-type strains. From that we argue that the inference drawn initially from studies on a single wild-type, namely that the profile displayed by it pointed to an adaptive role, was mistaken. We generalize the conclusion to suggest that physiological differences exhibited by microorganisms of the same species may, but need not, reflect adaptations to different environments. Rather, the differences could be related to the fact that microorganisms live in groups whose composition can vary between homogeneous (clonal) and heterogeneous (polyclonal). More than one physiological profile is consistent with the normal development of the group in a given environment; the alternatives are neutral. When studying microbial physiology and behavior, it is expected that the observations are made on a clonal population; genetic (and so phenotypic) heterogeneity is carefully guarded against. As the example from D. discoideum shows, an unintended consequence of overlooking phenotypic heterogeneity is that one can fall into the trap of accepting a seemingly plausible, but possibly erroneous, adaptive explanation for a "normal" wild-type phenotype.}, } @article {pmid31615963, year = {2019}, author = {Blank-Landeshammer, B and Teichert, I and Märker, R and Nowrousian, M and Kück, U and Sickmann, A}, title = {Combination of Proteogenomics with Peptide De Novo Sequencing Identifies New Genes and Hidden Posttranscriptional Modifications.}, journal = {mBio}, volume = {10}, number = {5}, pages = {}, pmid = {31615963}, issn = {2150-7511}, mesh = {Alternative Splicing/*genetics ; Genome, Fungal/*genetics ; Molecular Sequence Annotation ; Peptides/*metabolism ; Phylogeny ; Proteogenomics/*methods ; }, abstract = {Proteogenomics combines proteomics, genomics, and transcriptomics and has considerably improved genome annotation in poorly investigated phylogenetic groups for which homology information is lacking. Furthermore, it can be advantageous when reinvestigating well-annotated genomes. Here, we applied an advanced proteogenomics approach, combining standard proteogenomics with peptide de novo sequencing, to refine annotation of the well-studied model fungus Sordaria macrospora We investigated samples from different developmental and physiological conditions, resulting in the detection of 104 so-far hidden proteins and annotation changes in 575 genes, including 389 splice site refinements. Significantly, our approach provides peptide-level evidence for 113 single-amino-acid variations and 15 C-terminal protein elongations originating from A-to-I RNA editing, a phenomenon recently detected in fungi. Coexpression and phylostratigraphic analysis of the refined proteome suggest that new functions in evolutionarily young genes correlate with distinct developmental stages. In conclusion, our advanced proteogenomics approach supports and promotes functional studies of fungal model systems.IMPORTANCE Next-generation sequencing techniques have considerably increased the number of completely sequenced eukaryotic genomes. These genomes are mostly automatically annotated, and ab initio gene prediction is commonly combined with homology-based search approaches and often supported by transcriptomic data. The latter in particular improve the prediction of intron splice sites and untranslated regions. However, correct prediction of translation initiation sites (TIS), alternative splice junctions, and protein-coding potential remains challenging. Here, we present an advanced proteogenomics approach, namely, the combination of proteogenomics and de novo peptide sequencing analysis, in conjunction with Blast2GO and phylostratigraphy. Using the model fungus Sordaria macrospora as an example, we provide a comprehensive view of the proteome that not only increases the functional understanding of this multicellular organism at different developmental stages but also immensely enhances the genome annotation quality.}, } @article {pmid31610128, year = {2020}, author = {Jasper, H}, title = {Intestinal Stem Cell Aging: Origins and Interventions.}, journal = {Annual review of physiology}, volume = {82}, number = {}, pages = {203-226}, doi = {10.1146/annurev-physiol-021119-034359}, pmid = {31610128}, issn = {1545-1585}, mesh = {Aging/*physiology ; Animals ; Cellular Senescence/*physiology ; Epithelial Cells/physiology ; Humans ; Intestinal Mucosa/chemistry/physiology ; Intestines/*cytology/*physiology ; Regeneration/physiology ; Stem Cells/*physiology ; }, abstract = {Regenerative processes that maintain the function of the gastrointestinal (GI) epithelium are critical for health and survival of multicellular organisms. In insects and vertebrates, intestinal stem cells (ISCs) regenerate the GI epithelium. ISC function is regulated by intrinsic, local, and systemic stimuli to adjust regeneration to tissue demands. These control mechanisms decline with age, resulting in significant perturbation of intestinal homeostasis. Processes that lead to this decline have been explored intensively in Drosophila melanogaster in recent years and are now starting to be characterized in mammalian models. This review presents a model for age-related regenerative decline in the fly intestine and discusses recent findings that start to establish molecular mechanisms of age-related decline of mammalian ISC function.}, } @article {pmid31604443, year = {2019}, author = {Ramon-Mateu, J and Ellison, ST and Angelini, TE and Martindale, MQ}, title = {Regeneration in the ctenophore Mnemiopsis leidyi occurs in the absence of a blastema, requires cell division, and is temporally separable from wound healing.}, journal = {BMC biology}, volume = {17}, number = {1}, pages = {80}, pmid = {31604443}, issn = {1741-7007}, mesh = {Animals ; Body Patterning ; Cell Proliferation ; Ctenophora/*physiology ; Models, Biological ; *Regeneration ; *Wound Healing ; }, abstract = {BACKGROUND: The ability to regenerate is a widely distributed but highly variable trait among metazoans. A variety of modes of regeneration has been described for different organisms; however, many questions regarding the origin and evolution of these strategies remain unanswered. Most species of ctenophore (or "comb jellies"), a clade of marine animals that branch off at the base of the animal tree of life, possess an outstanding capacity to regenerate. However, the cellular and molecular mechanisms underlying this ability are unknown. We have used the ctenophore Mnemiopsis leidyi as a system to study wound healing and adult regeneration and provide some first-time insights of the cellular mechanisms involved in the regeneration of one of the most ancient extant group of multicellular animals.

RESULTS: We show that cell proliferation is activated at the wound site and is indispensable for whole-body regeneration. Wound healing occurs normally in the absence of cell proliferation forming a scar-less wound epithelium. No blastema-like structure is generated at the cut site, and pulse-chase experiments and surgical intervention show that cells originating in the main regions of cell proliferation (the tentacle bulbs) do not seem to contribute to the formation of new structures after surgical challenge, suggesting a local source of cells during regeneration. While exposure to cell-proliferation blocking treatment inhibits regeneration, the ability to regenerate is recovered when the treatment ends (days after the original cut), suggesting that ctenophore regenerative capabilities are constantly ready to be triggered and they are somehow separable of the wound healing process.

CONCLUSIONS: Ctenophore regeneration takes place through a process of cell proliferation-dependent non-blastemal-like regeneration and is temporally separable of the wound healing process. We propose that undifferentiated cells assume the correct location of missing structures and differentiate in place. The remarkable ability to replace missing tissue, the many favorable experimental features (e.g., optical clarity, high fecundity, rapid regenerative performance, stereotyped cell lineage, sequenced genome), and the early branching phylogenetic position in the animal tree, all point to the emergence of ctenophores as a new model system to study the evolution of animal regeneration.}, } @article {pmid31601898, year = {2019}, author = {Agić, H and Högström, AES and Moczydłowska, M and Jensen, S and Palacios, T and Meinhold, G and Ebbestad, JOR and Taylor, WL and Høyberget, M}, title = {Organically-preserved multicellular eukaryote from the early Ediacaran Nyborg Formation, Arctic Norway.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {14659}, pmid = {31601898}, issn = {2045-2322}, mesh = {Aquatic Organisms/cytology/*ultrastructure ; Arctic Regions ; *Biological Evolution ; Eukaryota/cytology/*ultrastructure ; Fossils/*ultrastructure ; Microscopy, Electrochemical, Scanning ; Norway ; }, abstract = {Eukaryotic multicellularity originated in the Mesoproterozoic Era and evolved multiple times since, yet early multicellular fossils are scarce until the terminal Neoproterozoic and often restricted to cases of exceptional preservation. Here we describe unusual organically-preserved fossils from mudrocks, that provide support for the presence of organisms with differentiated cells (potentially an epithelial layer) in the late Neoproterozoic. Cyathinema digermulense gen. et sp. nov. from the Nyborg Formation, Vestertana Group, Digermulen Peninsula in Arctic Norway, is a new carbonaceous organ-taxon which consists of stacked tubes with cup-shaped ends. It represents parts of a larger organism (multicellular eukaryote or a colony), likely with greater preservation potential than its other elements. Arrangement of open-ended tubes invites comparison with cells of an epithelial layer present in a variety of eukaryotic clades. This tissue may have benefitted the organism in: avoiding overgrowth, limiting fouling, reproduction, or water filtration. C. digermulense shares characteristics with extant and fossil groups including red algae and their fossils, demosponge larvae and putative sponge fossils, colonial protists, and nematophytes. Regardless of its precise affinity, C. digermulense was a complex and likely benthic marine eukaryote exhibiting cellular differentiation, and a rare occurrence of early multicellularity outside of Konservat-Lagerstätten.}, } @article {pmid31597590, year = {2020}, author = {Diggle, SP and Whiteley, M}, title = {Microbe Profile: Pseudomonas aeruginosa: opportunistic pathogen and lab rat.}, journal = {Microbiology (Reading, England)}, volume = {166}, number = {1}, pages = {30-33}, pmid = {31597590}, issn = {1465-2080}, support = {R01 GM116547/GM/NIGMS NIH HHS/United States ; R56 HL142857/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Biofilms/growth & development ; Biological Evolution ; Drug Resistance, Bacterial ; Genome, Bacterial/genetics ; Humans ; Phylogeny ; Pseudomonas Infections/*microbiology ; Pseudomonas aeruginosa/classification/genetics/*pathogenicity/*physiology ; Virulence ; }, abstract = {Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen and a model bacterium for studying virulence and bacterial social traits. While it can be isolated in low numbers from a wide variety of environments including soil and water, it can readily be found in almost any human/animal-impacted environment. It is a major cause of illness and death in humans with immunosuppressive and chronic conditions, and infections in these patients are difficult to treat due to a number of antibiotic resistance mechanisms and the organism's propensity to form multicellular biofilms.}, } @article {pmid31589468, year = {2019}, author = {Blutt, SE and Klein, OD and Donowitz, M and Shroyer, N and Guha, C and Estes, MK}, title = {Use of organoids to study regenerative responses to intestinal damage.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {317}, number = {6}, pages = {G845-G852}, pmid = {31589468}, issn = {1522-1547}, support = {R24 DK099803/DK/NIDDK NIH HHS/United States ; U01 DK103117/DK/NIDDK NIH HHS/United States ; P30 DK089502/DK/NIDDK NIH HHS/United States ; U24 DK085532/DK/NIDDK NIH HHS/United States ; R01 DK118904/DK/NIDDK NIH HHS/United States ; U19 AI116497/AI/NIAID NIH HHS/United States ; U01 DK085532/DK/NIDDK NIH HHS/United States ; U01 DK103168/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; }, mesh = {*Adult Stem Cells ; Animals ; Cells, Cultured/physiology/transplantation ; Humans ; *Intestinal Diseases/etiology/metabolism/therapy ; *Intestines/drug effects/radiation effects ; Models, Biological ; *Organoids/physiology/transplantation ; Regeneration/*physiology ; Tissue Engineering/methods ; }, abstract = {Intestinal organoid cultures provide an in vitro model system for studying pathways and mechanisms involved in epithelial damage and repair. Derived from either embryonic or induced pluripotent stem cells or adult intestinal stem cells or tissues, these self-organizing, multicellular structures contain polarized mature cells that recapitulate both the physiology and heterogeneity of the intestinal epithelium. These cultures provide a cutting-edge technology for defining regenerative pathways that are induced following radiation or chemical damage, which directly target the cycling intestinal stem cell, or damage resulting from viral, bacterial, or parasitic infection of the epithelium. Novel signaling pathways or biological mechanisms identified from organoid studies that mediate regeneration of the epithelium following damage are likely to be important targets of preventive or therapeutic modalities to mitigate intestinal injury. The evolution of these cultures to include more components of the intestinal wall and the ability to genetically modify them are key components for defining the mechanisms that modulate epithelial regeneration.}, } @article {pmid31589243, year = {2020}, author = {Arcas, A and Wilkinson, DG and Nieto, MÁ}, title = {The Evolutionary History of Ephs and Ephrins: Toward Multicellular Organisms.}, journal = {Molecular biology and evolution}, volume = {37}, number = {2}, pages = {379-394}, pmid = {31589243}, issn = {1537-1719}, support = {FC001217/WT_/Wellcome Trust/United Kingdom ; FC001217/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; FC001217/MRC_/Medical Research Council/United Kingdom ; FC001217/ARC_/Arthritis Research UK/United Kingdom ; }, mesh = {Animals ; Cell Communication ; Choanoflagellata/genetics/metabolism ; Ephrins/*genetics/*metabolism ; Evolution, Molecular ; Humans ; Phylogeny ; Porifera/genetics/metabolism ; Receptors, Eph Family/*genetics/*metabolism ; Signal Transduction ; Vertebrates/genetics/metabolism ; }, abstract = {Eph receptor (Eph) and ephrin signaling regulate fundamental developmental processes through both forward and reverse signaling triggered upon cell-cell contact. In vertebrates, they are both classified into classes A and B, and some representatives have been identified in many metazoan groups, where their expression and functions have been well studied. We have extended previous phylogenetic analyses and examined the presence of Eph and ephrins in the tree of life to determine their origin and evolution. We have found that 1) premetazoan choanoflagellates may already have rudimental Eph/ephrin signaling as they have an Eph-/ephrin-like pair and homologs of downstream-signaling genes; 2) both forward- and reverse-downstream signaling might already occur in Porifera since sponges have most genes involved in these types of signaling; 3) the nonvertebrate metazoan Eph is a type-B receptor that can bind ephrins regardless of their membrane-anchoring structure, glycosylphosphatidylinositol, or transmembrane; 4) Eph/ephrin cross-class binding is specific to Gnathostomata; and 5) kinase-dead Eph receptors can be traced back to Gnathostomata. We conclude that Eph/ephrin signaling is of older origin than previously believed. We also examined the presence of protein domains associated with functional characteristics and the appearance and conservation of downstream-signaling pathways to understand the original and derived functions of Ephs and ephrins. We find that the evolutionary history of these gene families points to an ancestral function in cell-cell interactions that could contribute to the emergence of multicellularity and, in particular, to the required segregation of cell populations.}, } @article {pmid31587642, year = {2019}, author = {López-Escardó, D and Grau-Bové, X and Guillaumet-Adkins, A and Gut, M and Sieracki, ME and Ruiz-Trillo, I}, title = {Reconstruction of protein domain evolution using single-cell amplified genomes of uncultured choanoflagellates sheds light on the origin of animals.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1786}, pages = {20190088}, pmid = {31587642}, issn = {1471-2970}, mesh = {Choanoflagellata/*genetics ; *Evolution, Molecular ; *Genome, Protozoan ; Protein Domains/*genetics ; }, abstract = {Understanding the origins of animal multicellularity is a fundamental biological question. Recent genome data have unravelled the role that co-option of pre-existing genes played in the origin of animals. However, there were also some important genetic novelties at the onset of Metazoa. To have a clear understanding of the specific genetic innovations and how they appeared, we need the broadest taxon sampling possible, especially among early-branching animals and their unicellular relatives. Here, we take advantage of single-cell genomics to expand our understanding of the genomic diversity of choanoflagellates, the sister-group to animals. With these genomes, we have performed an updated and taxon-rich reconstruction of protein evolution from the Last Eukaryotic Common Ancestor (LECA) to animals. Our novel data re-defines the origin of some genes previously thought to be metazoan-specific, like the POU transcription factor, which we show appeared earlier in evolution. Moreover, our data indicate that the acquisition of new genes at the stem of Metazoa was mainly driven by duplications and protein domain rearrangement processes at the stem of Metazoa. Furthermore, our analysis allowed us to reveal protein domains that are essential to the maintenance of animal multicellularity. Our analyses also demonstrate the utility of single-cell genomics from uncultured taxa to address evolutionary questions. This article is part of a discussion meeting issue 'Single cell ecology'.}, } @article {pmid31584936, year = {2019}, author = {Chang, J and Xu, Z and Li, M and Yang, M and Qin, H and Yang, J and Wu, S}, title = {Spatiotemporal cytoskeleton organizations determine morphogenesis of multicellular trichomes in tomato.}, journal = {PLoS genetics}, volume = {15}, number = {10}, pages = {e1008438}, pmid = {31584936}, issn = {1553-7404}, mesh = {Actin Cytoskeleton/genetics/metabolism ; Actin-Related Protein 2-3 Complex/genetics/metabolism ; Solanum lycopersicum/genetics/*growth & development/metabolism ; Microfilament Proteins/*genetics/metabolism ; Microtubules/genetics/metabolism ; *Morphogenesis ; Mutation ; Plant Proteins/*genetics/metabolism ; Spatio-Temporal Analysis ; Trichomes/genetics/*growth & development ; }, abstract = {Plant trichomes originate from epidermal cell, forming protective structure from abiotic and biotic stresses. Different from the unicellular trichome in Arabidopsis, tomato trichomes are multicellular structure and can be classified into seven different types based on cell number, shape and the presence of glandular cells. Despite the importance of tomato trichomes in insect resistance, our understanding of the tomato trichome morphogenesis remains elusive. In this study, we quantitatively analyzed morphological traits of trichomes in tomato and further performed live imaging of cytoskeletons in stably transformed lines with actin and microtubule markers. At different developmental stages, two types of cytoskeletons exhibited distinct patterns in different trichome cells, ranging from transverse, spiral to longitudinal. This gradual transition of actin filament angle from basal to top cells could correlate with the spatial expansion mode in different cells. Further genetic screen for aberrant trichome morphology led to the discovery of a number of independent mutations in SCAR/WAVE and ARP2/3 complex, which resulted in actin bundling and distorted trichomes. Disruption of microtubules caused isotropic expansion while abolished actin filaments entirely inhibited axial extension of trichomes, indicating that microtubules and actin filaments may control distinct aspects of trichome cell expansion. Our results shed light on the roles of cytoskeletons in the formation of multicellular structure of tomato trichomes.}, } @article {pmid31581262, year = {2019}, author = {Garud, A and Carrillo, AJ and Collier, LA and Ghosh, A and Kim, JD and Lopez-Lopez, B and Ouyang, S and Borkovich, KA}, title = {Genetic relationships between the RACK1 homolog cpc-2 and heterotrimeric G protein subunit genes in Neurospora crassa.}, journal = {PloS one}, volume = {14}, number = {10}, pages = {e0223334}, pmid = {31581262}, issn = {1932-6203}, support = {P01 GM068087/GM/NIGMS NIH HHS/United States ; R01 GM086565/GM/NIGMS NIH HHS/United States ; T34 GM062756/GM/NIGMS NIH HHS/United States ; }, mesh = {Genes, Fungal ; Heterotrimeric GTP-Binding Proteins/chemistry/*genetics/metabolism ; Models, Biological ; Mutation ; Neurospora crassa/classification/*genetics/immunology ; Phenotype ; Phylogeny ; Protein Binding ; Recombinant Proteins ; rho-Associated Kinases/chemistry/*genetics/metabolism ; }, abstract = {Receptor for Activated C Kinase-1 (RACK1) is a multifunctional eukaryotic scaffolding protein with a seven WD repeat structure. Among their many cellular roles, RACK1 homologs have been shown to serve as alternative Gβ subunits during heterotrimeric G protein signaling in many systems. We investigated genetic interactions between the RACK1 homolog cpc-2, the previously characterized Gβ subunit gnb-1 and other G protein signaling components in the multicellular filamentous fungus Neurospora crassa. Results from cell fractionation studies and from fluorescent microscopy of a strain expressing a CPC-2-GFP fusion protein revealed that CPC-2 is a cytoplasmic protein. Genetic epistasis experiments between cpc-2, the three Gα genes (gna-1, gna-2 and gna-3) and gnb-1 demonstrated that cpc-2 is epistatic to gna-2 with regards to basal hyphae growth rate and aerial hyphae height, while deletion of cpc-2 mitigates the increased macroconidiation on solid medium observed in Δgnb-1 mutants. Δcpc-2 mutants inappropriately produce conidiophores during growth in submerged culture and mutational activation of gna-3 alleviates this defect. Δcpc-2 mutants are female-sterile and fertility could not be restored by mutational activation of any of the three Gα genes. With the exception of macroconidiation on solid medium, double mutants lacking cpc-2 and gnb-1 exhibited more severe defects for all phenotypic traits, supporting a largely synergistic relationship between GNB-1 and CPC-2 in N. crassa.}, } @article {pmid31569378, year = {2019}, author = {Zárybnický, T and Matoušková, P and Ambrož, M and Šubrt, Z and Skálová, L and Boušová, I}, title = {The Selection and Validation of Reference Genes for mRNA and microRNA Expression Studies in Human Liver Slices Using RT-qPCR.}, journal = {Genes}, volume = {10}, number = {10}, pages = {}, pmid = {31569378}, issn = {2073-4425}, mesh = {14-3-3 Proteins/genetics/metabolism ; Adult ; Aged ; Cytochrome P-450 CYP1A2/genetics/metabolism ; Cytochrome P-450 CYP3A/genetics/metabolism ; Cytochrome P-450 Enzyme System/pharmacology ; Dimethyl Sulfoxide/pharmacology ; Female ; Gene Expression Profiling/*standards ; Humans ; Liver/drug effects/*metabolism ; Male ; MicroRNAs/*genetics/metabolism ; Middle Aged ; RNA, Messenger/*genetics/metabolism ; Real-Time Polymerase Chain Reaction/*standards ; Reference Standards ; Rifampin/pharmacology ; Transcriptome ; beta 2-Microglobulin/genetics/metabolism ; beta-Naphthoflavone/pharmacology ; }, abstract = {The selection of a suitable combination of reference genes (RGs) for data normalization is a crucial step for obtaining reliable and reproducible results from transcriptional response analysis using a reverse transcription-quantitative polymerase chain reaction. This is especially so if a three-dimensional multicellular model prepared from liver tissues originating from biologically diverse human individuals is used. The mRNA and miRNA RGs stability were studied in thirty-five human liver tissue samples and twelve precision-cut human liver slices (PCLS) treated for 24 h with dimethyl sulfoxide (controls) and PCLS treated with β-naphthoflavone (10 µM) or rifampicin (10 µM) as cytochrome P450 (CYP) inducers. Validation of RGs was performed by an expression analysis of CYP3A4 and CYP1A2 on rifampicin and β-naphthoflavone induction, respectively. Regarding mRNA, the best combination of RGs for the controls was YWHAZ and B2M, while YWHAZ and ACTB were selected for the liver samples and treated PCLS. Stability of all candidate miRNA RGs was comparable or better than that of generally used short non-coding RNA U6. The best combination for the control PCLS was miR-16-5p and miR-152-3p, in contrast to the miR-16-5b and miR-23b-3p selected for the treated PCLS. Our results showed that the candidate RGs were rather stable, especially for miRNA in human PCLS.}, } @article {pmid31568885, year = {2019}, author = {Thakur, R and Shiratori, T and Ishida, KI}, title = {Taxon-rich Multigene Phylogenetic Analyses Resolve the Phylogenetic Relationship Among Deep-branching Stramenopiles.}, journal = {Protist}, volume = {170}, number = {5}, pages = {125682}, doi = {10.1016/j.protis.2019.125682}, pmid = {31568885}, issn = {1618-0941}, mesh = {*Phylogeny ; Stramenopiles/*classification/*genetics ; Transcriptome ; }, abstract = {Stramenopiles are one of the major eukaryotic assemblages. This group comprises a wide range of species including photosynthetic unicellular and multicellular algae, fungus-like osmotrophic organisms and many free-living phagotrophic flagellates. However, the phylogeny of the Stramenopiles, especially relationships among deep-branching heterotrophs, has not yet been resolved because of a lack of adequate transcriptomic data for representative lineages. In this study, we performed multigene phylogenetic analyses of deep-branching Stramenopiles with improved taxon sampling. We sequenced transcriptomes of three deep-branching Stramenopiles: Incisomonas marina, Pseudophyllomitus vesiculosus and Platysulcus tardus. Phylogenetic analyses using 120 protein-coding genes and 56 taxa indicated that Pl. tardus is sister to all other Stramenopiles while Ps. vesiculosus is sister to MAST-4 and form a robust clade with the Labyrinthulea. The resolved phylogenetic relationships of deep-branching Stramenopiles provide insights into the ancestral traits of the Stramenopiles.}, } @article {pmid31568790, year = {2020}, author = {Newman, SA}, title = {Cell differentiation: What have we learned in 50 years?.}, journal = {Journal of theoretical biology}, volume = {485}, number = {}, pages = {110031}, doi = {10.1016/j.jtbi.2019.110031}, pmid = {31568790}, issn = {1095-8541}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation/genetics ; Eukaryota/genetics ; Evolution, Molecular ; Gene Expression Regulation ; *Gene Regulatory Networks ; }, abstract = {I revisit two theories of cell differentiation in multicellular organisms published a half-century ago, Stuart Kauffman's global genome regulatory dynamics (GGRD) model and Roy Britten's and Eric Davidson's modular gene regulatory network (MGRN) model, in light of newer knowledge of mechanisms of gene regulation in the metazoans (animals). The two models continue to inform hypotheses and computational studies of differentiation of lineage-adjacent cell types. However, their shared notion (based on bacterial regulatory systems) of gene switches and networks built from them have constrained progress in understanding the dynamics and evolution of differentiation. Recent work has described unique write-read-rewrite chromatin-based expression encoding in eukaryotes, as well metazoan-specific processes of gene activation and silencing in condensed-phase, enhancer-recruiting regulatory hubs, employing disordered proteins, including transcription factors, with context-dependent identities. These findings suggest an evolutionary scenario in which the origination of differentiation in animals, rather than depending exclusively on adaptive natural selection, emerged as a consequence of a type of multicellularity in which the novel metazoan gene regulatory apparatus was readily mobilized to amplify and exaggerate inherent cell functions of unicellular ancestors. The plausibility of this hypothesis is illustrated by the evolution of the developmental role of Grainyhead-like in the formation of epithelium.}, } @article {pmid31565856, year = {2019}, author = {Gilbert, SF}, title = {Evolutionary transitions revisited: Holobiont evo-devo.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {307-314}, doi = {10.1002/jez.b.22903}, pmid = {31565856}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; *Developmental Biology ; Host Microbial Interactions ; Life Cycle Stages ; Microbiota ; *Symbiosis ; }, abstract = {John T. Bonner lists four essential transformations in the evolution of life: the emergence of the eukaryotic cell, meiosis, multicellularity, and the nervous system. This paper analyses the mechanisms for those transitions in light of three of Dr. Bonner's earlier hypotheses: (a) that the organism is its life cycle, (b) that evolution consists of alterations of the life cycle, and (c) that development extends beyond the body and into interactions with other organisms. Using the notion of the holobiont life cycle, this paper attempts to show that these evolutionary transitions can be accomplished through various means of symbiosis. Perceiving the organism both as an interspecies consortium and as a life cycle supports a twofold redefinition of the organism as a holobiont constructed by integrating together the life cycles of several species. These findings highlight the importance of symbiosis and the holobiont development in analyses of evolution.}, } @article {pmid31552662, year = {2020}, author = {Wanninger, A and Wollesen, T}, title = {Methods in Brain Development of Molluscs.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2047}, number = {}, pages = {311-324}, doi = {10.1007/978-1-4939-9732-9_17}, pmid = {31552662}, issn = {1940-6029}, mesh = {Animals ; Brain/growth & development/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Immunohistochemistry/*methods ; In Situ Hybridization/*methods ; Microscopy, Confocal ; Mollusca/*growth & development/metabolism ; }, abstract = {Representatives of the phylum Mollusca have long been important models in neurobiological research. Recently, the routine application of immunocytochemistry and gene expression analyses in combination with confocal laserscanning microscopy has allowed fast generation of highly detailed reconstructions of neural structures of even the smallest multicellular animals, including early developmental stages. As a consequence, large-scale comparative analyses of neurogenesis-an important prerequisite for inferences concerning the evolution of animal nervous systems-are now possible in a reasonable amount of time. Herein, we describe immunocytochemical staining and in situ hybridization protocols for both, whole-mount preparations of developmental stages-usually 70-300 μm in size-as well as for vibratome and cryostat sections of complex brains. Although our procedures have been optimized for marine molluscs, they may easily be adapted to other (marine) organisms by the creative neurobiologist.}, } @article {pmid31542284, year = {2019}, author = {Barger, SR and James, ML and Pellenz, CD and Krendel, M and Sirotkin, V}, title = {Human myosin 1e tail but not motor domain replaces fission yeast Myo1 domains to support myosin-I function during endocytosis.}, journal = {Experimental cell research}, volume = {384}, number = {2}, pages = {111625}, pmid = {31542284}, issn = {1090-2422}, support = {R01 DK083345/DK/NIDDK NIH HHS/United States ; }, mesh = {Actins/metabolism ; Endocytosis/*physiology ; Humans ; Myosin Heavy Chains/*metabolism ; Myosin Type I/*metabolism ; Protein Domains/physiology ; Schizosaccharomyces/*metabolism ; Schizosaccharomyces pombe Proteins/*metabolism ; }, abstract = {In both unicellular and multicellular organisms, long-tailed class I myosins function in clathrin-mediated endocytosis. Myosin 1e (Myo1e) in vertebrates and Myo1 in fission yeast have similar domain organization, yet whether these proteins or their individual protein domains are functionally interchangeable remains unknown. In an effort to assess functional conservation of class I myosins, we tested whether human Myo1e could replace Myo1 in fission yeast Schizosaccharomyces pombe and found that it was unable to substitute for yeast Myo1. To determine if any individual protein domain is responsible for the inability of Myo1e to function in yeast, we created human-yeast myosin-I chimeras. By functionally testing these chimeric myosins in vivo, we concluded that the Myo1e motor domain is unable to function in yeast, even when combined with the yeast Myo1 tail and a full complement of yeast regulatory light chains. Conversely, the Myo1e tail, when attached to the yeast Myo1 motor domain, supports localization to endocytic actin patches and partially rescues the endocytosis defect in myo1Δ cells. Further dissection showed that both the TH1 and TH2-SH3 domains in the human Myo1e tail are required for localization and function of chimeric myosin-I at endocytic sites. Overall, this study provides insights into the role of individual myosin-I domains, expands the utility of fission yeast as a simple model system to study the effects of disease-associated MYO1E mutations, and supports a model of co-evolution between a myosin motor and its actin track.}, } @article {pmid31540916, year = {2019}, author = {Pukhlyakova, EA and Kirillova, AO and Kraus, YA and Zimmermann, B and Technau, U}, title = {A cadherin switch marks germ layer formation in the diploblastic sea anemone Nematostella vectensis.}, journal = {Development (Cambridge, England)}, volume = {146}, number = {20}, pages = {}, doi = {10.1242/dev.174623}, pmid = {31540916}, issn = {1477-9129}, mesh = {Animals ; Cadherins/*metabolism ; Ectoderm/cytology/metabolism ; Embryo, Nonmammalian/*cytology/*metabolism ; Endoderm/cytology/metabolism ; Germ Layers/*cytology/*metabolism ; Sea Anemones/*embryology/*metabolism ; }, abstract = {Morphogenesis is a shape-building process during development of multicellular organisms. During this process, the establishment and modulation of cell-cell contacts play an important role. Cadherins, the major cell adhesion molecules, form adherens junctions connecting epithelial cells. Numerous studies of Bilateria have shown that cadherins are associated with the regulation of cell differentiation, cell shape changes, cell migration and tissue morphogenesis. To date, the role of cadherins in non-bilaterians is unknown. Here, we study the expression and function of two paralogous classical cadherins, Cadherin 1 and Cadherin 3, in a diploblastic animal, the sea anemone Nematostella vectensis We show that a cadherin switch accompanies the formation of germ layers. Using specific antibodies, we show that both cadherins are localized to adherens junctions at apical and basal positions in ectoderm and endoderm. During gastrulation, partial epithelial-to-mesenchymal transition of endodermal cells is marked by stepwise downregulation of Cadherin 3 and upregulation of Cadherin 1. Knockdown experiments show that both cadherins are required for maintenance of tissue integrity and tissue morphogenesis. Thus, both sea anemones and bilaterians use independently duplicated cadherins combinatorially for tissue morphogenesis and germ layer differentiation.}, } @article {pmid31529373, year = {2021}, author = {Erwin, DH}, title = {Tempos and modes of collectivity in the history of life.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {140}, number = {4}, pages = {343-351}, pmid = {31529373}, issn = {1611-7530}, support = {NNA13AA90A//NASA Astrobiology Institute/ ; }, mesh = {Animals ; *Biological Evolution ; *Insecta ; Phylogeny ; }, abstract = {Collective integration and processing of information have increased through the history of life, through both the formation of aggregates in which the entities may have very different properties and which jointly coarse-grained environmental variables (ranging from widely varying metabolism in microbial consortia to the ecological diversity of species on reefs) and through collectives of similar entities (such as cells within an organism or social groups). Such increases have been implicated in significant transitions in the history of life, including aspects of the origin of life, the generation of pangenomes among microbes and microbial communities such as stromatolites, multicellularity and social insects. This contribution provides a preliminary overview of the dominant modes of collective information processing in the history of life, their phylogenetic distribution and extent of convergence, and the effects of new modes for integrating and acting upon information on the tempo of evolutionary change.}, } @article {pmid31521200, year = {2019}, author = {Rausch, P and Rühlemann, M and Hermes, BM and Doms, S and Dagan, T and Dierking, K and Domin, H and Fraune, S and von Frieling, J and Hentschel, U and Heinsen, FA and Höppner, M and Jahn, MT and Jaspers, C and Kissoyan, KAB and Langfeldt, D and Rehman, A and Reusch, TBH and Roeder, T and Schmitz, RA and Schulenburg, H and Soluch, R and Sommer, F and Stukenbrock, E and Weiland-Bräuer, N and Rosenstiel, P and Franke, A and Bosch, T and Baines, JF}, title = {Comparative analysis of amplicon and metagenomic sequencing methods reveals key features in the evolution of animal metaorganisms.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {133}, pmid = {31521200}, issn = {2049-2618}, mesh = {Animals ; Bacteria/classification/genetics ; Databases, Genetic ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenome/genetics/*physiology ; Microbiota/genetics/*physiology ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {BACKGROUND: The interplay between hosts and their associated microbiome is now recognized as a fundamental basis of the ecology, evolution, and development of both players. These interdependencies inspired a new view of multicellular organisms as "metaorganisms." The goal of the Collaborative Research Center "Origin and Function of Metaorganisms" is to understand why and how microbial communities form long-term associations with hosts from diverse taxonomic groups, ranging from sponges to humans in addition to plants.

METHODS: In order to optimize the choice of analysis procedures, which may differ according to the host organism and question at hand, we systematically compared the two main technical approaches for profiling microbial communities, 16S rRNA gene amplicon and metagenomic shotgun sequencing across our panel of ten host taxa. This includes two commonly used 16S rRNA gene regions and two amplification procedures, thus totaling five different microbial profiles per host sample.

CONCLUSION: While 16S rRNA gene-based analyses are subject to much skepticism, we demonstrate that many aspects of bacterial community characterization are consistent across methods. The resulting insight facilitates the selection of appropriate methods across a wide range of host taxa. Overall, we recommend single- over multi-step amplification procedures, and although exceptions and trade-offs exist, the V3 V4 over the V1 V2 region of the 16S rRNA gene. Finally, by contrasting taxonomic and functional profiles and performing phylogenetic analysis, we provide important and novel insight into broad evolutionary patterns among metaorganisms, whereby the transition of animals from an aquatic to a terrestrial habitat marks a major event in the evolution of host-associated microbial composition.}, } @article {pmid31517991, year = {2020}, author = {de Araújo Silva-Cardoso, IM and Meira, FS and Gomes, ACMM and Scherwinski-Pereira, JE}, title = {Histology, histochemistry and ultrastructure of pre-embryogenic cells determined for direct somatic embryogenesis in the palm tree Syagrus oleracea.}, journal = {Physiologia plantarum}, volume = {168}, number = {4}, pages = {845-875}, doi = {10.1111/ppl.13026}, pmid = {31517991}, issn = {1399-3054}, support = {426637/2016-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 001-2011/Grant 39//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 01.08.0597.01//Financiadora de Estudos e Projetos/ ; 01.13.0315.00//Financiadora de Estudos e Projetos/ ; }, mesh = {2,4-Dichlorophenoxyacetic Acid ; Arecaceae/*cytology ; Culture Media ; Indoleacetic Acids ; Plant Cells/*ultrastructure ; *Plant Somatic Embryogenesis Techniques ; Trees ; }, abstract = {Somatic embryogenesis in palm trees is, in general, a slow and highly complex process, with a predominance of the indirect route and, consequently, a lack of knowledge about the direct route. We present new knowledge related to the morphological, histochemical and ultrastructural aspects of the transition from somatic to embryogenic cells and direct formation of somatic embryos from mature zygotic embryos of Syagrus oleracea, a palm tree. The results support the general concept that 2,4-dichlorophenoxyacetic acid plays a critical role for the formation of somatic embryos of direct and multicellular origin. Seven days in medium with auxin were enough for the identification of embryogenic cells. These cells had a set of characteristics corresponding to totipotent stem cells. At 14 days on induction medium, nodular formations were observed in the distal region of inoculated embryos, which evolved into globular somatic embryos. At 120 days on induction medium, the quality of the somatic embryos was compromised. The dynamics of the mobilization of reserve compounds was also demonstrated, with emphasis on starch and protein as energy sources required for the embryogenic process. This study shows for the first time the anatomical and ultrastructural events involved in direct somatic embryogenesis in a palm tree and incites the scientific community to return to the discussion of classical concepts related to direct somatic embryogenesis, especially regarding the characteristics and location of determined pre-embryogenic cells.}, } @article {pmid31501435, year = {2019}, author = {Kiss, E and Hegedüs, B and Virágh, M and Varga, T and Merényi, Z and Kószó, T and Bálint, B and Prasanna, AN and Krizsán, K and Kocsubé, S and Riquelme, M and Takeshita, N and Nagy, LG}, title = {Comparative genomics reveals the origin of fungal hyphae and multicellularity.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {4080}, pmid = {31501435}, issn = {2041-1723}, mesh = {Evolution, Molecular ; Fungal Proteins/genetics/metabolism ; Fungi/*cytology/*genetics ; Genes, Fungal ; *Genomics ; Hyphae/*cytology/*genetics ; Morphogenesis/genetics ; Multigene Family ; Phagocytosis/genetics ; Phylogeny ; Yeasts/genetics ; }, abstract = {Hyphae represent a hallmark structure of multicellular fungi. The evolutionary origins of hyphae and of the underlying genes are, however, hardly known. By systematically analyzing 72 complete genomes, we here show that hyphae evolved early in fungal evolution probably via diverse genetic changes, including co-option and exaptation of ancient eukaryotic (e.g. phagocytosis-related) genes, the origin of new gene families, gene duplications and alterations of gene structure, among others. Contrary to most multicellular lineages, the origin of filamentous fungi did not correlate with expansions of kinases, receptors or adhesive proteins. Co-option was probably the dominant mechanism for recruiting genes for hypha morphogenesis, while gene duplication was apparently less prevalent, except in transcriptional regulators and cell wall - related genes. We identified 414 novel gene families that show correlated evolution with hyphae and that may have contributed to its evolution. Our results suggest that hyphae represent a unique multicellular organization that evolved by limited fungal-specific innovations and gene duplication but pervasive co-option and modification of ancient eukaryotic functions.}, } @article {pmid31480977, year = {2019}, author = {Fisher, RM and Regenberg, B}, title = {Multicellular group formation in Saccharomyces cerevisiae.}, journal = {Proceedings. Biological sciences}, volume = {286}, number = {1910}, pages = {20191098}, pmid = {31480977}, issn = {1471-2954}, mesh = {Biological Evolution ; Phenotype ; Saccharomyces cerevisiae/*physiology ; }, abstract = {Understanding how and why cells cooperate to form multicellular organisms is a central aim of evolutionary biology. Multicellular groups can form through clonal development (where daughter cells stick to mother cells after division) or by aggregation (where cells aggregate to form groups). These different ways of forming groups directly affect relatedness between individual cells, which in turn can influence the degree of cooperation and conflict within the multicellular group. It is hard to study the evolution of multicellularity by focusing only on obligately multicellular organisms, like complex animals and plants, because the factors that favour multicellular cooperation cannot be disentangled, as cells cannot survive and reproduce independently. We support the use of Saccharomyces cerevisiae as an ideal model for studying the very first stages of the evolution of multicellularity. This is because it can form multicellular groups both clonally and through aggregation and uses a family of proteins called 'flocculins' that determine the way in which groups form, making it particularly amenable to laboratory experiments. We briefly review current knowledge about multicellularity in S. cerevisiae and then propose a framework for making predictions about the evolution of multicellular phenotypes in yeast based on social evolution theory. We finish by explaining how S. cerevisiae is a particularly useful experimental model for the analysis of open questions concerning multicellularity.}, } @article {pmid31478136, year = {2019}, author = {Hartenstein, V and Martinez, P}, title = {Structure, development and evolution of the digestive system.}, journal = {Cell and tissue research}, volume = {377}, number = {3}, pages = {289-292}, pmid = {31478136}, issn = {1432-0878}, support = {R01 NS054814/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Digestion ; Digestive System/*cytology ; Immune System/physiology ; Phagocytosis/physiology ; }, abstract = {Living cells depend on a constant supply of energy-rich organic molecules from the environment. Small molecules pass into the interior of the cell via simple diffusion or active transport carried out by membrane bound transporters; macromolecules, or entire cells, are taken up by endocytosis/phagocytosis, and are degraded intracellularly in specialized membrane bound compartments (lysosomes). Whereas all cells are capable of transporting molecules through the membrane, the efficient procurement, digestion and uptake of nutrients have become the function of specialized cell types and organs, forming the digestive system in multicellular animals. In mammals, for example, the digestive system is comprised of glandular organs with classes of cells specialized in the secretion of enzymes for the extracellular digestion of food particles (e.g., exocrine cells of the salivary gland, pancreas), as well as other organs with absorptive function (e.g., small intestine). Numerous other cell types, such as smooth muscle cells, neurons and enteroendocrine cells, are associated with glandular cells and intestinal cells to promote the digestive process.}, } @article {pmid31474536, year = {2019}, author = {Gonçalves, AP and Heller, J and Span, EA and Rosenfield, G and Do, HP and Palma-Guerrero, J and Requena, N and Marletta, MA and Glass, NL}, title = {Allorecognition upon Fungal Cell-Cell Contact Determines Social Cooperation and Impacts the Acquisition of Multicellularity.}, journal = {Current biology : CB}, volume = {29}, number = {18}, pages = {3006-3017.e3}, doi = {10.1016/j.cub.2019.07.060}, pmid = {31474536}, issn = {1879-0445}, support = {S10 RR029668/RR/NCRR NIH HHS/United States ; S10 RR027303/RR/NCRR NIH HHS/United States ; }, mesh = {Alleles ; Amino Acid Sequence/genetics ; Cell Communication/*genetics/physiology ; Cell Fusion ; Cell Wall/*genetics/*metabolism ; Evolution, Molecular ; Fungal Proteins/genetics/metabolism ; Genes, Fungal/genetics ; Neurospora crassa/genetics/growth & development ; Phylogeny ; Polymorphism, Genetic/genetics ; }, abstract = {Somatic cell fusion and conspecific cooperation are crucial social traits for microbial unicellular-to-multicellular transitions, colony expansion, and substrate foraging but are also associated with risks of parasitism. We identified a cell wall remodeling (cwr) checkpoint that acts upon cell contact to assess genetic compatibility and regulate cell wall dissolution during somatic cell fusion in a wild population of the filamentous fungus Neurospora crassa. Non-allelic interactions between two linked loci, cwr-1 and cwr-2, were necessary and sufficient to block cell fusion: cwr-1 encodes a polysaccharide monooxygenase (PMO), a class of enzymes associated with extracellular degradative capacities, and cwr-2 encodes a predicted transmembrane protein. Mutations of sites in CWR-1 essential for PMO catalytic activity abolished the block in cell fusion between formerly incompatible strains. In Neurospora, alleles cwr-1 and cwr-2 were highly polymorphic, fell into distinct haplogroups, and showed trans-species polymorphisms. Distinct haplogroups and trans-species polymorphisms at cwr-1 and cwr-2 were also identified in the distantly related genus Fusarium, suggesting convergent evolution. Proteins involved in chemotropic processes showed extended localization at contact sites, suggesting that cwr regulates the transition between chemotropic growth and cell wall dissolution. Our work revealed an allorecognition surveillance system based on kind discrimination that inhibits cooperative behavior in fungi by blocking cell fusion upon contact, contributing to fungal immunity by preventing formation of chimeras between genetically non-identical colonies.}, } @article {pmid31456065, year = {2019}, author = {Cleri, F}, title = {Agent-based model of multicellular tumor spheroid evolution including cell metabolism.}, journal = {The European physical journal. E, Soft matter}, volume = {42}, number = {8}, pages = {112}, pmid = {31456065}, issn = {1292-895X}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Carcinogenesis/genetics/*metabolism/pathology ; *Clonal Evolution ; DNA Damage ; Glucose/metabolism ; Humans ; Markov Chains ; *Models, Theoretical ; Oxygen/metabolism ; Spheroids, Cellular/*metabolism/pathology ; Tumor Cells, Cultured ; }, abstract = {Computational models aiming at the spatio-temporal description of cancer evolution are a suitable framework for testing biological hypotheses from experimental data, and generating new ones. Building on our recent work (J. Theor. Biol. 389, 146 (2016)) we develop a 3D agent-based model, capable of tracking hundreds of thousands of interacting cells, over time scales ranging from seconds to years. Cell dynamics is driven by a Monte Carlo solver, incorporating partial differential equations to describe chemical pathways and the activation/repression of "genes", leading to the up- or down-regulation of specific cell markers. Each cell-agent of different kind (stem, cancer, stromal etc.) runs through its cycle, undergoes division, can exit to a dormant, senescent, necrotic state, or apoptosis, according to the inputs from its systemic network. The basic network at this stage describes glucose/oxygen/ATP cycling, and can be readily extended to cancer-cell specific markers. Eventual accumulation of chemical/radiation damage to each cell's DNA is described by a Markov chain of internal states, and by a damage-repair network, whose evolution is linked to the cell systemic network. Aimed at a direct comparison with experiments of tumorsphere growth from stem cells, the present model will allow to quantitatively study the role of transcription factors involved in the reprogramming and variable radio-resistance of simulated cancer-stem cells, evolving in a realistic computer simulation of a growing multicellular tumorsphere.}, } @article {pmid31451789, year = {2019}, author = {Bruno, L and Ramlall, V and Studer, RA and Sauer, S and Bradley, D and Dharmalingam, G and Carroll, T and Ghoneim, M and Chopin, M and Nutt, SL and Elderkin, S and Rueda, DS and Fisher, AG and Siggers, T and Beltrao, P and Merkenschlager, M}, title = {Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system.}, journal = {Nature immunology}, volume = {20}, number = {10}, pages = {1372-1380}, pmid = {31451789}, issn = {1529-2916}, support = {MC_U120027516/MRC_/Medical Research Council/United Kingdom ; 099276/WT_/Wellcome Trust/United Kingdom ; MC_UP_1102/5/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; R01 AI116829/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Cell Lineage ; Conserved Sequence ; Core Binding Factor alpha Subunits/*genetics ; Evolution, Molecular ; Gene Duplication ; Humans ; Immune System/*physiology ; Langerhans Cells/*physiology ; Mammals ; Organ Specificity/*genetics ; Signal Transduction ; T-Lymphocytes, Regulatory/*physiology ; Transcriptome ; }, abstract = {In multicellular organisms, duplicated genes can diverge through tissue-specific gene expression patterns, as exemplified by highly regulated expression of RUNX transcription factor paralogs with apparent functional redundancy. Here we asked what cell-type-specific biologies might be supported by the selective expression of RUNX paralogs during Langerhans cell and inducible regulatory T cell differentiation. We uncovered functional nonequivalence between RUNX paralogs. Selective expression of native paralogs allowed integration of transcription factor activity with extrinsic signals, while non-native paralogs enforced differentiation even in the absence of exogenous inducers. DNA binding affinity was controlled by divergent amino acids within the otherwise highly conserved RUNT domain and evolutionary reconstruction suggested convergence of RUNT domain residues toward submaximal strength. Hence, the selective expression of gene duplicates in specialized cell types can synergize with the acquisition of functional differences to enable appropriate gene expression, lineage choice and differentiation in the mammalian immune system.}, } @article {pmid31446445, year = {2019}, author = {Annunziata, R and Andrikou, C and Perillo, M and Cuomo, C and Arnone, MI}, title = {Development and evolution of gut structures: from molecules to function.}, journal = {Cell and tissue research}, volume = {377}, number = {3}, pages = {445-458}, doi = {10.1007/s00441-019-03093-9}, pmid = {31446445}, issn = {1432-0878}, support = {215781//Marie Curie ITN EVONET/ ; }, mesh = {Animals ; Biological Evolution ; *Gastrointestinal Tract/cytology/physiology ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Larva/physiology ; Sea Urchins/genetics/*physiology ; Starfish/genetics/*physiology ; Vertebrates/genetics/*physiology ; }, abstract = {The emergence of a specialized system for food digestion and nutrient absorption was a crucial innovation for multicellular organisms. Digestive systems with different levels of complexity evolved in different animals, with the endoderm-derived one-way gut of most bilaterians to be the prevailing and more specialized form. While the molecular events regulating the early phases of embryonic tissue specification have been deeply investigated in animals occupying different phylogenetic positions, the mechanisms underlying gut patterning and gut-associated structures differentiation are still mostly obscure. In this review, we describe the main discoveries in gut and gut-associated structures development in echinoderm larvae (mainly for sea urchin and, when available, for sea star) and compare them with existing information in vertebrates. An impressive degree of conservation emerges when comparing the transcription factor toolkits recruited for gut cells and tissue differentiation in animals as diverse as echinoderms and vertebrates, thus suggesting that their function emerged in the deuterostome ancestor.}, } @article {pmid31444931, year = {2019}, author = {Wu, F and Ma, C and Han, B and Meng, L and Hu, H and Fang, Y and Feng, M and Zhang, X and Rueppell, O and Li, J}, title = {Behavioural, physiological and molecular changes in alloparental caregivers may be responsible for selection response for female reproductive investment in honey bees.}, journal = {Molecular ecology}, volume = {28}, number = {18}, pages = {4212-4227}, doi = {10.1111/mec.15207}, pmid = {31444931}, issn = {1365-294X}, mesh = {Amino Acid Sequence ; Animals ; Arthropod Antennae/physiology ; Bees/*genetics/*physiology ; Behavior, Animal/*physiology ; Fatty Acids ; Female ; Genetic Association Studies ; Honey ; Insect Proteins/chemistry/metabolism ; Larva/physiology ; Pheromones/chemistry/metabolism ; Proteome/metabolism ; Proteomics ; Reproduction ; Volatile Organic Compounds/analysis ; }, abstract = {Reproductive investment is a central life history variable that influences all aspects of life. Hormones coordinate reproduction in multicellular organisms, but the mechanisms controlling the collective reproductive investment of social insects are largely unexplored. One important aspect of honey bee (Apis mellifera) reproductive investment consists of raising female-destined larvae into new queens by alloparental care of nurse bees in form of royal jelly provisioning. Artificial selection for commercial royal jelly production over 40 years has increased this reproductive investment by an order of magnitude. In a cross-fostering experiment, we establish that this shift in social phenotype is caused by nurse bees. We find no evidence for changes in larval signalling. Instead, the antennae of the nurse bees of the selected stock are more responsive to brood pheromones than control bees. Correspondingly, the selected royal jelly bee nurses are more attracted to brood pheromones than unselected control nurses. Comparative proteomics of the antennae from the selected and unselected stocks indicate putative molecular mechanisms, primarily changes in chemosensation and energy metabolism. We report expression differences of several candidate genes that correlate with the differences in reproductive investment. The functional relevance of these genes is supported by demonstrating that the corresponding proteins can competitively bind one previously described and one newly discovered brood pheromone. Thus, we suggest several chemosensory genes, most prominently OBP16 and CSP4, as candidate mechanisms controlling queen rearing, a key reproductive investment, in honey bees. These findings reveal novel aspects of pheromonal communication in honey bees and explain how sensory changes affect communication and lead to a drastic shift in colony-level resource allocation to sexual reproduction. Thus, pheromonal and hormonal communication may play similar roles for reproductive investment in superorganisms and multicellular organisms, respectively.}, } @article {pmid31444229, year = {2019}, author = {Draper, GW and Shoemark, DK and Adams, JC}, title = {Modelling the early evolution of extracellular matrix from modern Ctenophores and Sponges.}, journal = {Essays in biochemistry}, volume = {63}, number = {3}, pages = {389-405}, doi = {10.1042/EBC20180048}, pmid = {31444229}, issn = {1744-1358}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Ctenophora/*chemistry/genetics ; Extracellular Matrix/*genetics ; Extracellular Matrix Proteins/*analysis/chemistry/genetics ; Genomics ; Porifera/*chemistry/genetics ; Protein Domains ; Proteome/analysis ; Transcriptome ; }, abstract = {Animals (metazoans) include some of the most complex living organisms on Earth, with regard to their multicellularity, numbers of differentiated cell types, and lifecycles. The metazoan extracellular matrix (ECM) is well-known to have major roles in the development of tissues during embryogenesis and in maintaining homoeostasis throughout life, yet insight into the ECM proteins which may have contributed to the transition from unicellular eukaryotes to multicellular animals remains sparse. Recent phylogenetic studies place either ctenophores or poriferans as the closest modern relatives of the earliest emerging metazoans. Here, we review the literature and representative genomic and transcriptomic databases for evidence of ECM and ECM-affiliated components known to be conserved in bilaterians, that are also present in ctenophores and/or poriferans. Whereas an extensive set of related proteins are identifiable in poriferans, there is a strikingly lack of conservation in ctenophores. From this perspective, much remains to be learnt about the composition of ctenophore mesoglea. The principal ECM-related proteins conserved between ctenophores, poriferans, and bilaterians include collagen IV, laminin-like proteins, thrombospondin superfamily members, integrins, membrane-associated proteoglycans, and tissue transglutaminase. These are candidates for a putative ancestral ECM that may have contributed to the emergence of the metazoans.}, } @article {pmid31443631, year = {2019}, author = {Rozhok, A and DeGregori, J}, title = {Somatic maintenance impacts the evolution of mutation rate.}, journal = {BMC evolutionary biology}, volume = {19}, number = {1}, pages = {172}, pmid = {31443631}, issn = {1471-2148}, support = {R01 CA180175/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Body Size ; Computer Simulation ; Longevity ; *Models, Genetic ; Monte Carlo Method ; Mutation ; *Mutation Rate ; Neoplasms/genetics ; Phenotype ; Population Density ; Selection, Genetic ; }, abstract = {BACKGROUND: The evolution of multi-cellular animals has produced a conspicuous trend toward increased body size. This trend has introduced at least two novel problems: an expected elevated risk of somatic disorders, such as cancer, and declining evolvability due to generally reduced population size, lower reproduction rate and extended generation time. Low population size is widely recognized to explain the high mutation rates in animals by limiting the presumed universally negative selection acting on mutation rates.

RESULTS: Here, we present evidence from stochastic modeling that the direction and strength of selection acting on mutation rates is highly dependent on the evolution of somatic maintenance, and thus longevity, which modulates the cost of somatic mutations.

CONCLUSIONS: We argue that the impact of the evolution of longevity on mutation rates may have been critical in facilitating animal evolution.}, } @article {pmid31430180, year = {2019}, author = {D'Ario, M and Sablowski, R}, title = {Cell Size Control in Plants.}, journal = {Annual review of genetics}, volume = {53}, number = {}, pages = {45-65}, doi = {10.1146/annurev-genet-112618-043602}, pmid = {31430180}, issn = {1545-2948}, support = {BBS/E/J/00000594/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P013511/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M003825/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Cell Size ; DNA Replication ; Eukaryotic Cells/cytology ; Meristem/*cytology/growth & development ; Mitosis ; Models, Biological ; Plant Cells/*physiology ; Plant Development/genetics ; *Ploidies ; Yeasts/cytology/genetics ; }, abstract = {The genetic control of the characteristic cell sizes of different species and tissues is a long-standing enigma. Plants are convenient for studying this question in a multicellular context, as their cells do not move and are easily tracked and measured from organ initiation in the meristems to subsequent morphogenesis and differentiation. In this article, we discuss cell size control in plants compared with other organisms. As seen from yeast cells to mammalian cells, size homeostasis is maintained cell autonomously in the shoot meristem. In developing organs, vacuolization contributes to cell size heterogeneity and may resolve conflicts between growth control at the cellular and organ levels. Molecular mechanisms for cell size control have implications for how cell size responds to changes in ploidy, which are particularly important in plant development and evolution. We also discuss comparatively the functional consequences of cell size and their potential repercussions at higher scales, including genome evolution.}, } @article {pmid31419316, year = {2020}, author = {Fan, X and Han, W and Teng, L and Jiang, P and Zhang, X and Xu, D and Li, C and Pellegrini, M and Wu, C and Wang, Y and Kaczurowski, MJS and Lin, X and Tirichine, L and Mock, T and Ye, N}, title = {Single-base methylome profiling of the giant kelp Saccharina japonica reveals significant differences in DNA methylation to microalgae and plants.}, journal = {The New phytologist}, volume = {225}, number = {1}, pages = {234-249}, pmid = {31419316}, issn = {1469-8137}, mesh = {Chromosomes, Plant/genetics ; Cytosine/metabolism ; DNA Methylation/*genetics ; Evolution, Molecular ; Gene Expression Regulation, Plant ; Genome, Plant ; Heterozygote ; Kelp/*genetics ; Methyltransferases/genetics/metabolism ; Microalgae/*genetics ; Oxidoreductases, O-Demethylating/metabolism ; Plants/*genetics ; Promoter Regions, Genetic/genetics ; Transcriptome/genetics ; }, abstract = {Brown algae have convergently evolved plant-like body plans and reproductive cycles, which in plants are controlled by differential DNA methylation. This contribution provides the first single-base methylome profiles of haploid gametophytes and diploid sporophytes of a multicellular alga. Although only c. 1.4% of cytosines in Saccharina japonica were methylated mainly at CHH sites and characterized by 5-methylcytosine (5mC), there were significant differences between life-cycle stages. DNA methyltransferase 2 (DNMT2), known to efficiently catalyze tRNA methylation, is assumed to methylate the genome of S. japonica in the structural context of tRNAs as the genome does not encode any other DNA methyltransferases. Circular and long noncoding RNA genes were the most strongly methylated regulatory elements in S. japonica. Differential expression of genes was negatively correlated with DNA methylation with the highest methylation levels measured in both haploid gametophytes. Hypomethylated and highly expressed genes in diploid sporophytes included genes involved in morphogenesis and halogen metabolism. The data herein provide evidence that cytosine methylation, although occurring at a low level, is significantly contributing to the formation of different life-cycle stages, tissue differentiation and metabolism in brown algae.}, } @article {pmid31417549, year = {2019}, author = {Kim, HR and Jun, CD}, title = {T Cell Microvilli: Sensors or Senders?.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {1753}, pmid = {31417549}, issn = {1664-3224}, mesh = {Animals ; Antigen-Presenting Cells/cytology/*immunology ; Cell Communication/*immunology ; Cell-Derived Microparticles/*immunology ; Exosomes/*immunology ; Humans ; Microvilli/*immunology ; T-Lymphocytes/cytology/*immunology ; }, abstract = {Communication between cells is essential for multicellular life. During cognate immune interactions, T cells communicate with antigen-presenting cells (APC) via direct cell-cell contact or the release of molecules and vesicles containing T cell messages. A wide variety of mechanisms have been reported and among them a process called "trogocytosis" has traditionally been thought to be the fastest way to directly transfer membrane portions containing intact proteins from one cell to another; however, the mechanism is unverified. Trogocytosis has been distinguished from the generation of extracellular vesicles (EVs), a term that encompasses exosomes and microvesicles, as EVs are released via a contact-independent manner and are suggested to potentially send molecular messages over a distance. However, some previous reports regarding EVs in T cells may be misleading in terms of explaining their cellular origins. In addition, there is little evidence on how EVs are generated from T cells in vivo and function to regulate complex immune responses. A recent work demonstrated that T cell microvilli-thin and finger-like membrane protrusions-are highly fragile and easily separated as membrane particles by trogocytosis, forming a new class of EVs. Surprisingly, released T cell microvilli-derived particles act as vectors, transmitting T cell messages to cognate APCs. This review focuses on how T cell microvilli vesicles are connected with immune regulation mechanisms discovered previously.}, } @article {pmid31415772, year = {2020}, author = {Miller, WB and Torday, JS and Baluška, F}, title = {The N-space Episenome unifies cellular information space-time within cognition-based evolution.}, journal = {Progress in biophysics and molecular biology}, volume = {150}, number = {}, pages = {112-139}, doi = {10.1016/j.pbiomolbio.2019.08.006}, pmid = {31415772}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Cell Communication ; Cell Physiological Phenomena ; Cells ; Cognition/*physiology ; Genome ; *Homeostasis ; Humans ; Morphogenesis/*genetics ; Time Factors ; }, abstract = {Self-referential cellular homeostasis is maintained by the measured assessment of both internal status and external conditions based within an integrated cellular information field. This cellular field attachment to biologic information space-time coordinates environmental inputs by connecting the cellular senome, as the sum of the sensory experiences of the cell, with its genome and epigenome. In multicellular organisms, individual cellular information fields aggregate into a collective information architectural matrix, termed a N-space Episenome, that enables mutualized organism-wide information management. It is hypothesized that biological organization represents a dual heritable system constituted by both its biological materiality and a conjoining N-space Episenome. It is further proposed that morphogenesis derives from reciprocations between these inter-related facets to yield coordinated multicellular growth and development. The N-space Episenome is conceived as a whole cell informational projection that is heritable, transferable via cell division and essential for the synchronous integration of the diverse self-referential cells that constitute holobionts.}, } @article {pmid31413788, year = {2019}, author = {Fields, C and Levin, M}, title = {Somatic multicellularity as a satisficing solution to the prediction-error minimization problem.}, journal = {Communicative & integrative biology}, volume = {12}, number = {1}, pages = {119-132}, pmid = {31413788}, issn = {1942-0889}, abstract = {Adaptive success in the biosphere requires the dynamic ability to adjust physiological, transcriptional, and behavioral responses to environmental conditions. From chemical networks to organisms to whole communities, biological entities at all levels of organization seek to optimize their predictive power. Here, we argue that this fundamental drive provides a novel perspective on the origin of multicellularity. One way for unicellular organisms to minimize surprise with respect to external inputs is to be surrounded by reproductively-disabled, i.e. somatic copies of themselves - highly predictable agents which in effect reduce uncertainty in their microenvironments. We show that the transition to multicellularity can be modeled as a phase transition driven by environmental threats. We present modeling results showing how multicellular bodies can arise if non-reproductive somatic cells protect their reproductive parents from environmental lethality. We discuss how a somatic body can be interpreted as a Markov blanket around one or more reproductive cells, and how the transition to somatic multicellularity can be represented as a transition from exposure of reproductive cells to a high-uncertainty environment to their protection from environmental uncertainty by this Markov blanket. This is, effectively, a transition by the Markov blanket from transparency to opacity for the variational free energy of the environment. We suggest that the ability to arrest the cell cycle of daughter cells and redirect their resource utilization from division to environmental threat amelioration is the key innovation of obligate multicellular eukaryotes, that the nervous system evolved to exercise this control over long distances, and that cancer is an escape by somatic cells from the control of reproductive cells. Our quantitative model illustrates the evolutionary dynamics of this system, provides a novel hypothesis for the origin of multicellular animal bodies, and suggests a fundamental link between the architectures of complex organisms and information processing in proto-cognitive cellular agents.}, } @article {pmid31384725, year = {2019}, author = {Blum, P and Payne, S}, title = {Evidence of an Epigenetics System in Archaea.}, journal = {Epigenetics insights}, volume = {12}, number = {}, pages = {2516865719865280}, pmid = {31384725}, issn = {2516-8657}, abstract = {Changes in the phenotype of a cell or organism that are heritable but do not involve changes in DNA sequence are referred to as epigenetic. They occur primarily through the gain or loss of chemical modification of chromatin protein or DNA. Epigenetics is therefore a non-Mendelian process. The study of epigenetics in eukaryotes is expanding with advances in knowledge about the relationship between mechanism and phenotype and as a requirement for multicellularity and cancer. However, life also includes other groups or domains, notably the bacteria and archaea. The occurrence of epigenetics in these deep lineages is an emerging topic accompanied by controversy. In these non-eukaryotic organisms, epigenetics is critically important because it stimulates new evolutionary theory and refines perspective about biological action.}, } @article {pmid31380606, year = {2019}, author = {Newman, SA}, title = {Inherent forms and the evolution of evolution.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {331-338}, doi = {10.1002/jez.b.22895}, pmid = {31380606}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Chlorophyta ; Developmental Biology ; Dictyosteliida ; Morphogenesis ; }, abstract = {John Bonner presented a provocative conjecture that the means by which organisms evolve has itself evolved. The elements of his postulated nonuniformitarianism in the essay under discussion-the emergence of sex, the enhanced selection pressures on larger multicellular forms-center on a presumed close mapping of genotypic to phenotypic change. A different view emerges from delving into earlier work of Bonner's in which he proposed the concept of "neutral phenotypes" and "neutral morphologies" allied to D'Arcy Thompson's analysis of physical determinants of form and studied the conditional elicitation of intrinsic organizational properties of cell aggregates in social amoebae. By comparing the shared and disparate mechanistic bases of morphogenesis and developmental outcomes in the embryos of metazoans (animals), closely related nonmetazoan holozoans, more distantly related dictyostelids, and very distantly related volvocine algae, I conclude, in agreement with Bonner's earlier proposals, that understanding the evolution of multicellular evolution requires knowledge of the inherent forms of diversifying lineages, and that the relevant causative factors extend beyond genes and adaptation to the physics of materials.}, } @article {pmid31370870, year = {2019}, author = {Yeoh, LM and Goodman, CD and Mollard, V and McHugh, E and Lee, VV and Sturm, A and Cozijnsen, A and McFadden, GI and Ralph, SA}, title = {Alternative splicing is required for stage differentiation in malaria parasites.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {151}, pmid = {31370870}, issn = {1474-760X}, mesh = {*Alternative Splicing ; Animals ; Germ Cells/metabolism ; Life Cycle Stages/genetics ; Mice ; Plasmodium berghei/*genetics/growth & development/metabolism ; Transcription, Genetic ; }, abstract = {BACKGROUND: In multicellular organisms, alternative splicing is central to tissue differentiation and identity. Unicellular protists lack multicellular tissue but differentiate into variable cell types during their life cycles. The role of alternative splicing in transitions between cell types and establishing cellular identity is currently unknown in any unicellular organism.

RESULTS: To test whether alternative splicing in unicellular protists plays a role in cellular differentiation, we conduct RNA-seq to compare splicing in female and male sexual stages to asexual intraerythrocytic stages in the rodent malaria parasite Plasmodium berghei. We find extensive changes in alternative splicing between stages and a role for alternative splicing in sexual differentiation. Previously, general gametocyte differentiation was shown to be modulated by specific transcription factors. Here, we show that alternative splicing establishes a subsequent layer of regulation, controlling genes relating to consequent sex-specific differentiation of gametocytes.

CONCLUSIONS: We demonstrate that alternative splicing is reprogrammed during cellular differentiation of a unicellular protist. Disruption of an alternative splicing factor, PbSR-MG, perturbs sex-specific alternative splicing and decreases the ability of the parasites to differentiate into male gametes and oocysts, thereby reducing transmission between vertebrate and insect hosts. Our results reveal alternative splicing as an integral, stage-specific phenomenon in these protists and as a regulator of cellular differentiation that arose early in eukaryotic evolution.}, } @article {pmid31367038, year = {2019}, author = {Olin-Sandoval, V and Yu, JSL and Miller-Fleming, L and Alam, MT and Kamrad, S and Correia-Melo, C and Haas, R and Segal, J and Peña Navarro, DA and Herrera-Dominguez, L and Méndez-Lucio, O and Vowinckel, J and Mülleder, M and Ralser, M}, title = {Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism.}, journal = {Nature}, volume = {572}, number = {7768}, pages = {249-253}, pmid = {31367038}, issn = {1476-4687}, support = {200829/WT_/Wellcome Trust/United Kingdom ; FC001134/MRC_/Medical Research Council/United Kingdom ; FC001134/ARC_/Arthritis Research UK/United Kingdom ; FC001134/CRUK_/Cancer Research UK/United Kingdom ; W 1224/FWF_/Austrian Science Fund FWF/Austria ; 260809/ERC_/European Research Council/International ; FC001134/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Antioxidants/*metabolism ; Antiporters/metabolism ; Cadaverine/metabolism ; Glutamine/metabolism ; Glutathione/metabolism ; Lysine/*metabolism ; NADP/metabolism ; Organic Cation Transport Proteins/metabolism ; Ornithine Decarboxylase/metabolism ; Oxidants/metabolism ; Polyamines/*metabolism ; Reactive Oxygen Species/metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; }, abstract = {Both single and multicellular organisms depend on anti-stress mechanisms that enable them to deal with sudden changes in the environment, including exposure to heat and oxidants. Central to the stress response are dynamic changes in metabolism, such as the transition from the glycolysis to the pentose phosphate pathway-a conserved first-line response to oxidative insults[1,2]. Here we report a second metabolic adaptation that protects microbial cells in stress situations. The role of the yeast polyamine transporter Tpo1p[3-5] in maintaining oxidant resistance is unknown[6]. However, a proteomic time-course experiment suggests a link to lysine metabolism. We reveal a connection between polyamine and lysine metabolism during stress situations, in the form of a promiscuous enzymatic reaction in which the first enzyme of the polyamine pathway, Spe1p, decarboxylates lysine and forms an alternative polyamine, cadaverine. The reaction proceeds in the presence of extracellular lysine, which is taken up by cells to reach concentrations up to one hundred times higher than those required for growth. Such extensive harvest is not observed for the other amino acids, is dependent on the polyamine pathway and triggers a reprogramming of redox metabolism. As a result, NADPH-which would otherwise be required for lysine biosynthesis-is channelled into glutathione metabolism, leading to a large increase in glutathione concentrations, lower levels of reactive oxygen species and increased oxidant tolerance. Our results show that nutrient uptake occurs not only to enable cell growth, but when the nutrient availability is favourable it also enables cells to reconfigure their metabolism to preventatively mount stress protection.}, } @article {pmid31366234, year = {2019}, author = {Wessely, A and Waltera, A and Reichert, TE and Stöckl, S and Grässel, S and Bauer, RJ}, title = {Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D spheroids.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {11}, pages = {11884-11893}, pmid = {31366234}, issn = {1530-6860}, mesh = {Adipose Tissue/cytology/metabolism ; Alkaline Phosphatase/*metabolism ; Bone Marrow Cells/cytology/*metabolism ; Carcinoma, Squamous Cell/*metabolism/pathology ; Cell Culture Techniques/methods ; Cell Differentiation ; Cell Movement ; Cells, Cultured ; Enzyme Induction ; Head and Neck Neoplasms/*metabolism/pathology ; Humans ; Matrix Metalloproteinase 9/*metabolism ; Mesenchymal Stem Cells/cytology/*metabolism ; Spheroids, Cellular/*metabolism/pathology ; }, abstract = {Mesenchymal stem cells (MSCs) are multipotent progenitor cells capable of differentiating into adipocytic, osteogenic, chondrogenic, and myogenic lineages. There is growing evidence that MSCs home into the tumor microenvironment attracted by a variety of signals such as chemokines, growth factors, and cytokines. Tumor-homing stem cells may originate from bone marrow-derived MSCs (BMSCs) or adipose tissue-derived MSCs. Recent scientific data suggest that MSCs in combination with tumor cells can either promote or inhibit tumorigenic behavior. In head and neck squamous cell carcinoma (HNSCC), BMSCs are reported to be enriched with a potential negative role. Here, we evaluated the effect of BMSCs from 4 different donors in combination with 4 HNSCC cell lines in a 3-dimensional multicellular spheroid model. Heterogeneous combinations revealed an up-regulation of gene and protein expression of osteogenic markers runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP) together with a substantial secretion of matrix metalloproteinase 9. Moreover, heterogenous BMSC/tumor spheroids showed increased invasion compared with homogenous spheroids in a Boyden chamber invasion assay. Furthermore, inhibition of ALP resulted in a substantially decreased spreading of heterogeneous spheroids on laminin-rich matrix. In summary, our data suggest a prometastatic effect of BMSCs combined with HNSCC.-Wessely, A., Waltera, A., Reichert, T. E., Stöckl, S., Grässel, S., Bauer, R. J. Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D-spheroids.}, } @article {pmid31347665, year = {2019}, author = {Lu, TM and Kanda, M and Furuya, H and Satoh, N}, title = {Dicyemid Mesozoans: A Unique Parasitic Lifestyle and a Reduced Genome.}, journal = {Genome biology and evolution}, volume = {11}, number = {8}, pages = {2232-2243}, pmid = {31347665}, issn = {1759-6653}, mesh = {Animals ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; *Genome ; Invertebrates/classification/*genetics/growth & development ; Parasites/*genetics ; Phylogeny ; Proteins/*genetics ; Transcriptome ; }, abstract = {Dicyemids, previously called "mesozoans" (intermediates between unicellular protozoans and multicellular metazoans), are an enigmatic animal group. They have a highly simplified adult body, comprising only ∼30 cells, and they have a unique parasitic lifestyle. Recently, dicyemids were shown to be spiralians, with affinities to the Platyhelminthes. In order to understand molecular mechanisms involved in evolution of this odd animal, we sequenced the genome of Dicyema japonicum and a reference transcriptome assembly using mixed-stage samples. The D. japonicum genome features a high proportion of repetitive sequences that account for 49% of the genome. The dicyemid genome is reduced to ∼67.5 Mb with 5,012 protein-coding genes. Only four Hox genes exist in the genome, with no clustering. Gene distribution in KEGG pathways shows that D. japonicum has fewer genes in most pathways. Instead of eliminating entire critical metabolic pathways, parasitic lineages likely simplify pathways by eliminating pathway-specific genes, while genes with fundamental functions may be retained in multiple pathways. In principle, parasites can stand to lose genes that are unnecessary, in order to conserve energy. However, whether retained genes in incomplete pathways serve intermediate functions and how parasites overcome the physiological needs served by lost genes, remain to be investigated in future studies.}, } @article {pmid31339482, year = {2019}, author = {Guo, JS and Zhang, Z and Qiao, M and Yu, ZF}, title = {Phalangispora sinensis sp. nov. from Yunnan, China and two new members of Wiesneriomycetaceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {10}, pages = {3217-3223}, doi = {10.1099/ijsem.0.003612}, pmid = {31339482}, issn = {1466-5034}, mesh = {Ascomycota/*classification/isolation & purification ; China ; DNA, Fungal/genetics ; Mycological Typing Techniques ; *Phylogeny ; Sequence Analysis, DNA ; Spores, Fungal ; *Water Microbiology ; }, abstract = {Phalangispora sinensis, an aquatic hyphomycete collected from south-western PR China, is described as a new species. This new species is characterized by having multicellular branched conidia composed of a curved main axis and one or two laterals, with the laterals arising from the third or fourth cell of the base of the main axis. Combined analyses of the LSU, SSU, RPB2 and TEF1 gene sequence data revealed that Phalangispora and another aquatic hyphomycete genus, Setosynnema, belonged to Wiesneriomycetaceae, Tubeufiales, Dothideomycetes, Ascomycota.}, } @article {pmid31325911, year = {2019}, author = {Perez-Lamarque, B and Morlon, H}, title = {Characterizing symbiont inheritance during host-microbiota evolution: Application to the great apes gut microbiota.}, journal = {Molecular ecology resources}, volume = {19}, number = {6}, pages = {1659-1671}, doi = {10.1111/1755-0998.13063}, pmid = {31325911}, issn = {1755-0998}, support = {Programme Bettencourt//Ecole Doctorale FIRE/ ; //Ecole normale supérieure/ ; //Centre National de la Recherche Scientifique/ ; PANDA/ERC_/European Research Council/International ; /ERC_/European Research Council/International ; //École Normale Supérieure/ ; }, mesh = {Animals ; Bacteria/genetics ; DNA Barcoding, Taxonomic/methods ; Disease Transmission, Infectious ; Evolution, Molecular ; Gastrointestinal Microbiome/*genetics ; Hominidae/*microbiology ; Infectious Disease Transmission, Vertical ; Microbiota/*genetics ; Phylogeny ; Symbiosis/*genetics ; }, abstract = {Microbiota play a central role in the functioning of multicellular life, yet understanding their inheritance during host evolutionary history remains an important challenge. Symbiotic microorganisms are either acquired from the environment during the life of the host (i.e. environmental acquisition), transmitted across generations with a faithful association with their hosts (i.e. strict vertical transmission), or transmitted with occasional host switches (i.e. vertical transmission with horizontal switches). These different modes of inheritance affect microbes' diversification, which at the two extremes can be independent from that of their associated host or follow host diversification. The few existing quantitative tools for investigating the inheritance of symbiotic organisms rely on cophylogenetic approaches, which require knowledge of both host and symbiont phylogenies, and are therefore often not well adapted to DNA metabarcoding microbial data. Here, we develop a model-based framework for identifying vertically transmitted microbial taxa. We consider a model for the evolution of microbial sequences on a fixed host phylogeny that includes vertical transmission and horizontal host switches. This model allows estimating the number of host switches and testing for strict vertical transmission and independent evolution. We test our approach using simulations. Finally, we illustrate our framework on gut microbiota high-throughput sequencing data of the family Hominidae and identify several microbial taxonomic units, including fibrolytic bacteria involved in carbohydrate digestion, that tend to be vertically transmitted.}, } @article {pmid31311656, year = {2019}, author = {Smith, EA and Hodges, HC}, title = {The Spatial and Genomic Hierarchy of Tumor Ecosystems Revealed by Single-Cell Technologies.}, journal = {Trends in cancer}, volume = {5}, number = {7}, pages = {411-425}, pmid = {31311656}, issn = {2405-8025}, support = {R00 CA187565/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics ; Genetic Predisposition to Disease ; *Genome-Wide Association Study/methods ; *Genomics/methods ; Humans ; Immunomodulation ; Lymphocytes, Tumor-Infiltrating/immunology/metabolism/pathology ; Mutation ; Neoplasms/*genetics/*metabolism/pathology ; Single-Cell Analysis/methods ; *Tumor Microenvironment ; }, abstract = {Many malignancies display heterogeneous features that support cancer progression. Emerging high-resolution methods provide a view of heterogeneity that recognizes the influence of diverse cell types and cell states of the tumor microenvironment. Here we outline a hierarchical organization of tumor heterogeneity from a genomic perspective, summarize the origins of spatially patterned metabolic features, and review recent developments in single-cell and spatially resolved techniques for genome-wide study of multicellular tissues. We also discuss how integrating these approaches can yield new insights into human cancer and emerging immune therapies. Applying these technologies for the analysis of primary tumors, patient-derived xenografts, and in vitro systems holds great promise for understanding the hierarchical structure and environmental influences that underlie tumor ecosystems.}, } @article {pmid31311477, year = {2019}, author = {Boscaro, V and Husnik, F and Vannini, C and Keeling, PJ}, title = {Symbionts of the ciliate Euplotes: diversity, patterns and potential as models for bacteria-eukaryote endosymbioses.}, journal = {Proceedings. Biological sciences}, volume = {286}, number = {1907}, pages = {20190693}, pmid = {31311477}, issn = {1471-2954}, mesh = {Burkholderiaceae/classification/genetics/*physiology ; Euplotes/*microbiology ; Microbiota ; Phylogeny ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; *Symbiosis ; }, abstract = {Endosymbioses between bacteria and eukaryotes are enormously important in ecology and evolution, and as such are intensely studied. Despite this, the range of investigated hosts is narrow in the context of the whole eukaryotic tree of life: most of the information pertains to animal hosts, while most of the diversity is found in unicellular protists. A prominent case study is the ciliate Euplotes, which has repeatedly taken up the bacterium Polynucleobacter from the environment, triggering its transformation into obligate endosymbiont. This multiple origin makes the relationship an excellent model to understand recent symbioses, but Euplotes may host bacteria other than Polynucleobacter, and a more detailed knowledge of these additional interactions is needed in order to correctly interpret the system. Here, we present the first systematic survey of Euplotes endosymbionts, adopting a classical as well as a metagenomic approach, and review the state of knowledge. The emerging picture is indeed quite complex, with some Euplotes harbouring rich, stable prokaryotic communities not unlike those of multicellular animals. We provide insights into the distribution, evolution and diversity of these symbionts (including the establishment of six novel bacterial taxa), and outline differences and similarities with the most well-understood group of eukaryotic hosts: insects.}, } @article {pmid31310602, year = {2019}, author = {Karolak, A and Poonja, S and Rejniak, KA}, title = {Morphophenotypic classification of tumor organoids as an indicator of drug exposure and penetration potential.}, journal = {PLoS computational biology}, volume = {15}, number = {7}, pages = {e1007214}, pmid = {31310602}, issn = {1553-7358}, support = {U01 CA202229/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/administration & dosage/pharmacokinetics ; Computational Biology ; Computer Simulation ; Disease Progression ; Drug Screening Assays, Antitumor ; Humans ; Imaging, Three-Dimensional ; Models, Biological ; Neoplasms/*drug therapy/metabolism/*pathology ; Organoids/*drug effects/metabolism/*pathology ; Phenotype ; Surface Properties ; Tumor Cells, Cultured ; Tumor Microenvironment/drug effects/physiology ; }, abstract = {The dynamics of tumor progression is driven by multiple factors, which can be exogenous to the tumor (microenvironment) or intrinsic (genetic, epigenetic or due to intercellular interactions). While tumor heterogeneity has been extensively studied on the level of cell genetic profiles or cellular composition, tumor morphological diversity has not been given as much attention. The limited analysis of tumor morphophenotypes may be attributed to the lack of accurate models, both experimental and computational, capable of capturing changes in tumor morphology with fine levels of spatial detail. Using a three-dimensional, agent-based, lattice-free computational model, we generated a library of multicellular tumor organoids, the experimental analogues of in vivo tumors. By varying three biologically relevant parameters-cell radius, cell division age and cell sensitivity to contact inhibition, we showed that tumor organoids with similar growth dynamics can express distinct morphologies and possess diverse cellular compositions. Taking advantage of the high-resolution of computational modeling, we applied the quantitative measures of compactness and accessible surface area, concepts that originated from the structural biology of proteins. Based on these analyses, we demonstrated that tumor organoids with similar sizes may differ in features associated with drug effectiveness, such as potential exposure to the drug or the extent of drug penetration. Both these characteristics might lead to major differences in tumor organoid's response to therapy. This indicates that therapeutic protocols should not be based solely on tumor size, but take into account additional tumor features, such as their morphology or cellular packing density.}, } @article {pmid31302471, year = {2019}, author = {Newman, SA}, title = {Inherency and homomorphy in the evolution of development.}, journal = {Current opinion in genetics & development}, volume = {57}, number = {}, pages = {1-8}, doi = {10.1016/j.gde.2019.05.006}, pmid = {31302471}, issn = {1879-0380}, mesh = {Animals ; *Biological Evolution ; Body Patterning/*genetics/physiology ; Embryonic Development/*genetics/physiology ; Gene Expression Regulation, Developmental/genetics ; Physical Phenomena ; }, abstract = {Organismal development occurs when expression of certain genes leads to the mobilization of physical forces and effects that shape and pattern multicellular clusters. All materials exhibit preferred forms, but the inherent morphological motifs of some, such as liquids and crystalline solids are well-characterized. Recent work has shown that the origin of the animals (Metazoa) was accompanied by the acquisition by their developing tissues of liquid-like and liquid-crystalline properties. This and the novel capacity to produce stiff internal substrata (basal laminae) set these organisms apart from their closest relatives by the propensity (predictable from their material nature) to form complex bodies and organs. Once functional forms became established, however, they were susceptible to further genetic change as well as partial or full supplanting of original physical determinants by different ones. This results in the increasingly recognized phenomenon of homomorphy, the presence of the same structure in descendent organisms, brought about by transformed developmental mechanisms.}, } @article {pmid31295970, year = {2019}, author = {Joukov, V and De Nicolo, A}, title = {The Centrosome and the Primary Cilium: The Yin and Yang of a Hybrid Organelle.}, journal = {Cells}, volume = {8}, number = {7}, pages = {}, pmid = {31295970}, issn = {2073-4409}, mesh = {Animals ; Cell Cycle ; Cell Differentiation ; Centrioles/metabolism/physiology ; Centrosome/*metabolism/*physiology ; Cilia/genetics/*metabolism ; Humans ; Microtubule-Organizing Center/physiology ; Microtubules/physiology ; Mitosis/genetics ; Organelles/metabolism/physiology ; }, abstract = {Centrosomes and primary cilia are usually considered as distinct organelles, although both are assembled with the same evolutionary conserved, microtubule-based templates, the centrioles. Centrosomes serve as major microtubule- and actin cytoskeleton-organizing centers and are involved in a variety of intracellular processes, whereas primary cilia receive and transduce environmental signals to elicit cellular and organismal responses. Understanding the functional relationship between centrosomes and primary cilia is important because defects in both structures have been implicated in various diseases, including cancer. Here, we discuss evidence that the animal centrosome evolved, with the transition to complex multicellularity, as a hybrid organelle comprised of the two distinct, but intertwined, structural-functional modules: the centriole/primary cilium module and the pericentriolar material/centrosome module. The evolution of the former module may have been caused by the expanding cellular diversification and intercommunication, whereas that of the latter module may have been driven by the increasing complexity of mitosis and the requirement for maintaining cell polarity, individuation, and adhesion. Through its unique ability to serve both as a plasma membrane-associated primary cilium organizer and a juxtanuclear microtubule-organizing center, the animal centrosome has become an ideal integrator of extracellular and intracellular signals with the cytoskeleton and a switch between the non-cell autonomous and the cell-autonomous signaling modes. In light of this hypothesis, we discuss centrosome dynamics during cell proliferation, migration, and differentiation and propose a model of centrosome-driven microtubule assembly in mitotic and interphase cells. In addition, we outline the evolutionary benefits of the animal centrosome and highlight the hierarchy and modularity of the centrosome biogenesis networks.}, } @article {pmid31286803, year = {2019}, author = {Rezaei-Lotfi, S and Hunter, N and Farahani, RM}, title = {Coupled cycling programs multicellular self-organization of neural progenitors.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {18}, number = {17}, pages = {2040-2054}, pmid = {31286803}, issn = {1551-4005}, support = {R01 DE015272/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Humans ; Models, Theoretical ; Morphogenesis/*genetics ; Neural Stem Cells/*metabolism/pathology ; Neurogenesis/genetics ; Neurons/*metabolism/pathology ; beta Catenin/*genetics ; }, abstract = {Self-organization is central to the morphogenesis of multicellular organisms. However, the molecular platform that coordinates the robust emergence of complex morphological patterns from local interactions between cells remains unresolved. Here we demonstrate that neural self- organization is driven by coupled cycling of progenitor cells. In a coupled cycling mode, intercellular contacts relay extrinsic cues to override the intrinsic cycling rhythm of an individual cell and synchronize the population. The stringency of coupling and hence the synchronicity of the population is programmed by recruitment of a key coupler, β-catenin, into junctional complexes. As such, multicellular self-organization is driven by the same basic mathematical principle that governs synchronized behavior of macro-scale biological systems as diverse as the synchronized chirping of crickets, flashing of fireflies and schooling of fish; that is synchronization by coupling. It is proposed that coupled cycling foreshadows a fundamental adaptive change that facilitated evolution and diversification of multicellular life forms.}, } @article {pmid31285576, year = {2019}, author = {Staps, M and van Gestel, J and Tarnita, CE}, title = {Emergence of diverse life cycles and life histories at the origin of multicellularity.}, journal = {Nature ecology & evolution}, volume = {3}, number = {8}, pages = {1197-1205}, pmid = {31285576}, issn = {2397-334X}, mesh = {Animals ; *Biological Evolution ; }, abstract = {The evolution of multicellularity has given rise to a remarkable diversity of multicellular life cycles and life histories. Whereas some multicellular organisms are long-lived, grow through cell division, and repeatedly release single-celled propagules (for example, animals), others are short-lived, form by aggregation, and propagate only once, by generating large numbers of solitary cells (for example, cellular slime moulds). There are no systematic studies that explore how diverse multicellular life cycles can come about. Here, we focus on the origin of multicellularity and develop a mechanistic model to examine the primitive life cycles that emerge from a unicellular ancestor when an ancestral gene is co-opted for cell adhesion. Diverse life cycles readily emerge, depending on ecological conditions, group-forming mechanism, and ancestral constraints. Among these life cycles, we recapitulate both extremes of long-lived groups that propagate continuously and short-lived groups that propagate only once, with the latter type of life cycle being particularly favoured when groups can form by aggregation. Our results show how diverse life cycles and life histories can easily emerge at the origin of multicellularity, shaped by ancestral constraints and ecological conditions. Beyond multicellularity, this finding has similar implications for other major transitions, such as the evolution of sociality.}, } @article {pmid31267819, year = {2019}, author = {Etxebeste, O and Otamendi, A and Garzia, A and Espeso, EA and Cortese, MS}, title = {Rewiring of transcriptional networks as a major event leading to the diversity of asexual multicellularity in fungi.}, journal = {Critical reviews in microbiology}, volume = {45}, number = {5-6}, pages = {548-563}, doi = {10.1080/1040841X.2019.1630359}, pmid = {31267819}, issn = {1549-7828}, mesh = {Fungal Proteins/genetics/*metabolism ; Fungi/genetics/*growth & development/physiology ; *Gene Expression Regulation, Fungal ; Gene Regulatory Networks ; Reproduction, Asexual ; Spores, Fungal/genetics/growth & development/metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Complex multicellularity (CM) is characterized by the generation of three-dimensional structures that follow a genetically controlled program. CM emerged at least five times in evolution, one of them in fungi. There are two types of CM programs in fungi, leading, respectively, to the formation of sexual or asexual spores. Asexual spores foment the spread of mycoses, as they are the main vehicle for dispersion. In spite of this key dependence, there is great morphological diversity of asexual multicellular structures in fungi. To advance the understanding of the mechanisms that control initiation and progression of asexual CM and how they can lead to such a remarkable morphological diversification, we studied 503 fungal proteomes, representing all phyla and subphyla, and most known classes. Conservation analyses of 33 regulators of asexual development suggest stepwise emergence of transcription factors. While velvet proteins constitute one of the most ancient systems, the central regulator BrlA emerged late in evolution (with the class Eurotiomycetes). Some factors, such as MoConX4, seem to be species-specific. These observations suggest that the emergence and evolution of transcriptional regulators rewire transcriptional networks. This process could reach the species level, resulting in a vast diversity of morphologies.}, } @article {pmid31254720, year = {2019}, author = {Falz, AL and Müller-Schüssele, SJ}, title = {Physcomitrella as a model system for plant cell biology and organelle-organelle communication.}, journal = {Current opinion in plant biology}, volume = {52}, number = {}, pages = {7-13}, doi = {10.1016/j.pbi.2019.05.007}, pmid = {31254720}, issn = {1879-0356}, mesh = {*Bryopsida ; Genomics ; Models, Biological ; Organelles ; Plant Cells ; }, abstract = {In multicellular eukaryotic cells, metabolism and growth are sustained by the cooperative functioning of organelles in combination with cell-to-cell communication at the organism level. In land plants, multiple strategies have evolved to adapt to life outside water. As basal land plant, the moss Physcomitrella patens is used for comparative genomics, allowing to study lineage-specific features, as well as to track the evolution of fundamental parameters of plant cell organisation and physiology. P. patens is a versatile model for cell biology research, especially to investigate adaptive growth, stress biology as well as organelle dynamics and interactions. Recent advances include the use of genetically encoded biosensors for in vivo imaging of physiological parameters.}, } @article {pmid31239554, year = {2019}, author = {Ågren, JA and Davies, NG and Foster, KR}, title = {Enforcement is central to the evolution of cooperation.}, journal = {Nature ecology & evolution}, volume = {3}, number = {7}, pages = {1018-1029}, doi = {10.1038/s41559-019-0907-1}, pmid = {31239554}, issn = {2397-334X}, support = {209397/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; *Cooperative Behavior ; Humans ; Symbiosis ; }, abstract = {Cooperation occurs at all levels of life, from genomes, complex cells and multicellular organisms to societies and mutualisms between species. A major question for evolutionary biology is what these diverse systems have in common. Here, we review the full breadth of cooperative systems and find that they frequently rely on enforcement mechanisms that suppress selfish behaviour. We discuss many examples, including the suppression of transposable elements, uniparental inheritance of mitochondria and plastids, anti-cancer mechanisms, reciprocation and punishment in humans and other vertebrates, policing in eusocial insects and partner choice in mutualisms between species. To address a lack of accompanying theory, we develop a series of evolutionary models that show that the enforcement of cooperation is widely predicted. We argue that enforcement is an underappreciated, and often critical, ingredient for cooperation across all scales of biological organization.}, } @article {pmid31236128, year = {2019}, author = {Robu, A and Mironov, V and Neagu, A}, title = {Using Sacrificial Cell Spheroids for the Bioprinting of Perfusable 3D Tissue and Organ Constructs: A Computational Study.}, journal = {Computational and mathematical methods in medicine}, volume = {2019}, number = {}, pages = {7853586}, pmid = {31236128}, issn = {1748-6718}, mesh = {3T3 Cells ; Algorithms ; Animals ; Bioprinting/*methods ; Carcinoma, Lewis Lung/metabolism ; Computer Simulation ; Humans ; Hydrogels/*chemistry ; Metal Nanoparticles/chemistry ; Mice ; Monte Carlo Method ; Perfusion ; *Printing, Three-Dimensional ; Silicon/chemistry ; Spheroids, Cellular/*cytology ; Tissue Engineering/*methods ; Tissue Scaffolds ; }, abstract = {A long-standing problem in tissue engineering is the biofabrication of perfusable tissue constructs that can be readily connected to the patient's vasculature. It was partially solved by three-dimensional (3D) printing of sacrificial material (e.g., hydrogel) strands: upon incorporation in another cell-laden hydrogel, the strands were removed, leaving behind perfusable channels. Their complexity, however, did not match that of the native vasculature. Here, we propose to use multicellular spheroids as a sacrificial material and investigate their potential benefits in the context of 3D bioprinting of cell aggregates and/or cell-laden hydrogels. Our study is based on computer simulations of postprinting cellular rearrangements. The computational model of the biological system is built on a cubic lattice, whereas its evolution is simulated using the Metropolis Monte Carlo algorithm. The simulations describe structural changes in three types of tissue constructs: a tube made of a single cell type, a tube made of two cell types, and a cell-laden hydrogel slab that incorporates a branching tube. In all three constructs, the lumen is obtained after the elimination of the sacrificial cell population. Our study suggests that sacrificial cell spheroids (sacrospheres) enable one to print tissue constructs outfitted with a finer and more complex network of channels than the ones obtained so far. Moreover, cellular interactions might give rise to a tissue microarchitecture that lies beyond the bioprinter's resolution. Although more expensive than inert materials, sacrificial cells have the potential to bring further progress towards the biofabrication of fully vascularized tissue substitutes.}, } @article {pmid31227860, year = {2019}, author = {Tian, L and Zhang, B and Zhang, J and Zhang, T and Cai, Y and Qin, H and Metzner, W and Pan, Y}, title = {A magnetic compass guides the direction of foraging in a bat.}, journal = {Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology}, volume = {205}, number = {4}, pages = {619-627}, pmid = {31227860}, issn = {1432-1351}, mesh = {Animals ; Behavior, Animal/*physiology ; Chiroptera/*physiology ; Cues ; *Magnetic Fields ; Orientation, Spatial/*physiology ; }, abstract = {Previously, two studies have provided evidence that bats can use magnetic field cues for homing or roosting. For insectivorous bats, it is well established that foraging represents one of the most fundamental behaviors in animals relies on their ability to echolocate. Whether echolocating bats can also use magnetic cues during foraging remains unknown, however. Here, we tested the orientation behavior of Chinese noctules (Nyctalus plancyi) during foraging in a plus-shaped, 4-channel apparatus under different magnetic field conditions. To minimize the effects of spatial memory on orientation from repeated experiments, naïve bats were tested only once in each experimental condition. As expected, under geomagnetic field and a food resource offered conditions, the bats significantly preferred to enter the channel containing food, indicating that they primarily relied on direct sensory signals unrelated to magnetic cues. In contrast, when we offered food simultaneously in all four channels and minimized any differences in all other sensory signals available, the bats exhibited a clear directional preference to forage along the magnetic field direction under either geomagnetic field or a magnetic field in which the horizontal component was rotated by 90°. Our study offers a novel evidence for the importance of a geomagnetic field during foraging.}, } @article {pmid31217565, year = {2019}, author = {Patel, DS and Xu, N and Lu, H}, title = {Digging deeper: methodologies for high-content phenotyping in Caenorhabditis elegans.}, journal = {Lab animal}, volume = {48}, number = {7}, pages = {207-216}, pmid = {31217565}, issn = {1548-4475}, support = {R21 EB021676/EB/NIBIB NIH HHS/United States ; R21 EB020424/EB/NIBIB NIH HHS/United States ; R01 NS096581/NS/NINDS NIH HHS/United States ; R01 AG056436/AG/NIA NIH HHS/United States ; R21 DC015652/DC/NIDCD NIH HHS/United States ; R01 GM088333/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*genetics ; *Genetic Techniques/instrumentation ; Laboratory Animal Science/instrumentation/*methods ; *Phenotype ; }, abstract = {Deep phenotyping is an emerging conceptual paradigm and experimental approach aimed at measuring and linking many aspects of a phenotype to understand its underlying biology. To date, deep phenotyping has been applied mostly in cultured cells and used less in multicellular organisms. However, in the past decade, it has increasingly been recognized that deep phenotyping could lead to a better understanding of how genetics, environment and stochasticity affect the development, physiology and behavior of an organism. The nematode Caenorhabditis elegans is an invaluable model system for studying how genes affect a phenotypic trait, and new technologies have taken advantage of the worm's physical attributes to increase the throughput and informational content of experiments. Coupling of these technical advancements with computational and analytical tools has enabled a boom in deep-phenotyping studies of C. elegans. In this Review, we highlight how these new technologies and tools are digging into the biological origins of complex, multidimensional phenotypes.}, } @article {pmid31214991, year = {2019}, author = {Muras, V and Toulouse, C and Fritz, G and Steuber, J}, title = {Respiratory Membrane Protein Complexes Convert Chemical Energy.}, journal = {Sub-cellular biochemistry}, volume = {92}, number = {}, pages = {301-335}, doi = {10.1007/978-3-030-18768-2_10}, pmid = {31214991}, issn = {0306-0225}, mesh = {Archaea/cytology/enzymology/*metabolism ; Bacteria/cytology/enzymology/*metabolism ; Cell Membrane/*metabolism ; *Electron Transport ; *Energy Metabolism ; Membrane Proteins/*chemistry/*metabolism ; }, abstract = {The invention of a biological membrane which is used as energy storage system to drive the metabolism of a primordial, unicellular organism represents a key event in the evolution of life. The innovative, underlying principle of this key event is respiration. In respiration, a lipid bilayer with insulating properties is chosen as the site for catalysis of an exergonic redox reaction converting substrates offered from the environment, using the liberated Gibbs free energy (ΔG) for the build-up of an electrochemical H[+] (proton motive force, PMF) or Na[+] gradient (sodium motive force, SMF) across the lipid bilayer. Very frequently , several redox reactions are performed in a consecutive manner, with the first reaction delivering a product which is used as substrate for the second redox reaction, resulting in a respiratory chain. From today's perspective, the (mostly) unicellular bacteria and archaea seem to be much simpler and less evolved when compared to multicellular eukaryotes. However, they are overwhelmingly complex with regard to the various respiratory chains which permit survival in very different habitats of our planet, utilizing a plethora of substances to drive metabolism. This includes nitrogen, sulfur and carbon compounds which are oxidized or reduced by specialized, respiratory enzymes of bacteria and archaea which lie at the heart of the geochemical N, S and C-cycles. This chapter gives an overview of general principles of microbial respiration considering thermodynamic aspects, chemical reactions and kinetic restraints. The respiratory chains of Escherichia coli and Vibrio cholerae are discussed as models for PMF- versus SMF-generating processes, respectively. We introduce main redox cofactors of microbial respiratory enzymes, and the concept of intra-and interelectron transfer. Since oxygen is an electron acceptor used by many respiratory chains, the formation and removal of toxic oxygen radicals is described. Promising directions of future research are respiratory enzymes as novel bacterial targets, and biotechnological applications relying on respiratory complexes.}, } @article {pmid31212208, year = {2019}, author = {Masuyama, N and Mori, H and Yachie, N}, title = {DNA barcodes evolve for high-resolution cell lineage tracing.}, journal = {Current opinion in chemical biology}, volume = {52}, number = {}, pages = {63-71}, doi = {10.1016/j.cbpa.2019.05.014}, pmid = {31212208}, issn = {1879-0402}, mesh = {Animals ; Biomarkers ; *Cell Lineage ; Clustered Regularly Interspaced Short Palindromic Repeats ; *DNA Barcoding, Taxonomic ; Evolution, Molecular ; Humans ; Mutation ; Single-Cell Analysis ; }, abstract = {Mammalian development involves continuous dynamic processes in which cells propagate, differentiate, orchestrate, and decease to produce high-order functions. Although accurate cell lineage information can provide a strong foundation to understand such complex processes, the cell lineages involved in development of the whole mammalian body remain largely unclear, except for in early embryogenesis, which is observable under a microscope. With CRISPR genome editing, the concept of 'evolving DNA barcodes' has rapidly emerged for large-scale, high-resolution cell lineage tracing, where cell-embedded DNA barcodes continuously accumulate random mutations that are inherited from mother to daughter cells. Similar to evolutionary tree reconstruction using species' DNA sequences, cell lineages can be reconstructed using shared mutation patterns in the DNA barcodes identified using massively parallel sequencing. The dramatic developments of single-cell and imaging technologies have enabled analyses of the molecular and spatial architecture of heterogeneous cells. The evolving DNA barcodes can also consolidate this information on a reconstructed cell lineage tree and accelerate our understanding of multicellular organisms.}, } @article {pmid31209997, year = {2019}, author = {Bonner, JT}, title = {The evolution of evolution.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {8}, pages = {301-306}, doi = {10.1002/jez.b.22859}, pmid = {31209997}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Evolution, Molecular ; Nervous System ; Origin of Life ; Reproduction ; Selection, Genetic ; }, abstract = {In the past, most biologists, myself included, did not think of evolution as changing over time. The wonders of natural selection were always at hand and went into operation once there was life. However, with a little reflection it becomes obvious that evolution has changed-there has been an evolution of evolution. Evolution can be separated into four phases, or eras, that may or may not overlap. The first era starts with the evolution of life on earth, which led to single cells that multiply asexually. The second era takes advantage of the invention of sexual reproduction as evolution could now gallop forward because of a richer fare of diverse offspring for natural selection. The third era begins with the introduction of multicellularity. In the fourth era there is a radical innovation: the nervous system that arises animals by standard Darwinian selection. This has allowed major rapid changes to proceed, such as language that led to all the rapid progress we call civilization; a true revolution, and one that does not depend on the slow genetic changes of all other standard gene-controlled evolutionary steps.}, } @article {pmid31196608, year = {2019}, author = {Pirkmajer, S and Chibalin, AV}, title = {Hormonal regulation of Na[+]-K[+]-ATPase from the evolutionary perspective.}, journal = {Current topics in membranes}, volume = {83}, number = {}, pages = {315-351}, doi = {10.1016/bs.ctm.2019.01.009}, pmid = {31196608}, issn = {1063-5823}, mesh = {Animals ; *Biological Evolution ; Hormones/*metabolism ; Humans ; Sodium-Potassium-Exchanging ATPase/chemistry/*metabolism ; }, abstract = {Na[+]-K[+]-ATPase, an α/β heterodimer, is an ancient enzyme that maintains Na[+] and K[+] gradients, thus preserving cellular ion homeostasis. In multicellular organisms, this basic housekeeping function is integrated to fulfill the needs of specialized organs and preserve whole-body homeostasis. In vertebrates, Na[+]-K[+]-ATPase is essential for many fundamental physiological processes, such as nerve conduction, muscle contraction, nutrient absorption, and urine excretion. During vertebrate evolution, three key developments contributed to diversification and integration of Na[+]-K[+]-ATPase functions. Generation of novel α- and β-subunits led to formation of multiple Na[+]-K[+]-ATPase isoenyzmes with distinct functional characteristics. Development of a complex endocrine system enabled efficient coordination of diverse Na[+]-K[+]-ATPase functions. Emergence of FXYDs, small transmembrane proteins that regulate Na[+]-K[+]-ATPase, opened new ways to modulate its function. FXYDs are a vertebrate innovation and an important site of hormonal action, suggesting they played an especially prominent role in evolving interaction between Na[+]-K[+]-ATPase and the endocrine system in vertebrates.}, } @article {pmid31189954, year = {2019}, author = {Sogabe, S and Hatleberg, WL and Kocot, KM and Say, TE and Stoupin, D and Roper, KE and Fernandez-Valverde, SL and Degnan, SM and Degnan, BM}, title = {Pluripotency and the origin of animal multicellularity.}, journal = {Nature}, volume = {570}, number = {7762}, pages = {519-522}, doi = {10.1038/s41586-019-1290-4}, pmid = {31189954}, issn = {1476-4687}, mesh = {Animals ; Cell Proliferation ; *Cell Transdifferentiation ; Epithelial Cells/cytology/metabolism ; Evolution, Molecular ; *Models, Biological ; *Phylogeny ; Pluripotent Stem Cells/*cytology/metabolism ; Porifera/*cytology/metabolism ; Reproducibility of Results ; Transcriptome ; }, abstract = {A widely held-but rarely tested-hypothesis for the origin of animals is that they evolved from a unicellular ancestor, with an apical cilium surrounded by a microvillar collar, that structurally resembled modern sponge choanocytes and choanoflagellates[1-4]. Here we test this view of animal origins by comparing the transcriptomes, fates and behaviours of the three primary sponge cell types-choanocytes, pluripotent mesenchymal archaeocytes and epithelial pinacocytes-with choanoflagellates and other unicellular holozoans. Unexpectedly, we find that the transcriptome of sponge choanocytes is the least similar to the transcriptomes of choanoflagellates and is significantly enriched in genes unique to either animals or sponges alone. By contrast, pluripotent archaeocytes upregulate genes that control cell proliferation and gene expression, as in other metazoan stem cells and in the proliferating stages of two unicellular holozoans, including a colonial choanoflagellate. Choanocytes in the sponge Amphimedon queenslandica exist in a transient metastable state and readily transdifferentiate into archaeocytes, which can differentiate into a range of other cell types. These sponge cell-type conversions are similar to the temporal cell-state changes that occur in unicellular holozoans[5]. Together, these analyses argue against homology of sponge choanocytes and choanoflagellates, and the view that the first multicellular animals were simple balls of cells with limited capacity to differentiate. Instead, our results are consistent with the first animal cell being able to transition between multiple states in a manner similar to modern transdifferentiating and stem cells.}, } @article {pmid31185890, year = {2019}, author = {Yamashita, S and Nozaki, H}, title = {Embryogenesis of flattened colonies implies the innovation required for the evolution of spheroidal colonies in volvocine green algae.}, journal = {BMC evolutionary biology}, volume = {19}, number = {1}, pages = {120}, pmid = {31185890}, issn = {1471-2148}, mesh = {Basal Bodies/metabolism ; *Biological Evolution ; Cell Division ; Cell Nucleus/metabolism ; Chlorophyta/classification/cytology/*embryology ; Microtubules/metabolism ; Phylogeny ; Time-Lapse Imaging ; }, abstract = {BACKGROUND: Volvocine algae provide a suitable model for investigation of the evolution of multicellular organisms. Within this group, evolution of the body plan from flattened to spheroidal colonies is thought to have occurred independently in two different lineages, Volvocaceae and Astrephomene. Volvocacean species undergo inversion to form a spheroidal cell layer following successive cell divisions during embryogenesis. During inversion, the daughter protoplasts change their shape and develop acute chloroplast ends (opposite to basal bodies). By contrast, Astrephomene does not undergo inversion; rather, its daughter protoplasts rotate during successive cell divisions to form a spheroidal colony. However, the evolutionary pathways of these cellular events involved in the two tactics for formation of spheroidal colony are unclear, since the embryogenesis of extant volvocine genera with ancestral flattened colonies, such as Gonium and Tetrabaena, has not previously been investigated in detail.

RESULTS: We conducted time-lapse imaging by light microscopy and indirect immunofluorescence microscopy with staining of basal bodies, nuclei, and microtubules to observe embryogenesis in G. pectorale and T. socialis, which form 16-celled or 4-celled flattened colonies, respectively. In G. pectorale, a cup-shaped cell layer of the 16-celled embryo underwent gradual expansion after successive cell divisions, with the apical ends (position of basal bodies) of the square embryo's peripheral protoplasts separated from each other. In T. socialis, on the other hand, there was no apparent expansion of the daughter protoplasts in 4-celled embryos after successive cell divisions, however the two pairs of diagonally opposed daughter protoplasts shifted slightly and flattened after hatching. Neither of these two species exhibited rotation of daughter protoplasts during successive cell divisions as in Astrephomene or the formation of acute chloroplast ends of daughter protoplasts as in volvocacean inversion.

CONCLUSIONS: The present results indicate that the ancestor of Astrephomene might have newly acquired the rotation of daughter protoplasts after it diverged from the ancestor of Gonium, while the ancestor of Volvocaceae might have newly acquired the formation of acute chloroplast ends to complete inversion after divergence from the ancestor of Goniaceae (Gonium and Astrephomene).}, } @article {pmid31185009, year = {2019}, author = {Roy, M and Finley, SD}, title = {Metabolic reprogramming dynamics in tumor spheroids: Insights from a multicellular, multiscale model.}, journal = {PLoS computational biology}, volume = {15}, number = {6}, pages = {e1007053}, pmid = {31185009}, issn = {1553-7358}, mesh = {Cell Line, Tumor ; Cell Proliferation/physiology ; Computational Biology/*methods ; Humans ; Kinetics ; *Models, Biological ; Neoplasms/*metabolism ; Spheroids, Cellular/*metabolism ; }, abstract = {Mathematical modeling provides the predictive ability to understand the metabolic reprogramming and complex pathways that mediate cancer cells' proliferation. We present a mathematical model using a multiscale, multicellular approach to simulate avascular tumor growth, applied to pancreatic cancer. The model spans three distinct spatial and temporal scales. At the extracellular level, reaction diffusion equations describe nutrient concentrations over a span of seconds. At the cellular level, a lattice-based energy driven stochastic approach describes cellular phenomena including adhesion, proliferation, viability and cell state transitions, occurring on the timescale of hours. At the sub-cellular level, we incorporate a detailed kinetic model of intracellular metabolite dynamics on the timescale of minutes, which enables the cells to uptake and excrete metabolites and use the metabolites to generate energy and building blocks for cell growth. This is a particularly novel aspect of the model. Certain defined criteria for the concentrations of intracellular metabolites lead to cancer cell growth, proliferation or death. Overall, we model the evolution of the tumor in both time and space. Starting with a cluster of tumor cells, the model produces an avascular tumor that quantitatively and qualitatively mimics experimental measurements of multicellular tumor spheroids. Through our model simulations, we can investigate the response of individual intracellular species under a metabolic perturbation and investigate how that response contributes to the response of the tumor as a whole. The predicted response of intracellular metabolites under various targeted strategies are difficult to resolve with experimental techniques. Thus, the model can give novel predictions as to the response of the tumor as a whole, identifies potential therapies to impede tumor growth, and predicts the effects of those therapeutic strategies. In particular, the model provides quantitative insight into the dynamic reprogramming of tumor cells at the intracellular level in response to specific metabolic perturbations. Overall, the model is a useful framework to study targeted metabolic strategies for inhibiting tumor growth.}, } @article {pmid31175621, year = {2020}, author = {Root, A}, title = {Do cells use passwords in cell-state transitions? Is cell signaling sometimes encrypted?.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {139}, number = {1}, pages = {87-93}, pmid = {31175621}, issn = {1611-7530}, mesh = {Algorithms ; Animals ; Autoimmune Diseases/*metabolism ; Biological Evolution ; Biological Phenomena ; Chromatin/metabolism ; Computational Biology ; Entropy ; Environment ; Genome ; Humans ; Immune System ; *Models, Biological ; Neoplasms/*metabolism ; Neurons/metabolism ; Semantics ; *Signal Transduction ; }, abstract = {Organisms must maintain proper regulation including defense and healing. Life-threatening problems may be caused by pathogens or by a multicellular organism's own cells through cancer or autoimmune disorders. Life evolved solutions to these problems that can be conceptualized through the lens of information security, which is a well-developed field in computer science. Here I argue that taking an information security view of cells is not merely semantics, but useful to explain features of signaling, regulation, and defense. An information security perspective also offers a conduit for cross-fertilization of advanced ideas from computer science and the potential for biology to inform computer science. First, I consider whether cells use passwords, i.e., initiation sequences that are required for subsequent signals to have effects, by analyzing the concept of pioneer transcription factors in chromatin regulation and cellular reprogramming. Second, I consider whether cells may encrypt signal transduction cascades. Encryption could benefit cells by making it more difficult for pathogens or oncogenes to hijack cell networks. By using numerous molecules, cells may gain a security advantage in particular against viruses, whose genome sizes are typically under selection pressure. I provide a simple conceptual argument for how cells may perform encryption through posttranslational modifications, complex formation, and chromatin accessibility. I invoke information theory to provide a criterion of an entropy spike to assess whether a signaling cascade has encryption-like features. I discuss how the frequently invoked concept of context dependency may oversimplify more advanced features of cell signaling networks, such as encryption. Therefore, by considering that biochemical networks may be even more complex than commonly realized we may be better able to understand defenses against pathogens and pathologies.}, } @article {pmid31172192, year = {2019}, author = {St-Georges-Robillard, A and Cahuzac, M and Péant, B and Fleury, H and Lateef, MA and Ricard, A and Sauriol, A and Leblond, F and Mes-Masson, AM and Gervais, T}, title = {Long-term fluorescence hyperspectral imaging of on-chip treated co-culture tumour spheroids to follow clonal evolution.}, journal = {Integrative biology : quantitative biosciences from nano to macro}, volume = {11}, number = {4}, pages = {130-141}, doi = {10.1093/intbio/zyz012}, pmid = {31172192}, issn = {1757-9708}, mesh = {*Cell Culture Techniques ; Cell Line, Tumor ; Cell Proliferation/drug effects ; *Clonal Evolution ; *Coculture Techniques ; Drug Screening Assays, Antitumor ; Female ; Humans ; *Lab-On-A-Chip Devices ; Microfluidics ; Microscopy, Fluorescence/*methods ; Ovarian Neoplasms/drug therapy/pathology ; Spheroids, Cellular/*drug effects ; }, abstract = {Multicellular tumour spheroids are an ideal in vitro tumour model to study clonal heterogeneity and drug resistance in cancer research because different cell types can be mixed at will. However, measuring the individual response of each cell population over time is challenging: current methods are either destructive, such as flow cytometry, or cannot image throughout a spheroid, such as confocal microscopy. Our group previously developed a wide-field fluorescence hyperspectral imaging system to study spheroids formed and cultured in microfluidic chips. In the present study, two subclones of a single parental ovarian cancer cell line transfected to express different fluorophores were produced and co-culture spheroids were formed on-chip using ratios forming highly asymmetric subpopulations. We performed a 3D proliferation assay on each cell population forming the spheroids that matched the 2D growth behaviour. Response assays to PARP inhibitors and platinum-based drugs were also performed to follow the clonal evolution of mixed populations. Our experiments show that hyperspectral imaging can detect spheroid response before observing a decrease in spheroid diameter. Hyperspectral imaging and microfluidic-based spheroid assays provide a versatile solution to study clonal heterogeneity, able to measure response in subpopulations presenting as little as 10% of the initial spheroid.}, } @article {pmid31170405, year = {2019}, author = {Edgar, JA}, title = {L-ascorbic acid and the evolution of multicellular eukaryotes.}, journal = {Journal of theoretical biology}, volume = {476}, number = {}, pages = {62-73}, doi = {10.1016/j.jtbi.2019.06.001}, pmid = {31170405}, issn = {1095-8541}, mesh = {Aerobiosis/physiology ; Ascorbic Acid/*metabolism ; Eukaryotic Cells/cytology/*metabolism ; *Evolution, Molecular ; Photosynthesis/*physiology ; Plants/*metabolism ; }, abstract = {The lifeless earth was formed around 4.5 billion years ago and the first anaerobic unicellular "organisms" may have appeared half a billion years later. Despite subsequent prokaryotes (bacteria and archaea) evolving quite complex biochemistry and some eukaryote characteristics, the transition from unicellular prokaryotes to multicellular, aerobic eukaryotes took a further 2.5 billion years to begin. The key factor or factors that eventually caused this long-delayed transition is a question that has been a focus of considerable research and a topic of discussion over many years. On the basis of the extensive literature available and consideration of some of the characteristics that distinguish multicellular eukaryotes from prokaryotes, it is proposed that, as well as the development of oxygenic photosynthesis producing high levels of environmental oxygen and the formation of vital organelles such as aerobic adenosine triphosphate-generating mitochondria, the concurrent evolution of the L-ascorbic acid redox system should be considered as a key factor that led to the evolution of multicellular eukaryotes and it remains vitally involved in the maintenance of multicellularity and many other eukaryote characteristics.}, } @article {pmid31170137, year = {2019}, author = {Thomas, F and Madsen, T and Giraudeau, M and Misse, D and Hamede, R and Vincze, O and Renaud, F and Roche, B and Ujvari, B}, title = {Transmissible cancer and the evolution of sex.}, journal = {PLoS biology}, volume = {17}, number = {6}, pages = {e3000275}, pmid = {31170137}, issn = {1545-7885}, mesh = {Animals ; Biological Evolution ; Cell Transformation, Neoplastic/genetics ; Eukaryota ; Genotype ; Humans ; Recombination, Genetic/genetics/*physiology ; Reproduction/*genetics/*physiology ; Selection, Genetic/genetics ; Sexual Behavior/physiology ; }, abstract = {The origin and subsequent maintenance of sex and recombination are among the most elusive and controversial problems in evolutionary biology. Here, we propose a novel hypothesis, suggesting that sexual reproduction not only evolved to reduce the negative effects of the accumulation of deleterious mutations and processes associated with pathogen and/or parasite resistance but also to prevent invasion by transmissible selfish neoplastic cheater cells, henceforth referred to as transmissible cancer cells. Sexual reproduction permits systematic change of the multicellular organism's genotype and hence an enhanced detection of transmissible cancer cells by immune system. Given the omnipresence of oncogenic processes in multicellular organisms, together with the fact that transmissible cancer cells can have dramatic effects on their host fitness, our scenario suggests that the benefits of sex and concomitant recombination will be large and permanent, explaining why sexual reproduction is, despite its costs, the dominant mode of reproduction among eukaryotes.}, } @article {pmid31169232, year = {2019}, author = {Siddiqui, S and Singh, A and Faizi, N and Khalid, A}, title = {Cell cannibalism in oral cancer: A sign of aggressiveness, de-evolution, and retroversion of multicellularity.}, journal = {Journal of cancer research and therapeutics}, volume = {15}, number = {3}, pages = {631-637}, doi = {10.4103/jcrt.JCRT_504_17}, pmid = {31169232}, issn = {1998-4138}, mesh = {Aged ; Aged, 80 and over ; Analysis of Variance ; Biomarkers, Tumor ; *Cytophagocytosis ; Disease Progression ; Energy Metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating/immunology/metabolism/pathology ; Male ; Middle Aged ; Mouth Neoplasms/etiology/metabolism/*pathology ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Neutrophil Infiltration/immunology ; }, abstract = {BACKGROUND: According to Darwin's theory of evolution, complex creatures evolve from more simplistic ancestors. Dollo's law of irreversibility states that evolution is irreversible. However, cancer cells tend to follow anti-Dollo's law. Unfavorable conditions such as hypoxia, acidic pH and low nutrients cause the cancer cells to switch their lifestyle atavistically in order to survive. They start behaving like a unicellular organism. There is a switch from normal metabolism to Warburg effect and finally cannibalism. Cannibalism is a cell eating cell phenomenon. It is defined as a large cell enclosing a smaller one within its cytoplasm and is known by odd names such as "bird's eye cells" or "signet ring cells." Smaller tumor cells are found in the cytoplasm of larger tumor cells with crescent-shaped nucleus. Cannibalistic cells (CCs) are a feature of aggressive tumors. These cell types are vulnerable to metastasis.

AIM: The aim of this study is to identify CCs in various histological grades of oral squamous cell carcinoma (OSCC) and to relate them with the pattern of invasion, lymphocytic response (LR), and mitotic figures (Mfs). The purpose of the article is to establish it as a marker of aggressiveness and metastasis and as an evidence of de-evolution and retroversion of multicellularity.

MATERIALS AND METHODS: Sixty-five histologically confirmed cases of OSCC were studied. Pattern of invasion, LR, number of CCs, and Mfs were recorded on 5 μ hematoxylin and eosin-stained tissue sections. ANOVA and t-test were applied; P < 0.05 was considered statistically significant.

RESULTS: CCs were more in sections with patchy LR, increased Mfs, and grade IV pattern of invasion.

CONCLUSION: With increase in dedifferentiation, tumor cells start behaving like unicellular organisms with cell eating cell characteristics.}, } @article {pmid31163162, year = {2019}, author = {Ostrowski, EA}, title = {Enforcing Cooperation in the Social Amoebae.}, journal = {Current biology : CB}, volume = {29}, number = {11}, pages = {R474-R484}, doi = {10.1016/j.cub.2019.04.022}, pmid = {31163162}, issn = {1879-0445}, mesh = {*Biological Evolution ; Dictyostelium/*physiology ; *Microbial Interactions ; }, abstract = {Cooperation has been essential to the evolution of biological complexity, but many societies struggle to overcome internal conflicts and divisions. Dictyostelium discoideum, or the social amoeba, has been a useful model system for exploring these conflicts and how they can be resolved. When starved, these cells communicate, gather into groups, and build themselves into a multicellular fruiting body. Some cells altruistically die to form the rigid stalk, while the remainder sit atop the stalk, become spores, and disperse. Evolutionary theory predicts that conflict will arise over which cells die to form the stalk and which cells become spores and survive. The power of the social amoeba lies in the ability to explore how cooperation and conflict work across multiple levels, ranging from proximate mechanisms (how does it work?) to ultimate evolutionary answers (why does it work?). Recent studies point to solutions to the problem of ensuring fairness, such as the ability to suppress selfishness and to recognize and avoid unrelated individuals. This work confirms a central role for kin selection, but also suggests new explanations for how social amoebae might enforce cooperation. New approaches based on genomics are also enabling researchers to decipher for the first time the evolutionary history of cooperation and conflict and to determine its role in shaping the biology of multicellular organisms.}, } @article {pmid31155362, year = {2019}, author = {Russell, SL and Chappell, L and Sullivan, W}, title = {A symbiont's guide to the germline.}, journal = {Current topics in developmental biology}, volume = {135}, number = {}, pages = {315-351}, doi = {10.1016/bs.ctdb.2019.04.007}, pmid = {31155362}, issn = {1557-8933}, mesh = {Animals ; Cell Movement ; Embryo, Nonmammalian/microbiology ; Germ Cells/*physiology ; Stem Cells/cytology ; *Symbiosis ; }, abstract = {Microbial symbioses exhibit astounding adaptations, yet all symbionts face the problem of how to reliably associate with host offspring every generation. A common strategy is vertical transmission, in which symbionts are directly transmitted from the female to her offspring. The diversity of symbionts and vertical transmission mechanisms is as expansive as the diversity of eukaryotic host taxa that house them. However, there are several common themes among these mechanisms based on the degree to which symbionts associate with the host germline during transmission. In this review, we detail three distinct vertical transmission strategies, starting with associations that are transmitted from host somatic cells to offspring somatic cells, either due to lacking a germline or avoiding it. A second strategy involves somatically-localized symbionts that migrate into the germline during host development. The third strategy we discuss is one in which the symbiont maintains continuous association with the germline throughout development. Unexpectedly, the vast majority of documented vertically inherited symbionts rely on the second strategy: soma-to-germline migration. Given that not all eukaryotes contain a sequestered germline and instead produce offspring from somatic stem cell lineages, this soma-to-germline migration is discussed in the context of multicellular evolution. Lastly, as recent genomics data have revealed an abundance of horizontal gene transfer events from symbiotic and non-symbiotic bacteria to host genomes, we discuss their impact on eukaryotic host evolution.}, } @article {pmid31152521, year = {2019}, author = {Odendall, C and Kagan, JC}, title = {Host-Encoded Sensors of Bacteria: Our Windows into the Microbial World.}, journal = {Microbiology spectrum}, volume = {7}, number = {3}, pages = {}, pmid = {31152521}, issn = {2165-0497}, support = {R01 AI093589/AI/NIAID NIH HHS/United States ; R56 AI093589/AI/NIAID NIH HHS/United States ; R37 AI116550/AI/NIAID NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; U19 AI133524/AI/NIAID NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R01 AI116550/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*immunology/pathogenicity ; Bacterial Infections/*immunology/microbiology ; Evolution, Molecular ; Germ-Free Life ; Host-Pathogen Interactions/*immunology/*physiology ; Humans ; Neutrophil Infiltration ; Receptors, Pattern Recognition/immunology/*physiology ; Virulence Factors ; }, abstract = {Bacterial pathogens can be very efficient at causing disease and are the cause of some of the worst epidemics that have affected humanity. However, most infections are prevented by the actions of our immune system. Immune activation depends on the rapid detection of bacteria by a diverse family of sensory proteins known as pattern recognition receptors. These receptors detect conserved features of bacteria that are not found in humans but are often necessary for survival within the host or environment. In this review, we discuss the strategies used by pattern recognition receptors to detect bacteria and their products. We also discuss emerging evidence that some pattern recognition receptors can be activated by bacterial pathogens specifically, through the surveillance of host activities that are commonly targeted by virulence factors. This collection of surveillance mechanisms provides an interconnected network of defense, which is important to maintain the germ-free environment of the inner organs of humans and other multicellular organisms.}, } @article {pmid31118507, year = {2019}, author = {Loron, CC and François, C and Rainbird, RH and Turner, EC and Borensztajn, S and Javaux, EJ}, title = {Early fungi from the Proterozoic era in Arctic Canada.}, journal = {Nature}, volume = {570}, number = {7760}, pages = {232-235}, doi = {10.1038/s41586-019-1217-0}, pmid = {31118507}, issn = {1476-4687}, mesh = {Arctic Regions ; Canada ; *Fossils ; Fungi/*classification/*isolation & purification/ultrastructure ; History, Ancient ; Phylogeny ; Spectroscopy, Fourier Transform Infrared ; Time Factors ; }, abstract = {Fungi are crucial components of modern ecosystems. They may have had an important role in the colonization of land by eukaryotes, and in the appearance and success of land plants and metazoans[1-3]. Nevertheless, fossils that can unambiguously be identified as fungi are absent from the fossil record until the middle of the Palaeozoic era[4,5]. Here we show, using morphological, ultrastructural and spectroscopic analyses, that multicellular organic-walled microfossils preserved in shale of the Grassy Bay Formation (Shaler Supergroup, Arctic Canada), which dates to approximately 1,010-890 million years ago, have a fungal affinity. These microfossils are more than half a billion years older than previously reported unambiguous occurrences of fungi, a date which is consistent with data from molecular clocks for the emergence of this clade[6,7]. In extending the fossil record of the fungi, this finding also pushes back the minimum date for the appearance of eukaryotic crown group Opisthokonta, which comprises metazoans, fungi and their protist relatives[8,9].}, } @article {pmid31115328, year = {2019}, author = {Bornens, M}, title = {[Cell polarity and the innovation of the primary cilium/centrosome organ in Metazoa].}, journal = {Medecine sciences : M/S}, volume = {35}, number = {5}, pages = {452-461}, doi = {10.1051/medsci/2019092}, pmid = {31115328}, issn = {1958-5381}, mesh = {Animals ; Biological Evolution ; Brain/growth & development ; Cell Movement ; Cell Polarity ; Centrosome/*physiology ; Cilia/*physiology ; Embryonic Development ; Flagella ; Humans ; Sensation ; }, abstract = {Cell-autonomous polarity in Metazoans is inherited from ancestral unicellular organisms. We assume that permanent polarity in unicellular eukaryotes is required for cell motion and sensory reception and that the integration of these two activities corresponds to an evolutionary constrained cell function. While conserving the ancestral flagellum, Metazoans have co-opted a primary cilium/centrosome organ from it, ensuring similar functions, but in different cells, or in the same cell at different moments. We propose that the remodeling necessary to reach a new higher-level unit of selection in multi-cellular organisms, has been triggered by conflicts among individual cell polarities to reach an organismic polarity. We shall provisionally conclude that beyond critical consequences for embryo development, the conservation of cell-autonomous polarity in Metazoans has far reaching implications for the evolution of individuality.}, } @article {pmid31113629, year = {2019}, author = {Ballinger, MJ and Perlman, SJ}, title = {The defensive Spiroplasma.}, journal = {Current opinion in insect science}, volume = {32}, number = {}, pages = {36-41}, doi = {10.1016/j.cois.2018.10.004}, pmid = {31113629}, issn = {2214-5753}, mesh = {Animals ; Arthropods/*microbiology/*parasitology ; Fungi ; Nematoda ; Saporins ; Spiroplasma/*physiology ; Symbiosis ; Wasps ; }, abstract = {Defensive microbes are of great interest for their roles in arthropod health, disease transmission, and biocontrol efforts. Obligate bacterial passengers of arthropods, such as Spiroplasma, confer protection against the natural enemies of their hosts to improve their own fitness. Although known for less than a decade, Spiroplasma's defensive reach extends to diverse parasites, both microbial and multicellular. We provide an overview of known defensive phenotypes against nematodes, parasitoid wasps, and fungi, and highlight recent studies supporting the role of Spiroplasma-encoded ribosome-inactivating proteins in protection. With cellular features well-suited for life in the hemolymph, broad distribution among invertebrate hosts, and the capacity to repeatedly evolve vertical transmission, Spiroplasma may be uniquely equipped to form intimate, defensive associations to combat extracellular parasites. Along with insights into defensive mechanisms, recent significant advances have been made in male-killing - a phenotype with interesting evolutionary ties to defense. Finally, we look forward to an exciting decade using the genetic tools of Drosophila, and the rapidly-advancing tractability of Spiroplasma itself, to better understand mechanisms and evolution in defensive symbiosis.}, } @article {pmid31095603, year = {2019}, author = {Khan, MAW and Stephens, WZ and Mohammed, AD and Round, JL and Kubinak, JL}, title = {Does MHC heterozygosity influence microbiota form and function?.}, journal = {PloS one}, volume = {14}, number = {5}, pages = {e0215946}, pmid = {31095603}, issn = {1932-6203}, support = {DP2 AT008746/AT/NCCIH NIH HHS/United States ; N01AI95375/AI/NIAID NIH HHS/United States ; T32 AI055434/AI/NIAID NIH HHS/United States ; K22 AI123481/AI/NIAID NIH HHS/United States ; R56 AI107090/AI/NIAID NIH HHS/United States ; K22 AI095375/AI/NIAID NIH HHS/United States ; R21 AI109122/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Feces/microbiology ; Female ; Genetic Variation ; Genotype ; *Heterozygote ; Homozygote ; Major Histocompatibility Complex/*genetics ; Mice ; Microbiota/*genetics ; }, abstract = {MHC molecules are essential for the adaptive immune response, and they are the most polymorphic genetic loci in vertebrates. Extreme genetic variation at these loci is paradoxical given their central importance to host health. Classic models of MHC gene evolution center on antagonistic host-pathogen interactions to promote gene diversification and allelic diversity in host populations. However, all multicellular organisms are persistently colonized by their microbiota that perform essential metabolic functions for their host and protect from infection. Here, we provide data to support the hypothesis that MHC heterozygote advantage (a main force of selection thought to drive MHC gene evolution), may operate by enhancing fitness advantages conferred by the host's microbiome. We utilized fecal 16S rRNA gene sequences and their predicted metagenome datasets collected from multiple MHC congenic homozygote and heterozygote mouse strains to describe the influence of MHC heterozygosity on microbiome form and function. We find that in contrast to homozygosity at MHC loci, MHC heterozygosity promotes functional diversification of the microbiome, enhances microbial network connectivity, and results in enrichment for a variety of microbial functions that are positively associated with host fitness. We demonstrate that taxonomic and functional diversity of the microbiome is positively correlated in MHC heterozygote but not homozygote animals, suggesting that heterozygote microbiomes are more functionally adaptive under similar environmental conditions than homozygote microbiomes. Our data complement previous observations on the role of MHC polymorphism in sculpting microbiota composition, but also provide functional insights into how MHC heterozygosity may enhance host health by modulating microbiome form and function. We also provide evidence to support that MHC heterozygosity limits functional redundancy among commensal microbes and may enhance the metabolic versatility of their microbiome. Results from our analyses yield multiple testable predictions regarding the role of MHC heterozygosity on the microbiome that will help guide future research in the area of MHC-microbiome interactions.}, } @article {pmid31088261, year = {2019}, author = {Pichugin, Y and Park, HJ and Traulsen, A}, title = {Evolution of simple multicellular life cycles in dynamic environments.}, journal = {Journal of the Royal Society, Interface}, volume = {16}, number = {154}, pages = {20190054}, pmid = {31088261}, issn = {1742-5662}, mesh = {Animals ; *Biological Evolution ; *Environment ; *Life Cycle Stages ; *Models, Biological ; Reproduction ; *Selection, Genetic ; }, abstract = {The mode of reproduction is a critical characteristic of any species, as it has a strong effect on its evolution. As any other trait, the reproduction mode is subject to natural selection and may adapt to the environment. When the environment varies over time, different reproduction modes could be optimal at different times. The natural response to a dynamic environment seems to be bet hedging, where multiple reproductive strategies are stochastically executed. Here, we develop a framework for the evolution of simple multicellular life cycles in a dynamic environment. We use a matrix population model of undifferentiated multicellular groups undergoing fragmentation and ask which mode maximizes the population growth rate. Counterintuitively, we find that natural selection in dynamic environments generally tends to promote deterministic, not stochastic, reproduction modes.}, } @article {pmid31086369, year = {2019}, author = {Gao, Y and Traulsen, A and Pichugin, Y}, title = {Interacting cells driving the evolution of multicellular life cycles.}, journal = {PLoS computational biology}, volume = {15}, number = {5}, pages = {e1006987}, pmid = {31086369}, issn = {1553-7358}, mesh = {Animals ; Biological Evolution ; Cell Communication/*physiology ; Cell Division ; Computer Simulation ; Game Theory ; Humans ; Life Cycle Stages/genetics/*physiology ; Models, Biological ; Phenotype ; Reproduction ; }, abstract = {Evolution of complex multicellular life began from the emergence of a life cycle involving the formation of cell clusters. The opportunity for cells to interact within clusters provided them with an advantage over unicellular life forms. However, what kind of interactions may lead to the evolution of multicellular life cycles? Here, we combine evolutionary game theory with a model for the emergence of multicellular groups to investigate how cell interactions can influence reproduction modes during the early stages of the evolution of multicellularity. In our model, the presence of both cell types is maintained by stochastic phenotype switching during cell division. We identify evolutionary optimal life cycles as those which maximize the population growth rate. Among all interactions captured by two-player games, the vast majority promotes two classes of life cycles: (i) splitting into unicellular propagules or (ii) fragmentation into two offspring clusters of equal (or almost equal) size. Our findings indicate that the three most important characteristics, determining whether multicellular life cycles will evolve, are the average performance of homogeneous groups, heterogeneous groups, and solitary cells.}, } @article {pmid31086336, year = {2019}, author = {Chan, MM and Smith, ZD and Grosswendt, S and Kretzmer, H and Norman, TM and Adamson, B and Jost, M and Quinn, JJ and Yang, D and Jones, MG and Khodaverdian, A and Yosef, N and Meissner, A and Weissman, JS}, title = {Molecular recording of mammalian embryogenesis.}, journal = {Nature}, volume = {570}, number = {7759}, pages = {77-82}, pmid = {31086336}, issn = {1476-4687}, support = {T32 HG000047/HG/NHGRI NIH HHS/United States ; F32 GM116331/GM/NIGMS NIH HHS/United States ; RM1 HG009490/HG/NHGRI NIH HHS/United States ; R01 DA036858/DA/NIDA NIH HHS/United States ; R01 HD078679/HD/NICHD NIH HHS/United States ; P50 HG006193/HG/NHGRI NIH HHS/United States ; F32 GM125247/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Embryo, Mammalian/cytology/*embryology/*metabolism ; Embryonic Development/*genetics ; Embryonic Stem Cells/cytology/metabolism ; Endoderm/embryology/metabolism ; Female ; Fertilization ; Gastrulation ; Gene Expression Regulation, Developmental/genetics ; Male ; Mice ; Organ Specificity/genetics ; Phenotype ; Sequence Analysis, RNA ; Single-Cell Analysis ; }, abstract = {Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes.}, } @article {pmid31077747, year = {2019}, author = {Vinogradov, AE and Anatskaya, OV}, title = {Evolutionary framework of the human interactome: Unicellular and multicellular giant clusters.}, journal = {Bio Systems}, volume = {181}, number = {}, pages = {82-87}, doi = {10.1016/j.biosystems.2019.05.004}, pmid = {31077747}, issn = {1872-8324}, mesh = {*Biological Evolution ; Cluster Analysis ; *Databases, Genetic ; Evolution, Molecular ; Humans ; Protein Interaction Domains and Motifs ; Protein Interaction Mapping/*methods ; Protein Interaction Maps/*genetics ; }, abstract = {The main contradiction of multicellularity (MCM) is between the unicellular (UC) and multicellular (MC) levels. In human interactome we revealed two giant clusters with MC and UC medians (and several smaller ones with MC medians). The enrichment of these clusters by phylostrata and by functions support the MC versus UC division. The total interactome and the giant clusters show a core-periphery evolutionary growth. From viewpoint of the MCM, the most important is the placement of genes, appearing at UC evolutionary stage, in the MC clusters. Thus, genes involved in vesicle-mediated transport, cell cycle, cellular responses to stress, post-translational modifications and many diseases appeared at UC evolutionary stage but are placed mostly in MC clusters. Genes downregulated with age are enriched in UC cluster, whereas the upregulated genes are preferentially placed in MC giant cluster. The tumor suppressor and pluripotency regulating pathways are also enriched in MC giant cluster. Therefore, this cluster probably operates as 'internal manager' constraining runaway unicellularity. The clusters have denser interactions within than between them, therefore they can serve as attractors (stable states of dynamic systems) of cellular programs. Importantly, the UC cluster have a higher inside/outside connection ratio compared with MC clusters, which suggests a stronger attractor effect and may explain why cells of MC organisms are prone to oncogenesis. The evolutionary clustering of human interactome elucidates the MC control over functions appearing at UC evolutionary stage and can build a framework for biosystems studies focusing on the interplay between UC and MC levels.}, } @article {pmid31069269, year = {2019}, author = {Erkenbrack, EM and Thompson, JR}, title = {Cell type phylogenetics informs the evolutionary origin of echinoderm larval skeletogenic cell identity.}, journal = {Communications biology}, volume = {2}, number = {}, pages = {160}, pmid = {31069269}, issn = {2399-3642}, mesh = {Animal Shells/anatomy & histology/cytology/growth & development/*metabolism ; Animals ; Bayes Theorem ; Biological Evolution ; Echinodermata/classification/*genetics ; Embryo, Nonmammalian ; Extinction, Biological ; Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Larva/cytology/growth & development/*metabolism ; Mesoderm/cytology/growth & development/metabolism ; *Phylogeny ; Stem Cells/cytology/metabolism ; }, abstract = {The multiplicity of cell types comprising multicellular organisms begs the question as to how cell type identities evolve over time. Cell type phylogenetics informs this question by comparing gene expression of homologous cell types in distantly related taxa. We employ this approach to inform the identity of larval skeletogenic cells of echinoderms, a clade for which there are phylogenetically diverse datasets of spatial gene expression patterns. We determined ancestral spatial expression patterns of alx1, ets1, tbr, erg, and vegfr, key components of the skeletogenic gene regulatory network driving identity of the larval skeletogenic cell. Here we show ancestral state reconstructions of spatial gene expression of extant eleutherozoan echinoderms support homology and common ancestry of echinoderm larval skeletogenic cells. We propose larval skeletogenic cells arose in the stem lineage of eleutherozoans during a cell type duplication event that heterochronically activated adult skeletogenic cells in a topographically distinct tissue in early development.}, } @article {pmid31062469, year = {2019}, author = {Turan, ZG and Parvizi, P and Dönertaş, HM and Tung, J and Khaitovich, P and Somel, M}, title = {Molecular footprint of Medawar's mutation accumulation process in mammalian aging.}, journal = {Aging cell}, volume = {18}, number = {4}, pages = {e12965}, pmid = {31062469}, issn = {1474-9726}, support = {//Science Academy/International ; 114C040//Scientific and Technological Research Council of Turkey/International ; 215Z495//Scientific and Technological Research Council of Turkey/International ; //Middle East Technical University (METU)/International ; }, mesh = {Aging/*genetics ; Alleles ; Animals ; Databases, Genetic ; *Evolution, Molecular ; Genetic Drift ; Humans ; Macaca/genetics ; Mice ; *Mutation Accumulation ; Phenotype ; Rats ; *Selection, Genetic ; *Transcriptome ; Up-Regulation/genetics ; }, abstract = {Medawar's mutation accumulation hypothesis explains aging by the declining force of natural selection with age: Slightly deleterious germline mutations expressed in old age can drift to fixation and thereby lead to aging-related phenotypes. Although widely cited, empirical evidence for this hypothesis has remained limited. Here, we test one of its predictions that genes relatively highly expressed in old adults should be under weaker purifying selection than genes relatively highly expressed in young adults. Combining 66 transcriptome datasets (including 16 tissues from five mammalian species) with sequence conservation estimates across mammals, here we report that the overall conservation level of expressed genes is lower at old age compared to young adulthood. This age-related decrease in transcriptome conservation (ADICT) is systematically observed in diverse mammalian tissues, including the brain, liver, lung, and artery, but not in others, most notably in the muscle and heart. Where observed, ADICT is driven partly by poorly conserved genes being up-regulated during aging. In general, the more often a gene is found up-regulated with age among tissues and species, the lower its evolutionary conservation. Poorly conserved and up-regulated genes have overlapping functional properties that include responses to age-associated tissue damage, such as apoptosis and inflammation. Meanwhile, these genes do not appear to be under positive selection. Hence, genes contributing to old age phenotypes are found to harbor an excess of slightly deleterious alleles, at least in certain tissues. This supports the notion that genetic drift shapes aging in multicellular organisms, consistent with Medawar's mutation accumulation hypothesis.}, } @article {pmid31055860, year = {2019}, author = {Singer, D and Mitchell, EAD and Payne, RJ and Blandenier, Q and Duckert, C and Fernández, LD and Fournier, B and Hernández, CE and Granath, G and Rydin, H and Bragazza, L and Koronatova, NG and Goia, I and Harris, LI and Kajukało, K and Kosakyan, A and Lamentowicz, M and Kosykh, NP and Vellak, K and Lara, E}, title = {Dispersal limitations and historical factors determine the biogeography of specialized terrestrial protists.}, journal = {Molecular ecology}, volume = {28}, number = {12}, pages = {3089-3100}, doi = {10.1111/mec.15117}, pmid = {31055860}, issn = {1365-294X}, mesh = {Amoeba/*genetics ; Animals ; Butterflies/genetics ; Ecosystem ; Eukaryota/genetics ; Genetic Speciation ; Genetic Variation/*genetics ; North America ; *Phylogeny ; Plants/genetics ; Sphagnopsida/growth & development ; }, abstract = {Recent studies show that soil eukaryotic diversity is immense and dominated by micro-organisms. However, it is unclear to what extent the processes that shape the distribution of diversity in plants and animals also apply to micro-organisms. Major diversification events in multicellular organisms have often been attributed to long-term climatic and geological processes, but the impact of such processes on protist diversity has received much less attention as their distribution has often been believed to be largely cosmopolitan. Here, we quantified phylogeographical patterns in Hyalosphenia papilio, a large testate amoeba restricted to Holarctic Sphagnum-dominated peatlands, to test if the current distribution of its genetic diversity can be explained by historical factors or by the current distribution of suitable habitats. Phylogenetic diversity was higher in Western North America, corresponding to the inferred geographical origin of the H. papilio complex, and was lower in Eurasia despite extensive suitable habitats. These results suggest that patterns of phylogenetic diversity and distribution can be explained by the history of Holarctic Sphagnum peatland range expansions and contractions in response to Quaternary glaciations that promoted cladogenetic range evolution, rather than the contemporary distribution of suitable habitats. Species distributions were positively correlated with climatic niche breadth, suggesting that climatic tolerance is key to dispersal ability in H. papilio. This implies that, at least for large and specialized terrestrial micro-organisms, propagule dispersal is slow enough that historical processes may contribute to their diversification and phylogeographical patterns and may partly explain their very high overall diversity.}, } @article {pmid31046194, year = {2019}, author = {Biscotti, MA and Barucca, M and Carducci, F and Forconi, M and Canapa, A}, title = {The p53 gene family in vertebrates: Evolutionary considerations.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {332}, number = {6}, pages = {171-178}, doi = {10.1002/jez.b.22856}, pmid = {31046194}, issn = {1552-5015}, mesh = {Animals ; *Evolution, Molecular ; *Genes, p53 ; Phylogeny ; Protein Domains ; Vertebrates/classification/*genetics ; }, abstract = {The origin of the p53 gene family predates multicellular life since TP53 members of this gene family have been found in unicellular eukaryotes. In invertebrates one or two genes attributable to a TP53-like or TP63/73-like gene are present. The radiation into three genes, TP53, TP63, and TP73, has been reported as a vertebrate invention. TP53 is considered the "guardian of the genome" given its role in protecting cells against the DNA damage and cellular stressors. TP63 and TP73 play a role in epithelial development and neurogenesis, respectively. The evolution of the p53 gene family has been the subject of considerable analyses even if several questions remain still open. In this study we addressed the evolutionary history of the p53 gene family in vertebrates performing an extended microsyntenic investigation coupled with a phylogenetic analysis, together with protein domain organization and structure assessment. On the basis of our results we discussed a possible evolutionary scenario according to which a TP53/63/73 ancestor form gave rise to the current TP53 and a TP63/73 form, which in turn independently duplicated into two genes in agnathe and gnathostome lineages.}, } @article {pmid31040327, year = {2019}, author = {Salvi, M and Morbiducci, U and Amadeo, F and Santoro, R and Angelini, F and Chimenti, I and Massai, D and Messina, E and Giacomello, A and Pesce, M and Molinari, F}, title = {Automated Segmentation of Fluorescence Microscopy Images for 3D Cell Detection in human-derived Cardiospheres.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {6644}, pmid = {31040327}, issn = {2045-2322}, mesh = {Cell Culture Techniques ; Humans ; *Image Processing, Computer-Assisted/methods ; *Imaging, Three-Dimensional ; *Microscopy, Fluorescence ; Myoblasts, Cardiac/*cytology/*metabolism ; Reproducibility of Results ; Software ; Spheroids, Cellular ; }, abstract = {The 'cardiosphere' is a 3D cluster of cardiac progenitor cells recapitulating a stem cell niche-like microenvironment with a potential for disease and regeneration modelling of the failing human myocardium. In this multicellular 3D context, it is extremely important to decrypt the spatial distribution of cell markers for dissecting the evolution of cellular phenotypes by direct quantification of fluorescent signals in confocal microscopy. In this study, we present a fully automated method, named CARE ('CARdiosphere Evaluation'), for the segmentation of membranes and cell nuclei in human-derived cardiospheres. The proposed method is tested on twenty 3D-stacks of cardiospheres, for a total of 1160 images. Automatic results are compared with manual annotations and two open-source software designed for fluorescence microscopy. CARE performance was excellent in cardiospheres membrane segmentation and, in cell nuclei detection, the algorithm achieved the same performance as two expert operators. To the best of our knowledge, CARE is the first fully automated algorithm for segmentation inside in vitro 3D cell spheroids, including cardiospheres. The proposed approach will provide, in the future, automated quantitative analysis of markers distribution within the cardiac niche-like environment, enabling predictive associations between cell mechanical stresses and dynamic phenotypic changes.}, } @article {pmid31036299, year = {2019}, author = {Borisenko, I and Podgornaya, OI and Ereskovsky, AV}, title = {From traveler to homebody: Which signaling mechanisms sponge larvae use to become adult sponges?.}, journal = {Advances in protein chemistry and structural biology}, volume = {116}, number = {}, pages = {421-449}, doi = {10.1016/bs.apcsb.2019.02.002}, pmid = {31036299}, issn = {1876-1631}, mesh = {Animals ; Epithelial-Mesenchymal Transition ; Larva/cytology/growth & development ; Metamorphosis, Biological ; Porifera/*cytology/embryology/*growth & development ; *Signal Transduction ; }, abstract = {Cell-to-cell signaling is responsible for regulation of many developmental processes such as proliferation, cell migration, survival, cell fate specification and axis patterning. In this article we discussed the role of signaling in the metamorphosis of sponges with a focus on epithelial-mesenchymal transition (EMT) accompanying this event. Sponges (Porifera) are an ancient lineage of morphologically simple animals occupying a basal position on the tree of life. The study of these animals is necessary for understanding the origin of multicellularity and the evolution of developmental processes. Development of sponges is quite diverse. It finishes with the metamorphosis of a free-swimming larva into a young settled sponge. The outer surface of sponge larvae consists of a ciliated epithelial sheath, which ensures locomotion, while their internal structure varies from genus to genus. The fate of larval ciliated cells is the most intriguing aspect of metamorphosis. In this review we discuss the fate of larval ciliated cells, the processes going on in cells during metamorphosis at the molecular level and the regulation of this process. The review is based on information about several sponge species with a focus on Halisarca dujardini, Sycon ciliatum and Amphimedon queenslandica. In our model sponge, H. dujardini, ciliated cells leave the larval epithelium during metamorphosis and migrate to the internal cell mass as amoeboid cells to be differentiated into choanocytes of the juvenile sponge. Ciliated cells undergo EMT and internalize within minutes. As EMT involves the disappearance of adherens junctions and as cadherin, the main adherens junction protein, was identified in the transcriptome of several sponges, we suppose that EMT is regulated through cadherin-containing adherens junctions between ciliated cells. We failed to identify the master genes of EMT in the H. dujardini transcriptome, possibly because transcription was absent in the sequenced stages. They may be revealed by a search in the genome. The master genes themselves are controlled by various signaling pathways. Sponges have all the six signaling pathways conserved in Metazoa: Wnt, TGF-beta, Hedgehog, Notch, FGF and NO-dependent pathways. Summarizing the new data about intercellular communication in sponges, we can put forward two main questions regarding metamorphosis: (1) Which of the signaling pathways and in what hierarchical order are involved in metamorphosis? (2) How is the organization of a young sponge related to that of the larva or, in other words, is there a heredity of axes between the larva and the adult sponge?}, } @article {pmid31031789, year = {2019}, author = {Hajheidari, M and Koncz, C and Bucher, M}, title = {Chromatin Evolution-Key Innovations Underpinning Morphological Complexity.}, journal = {Frontiers in plant science}, volume = {10}, number = {}, pages = {454}, pmid = {31031789}, issn = {1664-462X}, abstract = {The history of life consists of a series of major evolutionary transitions, including emergence and radiation of complex multicellular eukaryotes from unicellular ancestors. The cells of multicellular organisms, with few exceptions, contain the same genome, however, their organs are composed of a variety of cell types that differ in both structure and function. This variation is largely due to the transcriptional activity of different sets of genes in different cell types. This indicates that complex transcriptional regulation played a key role in the evolution of complexity in eukaryotes. In this review, we summarize how gene duplication and subsequent evolutionary innovations, including the structural evolution of nucleosomes and chromatin-related factors, contributed to the complexity of the transcriptional system and provided a basis for morphological diversity.}, } @article {pmid31023220, year = {2019}, author = {Krishnan, A and Degnan, BM and Degnan, SM}, title = {The first identification of complete Eph-ephrin signalling in ctenophores and sponges reveals a role for neofunctionalization in the emergence of signalling domains.}, journal = {BMC evolutionary biology}, volume = {19}, number = {1}, pages = {96}, pmid = {31023220}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Ctenophora/*metabolism ; Ephrins/*metabolism ; Evolution, Molecular ; Humans ; Ligands ; Phylogeny ; Porifera/*metabolism ; Protein Binding ; Protein Domains ; Receptors, Eph Family/chemistry/*metabolism ; *Signal Transduction ; }, abstract = {BACKGROUND: Animals have a greater diversity of signalling pathways than their unicellular relatives, consistent with the evolution and expansion of these pathways occurring in parallel with the origin of animal multicellularity. However, the genomes of sponges and ctenophores - non-bilaterian basal animals - typically encode no, or far fewer, recognisable signalling ligands compared to bilaterians and cnidarians. For instance, the largest subclass of receptor tyrosine kinases (RTKs) in bilaterians, the Eph receptors (Ephs), are present in sponges and ctenophores, but their cognate ligands, the ephrins, have not yet been detected.

RESULTS: Here, we use an iterative HMM analysis to identify for the first time membrane-bound ephrins in sponges and ctenophores. We also expand the number of Eph-receptor subtypes identified in these animals and in cnidarians. Both sequence and structural analyses are consistent with the Eph ligand binding domain (LBD) and the ephrin receptor binding domain (RBD) having evolved via the co-option of ancient galactose-binding (discoidin-domain)-like and monodomain cupredoxin domains, respectively. Although we did not detect a complete Eph-ephrin signalling pathway in closely-related unicellular holozoans or in other non-metazoan eukaryotes, truncated proteins with Eph receptor LBDs and ephrin RBDs are present in some choanoflagellates. Together, these results indicate that Eph-ephrin signalling was present in the last common ancestor of extant metazoans, and perhaps even in the last common ancestor of animals and choanoflagellates. Either scenario pushes the origin of Eph-ephrin signalling back much earlier than previously reported.

CONCLUSIONS: We propose that the Eph-LBD and ephrin-RBD, which were ancestrally localised in the cytosol, became linked to the extracellular parts of two cell surface proteins before the divergence of sponges and ctenophores from the rest of the animal kingdom. The ephrin-RBD lost the ancestral capacity to bind copper, and the Eph-LBD became linked to an ancient RTK. The identification of divergent ephrin ligands in sponges and ctenophores suggests that these ligands evolve faster than their cognate receptors. As this may be a general phenomena, we propose that the sequence-structure approach used in this study may be usefully applied to other signalling systems where no, or a small number of, ligands have been identified.}, } @article {pmid31012964, year = {2019}, author = {Gunaratne, PH and Pan, Y and Rao, AK and Lin, C and Hernandez-Herrera, A and Liang, K and Rait, AS and Venkatanarayan, A and Benham, AL and Rubab, F and Kim, SS and Rajapakshe, K and Chan, CK and Mangala, LS and Lopez-Berestein, G and Sood, AK and Rowat, AC and Coarfa, C and Pirollo, KF and Flores, ER and Chang, EH}, title = {Activating p53 family member TAp63: A novel therapeutic strategy for targeting p53-altered tumors.}, journal = {Cancer}, volume = {125}, number = {14}, pages = {2409-2422}, pmid = {31012964}, issn = {1097-0142}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA160394/CA/NCI NIH HHS/United States ; P30 CA051008/CA/NCI NIH HHS/United States ; R01 CA218025/CA/NCI NIH HHS/United States ; R00 DK094981/DK/NIDDK NIH HHS/United States ; R35 CA197452/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; R01 CA132012/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; Binding Sites ; Cell Line, Tumor ; Cell Movement/drug effects ; Cisplatin/pharmacology/therapeutic use ; Drug Resistance, Neoplasm/drug effects ; Female ; Humans ; Liposomes ; Mice ; Mice, Nude ; MicroRNAs/administration & dosage/genetics/metabolism/*therapeutic use ; *Mutation, Missense ; Neoplasm Invasiveness/prevention & control ; Ovarian Neoplasms/*drug therapy/*genetics ; Protein Isoforms/genetics ; Signal Transduction/drug effects ; Transcription Factors/*genetics/metabolism ; Transcriptional Activation/*genetics ; Transfection ; Tumor Suppressor Protein p53/*genetics/metabolism ; Tumor Suppressor Proteins/*genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Over 96% of high-grade ovarian carcinomas and 50% of all cancers are characterized by alterations in the p53 gene. Therapeutic strategies to restore and/or reactivate the p53 pathway have been challenging. By contrast, p63, which shares many of the downstream targets and functions of p53, is rarely mutated in cancer.

METHODS: A novel strategy is presented for circumventing alterations in p53 by inducing the tumor-suppressor isoform TAp63 (transactivation domain of tumor protein p63) through its direct downstream target, microRNA-130b (miR-130b), which is epigenetically silenced and/or downregulated in chemoresistant ovarian cancer.

RESULTS: Treatment with miR-130b resulted in: 1) decreased migration/invasion in HEYA8 cells (p53 wild-type) and disruption of multicellular spheroids in OVCAR8 cells (p53-mutant) in vitro, 2) sensitization of HEYA8 and OVCAR8 cells to cisplatin (CDDP) in vitro and in vivo, and 3) transcriptional activation of TAp63 and the B-cell lymphoma (Bcl)-inhibitor B-cell lymphoma 2-like protein 11 (BIM). Overexpression of TAp63 was sufficient to decrease cell viability, suggesting that it is a critical downstream effector of miR-130b. In vivo, combined miR-130b plus CDDP exhibited greater therapeutic efficacy than miR-130b or CDDP alone. Mice that carried OVCAR8 xenograft tumors and were injected with miR-130b in 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) liposomes had a significant decrease in tumor burden at rates similar to those observed in CDDP-treated mice, and 20% of DOPC-miR-130b plus CDDP-treated mice were living tumor free. Systemic injections of scL-miR-130b plus CDDP in a clinically tested, tumor-targeted nanocomplex (scL) improved survival in 60% and complete remissions in 40% of mice that carried HEYA8 xenografts.

CONCLUSIONS: The miR-130b/TAp63 axis is proposed as a new druggable pathway that has the potential to uncover broad-spectrum therapeutic options for the majority of p53-altered cancers.}, } @article {pmid31006855, year = {2019}, author = {Sudianto, E}, title = {Digest: Banding together to battle adversaries has its consequences.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {6}, pages = {1320-1321}, doi = {10.1111/evo.13750}, pmid = {31006855}, issn = {1558-5646}, mesh = {Animals ; *Biological Evolution ; *Chlorella ; Cost-Benefit Analysis ; Predatory Behavior ; }, abstract = {Why did life evolve from single-celled to multicellular organisms? Could there be advantages to this transition? What about associated fitness costs? Kapsetaki and West found that although multicellularity allows Chlorella sorokiniana to avoid predation from similarly-sized predators, it also reduces their competitiveness when resources are limited.}, } @article {pmid31002570, year = {2019}, author = {Olito, C and Connallon, T}, title = {Sexually Antagonistic Variation and the Evolution of Dimorphic Sexual Systems.}, journal = {The American naturalist}, volume = {193}, number = {5}, pages = {688-701}, doi = {10.1086/702847}, pmid = {31002570}, issn = {1537-5323}, mesh = {Alleles ; *Biological Evolution ; Infertility/genetics ; *Models, Biological ; *Sex ; *Sex Characteristics ; }, abstract = {Multicellular Eukaryotes use a broad spectrum of sexual reproduction strategies, ranging from simultaneous hermaphroditism to complete dioecy (separate sexes). The evolutionary pathway from hermaphroditism to dioecy involves the spread of sterility alleles that eliminate female or male reproductive functions, producing unisexual individuals. Classical theory predicts that evolutionary transitions to dioecy are feasible when female and male sex functions genetically trade off with one another (allocation to sex functions is sexually antagonistic) and rates of self-fertilization and inbreeding depression are high within the ancestral hermaphrodite population. We show that genetic linkage between sterility alleles and loci under sexually antagonistic selection significantly alters these classical predictions. We identify three specific consequences of linkage for the evolution of dimorphic sexual systems. First, linkage broadens conditions for the invasion of unisexual sterility alleles, facilitating transitions to sexual systems that are intermediate between hermaphroditism and dioecy (androdioecy and gynodioecy). Second, linkage elevates the equilibrium frequencies of unisexual individuals within androdioecious and gynodioecious populations, which promotes subsequent transitions to full dioecy. Third, linkage dampens the role of inbreeding during transitions to androdioecy and gynodioecy, making these transitions feasible in outbred populations. We discuss implications of these results for the evolution of dimorphic reproductive systems and sex chromosomes.}, } @article {pmid30989827, year = {2019}, author = {Hehmeyer, J}, title = {Two potential evolutionary origins of the fruiting bodies of the dictyostelid slime moulds.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {94}, number = {5}, pages = {1591-1604}, doi = {10.1111/brv.12516}, pmid = {30989827}, issn = {1469-185X}, mesh = {*Biological Evolution ; Dictyostelium/classification/genetics/*physiology ; Fruiting Bodies, Fungal/genetics/*physiology ; Phylogeny ; Spores, Fungal/genetics/physiology ; }, abstract = {Dictyostelium discoideum and the other dictyostelid slime moulds ('social amoebae') are popular model organisms best known for their demonstration of sorocarpic development. In this process, many cells aggregate to form a multicellular unit that ultimately becomes a fruiting body bearing asexual spores. Several other unrelated microorganisms undergo comparable processes, and in some it is evident that their multicellular development evolved from the differentiation process of encystation. While it has been argued that the dictyostelid fruiting body had similar origins, it has also been proposed that dictyostelid sorocarpy evolved from the unicellular fruiting process found in other amoebozoan slime moulds. This paper reviews the developmental biology of the dictyostelids and other relevant organisms and reassesses the two hypotheses on the evolutionary origins of dictyostelid development. Recent advances in phylogeny, genetics, and genomics and transcriptomics indicate that further research is necessary to determine whether or not the fruiting bodies of the dictyostelids and their closest relatives, the myxomycetes and protosporangids, are homologous.}, } @article {pmid30989676, year = {2019}, author = {Ranjbaran, A and Latifi, Z and Nejabati, HR and Abroon, S and Mihanfar, A and Sadigh, AR and Fattahi, A and Nouri, M and Raffel, N}, title = {Exosome-based intercellular communication in female reproductive microenvironments.}, journal = {Journal of cellular physiology}, volume = {234}, number = {11}, pages = {19212-19222}, doi = {10.1002/jcp.28668}, pmid = {30989676}, issn = {1097-4652}, mesh = {Cell Communication/*genetics ; Cellular Microenvironment/genetics ; Drug Delivery Systems ; Exosomes/*genetics ; Female ; *Gene Transfer Techniques ; Genitalia, Female/*metabolism/pathology ; Humans ; Nanoparticles/therapeutic use ; }, abstract = {Different strategies are applied for cellular cross-talk and organization in multicellular organisms. Exosomes are a homogenous population of biological nanoparticles (30-100 nm), originated from multivesicular bodies. The exosomes (Exos) could regulate and affect both cellular physiology and pathophysiology in various organs, such as the female reproductive tract, by altering gene pathways and/or epigenetic programming. Besides, engineered Exos have the potential to be used as a novel drug and gene delivery tools. Here in this review, we discussed various aspects of exosome-based intercellular communication in female reproductive microenvironments. Furthermore, we addressed the findings and issues related to Exos in reproductive biology to give a better view of the involved molecular mechanisms. Moreover, clinical applications of the Exos and their isolation source/methods have been considered to throw some light on the progression of new biological, diagnostic, and therapeutic approaches in clinical embryology.}, } @article {pmid30989357, year = {2020}, author = {Pérez, P and Soto, T and Gómez-Gil, E and Cansado, J}, title = {Functional interaction between Cdc42 and the stress MAPK signaling pathway during the regulation of fission yeast polarized growth.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {23}, number = {1}, pages = {31-41}, doi = {10.1007/s10123-019-00072-6}, pmid = {30989357}, issn = {1618-1905}, support = {BIO2015-69958-P//Ministerio de Economía, Industria y Competitividad, Gobierno de España/ ; BFU2017-82423-P//Ministerio de Economía, Industria y Competitividad, Gobierno de España/ ; CSI068P17//Consejería de Educación, Junta de Castilla y León/ ; CLU-2017-03//Consejería de Educación, Junta de Castilla y León/ ; }, mesh = {Cell Polarity ; *Fungal Proteins ; *MAP Kinase Signaling System ; Phosphorylation ; Protein Binding ; Protein Transport ; Schizosaccharomyces/cytology/*physiology ; *Stress, Physiological ; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae/*metabolism ; }, abstract = {Cell polarization can be defined as the generation and maintenance of directional cellular organization. The spatial distribution and protein or lipid composition of the cell are not symmetric but organized in specialized domains which allow cells to grow and acquire a certain shape that is closely linked to their physiological function. The establishment and maintenance of polarized growth requires the coordination of diverse processes including cytoskeletal dynamics, membrane trafficking, and signaling cascade regulation. Some of the major players involved in the selection and maintenance of sites for polarized growth are Rho GTPases, which recognize the polarization site and transmit the signal to regulatory proteins of the cytoskeleton. Additionally, cytoskeletal organization, polarized secretion, and endocytosis are controlled by signaling pathways including those mediated by mitogen-activated protein kinases (MAPKs). Rho GTPases and the MAPK signaling pathways are strongly conserved from yeast to mammals, suggesting that the basic mechanisms of polarized growth have been maintained throughout evolution. For this reason, the study of how polarized growth is established and regulated in simple organisms such as the fission yeast Schizosaccharomyces pombe has contributed to broaden our knowledge about these processes in multicellular organisms. We review here the function of the Cdc42 GTPase and the stress activated MAPK (SAPK) signaling pathways during fission yeast polarized growth, and discuss the relevance of the crosstalk between both pathways.}, } @article {pmid30978201, year = {2019}, author = {Laundon, D and Larson, BT and McDonald, K and King, N and Burkhardt, P}, title = {The architecture of cell differentiation in choanoflagellates and sponge choanocytes.}, journal = {PLoS biology}, volume = {17}, number = {4}, pages = {e3000226}, pmid = {30978201}, issn = {1545-7885}, mesh = {Animals ; Cell Differentiation/genetics ; Choanoflagellata/genetics/metabolism/*physiology ; Microscopy, Electron, Transmission ; Morphogenesis/*physiology ; Phylogeny ; Porifera/genetics/*physiology ; }, abstract = {Although collar cells are conserved across animals and their closest relatives, the choanoflagellates, little is known about their ancestry, their subcellular architecture, or how they differentiate. The choanoflagellate Salpingoeca rosetta expresses genes necessary for animal development and can alternate between unicellular and multicellular states, making it a powerful model for investigating the origin of animal multicellularity and mechanisms underlying cell differentiation. To compare the subcellular architecture of solitary collar cells in S. rosetta with that of multicellular 'rosette' colonies and collar cells in sponges, we reconstructed entire cells in 3D through transmission electron microscopy on serial ultrathin sections. Structural analysis of our 3D reconstructions revealed important differences between single and colonial choanoflagellate cells, with colonial cells exhibiting a more amoeboid morphology consistent with higher levels of macropinocytotic activity. Comparison of multiple reconstructed rosette colonies highlighted the variable nature of cell sizes, cell-cell contact networks, and colony arrangement. Importantly, we uncovered the presence of elongated cells in some rosette colonies that likely represent a distinct and differentiated cell type, pointing toward spatial cell differentiation. Intercellular bridges within choanoflagellate colonies displayed a variety of morphologies and connected some but not all neighbouring cells. Reconstruction of sponge choanocytes revealed ultrastructural commonalities but also differences in major organelle composition in comparison to choanoflagellates. Together, our comparative reconstructions uncover the architecture of cell differentiation in choanoflagellates and sponge choanocytes and constitute an important step in reconstructing the cell biology of the last common ancestor of animals.}, } @article {pmid30967090, year = {2019}, author = {Cotter, SC and Pincheira-Donoso, D and Thorogood, R}, title = {Defences against brood parasites from a social immunity perspective.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1769}, pages = {20180207}, pmid = {30967090}, issn = {1471-2970}, mesh = {Animals ; Biological Evolution ; *Birds/parasitology/physiology ; *Cues ; *Host-Parasite Interactions ; *Insecta/parasitology/physiology ; *Recognition, Psychology ; *Social Behavior ; }, abstract = {Parasitic interactions are so ubiquitous that all multicellular organisms have evolved a system of defences to reduce their costs, whether the parasites they encounter are the classic parasites which feed on the individual, or brood parasites which usurp parental care. Many parallels have been drawn between defences deployed against both types of parasite, but typically, while defences against classic parasites have been selected to protect survival, those against brood parasites have been selected to protect the parent's inclusive fitness, suggesting that the selection pressures they impose are fundamentally different. However, there is another class of defences against classic parasites that have specifically been selected to protect an individual's inclusive fitness, known as social immunity. Social immune responses include the anti-parasite defences typically provided for others in kin-structured groups, such as the antifungal secretions produced by termite workers to protect the brood. Defences against brood parasites, therefore, are more closely aligned with social immune responses. Much like social immunity, host defences against brood parasitism are employed by a donor (a parent) for the benefit of one or more recipients (typically kin), and as with social defences against classic parasites, defences have therefore evolved to protect the donor's inclusive fitness, not the survival or ultimately the fitness of individual recipients This can lead to severe conflicts between the different parties, whose interests are not always aligned. Here, we consider defences against brood parasitism in the light of social immunity, at different stages of parasite encounter, addressing where conflicts occur and how they might be resolved. We finish with considering how this approach could help us to address longstanding questions in our understanding of brood parasitism. This article is part of the theme issue 'The coevolutionary biology of brood parasitism: from mechanism to pattern'.}, } @article {pmid30963641, year = {2019}, author = {Rêgo, A and Messina, FJ and Gompert, Z}, title = {Dynamics of genomic change during evolutionary rescue in the seed beetle Callosobruchus maculatus.}, journal = {Molecular ecology}, volume = {28}, number = {9}, pages = {2136-2154}, doi = {10.1111/mec.15085}, pmid = {30963641}, issn = {1365-294X}, mesh = {Adaptation, Physiological/genetics ; Animals ; Bayes Theorem ; Biological Evolution ; Coleoptera/*genetics ; Gene Frequency ; Genetic Drift ; Genetic Fitness ; Lens Plant ; Linkage Disequilibrium ; Models, Genetic ; Polymorphism, Single Nucleotide ; Seeds ; *Selection, Genetic ; }, abstract = {Rapid adaptation can prevent extinction when populations are exposed to extremely marginal or stressful environments. Factors that affect the likelihood of evolutionary rescue from extinction have been identified, but much less is known about the evolutionary dynamics (e.g., rates and patterns of allele frequency change) and genomic basis of successful rescue, particularly in multicellular organisms. We conducted an evolve-and-resequence experiment to investigate the dynamics of evolutionary rescue at the genetic level in the cowpea seed beetle, Callosobruchus maculatus, when it is experimentally shifted to a stressful host plant, lentil. Low survival (~1%) at the onset of the experiment caused population decline. But adaptive evolution quickly rescued the population, with survival rates climbing to 69% by the F5 generation and 90% by the F10 generation. Population genomic data showed that rescue likely was caused by rapid evolutionary change at multiple loci, with many alleles fixing or nearly fixing within five generations of selection on lentil. Selection on these loci was only moderately consistent in time, but parallel evolutionary changes were evident in sublines formed after the lentil line had passed through a bottleneck. By comparing estimates of selection and genomic change on lentil across five independent C. maculatus lines (the new lentil-adapted line, three long-established lines and one case of failed evolutionary rescue), we found that adaptation on lentil occurred via somewhat idiosyncratic evolutionary changes. Overall, our results suggest that evolutionary rescue in this system can be caused by very strong selection on multiple loci driving rapid and pronounced genomic change.}, } @article {pmid30958167, year = {2019}, author = {Nguyen, H and Koehl, MAR and Oakes, C and Bustamante, G and Fauci, L}, title = {Effects of cell morphology and attachment to a surface on the hydrodynamic performance of unicellular choanoflagellates.}, journal = {Journal of the Royal Society, Interface}, volume = {16}, number = {150}, pages = {20180736}, pmid = {30958167}, issn = {1742-5662}, mesh = {Cell Adhesion/*physiology ; Choanoflagellata/cytology/*physiology ; *Hydrodynamics ; *Models, Biological ; Surface Properties ; Swimming/*physiology ; }, abstract = {Choanoflagellates, eukaryotes that are important predators on bacteria in aquatic ecosystems, are closely related to animals and are used as a model system to study the evolution of animals from protozoan ancestors. The choanoflagellate Salpingoeca rosetta has a complex life cycle with different morphotypes, some unicellular and some multicellular. Here we use computational fluid dynamics to study the hydrodynamics of swimming and feeding by different unicellular stages of S. rosetta: a swimming cell with a collar of prey-capturing microvilli surrounding a single flagellum, a thecate cell attached to a surface and a dispersal-stage cell with a slender body, long flagellum and short collar. We show that a longer flagellum increases swimming speed, longer microvilli reduce speed and cell shape only affects speed when the collar is very short. The flux of prey-carrying water into the collar capture zone is greater for swimming than sessile cells, but this advantage decreases with collar size. Stalk length has little effect on flux for sessile cells. We show that ignoring the collar, as earlier models have done, overestimates flux and greatly overestimates the benefit to feeding performance of swimming versus being attached, and of a longer stalk for attached cells.}, } @article {pmid30952878, year = {2019}, author = {Baade, T and Paone, C and Baldrich, A and Hauck, CR}, title = {Clustering of integrin β cytoplasmic domains triggers nascent adhesion formation and reveals a protozoan origin of the integrin-talin interaction.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {5728}, pmid = {30952878}, issn = {2045-2322}, mesh = {Cytoplasm/*metabolism ; HEK293 Cells ; Humans ; Integrin beta Chains/*metabolism ; Protein Binding ; Talin/*metabolism ; }, abstract = {Integrins and integrin-dependent cell-matrix adhesions are essential for a number of physiological processes. Integrin function is tightly regulated via binding of cytoplasmic proteins to integrin intracellular domains. Yet, the complexity of cell-matrix adhesions in mammals, with more than 150 core adhesome proteins, complicates the analysis of integrin-associated protein complexes. Interestingly, the evolutionary origin of integrins dates back before the transition from unicellular life to complex multicellular animals. Though unicellular relatives of metazoa have a less complex adhesome, nothing is known about the initial steps of integrin activation and adhesion complex assembly in protozoa. Therefore, we developed a minimal, microscope-based system using chimeric integrins to investigate receptor-proximal events during focal adhesion assembly. Clustering of the human integrin β1 tail led to recruitment of talin, kindlin, and paxillin and mutation of the known talin binding site abolished recruitment of this protein. Proteins indirectly linked to integrins, such as vinculin, migfilin, p130[CAS], or zyxin were not enriched around the integrin β1 tail. With the exception of integrin β4 and integrin β8, the cytoplasmic domains of all human integrin β subunits supported talin binding. Likewise, the cytoplasmic domains of integrin β subunits expressed by the protozoan Capsaspora owczarzaki readily recruited talin and this interaction was based on an evolutionary conserved NPXY/F amino acid motif. The results we present here validate the use of our novel microscopic assay to uncover details of integrin-based protein-protein interactions in a cellular context and suggest that talin binding to integrin β cytoplasmic tails is an ancient feature of integrin regulation.}, } @article {pmid30949307, year = {2019}, author = {Bohlin, J and Pettersson, JH}, title = {Evolution of Genomic Base Composition: From Single Cell Microbes to Multicellular Animals.}, journal = {Computational and structural biotechnology journal}, volume = {17}, number = {}, pages = {362-370}, pmid = {30949307}, issn = {2001-0370}, abstract = {Whole genome sequencing (WGS) of thousands of microbial genomes has provided considerable insight into evolutionary mechanisms in the microbial world. While substantially fewer eukaryotic genomes are available for analyses the number is rapidly increasing. This mini-review summarizes broadly evolutionary dynamics of base composition in the different domains of life from the perspective of prokaryotes. Common and different evolutionary mechanisms influencing genomic base composition in eukaryotes and prokaryotes are discussed. The conclusion from the data currently available suggests that while there are similarities there are also striking differences in how genomic base composition has evolved within prokaryotes and eukaryotes. For instance, homologous recombination appears to increase GC content locally in eukaryotes due to a non-selective process termed GC-biased gene conversion (gBGC). For prokaryotes on the other hand, increase in genomic GC content seems to be driven by the environment and selection. We find that similar phenomena observed for some organisms in each respective domain may be caused by very different mechanisms: while gBGC and recombination rates appear to explain the negative correlation between GC3 (GC content based on the third codon nucleotides) and genome size in some eukaryotes uptake of AT rich DNA sequences is the main reason for a similar negative correlation observed in prokaryotes. We provide further examples that indicate that base composition in prokaryotes and eukaryotes have evolved under very different constraints.}, } @article {pmid30941746, year = {2019}, author = {Gulli, JG and Herron, MD and Ratcliff, WC}, title = {Evolution of altruistic cooperation among nascent multicellular organisms.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {5}, pages = {1012-1024}, pmid = {30941746}, issn = {1558-5646}, support = {NNA17BB05A/NASA/NASA/United States ; DGE-1148903//Division of Graduate Education/International ; NNX15AR33G/NASA/NASA/United States ; DEB-1723293//National Science Foundation/International ; NNA17BB05A/ImNASA/Intramural NASA/United States ; }, mesh = {*Biological Evolution ; Cell Death ; Cluster Analysis ; DNA, Fungal/analysis ; Genotype ; Models, Biological ; Yeasts/*genetics/*physiology ; }, abstract = {Cooperation is a classic solution to hostile environments that limit individual survival. In extreme cases this may lead to the evolution of new types of biological individuals (e.g., eusocial super-organisms). We examined the potential for interindividual cooperation to evolve via experimental evolution, challenging nascent multicellular "snowflake yeast" with an environment in which solitary multicellular clusters experienced low survival. In response, snowflake yeast evolved to form cooperative groups composed of thousands of multicellular clusters that typically survive selection. Group formation occurred through the creation of protein aggregates, only arising in strains with high (>2%) rates of cell death. Nonetheless, it was adaptive and repeatable, although ultimately evolutionarily unstable. Extracellular protein aggregates act as a common good, as they can be exploited by cheats that do not contribute to aggregate production. These results highlight the importance of group formation as a mechanism for surviving environmental stress, and underscore the remarkable ease with which even simple multicellular entities may evolve-and lose-novel social traits.}, } @article {pmid30925871, year = {2019}, author = {Kim, HM and Weber, JA and Lee, N and Park, SG and Cho, YS and Bhak, Y and Lee, N and Jeon, Y and Jeon, S and Luria, V and Karger, A and Kirschner, MW and Jo, YJ and Woo, S and Shin, K and Chung, O and Ryu, JC and Yim, HS and Lee, JH and Edwards, JS and Manica, A and Bhak, J and Yum, S}, title = {The genome of the giant Nomura's jellyfish sheds light on the early evolution of active predation.}, journal = {BMC biology}, volume = {17}, number = {1}, pages = {28}, pmid = {30925871}, issn = {1741-7007}, support = {R01 HD073104/HD/NICHD NIH HHS/United States ; R01 HD091846/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *Evolution, Molecular ; Genome/*physiology ; Phylogeny ; *Predatory Behavior ; Scyphozoa/genetics/*physiology ; }, abstract = {BACKGROUND: Unique among cnidarians, jellyfish have remarkable morphological and biochemical innovations that allow them to actively hunt in the water column and were some of the first animals to become free-swimming. The class Scyphozoa, or true jellyfish, are characterized by a predominant medusa life-stage consisting of a bell and venomous tentacles used for hunting and defense, as well as using pulsed jet propulsion for mobility. Here, we present the genome of the giant Nomura's jellyfish (Nemopilema nomurai) to understand the genetic basis of these key innovations.

RESULTS: We sequenced the genome and transcriptomes of the bell and tentacles of the giant Nomura's jellyfish as well as transcriptomes across tissues and developmental stages of the Sanderia malayensis jellyfish. Analyses of the Nemopilema and other cnidarian genomes revealed adaptations associated with swimming, marked by codon bias in muscle contraction and expansion of neurotransmitter genes, along with expanded Myosin type II family and venom domains, possibly contributing to jellyfish mobility and active predation. We also identified gene family expansions of Wnt and posterior Hox genes and discovered the important role of retinoic acid signaling in this ancient lineage of metazoans, which together may be related to the unique jellyfish body plan (medusa formation).

CONCLUSIONS: Taken together, the Nemopilema jellyfish genome and transcriptomes genetically confirm their unique morphological and physiological traits, which may have contributed to the success of jellyfish as early multi-cellular predators.}, } @article {pmid30923125, year = {2019}, author = {Pedchenko, V and Bauer, R and Pokidysheva, EN and Al-Shaer, A and Forde, NR and Fidler, AL and Hudson, BG and Boudko, SP}, title = {A chloride ring is an ancient evolutionary innovation mediating the assembly of the collagen IV scaffold of basement membranes.}, journal = {The Journal of biological chemistry}, volume = {294}, number = {20}, pages = {7968-7981}, pmid = {30923125}, issn = {1083-351X}, support = {R01 DK018381/DK/NIDDK NIH HHS/United States ; R25 DK096999/DK/NIDDK NIH HHS/United States ; T32 DK007569/DK/NIDDK NIH HHS/United States ; }, mesh = {Collagen Type IV/*chemistry ; Crystallography, X-Ray ; Humans ; *Models, Molecular ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; }, abstract = {Collagen IV scaffold is a principal component of the basement membrane (BM), a specialized extracellular matrix that is essential for animal multicellularity and tissue evolution. Scaffold assembly begins with the trimerization of α-chains into protomers inside the cell, which then are secreted and undergo oligomerization outside the cell. For the ubiquitous scaffold composed of α1- and α2-chains, both intracellular and extracellular stages are mediated by the noncollagenous domain (NC1). The association of protomers is chloride-dependent, whereby chloride ions induce interactions of the protomers' trimeric NC1 domains leading to NC1 hexamer formation. Here, we investigated the mechanisms, kinetics, and functionality of the chloride ion-mediated protomer assembly by using a single-chain technology to produce a stable NC1 trimer comprising α1, α2, and α1 NC1 monomers. We observed that in the presence of chloride, the single-chain NC1-trimer self-assembles into a hexamer, for which the crystal structure was determined. We discovered that a chloride ring, comprising 12 ions, induces the assembly of and stabilizes the NC1 hexamer. Furthermore, we found that the chloride ring is evolutionarily conserved across all animals, first appearing in cnidarians. These findings reveal a fundamental role for the chloride ring in the assembly of collagen IV scaffolds of BMs, a critical event enabling tissue evolution and development. Moreover, the single-chain technology is foundational for generating trimeric NC1 domains of other α-chain compositions to investigate the α121, α345, and α565 collagen IV scaffolds and to develop therapies for managing Alport syndrome, Goodpasture's disease, and cancerous tumor growth.}, } @article {pmid30919568, year = {2020}, author = {Zhu, SQ and Zhang, YJ and Abbas, MN and Hao, XW and Zhao, YZ and Liang, HH and Cui, HJ and Yang, LQ}, title = {Hedgehog promotes cell proliferation in the midgut of silkworm, Bombyx mori.}, journal = {Insect science}, volume = {27}, number = {4}, pages = {697-707}, doi = {10.1111/1744-7917.12672}, pmid = {30919568}, issn = {1744-7917}, support = {No. XDJK2015C129//Fundamental Research Funds for the Central Universities/ ; No. 2362015XK09//Fundamental Research Funds for the Central Universities/ ; No. XDJK2013B020//Fundamental Research Funds for the Central Universities/ ; No. 20120524//Fundamental Research Funds for the Central Universities/ ; CXTDX201601010//Chongqing University Innovation Team Building Program funded projects/ ; 2017ZBX10//Scientific Research Foundation of the Chongqing University of Arts and Sciences/ ; No. 31672496//National Natural Science Foundation of China/ ; cstc2016jcyjA0425//Natural Science Foundation of Chongqing/ ; XDJK2015C129//Fundamental Research Funds for the Central Universities/ ; 2362015XK09//Fundamental Research Funds for the Central Universities/ ; XDJK2013B020//Fundamental Research Funds for the Central Universities/ ; 20120524//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; Bombyx/genetics/growth & development/*physiology ; Cell Proliferation/*genetics ; Digestive System/metabolism ; Hedgehog Proteins/*genetics/metabolism ; Larva/genetics/growth & development/metabolism ; }, abstract = {The Hedgehog (Hh) signaling pathway is one of the major regulators of embryonic development and tissue homeostasis in multicellular organisms. However, the role of this pathway in the silkworm, especially in the silkworm midgut, remains poorly understood. Here, we report that Bombyx mori Hedgehog (BmHh) is expressed in most tissues of silkworm larvae and that its functions are well-conserved throughout evolution. We further demonstrate that the messenger RNA of four Hh signaling components, BmHh ligand, BmPtch receptor, signal transducer BmSmo and transcription factor BmCi, are all upregulated following Escherichia coli or Bacillus thuringiensis infection, indicating the activation of the Hh pathway. Simultaneously, midgut cell proliferation is strongly promoted. Conversely, the repression of Hh signal transduction with double-stranded RNA or cyclopamine inhibits the expression of BmHh and BmCi and reduces cell proliferation. Overall, these findings provide new insights into the Hh signaling pathway in the silkworm, B. mori.}, } @article {pmid30918953, year = {2019}, author = {Arimoto, A and Nishitsuji, K and Higa, Y and Arakaki, N and Hisata, K and Shinzato, C and Satoh, N and Shoguchi, E}, title = {A siphonous macroalgal genome suggests convergent functions of homeobox genes in algae and land plants.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {26}, number = {2}, pages = {183-192}, pmid = {30918953}, issn = {1756-1663}, mesh = {Caulerpa/*genetics ; Chlorophyta/genetics ; Embryophyta/genetics ; *Evolution, Molecular ; Gene Expression Profiling ; Genes, Homeobox/*genetics ; *Genome, Plant ; Genomics ; *Phylogeny ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; }, abstract = {Genome evolution and development of unicellular, multinucleate macroalgae (siphonous algae) are poorly known, although various multicellular organisms have been studied extensively. To understand macroalgal developmental evolution, we assembled the ∼26 Mb genome of a siphonous green alga, Caulerpa lentillifera, with high contiguity, containing 9,311 protein-coding genes. Molecular phylogeny using 107 nuclear genes indicates that the diversification of the class Ulvophyceae, including C. lentillifera, occurred before the split of the Chlorophyceae and Trebouxiophyceae. Compared with other green algae, the TALE superclass of homeobox genes, which expanded in land plants, shows a series of lineage-specific duplications in this siphonous macroalga. Plant hormone signalling components were also expanded in a lineage-specific manner. Expanded transport regulators, which show spatially different expression, suggest that the structural patterning strategy of a multinucleate cell depends on diversification of nuclear pore proteins. These results not only imply functional convergence of duplicated genes among green plants, but also provide insight into evolutionary roots of green plants. Based on the present results, we propose cellular and molecular mechanisms involved in the structural differentiation in the siphonous alga.}, } @article {pmid30915518, year = {2019}, author = {Kolasa, M and Ścibior, R and Mazur, MA and Kubisz, D and Dudek, K and Kajtoch, Ł}, title = {How Hosts Taxonomy, Trophy, and Endosymbionts Shape Microbiome Diversity in Beetles.}, journal = {Microbial ecology}, volume = {78}, number = {4}, pages = {995-1013}, pmid = {30915518}, issn = {1432-184X}, support = {DEC-2013/11/D/NZ8/00583//National Science Centre, Poland/ ; small grants for young researchers//Polish Ministry of Science and Higher Education/ ; }, mesh = {Animals ; Bacteria/*classification ; Bacterial Physiological Phenomena ; Coleoptera/classification/*microbiology/*physiology ; Feeding Behavior ; Microbiota/*physiology ; Phylogeny ; *Symbiosis ; }, abstract = {Bacterial communities play a crucial role in the biology, ecology, and evolution of multicellular organisms. In this research, the microbiome of 24 selected beetle species representing five families (Carabidae, Staphylinidae, Curculionidae, Chrysomelidae, Scarabaeidae) and three trophic guilds (carnivorous, herbivorous, detrivorous) was examined using 16S rDNA sequencing on the Illumina platform. The aim of the study was to compare diversity within and among species on various levels of organization, including evaluation of the impact of endosymbiotic bacteria. Collected data showed that beetles possess various bacterial communities and that microbiota of individuals of particular species hosts are intermixed. The most diverse microbiota were found in Carabidae and Scarabaeidae; the least diverse, in Staphylinidae. On higher organization levels, the diversity of bacteria was more dissimilar between families, while the most distinct with respect to their microbiomes were trophic guilds. Moreover, eight taxa of endosymbiotic bacteria were detected including common genera such as Wolbachia, Rickettsia, and Spiroplasma, as well as the rarely detected Cardinium, Arsenophonus, Buchnera, Sulcia, Regiella, and Serratia. There were no correlations among the abundance of the most common Wolbachia and Rickettsia; a finding that does not support the hypothesis that these bacteria occur interchangeably. The abundance of endosymbionts only weakly and negatively correlates with diversity of the whole microbiome in beetles. Overall, microbiome diversity was found to be more dependent on host phylogeny than on the abundance of endosymbionts. This is the first study in which bacteria diversity is compared between numerous species of beetles in a standardized manner.}, } @article {pmid30912879, year = {2019}, author = {Aripovsky, AV and Titov, VN}, title = {[Biologocally active peptides in metabolism regulation. Peptons, peptides, amino acids, fatty acids, lipoproteins, lipids, and the effect of nutriceuticals.].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {64}, number = {1}, pages = {14-23}, doi = {10.18821/0869-2084-2019-64-1-14-23}, pmid = {30912879}, issn = {0869-2084}, mesh = {Amino Acids ; Animals ; Dietary Proteins/metabolism ; *Dietary Supplements ; Fatty Acids ; Humans ; Lipids ; Lipoproteins ; Lysosomes ; Peptides/*metabolism ; Phylogeny ; Proteolysis ; }, abstract = {According to phylogenetic theory of general pathology, formation of multicellular organisms started when each cell (a unicellular organism) reached the first level of relative biological perfection. By that time the stimuli for perfection of the unicellular exhausted, and formation of the multicellular became a biological necessity. All cells, being associated, formed the second level of relative biological perfection within the principle of biological succession. The association included highly organized unicellular organisms with their specific autocrine biological functions and reactions. At the second level of relative biological perfection all humoral mediators in paracrine regulated cell communities (PC) and organs were predominantly hydrophilic and short living. They had a small molecular weight and were probably biologically active peptides (BAP). We believe that functional difference of PC and later of organs is based on differentiation of lysosomal function and production of various enzymes involved in proteolysis of dietary proteins. This allowed various PC and organs to form chemically and functionally different BAP pools from one protein upon proteolysis. Individual peptide pools in PC created the basis for morphologically and functionally different cells and organs. Cell that produces peptides can modify their concentration, chemical parameters and ratios by varying the selectivity of its proteases. In vivo regulation of metabolism by BAP has a common root in bacteria, plants and vertebrates, including Homo sapiens. The third level of relative biological perfection in the organism has formed in close association with cognitive biological function.}, } @article {pmid30912270, year = {2019}, author = {Hamant, O and Bhat, R and Nanjundiah, V and Newman, SA}, title = {Does resource availability help determine the evolutionary route to multicellularity?.}, journal = {Evolution & development}, volume = {21}, number = {3}, pages = {115-119}, pmid = {30912270}, issn = {1525-142X}, support = {ICTS/Prog-LivingMatter2018/04//International Centre for Theoretical Sciences (ICTS)/International ; ERC-2013-CoG-615739 "MechanoDevo"/ERC_/European Research Council/International ; 0412//CSIR/International ; 1586//SERB DST Early Career Grant/International ; }, mesh = {Animals ; *Biological Evolution ; *Gene Expression Regulation, Developmental ; *Genetic Variation ; }, abstract = {Genetic heterogeneity and homogeneity are associated with distinct sets of adaptive advantages and bottlenecks, both in developmental biology and population genetics. Whereas populations of individuals are usually genetically heterogeneous, most multicellular metazoans are genetically homogeneous. Observing that resource scarcity fuels genetic heterogeneity in populations, we propose that monoclonal development is compatible with the resource-rich and stable internal environments that complex multicellular bodies offer. In turn, polyclonal development persists in tumors and in certain metazoans, both exhibiting a closer dependence on external resources. This eco-evo-devo approach also suggests that multicellularity may originally have emerged through polyclonal development in early metazoans, because of their reduced shielding from environmental fluctuations.}, } @article {pmid30909510, year = {2019}, author = {Moffitt, L and Karimnia, N and Stephens, A and Bilandzic, M}, title = {Therapeutic Targeting of Collective Invasion in Ovarian Cancer.}, journal = {International journal of molecular sciences}, volume = {20}, number = {6}, pages = {}, pmid = {30909510}, issn = {1422-0067}, mesh = {Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; *Biomarkers, Tumor ; Clinical Studies as Topic ; Disease Management ; Drug Evaluation, Preclinical ; Female ; Humans ; *Molecular Targeted Therapy/methods ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplastic Stem Cells/drug effects/metabolism/pathology ; Ovarian Neoplasms/*etiology/pathology/*therapy ; Standard of Care ; Treatment Outcome ; }, abstract = {Ovarian cancer is the seventh most commonly diagnosed cancer amongst women and has the highest mortality rate of all gynaecological malignancies. It is a heterogeneous disease attributed to one of three cell types found within the reproductive milieu: epithelial, stromal, and germ cell. Each histotype differs in etiology, pathogenesis, molecular biology, risk factors, and prognosis. Furthermore, the origin of ovarian cancer remains unclear, with ovarian involvement secondary to the contribution of other gynaecological tissues. Despite these complexities, the disease is often treated as a single entity, resulting in minimal improvement to survival rates since the introduction of platinum-based chemotherapy over 30 years ago. Despite concerted research efforts, ovarian cancer remains one of the most difficult cancers to detect and treat, which is in part due to the unique mode of its dissemination. Ovarian cancers tend to invade locally to neighbouring tissues by direct extension from the primary tumour, and passively to pelvic and distal organs within the peritoneal fluid or ascites as multicellular spheroids. Once at their target tissue, ovarian cancers, like most epithelial cancers including colorectal, melanoma, and breast, tend to invade as a cohesive unit in a process termed collective invasion, driven by specialized cells termed "leader cells". Emerging evidence implicates leader cells as essential drivers of collective invasion and metastasis, identifying collective invasion and leader cells as a viable target for the management of metastatic disease. However, the development of targeted therapies specifically against this process and this subset of cells is lacking. Here, we review our understanding of metastasis, collective invasion, and the role of leader cells in ovarian cancer. We will discuss emerging research into the development of novel therapies targeting collective invasion and the leader cell population.}, } @article {pmid30904636, year = {2019}, author = {Setia, H and Muotri, AR}, title = {Brain organoids as a model system for human neurodevelopment and disease.}, journal = {Seminars in cell & developmental biology}, volume = {95}, number = {}, pages = {93-97}, pmid = {30904636}, issn = {1096-3634}, support = {R01 MH108528/MH/NIMH NIH HHS/United States ; R01 MH100175/MH/NIMH NIH HHS/United States ; R01 MH094753/MH/NIMH NIH HHS/United States ; R01 MH109885/MH/NIMH NIH HHS/United States ; R56 MH109587/MH/NIMH NIH HHS/United States ; }, mesh = {Brain/drug effects/*embryology/virology ; Environmental Pollutants/toxicity ; Humans ; *Models, Biological ; Nervous System Diseases/genetics/*pathology ; Organoids/drug effects/*embryology ; Viruses/metabolism ; }, abstract = {The ability to reproduce early stages of human neurodevelopment in the laboratory is one of the most exciting fields in modern neuroscience. The inaccessibility of the healthy human brain developing in utero has delayed our understanding of the initial steps in the formation of one of the most complex tissues in the body. Animal models, postmortem human tissues and cellular systems have been instrumental in contributing to our understanding of the human brain. However, all model systems have intrinsic limitations. The emerging field of brain organoids, which are three-dimensional self-assembled multicellular structures derived from human pluripotent stem cells, offers a promising complementary cellular model for the study of the human brain. Here, we will discuss the initial experiments that were the foundation for this emerging field, highlight recent uses of the technology and offer our perspective on future directions that might guide further exploratory experimentation to improve the human brain organoid model system.}, } @article {pmid30902897, year = {2019}, author = {Krizsán, K and Almási, É and Merényi, Z and Sahu, N and Virágh, M and Kószó, T and Mondo, S and Kiss, B and Bálint, B and Kües, U and Barry, K and Cseklye, J and Hegedüs, B and Henrissat, B and Johnson, J and Lipzen, A and Ohm, RA and Nagy, I and Pangilinan, J and Yan, J and Xiong, Y and Grigoriev, IV and Hibbett, DS and Nagy, LG}, title = {Transcriptomic atlas of mushroom development reveals conserved genes behind complex multicellularity in fungi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {15}, pages = {7409-7418}, pmid = {30902897}, issn = {1091-6490}, mesh = {*Agaricales/genetics/growth & development ; *Databases, Nucleic Acid ; *Fruiting Bodies, Fungal/genetics/growth & development ; *Fungal Proteins/biosynthesis/genetics ; Gene Expression Regulation, Fungal/physiology ; *Genes, Fungal ; Transcriptome/*physiology ; }, abstract = {The evolution of complex multicellularity has been one of the major transitions in the history of life. In contrast to simple multicellular aggregates of cells, it has evolved only in a handful of lineages, including animals, embryophytes, red and brown algae, and fungi. Despite being a key step toward the evolution of complex organisms, the evolutionary origins and the genetic underpinnings of complex multicellularity are incompletely known. The development of fungal fruiting bodies from a hyphal thallus represents a transition from simple to complex multicellularity that is inducible under laboratory conditions. We constructed a reference atlas of mushroom formation based on developmental transcriptome data of six species and comparisons of >200 whole genomes, to elucidate the core genetic program of complex multicellularity and fruiting body development in mushroom-forming fungi (Agaricomycetes). Nearly 300 conserved gene families and >70 functional groups contained developmentally regulated genes from five to six species, covering functions related to fungal cell wall remodeling, targeted protein degradation, signal transduction, adhesion, and small secreted proteins (including effector-like orphan genes). Several of these families, including F-box proteins, expansin-like proteins, protein kinases, and transcription factors, showed expansions in Agaricomycetes, many of which convergently expanded in multicellular plants and/or animals too, reflecting convergent solutions to genetic hurdles imposed by complex multicellularity among independently evolved lineages. This study provides an entry point to studying mushroom development and complex multicellularity in one of the largest clades of complex eukaryotic organisms.}, } @article {pmid30890741, year = {2019}, author = {Eilenberger, C and Rothbauer, M and Ehmoser, EK and Ertl, P and Küpcü, S}, title = {Effect of Spheroidal Age on Sorafenib Diffusivity and Toxicity in a 3D HepG2 Spheroid Model.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {4863}, pmid = {30890741}, issn = {2045-2322}, mesh = {*Cell Culture Techniques ; Cell Survival/*drug effects ; Hep G2 Cells ; Humans ; Sorafenib/*chemistry/toxicity ; Spheroids, Cellular/*drug effects ; }, abstract = {The enhanced predictive power of 3D multi-cellular spheroids in comparison to conventional monolayer cultures makes them a promising drug screening tool. However, clinical translation for pharmacology and toxicology is lagging its technological progression. Even though spheroids show a biological complexity resembling native tissue, standardization and validation of drug screening protocols are influenced by continuously changing physiological parameters during spheroid formation. Such cellular heterogeneities impede the comparability of drug efficacy studies and toxicological screenings. In this paper, we demonstrated that aside from already well-established physiological parameters, spheroidal age is an additional critical parameter that impacts drug diffusivity and toxicity in 3D cell culture models. HepG2 spheroids were generated and maintained on a self-assembled ultra-low attachment nanobiointerface and characterized regarding time-dependent changes in morphology, functionality as well as anti-cancer drug resistance. We demonstrated that spheroidal aging directly influences drug response due to the evolution of spheroid micro-structure and organo-typic functions, that alter inward diffusion, thus drug uptake.}, } @article {pmid30886348, year = {2019}, author = {Talbert, PB and Meers, MP and Henikoff, S}, title = {Old cogs, new tricks: the evolution of gene expression in a chromatin context.}, journal = {Nature reviews. Genetics}, volume = {20}, number = {5}, pages = {283-297}, pmid = {30886348}, issn = {1471-0064}, mesh = {Animals ; Biological Evolution ; *Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/genetics/history/metabolism ; DNA/*genetics/history/metabolism ; Eukaryotic Cells/cytology/metabolism ; *Genome ; Genomics/methods ; Histones/genetics/history/metabolism ; History, 21st Century ; History, Ancient ; Humans ; Nucleosomes/chemistry/*genetics/metabolism ; Prokaryotic Cells/cytology/metabolism ; Transcription Factors/genetics/history/metabolism ; *Transcription, Genetic ; }, abstract = {Sophisticated gene-regulatory mechanisms probably evolved in prokaryotes billions of years before the emergence of modern eukaryotes, which inherited the same basic enzymatic machineries. However, the epigenomic landscapes of eukaryotes are dominated by nucleosomes, which have acquired roles in genome packaging, mitotic condensation and silencing parasitic genomic elements. Although the molecular mechanisms by which nucleosomes are displaced and modified have been described, just how transcription factors, histone variants and modifications and chromatin regulators act on nucleosomes to regulate transcription is the subject of considerable ongoing study. We explore the extent to which these transcriptional regulatory components function in the context of the evolutionarily ancient role of chromatin as a barrier to processes acting on DNA and how chromatin proteins have diversified to carry out evolutionarily recent functions that accompanied the emergence of differentiation and development in multicellular eukaryotes.}, } @article {pmid30886148, year = {2019}, author = {Xu, S and Stapley, J and Gablenz, S and Boyer, J and Appenroth, KJ and Sree, KS and Gershenzon, J and Widmer, A and Huber, M}, title = {Low genetic variation is associated with low mutation rate in the giant duckweed.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {1243}, pmid = {30886148}, issn = {2041-1723}, mesh = {Africa ; Americas ; Araceae/classification/*genetics ; Asia ; DNA Mutational Analysis ; Europe ; *Genetic Variation ; *Genome, Plant ; *Mutation Rate ; Phylogeography ; Plant Dispersal/*genetics ; }, abstract = {Mutation rate and effective population size (Ne) jointly determine intraspecific genetic diversity, but the role of mutation rate is often ignored. Here we investigate genetic diversity, spontaneous mutation rate and Ne in the giant duckweed (Spirodela polyrhiza). Despite its large census population size, whole-genome sequencing of 68 globally sampled individuals reveals extremely low intraspecific genetic diversity. Assessed under natural conditions, the genome-wide spontaneous mutation rate is at least seven times lower than estimates made for other multicellular eukaryotes, whereas Ne is large. These results demonstrate that low genetic diversity can be associated with large-Ne species, where selection can reduce mutation rates to very low levels. This study also highlights that accurate estimates of mutation rate can help to explain seemingly unexpected patterns of genome-wide variation.}, } @article {pmid30883720, year = {2019}, author = {Kapsetaki, SE and West, SA}, title = {The costs and benefits of multicellular group formation in algae.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {6}, pages = {1296-1308}, doi = {10.1111/evo.13712}, pmid = {30883720}, issn = {1558-5646}, support = {//Alexander S. Onassis Public Benefit Foundation/International ; /ERC_/European Research Council/International ; //A.G. Leventis Foundation/International ; }, mesh = {Animals ; Biological Evolution ; Chlorella/*physiology ; Cost-Benefit Analysis ; Daphnia/*physiology ; *Food Chain ; *Life History Traits ; Microbial Interactions ; Ochromonas/*physiology ; *Predatory Behavior ; }, abstract = {The first step in the evolution of complex multicellular organisms involves single cells forming a cooperative group. Consequently, to understand multicellularity, we need to understand the costs and benefits associated with multicellular group formation. We found that in the facultatively multicellular algae Chlorella sorokiniana: (1) the presence of the flagellate Ochromonas danica or the crustacean Daphnia magna leads to the formation of multicellular groups; (2) the formation of multicellular groups reduces predation by O. danica, but not by the larger predator D. magna; (3) under conditions of relatively low light intensity, where competition for light is greater, multicellular groups grow slower than single cells; (4) in the absence of live predators, the proportion of cells in multicellular groups decreases at a rate that does not vary with light intensity. These results can explain why, in cases such as this algae species, multicellular group formation is facultative, in response to the presence of predators.}, } @article {pmid30863851, year = {2019}, author = {Shoemark, DK and Ziegler, B and Watanabe, H and Strompen, J and Tucker, RP and Özbek, S and Adams, JC}, title = {Emergence of a Thrombospondin Superfamily at the Origin of Metazoans.}, journal = {Molecular biology and evolution}, volume = {36}, number = {6}, pages = {1220-1238}, pmid = {30863851}, issn = {1537-1719}, support = {MR/K018043/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Anthozoa/genetics/metabolism ; *Biological Evolution ; Hydra/physiology ; Invertebrates/*genetics ; Multigene Family ; Thrombospondins/*genetics/metabolism ; }, abstract = {Extracellular matrix (ECM) is considered central to the evolution of metazoan multicellularity; however, the repertoire of ECM proteins in nonbilaterians remains unclear. Thrombospondins (TSPs) are known to be well conserved from cnidarians to vertebrates, yet to date have been considered a unique family, principally studied for matricellular functions in vertebrates. Through searches utilizing the highly conserved C-terminal region of TSPs, we identify undisclosed new families of TSP-related proteins in metazoans, designated mega-TSP, sushi-TSP, and poriferan-TSP, each with a distinctive phylogenetic distribution. These proteins share the TSP C-terminal region domain architecture, as determined by domain composition and analysis of molecular models against known structures. Mega-TSPs, the only form identified in ctenophores, are typically >2,700 aa and are also characterized by N-terminal leucine-rich repeats and central cadherin/immunoglobulin domains. In cnidarians, which have a well-defined ECM, Mega-TSP was expressed throughout embryogenesis in Nematostella vectensis, with dynamic endodermal expression in larvae and primary polyps and widespread ectodermal expression in adult Nematostella vectensis and Hydra magnipapillata polyps. Hydra Mega-TSP was also expressed during regeneration and siRNA-silencing of Mega-TSP in Hydra caused specific blockade of head regeneration. Molecular phylogenetic analyses based on the conserved TSP C-terminal region identified each of the TSP-related groups to form clades distinct from the canonical TSPs. We discuss models for the evolution of the newly defined TSP superfamily by gene duplications, radiation, and gene losses from a debut in the last metazoan common ancestor. Together, the data provide new insight into the evolution of ECM and tissue organization in metazoans.}, } @article {pmid30862622, year = {2019}, author = {Lenhart, BA and Meeks, B and Murphy, HA}, title = {Variation in Filamentous Growth and Response to Quorum-Sensing Compounds in Environmental Isolates of Saccharomyces cerevisiae.}, journal = {G3 (Bethesda, Md.)}, volume = {9}, number = {5}, pages = {1533-1544}, pmid = {30862622}, issn = {2160-1836}, support = {R15 GM122032/GM/NIGMS NIH HHS/United States ; }, mesh = {*Environmental Microbiology ; *Gene-Environment Interaction ; *Genetic Variation ; Genome, Fungal ; Genomics/methods ; Hyphae ; Polymorphism, Single Nucleotide ; *Quorum Sensing/drug effects ; Saccharomyces cerevisiae/drug effects/isolation & purification/*physiology ; }, abstract = {In fungi, filamentous growth is a major developmental transition that occurs in response to environmental cues. In diploid Saccharomyces cerevisiae, it is known as pseudohyphal growth and presumed to be a foraging mechanism. Rather than unicellular growth, multicellular filaments composed of elongated, attached cells spread over and into surfaces. This morphogenetic switch can be induced through quorum sensing with the aromatic alcohols phenylethanol and tryptophol. Most research investigating pseudohyphal growth has been conducted in a single lab background, Σ1278b. To investigate the natural variation in this phenotype and its induction, we assayed the diverse 100-genomes collection of environmental isolates. Using computational image analysis, we quantified the production of pseudohyphae and observed a large amount of variation. Population origin was significantly associated with pseudohyphal growth, with the West African population having the most. Surprisingly, most strains showed little or no response to exogenous phenylethanol or tryptophol. We also investigated the amount of natural genetic variation in pseudohyphal growth using a mapping population derived from a highly-heterozygous clinical isolate that contained as much phenotypic variation as the environmental panel. A bulk-segregant analysis uncovered five major peaks with candidate loci that have been implicated in the Σ1278b background. Our results indicate that the filamentous growth response is a generalized, highly variable phenotype in natural populations, while response to quorum sensing molecules is surprisingly rare. These findings highlight the importance of coupling studies in tractable lab strains with natural isolates in order to understand the relevance and distribution of well-studied traits.}, } @article {pmid30860988, year = {2019}, author = {Riahi, H and Brekelmans, C and Foriel, S and Merkling, SH and Lyons, TA and Itskov, PM and Kleefstra, T and Ribeiro, C and van Rij, RP and Kramer, JM and Schenck, A}, title = {The histone methyltransferase G9a regulates tolerance to oxidative stress-induced energy consumption.}, journal = {PLoS biology}, volume = {17}, number = {3}, pages = {e2006146}, pmid = {30860988}, issn = {1545-7885}, mesh = {Animals ; Antioxidants/metabolism ; Energy Metabolism/genetics/physiology ; Epigenesis, Genetic/genetics ; Glycogen Phosphorylase/genetics/metabolism ; Histone Methyltransferases/genetics/*metabolism ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Humans ; Male ; Oxidative Stress/genetics/physiology ; Phylogeny ; Sequence Analysis, RNA ; }, abstract = {Stress responses are crucial processes that require activation of genetic programs that protect from the stressor. Stress responses are also energy consuming and can thus be deleterious to the organism. The mechanisms coordinating energy consumption during stress response in multicellular organisms are not well understood. Here, we show that loss of the epigenetic regulator G9a in Drosophila causes a shift in the transcriptional and metabolic responses to oxidative stress (OS) that leads to decreased survival time upon feeding the xenobiotic paraquat. During OS exposure, G9a mutants show overactivation of stress response genes, rapid depletion of glycogen, and inability to access lipid energy stores. The OS survival deficiency of G9a mutants can be rescued by a high-sugar diet. Control flies also show improved OS survival when fed a high-sugar diet, suggesting that energy availability is generally a limiting factor for OS tolerance. Directly limiting access to glycogen stores by knocking down glycogen phosphorylase recapitulates the OS-induced survival defects of G9a mutants. We propose that G9a mutants are sensitive to stress because they experience a net reduction in available energy due to (1) rapid glycogen use, (2) an inability to access lipid energy stores, and (3) an overinduced transcriptional response to stress that further exacerbates energy demands. This suggests that G9a acts as a critical regulatory hub between the transcriptional and metabolic responses to OS. Our findings, together with recent studies that established a role for G9a in hypoxia resistance in cancer cell lines, suggest that G9a is of wide importance in controlling the cellular and organismal response to multiple types of stress.}, } @article {pmid30857590, year = {2019}, author = {Sicard, A and Pirolles, E and Gallet, R and Vernerey, MS and Yvon, M and Urbino, C and Peterschmitt, M and Gutierrez, S and Michalakis, Y and Blanc, S}, title = {A multicellular way of life for a multipartite virus.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {30857590}, issn = {2050-084X}, support = {ANR-14-CE02-0014//Agence Nationale de la Recherche/International ; }, mesh = {DNA Viruses ; DNA, Viral/*genetics ; *Genome, Viral ; In Situ Hybridization, Fluorescence ; Microscopy, Confocal ; Nanovirus/*genetics/physiology ; Plant Diseases/*virology ; Regression Analysis ; Vicia faba/*virology ; Virion/*genetics ; Virus Replication ; }, abstract = {A founding paradigm in virology is that the spatial unit of the viral replication cycle is an individual cell. Multipartite viruses have a segmented genome where each segment is encapsidated separately. In this situation the viral genome is not recapitulated in a single virus particle but in the viral population. How multipartite viruses manage to efficiently infect individual cells with all segments, thus with the whole genome information, is a long-standing but perhaps deceptive mystery. By localizing and quantifying the genome segments of a nanovirus in host plant tissues we show that they rarely co-occur within individual cells. We further demonstrate that distinct segments accumulate independently in different cells and that the viral system is functional through complementation across cells. Our observation deviates from the classical conceptual framework in virology and opens an alternative possibility (at least for nanoviruses) where the infection can operate at a level above the individual cell level, defining a viral multicellular way of life.}, } @article {pmid30851154, year = {2019}, author = {Kalsoom, N and Zafar, M and Ahmad, M and Sultana, S and Usma, A and Jabeen, A}, title = {Investigating Schizocarp morphology as a taxonomic tool in study of Apiaceae family by utilizing LM and SEM techniques.}, journal = {Microscopy research and technique}, volume = {82}, number = {7}, pages = {1012-1020}, doi = {10.1002/jemt.23248}, pmid = {30851154}, issn = {1097-0029}, mesh = {Apiaceae/*anatomy & histology/*classification ; Fruit/*anatomy & histology/ultrastructure ; *Microscopy ; *Microscopy, Electron, Scanning ; Phylogeny ; Pollen ; }, abstract = {In present study, the schizocarp morphology of 14 species belonging to Apiaceae family has been investigated. Light microscopy (LM) and scanning electron microscopy (SEM) have been utilized to highlight qualitative and quantitative features of studied species. Variations have been observed in macro- and micro-morphological features such as color, shape, symmetry, length, width, apex, epicuticular projections, surface patterns, anticlinal, and periclinal wall patterns. Schizocarp shapes observed were oval, round, triangular, linear, elliptic, and globose. Fruit was either homomorphic or heteromorphic. Crystalloids, stellate hair, multicellular spines, and platelets were mostly observed epicuticular projections. Surface patterns on the fruit surface were striate, rugulate-striate, reticulate, and striato-knotted. Both macro- and micro-morphological characters can serve as an important tool in classifying Apiaceae family at various taxonomic ranks. Substantial variations observed can assist as useful constraints at various taxonomic levels as they provide reliable and constant details. Disparities observed in schizocarp features can pave a path for Apiaceae family classification based on phylogenetic and molecular studies.}, } @article {pmid30848356, year = {2019}, author = {Bondarenko, N and Bondarenko, A and Starunov, V and Slyusarev, G}, title = {Comparative analysis of the mitochondrial genomes of Orthonectida: insights into the evolution of an invertebrate parasite species.}, journal = {Molecular genetics and genomics : MGG}, volume = {294}, number = {3}, pages = {715-727}, pmid = {30848356}, issn = {1617-4623}, support = {19-04-0021//Russian Foundation for Basic Research/ ; 17-74-10103//Russian Science Foundation/ ; 1.40.496.2017//Saint Petersburg State University/ ; }, mesh = {Animals ; Base Composition/genetics ; DNA, Mitochondrial/chemistry/genetics ; *Evolution, Molecular ; Gastropoda/parasitology ; *Gene Order ; Genes, Mitochondrial/*genetics ; Genome, Mitochondrial/*genetics ; Helminths/parasitology ; Host-Parasite Interactions ; Invertebrates/classification/*genetics/physiology ; Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Among invertebrates, only a few groups still have uncertain phylogenetic position, Orthonectida, a small group of rare multi-cellular parasites of marine invertebrates, being one of them. Recent molecular and morphological findings suggest that orthonectids belong to Lophotrochozoa and are close to Annelida. Nevertheless, phylogenetic relationships between orthonectids and annelids are unclear, and the phylogeny within the group itself has never been studied. Sequencing of mitochondrial genomes is used here to clarify this issue. Complete mt genomes of the orthonectids Intoshia variabili and Rhopalura litoralis were characterized and compared with Intoshia linei mt genome. Our results show that Orthonectida mt genomes have undergone reduction and gene loss, and that they have complicated organization revealed in strand asymmetry in nucleotide composition, in some features of intergenic non-coding regions, tRNA duplication and folding. Moreover, all species of Orthonectida have a unique gene order with complicated rearrangement landscape. Significant differences in mitochondrial genomes in the three orthonectid species could be explained by the fact that their host species belong to different taxa (flat worms, nemertines and gastropods). Among the analyzed mt genomes of Orthonectida, I. linei possesses the closest gene order to the ancestral genome. All Orthonectida species are monophyletic, and in the phylogenetic tree are close to Pleistoannelida, and specifically, to Clitellata.}, } @article {pmid30846531, year = {2019}, author = {Sequeira-Mendes, J and Vergara, Z and Peiró, R and Morata, J and Aragüez, I and Costas, C and Mendez-Giraldez, R and Casacuberta, JM and Bastolla, U and Gutierrez, C}, title = {Differences in firing efficiency, chromatin, and transcription underlie the developmental plasticity of the Arabidopsis DNA replication origins.}, journal = {Genome research}, volume = {29}, number = {5}, pages = {784-797}, pmid = {30846531}, issn = {1549-5469}, mesh = {Arabidopsis/*genetics/growth & development ; Base Composition/genetics ; Cells, Cultured ; Chromatin/metabolism ; *DNA Replication ; Heterochromatin/*genetics ; Replication Origin/*genetics ; Retroelements/genetics ; Transcription Initiation Site ; Transcription, Genetic ; }, abstract = {Eukaryotic genome replication depends on thousands of DNA replication origins (ORIs). A major challenge is to learn ORI biology in multicellular organisms in the context of growing organs to understand their developmental plasticity. We have identified a set of ORIs of Arabidopsis thaliana and their chromatin landscape at two stages of post-embryonic development. ORIs associate with multiple chromatin signatures including transcription start sites (TSS) but also proximal and distal regulatory regions and heterochromatin, where ORIs colocalize with retrotransposons. In addition, quantitative analysis of ORI activity led us to conclude that strong ORIs have high GC content and clusters of GGN trinucleotides. Development primarily influences ORI firing strength rather than ORI location. ORIs that preferentially fire at early developmental stages colocalize with GC-rich heterochromatin, but at later stages with transcribed genes, perhaps as a consequence of changes in chromatin features associated with developmental processes. Our study provides the set of ORIs active in an organism at the post-embryo stage that should allow us to study ORI biology in response to development, environment, and mutations with a quantitative approach. In a wider scope, the computational strategies developed here can be transferred to other eukaryotic systems.}, } @article {pmid30839008, year = {2019}, author = {Ruiz, MC and Kljun, J and Turel, I and Di Virgilio, AL and León, IE}, title = {Comparative antitumor studies of organoruthenium complexes with 8-hydroxyquinolines on 2D and 3D cell models of bone, lung and breast cancer.}, journal = {Metallomics : integrated biometal science}, volume = {11}, number = {3}, pages = {666-675}, doi = {10.1039/c8mt00369f}, pmid = {30839008}, issn = {1756-591X}, mesh = {Antineoplastic Agents/chemistry/*pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cisplatin/chemistry/pharmacology ; Humans ; Models, Biological ; Neoplasms/*metabolism ; Organometallic Compounds/chemistry/*pharmacology ; Oxyquinoline/chemistry/*pharmacology ; Ruthenium/pharmacology ; Ruthenium Compounds/chemistry/*pharmacology ; }, abstract = {The purpose of this work was to screen the antitumor actions of two metal organoruthenium-8-hydroxyquinolinato (Ru-hq) complexes to find a potential novel agent for bone, lung and breast chemotherapies. We showed that ruthenium compounds (1 and 2) impaired the cell viability of human bone (MG-63), lung (A549) and breast (MCF7) cancer cells with greater selectivity and specificity than cisplatin. Besides, complexes 1 and 2 decreased proliferation, migration and invasion on cell monolayers at lower concentrations (2.5-10 μM). In addition, both compounds induced genotoxicity revealed by the micronucleus test, which led to G2/M cell cycle arrest and induced the tumor cells to undergo apoptosis. On the other hand, in multicellular 3D models (multicellular spheroids; MCS), 1 and 2 overcame CDDP presenting lower IC50 values only in MCS of lung origin. Moreover, 1 outperformed 2 in MCS of bone and breast origin. Finally, our findings revealed that both compounds inhibited the cell invasion of multicellular spheroids, showing that complex 1 exhibited the most important antimetastatic action. Taken together, these results indicate that compound 1 is an interesting candidate to be tested on in vivo models as a novel strategy for anticancer therapy.}, } @article {pmid30826447, year = {2019}, author = {Fillinger, RJ and Anderson, MZ}, title = {Seasons of change: Mechanisms of genome evolution in human fungal pathogens.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {70}, number = {}, pages = {165-174}, doi = {10.1016/j.meegid.2019.02.031}, pmid = {30826447}, issn = {1567-7257}, mesh = {Evolution, Molecular ; Fungi/*genetics/*pathogenicity ; Genome, Fungal/*genetics ; Genomics ; Humans ; Mycoses/etiology/*genetics ; }, abstract = {Fungi are a diverse kingdom of organisms capable of thriving in various niches across the world including those in close association with multicellular eukaryotes. Fungal pathogens that contribute to human disease reside both within the host as commensal organisms of the microbiota and the environment. Their niche of origin dictates how infection initiates but also places specific selective pressures on the fungal pathogen that contributes to its genome organization and genetic repertoire. Recent efforts to catalogue genomic variation among major human fungal pathogens have unveiled evolutionary themes that shape the fungal genome. Mechanisms ranging from large scale changes such as aneuploidy and ploidy cycling as well as more targeted mutations like base substitutions and gene copy number variations contribute to the evolution of these species, which are often under multiple competing selective pressures with their host, environment, and other microbes. Here, we provide an overview of the major selective pressures and mechanisms acting to evolve the genome of clinically important fungal pathogens of humans.}, } @article {pmid30824779, year = {2019}, author = {Kabir, M and Wenlock, S and Doig, AJ and Hentges, KE}, title = {The Essentiality Status of Mouse Duplicate Gene Pairs Correlates with Developmental Co-Expression Patterns.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {3224}, pmid = {30824779}, issn = {2045-2322}, support = {BB/L018276/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Algorithms ; Animals ; Animals, Newborn ; Embryonic Development/*genetics ; Evolution, Molecular ; *Gene Duplication ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Developmental ; Genes, Duplicate/*genetics ; Genes, Essential/*genetics ; Humans ; Mice ; Models, Genetic ; Organogenesis/genetics ; }, abstract = {During the evolution of multicellular eukaryotes, gene duplication occurs frequently to generate new genes and/or functions. A duplicated gene may have a similar function to its ancestral gene. Therefore, it may be expected that duplicated genes are less likely to be critical for the survival of an organism, since there are multiple copies of the gene rendering each individual copy redundant. In this study, we explored the developmental expression patterns of duplicate gene pairs and the relationship between development co-expression and phenotypes resulting from the knockout of duplicate genes in the mouse. We define genes that generate lethal phenotypes in single gene knockout experiments as essential genes. We found that duplicate gene pairs comprised of two essential genes tend to be expressed at different stages of development, compared to duplicate gene pairs with at least one non-essential member, showing that the timing of developmental expression affects the ability of one paralogue to compensate for the loss of the other. Gene essentiality, developmental expression and gene duplication are thus closely linked.}, } @article {pmid30824706, year = {2019}, author = {Lurgi, M and Thomas, T and Wemheuer, B and Webster, NS and Montoya, JM}, title = {Modularity and predicted functions of the global sponge-microbiome network.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {992}, pmid = {30824706}, issn = {2041-1723}, mesh = {Animals ; Bacteria/classification/genetics ; Biodiversity ; Biological Evolution ; Ecology ; Host Microbial Interactions/*physiology ; Microbiota/genetics/*physiology ; Phylogeny ; Porifera/classification/*microbiology ; RNA, Ribosomal, 16S/genetics ; Species Specificity ; Symbiosis ; }, abstract = {Defining the organisation of species interaction networks and unveiling the processes behind their assembly is fundamental to understanding patterns of biodiversity, community stability and ecosystem functioning. Marine sponges host complex communities of microorganisms that contribute to their health and survival, yet the mechanisms behind microbiome assembly are largely unknown. We present the global marine sponge-microbiome network and reveal a modular organisation in both community structure and function. Modules are linked by a few sponge species that share microbes with other species around the world. Further, we provide evidence that abiotic factors influence the structuring of the sponge microbiome when considering all microbes present, but biotic interactions drive the assembly of more intimately associated 'core' microorganisms. These findings suggest that both ecological and evolutionary processes are at play in host-microbe network assembly. We expect mechanisms behind microbiome assembly to be consistent across multicellular hosts throughout the tree of life.}, } @article {pmid30803482, year = {2019}, author = {Trigos, AS and Pearson, RB and Papenfuss, AT and Goode, DL}, title = {Somatic mutations in early metazoan genes disrupt regulatory links between unicellular and multicellular genes in cancer.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {30803482}, issn = {2050-084X}, mesh = {Carcinogenesis ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; *Cell Transformation, Neoplastic ; Gene Dosage ; *Gene Regulatory Networks ; *Genes, Regulator ; Humans ; Neoplasms/*pathology ; *Point Mutation ; Transcription, Genetic ; }, abstract = {Extensive transcriptional alterations are observed in cancer, many of which activate core biological processes established in unicellular organisms or suppress differentiation pathways formed in metazoans. Through rigorous, integrative analysis of genomics data from a range of solid tumors, we show many transcriptional changes in tumors are tied to mutations disrupting regulatory interactions between unicellular and multicellular genes within human gene regulatory networks (GRNs). Recurrent point mutations were enriched in regulator genes linking unicellular and multicellular subnetworks, while copy-number alterations affected downstream target genes in distinctly unicellular and multicellular regions of the GRN. Our results depict drivers of tumourigenesis as genes that created key regulatory links during the evolution of early multicellular life, whose dysfunction creates widespread dysregulation of primitive elements of the GRN. Several genes we identified as important in this process were associated with drug response, demonstrating the potential clinical value of our approach.}, } @article {pmid30799483, year = {2019}, author = {Xie, P and Gao, M and Wang, C and Zhang, J and Noel, P and Yang, C and Von Hoff, D and Han, H and Zhang, MQ and Lin, W}, title = {SuperCT: a supervised-learning framework for enhanced characterization of single-cell transcriptomic profiles.}, journal = {Nucleic acids research}, volume = {47}, number = {8}, pages = {e48}, pmid = {30799483}, issn = {1362-4962}, support = {R01 MH109665/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cell Lineage/genetics ; Cluster Analysis ; Datasets as Topic ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; High-Throughput Nucleotide Sequencing ; Humans ; Mice ; Pancreatic Neoplasms/*genetics ; RNA, Small Cytoplasmic/genetics ; Sequence Analysis, RNA ; Single-Cell Analysis/*statistics & numerical data ; *Software ; *Supervised Machine Learning ; *Transcriptome ; }, abstract = {Characterization of individual cell types is fundamental to the study of multicellular samples. Single-cell RNAseq techniques, which allow high-throughput expression profiling of individual cells, have significantly advanced our ability of this task. Currently, most of the scRNA-seq data analyses are commenced with unsupervised clustering. Clusters are often assigned to different cell types based on the enriched canonical markers. However, this process is inefficient and arbitrary. In this study, we present a technical framework of training the expandable supervised-classifier in order to reveal the single-cell identities as soon as the single-cell expression profile is input. Using multiple scRNA-seq datasets we demonstrate the superior accuracy, robustness, compatibility and expandability of this new solution compared to the traditional methods. We use two examples of the model upgrade to demonstrate how the projected evolution of the cell-type classifier is realized.}, } @article {pmid30796309, year = {2019}, author = {Zhang, L and Tan, Y and Fan, S and Zhang, X and Zhang, Z}, title = {Phylostratigraphic analysis of gene co-expression network reveals the evolution of functional modules for ovarian cancer.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {2623}, pmid = {30796309}, issn = {2045-2322}, support = {31800185//National Natural Science Foundation of China (National Science Foundation of China)/International ; 31800185//National Natural Science Foundation of China (National Science Foundation of China)/International ; }, mesh = {Biomarkers, Tumor/genetics ; Databases, Genetic ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Genome, Human ; Humans ; Ovarian Neoplasms/*genetics ; *Phylogeny ; }, abstract = {Ovarian cancer (OV) is an extremely lethal disease. However, the evolutionary machineries of OV are still largely unknown. Here, we used a method that combines phylostratigraphy information with gene co-expression networks to extensively study the evolutionary compositions of OV. The present co-expression network construction yielded 18,549 nodes and 114,985 edges based on 307 OV expression samples obtained from the Genome Data Analysis Centers database. A total of 20 modules were identified as OV related clusters. The human genome sequences were divided into 19 phylostrata (PS), the majority (67.45%) of OV genes was already present in the eukaryotic ancestor. There were two strong peaks of the emergence of OV genes screened by hypergeometric test: the evolution of the multicellular metazoan organisms (PS5 and PS6, P value = 0.002) and the emergence of bony fish (PS11 and PS12, P value = 0.009). Hence, the origin of OV is far earlier than its emergence. The integrated analysis of the topology of OV modules and the phylogenetic data revealed an evolutionary pattern of OV in human, namely, OV modules have arisen step by step during the evolution of the respective lineages. New genes have evolved and become locked into a pathway, where more and more biological pathways are fixed into OV modules by recruiting new genes during human evolution.}, } @article {pmid30794780, year = {2019}, author = {Tucci, V and Isles, AR and Kelsey, G and Ferguson-Smith, AC and , }, title = {Genomic Imprinting and Physiological Processes in Mammals.}, journal = {Cell}, volume = {176}, number = {5}, pages = {952-965}, doi = {10.1016/j.cell.2019.01.043}, pmid = {30794780}, issn = {1097-4172}, support = {210757/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; 210757/Z/18/WT_/Wellcome Trust/United Kingdom ; MR/K011332/1/MRC_/Medical Research Council/United Kingdom ; BB/P002307/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/S000437/1/MRC_/Medical Research Council/United Kingdom ; MR/R022836/1/MRC_/Medical Research Council/United Kingdom ; BBS/E/B/000C0426/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/R009791/1/MRC_/Medical Research Council/United Kingdom ; BB/P008623/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/L010305/1/MRC_/Medical Research Council/United Kingdom ; MR/S00002X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Alleles ; Animals ; Biological Evolution ; Chromosomes ; DNA Methylation ; Epigenesis, Genetic/genetics/physiology ; Genomic Imprinting/*genetics/*physiology ; Mammals/*genetics/metabolism ; Physiological Phenomena ; }, abstract = {Complex multicellular organisms, such as mammals, express two complete sets of chromosomes per nucleus, combining the genetic material of both parents. However, epigenetic studies have demonstrated violations to this rule that are necessary for mammalian physiology; the most notable parental allele expression phenomenon is genomic imprinting. With the identification of endogenous imprinted genes, genomic imprinting became well-established as an epigenetic mechanism in which the expression pattern of a parental allele influences phenotypic expression. The expanding study of genomic imprinting is revealing a significant impact on brain functions and associated diseases. Here, we review key milestones in the field of imprinting and discuss mechanisms and systems in which imprinted genes exert a significant role.}, } @article {pmid30787483, year = {2019}, author = {Herron, MD and Borin, JM and Boswell, JC and Walker, J and Chen, IK and Knox, CA and Boyd, M and Rosenzweig, F and Ratcliff, WC}, title = {De novo origins of multicellularity in response to predation.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {2328}, pmid = {30787483}, issn = {2045-2322}, mesh = {Animals ; Cell Count ; Chlamydomonas reinhardtii/*cytology/ultrastructure ; Predatory Behavior/*physiology ; Rotifera/physiology ; }, abstract = {The transition from unicellular to multicellular life was one of a few major events in the history of life that created new opportunities for more complex biological systems to evolve. Predation is hypothesized as one selective pressure that may have driven the evolution of multicellularity. Here we show that de novo origins of simple multicellularity can evolve in response to predation. We subjected outcrossed populations of the unicellular green alga Chlamydomonas reinhardtii to selection by the filter-feeding predator Paramecium tetraurelia. Two of five experimental populations evolved multicellular structures not observed in unselected control populations within ~750 asexual generations. Considerable variation exists in the evolved multicellular life cycles, with both cell number and propagule size varying among isolates. Survival assays show that evolved multicellular traits provide effective protection against predation. These results support the hypothesis that selection imposed by predators may have played a role in some origins of multicellularity.}, } @article {pmid30787193, year = {2019}, author = {Dunning, LT and Olofsson, JK and Parisod, C and Choudhury, RR and Moreno-Villena, JJ and Yang, Y and Dionora, J and Quick, WP and Park, M and Bennetzen, JL and Besnard, G and Nosil, P and Osborne, CP and Christin, PA}, title = {Lateral transfers of large DNA fragments spread functional genes among grasses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {10}, pages = {4416-4425}, pmid = {30787193}, issn = {1091-6490}, support = {638333/ERC_/European Research Council/International ; MR/K001744/1/MRC_/Medical Research Council/United Kingdom ; BB/J004243/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Chromosomes, Plant ; DNA, Plant/*genetics ; *Gene Transfer, Horizontal ; *Genes, Plant ; Phylogeny ; Poaceae/classification/*genetics ; }, abstract = {A fundamental tenet of multicellular eukaryotic evolution is that vertical inheritance is paramount, with natural selection acting on genetic variants transferred from parents to offspring. This lineal process means that an organism's adaptive potential can be restricted by its evolutionary history, the amount of standing genetic variation, and its mutation rate. Lateral gene transfer (LGT) theoretically provides a mechanism to bypass many of these limitations, but the evolutionary importance and frequency of this process in multicellular eukaryotes, such as plants, remains debated. We address this issue by assembling a chromosome-level genome for the grass Alloteropsis semialata, a species surmised to exhibit two LGTs, and screen it for other grass-to-grass LGTs using genomic data from 146 other grass species. Through stringent phylogenomic analyses, we discovered 57 additional LGTs in the A. semialata nuclear genome, involving at least nine different donor species. The LGTs are clustered in 23 laterally acquired genomic fragments that are up to 170 kb long and have accumulated during the diversification of Alloteropsis. The majority of the 59 LGTs in A. semialata are expressed, and we show that they have added functions to the recipient genome. Functional LGTs were further detected in the genomes of five other grass species, demonstrating that this process is likely widespread in this globally important group of plants. LGT therefore appears to represent a potent evolutionary force capable of spreading functional genes among distantly related grass species.}, } @article {pmid30764885, year = {2019}, author = {Lipinska, AP and Serrano-Serrano, ML and Cormier, A and Peters, AF and Kogame, K and Cock, JM and Coelho, SM}, title = {Rapid turnover of life-cycle-related genes in the brown algae.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {35}, pmid = {30764885}, issn = {1474-760X}, support = {638240//European Research Council/International ; }, mesh = {*Evolution, Molecular ; Gene Duplication ; *Gene Expression ; Germ Cells, Plant ; Life Cycle Stages/*genetics ; Phaeophyceae/*genetics/growth & development/metabolism ; Phenotype ; *Selection, Genetic ; }, abstract = {BACKGROUND: Sexual life cycles in eukaryotes involve a cyclic alternation between haploid and diploid phases. While most animals possess a diploid life cycle, many plants and algae alternate between multicellular haploid (gametophyte) and diploid (sporophyte) generations. In many algae, gametophytes and sporophytes are independent and free-living and may present dramatic phenotypic differences. The same shared genome can therefore be subject to different, even conflicting, selection pressures during each of the life cycle generations. Here, we analyze the nature and extent of genome-wide, generation-biased gene expression in four species of brown algae with contrasting levels of dimorphism between life cycle generations.

RESULTS: We show that the proportion of the transcriptome that is generation-specific is broadly associated with the level of phenotypic dimorphism between the life cycle stages. Importantly, our data reveals a remarkably high turnover rate for life-cycle-related gene sets across the brown algae and highlights the importance not only of co-option of regulatory programs from one generation to the other but also of a role for newly emerged, lineage-specific gene expression patterns in the evolution of the gametophyte and sporophyte developmental programs in this major eukaryotic group. Moreover, we show that generation-biased genes display distinct evolutionary modes, with gametophyte-biased genes evolving rapidly at the coding sequence level whereas sporophyte-biased genes tend to exhibit changes in their patterns of expression.

CONCLUSION: Our analysis uncovers the characteristics, expression patterns, and evolution of generation-biased genes and underlines the selective forces that shape this previously underappreciated source of phenotypic diversity.}, } @article {pmid30763317, year = {2019}, author = {Raza, Q and Choi, JY and Li, Y and O'Dowd, RM and Watkins, SC and Chikina, M and Hong, Y and Clark, NL and Kwiatkowski, AV}, title = {Evolutionary rate covariation analysis of E-cadherin identifies Raskol as a regulator of cell adhesion and actin dynamics in Drosophila.}, journal = {PLoS genetics}, volume = {15}, number = {2}, pages = {e1007720}, pmid = {30763317}, issn = {1553-7404}, support = {R01 GM121534/GM/NIGMS NIH HHS/United States ; R01 HG009299/HG/NHGRI NIH HHS/United States ; R01 HL127711/HL/NHLBI NIH HHS/United States ; R01 GM086423/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/metabolism ; Actins/*metabolism ; Adherens Junctions/metabolism ; Animals ; Cadherins/*metabolism ; Cell Adhesion/*physiology ; Cell Membrane/metabolism ; Cell Movement/physiology ; Circadian Rhythm Signaling Peptides and Proteins/*metabolism ; Drosophila/*metabolism ; Drosophila Proteins/*metabolism ; Signal Transduction/physiology ; }, abstract = {The adherens junction couples the actin cytoskeletons of neighboring cells to provide the foundation for multicellular organization. The core of the adherens junction is the cadherin-catenin complex that arose early in the evolution of multicellularity to link actin to intercellular adhesions. Over time, evolutionary pressures have shaped the signaling and mechanical functions of the adherens junction to meet specific developmental and physiological demands. Evolutionary rate covariation (ERC) identifies proteins with correlated fluctuations in evolutionary rate that can reflect shared selective pressures and functions. Here we use ERC to identify proteins with evolutionary histories similar to the Drosophila E-cadherin (DE-cad) ortholog. Core adherens junction components α-catenin and p120-catenin displayed positive ERC correlations with DE-cad, indicating that they evolved under similar selective pressures during evolution between Drosophila species. Further analysis of the DE-cad ERC profile revealed a collection of proteins not previously associated with DE-cad function or cadherin-mediated adhesion. We then analyzed the function of a subset of ERC-identified candidates by RNAi during border cell (BC) migration and identified novel genes that function to regulate DE-cad. Among these, we found that the gene CG42684, which encodes a putative GTPase activating protein (GAP), regulates BC migration and adhesion. We named CG42684 raskol ("to split" in Russian) and show that it regulates DE-cad levels and actin protrusions in BCs. We propose that Raskol functions with DE-cad to restrict Ras/Rho signaling and help guide BC migration. Our results demonstrate that a coordinated selective pressure has shaped the adherens junction and this can be leveraged to identify novel components of the complexes and signaling pathways that regulate cadherin-mediated adhesion.}, } @article {pmid30760850, year = {2019}, author = {Junqueira Alves, C and Yotoko, K and Zou, H and Friedel, RH}, title = {Origin and evolution of plexins, semaphorins, and Met receptor tyrosine kinases.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {1970}, pmid = {30760850}, issn = {2045-2322}, support = {R01 NS092735/NS/NINDS NIH HHS/United States ; }, mesh = {Amino Acid Sequence/genetics ; Animals ; Biological Evolution ; Cell Adhesion Molecules/*genetics ; Choanoflagellata/*genetics ; Databases, Genetic ; Echinodermata/*genetics ; Humans ; Nerve Tissue Proteins/*genetics ; Protein Domains/genetics ; Proto-Oncogene Proteins c-met/*genetics ; Receptors, Cell Surface/genetics ; Semaphorins/*genetics ; }, abstract = {The transition from unicellular to multicellular organisms poses the question as to when genes that regulate cell-cell interactions emerged during evolution. The receptor and ligand pairing of plexins and semaphorins regulates cellular interactions in a wide range of developmental and physiological contexts. We surveyed here genomes of unicellular eukaryotes and of non-bilaterian and bilaterian Metazoa and performed phylogenetic analyses to gain insight into the evolution of plexin and semaphorin families. Remarkably, we detected plexins and semaphorins in unicellular choanoflagellates, indicating their evolutionary origin in a common ancestor of Choanoflagellida and Metazoa. The plexin domain structure is conserved throughout all clades; in contrast, semaphorins are structurally diverse. Choanoflagellate semaphorins are transmembrane proteins with multiple fibronectin type III domains following the N-terminal Sema domain (termed Sema-FN). Other previously not yet described semaphorin classes include semaphorins of Ctenophora with tandem immunoglobulin domains (Sema-IG) and secreted semaphorins of Echinoderamata (Sema-SP, Sema-SI). Our study also identified Met receptor tyrosine kinases (RTKs), which carry a truncated plexin extracellular domain, in several bilaterian clades, indicating evolutionary origin in a common ancestor of Bilateria. In addition, a novel type of Met-like RTK with a complete plexin extracellular domain was detected in Lophotrochozoa and Echinodermata (termed Met-LP RTK). Our findings are consistent with an ancient function of plexins and semaphorins in regulating cytoskeletal dynamics and cell adhesion that predates their role as axon guidance molecules.}, } @article {pmid30760717, year = {2019}, author = {Ferrari, C and Proost, S and Janowski, M and Becker, J and Nikoloski, Z and Bhattacharya, D and Price, D and Tohge, T and Bar-Even, A and Fernie, A and Stitt, M and Mutwil, M}, title = {Kingdom-wide comparison reveals the evolution of diurnal gene expression in Archaeplastida.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {737}, pmid = {30760717}, issn = {2041-1723}, mesh = {Chlorophyta/genetics ; *Circadian Rhythm ; Embryophyta/genetics ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Gene Expression Profiling/*methods ; Photosynthesis/genetics ; Phylogeny ; Rhodophyta/genetics ; Transcriptome/*genetics ; }, abstract = {Plants have adapted to the diurnal light-dark cycle by establishing elaborate transcriptional programs that coordinate many metabolic, physiological, and developmental responses to the external environment. These transcriptional programs have been studied in only a few species, and their function and conservation across algae and plants is currently unknown. We performed a comparative transcriptome analysis of the diurnal cycle of nine members of Archaeplastida, and we observed that, despite large phylogenetic distances and dramatic differences in morphology and lifestyle, diurnal transcriptional programs of these organisms are similar. Expression of genes related to cell division and the majority of biological pathways depends on the time of day in unicellular algae but we did not observe such patterns at the tissue level in multicellular land plants. Hence, our study provides evidence for the universality of diurnal gene expression and elucidates its evolutionary history among different photosynthetic eukaryotes.}, } @article {pmid30740458, year = {2019}, author = {Oborník, M}, title = {In the beginning was the word: How terminology drives our understanding of endosymbiotic organelles.}, journal = {Microbial cell (Graz, Austria)}, volume = {6}, number = {2}, pages = {134-141}, pmid = {30740458}, issn = {2311-2638}, abstract = {The names we give objects of research, to some extent, predispose our ways of thinking about them. Misclassifications of Oomycota, Microsporidia, Myxosporidia, and Helicosporidia have obviously affected not only their formal taxonomic names, but also the methods and approaches with which they have been investigated. Therefore, it is important to name biological entities with accurate terms in order to avoid discrepancies in researching them. The endosymbiotic origin of mitochondria and plastids is now the most accepted scenario for their evolution. Since it is apparent that there is no natural definitive border between bacteria and semiautonomous organelles, I propose that mitochondria and plastids should be called bacteria and classified accordingly, in the bacterial classification system. I discuss some consequences of this approach, including: i) the resulting "changes" in the abundances of bacteria, ii) the definitions of terms like microbiome or multicellularity, and iii) the concept of endosymbiotic domestication.}, } @article {pmid30729842, year = {2019}, author = {Tan, J and He, Q and Pentz, JT and Peng, C and Yang, X and Tsai, MH and Chen, Y and Ratcliff, WC and Jiang, L}, title = {Copper oxide nanoparticles promote the evolution of multicellularity in yeast.}, journal = {Nanotoxicology}, volume = {13}, number = {5}, pages = {597-605}, doi = {10.1080/17435390.2018.1553253}, pmid = {30729842}, issn = {1743-5404}, mesh = {*Biological Evolution ; Copper/*toxicity ; Gene Expression Regulation, Fungal/drug effects ; Nanoparticles/*toxicity ; Saccharomyces cerevisiae/cytology/*drug effects/genetics ; Transcriptome/drug effects ; }, abstract = {Engineered nanomaterials are rapidly becoming an essential component of modern technology. Thousands of tons of nanomaterials are manufactured, used, and subsequently released into the environment annually. While the presence of these engineered nanomaterials in the environment has profound effects on various biological systems in the short term, little work has been done to understand their consequences over long, evolutionary timescales. The evolution of multicellularity is a critical step in the origin of complex life on Earth and a unique strategy for microorganisms to alleviate adverse environmental impacts, yet the selective pressures that favor the evolution of multicellular groups remain poorly understood. Here, we show that engineered nanomaterials, specifically copper oxide nanoparticles (CuO NPs), promote the evolution of undifferentiated multicellularity in Baker's yeast (Saccharomyces cerevisiae strain Y55). Transcriptomic analysis suggests that multicellularity mitigates the negative effects of CuO NPs in yeast cells and shifts their metabolism from alcoholic fermentation towards aerobic respiration, potentially increasing resource efficiency and providing a fitness benefit during CuO NP exposure. Competition assays also confirm that the multicellular yeast possesses a fitness advantage when exposed to CuO NPs. Our results, therefore, demonstrate that nanoparticles can have profound and unexpected evolutionary consequences, underscoring the need for a more comprehensive understanding of the long-term biological impacts of nanomaterial pollution.}, } @article {pmid30728304, year = {2019}, author = {Peyraud, R and Mbengue, M and Barbacci, A and Raffaele, S}, title = {Intercellular cooperation in a fungal plant pathogen facilitates host colonization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {8}, pages = {3193-3201}, pmid = {30728304}, issn = {1091-6490}, support = {336808/ERC_/European Research Council/International ; }, mesh = {Arabidopsis/genetics/growth & development/*microbiology ; Ascomycota/genetics/*pathogenicity ; Genome, Plant/genetics ; Host-Pathogen Interactions/*genetics ; Hyphae/genetics/pathogenicity ; Plant Diseases/*genetics/microbiology ; }, abstract = {Cooperation is associated with major transitions in evolution such as the emergence of multicellularity. It is central to the evolution of many complex traits in nature, including growth and virulence in pathogenic bacteria. Whether cells of multicellular parasites function cooperatively during infection remains, however, largely unknown. Here, we show that hyphal cells of the fungal pathogen Sclerotinia sclerotiorum reprogram toward division of labor to facilitate the colonization of host plants. Using global transcriptome sequencing, we reveal that gene expression patterns diverge markedly in cells at the center and apex of hyphae during Arabidopsis thaliana colonization compared with in vitro growth. We reconstructed a genome-scale metabolic model for S. sclerotiorum and used flux balance analysis to demonstrate metabolic heterogeneity supporting division of labor between hyphal cells. Accordingly, continuity between the central and apical compartments of invasive hyphae was required for optimal growth in planta Using a multicell model of fungal hyphae, we show that this cooperative functioning enhances fungal growth predominantly during host colonization. Our work identifies cooperation in fungal hyphae as a mechanism emerging at the multicellular level to support host colonization and virulence.}, } @article {pmid30720904, year = {2019}, author = {Xiong, F and Ren, JJ and Yu, Q and Wang, YY and Kong, LJ and Otegui, MS and Wang, XL}, title = {AtBUD13 affects pre-mRNA splicing and is essential for embryo development in Arabidopsis.}, journal = {The Plant journal : for cell and molecular biology}, volume = {98}, number = {4}, pages = {714-726}, doi = {10.1111/tpj.14268}, pmid = {30720904}, issn = {1365-313X}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/classification/genetics/*metabolism ; Embryonic Development/genetics/*physiology ; Gene Expression Regulation, Developmental/genetics ; Gene Expression Regulation, Plant/genetics ; Genes, Plant/genetics ; Introns ; Mutation ; Nuclear Proteins/classification/genetics/*metabolism ; Phylogeny ; Plants, Genetically Modified ; Protein Domains ; RNA Precursors/genetics ; RNA Splicing ; RNA Splicing Factors/classification/genetics/*metabolism ; Sequence Alignment ; Sequence Analysis ; }, abstract = {Pre-mRNA splicing is an important step for gene expression regulation. Yeast Bud13p (bud-site selection protein 13) regulates the budding pattern and pre-mRNA splicing in yeast cells; however, no Bud13p homologs have been identified in plants. Here, we isolated two mutants that carry T-DNA insertions at the At1g31870 locus and shows early embryo lethality and seed abortion. At1g31870 encodes an Arabidopsis homolog of yeast Bud13p, AtBUD13. Although AtBUD13 homologs are widely distributed in eukaryotic organisms, phylogenetic analysis revealed that their protein domain organization is more complex in multicellular species. AtBUD13 is expressed throughout plant development including embryogenesis and AtBUD13 proteins is localized in the nucleus in Arabidopsis. RNA-seq analysis revealed that AtBUD13 mutation predominantly results in the intron retention, especially for shorter introns (≤100 bases). Within this group of genes, we identified 52 genes involved in embryogenesis, out of which 22 are involved in nucleic acid metabolism. Our results demonstrate that AtBUD13 plays critical roles in early embryo development by effecting pre-mRNA splicing.}, } @article {pmid30718271, year = {2019}, author = {Fischer, MS and Jonkers, W and Glass, NL}, title = {Integration of Self and Non-self Recognition Modulates Asexual Cell-to-Cell Communication in Neurospora crassa.}, journal = {Genetics}, volume = {211}, number = {4}, pages = {1255-1267}, pmid = {30718271}, issn = {1943-2631}, support = {P01 GM068087/GM/NIGMS NIH HHS/United States ; S10 OD021828/OD/NIH HHS/United States ; T32 GM007127/GM/NIGMS NIH HHS/United States ; }, mesh = {*Chemotaxis ; Fungal Proteins/genetics/metabolism ; MAP Kinase Signaling System ; Neurospora crassa/genetics/*physiology ; *Quorum Sensing ; }, abstract = {Cells rarely exist alone, which drives the evolution of diverse mechanisms for identifying and responding appropriately to the presence of other nearby cells. Filamentous fungi depend on somatic cell-to-cell communication and fusion for the development and maintenance of a multicellular, interconnected colony that is characteristic of this group of organisms. The filamentous fungus Neurospora crassa is a model for investigating the mechanisms of somatic cell-to-cell communication and fusion. N. crassa cells chemotropically grow toward genetically similar cells, which ultimately make physical contact and undergo cell fusion. Here, we describe the development of a Pprm1-luciferase reporter system that differentiates whether genes function upstream or downstream of a conserved MAP kinase (MAPK) signaling complex, by using a set of mutants required for communication and cell fusion. The vast majority of these mutants are deficient for self-fusion and for fusion when paired with wild-type cells. However, the Δham-11 mutant is unique in that it fails to undergo self-fusion, but chemotropic interactions and cell fusion are restored in Δham-11 + wild-type interactions. In genetically dissimilar cells, chemotropic interactions are regulated by genetic differences at doc-1 and doc-2, which regulate prefusion non-self recognition; cells with dissimilar doc-1 and doc-2 alleles show greatly reduced cell-fusion frequencies. Here, we show that HAM-11 functions in parallel with the DOC-1 and DOC-2 proteins to regulate the activity of the MAPK signaling complex. Together, our data support a model of integrated self and non-self recognition processes that modulate somatic cell-to-cell communication in N. crassa.}, } @article {pmid30715320, year = {2019}, author = {Voukantsis, D and Kahn, K and Hadley, M and Wilson, R and Buffa, FM}, title = {Modeling genotypes in their microenvironment to predict single- and multi-cellular behavior.}, journal = {GigaScience}, volume = {8}, number = {3}, pages = {}, pmid = {30715320}, issn = {2047-217X}, support = {23969/CRUK_/Cancer Research UK/United Kingdom ; CBIG:23969/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Cell Hypoxia ; Cell Lineage ; Cell Proliferation ; *Cellular Microenvironment ; Clonal Evolution ; Computer Simulation ; Gene Regulatory Networks ; Genotype ; Humans ; Mutation/genetics ; Signal Transduction ; Spheroids, Cellular/cytology ; }, abstract = {A cell's phenotype is the set of observable characteristics resulting from the interaction of the genotype with the surrounding environment, determining cell behavior. Deciphering genotype-phenotype relationships has been crucial to understanding normal and disease biology. Analysis of molecular pathways has provided an invaluable tool to such understanding; however, typically it does not consider the physical microenvironment, which is a key determinant of phenotype. In this study, we present a novel modeling framework that enables the study of the link between genotype, signaling networks, and cell behavior in a three-dimensional microenvironment. To achieve this, we bring together Agent-Based Modeling, a powerful computational modeling technique, and gene networks. This combination allows biological hypotheses to be tested in a controlled stepwise fashion, and it lends itself naturally to model a heterogeneous population of cells acting and evolving in a dynamic microenvironment, which is needed to predict the evolution of complex multi-cellular dynamics. Importantly, this enables modeling co-occurring intrinsic perturbations, such as mutations, and extrinsic perturbations, such as nutrient availability, and their interactions. Using cancer as a model system, we illustrate how this framework delivers a unique opportunity to identify determinants of single-cell behavior, while uncovering emerging properties of multi-cellular growth. This framework is freely available at http://www.microc.org.}, } @article {pmid30714631, year = {2019}, author = {Baluška, F and Reber, A}, title = {Sentience and Consciousness in Single Cells: How the First Minds Emerged in Unicellular Species.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {41}, number = {3}, pages = {e1800229}, doi = {10.1002/bies.201800229}, pmid = {30714631}, issn = {1521-1878}, mesh = {Animals ; Awareness/physiology ; Biological Evolution ; Cell Membrane/*physiology ; Consciousness/*physiology ; Cytoskeleton/*physiology ; Escherichia coli/physiology ; Humans ; Lipid Bilayers/chemistry ; Membrane Potential, Mitochondrial/physiology ; Plant Cells/physiology ; Polymers/chemistry ; Synaptic Potentials/physiology ; }, abstract = {A reductionistic, bottom-up, cellular-based concept of the origins of sentience and consciousness has been put forward. Because all life is based on cells, any evolutionary theory of the emergence of sentience and consciousness must be grounded in mechanisms that take place in prokaryotes, the simplest unicellular species. It has been posited that subjective awareness is a fundamental property of cellular life. It emerges as an inherent feature of, and contemporaneously with, the very first life-forms. All other varieties of mentation are the result of evolutionary mechanisms based on this singular event. Therefore, all forms of sentience and consciousness evolve from this original instantiation in prokaryotes. It has also been identified that three cellular structures and mechanisms that likely play critical roles here are excitable membranes, oscillating cytoskeletal polymers, and structurally flexible proteins. Finally, basic biophysical principles are proposed to guide those processes that underly the emergence of supracellular sentience from cellular sentience in multicellular organisms.}, } @article {pmid30705751, year = {2018}, author = {Kosach, V and Shkarina, K and Kravchenko, A and Tereshchenko, Y and Kovalchuk, E and Skoroda, L and Krotevych, M and Khoruzhenko, A}, title = {Nucleocytoplasmic distribution of S6K1 depends on the density and motility of MCF-7 cells in vitro.}, journal = {F1000Research}, volume = {7}, number = {}, pages = {1332}, pmid = {30705751}, issn = {2046-1402}, mesh = {*Breast Neoplasms ; Cell Movement ; Humans ; MCF-7 Cells ; Ribosomal Protein S6 Kinases, 70-kDa ; Signal Transduction ; }, abstract = {Background: The ribosomal protein S6 kinase 1 (S6K1) is one of the main components of the mTOR/S6K signal transduction pathway, which controls cellular metabolism, autophagy, growth, and proliferation. Overexpression of S6K1 was detected in tumors of different origin including breast cancer, and correlated with the worse disease outcome. In addition, significant accumulation of S6K1 was found in the nuclei of breast carcinoma cells suggesting the implication of kinase nuclear substrates in tumor progression. However, this aspect of S6K1 functioning is still poorly understood. The main aim of the present work was to study the subcellular localization of S6K1 in breast cancer cells with the focus on cell migration. Methods: Multicellular spheroids of MCF-7 cells were generated using agarose-coated Petri dishes. Cell migration was induced by spheroids seeding onto adhesive growth surface and subsequent cultivation for 24 to 72 hours. The subcellular localization of S6K1 was studied in human normal breast and cancer tissue samples, 2D and 3D MCF-7 cell cultures using immunofluorescence analysis and confocal microscopy. Results: Analysis of histological sections of human breast tissue samples revealed predominantly nuclear localization of S6K1 in breast malignant cells and its mainly cytoplasmic localization in conditionally normal cells. In vitro studies of MCF-7 cells demonstrated that the subcellular localization of S6K1 depends on the cell density in the monolayer culture. S6K1 relocalization from the cytoplasm into the nucleus was detected in MCF-7 cells migrating from multicellular spheroids onto growth surface. Immunofluorescence analysis of S6K1 and immunocoprecipitation assay revealed the colocalization and interaction between S6K1 and transcription factor TBR2 (T-box brain protein 2) in MCF-7 cells. Conclusions: Subcellular localization of S6K1 depends on the density and locomotor activity of the MCF-7 cells.}, } @article {pmid30691027, year = {2019}, author = {Salmina, K and Huna, A and Kalejs, M and Pjanova, D and Scherthan, H and Cragg, MS and Erenpreisa, J}, title = {The Cancer Aneuploidy Paradox: In the Light of Evolution.}, journal = {Genes}, volume = {10}, number = {2}, pages = {}, pmid = {30691027}, issn = {2073-4425}, mesh = {*Aneuploidy ; *Evolution, Molecular ; Genomic Instability ; HeLa Cells ; Humans ; Kinetochores/metabolism ; Mitosis ; Neoplasms/*genetics ; Recombination, Genetic ; Spindle Apparatus/genetics/metabolism ; }, abstract = {Aneuploidy should compromise cellular proliferation but paradoxically favours tumour progression and poor prognosis. Here, we consider this paradox in terms of our most recent observations of chemo/radio-resistant cells undergoing reversible polyploidy. The latter perform the segregation of two parental groups of end-to-end linked dyads by pseudo-mitosis creating tetraploid cells through a dysfunctional spindle. This is followed by autokaryogamy and a homologous pairing preceding a bi-looped endo-prophase. The associated RAD51 and DMC1/γ-H2AX double-strand break repair foci are tandemly situated on the AURKB/REC8/kinetochore doublets along replicated chromosome loops, indicative of recombination events. MOS-associated REC8-positive peri-nucleolar centromere cluster organises a monopolar spindle. The process is completed by reduction divisions (bi-polar or by radial cytotomy including pedogamic exchanges) and by the release of secondary cells and/or the formation of an embryoid. Together this process preserves genomic integrity and chromosome pairing, while tolerating aneuploidy by by-passing the mitotic spindle checkpoint. Concurrently, it reduces the chromosome number and facilitates recombination that decreases the mutation load of aneuploidy and lethality in the chemo-resistant tumour cells. This cancer life-cycle has parallels both within the cycling polyploidy of the asexual life cycles of ancient unicellular protists and cleavage embryos of early multicellulars, supporting the atavistic theory of cancer.}, } @article {pmid30689829, year = {2019}, author = {Parey, E and Crombach, A}, title = {Evolution of the Drosophila melanogaster Chromatin Landscape and Its Associated Proteins.}, journal = {Genome biology and evolution}, volume = {11}, number = {3}, pages = {660-677}, pmid = {30689829}, issn = {1759-6653}, mesh = {Animals ; Chromatin/classification/*genetics ; DNA-Binding Proteins/genetics ; Drosophila Proteins/genetics ; Drosophila melanogaster/*genetics ; *Evolution, Molecular ; Histone Code ; }, abstract = {In the nucleus of eukaryotic cells, genomic DNA associates with numerous protein complexes and RNAs, forming the chromatin landscape. Through a genome-wide study of chromatin-associated proteins in Drosophila cells, five major chromatin types were identified as a refinement of the traditional binary division into hetero- and euchromatin. These five types were given color names in reference to the Greek word chroma. They are defined by distinct but overlapping combinations of proteins and differ in biological and biochemical properties, including transcriptional activity, replication timing, and histone modifications. In this work, we assess the evolutionary relationships of chromatin-associated proteins and present an integrated view of the evolution and conservation of the fruit fly Drosophila melanogaster chromatin landscape. We combine homology prediction across a wide range of species with gene age inference methods to determine the origin of each chromatin-associated protein. This provides insight into the evolution of the different chromatin types. Our results indicate that for the euchromatic types, YELLOW and RED, young associated proteins are more specialized than old ones; and for genes found in either chromatin type, intron/exon structure is lineage-specific. Next, we provide evidence that a subset of GREEN-associated proteins is involved in a centromere drive in D. melanogaster. Our results on BLUE chromatin support the hypothesis that the emergence of Polycomb Group proteins is linked to eukaryotic multicellularity. In light of these results, we discuss how the regulatory complexification of chromatin links to the origins of eukaryotic multicellularity.}, } @article {pmid30686614, year = {2019}, author = {Perner, J and Gasser, RB and Oliveira, PL and Kopáček, P}, title = {Haem Biology in Metazoan Parasites - 'The Bright Side of Haem'.}, journal = {Trends in parasitology}, volume = {35}, number = {3}, pages = {213-225}, doi = {10.1016/j.pt.2019.01.001}, pmid = {30686614}, issn = {1471-5007}, mesh = {Adaptation, Physiological ; Animals ; Heme/biosynthesis/genetics/*metabolism ; Host-Parasite Interactions/*physiology ; }, abstract = {Traditionally, host haem has been recognized as a cytotoxic molecule that parasites need to eliminate or detoxify in order to survive. However, recent evidence indicates that some lineages of parasites have lost genes that encode enzymes involved specifically in endogenous haem biosynthesis. Such lineages thus need to acquire and utilize haem originating from their host animal, making it an indispensable molecule for their survival and reproduction. In multicellular parasites, host haem needs to be systemically distributed throughout their bodies to meet the haem demands in all cell and tissue types. Host haem also gets deposited in parasite eggs, enabling embryogenesis and reproduction. Clearly, a better understanding of haem biology in multicellular parasites should elucidate organismal adaptations to obligatory blood-feeding.}, } @article {pmid30685797, year = {2019}, author = {Nedelcu, AM}, title = {Independent evolution of complex development in animals and plants: deep homology and lateral gene transfer.}, journal = {Development genes and evolution}, volume = {229}, number = {1}, pages = {25-34}, pmid = {30685797}, issn = {1432-041X}, mesh = {Animals ; Conserved Sequence ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; Plant Proteins/chemistry/genetics ; Plants/genetics ; Protein Domains ; *Sequence Homology ; Transcription Factors/chemistry/genetics ; }, abstract = {The evolution of multicellularity is a premier example of phenotypic convergence: simple multicellularity evolved independently many times, and complex multicellular phenotypes are found in several distant groups. Furthermore, both animal and plant lineages have independently reached extreme levels of morphological, functional, and developmental complexity. This study explores the genetic basis for the parallel evolution of complex multicellularity and development in the animal and green plant (i.e., green algae and land plants) lineages. Specifically, the study (i) identifies the SAND domain-a DNA-binding domain with important roles in the regulation of cell proliferation and differentiation, as unique to animals, green algae, and land plants; and (ii) suggests that the parallel deployment of this ancestral domain in similar regulatory roles could have contributed to the independent evolution of complex development in these distant groups. Given the deep animal-green plant divergence, the limited distribution of the SAND domain is best explained by invoking a lateral gene transfer (LGT) event from a green alga to an early metazoan. The presence of a sequence motif specifically shared by a family of SAND-containing transcription factors involved in the evolution of complex multicellularity in volvocine algae and two types of SAND proteins that emerged early in the evolution of animals is consistent with this scenario. Overall, these findings imply that (i) in addition to be involved in the evolution of similar phenotypes, deep homologous sequences can also contribute to shaping parallel evolutionary trajectories in distant lineages, and (ii) LGT could provide an additional source of latent homologous sequences that can be deployed in analogous roles and affect the evolutionary potentials of distantly related groups.}, } @article {pmid30668717, year = {2019}, author = {Belato, FA and Schrago, CG and Coates, CJ and Halanych, KM and Costa-Paiva, EM}, title = {Newly Discovered Occurrences and Gene Tree of the Extracellular Globins and Linker Chains from the Giant Hexagonal Bilayer Hemoglobin in Metazoans.}, journal = {Genome biology and evolution}, volume = {11}, number = {3}, pages = {597-612}, pmid = {30668717}, issn = {1759-6653}, mesh = {Animals ; Globins/*genetics ; Invertebrates/*genetics ; *Phylogeny ; }, abstract = {Multicellular organisms depend on oxygen-carrying proteins to transport oxygen throughout the body; therefore, proteins such as hemoglobins (Hbs), hemocyanins, and hemerythrins are essential for maintenance of tissues and cellular respiration. Vertebrate Hbs are among the most extensively studied proteins; however, much less is known about invertebrate Hbs. Recent studies of hemocyanins and hemerythrins have demonstrated that they have much wider distributions than previously thought, suggesting that oxygen-binding protein diversity is underestimated across metazoans. Hexagonal bilayer hemoglobin (HBL-Hb), a blood pigment found exclusively in annelids, is a polymer comprised up to 144 extracellular globins and 36 linker chains. To further understand the evolutionary history of this protein complex, we explored the diversity of linkers and extracellular globins from HBL-Hbs using in silico approaches on 319 metazoan and one choanoflagellate transcriptomes. We found 559 extracellular globin and 414 linker genes transcribed in 171 species from ten animal phyla with new records in Echinodermata, Hemichordata, Brachiopoda, Mollusca, Nemertea, Bryozoa, Phoronida, Platyhelminthes, and Priapulida. Contrary to previous suggestions that linkers and extracellular globins emerged in the annelid ancestor, our findings indicate that they have putatively emerged before the protostome-deuterostome split. For the first time, we unveiled the comprehensive evolutionary history of metazoan HBL-Hb components, which consists of multiple episodes of gene gains and losses. Moreover, because our study design surveyed linkers and extracellular globins independently, we were able to cross-validate our results, significantly reducing the rate of false positives. We confirmed that the distribution of HBL-Hb components has until now been underestimated among animals.}, } @article {pmid30668691, year = {2019}, author = {Passow, CN and Bronikowski, AM and Blackmon, H and Parsai, S and Schwartz, TS and McGaugh, SE}, title = {Contrasting Patterns of Rapid Molecular Evolution within the p53 Network across Mammal and Sauropsid Lineages.}, journal = {Genome biology and evolution}, volume = {11}, number = {3}, pages = {629-643}, pmid = {30668691}, issn = {1759-6653}, support = {R01 AG049416/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; *Genes, p53 ; Phylogeny ; *Selection, Genetic ; Vertebrates/*genetics ; }, abstract = {Cancer is a threat to multicellular organisms, yet the molecular evolution of pathways that prevent the accumulation of genetic damage has been largely unexplored. The p53 network regulates how cells respond to DNA-damaging stressors. We know little about p53 network molecular evolution as a whole. In this study, we performed comparative genetic analyses of the p53 network to quantify the number of genes within the network that are rapidly evolving and constrained, and the association between lifespan and the patterns of evolution. Based on our previous published data set, we used genomes and transcriptomes of 34 sauropsids and 32 mammals to analyze the molecular evolution of 45 genes within the p53 network. We found that genes in the network exhibited evidence of positive selection and divergent molecular evolution in mammals and sauropsids. Specifically, we found more evidence of positive selection in sauropsids than mammals, indicating that sauropsids have different targets of selection. In sauropsids, more genes upstream in the network exhibited positive selection, and this observation is driven by positive selection in squamates, which is consistent with previous work showing rapid divergence and adaptation of metabolic and stress pathways in this group. Finally, we identified a negative correlation between maximum lifespan and the number of genes with evidence of divergent molecular evolution, indicating that species with longer lifespans likely experienced less variation in selection across the network. In summary, our study offers evidence that comparative genomic approaches can provide insights into how molecular networks have evolved across diverse species.}, } @article {pmid30667071, year = {2019}, author = {Coelho, SM and Mignerot, L and Cock, JM}, title = {Origin and evolution of sex-determination systems in the brown algae.}, journal = {The New phytologist}, volume = {222}, number = {4}, pages = {1751-1756}, doi = {10.1111/nph.15694}, pmid = {30667071}, issn = {1469-8137}, support = {638240/ERC_/European Research Council/International ; }, mesh = {*Biological Evolution ; Gene Regulatory Networks ; Genetic Loci ; Phaeophyceae/*genetics ; Sex Chromosomes ; }, abstract = {Sexual reproduction is a nearly universal feature of eukaryotic organisms. Meiosis appears to have had a single ancient origin, but the mechanisms underlying male or female sex determination are diverse and have emerged repeatedly and independently in the different eukaryotic groups. The brown algae are a group of multicellular photosynthetic eukaryotes that have a distinct evolutionary history compared with animals and plants, as they have been evolving independently for over 1 billion yr. Here, we review recent work using the brown alga Ectocarpus as a model organism to study haploid sex chromosomes, and highlight how the diversity of reproductive and life cycle features of the brown algae offer unique opportunities to characterize the evolutionary forces and the mechanisms underlying the evolution of sex determination.}, } @article {pmid30663729, year = {2019}, author = {Peel, S and Corrigan, AM and Ehrhardt, B and Jang, KJ and Caetano-Pinto, P and Boeckeler, M and Rubins, JE and Kodella, K and Petropolis, DB and Ronxhi, J and Kulkarni, G and Foster, AJ and Williams, D and Hamilton, GA and Ewart, L}, title = {Introducing an automated high content confocal imaging approach for Organs-on-Chips.}, journal = {Lab on a chip}, volume = {19}, number = {3}, pages = {410-421}, doi = {10.1039/c8lc00829a}, pmid = {30663729}, issn = {1473-0189}, mesh = {Animals ; Automation ; Drug Evaluation, Preclinical ; Humans ; Kidney/diagnostic imaging/drug effects ; *Lab-On-A-Chip Devices ; Liver/diagnostic imaging/drug effects ; Optical Imaging/*instrumentation ; Rats ; }, abstract = {Organ-Chips are micro-engineered systems that aim to recapitulate the organ microenvironment. Implementation of Organ-Chips within the pharmaceutical industry aims to improve the probability of success of drugs reaching late stage clinical trial by generating models for drug discovery that are of human origin and have disease relevance. We are adopting the use of Organ-Chips for enhancing pre-clinical efficacy and toxicity evaluation and prediction. Whilst capturing cellular phenotype via imaging in response to drug exposure is a useful readout in these models, application has been limited due to difficulties in imaging the chips at scale. Here we created an end-to-end, automated workflow to capture and analyse confocal images of multicellular Organ-Chips to assess detailed cellular phenotype across large batches of chips. By automating this process, we not only reduced acquisition time, but we also minimised process variability and user bias. This enabled us to establish, for the first time, a framework of statistical best practice for Organ-Chip imaging, creating the capability of using Organ-Chips and imaging for routine testing in drug discovery applications that rely on quantitative image data for decision making. We tested our approach using benzbromarone, whose mechanism of toxicity has been linked to mitochondrial damage with subsequent induction of apoptosis and necrosis, and staurosporine, a tool inducer of apoptosis. We also applied this workflow to assess the hepatotoxic effect of an active AstraZeneca drug candidate illustrating its applicability in drug safety assessment beyond testing tool compounds. Finally, we have demonstrated that this approach could be adapted to Organ-Chips of different shapes and sizes through application to a Kidney-Chip.}, } @article {pmid30659161, year = {2019}, author = {Rodríguez-Pascual, F}, title = {How evolution made the matrix punch at the multicellularity party.}, journal = {The Journal of biological chemistry}, volume = {294}, number = {3}, pages = {770-771}, pmid = {30659161}, issn = {1083-351X}, mesh = {Animals ; Basement Membrane/*metabolism ; *Evolution, Molecular ; Humans ; Protein Serine-Threonine Kinases/*genetics/*metabolism ; }, abstract = {The basement membrane is a specialized sheet-like form of the extracellular matrix that provides structural support to epithelial cells and tissues, while influencing multiple biological functions, and was essential in the transition to multicellularity. By exploring a variety of genomes, Darris et al. provide evidence that the emergence and divergence of a multifunctional Goodpasture antigen-binding protein (GPBP), a basement membrane constituent, played a role in this transition. These findings help to explain how GPBP contributed to the formation of these extracellular matrices and to more precisely define the transition to multicellular organisms.}, } @article {pmid30653459, year = {2019}, author = {Yoshida, T and Prudent, M and D'alessandro, A}, title = {Red blood cell storage lesion: causes and potential clinical consequences.}, journal = {Blood transfusion = Trasfusione del sangue}, volume = {17}, number = {1}, pages = {27-52}, pmid = {30653459}, issn = {2385-2070}, support = {R44 HL132172/HL/NHLBI NIH HHS/United States ; }, mesh = {*Blood Preservation ; Erythrocyte Transfusion/adverse effects/methods ; Erythrocytes/cytology/*metabolism ; Humans ; Oxygen/metabolism ; Pharmaceutical Solutions/pharmacology ; Time Factors ; }, abstract = {Red blood cells (RBCs) are a specialised organ that enabled the evolution of multicellular organisms by supplying a sufficient quantity of oxygen to cells that cannot obtain oxygen directly from ambient air via diffusion, thereby fueling oxidative phosphorylation for highly efficient energy production. RBCs have evolved to optimally serve this purpose by packing high concentrations of haemoglobin in their cytosol and shedding nuclei and other organelles. During their circulatory lifetimes in humans of approximately 120 days, RBCs are poised to transport oxygen by metabolic/redox enzymes until they accumulate damage and are promptly removed by the reticuloendothelial system. These elaborate evolutionary adaptions, however, are no longer effective when RBCs are removed from the circulation and stored hypothermically in blood banks, where they develop storage-induced damages ("storage lesions") that accumulate over the shelf life of stored RBCs. This review attempts to provide a comprehensive view of the literature on the subject of RBC storage lesions and their purported clinical consequences by incorporating the recent exponential growth in available data obtained from "omics" technologies in addition to that published in more traditional literature. To summarise this vast amount of information, the subject is organised in figures with four panels: i) root causes; ii) RBC storage lesions; iii) physiological effects; and iv) reported outcomes. The driving forces for the development of the storage lesions can be roughly classified into two root causes: i) metabolite accumulation/depletion, the target of various interventions (additive solutions) developed since the inception of blood banking; and ii) oxidative damages, which have been reported for decades but not addressed systemically until recently. Downstream physiological consequences of these storage lesions, derived mainly by in vitro studies, are described, and further potential links to clinical consequences are discussed. Interventions to postpone the onset and mitigate the extent of the storage lesion development are briefly reviewed. In addition, we briefly discuss the results from recent randomised controlled trials on the age of stored blood and clinical outcomes of transfusion.}, } @article {pmid30651122, year = {2019}, author = {Patthy, L}, title = {Exon skipping-rich transcriptomes of animals reflect the significance of exon-shuffling in metazoan proteome evolution.}, journal = {Biology direct}, volume = {14}, number = {1}, pages = {2}, pmid = {30651122}, issn = {1745-6150}, mesh = {Alternative Splicing ; Animals ; *Evolution, Molecular ; *Exons ; *Genome ; *Introns ; *Transcriptome ; }, abstract = {ᅟ: Animals are known to have higher rates of exon skipping than other eukaryotes. In a recent study, Grau-Bové et al. (Genome Biology 19:135, 2018) have used RNA-seq data across 65 eukaryotic species to investigate when and how this high prevalence of exon skipping evolved. They have found that bilaterian Metazoa have significantly increased exon skipping frequencies compared to all other eukaryotic groups and that exon skipping in nearly all animals, including non-bilaterians, is strongly enriched for frame-preserving events. The authors have hypothesized that "the increase of exon skipping rates in animals followed a two-step process. First, exon skipping in early animals became enriched for frame-preserving events. Second, bilaterian ancestors dramatically increased their exon skipping frequencies, likely driven by the interplay between a shift in their genome architectures towards more exon definition and recruitment of frame-preserving exon skipping events to functionally diversify their cell-specific proteomes." Here we offer a different explanation for the higher frequency of frame-preserving exon skipping in Metzoa than in all other eukaryotes. In our view these observations reflect the fact that the majority of multidomain proteins unique to metazoa and indispensable for metazoan type multicellularity were assembled by exon-shuffling from 'symmetrical' modules (i.e. modules flanked by introns of the same phase), whereas this type of protein evolution played a minor role in other groups of eukaryotes, including plants. The higher frequency of 'symmetrical' exons in Metazoan genomes provides an explanation for the enrichment for frame-preserving events since skipping or inclusion of 'symmetrical' modules during alternative splicing does not result in a reading-frame shift. REVIEWERS: This article was reviewed by Manuel Irimia, Ashish Lal and Erez Levanon. The reviewers were nominated by the Editorial Board.}, } @article {pmid30649338, year = {2019}, author = {Russell, SL}, title = {Transmission mode is associated with environment type and taxa across bacteria-eukaryote symbioses: a systematic review and meta-analysis.}, journal = {FEMS microbiology letters}, volume = {366}, number = {3}, pages = {}, doi = {10.1093/femsle/fnz013}, pmid = {30649338}, issn = {1574-6968}, mesh = {Bacteria/classification ; *Bacterial Physiological Phenomena ; *Biological Evolution ; *Environment ; Eukaryota/*physiology ; Host-Pathogen Interactions/*physiology ; Phylogeny ; Symbiosis/*physiology ; }, abstract = {Symbiotic associations between bacteria and eukaryotes exhibit a range of transmission strategies. The rates and distributions of transmission modes have not been thoroughly investigated across associations, despite their consequences on symbiont and host evolution. To address this empirically, I compiled data from the literature on bacteria-multicellular eukaryote associations for which transmission mode data was available. Of the total 528 analyzed symbioses, 21.2% were strictly horizontally transmitted, 36.0% exhibited some form of mixed mode transmission and 42.8% were strictly vertically transmitted. Controlling for phylogenetically independent symbiosis events revealed modes were approximately equally distributed among the 113 independent associations, at 32.1%+/-0.57% horizontal, 37.8%+/-1.4% mixed mode and 31.1%+/-1.3% vertical transmission. Binning symbioses by environment revealed an abundance of vertical transmission on land and a lack of it in aquatic environments. The naturally occurring uneven distribution of taxa among environments prevented controlling for host/symbiont phylogeny. However, the results were robust over a large number of independently evolved associations, suggesting that many vertically transmitted bacteria are capable of mixed mode transmission and barriers exist that reduce the rate of horizontal transmission events. Thus, both the environment type and host/symbiont taxa influence symbiont transmission mode evolution.}, } @article {pmid30644818, year = {2019}, author = {Arun, A and Coelho, SM and Peters, AF and Bourdareau, S and Pérès, L and Scornet, D and Strittmatter, M and Lipinska, AP and Yao, H and Godfroy, O and Montecinos, GJ and Avia, K and Macaisne, N and Troadec, C and Bendahmane, A and Cock, JM}, title = {Convergent recruitment of TALE homeodomain life cycle regulators to direct sporophyte development in land plants and brown algae.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {30644818}, issn = {2050-084X}, support = {ERC-SEXYPARTH/ERC_/European Research Council/International ; ANR-10-BLAN-1727//Agence Nationale de la Recherche/International ; Marinexus//Interreg Program France -England/International ; European Erasmus Mundus program//European Commission/International ; Marinexus//Interreg Program France (Channel)-England/International ; ANR-10-LABX-40//Agence Nationale de la Recherche/International ; 638240/ERC_/European Research Council/International ; ANR-10-BTBR-04-01//Agence Nationale de la Recherche/International ; }, mesh = {Amino Acid Sequence ; Embryophyta/genetics/*growth & development/*metabolism ; Evolution, Molecular ; Gene Expression Regulation, Plant ; Homeodomain Proteins/chemistry/genetics/*metabolism ; Mutation/genetics ; Phaeophyceae/genetics/*growth & development/*metabolism ; Phenotype ; Plant Proteins/*metabolism ; Protein Binding ; Protein Domains ; RNA, Messenger/genetics/metabolism ; Transcription Factors/chemistry/genetics ; }, abstract = {Three amino acid loop extension homeodomain transcription factors (TALE HD TFs) act as life cycle regulators in green algae and land plants. In mosses these regulators are required for the deployment of the sporophyte developmental program. We demonstrate that mutations in either of two TALE HD TF genes, OUROBOROS or SAMSARA, in the brown alga Ectocarpus result in conversion of the sporophyte generation into a gametophyte. The OUROBOROS and SAMSARA proteins heterodimerise in a similar manner to TALE HD TF life cycle regulators in the green lineage. These observations demonstrate that TALE-HD-TF-based life cycle regulation systems have an extremely ancient origin, and that these systems have been independently recruited to regulate sporophyte developmental programs in at least two different complex multicellular eukaryotic supergroups, Archaeplastida and Chromalveolata.}, } @article {pmid30633881, year = {2019}, author = {Khalil, AA and de Rooij, J}, title = {Cadherin mechanotransduction in leader-follower cell specification during collective migration.}, journal = {Experimental cell research}, volume = {376}, number = {1}, pages = {86-91}, doi = {10.1016/j.yexcr.2019.01.006}, pmid = {30633881}, issn = {1090-2422}, mesh = {Actomyosin/genetics ; Animals ; Cadherins/chemistry/*genetics ; Cell Movement/*genetics ; Cell Polarity/*genetics ; Humans ; Intercellular Junctions/genetics ; Mechanotransduction, Cellular/*genetics ; Microtubules/genetics ; }, abstract = {Collective invasion drives the spread of multicellular cancer groups, into the normal tissue surrounding several epithelial tumors. Collective invasion recapitulates various aspects of the multicellular organization and collective migration that take place during normal development and repair. Collective migration starts with the specification of leader cells in which a polarized, migratory phenotype is established. Leader cells initiate and organize the migration of follower cells, to allow the group of cells to move as a cohesive and polarized unit. Leader-follower specification is essential for coordinated and directional collective movement. Forces exerted by cohesive cells represent key signals that dictate multicellular coordination and directionality. Physical forces originate from the contraction of the actomyosin cytoskeleton, which is linked between cells via cadherin-based cell-cell junctions. The cadherin complex senses and transduces fluctuations in forces into biochemical signals that regulate processes like cell proliferation, motility and polarity. With cadherin junctions being maintained in most collective movements the cadherin complex is ideally positioned to integrate mechanical information into the organization of collective cell migration. Here we discuss the potential roles of cadherin mechanotransduction in the diverse aspects of leader versus follower cell specification during collective migration and neoplastic invasion.}, } @article {pmid30633408, year = {2019}, author = {Škaloud, P and Škaloudová, M and Doskočilová, P and Kim, JI and Shin, W and Dvořák, P}, title = {Speciation in protists: Spatial and ecological divergence processes cause rapid species diversification in a freshwater chrysophyte.}, journal = {Molecular ecology}, volume = {28}, number = {5}, pages = {1084-1095}, doi = {10.1111/mec.15011}, pmid = {30633408}, issn = {1365-294X}, support = {17-13254S//Czech Science Foundation/International ; NRF-2015R1A2A2A01003192//National Research Foundation of Korea/International ; }, mesh = {Biodiversity ; *Biological Evolution ; Chrysophyta/*genetics/growth & development ; DNA, Mitochondrial/genetics ; *Ecosystem ; Fresh Water ; *Genetic Speciation ; Haplotypes/genetics ; Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Although eukaryotic microorganisms are extremely numerous, diverse and essential to global ecosystem functioning, they are largely understudied by evolutionary biologists compared to multicellular macroscopic organisms. In particular, very little is known about the speciation mechanisms which may give rise to the diversity of microscopic eukaryotes. It was postulated that the enormous population sizes and ubiquitous distribution of these organisms could lead to a lack of population differentiation and therefore very low speciation rates. However, such assumptions have traditionally been based on morphospecies, which may not accurately reflect the true diversity, missing cryptic taxa. In this study, we aim to articulate the major diversification mechanisms leading to the contemporary molecular diversity by using a colonial freshwater flagellate, Synura sphagnicola, as an example. Phylogenetic analysis of five sequenced loci showed that S. sphagnicola differentiated into two morphologically distinct lineages approximately 15.4 million years ago, which further diverged into several evolutionarily recent haplotypes during the late Pleistocene. The most recent haplotypes are ecologically and biogeographically much more differentiated than the old lineages, presumably because of their persistent differentiation after the allopatric speciation events. Our study shows that in microbial eukaryotes, species diversification via the colonization of new geographical regions or ecological resources occurs much more readily than was previously thought. Consequently, divergence times of microorganisms in some lineages may be equivalent to the estimated times of speciation in plants and animals.}, } @article {pmid30626024, year = {2019}, author = {Oxford, JT and Reeck, JC and Hardy, MJ}, title = {Extracellular Matrix in Development and Disease.}, journal = {International journal of molecular sciences}, volume = {20}, number = {1}, pages = {}, pmid = {30626024}, issn = {1422-0067}, support = {P20 GM103408/GM/NIGMS NIH HHS/United States ; P20 GM109095/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Disease ; Extracellular Matrix/*metabolism ; *Growth and Development ; Humans ; Integrins/metabolism ; Muscles/metabolism ; Reproduction ; Tissue Engineering ; }, abstract = {The evolution of multicellular metazoan organisms was marked by the inclusion of an extracellular matrix (ECM), a multicomponent, proteinaceous network between cells that contributes to the spatial arrangement of cells and the resulting tissue organization. [...].}, } @article {pmid30612623, year = {2019}, author = {Bowman, JL and Briginshaw, LN and Florent, SN}, title = {Evolution and co-option of developmental regulatory networks in early land plants.}, journal = {Current topics in developmental biology}, volume = {131}, number = {}, pages = {35-53}, doi = {10.1016/bs.ctdb.2018.10.001}, pmid = {30612623}, issn = {1557-8933}, mesh = {*Biological Evolution ; Embryophyta/*genetics/*growth & development ; *Gene Expression Regulation, Plant ; *Gene Regulatory Networks ; Plant Proteins/*genetics ; }, abstract = {Land plants evolved from an ancestral alga from which they inherited developmental and physiological characters. A key innovation of land plants is a life cycle with an alternation of generations, with both haploid gametophyte and diploid sporophyte generations having complex multicellular bodies. The origins of the developmental genetic programs patterning these bodies, whether inherited from an algal ancestor or evolved de novo, and whether programs were co-opted between generations, are largely open questions. We first provide a framework for land plant evolution and co-option of developmental regulatory pathways and then examine two cases in more detail.}, } @article {pmid30612620, year = {2019}, author = {Hackenberg, D and Twell, D}, title = {The evolution and patterning of male gametophyte development.}, journal = {Current topics in developmental biology}, volume = {131}, number = {}, pages = {257-298}, doi = {10.1016/bs.ctdb.2018.10.008}, pmid = {30612620}, issn = {1557-8933}, support = {BB/N005090/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; *Gametogenesis, Plant ; *Plant Physiological Phenomena ; *Plants ; Pollen/*cytology/*physiology ; }, abstract = {The reproductive adaptations of land plants have played a key role in their terrestrial colonization and radiation. This encompasses mechanisms used for the production, dispersal and union of gametes to support sexual reproduction. The production of small motile male gametes and larger immotile female gametes (oogamy) in specialized multicellular gametangia evolved in the charophyte algae, the closest extant relatives of land plants. Reliance on water and motile male gametes for sexual reproduction was retained by bryophytes and basal vascular plants, but was overcome in seed plants by the dispersal of pollen and the guided delivery of non-motile sperm to the female gametes. Here we discuss the evolutionary history of male gametogenesis in streptophytes (green plants) and the underlying developmental biology, including recent advances in bryophyte and angiosperm models. We conclude with a perspective on research trends that promise to deliver a deeper understanding of the evolutionary and developmental mechanisms of male gametogenesis in plants.}, } @article {pmid30612613, year = {2019}, author = {Szövényi, P and Waller, M and Kirbis, A}, title = {Evolution of the plant body plan.}, journal = {Current topics in developmental biology}, volume = {131}, number = {}, pages = {1-34}, doi = {10.1016/bs.ctdb.2018.11.005}, pmid = {30612613}, issn = {1557-8933}, mesh = {*Biological Evolution ; Embryophyta/genetics/*growth & development ; Phylogeny ; Plant Leaves/genetics/*growth & development ; Plant Roots/genetics/*growth & development ; }, abstract = {Land plants evolved about 470 million years ago or even earlier, in a biological crust-dominated terrestrial flora. The origin of land plants was probably one of the most significant events in Earth's history, which ultimately contributed to the greening of the terrestrial environment and opened up the way for the diversification of both plant and non-plant lineages. Fossil and phylogenetic evidence suggest that land plants have evolved from fresh-water charophycean algae, which were physiologically, genetically, and developmentally potentiated to make the transition to land. Since all land plants have biphasic life cycles, in contrast to the haplontic life cycle of Charophytes, the evolution of land plants was linked to the origin of a multicellular sporophytic phase. Land plants have evolved complex body plans in a way that overall complexity increased toward the tip of the land plant tree of life. Early forms were unbranched, with terminal sporangia and simple rhizoid rooting structures but without vasculature and leaves. Later on, branched forms with lateral sporangia appeared and paved the route for the evolution for indeterminacy. Finally, leaves and roots evolved to enable efficient nutrient transport to support a large plant body. The fossil record also suggests that almost all plant organs, such as leaves and roots, evolved multiple times independently over the course of land plant evolution. In this review, we summarize the current knowledge on the evolution of the land plant body plan by combining evidence of the fossil record, phylogenetics, and developmental biology.}, } @article {pmid30590727, year = {2019}, author = {Tsitsekian, D and Daras, G and Alatzas, A and Templalexis, D and Hatzopoulos, P and Rigas, S}, title = {Comprehensive analysis of Lon proteases in plants highlights independent gene duplication events.}, journal = {Journal of experimental botany}, volume = {70}, number = {7}, pages = {2185-2197}, pmid = {30590727}, issn = {1460-2431}, mesh = {Base Sequence ; *Evolution, Molecular ; *Gene Duplication ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Plants/*genetics/metabolism ; Protease La/*genetics/metabolism ; Sequence Alignment ; }, abstract = {The degradation of damaged proteins is essential for cell viability. Lon is a highly conserved ATP-dependent serine-lysine protease that maintains proteostasis. We performed a comparative genome-wide analysis to determine the evolutionary history of Lon proteases. Prokaryotes and unicellular eukaryotes retained a single Lon copy, whereas multicellular eukaryotes acquired a peroxisomal copy, in addition to the mitochondrial gene, to sustain the evolution of higher order organ structures. Land plants developed small Lon gene families. Despite the Lon2 peroxisomal paralog, Lon genes triplicated in the Arabidopsis lineage through sequential evolutionary events including whole-genome and tandem duplications. The retention of Lon1, Lon4, and Lon3 triplicates relied on their differential and even contrasting expression patterns, distinct subcellular targeting mechanisms, and functional divergence. Lon1 seems similar to the pre-duplication ancestral gene unit, whereas the duplication of Lon3 and Lon4 is evolutionarily recent. In the wider context of plant evolution, papaya is the only genome with a single ancestral Lon1-type gene. The evolutionary trend among plants is to acquire Lon copies with ambiguous pre-sequences for dual-targeting to mitochondria and chloroplasts, and a substrate recognition domain that deviates from the ancestral Lon1 type. Lon genes constitute a paradigm of dynamic evolution contributing to understanding the functional fate of gene duplicates.}, } @article {pmid30590062, year = {2019}, author = {Måløy, M and Måløy, F and Lahoz-Beltrá, R and Carlos Nuño, J and Bru, A}, title = {An extended Moran process that captures the struggle for fitness.}, journal = {Mathematical biosciences}, volume = {308}, number = {}, pages = {81-104}, doi = {10.1016/j.mbs.2018.12.014}, pmid = {30590062}, issn = {1879-3134}, mesh = {Animals ; *Biological Evolution ; *Environment ; *Game Theory ; Humans ; *Models, Biological ; *Population Dynamics ; Stochastic Processes ; }, abstract = {When a new type of individual appears in a stable population, the newcomer is typically not advantageous. Due to stochasticity, the new type can grow in numbers, but the newcomers can only become advantageous if they manage to change the environment in such a way that they increase their fitness. This dynamics is observed in several situations in which a relatively stable population is invaded by an alternative strategy, for instance the evolution of cooperation among bacteria, the invasion of cancer in a multicellular organism and the evolution of ideas that contradict social norms. These examples also show that, by generating different versions of itself, the new type increases the probability of winning the struggle for fitness. Our model captures the imposed cooperation whereby the first generation of newcomers dies while changing the environment such that the next generations become more advantageous.}, } @article {pmid30585312, year = {2019}, author = {Denbo, S and Aono, K and Kai, T and Yagasaki, R and Ruiz-Trillo, I and Suga, H}, title = {Revision of the Capsaspora genome using read mating information adjusts the view on premetazoan genome.}, journal = {Development, growth & differentiation}, volume = {61}, number = {1}, pages = {34-42}, doi = {10.1111/dgd.12587}, pmid = {30585312}, issn = {1440-169X}, support = {16K07468//JSPS KAKENHI/ ; //NOVARTIS Foundation/ ; //ITOH Science Foundation/ ; //Naito Foundation/ ; //Prefectural University of Hiroshima JUTEN Grant/ ; ERC-2012-Co-616960//European Research Council Consolidator Grant/ ; BFU2014-57779-P//European Research Council Consolidator Grant/ ; BFU2017-90114-P//European Research Council Consolidator Grant/ ; //Ministerio de Economía y Competitividad (MINECO)/ ; //Agencia Estatal de Investigación (AEI)/ ; //Fondo Europeo de Desarrollo Regional (FEDER)/ ; }, mesh = {Animals ; Chromosomes/genetics ; Eukaryota/enzymology/*genetics/metabolism ; Genome/*genetics ; Phylogeny ; Protein-Tyrosine Kinases/genetics ; }, abstract = {The genome sequences of unicellular holozoans, the closest relatives to animals, are shedding light on the evolution of animal multicellularity, shaping the genetic contents of the putative premetazoans. However, the assembly quality of the genomes remains poor compared to the major model organisms such as human and fly. Improving the assembly is critical for precise comparative genomics studies and further molecular biological studies requiring accurate sequence information such as enhancer analysis and genome editing. In this report, we present a new strategy to improve the assembly by fully exploiting the information of Illumina mate-pair reads. By visualizing the distance and orientation of the mapped read pairs, we could highlight the regions where possible assembly errors exist in the genome sequence of Capsaspora, a lineage of unicellular holozoans. Manual modification of these errors repaired 590 assembly problems in total and reassembled 84 supercontigs into 55. Our telomere prediction analysis using the read pairs containing the pan-eukaryotic telomere-like sequence identified at least 13 chromosomes. The resulting new assembly posed us a re-annotation of 112 genes, including 15 putative receptor protein tyrosine kinases. Our strategy thus provides a useful approach for improving assemblies of draft genomes, and the new Capsaspora genome offers us an opportunity to adjust the view on the genome of the unicellular animal ancestor.}, } @article {pmid30578282, year = {2019}, author = {Zhao, YG and Zhang, H}, title = {Autophagosome maturation: An epic journey from the ER to lysosomes.}, journal = {The Journal of cell biology}, volume = {218}, number = {3}, pages = {757-770}, pmid = {30578282}, issn = {1540-8140}, mesh = {Animals ; *Autophagic Cell Death ; Autophagosomes/*metabolism/pathology ; Biological Transport, Active ; Endoplasmic Reticulum/*metabolism/pathology ; Humans ; Lysosomes/*metabolism/pathology ; Neurodegenerative Diseases/*metabolism/pathology ; }, abstract = {Macroautophagy involves the sequestration of cytoplasmic contents in a double-membrane autophagosome and their delivery to lysosomes for degradation. In multicellular organisms, nascent autophagosomes fuse with vesicles originating from endolysosomal compartments before forming degradative autolysosomes, a process known as autophagosome maturation. ATG8 family members, tethering factors, Rab GTPases, and SNARE proteins act coordinately to mediate fusion of autophagosomes with endolysosomal vesicles. The machinery mediating autophagosome maturation is under spatiotemporal control and provides regulatory nodes to integrate nutrient availability with autophagy activity. Dysfunction of autophagosome maturation is associated with various human diseases, including neurodegenerative diseases, Vici syndrome, cancer, and lysosomal storage disorders. Understanding the molecular mechanisms underlying autophagosome maturation will provide new insights into the pathogenesis and treatment of these diseases.}, } @article {pmid30576875, year = {2019}, author = {Ortega-Escalante, JA and Kwok, O and Miller, SM}, title = {New Selectable Markers for Volvox carteri Transformation.}, journal = {Protist}, volume = {170}, number = {1}, pages = {52-63}, doi = {10.1016/j.protis.2018.11.002}, pmid = {30576875}, issn = {1618-0941}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacillus cereus/genetics ; Cinnamates/*pharmacology ; Coccidioides/genetics ; Drug Resistance, Microbial/*genetics ; Genes, Bacterial/genetics ; Genes, Fungal/genetics ; Genetic Markers/genetics ; Hygromycin B/*analogs & derivatives/pharmacology ; Microorganisms, Genetically-Modified/genetics ; Nucleosides/pharmacology ; Transformation, Genetic/drug effects/*genetics ; Volvox/drug effects/*genetics ; }, abstract = {Volvox carteri is an excellent model for investigating the evolution of multicellularity and cell differentiation, and the rate of future progress with this system will depend on improved molecular genetic tools. Several selectable markers for nuclear transformation of V. carteri have been developed, including the nitrate reductase (nitA) gene, but it would be useful to have additional markers to multiplex transgenes in this species. To further facilitate molecular genetic analyses of V. carteri, we developed two new selectable markers that provide rapid, easily selected, and stable resistance to the antibiotics hygromycin and blasticidin. We generated constructs with Volvox-specific regulatory sequences and codon-optimized hygromycin (VcHyg) and blasticidin (VcBlast) resistance genes from Coccidioides posadasii and Bacillus cereus, respectively. With these constructs, transformants were obtained via biolistic bombardment at rates of 0.5-13 per million target cells bombarded. Antibiotic-resistant survivors were readily isolated 7days post bombardment. VcHyg and VcBlast transgenes and transcripts were detected in transformants. Co-transformation rates using the VcHyg or VcBlast markers with unselected genes were comparable to those obtained with nitA. These results indicate that the pVcHyg and pVcBlast plasmids are highly efficient and convenient for transforming and co-transforming a broad range of V. carteri strains.}, } @article {pmid30568302, year = {2019}, author = {Chen, Y and Ikeda, K and Yoneshiro, T and Scaramozza, A and Tajima, K and Wang, Q and Kim, K and Shinoda, K and Sponton, CH and Brown, Z and Brack, A and Kajimura, S}, title = {Thermal stress induces glycolytic beige fat formation via a myogenic state.}, journal = {Nature}, volume = {565}, number = {7738}, pages = {180-185}, pmid = {30568302}, issn = {1476-4687}, support = {R56 AR060868/AR/NIAMS NIH HHS/United States ; R01 AR061002/AR/NIAMS NIH HHS/United States ; P30 DK063720/DK/NIDDK NIH HHS/United States ; R01 DK097441/DK/NIDDK NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; P30 DK026687/DK/NIDDK NIH HHS/United States ; R01 DK112268/DK/NIDDK NIH HHS/United States ; R01 AR060868/AR/NIAMS NIH HHS/United States ; R01 DK108822/DK/NIDDK NIH HHS/United States ; }, mesh = {Acclimatization ; Adipose Tissue, Beige/*cytology/*metabolism ; Adipose Tissue, White/cytology/metabolism ; Animals ; Cell Differentiation ; Cell Survival ; *Cold Temperature ; *Cold-Shock Response ; Energy Metabolism ; GA-Binding Protein Transcription Factor/metabolism ; *Glycolysis ; Homeostasis ; Male ; Mice ; *Muscle Development ; MyoD Protein/metabolism ; Myoblasts/cytology ; Receptors, Adrenergic, beta/metabolism ; }, abstract = {Environmental cues profoundly affect cellular plasticity in multicellular organisms. For instance, exercise promotes a glycolytic-to-oxidative fibre-type switch in skeletal muscle, and cold acclimation induces beige adipocyte biogenesis in adipose tissue. However, the molecular mechanisms by which physiological or pathological cues evoke developmental plasticity remain incompletely understood. Here we report a type of beige adipocyte that has a critical role in chronic cold adaptation in the absence of β-adrenergic receptor signalling. This beige fat is distinct from conventional beige fat with respect to developmental origin and regulation, and displays enhanced glucose oxidation. We therefore refer to it as glycolytic beige fat. Mechanistically, we identify GA-binding protein α as a regulator of glycolytic beige adipocyte differentiation through a myogenic intermediate. Our study reveals a non-canonical adaptive mechanism by which thermal stress induces progenitor cell plasticity and recruits a distinct form of thermogenic cell that is required for energy homeostasis and survival.}, } @article {pmid30563248, year = {2018}, author = {Wang, Z and Zhou, W and Hameed, MS and Liu, J and Zeng, X}, title = {Characterization and Expression Profiling of Neuropeptides and G-Protein-Coupled Receptors (GPCRs) for Neuropeptides in the Asian Citrus Psyllid, Diaphorina citri (Hemiptera: Psyllidae).}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, pmid = {30563248}, issn = {1422-0067}, support = {31572314//National Natural Science Foundation of China/ ; 2017YFD0202005//National Key Research and Development Program of China/ ; 2015B090903076//Department of Science and Technology of Guangdong Province/ ; }, mesh = {Animals ; Citrus/*parasitology ; Evolution, Molecular ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Developmental ; Hemiptera/genetics/*growth & development ; Insect Proteins/genetics ; Neuropeptides/*genetics ; Organ Specificity ; Phylogeny ; Real-Time Polymerase Chain Reaction ; Receptors, G-Protein-Coupled/*genetics ; Sequence Analysis, RNA ; }, abstract = {Neuropeptides are endogenous active substances that widely exist in multicellular biological nerve tissue and participate in the function of the nervous system, and most of them act on neuropeptide receptors. In insects, neuropeptides and their receptors play important roles in controlling a multitude of physiological processes. In this project, we sequenced the transcriptome from twelve tissues of the Asian citrus psyllid, Diaphorina citri Kuwayama. A total of 40 candidate neuropeptide genes and 42 neuropeptide receptor genes were identified. Among the neuropeptide receptor genes, 35 of them belong to the A-family (or rhodopsin-like), four of them belong to the B-family (or secretin-like), and three of them are leucine-rich repeat-containing G-protein-coupled receptors. The expression profile of the 82 genes across developmental stages was determined by qRT-PCR. Our study provides the first investigation on the genes of neuropeptides and their receptors in D. citri, which may play key roles in regulating the physiology and behaviors of D. citri.}, } @article {pmid30560372, year = {2019}, author = {Dadar, M and Shahali, Y and Chakraborty, S and Prasad, M and Tahoori, F and Tiwari, R and Dhama, K}, title = {Antiinflammatory peptides: current knowledge and promising prospects.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {68}, number = {2}, pages = {125-145}, pmid = {30560372}, issn = {1420-908X}, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Humans ; Immune System/physiology ; Inflammation/complications/*drug therapy/*physiopathology ; Peptides/*pharmacology/*physiology ; }, abstract = {BACKGROUND: Inflammation is part of the regular host reaction to injury or infection caused by toxic factors, pathogens, damaged cells, irritants, and allergens. Antiinflammatory peptides (AIPs) are present in all living organisms, and many peptides from herbal, mammalian, bacterial, and marine origins have been shown to have antimicrobial and/or antiinflammatory properties.

METHODS: In this study, we investigated the effects of antiinflammatory peptides on inflammation, and highlighted the underlying mechanisms responsible for these effects.

RESULTS: In multicellular organisms, including humans, AIPs constitute an essential part of their immune system. In addition, numerous natural and synthetic AIPs are effective immunomodulators and can interfere with signal transduction pathways involved in inflammatory cytokine expression. Among them, some peptides such as antiflammin, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), and those derived from velvet antler proteins, bee venom, horse fly salivary gland, and bovine β-casein have received considerable attention over the past few years.

CONCLUSION: This article presents an overview on the major properties and mechanisms of action associated with AIPs as immunomodulatory, chemotactic, antioxidant, and antimicrobial agents. In addition, the results of various studies dealing with effects of AIPs on numerous classical models of inflammation are reviewed and discussed.}, } @article {pmid30554805, year = {2019}, author = {Stein, WD}, title = {The ages of the cancer-associated genes.}, journal = {Seminars in oncology}, volume = {46}, number = {1}, pages = {10-18}, doi = {10.1053/j.seminoncol.2018.11.001}, pmid = {30554805}, issn = {1532-8708}, mesh = {Carcinoma/genetics ; *Evolution, Molecular ; Genome, Human/*genetics ; Humans ; Lymphoma/genetics ; Mutation/genetics ; Neoplasms/*genetics/pathology ; Open Reading Frames/*genetics ; Sarcoma/genetics ; }, abstract = {In the accompanying manuscript (Litman and Stein, 2018) we list the ages of all the protein-coding genes and of many of the noncoding genes of the human genome. The present manuscript uses those results to derive the ages of the genes on the COSMIC list of somatic mutations in cancer. The lymphoma-associated genes in the COSMIC list are younger than the sarcoma-associated or the carcinoma-associated genes, or the genes shared by lymphomas and carcinomas. Genes that accreted to the evolving genome with the appearance of the fish are major contributors to the sarcoma-, lymphoma-, or carcinoma-associated gene sets, but it is genes accreted during the development of multicellularity that contribute most to the genes common to the classes. Genes arising with the evolution of the fish are also dominant in a list of noncoding genes associated with cancer. A list is provided of the COSMIC genes which have not yet been reported as drug targets.}, } @article {pmid30553725, year = {2018}, author = {Taggart, JC and Li, GW}, title = {Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes.}, journal = {Cell systems}, volume = {7}, number = {6}, pages = {580-589.e4}, pmid = {30553725}, issn = {2405-4712}, support = {R35 GM124732/GM/NIGMS NIH HHS/United States ; T32 GM007287/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Multiprotein Complexes/genetics/*metabolism ; *Protein Biosynthesis ; Protein Subunits/genetics/metabolism ; Ribosomes/genetics/*metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Zebrafish ; }, abstract = {Constituents of multiprotein complexes are required at well-defined levels relative to each other. However, it remains unknown whether eukaryotic cells typically produce precise amounts of subunits, or instead rely on degradation to mitigate imprecise production. Here, we quantified the production rates of multiprotein complexes in unicellular and multicellular eukaryotes using ribosome profiling. By resolving read-mapping ambiguities, which occur for a large fraction of ribosome footprints and distort quantitation accuracy in eukaryotes, we found that obligate components of multiprotein complexes are produced in proportion to their stoichiometry, indicating that their abundances are already precisely tuned at the synthesis level. By systematically interrogating the impact of gene dosage variations in budding yeast, we found a general lack of negative feedback regulation protecting the normally precise rates of subunit synthesis. These results reveal a core principle of proteome homeostasis and highlight the evolution toward quantitative control at every step in the central dogma.}, } @article {pmid30541961, year = {2018}, author = {Hayakawa, IS and Inouye, K}, title = {Species recognition in social amoebae.}, journal = {Journal of biosciences}, volume = {43}, number = {5}, pages = {1025-1036}, pmid = {30541961}, issn = {0973-7138}, mesh = {Biological Evolution ; Dictyostelium/classification/*genetics ; *Genes, Protozoan ; *Genome, Protozoan ; Phylogeny ; Reproduction ; Species Specificity ; }, abstract = {Aggregative multicellularity requires the ability of cells to recognise conspecifics. Social amoebae are among the best studied of such organisms, but the mechanism and evolutionary background of species recognition remained to be investigated. Here we show that heterologous expression of a single Dictyostelium purpureum gene is sufficient for D. discoideum cells to efficiently make chimaeric fruiting bodies with D. purpureum cells. This gene forms a bidirectional pair with another gene on the D. purpureum genome, and they are both highly polymorphic among independent wild isolates of the same mating group that do not form chimaeric fruiting bodies with each other. These paired genes are both structurally similar to D. discoideum tgrB1/C1 pair, which is responsible for clonal discrimination within that species, suggesting that these tgr genes constitute the species recognition system that has attained a level of precision capable of discriminating between clones within a species. Analysis of the available genome sequences of social amoebae revealed that such gene pairs exist only within the clade composed of species that produce precursors of sterile stalk cells (prestalk cells), suggesting concurrent evolution of a precise allorecognition system and a new 'worker' cell-type dedicated to transporting and supporting the reproductive cells.}, } @article {pmid30538242, year = {2018}, author = {Higo, A and Kawashima, T and Borg, M and Zhao, M and López-Vidriero, I and Sakayama, H and Montgomery, SA and Sekimoto, H and Hackenberg, D and Shimamura, M and Nishiyama, T and Sakakibara, K and Tomita, Y and Togawa, T and Kunimoto, K and Osakabe, A and Suzuki, Y and Yamato, KT and Ishizaki, K and Nishihama, R and Kohchi, T and Franco-Zorrilla, JM and Twell, D and Berger, F and Araki, T}, title = {Transcription factor DUO1 generated by neo-functionalization is associated with evolution of sperm differentiation in plants.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5283}, pmid = {30538242}, issn = {2041-1723}, support = {I 2163/FWF_/Austrian Science Fund FWF/Austria ; M 2539/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Cell Differentiation ; Chlorophyta/classification/genetics/growth & development/metabolism ; *Evolution, Molecular ; Germ Cells, Plant/*cytology/metabolism ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants/classification/genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Evolutionary mechanisms underlying innovation of cell types have remained largely unclear. In multicellular eukaryotes, the evolutionary molecular origin of sperm differentiation is unknown in most lineages. Here, we report that in algal ancestors of land plants, changes in the DNA-binding domain of the ancestor of the MYB transcription factor DUO1 enabled the recognition of a new cis-regulatory element. This event led to the differentiation of motile sperm. After neo-functionalization, DUO1 acquired sperm lineage-specific expression in the common ancestor of land plants. Subsequently the downstream network of DUO1 was rewired leading to sperm with distinct morphologies. Conjugating green algae, a sister group of land plants, accumulated mutations in the DNA-binding domain of DUO1 and lost sperm differentiation. Our findings suggest that the emergence of DUO1 was the defining event in the evolution of sperm differentiation and the varied modes of sexual reproduction in the land plant lineage.}, } @article {pmid30532226, year = {2018}, author = {Shan, M and Dai, D and Vudem, A and Varner, JD and Stroock, AD}, title = {Multi-scale computational study of the Warburg effect, reverse Warburg effect and glutamine addiction in solid tumors.}, journal = {PLoS computational biology}, volume = {14}, number = {12}, pages = {e1006584}, pmid = {30532226}, issn = {1553-7358}, mesh = {Cell Line, Tumor ; Cell Proliferation ; Citric Acid Cycle/physiology ; Glucose/metabolism ; Glutamine/*metabolism ; Glycolysis/*physiology ; Humans ; Kinetics ; Lactic Acid/metabolism ; Metabolic Networks and Pathways/physiology ; Metabolome ; Neoplasms/metabolism ; Oxygen/metabolism ; Tumor Microenvironment/*physiology ; }, abstract = {Cancer metabolism has received renewed interest as a potential target for cancer therapy. In this study, we use a multi-scale modeling approach to interrogate the implications of three metabolic scenarios of potential clinical relevance: the Warburg effect, the reverse Warburg effect and glutamine addiction. At the intracellular level, we construct a network of central metabolism and perform flux balance analysis (FBA) to estimate metabolic fluxes; at the cellular level, we exploit this metabolic network to calculate parameters for a coarse-grained description of cellular growth kinetics; and at the multicellular level, we incorporate these kinetic schemes into the cellular automata of an agent-based model (ABM), iDynoMiCS. This ABM evaluates the reaction-diffusion of the metabolites, cellular division and motion over a simulation domain. Our multi-scale simulations suggest that the Warburg effect provides a growth advantage to the tumor cells under resource limitation. However, we identify a non-monotonic dependence of growth rate on the strength of glycolytic pathway. On the other hand, the reverse Warburg scenario provides an initial growth advantage in tumors that originate deeper in the tissue. The metabolic profile of stromal cells considered in this scenario allows more oxygen to reach the tumor cells in the deeper tissue and thus promotes tumor growth at earlier stages. Lastly, we suggest that glutamine addiction does not confer a selective advantage to tumor growth with glutamine acting as a carbon source in the tricarboxylic acid (TCA) cycle, any advantage of glutamine uptake must come through other pathways not included in our model (e.g., as a nitrogen donor). Our analysis illustrates the importance of accounting explicitly for spatial and temporal evolution of tumor microenvironment in the interpretation of metabolic scenarios and hence provides a basis for further studies, including evaluation of specific therapeutic strategies that target metabolism.}, } @article {pmid30532131, year = {2018}, author = {Khasin, M and Cahoon, RR and Nickerson, KW and Riekhof, WR}, title = {Molecular machinery of auxin synthesis, secretion, and perception in the unicellular chlorophyte alga Chlorella sorokiniana UTEX 1230.}, journal = {PloS one}, volume = {13}, number = {12}, pages = {e0205227}, pmid = {30532131}, issn = {1932-6203}, mesh = {Biological Transport, Active/physiology ; Chlorella/genetics/*metabolism ; *Evolution, Molecular ; Indoleacetic Acids/*metabolism ; Plant Proteins/genetics/*metabolism ; Receptors, Cell Surface/genetics/*metabolism ; Signal Transduction/*physiology ; }, abstract = {Indole-3-acetic acid is a ubiquitous small molecule found in all domains of life. It is the predominant and most active auxin in seed plants, where it coordinates a variety of complex growth and development processes. The potential origin of auxin signaling in algae remains a matter of some controversy. In order to clarify the evolutionary context of algal auxin signaling, we undertook a genomic survey to assess whether auxin acts as a signaling molecule in the emerging model chlorophyte Chlorella sorokiniana UTEX 1230. C. sorokiniana produces the auxin indole-3-acetic acid (IAA), which was present in both the cell pellet and in the supernatant at a concentration of ~ 1 nM, and its genome encodes orthologs of genes related to auxin synthesis, transport, and signaling in higher plants. Candidate orthologs for the canonical AUX/IAA signaling pathway were not found; however, auxin-binding protein 1 (ABP1), an alternate auxin receptor, is present and highly conserved at essential auxin binding and zinc coordinating residues. Additionally, candidate orthologs for PIN proteins, responsible for intercellular, vectorial auxin transport in higher plants, were not found, but PILs (PIN-Like) proteins, a recently discovered family that mediates intracellular auxin transport, were identified. The distribution of auxin related gene in this unicellular chlorophyte demonstrates that a core suite of auxin signaling components was present early in the evolution of plants. Understanding the simplified auxin signaling pathways in chlorophytes will aid in understanding phytohormone signaling and crosstalk in seed plants, and in understanding the diversification and integration of developmental signals during the evolution of multicellular plants.}, } @article {pmid30520011, year = {2019}, author = {Rebolleda-Gómez, M and Travisano, M}, title = {Adaptation, chance, and history in experimental evolution reversals to unicellularity.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {73-83}, pmid = {30520011}, issn = {1558-5646}, support = {//John Templeton Foundation/International ; 1051115//Division of Environmental Biology/International ; }, mesh = {*Adaptation, Biological ; *Biological Evolution ; Saccharomyces cerevisiae/*physiology ; }, abstract = {Evolution is often deemed irreversible. The evolution of complex traits that require many mutations makes their reversal unlikely. Even in simpler traits, reversals might become less likely as neutral or beneficial mutations, with deleterious effects in the ancestral context, become fixed in the novel background. This is especially true in changes that involve large reorganizations of the organism and its interactions with the environment. The evolution of multicellularity involves the reorganization of previously autonomous cells into a more complex organism; despite the complexity of this change, single cells have repeatedly evolved from multicellular ancestors. These repeated reversals to unicellularity undermine the generality of Dollo's law. In this article, we evaluated the dynamics of reversals to unicellularity from recently evolved multicellular phenotypes of the brewers yeast Saccharomyces cerevisae. Even though multicellularity in this system evolved recently, it involves the evolution of new levels of selection. Strong selective pressures against multicellularity lead to rapid reversibility to single cells in all of our replicate lines, whereas counterselection favoring multicellularity led to minimal reductions to the rates of reversal. History and chance played an important role in the tempo and mode of reversibility, highlighting the interplay of deterministic and stochastic events in evolutionary reversals.}, } @article {pmid30519187, year = {2018}, author = {Fux, JE and Mehta, A and Moffat, J and Spafford, JD}, title = {Eukaryotic Voltage-Gated Sodium Channels: On Their Origins, Asymmetries, Losses, Diversification and Adaptations.}, journal = {Frontiers in physiology}, volume = {9}, number = {}, pages = {1406}, pmid = {30519187}, issn = {1664-042X}, abstract = {The appearance of voltage-gated, sodium-selective channels with rapid gating kinetics was a limiting factor in the evolution of nervous systems. Two rounds of domain duplications generated a common 24 transmembrane segment (4 × 6 TM) template that is shared amongst voltage-gated sodium (Nav1 and Nav2) and calcium channels (Cav1, Cav2, and Cav3) and leak channel (NALCN) plus homologs from yeast, different single-cell protists (heterokont and unikont) and algae (green and brown). A shared architecture in 4 × 6 TM channels include an asymmetrical arrangement of extended extracellular L5/L6 turrets containing a 4-0-2-2 pattern of cysteines, glycosylated residues, a universally short III-IV cytoplasmic linker and often a recognizable, C-terminal PDZ binding motif. Six intron splice junctions are conserved in the first domain, including a rare U12-type of the minor spliceosome provides support for a shared heritage for sodium and calcium channels, and a separate lineage for NALCN. The asymmetrically arranged pores of 4x6 TM channels allows for a changeable ion selectivity by means of a single lysine residue change in the high field strength site of the ion selectivity filter in Domains II or III. Multicellularity and the appearance of systems was an impetus for Nav1 channels to adapt to sodium ion selectivity and fast ion gating. A non-selective, and slowly gating Nav2 channel homolog in single cell eukaryotes, predate the diversification of Nav1 channels from a basal homolog in a common ancestor to extant cnidarians to the nine vertebrate Nav1.x channel genes plus Nax. A close kinship between Nav2 and Nav1 homologs is evident in the sharing of most (twenty) intron splice junctions. Different metazoan groups have lost their Nav1 channel genes altogether, while vertebrates rapidly expanded their gene numbers. The expansion in vertebrate Nav1 channel genes fills unique functional niches and generates overlapping properties contributing to redundancies. Specific nervous system adaptations include cytoplasmic linkers with phosphorylation sites and tethered elements to protein assemblies in First Initial Segments and nodes of Ranvier. Analogous accessory beta subunit appeared alongside Nav1 channels within different animal sub-phyla. Nav1 channels contribute to pace-making as persistent or resurgent currents, the former which is widespread across animals, while the latter is a likely vertebrate adaptation.}, } @article {pmid30518860, year = {2018}, author = {Rosental, B and Kowarsky, M and Seita, J and Corey, DM and Ishizuka, KJ and Palmeri, KJ and Chen, SY and Sinha, R and Okamoto, J and Mantalas, G and Manni, L and Raveh, T and Clarke, DN and Tsai, JM and Newman, AM and Neff, NF and Nolan, GP and Quake, SR and Weissman, IL and Voskoboynik, A}, title = {Complex mammalian-like haematopoietic system found in a colonial chordate.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {425-429}, pmid = {30518860}, issn = {1476-4687}, support = {T32 AI007290/AI/NIAID NIH HHS/United States ; R01 AG037968/AG/NIA NIH HHS/United States ; T32 AR050942/AR/NIAMS NIH HHS/United States ; T32HL120824-03/HL/NHLBI NIH HHS/United States ; R01 GM100315/GM/NIGMS NIH HHS/United States ; R56 AI089968/AI/NIAID NIH HHS/United States ; T32 HL120824/HL/NHLBI NIH HHS/United States ; 5T32AI07290-28/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Cell Lineage ; Cytotoxicity, Immunologic ; Female ; Flow Cytometry ; *Hematopoiesis ; Hematopoietic Stem Cells/cytology/immunology ; Hematopoietic System/*cytology ; Immunity, Cellular ; Isoantigens/immunology ; Male ; Mammals/anatomy & histology/*blood ; Myeloid Cells/cytology/immunology ; Phagocytosis/immunology ; *Phylogeny ; Stem Cell Niche ; Transcriptome/genetics ; Urochordata/anatomy & histology/*cytology/genetics/immunology ; }, abstract = {Haematopoiesis is an essential process that evolved in multicellular animals. At the heart of this process are haematopoietic stem cells (HSCs), which are multipotent and self-renewing, and generate the entire repertoire of blood and immune cells throughout an animal's life[1]. Although there have been comprehensive studies on self-renewal, differentiation, physiological regulation and niche occupation in vertebrate HSCs, relatively little is known about the evolutionary origin and niches of these cells. Here we describe the haematopoietic system of Botryllus schlosseri, a colonial tunicate that has a vasculature and circulating blood cells, and interesting stem-cell biology and immunity characteristics[2-8]. Self-recognition between genetically compatible B. schlosseri colonies leads to the formation of natural parabionts with shared circulation, whereas incompatible colonies reject each other[3,4,7]. Using flow cytometry, whole-transcriptome sequencing of defined cell populations and diverse functional assays, we identify HSCs, progenitors, immune effector cells and an HSC niche, and demonstrate that self-recognition inhibits allospecific cytotoxic reactions. Our results show that HSC and myeloid lineage immune cells emerged in a common ancestor of tunicates and vertebrates, and also suggest that haematopoietic bone marrow and the B. schlosseri endostyle niche evolved from a common origin.}, } @article {pmid30510177, year = {2018}, author = {Kayser, J and Schreck, CF and Gralka, M and Fusco, D and Hallatschek, O}, title = {Collective motion conceals fitness differences in crowded cellular populations.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {125-134}, pmid = {30510177}, issn = {2397-334X}, support = {R01 GM115851/GM/NIGMS NIH HHS/United States ; }, mesh = {Biofilms/*growth & development ; *Biological Evolution ; Biomechanical Phenomena ; Humans ; *Microbiota/genetics ; *Models, Biological ; Mutation ; Saccharomyces cerevisiae/genetics/*growth & development ; }, abstract = {Many cellular populations are tightly packed, such as microbial colonies and biofilms, or tissues and tumours in multicellular organisms. The movement of one cell in these crowded assemblages requires motion of others, so that cell displacements are correlated over many cell diameters. Whenever movement is important for survival or growth, these correlated rearrangements could couple the evolutionary fate of different lineages. However, little is known about the interplay between mechanical forces and evolution in dense cellular populations. Here, by tracking slower-growing clones at the expanding edge of yeast colonies, we show that the collective motion of cells prevents costly mutations from being weeded out rapidly. Joint pushing by neighbouring cells generates correlated movements that suppress the differential displacements required for selection to act. This mechanical screening of fitness differences allows slower-growing mutants to leave more descendants than expected under non-mechanical models, thereby increasing their chance for evolutionary rescue. Our work suggests that, in crowded populations, cells cooperate with surrounding neighbours through inevitable mechanical interactions. This effect has to be considered when predicting evolutionary outcomes, such as the emergence of drug resistance or cancer evolution.}, } @article {pmid30500812, year = {2018}, author = {Medina-Castellanos, E and Villalobos-Escobedo, JM and Riquelme, M and Read, ND and Abreu-Goodger, C and Herrera-Estrella, A}, title = {Danger signals activate a putative innate immune system during regeneration in a filamentous fungus.}, journal = {PLoS genetics}, volume = {14}, number = {11}, pages = {e1007390}, pmid = {30500812}, issn = {1553-7404}, support = {BB/P027849/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Biomarkers ; Calcium/metabolism ; Gene Expression Regulation, Fungal ; *Host-Pathogen Interactions ; Hyphae ; *Immunity, Innate ; Mycoses/immunology/*microbiology ; *Regeneration ; *Signal Transduction ; Trichoderma/*physiology ; }, abstract = {The ability to respond to injury is a biological process shared by organisms of different kingdoms that can even result in complete regeneration of a part or structure that was lost. Due to their immobility, multicellular fungi are prey to various predators and are therefore constantly exposed to mechanical damage. Nevertheless, our current knowledge of how fungi respond to injury is scarce. Here we show that activation of injury responses and hyphal regeneration in the filamentous fungus Trichoderma atroviride relies on the detection of two danger or alarm signals. As an early response to injury, we detected a transient increase in cytosolic free calcium ([Ca2+]c) that was promoted by extracellular ATP, and which is likely regulated by a mechanism of calcium-induced calcium-release. In addition, we demonstrate that the mitogen activated protein kinase Tmk1 plays a key role in hyphal regeneration. Calcium- and Tmk1-mediated signaling cascades activated major transcriptional changes early following injury, including induction of a set of regeneration associated genes related to cell signaling, stress responses, transcription regulation, ribosome biogenesis/translation, replication and DNA repair. Interestingly, we uncovered the activation of a putative fungal innate immune response, including the involvement of HET domain genes, known to participate in programmed cell death. Our work shows that fungi and animals share danger-signals, signaling cascades, and the activation of the expression of genes related to immunity after injury, which are likely the result of convergent evolution.}, } @article {pmid30498215, year = {2018}, author = {Billerbeck, S and Brisbois, J and Agmon, N and Jimenez, M and Temple, J and Shen, M and Boeke, JD and Cornish, VW}, title = {A scalable peptide-GPCR language for engineering multicellular communication.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5057}, pmid = {30498215}, issn = {2041-1723}, support = {R01 AI110794/AI/NIAID NIH HHS/United States ; S10 RR027050/RR/NCRR NIH HHS/United States ; T32 GM007308/GM/NIGMS NIH HHS/United States ; T32 GM066704/GM/NIGMS NIH HHS/United States ; }, mesh = {Computational Biology/methods ; Peptides/genetics/*metabolism ; Protein Binding ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Signal Transduction ; Synthetic Biology/methods ; }, abstract = {Engineering multicellularity is one of the next breakthroughs for Synthetic Biology. A key bottleneck to building multicellular systems is the lack of a scalable signaling language with a large number of interfaces that can be used simultaneously. Here, we present a modular, scalable, intercellular signaling language in yeast based on fungal mating peptide/G-protein-coupled receptor (GPCR) pairs harnessed from nature. First, through genome-mining, we assemble 32 functional peptide-GPCR signaling interfaces with a range of dose-response characteristics. Next, we demonstrate that these interfaces can be combined into two-cell communication links, which serve as assembly units for higher-order communication topologies. Finally, we show 56 functional, two-cell links, which we use to assemble three- to six-member communication topologies and a three-member interdependent community. Importantly, our peptide-GPCR language is scalable and tunable by genetic encoding, requires minimal component engineering, and should be massively scalable by further application of our genome mining pipeline or directed evolution.}, } @article {pmid30484227, year = {2018}, author = {Trosko, JE}, title = {The Role of the Mitochondria in the Evolution of Stem Cells, Including MUSE Stem Cells and Their Biology.}, journal = {Advances in experimental medicine and biology}, volume = {1103}, number = {}, pages = {131-152}, doi = {10.1007/978-4-431-56847-6_7}, pmid = {30484227}, issn = {0065-2598}, mesh = {Adult Stem Cells/cytology ; *Biological Evolution ; Cell Differentiation ; Humans ; Induced Pluripotent Stem Cells/cytology ; Mitochondria/*physiology ; Pluripotent Stem Cells/*cytology ; }, abstract = {From the transition of single-cell organisms to multicellularity of metazoans, evolutionary pressures selected new genes and phenotypes to cope with the oxygenation of the Earth's environment, especially via the symbiotic acquisition of the mitochondrial organelle. There were many new genes and phenotypes that appeared, namely, stem cells, low-oxygen-micro-environments to house these genes ("niches"), new epigenetic mechanisms to regulate , selectively, the gene repertoire to control proliferation, differentiation, apoptosis, senescence and DNA protection mechanisms, including antioxidant genes and DNA repair. This transition required a critical regulation of the metabolism of glucose to produce energy for both the stem cell quiescent state and the energy-requiring differentiated state. While the totipotent-, embryonic-, pluripotent-, and a few adult organ-specific stem cells were recognized, only relatively recently, because of the isolation of somatic cell nuclear transfer (SCNT) stem cells and "induced pluripotent stem" cells, challenges to the origin of these "iPS" cells have been made. The isolation and characterization of human MUSE stem cells and more adult organ-specific adult stem cells have indicated that these MUSE cells have many shared characteristics of the "iPS" cells, yet they do not form teratomas but can give rise to the trigeminal cell layers. While the MUSE cells are a subset of human fibroblastic cells, they have not been characterized, yet, for the mitochondrial metabolic genes, either in the stem cell state or during their differentiation processes. A description of other human adult stem cells will be made to set future studies of how the MUSE stem cells compare to all other stem cells.}, } @article {pmid30478288, year = {2019}, author = {Pollier, J and Vancaester, E and Kuzhiumparambil, U and Vickers, CE and Vandepoele, K and Goossens, A and Fabris, M}, title = {A widespread alternative squalene epoxidase participates in eukaryote steroid biosynthesis.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {226-233}, doi = {10.1038/s41564-018-0305-5}, pmid = {30478288}, issn = {2058-5276}, mesh = {Biosynthetic Pathways ; Coenzymes ; Diatoms/enzymology/genetics/metabolism ; Eukaryota/classification/*enzymology/genetics/metabolism ; Gene Expression ; Genetic Complementation Test ; Membrane Proteins/chemistry/genetics/metabolism ; Mixed Function Oxygenases/chemistry/*genetics/*metabolism ; Phylogeny ; Protein Conformation ; Saccharomyces cerevisiae/drug effects/enzymology/genetics/metabolism ; Squalene/analogs & derivatives/metabolism ; Squalene Monooxygenase/chemistry/genetics/metabolism ; Steroids/*biosynthesis ; Terbinafine/pharmacology ; }, abstract = {Steroids are essential triterpenoid molecules that are present in all eukaryotes and modulate the fluidity and flexibility of cell membranes. Steroids also serve as signalling molecules that are crucial for growth, development and differentiation of multicellular organisms[1-3]. The steroid biosynthetic pathway is highly conserved and is key in eukaryote evolution[4-7]. The flavoprotein squalene epoxidase (SQE) catalyses the first oxygenation reaction in this pathway and is rate limiting. However, despite its conservation in animals, plants and fungi, several phylogenetically widely distributed eukaryote genomes lack an SQE-encoding gene[7,8]. Here, we discovered and characterized an alternative SQE (AltSQE) belonging to the fatty acid hydroxylase superfamily. AltSQE was identified through screening of a gene library of the diatom Phaeodactylum tricornutum in a SQE-deficient yeast. In accordance with its divergent protein structure and need for cofactors, we found that AltSQE is insensitive to the conventional SQE inhibitor terbinafine. AltSQE is present in many eukaryotic lineages but is mutually exclusive with SQE and shows a patchy distribution within monophyletic clades. Our discovery provides an alternative element for the conserved steroid biosynthesis pathway, raises questions about eukaryote metabolic evolution and opens routes to develop selective SQE inhibitors to control hazardous organisms.}, } @article {pmid30477635, year = {2018}, author = {Nissen, SB and Rønhild, S and Trusina, A and Sneppen, K}, title = {Theoretical tool bridging cell polarities with development of robust morphologies.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30477635}, issn = {2050-084X}, mesh = {Animals ; Biomechanical Phenomena ; Cell Adhesion ; Cell Polarity ; Cell Proliferation ; Collagen/chemistry ; Computer Simulation ; Drug Combinations ; Eukaryotic Cells/*cytology/physiology ; Gastrulation/*physiology ; Laminin/chemistry ; Machine Learning ; *Models, Biological ; Organoids/cytology/physiology ; Proteoglycans/chemistry ; Sea Urchins/*cytology/physiology ; }, abstract = {Despite continual renewal and damages, a multicellular organism is able to maintain its complex morphology. How is this stability compatible with the complexity and diversity of living forms? Looking for answers at protein level may be limiting as diverging protein sequences can result in similar morphologies. Inspired by the progressive role of apical-basal and planar cell polarity in development, we propose that stability, complexity, and diversity are emergent properties in populations of proliferating polarized cells. We support our hypothesis by a theoretical approach, developed to effectively capture both types of polar cell adhesions. When applied to specific cases of development - gastrulation and the origins of folds and tubes - our theoretical tool suggests experimentally testable predictions pointing to the strength of polar adhesion, restricted directions of cell polarities, and the rate of cell proliferation to be major determinants of morphological diversity and stability.}, } @article {pmid30473004, year = {2018}, author = {Gruenheit, N and Parkinson, K and Brimson, CA and Kuwana, S and Johnson, EJ and Nagayama, K and Llewellyn, J and Salvidge, WM and Stewart, B and Keller, T and van Zon, W and Cotter, SL and Thompson, CRL}, title = {Cell Cycle Heterogeneity Can Generate Robust Cell Type Proportioning.}, journal = {Developmental cell}, volume = {47}, number = {4}, pages = {494-508.e4}, pmid = {30473004}, issn = {1878-1551}, support = {/WT_/Wellcome Trust/United Kingdom ; BB/M007146/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 105610/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; 095643/A/11/Z/WT_/Wellcome Trust/United Kingdom ; 101582/Z/13/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Cycle/*physiology ; Cell Differentiation/*physiology ; Cell Division/*physiology ; Cell Lineage/physiology ; Dictyostelium/*metabolism ; Spores, Fungal/metabolism ; }, abstract = {Cell-cell heterogeneity can facilitate lineage choice during embryonic development because it primes cells to respond to differentiation cues. However, remarkably little is known about the origin of heterogeneity or whether intrinsic and extrinsic variation can be controlled to generate reproducible cell type proportioning seen in vivo. Here, we use experimentation and modeling in D. discoideum to demonstrate that population-level cell cycle heterogeneity can be optimized to generate robust cell fate proportioning. First, cell cycle position is quantitatively linked to responsiveness to differentiation-inducing signals. Second, intrinsic variation in cell cycle length ensures cells are randomly distributed throughout the cell cycle at the onset of multicellular development. Finally, extrinsic perturbation of optimal cell cycle heterogeneity is buffered by compensatory changes in global signal responsiveness. These studies thus illustrate key regulatory principles underlying cell-cell heterogeneity optimization and the generation of robust and reproducible fate choice in development.}, } @article {pmid30458131, year = {2018}, author = {Titus, MA and Goodson, HV}, title = {Developing Evolutionary Cell Biology.}, journal = {Developmental cell}, volume = {47}, number = {4}, pages = {395-396}, doi = {10.1016/j.devcel.2018.11.006}, pmid = {30458131}, issn = {1878-1551}, mesh = {Animals ; Biological Evolution ; *Choanoflagellata ; *Phylogeny ; Septins ; Transfection ; }, abstract = {Recent advances in both phylogenetic comparisons and the development of experimentally tractable organisms, in the growing field of evolutionary cell biology, pave the way for gaining a molecular understanding of the development of multicellularity in the animal lineage.}, } @article {pmid30445510, year = {2019}, author = {Saxena, AS and Salomon, MP and Matsuba, C and Yeh, SD and Baer, CF}, title = {Evolution of the Mutational Process under Relaxed Selection in Caenorhabditis elegans.}, journal = {Molecular biology and evolution}, volume = {36}, number = {2}, pages = {239-251}, pmid = {30445510}, issn = {1537-1719}, support = {R01 GM072639/GM/NIGMS NIH HHS/United States ; R01 GM107227/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Caenorhabditis elegans/*genetics ; DNA Copy Number Variations ; Genetic Fitness ; *Genetic Load ; Microsatellite Repeats ; *Mutation ; Recombination, Genetic ; Selection, Genetic ; }, abstract = {The mutational process varies at many levels, from within genomes to among taxa. Many mechanisms have been linked to variation in mutation, but understanding of the evolution of the mutational process is rudimentary. Physiological condition is often implicated as a source of variation in microbial mutation rate and may contribute to mutation rate variation in multicellular organisms.Deleterious mutations are an ubiquitous source of variation in condition. We test the hypothesis that the mutational process depends on the underlying mutation load in two groups of Caenorhabditis elegans mutation accumulation (MA) lines that differ in their starting mutation loads. "First-order MA" (O1MA) lines maintained under minimal selection for ∼250 generations were divided into high-fitness and low-fitness groups and sets of "second-order MA" (O2MA) lines derived from each O1MA line were maintained for ∼150 additional generations. Genomes of 48 O2MA lines and their progenitors were sequenced. There is significant variation among O2MA lines in base-substitution rate (µbs), but no effect of initial fitness; the indel rate is greater in high-fitness O2MA lines. Overall, µbs is positively correlated with recombination and proximity to short tandem repeats and negatively correlated with 10 bp and 1 kb GC content. However, probability of mutation is sufficiently predicted by the three-nucleotide motif alone. Approximately 90% of the variance in standing nucleotide variation is explained by mutability. Total mutation rate increased in the O2MA lines, as predicted by the "drift barrier" model of mutation rate evolution. These data, combined with experimental estimates of fitness, suggest that epistasis is synergistic.}, } @article {pmid30444659, year = {2018}, author = {Rebolleda-Gómez, M and Travisano, M}, title = {The Cost of Being Big: Local Competition, Importance of Dispersal, and Experimental Evolution of Reversal to Unicellularity.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {731-744}, doi = {10.1086/700095}, pmid = {30444659}, issn = {1537-5323}, mesh = {*Biological Evolution ; Computer Simulation ; Saccharomyces cerevisiae/cytology/genetics/*growth & development ; }, abstract = {Multicellularity provides multiple benefits. Nonetheless, unicellularity is ubiquitous, and there have been multiple cases of evolutionary reversal to a unicellular organization. In this article, we explore some of the costs of multicellularity as well as the possibility and dynamics of evolutionary reversals to unicellularity. We hypothesize that recently evolved multicellular organisms would face a high cost of increased competition for local resources in spatially structured environments because of larger size and increased cell densities. To test this hypothesis we conducted competition assays, computer simulations, and selection experiments using isolates of Saccharomyces cerevisiae that recently evolved multicellularity. In well-mixed environments, multicellular isolates had lower growth rates relative to their unicellular ancestor because of limitations of space and resource acquisition. In structured environments with localized resources, cells in both multicellular and unicellular isolates grew at a similar rate. Despite similar growth, higher local density of cells in multicellular groups led to increased competition and higher fitness costs in spatially structured environments. In structured environments all of the multicellular isolates rapidly evolved a predominantly unicellular life cycle, while in well-mixed environments reversal was more gradual. Taken together, these results suggest that a lack of dispersal, leading to higher local competition, might have been one of the main constraints in the evolution of early multicellular forms.}, } @article {pmid30429351, year = {2019}, author = {Ayoubian, H and Ludwig, N and Fehlmann, T and Menegatti, J and Gröger, L and Anastasiadou, E and Trivedi, P and Keller, A and Meese, E and Grässer, FA}, title = {Epstein-Barr Virus Infection of Cell Lines Derived from Diffuse Large B-Cell Lymphomas Alters MicroRNA Loading of the Ago2 Complex.}, journal = {Journal of virology}, volume = {93}, number = {3}, pages = {}, pmid = {30429351}, issn = {1098-5514}, mesh = {Argonaute Proteins/genetics/*metabolism ; Epstein-Barr Virus Infections/*genetics/metabolism/virology ; *Gene Expression Regulation, Neoplastic ; Herpesvirus 4, Human/*isolation & purification ; High-Throughput Nucleotide Sequencing ; Humans ; Lymphoma, Large B-Cell, Diffuse/*genetics/metabolism/virology ; MicroRNAs/*genetics ; Tumor Cells, Cultured ; }, abstract = {Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoid tumor which is occasionally Epstein-Barr virus (EBV) positive and is further subtyped as activated B-cell DLBCL (ABC-DLBCL) and germinal center B-cell DLBCL (GCB-DLBCL), which has implications for prognosis and treatment. We performed Ago2 RNA immunoprecipitation followed by high-throughput RNA sequencing (Ago2-RIP-seq) to capture functionally active microRNAs (miRNAs) in EBV-negative ABC-DLBCL and GCB-DLBCL cell lines and their EBV-infected counterparts. In parallel, total miRNA profiles of these cells were determined to capture the cellular miRNA profile for comparison with the functionally active profile. Selected miRNAs with differential abundances were validated using real-time quantitative PCR (RT-qPCR) and Northern blotting. We found 6 miRNAs with differential abundances (2 upregulated and 4 downregulated miRNAs) between EBV-negative and -positive ABC-DLBCL cells and 12 miRNAs with differential abundances (3 upregulated and 9 downregulated miRNAs) between EBV-negative and -positive GCB-DLBCL cells. Eight and twelve miRNAs were confirmed using RT-qPCR in ABC-DLBCL and GCB-DLBCL cells, respectively. Selected miRNAs were analyzed in additional type I/II versus type III EBV latency DLBCL cell lines. Furthermore, upregulation of miR-221-3p and downregulation of let7c-5p in ABC-DLBCL cells and upregulation of miR-363-3p and downregulation of miR-423-5p in GCB-DLBCL cells were verified using RIP-Northern blotting. Our comprehensive sequence analysis of the DLBCL miRNA profiles identified sets of deregulated miRNAs by Ago2-RIP-seq. Our Ago2-IP-seq miRNA profile could be considered an important data set for the detection of deregulated functionally active miRNAs in DLBCLs and could possibly lead to the identification of miRNAs as biomarkers for the classification of DLBCLs or even as targets for personalized targeted treatment.IMPORTANCE Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive tumor of lymphoid origin which is occasionally Epstein-Barr virus (EBV) positive. MicroRNAs are found in most multicellular organisms and even in viruses such as EBV. They regulate the synthesis of proteins by binding to their cognate mRNA. MicroRNAs are tethered to their target mRNAs by "Argonaute" proteins. Here we compared the overall miRNA content of the Ago2 complex by differential loading to the overall content of miRNAs in two DLBCL cell lines and their EBV-converted counterparts. In all cell lines, the Ago2 load was different from the overall expression of miRNAs. In addition, the loading of the Ago2 complex was changed upon infection with EBV. This indicates that the virus not only changes the overall content of miRNAs but also influences the expression of proteins by affecting the Ago complexes.}, } @article {pmid30427935, year = {2018}, author = {Schneider, P and Greischar, MA and Birget, PLG and Repton, C and Mideo, N and Reece, SE}, title = {Adaptive plasticity in the gametocyte conversion rate of malaria parasites.}, journal = {PLoS pathogens}, volume = {14}, number = {11}, pages = {e1007371}, pmid = {30427935}, issn = {1553-7374}, support = {NE/K006029/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 202769/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adaptation, Biological/physiology ; Adaptation, Physiological/*physiology ; Animals ; Biological Evolution ; Computer Simulation ; Erythrocytes/parasitology ; Host-Parasite Interactions ; Malaria/*parasitology ; Models, Theoretical ; Parasites ; Plasmodium/*physiology ; Plasmodium chabaudi/physiology ; Reproduction/physiology ; Reproduction, Asexual/physiology ; }, abstract = {Sexually reproducing parasites, such as malaria parasites, experience a trade-off between the allocation of resources to asexual replication and the production of sexual forms. Allocation by malaria parasites to sexual forms (the conversion rate) is variable but the evolutionary drivers of this plasticity are poorly understood. We use evolutionary theory for life histories to combine a mathematical model and experiments to reveal that parasites adjust conversion rate according to the dynamics of asexual densities in the blood of the host. Our model predicts the direction of change in conversion rates that returns the greatest fitness after perturbation of asexual densities by different doses of antimalarial drugs. The loss of a high proportion of asexuals is predicted to elicit increased conversion (terminal investment), while smaller losses are managed by reducing conversion (reproductive restraint) to facilitate within-host survival and future transmission. This non-linear pattern of allocation is consistent with adaptive reproductive strategies observed in multicellular organisms. We then empirically estimate conversion rates of the rodent malaria parasite Plasmodium chabaudi in response to the killing of asexual stages by different doses of antimalarial drugs and forecast the short-term fitness consequences of these responses. Our data reveal the predicted non-linear pattern, and this is further supported by analyses of previous experiments that perturb asexual stage densities using drugs or within-host competition, across multiple parasite genotypes. Whilst conversion rates, across all datasets, are most strongly influenced by changes in asexual density, parasites also modulate conversion according to the availability of red blood cell resources. In summary, increasing conversion maximises short-term transmission and reducing conversion facilitates in-host survival and thus, future transmission. Understanding patterns of parasite allocation to reproduction matters because within-host replication is responsible for disease symptoms and between-host transmission determines disease spread.}, } @article {pmid30415103, year = {2018}, author = {Schuler, GA and Tice, AK and Pearce, RA and Foreman, E and Stone, J and Gammill, S and Willson, JD and Reading, C and Silberman, JD and Brown, MW}, title = {Phylogeny and Classification of Novel Diversity in Sainouroidea (Cercozoa, Rhizaria) Sheds Light on a Highly Diverse and Divergent Clade.}, journal = {Protist}, volume = {169}, number = {6}, pages = {853-874}, doi = {10.1016/j.protis.2018.08.002}, pmid = {30415103}, issn = {1618-0941}, mesh = {Cercozoa/*classification/cytology/genetics/*isolation & purification ; Cluster Analysis ; DNA, Protozoan/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Environmental Microbiology ; Microscopy ; Microscopy, Electron, Transmission ; *Phylogeny ; RNA, Ribosomal, 18S/genetics ; Sequence Analysis, DNA ; }, abstract = {Sainouroidea is a molecularly diverse clade of cercozoan flagellates and amoebae in the eukaryotic supergroup Rhizaria. Previous 18S rDNA environmental sequencing of globally collected fecal and soil samples revealed great diversity and high sequence divergence in the Sainouroidea. However, a very limited amount of this diversity has been observed or described. The two described genera of amoebae in this clade are Guttulinopsis, which displays aggregative multicellularity, and Rosculus, which does not. Although the identity of Guttulinopsis is straightforward due to the multicellular fruiting bodies they form, the same is not true for Rosculus, and the actual identity of the original isolate is unclear. Here we isolated amoebae with morphologies like that of Guttulinopsis and Rosculus from many environments and analyzed them using 18S rDNA sequencing, light microscopy, and transmission electron microscopy. We define a molecular species concept for Sainouroidea that resulted in the description of 4 novel genera and 12 novel species of naked amoebae. Aggregative fruiting is restricted to the genus Guttulinopsis, but other than this there is little morphological variation amongst these taxa. Taken together, simple identification of these amoebae is problematic and potentially unresolvable without the 18S rDNA sequence.}, } @article {pmid30410727, year = {2018}, author = {Morris, JJ}, title = {What is the hologenome concept of evolution?.}, journal = {F1000Research}, volume = {7}, number = {}, pages = {}, pmid = {30410727}, issn = {2046-1402}, mesh = {Animals ; *Biological Evolution ; Biota ; Genome ; Humans ; Microbiota/*genetics ; Phenotype ; Selection, Genetic ; }, abstract = {All multicellular organisms are colonized by microbes, but a gestalt study of the composition of microbiome communities and their influence on the ecology and evolution of their macroscopic hosts has only recently become possible. One approach to thinking about the topic is to view the host-microbiome ecosystem as a "holobiont". Because natural selection acts on an organism's realized phenotype, and the phenotype of a holobiont is the result of the integrated activities of both the host and all of its microbiome inhabitants, it is reasonable to think that evolution can act at the level of the holobiont and cause changes in the "hologenome", or the collective genomic content of all the individual bionts within the holobiont. This relatively simple assertion has nevertheless been controversial within the microbiome community. Here, I provide a review of recent work on the hologenome concept of evolution. I attempt to provide a clear definition of the concept and its implications and to clarify common points of disagreement.}, } @article {pmid30404915, year = {2018}, author = {Gao, A and Shrinivas, K and Lepeudry, P and Suzuki, HI and Sharp, PA and Chakraborty, AK}, title = {Evolution of weak cooperative interactions for biological specificity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11053-E11060}, pmid = {30404915}, issn = {1091-6490}, support = {P01 CA042063/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Cell Physiological Phenomena ; *Computer Simulation ; Humans ; *Models, Biological ; Protein Domains/physiology ; Proteins/metabolism ; }, abstract = {A hallmark of biological systems is that particular functions and outcomes are realized in specific contexts, such as when particular signals are received. One mechanism for mediating specificity is described by Fisher's "lock and key" metaphor, exemplified by enzymes that bind selectively to a particular substrate via specific finely tuned interactions. Another mechanism, more prevalent in multicellular organisms, relies on multivalent weak cooperative interactions. Its importance has recently been illustrated by the recognition that liquid-liquid phase transitions underlie the formation of membraneless condensates that perform specific cellular functions. Based on computer simulations of an evolutionary model, we report that the latter mechanism likely became evolutionarily prominent when a large number of tasks had to be performed specifically for organisms to function properly. We find that the emergence of weak cooperative interactions for mediating specificity results in organisms that can evolve to accomplish new tasks with fewer, and likely less lethal, mutations. We argue that this makes the system more capable of undergoing evolutionary changes robustly, and thus this mechanism has been repeatedly positively selected in increasingly complex organisms. Specificity mediated by weak cooperative interactions results in some useful cross-reactivity for related tasks, but at the same time increases susceptibility to misregulation that might lead to pathologies.}, } @article {pmid30404807, year = {2019}, author = {Palmer, WH and Joosten, J and Overheul, GJ and Jansen, PW and Vermeulen, M and Obbard, DJ and Van Rij, RP}, title = {Induction and Suppression of NF-κB Signalling by a DNA Virus of Drosophila.}, journal = {Journal of virology}, volume = {93}, number = {3}, pages = {}, pmid = {30404807}, issn = {1098-5514}, mesh = {Animals ; DNA Viruses/*immunology ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/growth & development/*metabolism/virology ; Female ; Immunity, Innate/*immunology ; NF-kappa B/antagonists & inhibitors/genetics/*metabolism ; RNA Interference ; Signal Transduction ; Toll-Like Receptors/genetics/metabolism ; Viral Proteins/genetics/*metabolism ; Virus Replication/*immunology ; }, abstract = {Interactions between the insect immune system and RNA viruses have been extensively studied in Drosophila, in which RNA interference, NF-κB, and JAK-STAT pathways underlie antiviral immunity. In response to RNA interference, insect viruses have convergently evolved suppressors of this pathway that act by diverse mechanisms to permit viral replication. However, interactions between the insect immune system and DNA viruses have received less attention, primarily because few Drosophila-infecting DNA virus isolates are available. In this study, we used a recently isolated DNA virus of Drosophila melanogaster, Kallithea virus (KV; family Nudiviridae), to probe known antiviral immune responses and virus evasion tactics in the context of DNA virus infection. We found that fly mutants for RNA interference and immune deficiency (Imd), but not Toll, pathways are more susceptible to Kallithea virus infection. We identified the Kallithea virus-encoded protein gp83 as a potent inhibitor of Toll signalling, suggesting that Toll mediates antiviral defense against Kallithea virus infection but that it is suppressed by the virus. We found that Kallithea virus gp83 inhibits Toll signalling through the regulation of NF-κB transcription factors. Furthermore, we found that gp83 of the closely related Drosophila innubila nudivirus (DiNV) suppresses D. melanogaster Toll signalling, suggesting an evolutionarily conserved function of Toll in defense against DNA viruses. Together, these results provide a broad description of known antiviral pathways in the context of DNA virus infection and identify the first Toll pathway inhibitor in a Drosophila virus, extending the known diversity of insect virus-encoded immune inhibitors.IMPORTANCE Coevolution of multicellular organisms and their natural viruses may lead to an intricate relationship in which host survival requires effective immunity and virus survival depends on evasion of such responses. Insect antiviral immunity and reciprocal virus immunosuppression tactics have been well studied in Drosophila melanogaster, primarily during RNA, but not DNA, virus infection. Therefore, we describe interactions between a recently isolated Drosophila DNA virus (Kallithea virus [KV]) and immune processes known to control RNA viruses, such as RNA interference (RNAi) and Imd pathways. We found that KV suppresses the Toll pathway and identified gp83 as a KV-encoded protein that underlies this suppression. This immunosuppressive ability is conserved in another nudivirus, suggesting that the Toll pathway has conserved antiviral activity against DNA nudiviruses, which have evolved suppressors in response. Together, these results indicate that DNA viruses induce and suppress NF-κB responses, and they advance the application of KV as a model to study insect immunity.}, } @article {pmid30396330, year = {2018}, author = {Joo, S and Wang, MH and Lui, G and Lee, J and Barnas, A and Kim, E and Sudek, S and Worden, AZ and Lee, JH}, title = {Common ancestry of heterodimerizing TALE homeobox transcription factors across Metazoa and Archaeplastida.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {136}, pmid = {30396330}, issn = {1741-7007}, mesh = {Animals ; Computational Biology ; *Dimerization ; *Evolution, Molecular ; *Genes, Homeobox ; Phylogeny ; Plants/*genetics ; Transcription Factors/chemistry/*genetics ; }, abstract = {BACKGROUND: Complex multicellularity requires elaborate developmental mechanisms, often based on the versatility of heterodimeric transcription factor (TF) interactions. Homeobox TFs in the TALE superclass are deeply embedded in the gene regulatory networks that orchestrate embryogenesis. Knotted-like homeobox (KNOX) TFs, homologous to animal MEIS, have been found to drive the haploid-to-diploid transition in both unicellular green algae and land plants via heterodimerization with other TALE superclass TFs, demonstrating remarkable functional conservation of a developmental TF across lineages that diverged one billion years ago. Here, we sought to delineate whether TALE-TALE heterodimerization is ancestral to eukaryotes.

RESULTS: We analyzed TALE endowment in the algal radiations of Archaeplastida, ancestral to land plants. Homeodomain phylogeny and bioinformatics analysis partitioned TALEs into two broad groups, KNOX and non-KNOX. Each group shares previously defined heterodimerization domains, plant KNOX-homology in the KNOX group and animal PBC-homology in the non-KNOX group, indicating their deep ancestry. Protein-protein interaction experiments showed that the TALEs in the two groups all participated in heterodimerization.

CONCLUSIONS: Our study indicates that the TF dyads consisting of KNOX/MEIS and PBC-containing TALEs must have evolved early in eukaryotic evolution. Based on our results, we hypothesize that in early eukaryotes, the TALE heterodimeric configuration provided transcription-on switches via dimerization-dependent subcellular localization, ensuring execution of the haploid-to-diploid transition only when the gamete fusion is correctly executed between appropriate partner gametes. The TALE switch then diversified in the several lineages that engage in a complex multicellular organization.}, } @article {pmid30395805, year = {2020}, author = {Ten Tusscher, K}, title = {Of mice and plants: Comparative developmental systems biology.}, journal = {Developmental biology}, volume = {460}, number = {1}, pages = {32-39}, doi = {10.1016/j.ydbio.2018.10.024}, pmid = {30395805}, issn = {1095-564X}, mesh = {Animals ; Body Patterning/*physiology ; Developmental Biology ; Embryonic Development/*physiology ; Gene Expression Regulation, Developmental/*genetics ; Mice ; Models, Biological ; Plant Shoots/*embryology ; Plants ; Signal Transduction/*physiology ; Systems Biology ; }, abstract = {Multicellular animals and plants represent independent evolutionary experiments with complex multicellular bodyplans. Differences in their life history, a mobile versus sessile lifestyle, and predominant embryonic versus postembryonic development, have led to the evolution of highly different body plans. However, also many intriguing parallels exist. Extension of the vertebrate body axis and its segmentation into somites bears striking resemblance to plant root growth and the concomittant prepatterning of lateral root competent sites. Likewise, plant shoot phyllotaxis displays similarities with vertebrate limb and digit patterning. Additionally, both plants and animals use complex signalling systems combining systemic and local signals to fine tune and coordinate organ growth across their body. Identification of these striking examples of convergent evolution provides support for the existence of general design principles: the idea that for particular patterning demands, evolution is likely to arrive at highly similar developmental patterning mechanisms. Furthermore, focussing on these parallels may aid in identifying core mechanistic principles, often obscured by the highly complex nature of multiscale patterning processes.}, } @article {pmid30389796, year = {2019}, author = {Bull, JK and Flynn, JM and Chain, FJJ and Cristescu, ME}, title = {Fitness and Genomic Consequences of Chronic Exposure to Low Levels of Copper and Nickel in Daphnia pulex Mutation Accumulation Lines.}, journal = {G3 (Bethesda, Md.)}, volume = {9}, number = {1}, pages = {61-71}, pmid = {30389796}, issn = {2160-1836}, mesh = {Animals ; Copper/toxicity ; Daphnia/drug effects/*genetics ; Genetic Fitness/drug effects/*genetics ; Genome/*drug effects ; Mutation/drug effects ; Mutation Accumulation ; Mutation Rate ; Nickel/toxicity ; Reproduction/*drug effects/genetics ; Sequence Deletion/drug effects ; }, abstract = {In at least some unicellular organisms, mutation rates are temporarily raised upon exposure to environmental stress, potentially contributing to the evolutionary response to stress. Whether this is true for multicellular organisms, however, has received little attention. This study investigated the effects of chronic mild stress, in the form of low-level copper and nickel exposure, on mutational processes in Daphnia pulex using a combination of mutation accumulation, whole genome sequencing and life-history assays. After over 100 generations of mutation accumulation, we found no effects of metal exposure on the rates of single nucleotide mutations and of loss of heterozygosity events, the two mutation classes that occurred in sufficient numbers to allow statistical analysis. Similarly, rates of decline in fitness, as measured by intrinsic rate of population increase and of body size at first reproduction, were negligibly affected by metal exposure. We can reject the possibility that Daphnia were insufficiently stressed to invoke genetic responses as we have previously shown rates of large-scale deletions and duplications are elevated under metal exposure in this experiment. Overall, the mutation accumulation lines did not significantly depart from initial values for phenotypic traits measured, indicating the lineage used was broadly mutationally robust. Taken together, these results indicate that the mutagenic effects of chronic low-level exposure to these metals are restricted to certain mutation classes and that fitness consequences are likely minor and therefore unlikely to be relevant in determining the evolutionary responses of populations exposed to these stressors.}, } @article {pmid30386324, year = {2018}, author = {Yap, GS and Gause, WC}, title = {Helminth Infections Induce Tissue Tolerance Mitigating Immunopathology but Enhancing Microbial Pathogen Susceptibility.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2135}, pmid = {30386324}, issn = {1664-3224}, support = {R01 AI131634/AI/NIAID NIH HHS/United States ; R01 AI134040/AI/NIAID NIH HHS/United States ; R01 DK113790/DK/NIDDK NIH HHS/United States ; R56 AI124691/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacterial Infections/*immunology/pathology ; Disease Susceptibility ; Helminthiasis/*immunology/pathology ; Host-Parasite Interactions/*immunology ; Humans ; *Lymphocyte Activation ; Protozoan Infections/*immunology/pathology ; T-Lymphocytes/*immunology/pathology ; Virus Diseases/*immunology/pathology ; }, abstract = {Helminths are ubiquitous and have chronically infected vertebrates throughout their evolution. As such helminths have likely exerted considerable selection pressure on our immune systems. The large size of multicellular helminths and their limited replicative capacity in the host necessarily elicits different host protective mechanisms than the immune response evoked by microbial pathogens such as bacteria, viruses and intracellular parasites. The cellular damage resulting from helminth migration through tissues is a major trigger of the type 2 and regulatory immune responses, which activates wound repair mechanisms that increases tissue tolerance to injury and resistance mechanisms that enhance resistance to further colonization with larval stages. While these wound healing and anti-inflammatory responses may be beneficial to the helminth infected host, they may also compromise the host's ability to mount protective immune responses to microbial pathogens. In this review we will first describe helminth-induced tolerance mechanisms that develop in specific organs including the lung and the intestine, and how adaptive immunity may contribute to these responses through differential activation of T cells in the secondary lymphoid organs. We will then integrate studies that have examined how the immune response is modulated in these specific tissues during coinfection of helminths with viruses, protozoa, and bacteria.}, } @article {pmid30377252, year = {2019}, author = {Darris, C and Revert, F and Revert-Ros, F and Gozalbo-Rovira, R and Feigley, A and Fidler, A and Lopez-Pascual, E and Saus, J and Hudson, BG}, title = {Unicellular ancestry and mechanisms of diversification of Goodpasture antigen-binding protein.}, journal = {The Journal of biological chemistry}, volume = {294}, number = {3}, pages = {759-769}, pmid = {30377252}, issn = {1083-351X}, support = {R01 DK018381/DK/NIDDK NIH HHS/United States ; R25 DK096999/DK/NIDDK NIH HHS/United States ; }, mesh = {Basement Membrane/metabolism ; *Evolution, Molecular ; Humans ; Isoenzymes/genetics/metabolism ; Protein Serine-Threonine Kinases/genetics/*metabolism ; }, abstract = {The emergence of the basement membrane (BM), a specialized form of extracellular matrix, was essential in the unicellular transition to multicellularity. However, the mechanism is unknown. Goodpasture antigen-binding protein (GPBP), a BM protein, was uniquely poised to play diverse roles in this transition owing to its multiple isoforms (GPBP-1, -2, and -3) with varied intracellular and extracellular functions (ceramide trafficker and protein kinase). We sought to determine the evolutionary origin of GPBP isoforms. Our findings reveal the presence of GPBP in unicellular protists, with GPBP-2 as the most ancient isoform. In vertebrates, GPBP-1 assumed extracellular function that is further enhanced by membrane-bound GPBP-3 in mammalians, whereas GPBP-2 retained intracellular function. Moreover, GPBP-2 possesses a dual intracellular/extracellular function in cnidarians, an early nonbilaterian group. We conclude that GPBP functioning both inside and outside the cell was of fundamental importance for the evolutionary transition to animal multicellularity and tissue evolution.}, } @article {pmid30368592, year = {2019}, author = {Niklas, KJ and Wayne, R and Benítez, M and Newman, SA}, title = {Polarity, planes of cell division, and the evolution of plant multicellularity.}, journal = {Protoplasma}, volume = {256}, number = {3}, pages = {585-599}, pmid = {30368592}, issn = {1615-6102}, mesh = {*Biological Evolution ; *Cell Division ; *Cell Polarity ; Meristem/cytology ; Phylogeny ; Plant Cells/*metabolism ; }, abstract = {Organisms as diverse as bacteria, fungi, plants, and animals manifest a property called "polarity." The literature shows that polarity emerges as a consequence of different mechanisms in different lineages. However, across all unicellular and multicellular organisms, polarity is evident when cells, organs, or organisms manifest one or more of the following: orientation, axiation, and asymmetry. Here, we review the relationships among these three features in the context of cell division and the evolution of multicellular polarity primarily in plants (defined here to include the algae). Data from unicellular and unbranched filamentous organisms (e.g., Chlamydomonas and Ulothrix) show that cell orientation and axiation are marked by cytoplasmic asymmetries. Branched filamentous organisms (e.g., Cladophora and moss protonema) require an orthogonal reorientation of axiation, or a localized cell asymmetry (e.g., "tip" growth in pollen tubes and fungal hyphae). The evolution of complex multicellular meristematic polarity required a third reorientation of axiation. These transitions show that polarity and the orientation of the future plane(s) of cell division are dyadic dynamical patterning modules that were critical for multicellular eukaryotic organisms.}, } @article {pmid30362942, year = {2018}, author = {Castiglione, GM and Chang, BS}, title = {Functional trade-offs and environmental variation shaped ancient trajectories in the evolution of dim-light vision.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30362942}, issn = {2050-084X}, support = {Discovery grant//Natural Sciences and Engineering Research Council of Canada/International ; }, mesh = {*Adaptation, Biological ; Animals ; *Biological Evolution ; Epistasis, Genetic ; Light ; Rhodopsin/genetics ; Selection, Genetic ; *Vertebrates ; Vision, Ocular/*physiology ; }, abstract = {Trade-offs between protein stability and activity can restrict access to evolutionary trajectories, but widespread epistasis may facilitate indirect routes to adaptation. This may be enhanced by natural environmental variation, but in multicellular organisms this process is poorly understood. We investigated a paradoxical trajectory taken during the evolution of tetrapod dim-light vision, where in the rod visual pigment rhodopsin, E122 was fixed 350 million years ago, a residue associated with increased active-state (MII) stability but greatly diminished rod photosensitivity. Here, we demonstrate that high MII stability could have likely evolved without E122, but instead, selection appears to have entrenched E122 in tetrapods via epistatic interactions with nearby coevolving sites. In fishes by contrast, selection may have exploited these epistatic effects to explore alternative trajectories, but via indirect routes with low MII stability. Our results suggest that within tetrapods, E122 and high MII stability cannot be sacrificed-not even for improvements to rod photosensitivity.}, } @article {pmid30357728, year = {2018}, author = {Fitzgerald, RS}, title = {O2/CO2: Biological Detection to Homeostatic Control.}, journal = {Advances in experimental medicine and biology}, volume = {1071}, number = {}, pages = {1-12}, doi = {10.1007/978-3-319-91137-3_1}, pmid = {30357728}, issn = {0065-2598}, mesh = {Animals ; Atmosphere ; Carbon Dioxide/*analysis/physiology ; *Homeostasis ; Oxygen/*analysis/physiology ; Photosynthesis ; }, abstract = {Oxygen (O2) and Carbon Dioxide (CO2) are the two gases to be detected and controlled. Of interest might be a query of the evolutionary origin of each. From the cooling of the Big Bang (~13.8 Billion Years Ago [BYA]) came a quark-gluon plasma from which protons and neutrons emerged, producing H, He, Li. As H and He collapsed into the first stars at ~13.3 BYA carbon and monatomic oxygen were generated. Some 3 billion years ago greater amounts of diatomic oxygen (O2) were provided by earth's photosynthesizing bacteria until earth's atmosphere had sufficient amounts to sustain the life processes of multicellular animals, and finally higher vertebrates. Origin of CO2 is somewhat unclear, though it probably came from the erupting early volcanoes. Photosynthesis produced sugars with O2 a waste product. Animal life took sugars and O2 needed for life. Clearly, animal detection and control of each was critical. Many chapters involving great heroes describe phases involved in detecting each, both in the CNS and in peripheral detectors. The carotid body (CB) has played a crucial role in the detection of each. What reflex responses the stimulated CB generates, and the mechanisms as to how it does so have been a fascinating story over the last 1.5 centuries, but principally over the last 50 years. Explorations to detect these gases have proceeded from the organismal/system/ organ levels down to the sub-cell and genetic levels.}, } @article {pmid30348074, year = {2018}, author = {Kin, K and Forbes, G and Cassidy, A and Schaap, P}, title = {Cell-type specific RNA-Seq reveals novel roles and regulatory programs for terminally differentiated Dictyostelium cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {764}, pmid = {30348074}, issn = {1471-2164}, support = {742288//H2020 European Research Council/ ; ALTF 295-2015//European Molecular Biology Organization/ ; H28-1002//Japan Society for the Promotion of Science/ ; }, mesh = {Dictyostelium/*cytology/*genetics/metabolism ; Gene Expression Regulation ; Gene Ontology ; Metabolic Networks and Pathways/genetics ; RNA, Protozoan/*genetics ; *Sequence Analysis, RNA ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: A major hallmark of multicellular evolution is increasing complexity by the evolution of new specialized cell types. During Dictyostelid evolution novel specialization occurred within taxon group 4. We here aim to retrace the nature and ancestry of the novel "cup" cells by comparing their transcriptome to that of other cell types.

RESULTS: RNA-Seq was performed on purified mature spore, stalk and cup cells and on vegetative amoebas. Clustering and phylogenetic analyses showed that cup cells were most similar to stalk cells, suggesting that they share a common ancestor. The affinity between cup and stalk cells was also evident from promoter-reporter studies of newly identified cell-type genes, which revealed late expression in cups of many stalk genes. However, GO enrichment analysis reveal the unexpected prominence of GTPase mediated signalling in cup cells, in contrast to enrichment of autophagy and cell wall synthesis related transcripts in stalk cells. Combining the cell type RNA-Seq data with developmental expression profiles revealed complex expression dynamics in each cell type as well as genes exclusively expressed during terminal differentiation. Most notable were nine related hssA-like genes that were highly and exclusively expressed in cup cells.

CONCLUSIONS: This study reveals the unique transcriptomes of the mature cup, stalk and spore cells of D. discoideum and provides insight into the ancestry of cup cells and roles in signalling that were not previously realized. The data presented in this study will serve as an important resource for future studies into the regulation and evolution of cell type specialization.}, } @article {pmid30339672, year = {2018}, author = {Crombie, TA and Saber, S and Saxena, AS and Egan, R and Baer, CF}, title = {Head-to-head comparison of three experimental methods of quantifying competitive fitness in C. elegans.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0201507}, pmid = {30339672}, issn = {1932-6203}, support = {R01 GM107227/GM/NIGMS NIH HHS/United States ; S10 OD012006/OD/NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Automation ; Biological Evolution ; Caenorhabditis elegans/*genetics/*physiology ; *Genetic Fitness ; Genotype ; Green Fluorescent Proteins/metabolism ; Models, Biological ; Models, Statistical ; Reproducibility of Results ; Software ; }, abstract = {Organismal fitness is relevant in many contexts in biology. The most meaningful experimental measure of fitness is competitive fitness, when two or more entities (e.g., genotypes) are allowed to compete directly. In theory, competitive fitness is simple to measure: an experimental population is initiated with the different types in known proportions and allowed to evolve under experimental conditions to a predefined endpoint. In practice, there are several obstacles to obtaining robust estimates of competitive fitness in multicellular organisms, the most pervasive of which is simply the time it takes to count many individuals of different types from many replicate populations. Methods by which counting can be automated in high throughput are desirable, but for automated methods to be useful, the bias and technical variance associated with the method must be (a) known, and (b) sufficiently small relative to other sources of bias and variance to make the effort worthwhile. The nematode Caenorhabditis elegans is an important model organism, and the fitness effects of genotype and environmental conditions are often of interest. We report a comparison of three experimental methods of quantifying competitive fitness, in which wild-type strains are competed against GFP-marked competitors under standard laboratory conditions. Population samples were split into three replicates and counted (1) "by eye" from a saved image, (2) from the same image using CellProfiler image analysis software, and (3) with a large particle flow cytometer (a "worm sorter"). From 720 replicate samples, neither the frequency of wild-type worms nor the among-sample variance differed significantly between the three methods. CellProfiler and the worm sorter provide at least a tenfold increase in sample handling speed with little (if any) bias or increase in variance.}, } @article {pmid30336184, year = {2019}, author = {Miller, WB and Torday, JS and Baluška, F}, title = {Biological evolution as defense of 'self'.}, journal = {Progress in biophysics and molecular biology}, volume = {142}, number = {}, pages = {54-74}, doi = {10.1016/j.pbiomolbio.2018.10.002}, pmid = {30336184}, issn = {1873-1732}, mesh = {*Biological Evolution ; Cell Physiological Phenomena ; Cells/metabolism ; Cognition/physiology ; Consciousness/*physiology ; Emotions/physiology ; Homeostasis/physiology ; Humans ; Intelligence/physiology ; Signal Transduction ; }, abstract = {Although the origin of self-referential consciousness is unknown, it can be argued that the instantiation of self-reference was the commencement of the living state as phenomenal experientiality. As self-referential cognition is demonstrated by all living organisms, life can be equated with the sustenance of cellular homeostasis in the continuous defense of 'self'. It is proposed that the epicenter of 'self' is perpetually embodied within the basic cellular form in which it was instantiated. Cognition-Based Evolution argues that all of biological and evolutionary development represents the perpetual autopoietic defense of self-referential basal cellular states of homeostatic preference. The means by which these states are attained and maintained is through self-referential measurement of information and its communication. The multicellular forms, either as biofilms or holobionts, represent the cellular attempt to achieve maximum states of informational distinction and energy efficiency through individual and collective means. In this frame, consciousness, self-consciousness and intelligence can be identified as forms of collective cellular phenotype directed towards the defense of fundamental cellular self-reference.}, } @article {pmid30325443, year = {2018}, author = {Skaldin, M and Tuittila, M and Zavialov, AV and Zavialov, AV}, title = {Secreted Bacterial Adenosine Deaminase Is an Evolutionary Precursor of Adenosine Deaminase Growth Factor.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2851-2861}, doi = {10.1093/molbev/msy193}, pmid = {30325443}, issn = {1537-1719}, mesh = {Adenosine Deaminase/*genetics ; Amino Acid Sequence ; Bacterial Proteins/*genetics ; Drosophila Proteins/genetics ; *Evolution, Molecular ; Intercellular Signaling Peptides and Proteins/genetics ; Multigene Family ; Phylogeny ; }, abstract = {Adenosine deaminases (ADAs) play a pivotal role in regulating the level of adenosine, an important signaling molecule that controls a variety of cellular responses. Two distinct ADAs, ADA1 and adenosine deaminase growth factor (ADGF aka ADA2), are known. Cytoplasmic ADA1 plays a key role in purine metabolism and is widely distributed from prokaryotes to mammals. On the other hand, secreted ADGF/ADA2 is a cell-signaling protein that was thought to be present only in multicellular organisms. Here, we discovered a bacterial homologue of ADGF/ADA2. Bacterial and eukaryotic ADGF/ADA2 possess the dimerization and PRB domains characteristic for the family, have nearly identical catalytic sites, and show similar catalytic characteristics. Most surprisingly, the bacterial enzyme has a signal sequence similar to that of eukaryotic ADGF/ADA2 and is specifically secreted into the extracellular space, where it may potentially control the level of extracellular adenosine. This finding provides the first example of evolution of an extracellular eukaryotic signaling protein from a secreted bacterial analogue with identical activity and suggests a potential role of ADGF/ADA2 in bacterial communication.}, } @article {pmid30323207, year = {2018}, author = {Zumberge, JA and Love, GD and Cárdenas, P and Sperling, EA and Gunasekera, S and Rohrssen, M and Grosjean, E and Grotzinger, JP and Summons, RE}, title = {Demosponge steroid biomarker 26-methylstigmastane provides evidence for Neoproterozoic animals.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1709-1714}, pmid = {30323207}, issn = {2397-334X}, support = {80NSSC18K1085//Intramural NASA/United States ; }, mesh = {Animals ; *Biological Evolution ; Biomarkers/*analysis ; *Fossils ; Phylogeny ; Porifera/*chemistry ; Steroids/*analysis ; }, abstract = {Sterane biomarkers preserved in ancient sedimentary rocks hold promise for tracking the diversification and ecological expansion of eukaryotes. The earliest proposed animal biomarkers from demosponges (Demospongiae) are recorded in a sequence around 100 Myr long of Neoproterozoic-Cambrian marine sedimentary strata from the Huqf Supergroup, South Oman Salt Basin. This C30 sterane biomarker, informally known as 24-isopropylcholestane (24-ipc), possesses the same carbon skeleton as sterols found in some modern-day demosponges. However, this evidence is controversial because 24-ipc is not exclusive to demosponges since 24-ipc sterols are found in trace amounts in some pelagophyte algae. Here, we report a new fossil sterane biomarker that co-occurs with 24-ipc in a suite of late Neoproterozoic-Cambrian sedimentary rocks and oils, which possesses a rare hydrocarbon skeleton that is uniquely found within extant demosponge taxa. This sterane is informally designated as 26-methylstigmastane (26-mes), reflecting the very unusual methylation at the terminus of the steroid side chain. It is the first animal-specific sterane marker detected in the geological record that can be unambiguously linked to precursor sterols only reported from extant demosponges. These new findings strongly suggest that demosponges, and hence multicellular animals, were prominent in some late Neoproterozoic marine environments at least extending back to the Cryogenian period.}, } @article {pmid30318349, year = {2018}, author = {Bråte, J and Neumann, RS and Fromm, B and Haraldsen, AAB and Tarver, JE and Suga, H and Donoghue, PCJ and Peterson, KJ and Ruiz-Trillo, I and Grini, PE and Shalchian-Tabrizi, K}, title = {Unicellular Origin of the Animal MicroRNA Machinery.}, journal = {Current biology : CB}, volume = {28}, number = {20}, pages = {3288-3295.e5}, pmid = {30318349}, issn = {1879-0445}, mesh = {Animals ; Base Sequence ; *Evolution, Molecular ; Mesomycetozoea/*genetics/metabolism ; MicroRNAs/*genetics/metabolism ; Phylogeny ; }, abstract = {The emergence of multicellular animals was associated with an increase in phenotypic complexity and with the acquisition of spatial cell differentiation and embryonic development. Paradoxically, this phenotypic transition was not paralleled by major changes in the underlying developmental toolkit and regulatory networks. In fact, most of these systems are ancient, established already in the unicellular ancestors of animals [1-5]. In contrast, the Microprocessor protein machinery, which is essential for microRNA (miRNA) biogenesis in animals, as well as the miRNA genes themselves produced by this Microprocessor, have not been identified outside of the animal kingdom [6]. Hence, the Microprocessor, with the key proteins Pasha and Drosha, is regarded as an animal innovation [7-9]. Here, we challenge this evolutionary scenario by investigating unicellular sister lineages of animals through genomic and transcriptomic analyses. We identify in Ichthyosporea both Drosha and Pasha (DGCR8 in vertebrates), indicating that the Microprocessor complex evolved long before the last common ancestor of animals, consistent with a pre-metazoan origin of most of the animal developmental gene elements. Through small RNA sequencing, we also discovered expressed bona fide miRNA genes in several species of the ichthyosporeans harboring the Microprocessor. A deep, pre-metazoan origin of the Microprocessor and miRNAs comply with a view that the origin of multicellular animals was not directly linked to the innovation of these key regulatory components.}, } @article {pmid30309963, year = {2018}, author = {Armon, S and Bull, MS and Aranda-Diaz, A and Prakash, M}, title = {Ultrafast epithelial contractions provide insights into contraction speed limits and tissue integrity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10333-E10341}, pmid = {30309963}, issn = {1091-6490}, mesh = {Actins/metabolism ; Animals ; Aquatic Organisms/metabolism/*physiology ; Cells, Cultured ; Epithelial Cells/metabolism/*physiology ; Epithelium/metabolism/*physiology ; Myosins/metabolism ; Placozoa/metabolism/*physiology ; }, abstract = {By definition of multicellularity, all animals need to keep their cells attached and intact, despite internal and external forces. Cohesion between epithelial cells provides this key feature. To better understand fundamental limits of this cohesion, we study the epithelium mechanics of an ultrathin (∼25 μm) primitive marine animal Trichoplax adhaerens, composed essentially of two flat epithelial layers. With no known extracellular matrix and no nerves or muscles, T. adhaerens has been claimed to be the "simplest known living animal," yet is still capable of coordinated locomotion and behavior. Here we report the discovery of the fastest epithelial cellular contractions known in any metazoan, to be found in T. adhaerens dorsal epithelium (50% shrinkage of apical cell area within one second, at least an order of magnitude faster than other known examples). Live imaging reveals emergent contractile patterns that are mostly sporadic single-cell events, but also include propagating contraction waves across the tissue. We show that cell contraction speed can be explained by current models of nonmuscle actin-myosin bundles without load, while the tissue architecture and unique mechanical properties are softening the tissue, minimizing the load on a contracting cell. We propose a hypothesis, in which the physiological role of the contraction dynamics is to resist external stresses while avoiding tissue rupture ("active cohesion"), a concept that can be further applied to engineering of active materials.}, } @article {pmid30295813, year = {2018}, author = {Sperling, EA and Stockey, RG}, title = {The Temporal and Environmental Context of Early Animal Evolution: Considering All the Ingredients of an "Explosion".}, journal = {Integrative and comparative biology}, volume = {58}, number = {4}, pages = {605-622}, doi = {10.1093/icb/icy088}, pmid = {30295813}, issn = {1557-7023}, mesh = {Animals ; *Biological Evolution ; Fossils/*anatomy & histology ; Invertebrates/*anatomy & histology/classification ; Phylogeny ; }, abstract = {Animals originated and evolved during a unique time in Earth history-the Neoproterozoic Era. This paper aims to discuss (1) when landmark events in early animal evolution occurred, and (2) the environmental context of these evolutionary milestones, and how such factors may have affected ecosystems and body plans. With respect to timing, molecular clock studies-utilizing a diversity of methodologies-agree that animal multicellularity had arisen by ∼800 million years ago (Ma) (Tonian period), the bilaterian body plan by ∼650 Ma (Cryogenian), and divergences between sister phyla occurred ∼560-540 Ma (late Ediacaran). Most purported Tonian and Cryogenian animal body fossils are unlikely to be correctly identified, but independent support for the presence of pre-Ediacaran animals is recorded by organic geochemical biomarkers produced by demosponges. This view of animal origins contrasts with data from the fossil record, and the taphonomic question of why animals were not preserved (if present) remains unresolved. Neoproterozoic environments demanding small, thin, body plans, and lower abundance/rarity in populations may have played a role. Considering environmental conditions, geochemical data suggest that animals evolved in a relatively low-oxygen ocean. Here, we present new analyses of sedimentary total organic carbon contents in shales suggesting that the Neoproterozoic ocean may also have had lower primary productivity-or at least lower quantities of organic carbon reaching the seafloor-compared with the Phanerozoic. Indeed, recent modeling efforts suggest that low primary productivity is an expected corollary of a low-O2 world. Combined with an inability to inhabit productive regions in a low-O2 ocean, earliest animal communities would likely have been more food limited than generally appreciated, impacting both ecosystem structure and organismal behavior. In light of this, we propose the "fire triangle" metaphor for environmental influences on early animal evolution. Moving toward consideration of all environmental aspects of the Cambrian radiation (fuel, heat, and oxidant) will ultimately lead to a more holistic view of the event.}, } @article {pmid30288746, year = {2018}, author = {Stiller, JW and Yang, C and Collén, J and Kowalczyk, N and Thompson, BE}, title = {Evolution and expression of core SWI/SNF genes in red algae.}, journal = {Journal of phycology}, volume = {54}, number = {6}, pages = {879-887}, doi = {10.1111/jpy.12795}, pmid = {30288746}, issn = {1529-8817}, support = {0741907//NSF Research Collaboration Network/International ; DE-AC02-05CH11231//U.S. Department of Energy Joint Genome Institute/International ; }, mesh = {Algal Proteins/*genetics/metabolism ; *Chromatin Assembly and Disassembly ; Genome ; Reverse Transcriptase Polymerase Chain Reaction ; Rhodophyta/*genetics/metabolism ; *Transcription, Genetic ; Transcriptome ; }, abstract = {Red algae are the oldest identifiable multicellular eukaryotes, with a fossil record dating back more than a billion years. During that time two major rhodophyte lineages, bangiophytes and florideophytes, have evolved varied levels of morphological complexity. These two groups are distinguished, in part, by different patterns of multicellular development, with florideophytes exhibiting a far greater diversity of morphologies. Interestingly, during their long evolutionary history, there is no record of a rhodophyte achieving the kinds of cellular and tissue-specific differentiation present in other multicellular algal lineages. To date, the genetic underpinnings of unique aspects of red algal development are largely unexplored; however, they must reflect the complements and patterns of expression of key regulatory genes. Here we report comparative evolutionary and gene expression analyses of core subunits of the SWI/SNF chromatin-remodeling complex, which is implicated in cell differentiation and developmental regulation in more well studied multicellular groups. Our results suggest that a single, canonical SWI/SNF complex was present in the rhodophyte ancestor, with gene duplications and evolutionary diversification of SWI/SNF subunits accompanying the evolution of multicellularity in the common ancestor of bangiophytes and florideophytes. Differences in how SWI/SNF chromatin remodeling evolved subsequently, in particular gene losses and more rapid divergence of SWI3 and SNF5 in bangiophytes, could help to explain why they exhibit a more limited range of morphological complexity than their florideophyte cousins.}, } @article {pmid30281390, year = {2018}, author = {Booth, DS and Szmidt-Middleton, H and King, N}, title = {Transfection of choanoflagellates illuminates their cell biology and the ancestry of animal septins.}, journal = {Molecular biology of the cell}, volume = {29}, number = {25}, pages = {3026-3038}, pmid = {30281390}, issn = {1939-4586}, mesh = {Choanoflagellata/*genetics/physiology ; Evolution, Molecular ; Fluorescent Dyes ; Genetic Markers ; Plasmids ; Septins/genetics/*physiology ; Transfection/*methods ; }, abstract = {As the closest living relatives of animals, choanoflagellates offer unique insights into animal origins and core mechanisms underlying animal cell biology. However, unlike traditional model organisms, such as yeast, flies, and worms, choanoflagellates have been refractory to DNA delivery methods for expressing foreign genes. Here we report a robust method for expressing transgenes in the choanoflagellate Salpingoeca rosetta, overcoming barriers that have previously hampered DNA delivery and expression. To demonstrate how this method accelerates the study of S. rosetta cell biology, we engineered a panel of fluorescent protein markers that illuminate key features of choanoflagellate cells. We then investigated the localization of choanoflagellate septins, a family of GTP-binding cytoskeletal proteins that are hypothesized to regulate multicellular rosette development in S. rosetta. Fluorescently tagged septins localized to the basal poles of S. rosetta single cells and rosettes in a pattern resembling septin localization in animal epithelia. The establishment of transfection in S. rosetta and its application to the study of septins represent critical advances in the use of S. rosetta as an experimental model for investigating choanoflagellate cell biology, core mechanisms underlying animal cell biology, and the origin of animals.}, } @article {pmid30270425, year = {2018}, author = {Joshi, J and Guttal, V}, title = {Demographic noise and cost of greenbeard can facilitate greenbeard cooperation.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2595-2607}, doi = {10.1111/evo.13615}, pmid = {30270425}, issn = {1558-5646}, support = {DBT-IISc partnership program//Department of Biotechnology , Ministry of Science and Technology/International ; DST-FIST//Department of Science and Technology, Ministry of Science and Technology/International ; Mathematical Biology Phase II (SR/S4/MS:799/12)//Department of Science and Technology, Ministry of Science and Technology/International ; ICTS/Prog-PGE2018/03//International Centre for Theoretical Sciences/International ; }, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Biological Evolution ; Game Theory ; *Models, Genetic ; Mutation ; Selection, Genetic ; }, abstract = {Cooperation among organisms, where cooperators suffer a personal cost to benefit others, is ubiquitous in nature. Greenbeard is a key mechanism for the evolution of cooperation, where a single gene or a set of linked genes codes for both cooperation and a phenotypic tag (metaphorically called "green beard"). Greenbeard cooperation is typically thought to decline over time since defectors can also evolve the tag. However, models of tag-based cooperation typically ignore two key realistic features: populations are finite, and that phenotypic tags can be costly. We develop an analytical model for coevolutionary dynamics of two evolvable traits in finite populations with mutations: costly cooperation and a costly tag. We show that an interplay of demographic noise and cost of the tag can induce coevolutionary cycling, where the evolving population does not reach a steady state but spontaneously switches between cooperative tag-carrying and noncooperative tagless states. Such dynamics allows the tag to repeatedly reappear even after it is invaded by defectors. Thus, we highlight the surprising possibility that the cost of the tag, together with demographic noise, can facilitate the evolution of greenbeard cooperation. We discuss implications of these findings in the context of the evolution of quorum sensing and multicellularity.}, } @article {pmid30270182, year = {2018}, author = {Thomas, GWC and Wang, RJ and Puri, A and Harris, RA and Raveendran, M and Hughes, DST and Murali, SC and Williams, LE and Doddapaneni, H and Muzny, DM and Gibbs, RA and Abee, CR and Galinski, MR and Worley, KC and Rogers, J and Radivojac, P and Hahn, MW}, title = {Reproductive Longevity Predicts Mutation Rates in Primates.}, journal = {Current biology : CB}, volume = {28}, number = {19}, pages = {3193-3197.e5}, pmid = {30270182}, issn = {1879-0445}, support = {HHSN272201200031C/AI/NIAID NIH HHS/United States ; P40 OD010938/OD/NIH HHS/United States ; }, mesh = {Animals ; Aotidae/genetics ; Genetic Fitness/*genetics ; Genetics, Population/methods ; Genome/genetics ; Humans ; Longevity/*genetics ; Mutation ; *Mutation Rate ; Pedigree ; Population Density ; Primates/genetics ; Reproduction ; }, abstract = {Mutation rates vary between species across several orders of magnitude, with larger organisms having the highest per-generation mutation rates. Hypotheses for this pattern typically invoke physiological or population-genetic constraints imposed on the molecular machinery preventing mutations [1]. However, continuing germline cell division in multicellular eukaryotes means that organisms with longer generation times and of larger size will leave more mutations to their offspring simply as a byproduct of their increased lifespan [2, 3]. Here, we deeply sequence the genomes of 30 owl monkeys (Aotus nancymaae) from six multi-generation pedigrees to demonstrate that paternal age is the major factor determining the number of de novo mutations in this species. We find that owl monkeys have an average mutation rate of 0.81 × 10[-8] per site per generation, roughly 32% lower than the estimate in humans. Based on a simple model of reproductive longevity that does not require any changes to the mutational machinery, we show that this is the expected mutation rate in owl monkeys. We further demonstrate that our model predicts species-specific mutation rates in other primates, including study-specific mutation rates in humans based on the average paternal age. Our results suggest that variation in life history traits alone can explain variation in the per-generation mutation rate among primates, and perhaps among a wide range of multicellular organisms.}, } @article {pmid30262973, year = {2018}, author = {Khurana, GK and Vishwakarma, P and Puri, N and Lynn, AM}, title = {Phylogenetic Analysis of the vesicular fusion SNARE machinery revealing its functional divergence across Eukaryotes.}, journal = {Bioinformation}, volume = {14}, number = {7}, pages = {361-368}, pmid = {30262973}, issn = {0973-2063}, abstract = {Proteins of the SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) family play a significant role in all vesicular fusion events involved in endocytic and exocytic pathways. These proteins act as molecular machines that assemble into tight four-helix bundle complex, bridging the opposing membranes into close proximity forming membrane fusion. Almost all SNARE proteins share a 53 amino acid coiled-coil domain, which is mostly linked to the transmembrane domain at the C-terminal end. Despite significant variations between SNARE sequences across species, the SNARE mediated membrane fusion is evolutionary conserved in all eukaryotes. It is of interest to compare the functional divergence of SNARE proteins across various eukaryotic groups during evolution. Here, we report an exhaustive phylogeny of the SNARE proteins retrieved from SNARE database including plants, animals, fungi and protists. The Initial phylogeny segregated SNARE protein sequences into five well-supported clades Qa, Qb, Qc, Qbc and R reflective of their positions in the four-helix SNARE complex. Further to improve resolution the Qa, Qb, Qc and R family specific trees were reconstructed, each of these were further segregated into organelle specific clades at first and later diverged into lineage specific subgroups. This revealed that most of the SNARE orthologs are conserved at subcellular locations or at trafficking pathways across various species during eukaryotic evolution. The paralogous expansion in SNARE repertoire was observed at metazoans (animals) and plants independently during eukaryotic evolution. However, results also show that the multi-cellular and saprophytic fungi have limited SNAREs.}, } @article {pmid30256189, year = {2018}, author = {Almeida, LV and Coqueiro-Dos-Santos, A and Rodriguez-Luiz, GF and McCulloch, R and Bartholomeu, DC and Reis-Cunha, JL}, title = {Chromosomal copy number variation analysis by next generation sequencing confirms ploidy stability in Trypanosoma brucei subspecies.}, journal = {Microbial genomics}, volume = {4}, number = {10}, pages = {}, pmid = {30256189}, issn = {2057-5858}, support = {BB/M028909/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 206815/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; BB/K006495/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; BB/N016165/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; G0401553/MRC_/Medical Research Council/United Kingdom ; 104111/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Chromosomes/*genetics/metabolism ; *DNA Copy Number Variations ; DNA Replication/physiology ; DNA, Protozoan/biosynthesis/genetics ; High-Throughput Nucleotide Sequencing ; In Situ Hybridization, Fluorescence ; Leishmania/genetics/metabolism ; *Phylogeny ; *Ploidies ; Species Specificity ; Trypanosoma brucei brucei/*genetics/metabolism ; Trypanosoma cruzi/*genetics/metabolism ; }, abstract = {Although aneuploidy usually results in severe abnormalities in multicellular eukaryotes, recent data suggest that it could be beneficial for unicellular eukaryotes, such as yeast and trypanosomatid parasites, providing increased survival under stressful conditions. Among characterized trypanosomatids, Trypanosoma cruzi, Trypanosoma brucei and species from the genus Leishmania stand out due to their importance in public health, infecting around 20 million people worldwide. The presence of aneuploidies in T. cruzi and Leishmania was recently confirmed by analysis based on next generation sequencing (NGS) and fluorescence in situ hybridization, where they have been associated with adaptation during transmission between their insect vectors and mammalian hosts and in promoting drug resistance. Although chromosomal copy number variations (CCNVs) are present in the aforementioned species, PFGE and fluorescence cytophotometry analyses suggest that aneuploidies are absent from T. brucei. A re-evaluation of CCNV in T. b gambiense based on NGS reads confirmed the absence of aneuploidies in this subspecies. However, the presence of aneuploidies in the other two T. brucei subspecies, T. b. brucei and T. b. rhodesiense, has not been evaluated using NGS approaches. In the present work, we tested for aneuploidies in 26 T. brucei isolates, including samples from the three T. brucei subspecies, by both allele frequency and read depth coverage analyses. These analyses showed that none of the T. brucei subspecies presents aneuploidies, which could be related to differences in the mechanisms of DNA replication and recombination in these parasites when compared with Leishmania.}, } @article {pmid30254228, year = {2018}, author = {Chen, X and Köllner, TG and Shaulsky, G and Jia, Q and Dickschat, JS and Gershenzon, J and Chen, F}, title = {Diversity and Functional Evolution of Terpene Synthases in Dictyostelid Social Amoebae.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14361}, pmid = {30254228}, issn = {2045-2322}, support = {R35 GM118016/GM/NIGMS NIH HHS/United States ; }, mesh = {Alkyl and Aryl Transferases/*genetics/*metabolism ; Biocatalysis ; Dictyostelium/*enzymology/*genetics/growth & development/metabolism ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Phylogeny ; Species Specificity ; Terpenes/chemistry/metabolism ; Volatilization ; }, abstract = {Dictyostelids, or social amoebae, have a unique life style in forming multicellular fruiting bodies from unicellular amoeboids upon starvation. Recently, dictyostelids were found to contain terpene synthase (TPS) genes, a gene type of secondary metabolism previously known to occur only in plants, fungi and bacteria. Here we report an evolutionary functional study of dictyostelid TPS genes. The number of TPS genes in six species of dictyostelids examined ranges from 1 to 19; and the model species Dictyostelium purpureum contains 12 genes. Using in vitro enzyme assays, the 12 TPS genes from D. purpureum were shown to encode functional enzymes with distinct product profiles. The expression of the 12 TPS genes in D. purpureum is developmentally regulated. During multicellular development, D. purpureum releases a mixture of volatile terpenes dominated by sesquiterpenes that are the in vitro products of a subset of the 12 TPS genes. The quality and quantity of the terpenes released from D. purpureum, however, bear little resemblance to those of D. discoideum, a closely related dictyostelid. Despite these variations, the conserved clade of dictyostelid TPSs, which have an evolutionary distance of more than 600 million years, has the same biochemical function, catalyzing the formation of a sesquiterpene protoillud-7-ene. Taken together, our results indicate that the dynamic evolution of dictyostelid TPS genes includes both purifying selection of an orthologous group and species-specific expansion with functional divergence. Consequently, the terpenes produced by these TPSs most likely have conserved as well as species-adaptive biological functions as chemical languages in dictyostelids.}, } @article {pmid30231028, year = {2018}, author = {Lau, AYT and Cheng, X and Cheng, CK and Nong, W and Cheung, MK and Chan, RH and Hui, JHL and Kwan, HS}, title = {Discovery of microRNA-like RNAs during early fruiting body development in the model mushroom Coprinopsis cinerea.}, journal = {PloS one}, volume = {13}, number = {9}, pages = {e0198234}, pmid = {30231028}, issn = {1932-6203}, mesh = {Base Sequence ; Coprinus/*genetics ; Fruiting Bodies, Fungal/*genetics ; Fungal Proteins/genetics ; Gene Expression Regulation, Fungal ; Genome, Fungal ; Genomics ; High-Throughput Nucleotide Sequencing ; MicroRNAs/*genetics ; Phylogeny ; RNA, Fungal/*genetics ; Transcriptome ; }, abstract = {Coprinopsis cinerea is a model mushroom particularly suited for the study of fungal fruiting body development and the evolution of multicellularity in fungi. While microRNAs (miRNAs) have been extensively studied in animals and plants for their essential roles in post-transcriptional regulation of gene expression, miRNAs in fungi are less well characterized and their potential roles in controlling mushroom development remain unknown. To identify miRNA-like RNAs (milRNAs) in C. cinerea and explore their expression patterns during the early developmental transition of mushroom development, small RNA libraries of vegetative mycelium and primordium were generated and putative milRNA candidates were identified following the standards of miRNA prediction in animals and plants. Two out of 22 novel predicted milRNAs, cci-milR-12c and cci-milR-13e-5p, were validated by northern blot and stem-loop reverse transcription real-time PCR. Cci-milR-12c was differentially expressed whereas the expression levels of cci-milR-13e-5p were similar in the two developmental stages. Target prediction of the validated milRNAs resulted in genes associated with fruiting body development, including pheromone, hydrophobin, cytochrome P450, and protein kinase. Essential genes for miRNA biogenesis, including three coding for Dicer-like (DCL), one for Argonaute (AGO), one for AGO-like and one for quelling deficient-2 (QDE-2) proteins, were also identified in the C. cinerea genome. Phylogenetic analysis showed that the DCL and AGO proteins of C. cinerea were more closely related to those in other basidiomycetes and ascomycetes than to those in animals and plants. Taken together, our findings provided the first evidence for milRNAs in the model mushroom and their potential roles in regulating fruiting body development. New information on the evolutionary relationship of milRNA biogenesis proteins across kingdoms has also provided new insights for guiding further functional and evolutionary studies of miRNAs.}, } @article {pmid30225671, year = {2019}, author = {Xue, S and Dong, M and Liu, X and Xu, S and Pang, J and Zhang, W and Weng, Y and Ren, H}, title = {Classification of fruit trichomes in cucumber and effects of plant hormones on type II fruit trichome development.}, journal = {Planta}, volume = {249}, number = {2}, pages = {407-416}, pmid = {30225671}, issn = {1432-2048}, support = {31672159//National Natural Science Foundation of China/ ; 2016YFD0101705//National Key Research and Development Program of China/ ; BAIC01-2017//Project of Beijing Agricultural Innovation Consortium/ ; }, mesh = {Benzyl Compounds/pharmacology ; Cucumis sativus/*anatomy & histology/growth & development/ultrastructure ; Fruit/*anatomy & histology/growth & development/ultrastructure ; Gibberellins/pharmacology ; Microscopy, Electron, Scanning ; Plant Growth Regulators/*pharmacology ; Purines/pharmacology ; Trichomes/*classification/drug effects/growth & development/ultrastructure ; }, abstract = {Cucumber fruit trichomes could be classified into eight types; all of them are multicellular with complex and different developmental processes as compared with unicellular trichomes in other plants. The fruit trichomes or fruit spines of cucumber, Cucumis sativus L., are highly specialized structures originating from epidermal cells with diverse morphology, which grow perpendicular to the fruit surface. To understand the underlying molecular mechanisms of fruit trichome development, in this study, we conducted morphological characterization and classification of cucumber fruit trichomes and their developmental processes. We examined the fruit trichomes among 200 cucumber varieties, which could be classified into eight morphologically distinct types (I-VIII). Investigation of the organogenesis of the eight types of trichomes revealed two main developmental patterns. The development of glandular trichomes had multiple stages including initiation and expansion of the trichome precursor cell protuberating out of the epidermal surface, followed by periclinal bipartition to two cells (top and bottom) which later formed the head region and the stalk, respectively, through subsequent cell divisions. The non-glandular trichome development started with the expansion of the precursor cell perpendicularly to the epidermal plane followed by cell periclinal division to form a stalk comprising of some rectangle cells and a pointed apex cell. The base cell then started anticlinal bipartition to two cells, which then underwent many cell divisions to form a multicellular spherical structure. In addition, phytohormones as environmental cues were closely related to trichome development. We found that GA and BAP were capable of increasing trichome number per fruit with distinct effects under different concentrations.}, } @article {pmid30220504, year = {2018}, author = {De Clerck, O and Kao, SM and Bogaert, KA and Blomme, J and Foflonker, F and Kwantes, M and Vancaester, E and Vanderstraeten, L and Aydogdu, E and Boesger, J and Califano, G and Charrier, B and Clewes, R and Del Cortona, A and D'Hondt, S and Fernandez-Pozo, N and Gachon, CM and Hanikenne, M and Lattermann, L and Leliaert, F and Liu, X and Maggs, CA and Popper, ZA and Raven, JA and Van Bel, M and Wilhelmsson, PKI and Bhattacharya, D and Coates, JC and Rensing, SA and Van Der Straeten, D and Vardi, A and Sterck, L and Vandepoele, K and Van de Peer, Y and Wichard, T and Bothwell, JH}, title = {Insights into the Evolution of Multicellularity from the Sea Lettuce Genome.}, journal = {Current biology : CB}, volume = {28}, number = {18}, pages = {2921-2933.e5}, doi = {10.1016/j.cub.2018.08.015}, pmid = {30220504}, issn = {1879-0445}, mesh = {*Biological Evolution ; Chromosome Mapping ; *Genome ; *Life History Traits ; Multigene Family ; Ulva/*genetics/growth & development ; }, abstract = {We report here the 98.5 Mbp haploid genome (12,924 protein coding genes) of Ulva mutabilis, a ubiquitous and iconic representative of the Ulvophyceae or green seaweeds. Ulva's rapid and abundant growth makes it a key contributor to coastal biogeochemical cycles; its role in marine sulfur cycles is particularly important because it produces high levels of dimethylsulfoniopropionate (DMSP), the main precursor of volatile dimethyl sulfide (DMS). Rapid growth makes Ulva attractive biomass feedstock but also increasingly a driver of nuisance "green tides." Ulvophytes are key to understanding the evolution of multicellularity in the green lineage, and Ulva morphogenesis is dependent on bacterial signals, making it an important species with which to study cross-kingdom communication. Our sequenced genome informs these aspects of ulvophyte cell biology, physiology, and ecology. Gene family expansions associated with multicellularity are distinct from those of freshwater algae. Candidate genes, including some that arose following horizontal gene transfer from chromalveolates, are present for the transport and metabolism of DMSP. The Ulva genome offers, therefore, new opportunities to understand coastal and marine ecosystems and the fundamental evolution of the green lineage.}, } @article {pmid30218496, year = {2018}, author = {Kulkarni, P and Uversky, VN}, title = {Intrinsically Disordered Proteins: The Dark Horse of the Dark Proteome.}, journal = {Proteomics}, volume = {18}, number = {21-22}, pages = {e1800061}, doi = {10.1002/pmic.201800061}, pmid = {30218496}, issn = {1615-9861}, mesh = {Animals ; Humans ; Intrinsically Disordered Proteins/*chemistry/*metabolism ; Protein Conformation ; Proteome/chemistry/metabolism ; }, abstract = {A good portion of the 'protein universe' embodies the 'dark proteome'. The latter comprises proteins not amenable to experimental structure determination by existing means and inaccessible to homology modeling. Hence, the dark proteome has remained largely unappreciated. Intrinsically disordered proteins (IDPs) that lack rigid 3D structure are a major component of this dark proteome across all three kingdoms of life. Despite lack of structure, IDPs play critical roles in numerous important biological processes. Furthermore, IDPs serve as crucial constituents of proteinaceous membrane-less organelles (PMLOs), where they often serve as drivers and controllers of biological liquid-liquid phase transitions responsible for the PMLO biogenesis. In this perspective, the role of IDPs is discussed in i) the origin of prebiotic life and the evolution of the first independent primordial living unit akin to Tibor Gánti's chemoton, which preceded the Last Universal Common Ancestor (LUCA), ii) role in multicellularity and hence, in major evolutionary transitions, and iii), their role in phenotypic switching, and the emergence of new traits and adaptive opportunities via non-genetic, protein-based mechanisms. The emerging picture suggests that despite being major constituents of the dark matter, IDPs may be the dark horse in the protein universe.}, } @article {pmid30214674, year = {2018}, author = {Baluška, F and Miller, WB}, title = {Senomic view of the cell: Senome versus Genome.}, journal = {Communicative & integrative biology}, volume = {11}, number = {3}, pages = {1-9}, pmid = {30214674}, issn = {1942-0889}, abstract = {In the legacy of Thomas Henry Huxley, and his 'epigenetic' philosophy of biology, cells are proposed to represent a trinity of three memory-storing media: Senome, Epigenome, and Genome that together comprise a cell-wide informational architecture. Our current preferential focus on the Genome needs to be complemented by a similar focus on the Epigenome and a here proposed Senome, representing the sum of all the sensory experiences of the cognitive cell and its sensing apparatus. Only then will biology be in a position to embrace the whole complexity of the eukaryotic cell, understanding its true nature which allows the communicative assembly of cells in the form of sentient multicellular organisms.}, } @article {pmid30212236, year = {2018}, author = {Zhang, L and Vijg, J}, title = {Somatic Mutagenesis in Mammals and Its Implications for Human Disease and Aging.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {397-419}, pmid = {30212236}, issn = {1545-2948}, support = {U01 HL145560/HL/NHLBI NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; R01 CA180126/CA/NCI NIH HHS/United States ; P30 AG038072/AG/NIA NIH HHS/United States ; P01 AG017242/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*genetics/pathology ; Clonal Evolution/genetics ; Genetic Diseases, Inborn/*genetics/pathology ; Genome, Human/*genetics ; Germ-Line Mutation/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Mutagenesis/*genetics ; Mutation/genetics ; }, abstract = {DNA mutations as a consequence of errors during DNA damage repair, replication, or mitosis are the substrate for evolution. In multicellular organisms, mutations can occur in the germline and also in somatic tissues, where they are associated with cancer and other chronic diseases and possibly with aging. Recent advances in high-throughput sequencing have made it relatively easy to study germline de novo mutations, but in somatic cells, the vast majority of mutations are low-abundant and can be detected only in clonal lineages, such as tumors, or single cells. Here we review recent results on somatic mutations in normal human and animal tissues with a focus on their possible functional consequences.}, } @article {pmid30199707, year = {2018}, author = {Niazi, S and Purohit, M and Niazi, JH}, title = {Role of p53 circuitry in tumorigenesis: A brief review.}, journal = {European journal of medicinal chemistry}, volume = {158}, number = {}, pages = {7-24}, doi = {10.1016/j.ejmech.2018.08.099}, pmid = {30199707}, issn = {1768-3254}, mesh = {Animals ; Carcinogenesis/drug effects/*metabolism/pathology ; Drug Discovery ; Humans ; Models, Molecular ; Proteasome Endopeptidase Complex/metabolism ; Protein Isoforms/metabolism ; Proto-Oncogene Proteins c-mdm2/metabolism ; Tumor Suppressor Protein p53/*metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism ; }, abstract = {Maintenance of genome integrity under the stressed condition is paramount for normal functioning of cells in the multicellular organisms. Cells are programmed to protect their genome through specialized adaptive mechanisms which will help decide their fate under stressed conditions. These mechanisms are the outcome of activation of the intricate circuitries that are regulated by the p53 master protein. In this paper, we provided a comprehensive review on p53, p53 homologues and their isoforms, including a description about the ubiquitin-proteasome system emphasizing its role in p53 regulation. p53 induced E3(Ub)-ligases are an integral part of the ubiquitin-proteasome system. This review outlines the roles of important E3(Ub)-ligases and their splice variants in maintaining cellular p53 protein homeostasis. It also covers up-to-date and relevant information on small molecule Mdm2 inhibitors originated from different organizations. The review ends with a discussion on future prospects and investigation directives for the development of next-generation modulators as p53 therapeutics.}, } @article {pmid30191307, year = {2019}, author = {Váchová, L and Palková, Z}, title = {Diverse roles of Tup1p and Cyc8p transcription regulators in the development of distinct types of yeast populations.}, journal = {Current genetics}, volume = {65}, number = {1}, pages = {147-151}, pmid = {30191307}, issn = {1432-0983}, support = {LQ1604 NPU II//Ministry of Education, Youth and Sports/ ; RVO61388971//Czech Academy of Sciences/ ; CZ.1.05/1.1.00/02.0109 BIOCEV//European Regional Development Fund and Ministry of Education, Youth and Sports/ ; }, mesh = {Biofilms ; Cell Wall/genetics/metabolism ; *Gene Expression Regulation, Fungal ; Nuclear Proteins/*genetics/metabolism ; Repressor Proteins/*genetics/metabolism ; Saccharomyces cerevisiae/classification/*genetics/physiology ; Saccharomyces cerevisiae Proteins/*genetics/metabolism ; Species Specificity ; }, abstract = {Yeasts create multicellular structures of varying complexity, such as more complex colonies and biofilms and less complex flocs, each of which develops via different mechanisms. Colony biofilms originate from one or more cells that, through growth and division, develop a complicated three-dimensional structure consisting of aerial parts, agar-embedded invasive parts and a central cavity, filled with extracellular matrix. In contrast, flocs arise relatively quickly by aggregation of planktonic cells growing in liquid cultures after they reach the appropriate growth phase and/or exhaust nutrients such as glucose. Creation of both types of structures is dependent on the presence of flocculins: Flo11p in the former case and Flo1p in the latter. We recently showed that formation of both types of structures by wild Saccharomyces cerevisiae strain BR-F is regulated via transcription regulators Tup1p and Cyc8p, but in a divergent manner. Biofilm formation is regulated by Cyc8p and Tup1p antagonistically: Cyc8p functions as a repressor of FLO11 gene expression and biofilm formation, whereas Tup1p counteracts the Cyc8p repressor function and positively regulates biofilm formation and Flo11p expression. In addition, Tup1p stabilizes Flo11p probably by repressing a gene coding for a cell wall or extracellular protease that is involved in Flo11p degradation. In contrast, formation of BR-F flocs is co-repressed by the Cyc8p-Tup1p complex. These findings point to different mechanisms involved in yeast multicellularity.}, } @article {pmid30177778, year = {2018}, author = {Waters, AJ and Capriotti, P and Gaboriau, DCA and Papathanos, PA and Windbichler, N}, title = {Rationally-engineered reproductive barriers using CRISPR & CRISPRa: an evaluation of the synthetic species concept in Drosophila melanogaster.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {13125}, pmid = {30177778}, issn = {2045-2322}, support = {335724/ERC_/European Research Council/International ; }, mesh = {Animals ; Base Sequence ; CRISPR-Associated Protein 9/genetics/metabolism ; *CRISPR-Cas Systems ; Drosophila Proteins/*genetics ; Drosophila melanogaster/*genetics ; Female ; Gene Editing/*methods ; *Genes, Insect ; Genes, Lethal ; Genetic Fitness ; Genetic Loci ; *Genome, Insect ; Homeodomain Proteins/*genetics ; INDEL Mutation ; Male ; Population Control/methods ; Promoter Regions, Genetic ; RNA, Guide, CRISPR-Cas Systems/genetics/metabolism ; Reproductive Isolation ; Sequence Alignment ; Transcription Factors/*genetics ; Transcriptional Activation ; }, abstract = {The ability to erect rationally-engineered reproductive barriers in animal or plant species promises to enable a number of biotechnological applications such as the creation of genetic firewalls, the containment of gene drives or novel population replacement and suppression strategies for genetic control. However, to date no experimental data exist that explores this concept in a multicellular organism. Here we examine the requirements for building artificial reproductive barriers in the metazoan model Drosophila melanogaster by combining CRISPR-based genome editing and transcriptional transactivation (CRISPRa) of the same loci. We directed 13 single guide RNAs (sgRNAs) to the promoters of 7 evolutionary conserved genes and used 11 drivers to conduct a misactivation screen. We identify dominant-lethal activators of the eve locus and find that they disrupt development by strongly activating eve outside its native spatio-temporal context. We employ the same set of sgRNAs to isolate, by genome editing, protective INDELs that render these loci resistant to transactivation without interfering with target gene function. When these sets of genetic components are combined we find that complete synthetic lethality, a prerequisite for most applications, is achievable using this approach. However, our results suggest a steep trade-off between the level and scope of dCas9 expression, the degree of genetic isolation achievable and the resulting impact on fly fitness. The genetic engineering strategy we present here allows the creation of single or multiple reproductive barriers and could be applied to other multicellular organisms such as disease vectors or transgenic organisms of economic importance.}, } @article {pmid30171399, year = {2018}, author = {Liu, Y and Liu, D and Khan, AR and Liu, B and Wu, M and Huang, L and Wu, J and Song, G and Ni, H and Ying, H and Yu, H and Gan, Y}, title = {NbGIS regulates glandular trichome initiation through GA signaling in tobacco.}, journal = {Plant molecular biology}, volume = {98}, number = {1-2}, pages = {153-167}, pmid = {30171399}, issn = {1573-5028}, support = {31570183; 31529001; 31661143004//National Natural Science Foundation of China/ ; LZ15C020001//Zhejiang Provincial Natural Science Foundation of China/ ; 2015CB150200//Major State Basic Research Development Program/ ; 2016YFD0100701//the National Key R & D Program of China/ ; }, mesh = {Amino Acid Sequence ; Biosynthetic Pathways/genetics ; Gene Expression Regulation, Plant ; Genes, Plant ; Gibberellins/biosynthesis/*metabolism ; Phenotype ; Phylogeny ; Plant Development/genetics ; Plant Proteins/chemistry/*metabolism ; Plant Shoots/physiology ; Plants, Genetically Modified ; *Signal Transduction ; Nicotiana/genetics/growth & development/*metabolism ; Trichomes/*growth & development/*metabolism/ultrastructure ; }, abstract = {A novel gene NbGIS positively regulates glandular trichome initiation through GA Signaling in tobacco. NbMYB123-like regulates glandular trichome initiation by acting downstream of NbGIS in tobacco. Glandular trichome is a specialized multicellular structure which has capability to synthesize and secrete secondary metabolites and protects plants from biotic and abiotic stresses. Our previous results revealed that a C2H2 zinc-finger transcription factor GIS and its sub-family genes act upstream of GL3/EGL3-GL1-TTG1 transcriptional activator complex to regulate trichome initiation in Arabidopsis. In this present study, we found that NbGIS could positively regulate glandular trichome development in Nicotiana benthamiana (tobacco). Our result demonstrated that 35S:NbGIS lines exhibited much higher densities of trichome on leaves, main stems, lateral branches and sepals than WT plants, while NbGIS:RNAi lines had the opposite phenotypes. Furthermore, our results also showed that NbGIS was required in response to GA signal to control glandular trichome initiation in Nicotiana benthamiana. In addition, our results also showed that NbGIS significantly influenced GA accumulation and expressions of marker genes of the GA biosynthesis, might result in the changes of growth and maturation in tobacco. Lastly, our results also showed that NbMYB123-like regulated glandular trichome initiation in tobacco by acting downstream of NbGIS. These findings provide new insights to discover the molecular mechanism by which C2H2 transcriptional factors regulates glandular trichome initiation through GA signaling pathway in tobacco.}, } @article {pmid30170750, year = {2018}, author = {Atkinson, SD and Bartholomew, JL and Lotan, T}, title = {Myxozoans: Ancient metazoan parasites find a home in phylum Cnidaria.}, journal = {Zoology (Jena, Germany)}, volume = {129}, number = {}, pages = {66-68}, doi = {10.1016/j.zool.2018.06.005}, pmid = {30170750}, issn = {1873-2720}, mesh = {Animals ; Biological Evolution ; Cnidaria/*parasitology ; Host-Parasite Interactions ; Myxozoa/genetics/*physiology ; Parasites ; }, abstract = {Myxozoans are endoparasites with complex life cycles that alternate between invertebrate and vertebrate hosts. Though considered protozoans for over 150 years, they are now recognized as metazoans, given their multicellularity and ultrastructural features. In recognition of synapomorphies and cnidarian-specific genes, myxozoans were placed recently within the phylum Cnidaria. Although they have lost genetic and structural complexity on the path to parasitism, myxozoans have retained characteristic cnidarian cnidocysts, but use them for initiating host infection. Myxozoans represent at least 20% of phylum Cnidaria, but as a result of rapid evolution, extensive diversification and host specialization, they are probably at least as diverse as their free-living relatives. The ability of myxozoans to infect freshwater, marine and terrestrial hosts implies that Cnidaria are no longer constrained to the aquatic environment.}, } @article {pmid30159848, year = {2018}, author = {Chi, C and Wang, L and Lan, W and Zhao, L and Su, Y}, title = {PpV, acting via the JNK pathway, represses apoptosis during normal development of Drosophila wing.}, journal = {Apoptosis : an international journal on programmed cell death}, volume = {23}, number = {9-10}, pages = {554-562}, doi = {10.1007/s10495-018-1479-2}, pmid = {30159848}, issn = {1573-675X}, mesh = {Animals ; Apoptosis/*genetics ; Drosophila melanogaster/genetics/growth & development ; Embryonic Development/genetics ; Gene Expression Regulation, Developmental ; Imaginal Discs/growth & development/metabolism ; JNK Mitogen-Activated Protein Kinases/*genetics ; MAP Kinase Signaling System/genetics ; Phosphoprotein Phosphatases/*genetics ; Wings, Animal/*growth & development/metabolism ; }, abstract = {Apoptosis is one of the main fundamental biological processes required for development of multicellular organisms. Inappropriate regulation of apoptosis can lead to severe developmental abnormalities and diseases. Therefore, the control of apoptosis, not only for its activation but also for its inhibition, is critically important during development. In contrast to the extensive studies of apoptosis induction, its inhibitory mechanisms that are even more vital in certain populations of cells actually are very far from being well understood. Here we report an inhibitory role of protein phosphatase V (PpV), a serine/threonine protein phosphatase, in controlling the apoptosis during Drosophila wing development. We observed that inhibition of ppv by RNAi in wing imaginal discs induced ectopic cell death and caspase activation, thus, resulted in a defective adult wing. Moreover, knocking-down ppv triggered the activation of c-Jun N-terminal kinase (JNK) signal, an evolutionarily conserved intracellular signaling that has been implicated to modulate the apoptotic machinery in many biological and experimental systems. Disrupting the JNK signal transduction was adequate to suppress the ppv effects for wing development. Together, we provided the evidence to demonstrate that ppv is required for normal wing development in maintaining the silence of apoptotic signal possibly through JNK pathway.}, } @article {pmid30158313, year = {2018}, author = {Bernadou, A and Schrader, L and Pable, J and Hoffacker, E and Meusemann, K and Heinze, J}, title = {Stress and early experience underlie dominance status and division of labour in a clonal insect.}, journal = {Proceedings. Biological sciences}, volume = {285}, number = {1885}, pages = {}, pmid = {30158313}, issn = {1471-2954}, mesh = {Animals ; Ants/growth & development/*physiology ; Larva/growth & development/physiology ; Life Change Events ; Population Dynamics ; Social Dominance ; *Stress, Physiological ; }, abstract = {Cooperation and division of labour are fundamental in the 'major transitions' in evolution. While the factors regulating cell differentiation in multi-cellular organisms are quite well understood, we are just beginning to unveil the mechanisms underlying individual specialization in cooperative groups of animals. Clonal ants allow the study of which factors influence task allocation without confounding variation in genotype and morphology. Here, we subjected larvae and freshly hatched workers of the clonal ant Platythyrea punctata to different rearing conditions and investigated how these manipulations affected division of labour among pairs of oppositely treated, same-aged clonemates. High rearing temperature, physical stress, injury and malnutrition increased the propensity of individuals to become subordinate foragers rather than dominant reproductives. This is reflected in changed gene regulation: early stages of division of labour were associated with different expression of genes involved in nutrient signalling pathways, metabolism and the phenotypic response to environmental stimuli. Many of these genes appear to be capable of responding to a broad range of stressors. They might link environmental stimuli to behavioural and phenotypic changes and could therefore be more broadly involved in caste differentiation in social insects. Our experiments also shed light on the causes of behavioural variation among genetically identical individuals.}, } @article {pmid30149856, year = {2018}, author = {Strauss, J and Wilkinson, C and Vidilaseris, K and Harborne, SPD and Goldman, A}, title = {A Simple Strategy to Determine the Dependence of Membrane-Bound Pyrophosphatases on K[+] as a Cofactor.}, journal = {Methods in enzymology}, volume = {607}, number = {}, pages = {131-156}, doi = {10.1016/bs.mie.2018.04.018}, pmid = {30149856}, issn = {1557-7988}, support = {BB/M021610/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Catalysis ; Cations, Monovalent/metabolism ; Cell Membrane/*metabolism ; Coenzymes/*metabolism ; Diphosphates/metabolism ; Enzyme Assays/instrumentation/*methods ; Hydrolysis ; Models, Molecular ; Mutagenesis, Site-Directed ; Potassium/*metabolism ; Pyrophosphatases/chemistry/genetics/isolation & purification/*metabolism ; Recombinant Proteins/chemistry/genetics/isolation & purification/metabolism ; Saccharomyces cerevisiae ; }, abstract = {Membrane-bound pyrophosphatases (mPPases) couple pyrophosphate hydrolysis to H[+] and/or Na[+] pumping across membranes and are found in all domains of life except for multicellular animals including humans. They are important for development and stress resistance in plants. Furthermore, mPPases play a role in virulence of human pathogens that cause severe diseases such as malaria and African sleeping sickness. Sequence analysis, functional studies, and recently solved crystal structures have contributed to the understanding of the mPPase catalytic cycle. However, several key mechanistic features remain unknown. During evolution, several subgroups of mPPases differing in their pumping specificity and cofactor dependency arose. mPPases are classified into one of five subgroups, usually by sequence analysis. However, classification based solely on sequence has been inaccurate in several instances due to our limited understanding of the molecular mechanism of mPPases. Thus, pumping specificity and cofactor dependency of mPPases require experimental confirmation. Here, we describe a simple method for the determination of K[+] dependency in mPPases using a hydrolytic activity assay. By coupling these dependency studies with site-directed mutagenesis, we have begun to build a better understanding of the molecular mechanisms of mPPases. We optimized the assay for thermostable mPPases that are commonly used as model systems in our lab, but the method is equally applicable to mesophilic mPPases with minor modifications.}, } @article {pmid30134151, year = {2018}, author = {Stone, R and Portegys, T and Mikhailovsky, G and Alicea, B}, title = {Origins of the Embryo: Self-organization through cybernetic regulation.}, journal = {Bio Systems}, volume = {173}, number = {}, pages = {73-82}, doi = {10.1016/j.biosystems.2018.08.005}, pmid = {30134151}, issn = {1872-8324}, mesh = {Algorithms ; Animals ; Biological Evolution ; *Cybernetics ; Developmental Biology/history ; Ecosystem ; *Embryonic Development ; Entropy ; History, 19th Century ; History, 20th Century ; Humans ; *Models, Biological ; Phenotype ; Thermodynamics ; }, abstract = {The construction of an embryo from a single cell precursor is a highly complex process. Evolutionary emergence of the first embryos is even more complex, and involves both a transition to multicellularity along with the establishment of developmental mechanisms. We propose that embryogenesis relies on a community of cells conforming to a regulatory model of emergent multicellularity. This model draws together multiple threads in the scientific literature, from complexity theory to cybernetics, and from thermodynamic entropy to artificial life. All of these strands come together to inform a model of goal-oriented regulation for emergent structures in early life. This is an important step in the evolution of early life, as well as the emergence of complex life in the earliest habitats. Our model, called the cybernetic embryo, allows for a systems-level view of the embryogenetic process.}, } @article {pmid30125231, year = {2018}, author = {Hanschen, ER and Herron, MD and Wiens, JJ and Nozaki, H and Michod, RE}, title = {Multicellularity Drives the Evolution of Sexual Traits.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {E93-E105}, pmid = {30125231}, issn = {1537-5323}, support = {NNA17BB05A/ImNASA/Intramural NASA/United States ; T32 GM084905/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Chlamydomonas reinhardtii/*genetics ; Meiosis ; *Sex Characteristics ; Volvox/*genetics ; }, abstract = {From the male peacock's tail plumage to the floral displays of flowering plants, traits related to sexual reproduction are often complex and exaggerated. Why has sexual reproduction become so complicated? Why have such exaggerated sexual traits evolved? Early work posited a connection between multicellularity and sexual traits such as anisogamy (i.e., the evolution of small sperm and large eggs). Anisogamy then drives the evolution of other forms of sexual dimorphism. Yet the relationship between multicellularity and the evolution of sexual traits has not been empirically tested. Given their extensive variation in both multicellular complexity and sexual systems, the volvocine green algae offer a tractable system for understanding the interrelationship of multicellular complexity and sex. Here we show that species with greater multicellular complexity have a significantly larger number of derived sexual traits, including anisogamy, internal fertilization, and secondary sexual dimorphism. Our results demonstrate that anisogamy repeatedly evolved from isogamous multicellular ancestors and that anisogamous species are larger and produce larger zygotes than isogamous species. In the volvocine algae, the evolution of multicellularity likely drives the evolution of anisogamy, and anisogamy subsequently drives secondary sexual dimorphism. Multicellularity may set the stage for the overall diversity of sexual complexity throughout the Tree of Life.}, } @article {pmid30113099, year = {2018}, author = {Stelbrink, B and Jovanovska, E and Levkov, Z and Ognjanova-Rumenova, N and Wilke, T and Albrecht, C}, title = {Diatoms do radiate: evidence for a freshwater species flock.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1969-1975}, doi = {10.1111/jeb.13368}, pmid = {30113099}, issn = {1420-9101}, mesh = {Diatoms/*genetics/*physiology ; *Evolution, Molecular ; Fossils ; *Fresh Water ; *Genetic Variation ; *Phylogeny ; Time Factors ; }, abstract = {Due to the ubiquity and high dispersal capacity of unicellular eukaryotes, their often extraordinary diversity found in isolated and long-lived ecosystems such as ancient lakes is typically attributed to multiple colonization events rather than to in situ speciation. However, respective evolutionary studies are very scarce and the often high number of species flocks in ancient lakes across multicellular taxa raises the question whether unicellular species, such as diatoms, may radiate as well. Here, we use an integrative approach that includes molecular data from benthic diatom species of the genus Aneumastus endemic to ancient Lake Ohrid, fossil data obtained from the sediment record of a recent deep-drilling project and biogeographical information to test if this group, indeed, constitutes a species flock. Molecular-clock and phylogenetic analyses indicate a young monophyletic group of several endemic species. Molecular, fossil and biogeographical data strongly suggest a rapid intralacustrine diversification, which was possibly triggered by the emergence of novel habitats. This finding is the first evidence for a species flock in diatoms and suggests that in situ speciation is also a relevant evolutionary process for unicellular eukaryotes in isolated ecosystems.}, } @article {pmid30111663, year = {2018}, author = {Grimes, DR and Currell, FJ}, title = {Oxygen diffusion in ellipsoidal tumour spheroids.}, journal = {Journal of the Royal Society, Interface}, volume = {15}, number = {145}, pages = {}, pmid = {30111663}, issn = {1742-5662}, support = {19834/CRUK_/Cancer Research UK/United Kingdom ; A19834/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Cell Line, Tumor ; Humans ; *Models, Biological ; Neoplasms/*metabolism/pathology ; Oxygen/*metabolism ; *Oxygen Consumption ; Spheroids, Cellular/*metabolism/pathology ; }, abstract = {Oxygen plays a central role in cellular metabolism, in both healthy and tumour tissue. The presence and concentration of molecular oxygen in tumours has a substantial effect on both radiotherapy response and tumour evolution, and as a result the oxygen micro-environment is an area of intense research interest. Multi-cellular tumour spheroids closely mimic real avascular tumours, and in particular they exhibit physiologically relevant heterogeneous oxygen distribution. This property has made them a vital part of in vitro experimentation. For ideal spheroids, their heterogeneous oxygen distributions can be predicted from theory, allowing determination of cellular oxygen consumption rate (OCR) and anoxic extent. However, experimental tumour spheroids often depart markedly from perfect sphericity. There has been little consideration of this reality. To date, the question of how far an ellipsoid can diverge from perfect sphericity before spherical assumptions break down remains unanswered. In this work, we derive equations governing oxygen distribution (and, more generally, nutrient and drug distribution) in both prolate and oblate tumour ellipsoids, and quantify the theoretical limits of the assumption that the spheroid is a perfect sphere. Results of this analysis yield new methods for quantifying OCR in ellipsoidal spheroids, and how this can be applied to markedly increase experimental throughput and quality.}, } @article {pmid30102347, year = {2018}, author = {Gaouda, H and Hamaji, T and Yamamoto, K and Kawai-Toyooka, H and Suzuki, M and Noguchi, H and Minakuchi, Y and Toyoda, A and Fujiyama, A and Nozaki, H and Smith, DR}, title = {Exploring the Limits and Causes of Plastid Genome Expansion in Volvocine Green Algae.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2248-2254}, pmid = {30102347}, issn = {1759-6653}, mesh = {Chlorophyta/genetics ; DNA, Algal/*genetics ; Evolution, Molecular ; *Genome, Plastid ; Plastids/genetics ; Sequence Analysis, DNA ; Volvox/*genetics ; }, abstract = {Plastid genomes are not normally celebrated for being large. But researchers are steadily uncovering algal lineages with big and, in rare cases, enormous plastid DNAs (ptDNAs), such as volvocine green algae. Plastome sequencing of five different volvocine species has revealed some of the largest, most repeat-dense plastomes on record, including that of Volvox carteri (∼525 kb). Volvocine algae have also been used as models for testing leading hypotheses on organelle genome evolution (e.g., the mutational hazard hypothesis), and it has been suggested that ptDNA inflation within this group might be a consequence of low mutation rates and/or the transition from a unicellular to multicellular existence. Here, we further our understanding of plastome size variation in the volvocine line by examining the ptDNA sequences of the colonial species Yamagishiella unicocca and Eudorina sp. NIES-3984 and the multicellular Volvox africanus, which are phylogenetically situated between species with known ptDNA sizes. Although V. africanus is closely related and similar in multicellular organization to V. carteri, its ptDNA was much less inflated than that of V. carteri. Synonymous- and noncoding-site nucleotide substitution rate analyses of these two Volvox ptDNAs suggest that there are drastically different plastid mutation rates operating in the coding versus intergenic regions, supporting the idea that error-prone DNA repair in repeat-rich intergenic spacers is contributing to genome expansion. Our results reinforce the idea that the volvocine line harbors extremes in plastome size but ultimately shed doubt on some of the previously proposed hypotheses for ptDNA inflation within the lineage.}, } @article {pmid30099198, year = {2018}, author = {Lazzari, G and Nicolas, V and Matsusaki, M and Akashi, M and Couvreur, P and Mura, S}, title = {Multicellular spheroid based on a triple co-culture: A novel 3D model to mimic pancreatic tumor complexity.}, journal = {Acta biomaterialia}, volume = {78}, number = {}, pages = {296-307}, doi = {10.1016/j.actbio.2018.08.008}, pmid = {30099198}, issn = {1878-7568}, mesh = {Cell Death ; Cell Line, Tumor ; Cell Survival ; Coculture Techniques ; Fibroblasts/cytology/metabolism ; Human Umbilical Vein Endothelial Cells/cytology/metabolism ; Humans ; *Models, Biological ; Pancreatic Neoplasms/*pathology ; Spheroids, Cellular/*pathology ; Tumor Microenvironment ; }, abstract = {UNLABELLED: The preclinical drug screening of pancreatic cancer treatments suffers from the absence of appropriate models capable to reproduce in vitro the heterogeneous tumor microenvironment and its stiff desmoplasia. Driven by this pressing need, we describe in this paper the conception and the characterization of a novel 3D tumor model consisting of a triple co-culture of pancreatic cancer cells (PANC-1), fibroblasts (MRC-5) and endothelial cells (HUVEC), which assembled to form a hetero-type multicellular tumor spheroid (MCTS). By histological analyses and Selective Plain Illumination Microscopy (SPIM) we have monitored the spatial distribution of each cell type and the evolution of the spheroid composition. Results revealed the presence of a core rich in fibroblasts and fibronectin in which endothelial cells were homogeneously distributed. The integration of the three cell types enabled to reproduce in vitro with fidelity the influence of the surrounding environment on the sensitivity of cancer cells to chemotherapy. To our knowledge, this is the first time that a scaffold-free pancreatic cancer spheroid model combining both tumor and multiple stromal components has been designed. It holds the possibility to become an advantageous tool for a pertinent assessment of the efficacy of various therapeutic strategies.

STATEMENT OF SIGNIFICANCE: Pancreatic tumor microenvironment is characterized by abundant fibrosis and aberrant vasculature. Aiming to reproduce in vitro these features, cancer cells have been already co-cultured with fibroblasts or endothelial cells separately but the integration of both these essential components of the pancreatic tumor microenvironment in a unique system, although urgently needed, was still missing. In this study, we successfully integrated cellular and acellular microenvironment components (i.e., fibroblasts, endothelial cells, fibronectin) in a hetero-type scaffold-free multicellular tumor spheroid. This new 3D triple co-culture model closely mimicked the resistance to treatments observed in vivo, resulting in a reduction of cancer cell sensitivity to the anticancer treatment.}, } @article {pmid30089142, year = {2018}, author = {Tverskoi, D and Makarenkov, V and Aleskerov, F}, title = {Modeling functional specialization of a cell colony under different fecundity and viability rates and resource constraint.}, journal = {PloS one}, volume = {13}, number = {8}, pages = {e0201446}, pmid = {30089142}, issn = {1932-6203}, mesh = {Biological Evolution ; Cell Communication/*physiology ; Cell Differentiation/*physiology ; Cell Survival/physiology ; Chlorophyta/cytology/*physiology ; Fertility/*physiology ; Germ Cells, Plant/physiology ; *Models, Biological ; }, abstract = {The emergence of functional specialization is a core problem in biology. In this work we focus on the emergence of reproductive (germ) and vegetative viability-enhancing (soma) cell functions (or germ-soma specialization). We consider a group of cells and assume that they contribute to two different evolutionary tasks, fecundity and viability. The potential of cells to contribute to fitness components is traded off. As embodied in current models, the curvature of the trade-off between fecundity and viability is concave in small-sized organisms and convex in large-sized multicellular organisms. We present a general mathematical model that explores how the division of labor in a cell colony depends on the trade-off curvatures, a resource constraint and different fecundity and viability rates. Moreover, we consider the case of different trade-off functions for different cells. We describe the set of all possible solutions of the formulated mathematical programming problem and show some interesting examples of optimal specialization strategies found for our objective fitness function. Our results suggest that the transition to specialized organisms can be achieved in several ways. The evolution of Volvocalean green algae is considered to illustrate the application of our model. The proposed model can be generalized to address a number of important biological issues, including the evolution of specialized enzymes and the emergence of complex organs.}, } @article {pmid30086318, year = {2018}, author = {Furumizu, C and Hirakawa, Y and Bowman, JL and Sawa, S}, title = {3D Body Evolution: Adding a New Dimension to Colonize the Land.}, journal = {Current biology : CB}, volume = {28}, number = {15}, pages = {R838-R840}, doi = {10.1016/j.cub.2018.06.040}, pmid = {30086318}, issn = {1879-0445}, mesh = {*Bryopsida ; }, abstract = {Complex multicellular plant bodies evolved in both generations of land plants. A new study demonstrates that CLAVATA3-like peptides function via conserved receptors in Physcomitrella patens as key molecules for morphological innovation of 3D growth in land plants.}, } @article {pmid30082786, year = {2018}, author = {Li, Z and Fu, X and Wang, Y and Liu, R and He, Y}, title = {Polycomb-mediated gene silencing by the BAH-EMF1 complex in plants.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1254-1261}, doi = {10.1038/s41588-018-0190-0}, pmid = {30082786}, issn = {1546-1718}, mesh = {Arabidopsis/genetics ; Arabidopsis Proteins/*genetics ; Chromatin/genetics ; Epigenesis, Genetic/genetics ; Flowers/genetics ; Gene Expression Regulation, Plant/genetics ; Gene Silencing/*physiology ; Genes, Plant/*genetics ; Histones/genetics ; Polycomb Repressive Complex 1/genetics ; Polycomb Repressive Complex 2/genetics ; Polycomb-Group Proteins/*genetics ; }, abstract = {Polycomb proteins implement genome-wide transcriptional repression in multicellular organisms. The evolutionarily conserved Polycomb repressive complex 2 (PRC2) catalyzes histone H3 Lys27 trimethylation (H3K27me3) that is read and effected by Polycomb repressive complex 1 (PRC1) in animals, but the interpretation of this mark remains unclear in plants. Here we report that in the eudicot Arabidopsis thaliana two homologous BAH (Bromo adjacent homology) domain-containing proteins form a plant-specific complex with EMBRYONIC FLOWER 1 (EMF1), and that the BAH-EMF1 complex (BAH-EMF1c) reads and effects the H3K27me3 mark and mediates genome-wide transcriptional repression. Furthermore, in the monocot rice a homolog of the Arabidopsis BAH-domain proteins also binds methylated H3K27 and forms a complex with the rice homolog of EMF1, suggesting that BAH-EMF1c is conserved in flowering plants. Therefore, our results show that the plant-specific BAH-EMF1c fulfills PRC1-like functions in higher plants, suggesting a convergent evolution of PRC1 activity in plants and animals.}, } @article {pmid30082277, year = {2018}, author = {Usui, H and Nishiwaki, A and Landiev, L and Kacza, J and Eichler, W and Wako, R and Kato, A and Takase, N and Kuwayama, S and Ohashi, K and Yafai, Y and Bringmann, A and Kubota, A and Ogura, Y and Seeger, J and Wiedemann, P and Yasukawa, T}, title = {In vitro drusen model - three-dimensional spheroid culture of retinal pigment epithelial cells.}, journal = {Journal of cell science}, volume = {132}, number = {4}, pages = {}, doi = {10.1242/jcs.215798}, pmid = {30082277}, issn = {1477-9137}, mesh = {Amyloid beta-Peptides/metabolism ; Biomarkers/metabolism ; Bruch Membrane/*metabolism ; Epithelial Cells/metabolism ; Humans ; Imaging, Three-Dimensional/methods ; Macular Degeneration/metabolism/pathology ; Retina/*metabolism/pathology ; Retinal Pigment Epithelium/*metabolism/pathology ; Retinal Pigments/*metabolism ; Spheroids, Cellular/metabolism ; }, abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50 years of age in many developed countries. Drusen are yellowish extracellular deposits beneath retinal pigment epithelium (RPE) found in aging eyes and considered as a biomarker of AMD. However, the biogenesis of drusen has not been elucidated. We reported previously that multicellular spheroids of human RPE cells constructed a well-differentiated monolayer of RPE with a Bruch's membrane. We determined that RPE spheroids exhibited drusen formation between the RPE and Bruch's membrane with expression of many drusen-associated proteins, such as amyloid β and complement components, the expression of which was altered by a challenge with oxidative stress. Artificial lipofuscin-loaded RPE spheroids yielded drusen more frequently. In the current study, we showed that drusen originates from the RPE. This culture system is an attractive tool for use as an in vitro drusen model, which might help elucidate the biogenesis of drusen and the pathogenesis of related diseases, such as AMD.}, } @article {pmid30078827, year = {2018}, author = {Oka, M and Yoneda, Y}, title = {Importin α: functions as a nuclear transport factor and beyond.}, journal = {Proceedings of the Japan Academy. Series B, Physical and biological sciences}, volume = {94}, number = {7}, pages = {259-274}, pmid = {30078827}, issn = {1349-2896}, mesh = {Active Transport, Cell Nucleus ; Animals ; Cell Nucleus/*metabolism ; Humans ; Neurons/cytology/metabolism ; Nuclear Pore/metabolism ; alpha Karyopherins/*metabolism ; }, abstract = {Nucleocytoplasmic transport is an essential process in eukaryotes. The molecular mechanisms underlying nuclear transport that involve the nuclear transport receptor, small GTPase Ran, and the nuclear pore complex are highly conserved from yeast to humans. On the other hand, it has become clear that the nuclear transport system diverged during evolution to achieve various physiological functions in multicellular eukaryotes. In this review, we first summarize the molecular mechanisms of nuclear transport and how these were elucidated. Then, we focus on the diverse functions of importin α, which acts not merely an import factor but also as a multi-functional protein contributing to a variety of cellular functions in higher eukaryotes.}, } @article {pmid30068565, year = {2018}, author = {Bornens, M}, title = {Cell polarity: having and making sense of direction-on the evolutionary significance of the primary cilium/centrosome organ in Metazoa.}, journal = {Open biology}, volume = {8}, number = {8}, pages = {}, pmid = {30068565}, issn = {2046-2441}, mesh = {Animals ; Biological Evolution ; Cell Movement ; Cell Polarity ; Centrosome/*metabolism ; Cilia/*metabolism ; Planarians/*physiology ; }, abstract = {Cell-autonomous polarity in Metazoans is evolutionarily conserved. I assume that permanent polarity in unicellular eukaryotes is required for cell motion and sensory reception, integration of these two activities being an evolutionarily constrained function. Metazoans are unique in making cohesive multicellular organisms through complete cell divisions. They evolved a primary cilium/centrosome (PC/C) organ, ensuring similar functions to the basal body/flagellum of unicellular eukaryotes, but in different cells, or in the same cell at different moments. The possibility that this innovation contributed to the evolution of individuality, in being instrumental in the early specification of the germ line during development, is further discussed. Then, using the example of highly regenerative organisms like planarians, which have lost PC/C organ in dividing cells, I discuss the possibility that part of the remodelling necessary to reach a new higher-level unit of selection in multi-cellular organisms has been triggered by conflicts among individual cell polarities to reach an organismic polarity. Finally, I briefly consider organisms with a sensorimotor organ like the brain that requires exceedingly elongated polarized cells for its activity. I conclude that beyond critical consequences for embryo development, the conservation of cell-autonomous polarity in Metazoans had far-reaching implications for the evolution of individuality.}, } @article {pmid30066215, year = {2018}, author = {Stencel, A and Wloch-Salamon, DM}, title = {Some theoretical insights into the hologenome theory of evolution and the role of microbes in speciation.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {137}, number = {2}, pages = {197-206}, pmid = {30066215}, issn = {1611-7530}, support = {2018/28/T/HS1/00201//Narodowe Centrum Nauki/ ; Opus 2017/25/B/NZ8/01035//Narodowe Centrum Nauki/ ; DS/762 - K/ZDS/007338//Uniwersytet Jagielloński w Krakowie/ ; }, mesh = {*Adaptation, Biological ; Adaptation, Physiological/genetics ; Animals ; *Genetic Speciation ; Host-Parasite Interactions/genetics ; Microbiota ; Philosophy ; Plants ; Species Specificity ; *Symbiosis ; }, abstract = {Research on symbiotic communities (microbiomes) of multicellular organisms seems to be changing our understanding of how species of plants and animals have evolved over millions of years. The quintessence of these discoveries is the emergence of the hologenome theory of evolution, founded on the concept that a holobiont (a host along with all of its associated symbiotic microorganisms) acts a single unit of selection in the process of evolution. Although the hologenome theory has become very popular among certain scientific circles, its principles are still being debated. In this paper, we argue, firstly, that only a very small number of symbiotic microorganisms are sufficiently integrated into multicellular organisms to act in concert with them as units of selection, thus rendering claims that holobionts are units of selection invalid. Secondly, even though holobionts are not units of selection, they can still constitute genuine units from an evolutionary perspective, provided we accept certain constraints: mainly, they should be considered units of co-operation. Thirdly, we propose a reconciliation of the role of symbiotic microorganisms with the theory of speciation through the use of a developed framework. Mainly, we will argue that, in order to understand the role of microorganisms in the speciation of multicellular organisms, it is not necessary to consider holobionts units of selection; it is sufficient to consider them units of co-operation.}, } @article {pmid30061903, year = {2018}, author = {Benítez, M and Hernández-Hernández, V and Newman, SA and Niklas, KJ}, title = {Dynamical Patterning Modules, Biogeneric Materials, and the Evolution of Multicellular Plants.}, journal = {Frontiers in plant science}, volume = {9}, number = {}, pages = {871}, pmid = {30061903}, issn = {1664-462X}, abstract = {Comparative analyses of developmental processes across a broad spectrum of organisms are required to fully understand the mechanisms responsible for the major evolutionary transitions among eukaryotic photosynthetic lineages (defined here as the polyphyletic algae and the monophyletic land plants). The concepts of dynamical patterning modules (DPMs) and biogeneric materials provide a framework for studying developmental processes in the context of such comparative analyses. In the context of multicellularity, DPMs are defined as sets of conserved gene products and molecular networks, in conjunction with the physical morphogenetic and patterning processes they mobilize. A biogeneric material is defined as mesoscale matter with predictable morphogenetic capabilities that arise from complex cellular conglomerates. Using these concepts, we outline some of the main events and transitions in plant evolution, and describe the DPMs and biogeneric properties associated with and responsible for these transitions. We identify four primary DPMs that played critical roles in the evolution of multicellularity (i.e., the DPMs responsible for cell-to-cell adhesion, identifying the future cell wall, cell differentiation, and cell polarity). Three important conclusions emerge from a broad phyletic comparison: (1) DPMs have been achieved in different ways, even within the same clade (e.g., phycoplastic cell division in the Chlorophyta and phragmoplastic cell division in the Streptophyta), (2) DPMs had their origins in the co-option of molecular species present in the unicellular ancestors of multicellular plants, and (3) symplastic transport mediated by intercellular connections, particularly plasmodesmata, was critical for the evolution of complex multicellularity in plants.}, } @article {pmid30061561, year = {2018}, author = {Stewart, AD and Rice, WR}, title = {Arrest of sex-specific adaptation during the evolution of sexual dimorphism in Drosophila.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1507-1513}, doi = {10.1038/s41559-018-0613-4}, pmid = {30061561}, issn = {2397-334X}, support = {1R01HD057974-01/NH/NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *Body Size ; Drosophila melanogaster/*anatomy & histology ; Female ; Male ; *Sex Characteristics ; }, abstract = {Sexually antagonistic selection arises when a trait expressed in both sexes (a shared trait) is selected towards different, sex-specific optima. Sex-discordant selection causes different alleles to be favoured in each sex (intralocus sexual conflict). A key parameter responsible for generating this conflict is the intersexual genetic correlation (rMF), which determines the degree to which heritable genetic variation for the shared trait produces a similar phenotype in both sexes. A strong, positive rMF interferes with adaptation when there is sex-discordant selection. In principle, the rMF can evolve in response to sex-discordant selection: the faster it declines, the faster the resolution of intralocus sexual conflict. Here, we use Drosophila melanogaster to quantify the time scale over which a strong, positive rMF impedes a response to sex-discordant selection for a canonical quantitative trait (body size) with an exceptionally long (250 generations) selection experiment for a complex multicellular organism. We found that, compared with rapid and substantial evolution under sex-concordant selection, a high rMF arrested sex-specific adaptation for 100 generations in females and a minimum of 250 generations in males. Our study demonstrates that a high rMF can lead to a protracted period of adaptive stalemate during the evolution of sexual dimorphism.}, } @article {pmid30061406, year = {2018}, author = {Dunn, BS and Rush, L and Lu, JY and Xu, T}, title = {Mutations in the Drosophila tricellular junction protein M6 synergize with Ras[V12] to induce apical cell delamination and invasion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8358-8363}, pmid = {30061406}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cell Movement ; Drosophila Proteins/genetics/*physiology ; Drosophila melanogaster/genetics ; Intercellular Junctions/*physiology ; *Mutation ; Myosin Type II/physiology ; *Neoplasm Invasiveness ; Neoplasm Metastasis ; ras Proteins/*physiology ; rhoA GTP-Binding Protein/physiology ; }, abstract = {Complications from metastasis are responsible for the majority of cancer-related deaths. Despite the outsized medical impact of metastasis, remarkably little is known about one of the key early steps of metastasis: departure of a tumor cell from its originating tissue. It is well documented that cellular delamination in the basal direction can induce invasive behaviors, but it remains unknown if apical cell delamination can induce migration and invasion in a cancer context. To explore this feature of cancer progression, we performed a genetic screen in Drosophila and discovered that mutations in the protein M6 synergize with oncogenic Ras to drive invasion following apical delamination without crossing a basement membrane. Mechanistically, we observed that M6-deficient Ras[V12] clones delaminate as a result of alterations in a Canoe-RhoA-myosin II axis that is necessary for both the delamination and invasion phenotypes. To uncover the cellular roles of M6, we show that it localizes to tricellular junctions in epithelial tissues where it is necessary for the structural integrity of multicellular contacts. This work provides evidence that apical delamination can precede invasion and highlights the important role that tricellular junction integrity can play in this process.}, } @article {pmid30059538, year = {2018}, author = {Waldron, FM and Stone, GN and Obbard, DJ}, title = {Metagenomic sequencing suggests a diversity of RNA interference-like responses to viruses across multicellular eukaryotes.}, journal = {PLoS genetics}, volume = {14}, number = {7}, pages = {e1007533}, pmid = {30059538}, issn = {1553-7404}, support = {/WT_/Wellcome Trust/United Kingdom ; WT095831/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Annelida/genetics/immunology/microbiology ; Argonaute Proteins/genetics ; Cnidaria/genetics/immunology/microbiology ; DNA Transposable Elements/genetics ; Echinodermata/genetics/immunology/microbiology ; Host Microbial Interactions/*genetics/immunology ; *Metagenomics ; Mollusca/genetics/immunology/microbiology ; Phaeophyceae/genetics/immunology/microbiology ; Phylogeny ; Porifera/genetics/immunology/microbiology ; RNA Interference/*immunology ; RNA Viruses/genetics/*immunology ; RNA, Small Interfering/genetics/metabolism ; RNA, Viral/*genetics/immunology ; Ribonuclease III/genetics ; Sequence Analysis, RNA ; }, abstract = {RNA interference (RNAi)-related pathways target viruses and transposable element (TE) transcripts in plants, fungi, and ecdysozoans (nematodes and arthropods), giving protection against infection and transmission. In each case, this produces abundant TE and virus-derived 20-30nt small RNAs, which provide a characteristic signature of RNAi-mediated defence. The broad phylogenetic distribution of the Argonaute and Dicer-family genes that mediate these pathways suggests that defensive RNAi is ancient, and probably shared by most animal (metazoan) phyla. Indeed, while vertebrates had been thought an exception, it has recently been argued that mammals also possess an antiviral RNAi pathway, although its immunological relevance is currently uncertain and the viral small RNAs (viRNAs) are not easily detectable. Here we use a metagenomic approach to test for the presence of viRNAs in five species from divergent animal phyla (Porifera, Cnidaria, Echinodermata, Mollusca, and Annelida), and in a brown alga-which represents an independent origin of multicellularity from plants, fungi, and animals. We use metagenomic RNA sequencing to identify around 80 virus-like contigs in these lineages, and small RNA sequencing to identify viRNAs derived from those viruses. We identified 21U small RNAs derived from an RNA virus in the brown alga, reminiscent of plant and fungal viRNAs, despite the deep divergence between these lineages. However, contrary to our expectations, we were unable to identify canonical (i.e. Drosophila- or nematode-like) viRNAs in any of the animals, despite the widespread presence of abundant micro-RNAs, and somatic transposon-derived piwi-interacting RNAs. We did identify a distinctive group of small RNAs derived from RNA viruses in the mollusc. However, unlike ecdysozoan viRNAs, these had a piRNA-like length distribution but lacked key signatures of piRNA biogenesis. We also identified primary piRNAs derived from putatively endogenous copies of DNA viruses in the cnidarian and the echinoderm, and an endogenous RNA virus in the mollusc. The absence of canonical virus-derived small RNAs from our samples may suggest that the majority of animal phyla lack an antiviral RNAi response. Alternatively, these phyla could possess an antiviral RNAi response resembling that reported for vertebrates, with cryptic viRNAs not detectable through simple metagenomic sequencing of wild-type individuals. In either case, our findings show that the antiviral RNAi responses of arthropods and nematodes, which are highly divergent from each other and from that of plants and fungi, are also highly diverged from the most likely ancestral metazoan state.}, } @article {pmid30028958, year = {2018}, author = {Campbell, FC and Loughrey, MB and McClements, J and Deevi, RK and Javadi, A and Rainey, L}, title = {Mechanistic Insights into Colorectal Cancer Phenomics from Fundamental and Organotypic Model Studies.}, journal = {The American journal of pathology}, volume = {188}, number = {9}, pages = {1936-1948}, pmid = {30028958}, issn = {1525-2191}, support = {15342/CRUK_/Cancer Research UK/United Kingdom ; MR/L015110/1/MRC_/Medical Research Council/United Kingdom ; C9136/A15342/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Colorectal Neoplasms/*pathology ; *Disease Models, Animal ; Humans ; Organ Culture Techniques/*methods ; }, abstract = {Colorectal cancer (CRC) diagnosis and prognostic stratification are based on histopathologic assessment of cell or nuclear pleomorphism, aberrant mitotic figures, altered glandular architecture, and other phenomic abnormalities. This complexity is driven by oncogenic perturbation of tightly coordinated spatiotemporal signaling to disrupt multiple scales of tissue organization. This review clarifies molecular and cellular mechanisms underlying common CRC histologic features and helps understand how the CRC genome controls core aspects of tumor aggressiveness. It further explores a spatiotemporal framework for CRC phenomics based on regulation of living cells in fundamental and organotypic model systems. The review also discusses tissue homeostasis, considers distinct classes of oncogenic perturbations, and evolution of cellular or multicellular cancer phenotypes. It further explores the molecular controls of cribriform, micropapillary, and high-grade CRC morphology in organotypic culture models and assesses relevant translational studies. In addition, the review delves into complexities of morphologic plasticity whereby a single molecular signature generates heterogeneous cancer phenotypes, and, conversely, morphologically homogeneous tumors show substantive molecular diversity. Principles outlined may aid mechanistic interpretation of omics data in a setting of cancer pathology, provide insight into CRC consensus molecular subtypes, and better define principles for CRC prognostic stratification.}, } @article {pmid29992410, year = {2018}, author = {Leong, SP and Aktipis, A and Maley, C}, title = {Cancer initiation and progression within the cancer microenvironment.}, journal = {Clinical & experimental metastasis}, volume = {35}, number = {5-6}, pages = {361-367}, pmid = {29992410}, issn = {1573-7276}, mesh = {Carcinogenesis/*genetics ; Cell Proliferation/*genetics ; Disease Progression ; Humans ; Melanoma/*genetics/pathology ; Neoplasm Metastasis ; Tumor Microenvironment/*genetics ; }, abstract = {Within the cancer microenvironment, the growth and proliferation of cancer cells in the primary site as well as in the metastatic site represent a global biological phenomenon. To understand the growth, proliferation and progression of cancer either by local expansion and/or metastasis, it is important to understand the cancer microenvironment and host response to cancer growth. Melanoma is an excellent model to study the interaction of cancer initiation and growth in relationship to its microenvironment. Social evolution with cooperative cellular groups within an organism is what gives rise to multicellularity in the first place. Cancer cells evolve to exploit their cellular environment. The foundations of multicellular cooperation break down in cancer because those cells that misbehave have an evolutionary advantage over their normally behaving neighbors. It is important to classify evolutionary and ecological aspects of cancer growth, thus, data for cancer growth and outcomes need to be collected to define these parameters so that accurate predictions of how cancer cells may proliferate and metastasize can be developed.}, } @article {pmid29981215, year = {2018}, author = {Chang, J and Yu, T and Yang, Q and Li, C and Xiong, C and Gao, S and Xie, Q and Zheng, F and Li, H and Tian, Z and Yang, C and Ye, Z}, title = {Hair, encoding a single C2H2 zinc-finger protein, regulates multicellular trichome formation in tomato.}, journal = {The Plant journal : for cell and molecular biology}, volume = {96}, number = {1}, pages = {90-102}, doi = {10.1111/tpj.14018}, pmid = {29981215}, issn = {1365-313X}, mesh = {Alleles ; CYS2-HIS2 Zinc Fingers/*physiology ; Capsicum ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Genome-Wide Association Study ; Solanum lycopersicum/genetics/growth & development/*metabolism ; Plant Proteins/genetics/*physiology ; Plants, Genetically Modified ; Nicotiana ; Trichomes/*growth & development ; Two-Hybrid System Techniques ; }, abstract = {Trichomes originate from the epidermal cells of nearly all terrestrial plants, which are specialized unicellular or multicellular structures. Although the molecular mechanism regulating unicellular trichome formation has been extensively characterized, most of the genes essential for multicellular trichome formation remain unknown. In this study, we identified an associated locus on the long arm of chromosome 10 using a genome-wide association study (GWAS) on type-I trichomes of 180 diverse Solanum lycopersicum (tomato) accessions. Using map-based cloning we then cloned the key gene controlling the initiation of this type of trichome, named Hair (H), which encodes a single C2H2 zinc-finger protein. Transgenic experiments showed that hair-absent phenotype is caused by the deletion of the entire coding region of H. We identified three alleles of H containing several missense mutations and a nucleotide deletion, which result in amino acid substitutions and a reading frame shift, respectively. In addition, knockdown of H or Woolly (Wo) represses the formation of type-I trichomes, suggesting that both regulators may function as a heterodimer. Direct protein-protein interaction between them was further detected through pull-down and yeast two-hybrid assays. In addition, ectopic expression of H in Nicotiana tabacum (tobacco) and expression of its homologs from Capsicum annuum (pepper) and tobacco in tomato can trigger trichome formation. Taken together, these findings suggest that the H gene may be functionally conserved in multicellular trichome formation in Solanaceae species.}, } @article {pmid29966484, year = {2018}, author = {Liao, Z and Kjellin, J and Hoeppner, MP and Grabherr, M and Söderbom, F}, title = {Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis in the social amoeba Dictyostelium discoideum.}, journal = {RNA biology}, volume = {15}, number = {7}, pages = {937-954}, pmid = {29966484}, issn = {1555-8584}, mesh = {Adaptation, Biological ; Biological Evolution ; Dictyostelium/genetics/*metabolism ; Gene Knockout Techniques ; Genome, Protozoan/genetics ; High-Throughput Nucleotide Sequencing ; MicroRNAs/analysis/*biosynthesis/genetics ; Oligonucleotide Probes/analysis/genetics/metabolism ; Promoter Regions, Genetic/genetics ; Protozoan Proteins/genetics/*metabolism ; RNA, Protozoan/analysis/*biosynthesis/genetics ; Ribonuclease III/genetics/*metabolism ; Transcription, Genetic ; }, abstract = {Micro (mi)RNAs regulate gene expression in many eukaryotic organisms where they control diverse biological processes. Their biogenesis, from primary transcripts to mature miRNAs, have been extensively characterized in animals and plants, showing distinct differences between these phylogenetically distant groups of organisms. However, comparably little is known about miRNA biogenesis in organisms whose evolutionary position is placed in between plants and animals and/or in unicellular organisms. Here, we investigate miRNA maturation in the unicellular amoeba Dictyostelium discoideum, belonging to Amoebozoa, which branched out after plants but before animals. High-throughput sequencing of small RNAs and poly(A)-selected RNAs demonstrated that the Dicer-like protein DrnB is required, and essentially specific, for global miRNA maturation in D. discoideum. Our RNA-seq data also showed that longer miRNA transcripts, generally preceded by a T-rich putative promoter motif, accumulate in a drnB knock-out strain. For two model miRNAs we defined the transcriptional start sites (TSSs) of primary (pri)-miRNAs and showed that they carry the RNA polymerase II specific m[7]G-cap. The generation of the 3'-ends of these pri-miRNAs differs, with pri-mir-1177 reading into the downstream gene, and pri-mir-1176 displaying a distinct end. This 3´-end is processed to shorter intermediates, stabilized in DrnB-depleted cells, of which some carry a short oligo(A)-tail. Furthermore, we identified 10 new miRNAs, all DrnB dependent and developmentally regulated. Thus, the miRNA machinery in D. discoideum shares features with both plants and animals, which is in agreement with its evolutionary position and perhaps also an adaptation to its complex lifestyle: unicellular growth and multicellular development.}, } @article {pmid29961831, year = {2018}, author = {Zhao, J and Yuan, S and Gao, B and Zhu, S}, title = {Molecular diversity of fungal inhibitor cystine knot peptides evolved by domain repeat and fusion.}, journal = {FEMS microbiology letters}, volume = {365}, number = {15}, pages = {}, doi = {10.1093/femsle/fny158}, pmid = {29961831}, issn = {1574-6968}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Evolution, Molecular ; Exons ; Fungal Proteins/chemistry/genetics/metabolism ; Fungi/chemistry/classification/*genetics/metabolism ; Genetic Variation ; Genome, Fungal ; Introns ; Peptides/*chemistry/*genetics/metabolism ; Phylogeny ; Protein Domains ; Sequence Alignment ; }, abstract = {Peptides with the inhibitor cystine knot (ICK) motif are extensively present in animals and plants where they exert a diversity of biological functions. However, few studies have been undertaken on this class of peptides in fungi. In this work, we identify a total of 386 fungal ICK peptides and proteins containing this motif by computational data mining of fungal genome databases, which exhibit 14 different exon-intron structures. According to their domain architectures, these proteins are classified into three distinct structural types, including single domains, tandem repeat domains and fusion domains, in which six families belonging to single or tandem repeat domains show remarkable sequence similarity to those from animals and plants, suggesting their orthologous relationship. Extremely high molecular diversity in fungal ICKs might be attributable to different genetic mechanisms, such as gene/domain duplication and fusion. This work not only enlarges the number of ICK peptides in multicellular organisms, but also uncovers their complex evolutionary history in a specific lineage.}, } @article {pmid29954963, year = {2018}, author = {Pennisi, E}, title = {Is cancer a breakdown of multicellularity?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1391}, doi = {10.1126/science.360.6396.1391}, pmid = {29954963}, issn = {1095-9203}, mesh = {*Biological Evolution ; Carcinogenesis/genetics/*pathology ; Gene Regulatory Networks ; Humans ; Neoplasms/genetics/*pathology ; }, } @article {pmid29942020, year = {2018}, author = {Sebé-Pedrós, A and Chomsky, E and Pang, K and Lara-Astiaso, D and Gaiti, F and Mukamel, Z and Amit, I and Hejnol, A and Degnan, BM and Tanay, A}, title = {Early metazoan cell type diversity and the evolution of multicellular gene regulation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1176-1188}, pmid = {29942020}, issn = {2397-334X}, support = {309706/ERC_/European Research Council/International ; }, mesh = {Animals ; *Biological Evolution ; Ctenophora/*cytology/genetics ; Placozoa/*cytology/genetics ; Porifera/*cytology/genetics ; Sequence Analysis, RNA ; Transcription, Genetic/*physiology ; }, abstract = {A hallmark of metazoan evolution is the emergence of genomic mechanisms that implement cell-type-specific functions. However, the evolution of metazoan cell types and their underlying gene regulatory programmes remains largely uncharacterized. Here, we use whole-organism single-cell RNA sequencing to map cell-type-specific transcription in Porifera (sponges), Ctenophora (comb jellies) and Placozoa species. We describe the repertoires of cell types in these non-bilaterian animals, uncovering diverse instances of previously unknown molecular signatures, such as multiple types of peptidergic cells in Placozoa. Analysis of the regulatory programmes of these cell types reveals variable levels of complexity. In placozoans and poriferans, sequence motifs in the promoters are predictive of cell-type-specific programmes. By contrast, the generation of a higher diversity of cell types in ctenophores is associated with lower specificity of promoter sequences and the existence of distal regulatory elements. Our findings demonstrate that metazoan cell types can be defined by networks of transcription factors and proximal promoters, and indicate that further genome regulatory complexity may be required for more diverse cell type repertoires.}, } @article {pmid29939836, year = {2018}, author = {Pashov, A and Hernandez Puente, CV and Ibrahim, SM and Monzavi-Karbassi, B and Makhoul, I and Kieber-Emmons, T}, title = {Thinking Cancer.}, journal = {Monoclonal antibodies in immunodiagnosis and immunotherapy}, volume = {37}, number = {3}, pages = {117-125}, doi = {10.1089/mab.2018.0014}, pmid = {29939836}, issn = {2167-9436}, mesh = {Animals ; Anthroposophy ; Autoantibodies/biosynthesis/genetics ; B7-H1 Antigen/*genetics/immunology ; Cell Transformation, Neoplastic/*genetics/immunology/pathology ; *Epigenesis, Genetic ; *Gene Expression Regulation, Neoplastic ; Gene-Environment Interaction ; Homeostasis/genetics/immunology ; Humans ; Immunity, Innate ; Interferon-gamma/genetics/immunology ; Mutation ; Neoplasm Proteins/*genetics/immunology ; Neoplasms/*genetics/immunology/pathology ; }, abstract = {Evolutionary theories are necessarily invoked for understanding cancer development at the level of species, at the level of cells and tissues, and for developing effective therapies. It is crucial to view cancer in a Darwinian light, where the differential survival of individual cells is based on heritable variations. In the process of this somatic evolution, multicellularity controls are overridden by cancer cells, which become increasingly autonomous. Ecological epigenetics also helps understand how rogue cells that have basically the same DNA as their normal cell counterpart overcome the tissue homeostasis. As we struggle to wrap our minds around the complexity of these phenomena, we apply often times anthropomorphic terms, such as subversion, hijacking, or hacking, to describe especially the most complex among them-the interaction of tumors with the immune system. In this commentary we highlight examples of the anthropomorphic thinking of cancer and try to put into context the relative meaning of terms and the mechanisms that are oftentimes invoked to justify those terms.}, } @article {pmid29938763, year = {2018}, author = {Funayama, N}, title = {The cellular and molecular bases of the sponge stem cell systems underlying reproduction, homeostasis and regeneration.}, journal = {The International journal of developmental biology}, volume = {62}, number = {6-7-8}, pages = {513-525}, doi = {10.1387/ijdb.180016nf}, pmid = {29938763}, issn = {1696-3547}, mesh = {Animals ; Cell Differentiation/genetics/physiology ; Cell Plasticity/genetics/physiology ; Cell Transdifferentiation/genetics/physiology ; Gene Expression Profiling ; Homeostasis/genetics/*physiology ; Porifera/cytology/genetics/*physiology ; Regeneration/genetics/*physiology ; Reproduction/genetics/physiology ; Stem Cells/cytology/metabolism/*physiology ; }, abstract = {The evolution of multicellular organisms is generally thought (and seems likely) to have been accompanied by the evolution of a stem cell system. Sponges, some of the early-evolved metazoans, have totipotent/pluripotent stem cells. Thus, uncovering the cellular and molecular bases of the sponge stem cells will not only be crucial for understanding the ancestral gene repertoire of animal stem cells, but will also give us clues to understanding the evolution of molecular mechanisms for maintaining multipotency (pluripotency) and differentiation ability during animal evolution. Sponges (Porifera) are a large phylum that includes an enormous number of species, whose cellular compositions and life cycles show striking variations. In the last decade, methodologies for molecular studies and sequencing resources have dramatically advanced and made it possible to clearly define stem cells in sponges in cellular and molecular terms. In this review, together with recent studies of sponges in various classes, the following issues will be discussed: i) recent findings that revealed that the previously proposed model that "archeocytes and choanocytes are the two types of stem cells" originally based on work in demosponges can be applied as a unified view of the stem cell system in sponges that have various cellular organizations, ii) the fact that sponge cells are more plastic than previously thought, as shown by recent studies of sponge regeneration both from dissociated cells and upon injury, and iii) the importance of transdifferentiation in sponge stem cell systems and regeneration.}, } @article {pmid29914363, year = {2018}, author = {Dunning Hotopp, JC}, title = {Grafting or pruning in the animal tree: lateral gene transfer and gene loss?.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {470}, pmid = {29914363}, issn = {1471-2164}, support = {R01 CA206188/CA/NCI NIH HHS/United States ; ABI-1457957//National Science Foundation/ ; 1-R01-CA206188//National Cancer Institute/ ; }, mesh = {Animals ; Bacteria/*genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genome ; Humans ; Phylogeny ; Prokaryotic Cells/*metabolism ; }, abstract = {BACKGROUND: Lateral gene transfer (LGT), also known as horizontal gene transfer, into multicellular eukaryotes with differentiated tissues, particularly gonads, continues to be met with skepticism by many prominent evolutionary and genomic biologists. A detailed examination of 26 animal genomes identified putative LGTs in invertebrate and vertebrate genomes, concluding that there are fewer predicted LGTs in vertebrates/chordates than invertebrates, but there is still evidence of LGT into chordates, including humans. More recently, a reanalysis of a subset of these putative LGTs into vertebrates concluded that there is not horizontal gene transfer in the human genome. One of the genes in dispute is an N-acyl-aromatic-L-amino acid amidohydrolase (ENSG00000132744), which encodes ACY3. This gene was initially identified as a putative bacteria-chordate LGT but was later debunked as it has a significant BLAST match to a more recently deposited genome of Saccoglossus kowalevskii, a flatworm, Metazoan, and hemichordate.

RESULTS: Using BLAST searches, HMM searches, and phylogenetics to assess the evidence for LGT, gene loss, and rate variation in ACY3/ASPA homologues, the most parsimonious explanation for the distribution of ACY3/ASPA genes in eukaryotes involves both gene loss and bacteria-animal LGT, albeit LGT that occurred hundreds of millions of years ago prior to the divergence of gnathostomes.

CONCLUSIONS: ACY3/ASPA is most likely a bacteria-animal LGT. LGTs at these time scales in the ancestors of humans are not unexpected given the many known, well-characterized, and adaptive LGTs from bacteria to insects and nematodes.}, } @article {pmid29899159, year = {2018}, author = {Zarkoob, H and Chinnathambi, S and Selby, JC and Sander, EA}, title = {Substrate deformations induce directed keratinocyte migration.}, journal = {Journal of the Royal Society, Interface}, volume = {15}, number = {143}, pages = {}, pmid = {29899159}, issn = {1742-5662}, mesh = {Amides/pharmacology ; Cell Line ; *Cell Movement ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Humans ; Keratinocytes/*metabolism/pathology ; Pyridines/pharmacology ; *Signal Transduction ; *Wound Healing ; rho GTP-Binding Proteins/antagonists & inhibitors/metabolism ; rho-Associated Kinases/antagonists & inhibitors/metabolism ; }, abstract = {Cell migration is an essential part of many (patho)physiological processes, including keratinocyte re-epithelialization of healing wounds. Physical forces and mechanical cues from the wound bed (in addition to biochemical signals) may also play an important role in the healing process. Previously, we explored this possibility and found that polyacrylamide (PA) gel stiffness affected human keratinocyte behaviour and that mechanical deformations in soft (approx. 1.2 kPa) PA gels produced by neighbouring cells appeared to influence the process of de novo epithelial sheet formation. To clearly demonstrate that keratinocytes do respond to such deformations, we conducted a series of experiments where we observed the response of single keratinocytes to a prescribed local substrate deformation that mimicked a neighbouring cell or evolving multicellular aggregate via a servo-controlled microneedle. We also examined the effect of adding either Y27632 or blebbistatin on cell response. Our results indicate that keratinocytes do sense and respond to mechanical signals comparable to those that originate from substrate deformations imposed by neighbouring cells, a finding that could have important implications for the process of keratinocyte re-epithelialization that takes place during wound healing. Furthermore, the Rho/ROCK pathway and the engagement of NM II are both essential to substrate deformation-directed keratinocyte migration.}, } @article {pmid29892951, year = {2018}, author = {Gao, Q and Xu, S and Zhu, X and Wang, L and Yang, Z and Zhao, X}, title = {Genome-wide identification and characterization of the RIO atypical kinase family in plants.}, journal = {Genes & genomics}, volume = {40}, number = {6}, pages = {669-683}, pmid = {29892951}, issn = {2092-9293}, support = {31601385//National Natural Science Foundation of China/International ; 2016ZX08012-002//National Science and Technology Major Project/International ; 2014AA10A601-5//National High-tech R&D Program/International ; BK20160429//Natural Science Foundation of Jiangsu Province/International ; 16KJB210001//Natural Science Research Project in Universities of Jiangsu Province/International ; PPZY2015A018//Top-notch Academic Programs Project of Jiangsu Higher Education Institutions/International ; }, mesh = {Amino Acid Sequence/genetics ; Arabidopsis/genetics ; Gene Expression Regulation, Plant/genetics ; Genes, Plant/genetics ; Multigene Family ; Oryza/genetics ; Phylogeny ; Plant Proteins/genetics ; Plants/genetics ; Protein Serine-Threonine Kinases/*genetics/metabolism ; Sequence Alignment/methods ; Transcriptome/genetics ; Viridiplantae/*genetics ; Zea mays/genetics ; }, abstract = {Members of the right open reading frame (RIO) atypical kinase family are present in all three domains of life. In eukaryotes, three subfamilies have been identified: RIO1, RIO2, and RIO3. Studies have shown that the yeast and human RIO1 and RIO2 kinases are essential for the biogenesis of small ribosomal subunits. Thus far, RIO3 has been found only in multicellular eukaryotes. In this study, we systematically identified members of the RIO gene family in 37 species representing the major evolutionary lineages in Viridiplantae. A total of 84 RIO genes were identified; among them, 41 were classified as RIO1 and 43 as RIO2. However, no RIO3 gene was found in any of the species examined. Phylogenetic trees constructed for plant RIO1 and RIO2 proteins were generally congruent with the species phylogeny. Subcellular localization analyses showed that the plant RIO proteins were localized mainly in the nucleus and/or cytoplasm. Expression profile analysis of rice, maize, and Arabidopsis RIO genes in different tissues revealed similar expression patterns between RIO1 and RIO2 genes, and their expression levels were high in certain tissues. In addition, the expressions of plant RIO genes were regulated by two drugs: mycophenolic acid and actinomycin D. Function prediction using genome-wide coexpression analysis revealed that most plant RIO genes may be involved in ribosome biogenesis. Our results will be useful for the evolutionary analysis of the ancient RIO kinase family and provide a basis for further functional characterization of RIO genes in plants.}, } @article {pmid29891718, year = {2018}, author = {Smith, CCR and Tittes, S and Mendieta, JP and Collier-Zans, E and Rowe, HC and Rieseberg, LH and Kane, NC}, title = {Genetics of alternative splicing evolution during sunflower domestication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6768-6773}, pmid = {29891718}, issn = {1091-6490}, mesh = {*Alternative Splicing ; Domestication ; *Evolution, Molecular ; Helianthus/*genetics ; Plant Breeding ; Plant Proteins/genetics/metabolism ; Protein Isoforms/genetics/metabolism ; Quantitative Trait Loci ; RNA, Plant/*genetics ; Spliceosomes ; Transcriptome ; }, abstract = {Alternative splicing enables organisms to produce the diversity of proteins necessary for multicellular life by using relatively few protein-coding genes. Although differences in splicing have been identified among divergent taxa, the shorter-term evolution of splicing is understudied. The origins of novel splice forms, and the contributions of alternative splicing to major evolutionary transitions, are largely unknown. This study used transcriptomes of wild and domesticated sunflowers to examine splice differentiation and regulation during domestication. We identified substantial splicing divergence between wild and domesticated sunflowers, mainly in the form of intron retention. Transcripts with divergent splicing were enriched for seed-development functions, suggesting that artificial selection impacted splicing patterns. Mapping of quantitative trait loci (QTLs) associated with 144 differential splicing cases revealed primarily trans-acting variation affecting splicing patterns. A large proportion of identified QTLs contain known spliceosome proteins and are associated with splicing variation in multiple genes. Examining a broader set of wild and domesticated sunflower genotypes revealed that most differential splicing patterns in domesticated sunflowers likely arose from standing variation in wild Helianthus annuus and gained frequency during the domestication process. However, several domesticate-associated splicing patterns appear to be introgressed from other Helianthus species. These results suggest that sunflower domestication involved selection on pleiotropic regulatory alleles. More generally, our findings indicate that substantial differences in isoform abundances arose rapidly during a recent evolutionary transition and appear to contribute to adaptation and population divergence.}, } @article {pmid29889237, year = {2018}, author = {Leys, SP and Kahn, AS}, title = {Oxygen and the Energetic Requirements of the First Multicellular Animals.}, journal = {Integrative and comparative biology}, volume = {58}, number = {4}, pages = {666-676}, doi = {10.1093/icb/icy051}, pmid = {29889237}, issn = {1557-7023}, mesh = {Animals ; *Biological Evolution ; Ctenophora/*physiology ; *Ecosystem ; *Life History Traits ; Porifera/*physiology ; }, abstract = {The appearance of multicellular animals during the Neoproterozoic Era is thought to have coincided with oxygenation of the oceans; however, we know little about the physiological needs of early animals or about the environment they lived in. Approaches using biomarkers, fossils, and phylogenomics have provided some hints of the types of animals that may have been present during the Neoproterozoic, but extant animals are our best modern links to the theoretical ancestors of animals. Neoproterozoic oceans were low energy habitats, with low oxygen concentrations and sparse food availability for the first animals. We examined tolerance of extant ctenophores and sponges-as representatives of extant lineages of the earliest known metazoan groups-to feeding and oxygen use. A review of respiration rates in species across several phyla suggests that suspension feeders in general have a wide range of metabolic rates, but sponges have some of the highest of invertebrates and ctenophores some of the lowest. Our own studies on the metabolism of two groups of deep water sponges show that sponges have different approaches to deal with the cost of filtration and low food availability. We also confirmed that deep water sponges tolerate periods of hypoxia, but at the cost of filtration, indicating that normal feeding is energetically expensive. Predictions of oxygen levels in the Neoproterozoic suggest the last common ancestor of multicellular animals was unlikely to have filtered like modern sponges. Getting enough food at low oxygen would have been a more important driver of the evolution of early body plans.}, } @article {pmid29880641, year = {2018}, author = {Miller, PW and Pokutta, S and Mitchell, JM and Chodaparambil, JV and Clarke, DN and Nelson, WJ and Weis, WI and Nichols, SA}, title = {Analysis of a vinculin homolog in a sponge (phylum Porifera) reveals that vertebrate-like cell adhesions emerged early in animal evolution.}, journal = {The Journal of biological chemistry}, volume = {293}, number = {30}, pages = {11674-11686}, pmid = {29880641}, issn = {1083-351X}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; R01 GM056169/GM/NIGMS NIH HHS/United States ; R01 GM114462/GM/NIGMS NIH HHS/United States ; R35 GM118064/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/analysis/metabolism ; Animals ; Cell Adhesion ; Focal Adhesions/metabolism ; Models, Molecular ; Porifera/*cytology/metabolism/ultrastructure ; Protein Binding ; Protein Conformation ; Pseudopodia/metabolism/ultrastructure ; Talin/analysis/metabolism ; Vinculin/analysis/*metabolism ; }, abstract = {The evolution of cell-adhesion mechanisms in animals facilitated the assembly of organized multicellular tissues. Studies in traditional animal models have revealed two predominant adhesion structures, the adherens junction (AJ) and focal adhesions (FAs), which are involved in the attachment of neighboring cells to each other and to the secreted extracellular matrix (ECM), respectively. The AJ (containing cadherins and catenins) and FAs (comprising integrins, talin, and paxillin) differ in protein composition, but both junctions contain the actin-binding protein vinculin. The near ubiquity of these structures in animals suggests that AJ and FAs evolved early, possibly coincident with multicellularity. However, a challenge to this perspective is that previous studies of sponges-a divergent animal lineage-indicate that their tissues are organized primarily by an alternative, sponge-specific cell-adhesion mechanism called "aggregation factor." In this study, we examined the structure, biochemical properties, and tissue localization of a vinculin ortholog in the sponge Oscarella pearsei (Op). Our results indicate that Op vinculin localizes to both cell-cell and cell-ECM contacts and has biochemical and structural properties similar to those of vertebrate vinculin. We propose that Op vinculin played a role in cell adhesion and tissue organization in the last common ancestor of sponges and other animals. These findings provide compelling evidence that sponge tissues are indeed organized like epithelia in other animals and support the notion that AJ- and FA-like structures extend to the earliest periods of animal evolution.}, } @article {pmid29875290, year = {2018}, author = {Ye, AY and Dou, Y and Yang, X and Wang, S and Huang, AY and Wei, L}, title = {A model for postzygotic mosaicisms quantifies the allele fraction drift, mutation rate, and contribution to de novo mutations.}, journal = {Genome research}, volume = {28}, number = {7}, pages = {943-951}, pmid = {29875290}, issn = {1549-5469}, mesh = {Alleles ; Child ; Female ; Genome, Human/genetics ; Humans ; Male ; Mosaicism ; Mutation/*genetics ; Mutation Rate ; Pedigree ; Polymorphism, Single Nucleotide/*genetics ; }, abstract = {The allele fraction (AF) distribution, occurrence rate, and evolutionary contribution of postzygotic single-nucleotide mosaicisms (pSNMs) remain largely unknown. In this study, we developed a mathematical model to describe the accumulation and AF drift of pSNMs during the development of multicellular organisms. By applying the model, we quantitatively analyzed two large-scale data sets of pSNMs identified from human genomes. We found that the postzygotic mutation rate per cell division during early embryogenesis, especially during the first cell division, was higher than the average mutation rate in either male or female gametes. We estimated that the stochastic cell death rate per cell cleavage during human embryogenesis was ∼5%, and parental pSNMs occurring during the first three cell divisions contributed to ∼10% of the de novo mutations observed in children. We further demonstrated that the genomic profiles of pSNMs could be used to measure the divergence distance between tissues. Our results highlight the importance of pSNMs in estimating recurrence risk and clarified the quantitative relationship between postzygotic and de novo mutations.}, } @article {pmid29866913, year = {2018}, author = {Grüter, C and Jongepier, E and Foitzik, S}, title = {Insect societies fight back: the evolution of defensive traits against social parasites.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866913}, issn = {1471-2970}, mesh = {Aggression ; Animals ; *Biological Evolution ; *Host-Parasite Interactions ; Insecta/*parasitology/*physiology ; Reproduction ; Social Behavior ; }, abstract = {Insect societies face many social parasites that exploit their altruistic behaviours or their resources. Due to the fitness costs these social parasites incur, hosts have evolved various behavioural, chemical, architectural and morphological defence traits. Similar to bacteria infecting multicellular hosts, social parasites have to successfully go through several steps to exploit their hosts. Here, we review how social insects try to interrupt this sequence of events. They can avoid parasite contact by choosing to nest in parasite-free locales or evade attacks by adapting their colony structure. Once social parasites attack, hosts attempt to detect them, which can be facilitated by adjustments in colony odour. If social parasites enter the nest, hosts can either aggressively defend their colony or take their young and flee. Nest structures are often shaped to prevent social parasite invasion or to safeguard host resources. Finally, if social parasites successfully establish themselves in host nests, hosts can rebel by killing the parasite brood or by reproducing in the parasites' presence. Hosts of social parasites can therefore develop multiple traits, leading to the evolution of complex defence portfolios of co-dependent traits. Social parasites can respond to these multi-level defences with counter-adaptations, potentially leading to geographical mosaics of coevolution.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29860723, year = {2018}, author = {Mustafin, RN and Khusnutdinova, EK}, title = {[Epigenetic hypothesis of the role of peptides in aging.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {31}, number = {1}, pages = {10-20}, pmid = {29860723}, issn = {1561-9125}, mesh = {Aging/*genetics ; *Epigenesis, Genetic ; Humans ; Peptides/*genetics ; RNA, Long Noncoding ; }, abstract = {In regulation of gene expression in the ontogenesis of multicellular eukaryotes, in addition to transcription factors, an important role is played by epigenetic factors that control the release of genetic information in each cell division. Many binding sites for the transcription factors were derived from transposons sequences. Mobile elements are also important sources of non-coding RNA. Due to this, transposons have an indirect effect on gene expression and genome methylation. In evolution, transposons serve as important sources for the origin of new protein and proteins domains. A number of studies have identified that long non-coding RNAs and microRNAs can be translated into functional peptides. At the same time, transposons remain active in the hypothalamus of adult humans, which is consistent with the transcription of non-coding RNAs in these structures, which may be key in aging.}, } @article {pmid29856957, year = {2018}, author = {Sebé-Pedrós, A and Saudemont, B and Chomsky, E and Plessier, F and Mailhé, MP and Renno, J and Loe-Mie, Y and Lifshitz, A and Mukamel, Z and Schmutz, S and Novault, S and Steinmetz, PRH and Spitz, F and Tanay, A and Marlow, H}, title = {Cnidarian Cell Type Diversity and Regulation Revealed by Whole-Organism Single-Cell RNA-Seq.}, journal = {Cell}, volume = {173}, number = {6}, pages = {1520-1534.e20}, doi = {10.1016/j.cell.2018.05.019}, pmid = {29856957}, issn = {1097-4172}, support = {724824/ERC_/European Research Council/International ; }, mesh = {Actins/chemistry ; Amino Acid Motifs ; Animals ; Chromatin/metabolism ; Cluster Analysis ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Genome ; Genomics ; Neurons/*physiology ; Phylogeny ; *RNA ; Sea Anemones/genetics/*physiology ; Sequence Analysis, RNA ; Transcriptome ; Tubulin/chemistry ; }, abstract = {The emergence and diversification of cell types is a leading factor in animal evolution. So far, systematic characterization of the gene regulatory programs associated with cell type specificity was limited to few cell types and few species. Here, we perform whole-organism single-cell transcriptomics to map adult and larval cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal with complex tissue-level body-plan organization. We uncover eight broad cell classes in Nematostella, including neurons, cnidocytes, and digestive cells. Each class comprises different subtypes defined by the expression of multiple specific markers. In particular, we characterize a surprisingly diverse repertoire of neurons, which comparative analysis suggests are the result of lineage-specific diversification. By integrating transcription factor expression, chromatin profiling, and sequence motif analysis, we identify the regulatory codes that underlie Nematostella cell-specific expression. Our study reveals cnidarian cell type complexity and provides insights into the evolution of animal cell-specific genomic regulation.}, } @article {pmid29851258, year = {2018}, author = {Schaefke, B and Sun, W and Li, YS and Fang, L and Chen, W}, title = {The evolution of posttranscriptional regulation.}, journal = {Wiley interdisciplinary reviews. RNA}, volume = {9}, number = {5}, pages = {e1485}, doi = {10.1002/wrna.1485}, pmid = {29851258}, issn = {1757-7012}, abstract = {"DNA makes RNA makes protein." After transcription, mRNAs undergo a series of intertwining processes to be finally translated into functional proteins. The "posttranscriptional" regulation (PTR) provides cells an extended option to fine-tune their proteomes. To meet the demands of complex organism development and the appropriate response to environmental stimuli, every step in these processes needs to be finely regulated. Moreover, changes in these regulatory processes are important driving forces underlying the evolution of phenotypic differences across different species. The major PTR mechanisms discussed in this review include the regulation of splicing, polyadenylation, decay, and translation. For alternative splicing and polyadenylation, we mainly discuss their evolutionary dynamics and the genetic changes underlying the regulatory differences in cis-elements versus trans-factors. For mRNA decay and translation, which, together with transcription, determine the cellular RNA or protein abundance, we focus our discussion on how their divergence coordinates with transcriptional changes to shape the evolution of gene expression. Then to highlight the importance of PTR in the evolution of higher complexity, we focus on their roles in two major phenomena during eukaryotic evolution: the evolution of multicellularity and the division of labor between different cell types and tissues; and the emergence of diverse, often highly specialized individual phenotypes, especially those concerning behavior in eusocial insects. This article is categorized under: RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution Translation > Translation Regulation RNA Processing > Splicing Regulation/Alternative Splicing.}, } @article {pmid29850801, year = {2018}, author = {Nishiyama, E and Ohshima, K}, title = {Cross-Kingdom Commonality of a Novel Insertion Signature of RTE-Related Short Retroposons.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1471-1483}, pmid = {29850801}, issn = {1759-6653}, mesh = {Animals ; DNA Transposable Elements/*genetics ; Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome, Plant/genetics ; Lizards/genetics ; Long Interspersed Nucleotide Elements/genetics ; Magnoliopsida/genetics ; Mammals/genetics ; Microsatellite Repeats/genetics ; Mutagenesis, Insertional/methods ; Phylogeny ; Retroelements/*genetics ; Reverse Transcription/genetics ; Short Interspersed Nucleotide Elements/genetics ; }, abstract = {In multicellular organisms, such as vertebrates and flowering plants, horizontal transfer (HT) of genetic information is thought to be a rare event. However, recent findings unveiled unexpectedly frequent HT of RTE-clade LINEs. To elucidate the molecular footprints of the genomic integration machinery of RTE-related retroposons, the sequence patterns surrounding the insertion sites of plant Au-like SINE families were analyzed in the genomes of a wide variety of flowering plants. A novel and remarkable finding regarding target site duplications (TSDs) for SINEs was they start with thymine approximately one helical pitch (ten nucleotides) downstream of a thymine stretch. This TSD pattern was found in RTE-clade LINEs, which share the 3'-end sequence of these SINEs, in the genome of leguminous plants. These results demonstrably show that Au-like SINEs were mobilized by the enzymatic machinery of RTE-clade LINEs. Further, we discovered the same TSD pattern in animal SINEs from lizard and mammals, in which the RTE-clade LINEs sharing the 3'-end sequence with these animal SINEs showed a distinct TSD pattern. Moreover, a significant correlation was observed between the first nucleotide of TSDs and microsatellite-like sequences found at the 3'-ends of SINEs and LINEs. We propose that RTE-encoded protein could preferentially bind to a DNA region that contains a thymine stretch to cleave a phosphodiester bond downstream of the stretch. Further, determination of cleavage sites and/or efficiency of primer sites for reverse transcription may depend on microsatellite-like repeats in the RNA template. Such a unique mechanism may have enabled retroposons to successfully expand in frontier genomes after HT.}, } @article {pmid29849168, year = {2018}, author = {Woo, C and An, C and Xu, S and Yi, SM and Yamamoto, N}, title = {Taxonomic diversity of fungi deposited from the atmosphere.}, journal = {The ISME journal}, volume = {12}, number = {8}, pages = {2051-2060}, pmid = {29849168}, issn = {1751-7370}, mesh = {*Air Microbiology ; Atmosphere ; Environmental Monitoring ; Fungi/*classification/genetics/*isolation & purification ; Phylogeny ; Spores, Fungal/classification/genetics/isolation & purification ; }, abstract = {Fungi release spores into the global atmosphere. The emitted spores are deposited to the surface of the Earth by sedimentation (dry deposition) and precipitation (wet deposition), and therefore contribute to the global cycling of substances. However, knowledge is scarce regarding the diversities of fungi deposited from the atmosphere. Here, an automatic dry and wet deposition sampler and high-throughput sequencing plus quantitative PCR were used to observe taxonomic diversities and flux densities of atmospheric fungal deposition. Taxon-specific fungal deposition velocities and aerodynamic diameters (da) were determined using a collocated cascade impactor for volumetric, particle-size-resolved air sampling. Large multicellular spore-producing dothideomycetes (da ≥ 10.0 μm) were predominant in dry deposition, with a mean velocity of 0.80 cm s[-1] for all fungal taxa combined. Higher taxonomic richness was observed in fungal assemblages in wet deposition than in dry deposition, suggesting the presence of fungal taxa that are deposited only in wet form. In wet deposition, agaricomycetes, including mushroom-forming fungi, and sordariomycetes, including plant pathogenic species, were enriched, indicating that such fungal spores serve as nuclei in clouds, and/or are discharged preferentially during precipitation. Moreover, this study confirmed that fungal assemblage memberships and structures were significantly different between dry and wet deposition (P-test, p < 0.001). Overall, these findings suggest taxon-specific involvement of fungi in precipitation, and provide important insights into potential links between environmental changes that can disturb regional microbial communities (e.g., deforestation) and changes in precipitation patterns that might be mediated by changes in microbial communities in the atmosphere.}, } @article {pmid29848439, year = {2018}, author = {Hamada, M and Schröder, K and Bathia, J and Kürn, U and Fraune, S and Khalturina, M and Khalturin, K and Shinzato, C and Satoh, N and Bosch, TC}, title = {Metabolic co-dependence drives the evolutionarily ancient Hydra-Chlorella symbiosis.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {29848439}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; Chlorella/drug effects/genetics/*metabolism ; Conserved Sequence ; Darkness ; Epithelial Cells/drug effects/metabolism ; Gene Expression Regulation ; Genome ; Hydra/drug effects/genetics/growth & development/*metabolism ; Molecular Sequence Annotation ; Nitrates/metabolism ; Nitrogen/metabolism ; Photosynthesis/genetics ; RNA, Ribosomal, 18S/genetics/metabolism ; Species Specificity ; Sugars/pharmacology ; *Symbiosis/drug effects/genetics ; }, abstract = {Many multicellular organisms rely on symbiotic associations for support of metabolic activity, protection, or energy. Understanding the mechanisms involved in controlling such interactions remains a major challenge. In an unbiased approach we identified key players that control the symbiosis between Hydra viridissima and its photosynthetic symbiont Chlorella sp. A99. We discovered significant up-regulation of Hydra genes encoding a phosphate transporter and glutamine synthetase suggesting regulated nutrition supply between host and symbionts. Interestingly, supplementing the medium with glutamine temporarily supports in vitro growth of the otherwise obligate symbiotic Chlorella, indicating loss of autonomy and dependence on the host. Genome sequencing of Chlorella sp. A99 revealed a large number of amino acid transporters and a degenerated nitrate assimilation pathway, presumably as consequence of the adaptation to the host environment. Our observations portray ancient symbiotic interactions as a codependent partnership in which exchange of nutrients appears to be the primary driving force.}, } @article {pmid29846592, year = {2018}, author = {Paps, J}, title = {What Makes an Animal? The Molecular Quest for the Origin of the Animal Kingdom.}, journal = {Integrative and comparative biology}, volume = {58}, number = {4}, pages = {654-665}, doi = {10.1093/icb/icy036}, pmid = {29846592}, issn = {1557-7023}, mesh = {Animals ; *Biological Evolution ; Evolution, Molecular ; Genome ; Genomics/*methods ; Invertebrates/classification/*genetics ; Molecular Biology/*methods ; *Phylogeny ; Vertebrates/classification/genetics ; }, abstract = {What makes an animal? To find the answer we need to integrate data from disciplines such as phylogenetics, paleontology, ecology, development, anatomy, and physiology, as well as molecular biology and genomics. Knowledge of which groups branched before and after the origin of animals is essential. Recent advances in molecular phylogenetics, together with the discovery of new eukaryotic lineages, have drawn a new picture of the ancestry of animals. The nature of the early diverging animal lineages and the timing of the transition are in a state of flux. Various factors have been linked to this striking transition to multicellularity, including changes in environmental conditions and the ecological interactions between unicellular eukaryotes. The current wealth of genomic data has also shed new light on this question. The analysis of the genome of various close relatives of animals has revealed the importance that recycling of ancient genes into metazoan biological functions played into animal origins. A recent study reconstructing the genome of the last common ancestor of extant animals has unveiled an unprecedented emergence of new genes, highlighting the role of genomic novelty in the origin of metazoans.}, } @article {pmid29844338, year = {2018}, author = {Pinhal, D and Bovolenta, LA and Moxon, S and Oliveira, AC and Nachtigall, PG and Acencio, ML and Patton, JG and Hilsdorf, AWS and Lemke, N and Martins, C}, title = {Genome-wide microRNA screening in Nile tilapia reveals pervasive isomiRs' transcription, sex-biased arm switching and increasing complexity of expression throughout development.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {8248}, pmid = {29844338}, issn = {2045-2322}, mesh = {Animals ; Cichlids/*genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genetic Testing ; Genome-Wide Association Study ; Genomics/*methods ; Life Cycle Stages ; Male ; MicroRNAs/*genetics ; Protein Isoforms/*genetics ; Sequence Analysis, RNA ; Sex Characteristics ; Transcription, Genetic ; }, abstract = {MicroRNAs (miRNAs) are key regulators of gene expression in multicellular organisms. The elucidation of miRNA function and evolution depends on the identification and characterization of miRNA repertoire of strategic organisms, as the fast-evolving cichlid fishes. Using RNA-seq and comparative genomics we carried out an in-depth report of miRNAs in Nile tilapia (Oreochromis niloticus), an emergent model organism to investigate evo-devo mechanisms. Five hundred known miRNAs and almost one hundred putative novel vertebrate miRNAs have been identified, many of which seem to be teleost-specific, cichlid-specific or tilapia-specific. Abundant miRNA isoforms (isomiRs) were identified with modifications in both 5p and 3p miRNA transcripts. Changes in arm usage (arm switching) of nine miRNAs were detected in early development, adult stage and even between male and female samples. We found an increasing complexity of miRNA expression during ontogenetic development, revealing a remarkable synchronism between the rate of new miRNAs recruitment and morphological changes. Overall, our results enlarge vertebrate miRNA collection and reveal a notable differential ratio of miRNA arms and isoforms influenced by sex and developmental life stage, providing a better picture of the evolutionary and spatiotemporal dynamics of miRNAs.}, } @article {pmid29807994, year = {2018}, author = {Cooper, GA and West, SA}, title = {Division of labour and the evolution of extreme specialization.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1161-1167}, doi = {10.1038/s41559-018-0564-9}, pmid = {29807994}, issn = {2397-334X}, mesh = {Animals ; *Biological Evolution ; *Cooperative Behavior ; Models, Biological ; *Selection, Genetic ; Social Behavior ; }, abstract = {Division of labour is a common feature of social groups, from biofilms to complex animal societies. However, we lack a theoretical framework that can explain why division of labour has evolved on certain branches of the tree of life but not others. Here, we model the division of labour over a cooperative behaviour, considering both when it should evolve and the extent to which the different types should become specialized. We found that: (1) division of labour is usually-but not always-favoured by high efficiency benefits to specialization and low within-group conflict; and (2) natural selection favours extreme specialization, where some individuals are completely dependent on the helping behaviour of others. We make a number of predictions, several of which are supported by the existing empirical data, from microbes and animals, while others suggest novel directions for empirical work. More generally, we show how division of labour can lead to mutual dependence between different individuals and hence drive major evolutionary transitions, such as those to multicellularity and eusociality.}, } @article {pmid29802408, year = {2018}, author = {Reeves, MQ and Kandyba, E and Harris, S and Del Rosario, R and Balmain, A}, title = {Multicolour lineage tracing reveals clonal dynamics of squamous carcinoma evolution from initiation to metastasis.}, journal = {Nature cell biology}, volume = {20}, number = {6}, pages = {699-709}, pmid = {29802408}, issn = {1476-4679}, support = {U01 CA176287/CA/NCI NIH HHS/United States ; U01 CA217864/CA/NCI NIH HHS/United States ; R35 CA210018/CA/NCI NIH HHS/United States ; F31 CA206459/CA/NCI NIH HHS/United States ; T32 GM008568/GM/NIGMS NIH HHS/United States ; R01 CA184510/CA/NCI NIH HHS/United States ; }, mesh = {9,10-Dimethyl-1,2-benzanthracene ; Animals ; Carcinoma, Squamous Cell/chemically induced/*genetics/metabolism/secondary ; *Cell Lineage ; Cell Movement/*genetics ; Cell Proliferation/genetics ; Cell Transformation, Neoplastic/chemically induced/*genetics/metabolism/pathology ; *Clonal Evolution ; Epithelial Cells/metabolism/*pathology ; Female ; Gene Expression Regulation, Neoplastic ; Genes, ras ; Genetic Predisposition to Disease ; Male ; Mice, Transgenic ; Mutation ; Neoplasms, Experimental/chemically induced/*genetics/metabolism/pathology ; Phenotype ; Skin Neoplasms/chemically induced/*genetics/metabolism/pathology ; Tetradecanoylphorbol Acetate ; Time Factors ; Tumor Burden/genetics ; }, abstract = {Tumour cells are subjected to evolutionary selection pressures during progression from initiation to metastasis. We analysed the clonal evolution of squamous skin carcinomas induced by DMBA/TPA treatment using the K5CreER-Confetti mouse and stage-specific lineage tracing. We show that benign tumours are polyclonal, but only one population contains the Hras driver mutation. Thus, benign papillomas are monoclonal in origin but recruit neighbouring epithelial cells during growth. Papillomas that never progress to malignancy retain several distinct clones, whereas progression to carcinoma is associated with a clonal sweep. Newly generated clones within carcinomas demonstrate intratumoural invasion and clonal intermixing, often giving rise to metastases containing two or more distinct clones derived from the matched primary tumour. These data demonstrate that late-stage tumour progression and dissemination are governed by evolutionary selection pressures that operate at a multicellular level and, therefore, differ from the clonal events that drive initiation and the benign-malignant transition.}, } @article {pmid29797026, year = {2018}, author = {Hauser, CJ and Otterbein, LE}, title = {Danger signals from mitochondrial DAMPS in trauma and post-injury sepsis.}, journal = {European journal of trauma and emergency surgery : official publication of the European Trauma Society}, volume = {44}, number = {3}, pages = {317-324}, pmid = {29797026}, issn = {1863-9941}, support = {W81XWH-16-1-0464//U.S. Department of Defense/ ; }, mesh = {Alarmins/*immunology ; Animals ; Humans ; Immunity, Innate ; Inflammation/*immunology ; Mitochondria/*immunology ; Signal Transduction/immunology ; Wounds and Injuries/*immunology ; }, abstract = {In all multicellular organisms, immediate host responses to both sterile and infective threat are initiated by very primitive systems now grouped together under the general term 'danger responses'. Danger signals are generated when primitive 'pattern recognition receptors' (PRR) encounter activating 'alarmins'. These molecular species may be of pathogenic infective origin (pathogen-associated molecular patterns) or of sterile endogenous origin (danger-associated molecular patterns). There are many sterile and infective alarmins and there is considerable overlap in their ability to activate PRR, but in all cases the end result is inflammation. It is the overlap between sterile and infective signals acting via a relatively limited number of PRR that generally underlies the great clinical similarity we see between sterile and infective systemic inflammatory responses. Mitochondria (MT) are evolutionarily derived from bacteria, and thus they sit at the crossroads between sterile and infective danger signal pathways. Many of the molecular species in mitochondria are alarmins, and so the release of MT from injured cells results in a wide variety of inflammatory events. This paper discusses the known participation of MT in inflammation and reviews what is known about how the major.}, } @article {pmid29789717, year = {2018}, author = {Al Habyan, S and Kalos, C and Szymborski, J and McCaffrey, L}, title = {Multicellular detachment generates metastatic spheroids during intra-abdominal dissemination in epithelial ovarian cancer.}, journal = {Oncogene}, volume = {37}, number = {37}, pages = {5127-5135}, pmid = {29789717}, issn = {1476-5594}, mesh = {Abdomen/*pathology ; Anoikis/physiology ; Ascites/pathology ; Carcinoma, Ovarian Epithelial/*pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm/physiology ; Female ; Humans ; Neoplasm Recurrence, Local/pathology ; Ovarian Neoplasms/*pathology ; Spheroids, Cellular/*pathology ; }, abstract = {Ovarian cancer is the most lethal gynecological cancer, where survival rates have had modest improvement over the last 30 years. Metastasis of cancer cells is a major clinical problem, and patient mortality occurs when ovarian cancer cells spread beyond the confinement of ovaries. Disseminated ovarian cancer cells typically spread within the abdomen, where ascites accumulation aids in their transit. Metastatic ascites contain multicellular spheroids, which promote chemo-resistance and recurrence. However, little is known about the origin and mechanisms through which spheroids arise. Using live-imaging of 3D culture models and animal models, we report that epithelial ovarian cancer (EOC) cells, the most common type of ovarian cancer, can spontaneously detach as either single cells or clusters. We report that clusters are more resistant to anoikis and have a potent survival advantage over single cells. Using in vivo lineage tracing, we found that multicellular spheroids arise preferentially from collective detachment, rather than aggregation in the abdomen. Finally, we report that multicellular spheroids from collective detachment are capable of seeding intra-abdominal metastases that retain intra-tumoral heterogeneity from the primary tumor.}, } @article {pmid29788279, year = {2018}, author = {Tarver, JE and Taylor, RS and Puttick, MN and Lloyd, GT and Pett, W and Fromm, B and Schirrmeister, BE and Pisani, D and Peterson, KJ and Donoghue, PCJ}, title = {Well-Annotated microRNAomes Do Not Evidence Pervasive miRNA Loss.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1457-1470}, pmid = {29788279}, issn = {1759-6653}, support = {BB/N000919/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Conserved Sequence/genetics ; Evolution, Molecular ; MicroRNAs/*genetics ; Molecular Sequence Annotation/methods ; Phenotype ; Phylogeny ; }, abstract = {microRNAs are conserved noncoding regulatory factors implicated in diverse physiological and developmental processes in multicellular organisms, as causal macroevolutionary agents and for phylogeny inference. However, the conservation and phylogenetic utility of microRNAs has been questioned on evidence of pervasive loss. Here, we show that apparent widespread losses are, largely, an artefact of poorly sampled and annotated microRNAomes. Using a curated data set of animal microRNAomes, we reject the view that miRNA families are never lost, but they are rarely lost (92% are never lost). A small number of families account for a majority of losses (1.7% of families account for >45% losses), and losses are associated with lineages exhibiting phenotypic simplification. Phylogenetic analyses based on the presence/absence of microRNA families among animal lineages, and based on microRNA sequences among Osteichthyes, demonstrate the power of these small data sets in phylogenetic inference. Perceptions of widespread evolutionary loss of microRNA families are due to the uncritical use of public archives corrupted by spurious microRNA annotations, and failure to discriminate false absences that occur because of incomplete microRNAome annotation.}, } @article {pmid29775683, year = {2018}, author = {Dechristé, G and Fehrenbach, J and Griseti, E and Lobjois, V and Poignard, C}, title = {Viscoelastic modeling of the fusion of multicellular tumor spheroids in growth phase.}, journal = {Journal of theoretical biology}, volume = {454}, number = {}, pages = {102-109}, doi = {10.1016/j.jtbi.2018.05.005}, pmid = {29775683}, issn = {1095-8541}, mesh = {Cell Fusion ; *Cell Proliferation ; HCT116 Cells ; Humans ; Kinetics ; *Models, Theoretical ; Neoplasms/*pathology/physiopathology ; Rheology ; Spheroids, Cellular/*pathology/*physiology ; Surface Tension ; Viscoelastic Substances/metabolism ; }, abstract = {BACKGROUND: Since several decades, the experiments have highlighted the analogy of fusing cell aggregates with liquid droplets. The physical macroscopic models have been derived under incompressible assumptions. The aim of this paper is to provide a 3D model of growing spheroids, which is more relevant regarding embryo cell aggregates or tumor cell spheroids.

METHODS: We extend the past approach to a compressible 3D framework in order to account for the tumor spheroid growth. We exhibit the crucial importance of the effective surface tension, and of the inner pressure of the spheroid to describe precisely the fusion. The experimental data were obtained on spheroids of colon carcinoma human cells (HCT116 cell line). After 3 or 6 days of culture, two identical spheroids were transferred in one well and their fusion was monitored by live videomicroscopy acquisition each 2 h during 72 h. From these images the neck radius and the diameter of the assembly of the fusing spheroids are extracted.

RESULTS: The numerical model is fitted with the experiments. It is worth noting that the time evolution of both neck radius and spheroid diameter are quantitatively obtained. The interesting feature lies in the fact that such measurements characterise the macroscopic rheological properties of the tumor spheroids.

CONCLUSIONS: The experimental determination of the kinetics of neck radius and overall diameter during spheroids fusion characterises the rheological properties of the spheroids. The consistency of the model is shown by fitting the model with two different experiments, enhancing the importance of both surface tension and cell proliferation.

GENERAL SIGNIFICANCE: The paper sheds new light on the macroscopic rheological properties of tumor spheroids. It emphasizes the role of the surface tension and the inner pressure in the fusion of growing spheroid. Under geometrical assumptions, the model reduces to a 2-parameter differential equation fit with experimental measurements. The 3-D partial differential system makes it possible to study the fusion of spheroids in non-symmetrical or more general frameworks.}, } @article {pmid29755113, year = {2018}, author = {Jézéquel, P and Campone, M}, title = {Comment on "How the evolution of multicellularity set the stage for cancer".}, journal = {British journal of cancer}, volume = {119}, number = {1}, pages = {133-134}, pmid = {29755113}, issn = {1532-1827}, mesh = {Humans ; *Neoplasms ; }, } @article {pmid29752387, year = {2018}, author = {Parra-Acero, H and Ros-Rocher, N and Perez-Posada, A and Kożyczkowska, A and Sánchez-Pons, N and Nakata, A and Suga, H and Najle, SR and Ruiz-Trillo, I}, title = {Transfection of Capsaspora owczarzaki, a close unicellular relative of animals.}, journal = {Development (Cambridge, England)}, volume = {145}, number = {10}, pages = {}, pmid = {29752387}, issn = {1477-9129}, mesh = {Animals ; Biological Evolution ; DNA/*genetics ; Evolution, Molecular ; Gene Expression Regulation/genetics ; Genome, Protozoan/*genetics ; Mesomycetozoea/*genetics ; Plasmids/*genetics ; Transfection/*methods ; }, abstract = {How animals emerged from their unicellular ancestor remains a major evolutionary question. New genome data from the closest unicellular relatives of animals have provided important insights into the evolution of animal multicellularity. We know that the unicellular ancestor of animals had an unexpectedly complex genetic repertoire, including many genes that are key to animal development and multicellularity. Thus, assessing the function of these genes among unicellular relatives of animals is key to understanding how they were co-opted at the onset of the Metazoa. However, such analyses have been hampered by the lack of genetic tools. Progress has been made in choanoflagellates and teretosporeans, two of the three lineages closely related to animals, whereas no tools are yet available for functional analysis in the third lineage: the filastereans. Importantly, filastereans have a striking repertoire of genes involved in transcriptional regulation and other developmental processes. Here, we describe a reliable transfection method for the filasterean Capsaspora owczarzaki We also provide a set of constructs for visualising subcellular structures in live cells. These tools convert Capsaspora into a unique experimentally tractable organism to use to investigate the origin and evolution of animal multicellularity.}, } @article {pmid29738987, year = {2018}, author = {Tasic, B}, title = {Single cell transcriptomics in neuroscience: cell classification and beyond.}, journal = {Current opinion in neurobiology}, volume = {50}, number = {}, pages = {242-249}, doi = {10.1016/j.conb.2018.04.021}, pmid = {29738987}, issn = {1873-6882}, mesh = {Animals ; Biological Evolution ; Humans ; Neurons/classification/*metabolism ; *Neurosciences ; Single-Cell Analysis/methods ; Transcriptome/*physiology ; }, abstract = {Biology has been facing a daunting problem since the cell was understood to be the building block of metazoans: how do we study multicellular systems, when a universal approach to characterize their building blocks and classify them does not exist? Metazoan diversity has not helped: there are many model and non-model organisms, developmental and adult stages, healthy and diseased states. Here, I review the application of single cell transcriptomics to cell classification in neuroscience and its corollaries: the differentially expressed genes discovered in this process are a treasure trove for understanding cell type function and enabling specific access to those types. The advancements and widespread adoption of single-cell transcriptomics are bound to transform our understanding of neural system development, function, pathology and evolution.}, } @article {pmid29735660, year = {2018}, author = {Elsner, D and Meusemann, K and Korb, J}, title = {Longevity and transposon defense, the case of termite reproductives.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5504-5509}, pmid = {29735660}, issn = {1091-6490}, mesh = {Animals ; *DNA Transposable Elements ; *Gene Expression Regulation ; High-Throughput Nucleotide Sequencing ; Isoptera/*genetics ; *Longevity ; RNA, Small Interfering/*genetics ; *Reproduction ; }, abstract = {Social insects are promising new models in aging research. Within single colonies, longevity differences of several magnitudes exist that can be found elsewhere only between different species. Reproducing queens (and, in termites, also kings) can live for several decades, whereas sterile workers often have a lifespan of a few weeks only. We studied aging in the wild in a highly social insect, the termite Macrotermes bellicosus, which has one of the most pronounced longevity differences between reproductives and workers. We show that gene-expression patterns differed little between young and old reproductives, implying negligible aging. By contrast, old major workers had many genes up-regulated that are related to transposable elements (TEs), which can cause aging. Strikingly, genes from the PIWI-interacting RNA (piRNA) pathway, which are generally known to silence TEs in the germline of multicellular animals, were down-regulated only in old major workers but not in reproductives. Continued up-regulation of the piRNA defense commonly found in the germline of animals can explain the long life of termite reproductives, implying somatic cooption of germline defense during social evolution. This presents a striking germline/soma analogy as envisioned by the superorganism concept: the reproductives and workers of a colony reflect the germline and soma of multicellular animals, respectively. Our results provide support for the disposable soma theory of aging.}, } @article {pmid29731304, year = {2018}, author = {Maclean, AE and Hertle, AP and Ligas, J and Bock, R and Balk, J and Meyer, EH}, title = {Absence of Complex I Is Associated with Diminished Respiratory Chain Function in European Mistletoe.}, journal = {Current biology : CB}, volume = {28}, number = {10}, pages = {1614-1619.e3}, doi = {10.1016/j.cub.2018.03.036}, pmid = {29731304}, issn = {1879-0445}, mesh = {Electron Transport/*physiology ; Electron Transport Complex I/*genetics/metabolism ; Mitochondria/*metabolism ; Oxidative Phosphorylation ; Viscum album/*genetics/metabolism ; }, abstract = {Parasitism is a life history strategy found across all domains of life whereby nutrition is obtained from a host. It is often associated with reductive evolution of the genome, including loss of genes from the organellar genomes [1, 2]. In some unicellular parasites, the mitochondrial genome (mitogenome) has been lost entirely, with far-reaching consequences for the physiology of the organism [3, 4]. Recently, mitogenome sequences of several species of the hemiparasitic plant mistletoe (Viscum sp.) have been reported [5, 6], revealing a striking loss of genes not seen in any other multicellular eukaryotes. In particular, the nad genes encoding subunits of respiratory complex I are all absent and other protein-coding genes are also lost or highly diverged in sequence, raising the question what remains of the respiratory complexes and mitochondrial functions. Here we show that oxidative phosphorylation (OXPHOS) in European mistletoe, Viscum album, is highly diminished. Complex I activity and protein subunits of complex I could not be detected. The levels of complex IV and ATP synthase were at least 5-fold lower than in the non-parasitic model plant Arabidopsis thaliana, whereas alternative dehydrogenases and oxidases were higher in abundance. Carbon flux analysis indicates that cytosolic reactions including glycolysis are greater contributors to ATP synthesis than the mitochondrial tricarboxylic acid (TCA) cycle. Our results describe the extreme adjustments in mitochondrial functions of the first reported multicellular eukaryote without complex I.}, } @article {pmid29730580, year = {2018}, author = {Vijay, K}, title = {Toll-like receptors in immunity and inflammatory diseases: Past, present, and future.}, journal = {International immunopharmacology}, volume = {59}, number = {}, pages = {391-412}, pmid = {29730580}, issn = {1878-1705}, mesh = {Animals ; Genetic Predisposition to Disease ; Humans ; *Immunity, Innate ; Infections/genetics/immunology ; Inflammation/genetics/*immunology ; Polymorphism, Genetic ; Toll-Like Receptors/genetics/*immunology ; }, abstract = {The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.}, } @article {pmid29728614, year = {2018}, author = {Pehr, K and Love, GD and Kuznetsov, A and Podkovyrov, V and Junium, CK and Shumlyanskyy, L and Sokur, T and Bekker, A}, title = {Ediacara biota flourished in oligotrophic and bacterially dominated marine environments across Baltica.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {1807}, pmid = {29728614}, issn = {2041-1723}, mesh = {Asia ; Bacteria/growth & development ; Biological Evolution ; Biomarkers/analysis ; *Biota ; Ecosystem ; Europe ; *Fossils ; Geography ; Geologic Sediments/*chemistry/*microbiology ; Hydrocarbons/analysis ; Lipids/analysis ; Prochlorococcus/growth & development ; Synechococcus/growth & development ; }, abstract = {Middle-to-late Ediacaran (575-541 Ma) marine sedimentary rocks record the first appearance of macroscopic, multicellular body fossils, yet little is known about the environments and food sources that sustained this enigmatic fauna. Here, we perform a lipid biomarker and stable isotope (δ[15]Ntotal and δ[13]CTOC) investigation of exceptionally immature late Ediacaran strata (<560 Ma) from multiple locations across Baltica. Our results show that the biomarker assemblages encompass an exceptionally wide range of hopane/sterane ratios (1.6-119), which is a broad measure of bacterial/eukaryotic source organism inputs. These include some unusually high hopane/sterane ratios (22-119), particularly during the peak in diversity and abundance of the Ediacara biota. A high contribution of bacteria to the overall low productivity may have bolstered a microbial loop, locally sustaining dissolved organic matter as an important organic nutrient. These oligotrophic, shallow-marine conditions extended over hundreds of kilometers across Baltica and persisted for more than 10 million years.}, } @article {pmid29718307, year = {2018}, author = {Tarhan, LG and Droser, ML and Cole, DB and Gehling, JG}, title = {Ecological Expansion and Extinction in the Late Ediacaran: Weighing the Evidence for Environmental and Biotic Drivers.}, journal = {Integrative and comparative biology}, volume = {58}, number = {4}, pages = {688-702}, doi = {10.1093/icb/icy020}, pmid = {29718307}, issn = {1557-7023}, mesh = {Animals ; *Biological Evolution ; Biota ; Fossils/*anatomy & histology ; Invertebrates/*anatomy & histology/*physiology ; }, abstract = {The Ediacara Biota, Earth's earliest communities of complex, macroscopic, multicellular organisms, appeared during the late Ediacaran Period, just prior to the Cambrian Explosion. Ediacara fossil assemblages consist of exceptionally preserved soft-bodied forms of enigmatic morphology and affinity which nonetheless represent a critical stepping-stone in the evolution of complex animal ecosystems. The Ediacara Biota has historically been divided into three successive Assemblages-the Avalon, the White Sea, and the Nama. Although the oldest (Avalon) Assemblage documents the initial appearance of several groups of Ediacara taxa, the two younger (White Sea and Nama) Assemblages record a particularly striking suite of ecological innovations, including the appearance of diverse Ediacara body plans-in tandem with the rise of bilaterian animals-as well as the emergence of novel ecological strategies such as movement, sexual reproduction, biomineralization, and the development of dense, heterogeneous benthic communities. Many of these ecological innovations appear to be linked to adaptations to heterogeneous substrates and shallow and energetic marine settings. In spite of these innovations, the majority of Ediacara taxa disappear by the end of the Ediacaran, with interpretations for this disappearance historically ranging from the closing of preservational windows to environmentally or biotically mediated extinction. However, in spite of the unresolved affinity and eventual extinction of individual Ediacara taxa, these distinctive ecological strategies persist across the Ediacaran-Cambrian boundary and are characteristic of younger animal-dominated communities of the Phanerozoic. The late Ediacaran emergence of these strategies may, therefore, have facilitated subsequent radiations of the Cambrian. In this light, the Ediacaran and Cambrian Periods, although traditionally envisioned as separate worlds, are likely to have been part of an ecological and evolutionary continuum.}, } @article {pmid29717623, year = {2018}, author = {Steinbach, SK and Wang, T and Carruthers, MH and Li, A and Besla, R and Johnston, AP and Robbins, CS and Husain, M}, title = {Aortic Sca-1[+] Progenitor Cells Arise from the Somitic Mesoderm Lineage in Mice.}, journal = {Stem cells and development}, volume = {27}, number = {13}, pages = {888-897}, doi = {10.1089/scd.2018.0038}, pmid = {29717623}, issn = {1557-8534}, support = {MOP136850//CIHR/Canada ; MOP14648//CIHR/Canada ; }, mesh = {Animals ; Antigens, Ly/*metabolism ; Aorta/*metabolism ; Cell Differentiation/physiology ; Cell Lineage/*physiology ; Membrane Proteins/*metabolism ; Mesoderm/*metabolism ; Mice ; Myocytes, Smooth Muscle/metabolism ; Myogenic Regulatory Factor 5/metabolism ; SOXB1 Transcription Factors/metabolism ; Somites/*metabolism ; Stem Cells/*metabolism ; Transforming Growth Factor beta3/metabolism ; }, abstract = {Sca-1[+] progenitor cells in the adult mouse aorta are known to generate vascular smooth muscle cells (VSMCs), but their embryological origins and temporal abundance are not known. Using tamoxifen-inducible Myf5-Cre[ER] mice, we demonstrate that Sca-1[+] adult aortic cells arise from the somitic mesoderm beginning at E8.5 and continue throughout somitogenesis. Myf5 lineage-derived Sca-1[+] cells greatly expand in situ, starting at 4 weeks of age, and become a major source of aortic Sca-1[+] cells by 6 weeks of age. Myf5-derived adult aortic cells are capable of forming multicellular sphere-like structures in vitro and express the pluripotency marker Sox2. Exposure to transforming growth factor-β3 induces these spheres to differentiate into calponin-expressing VSMCs. Pulse-chase experiments using tamoxifen-inducible Sox2-Cre[ERT2] mice at 8 weeks of age demonstrate that ∼35% of all adult aortic Sca-1[+] cells are derived from Sox2[+] cells. The present study demonstrates that aortic Sca-1[+] progenitor cells are derived from the somitic mesoderm formed at the earliest stages of somitogenesis and from Sox2-expressing progenitors in adult mice.}, } @article {pmid29709110, year = {2018}, author = {Simon, CS and Hadjantonakis, AK and Schröter, C}, title = {Making lineage decisions with biological noise: Lessons from the early mouse embryo.}, journal = {Wiley interdisciplinary reviews. Developmental biology}, volume = {7}, number = {4}, pages = {e319}, pmid = {29709110}, issn = {1759-7692}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 DK084391/DK/NIDDK NIH HHS/United States ; R01 HD094868/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Blastocyst/cytology/metabolism/*physiology ; Cell Differentiation/genetics/*physiology ; Cell Lineage/genetics/physiology ; Embryo, Mammalian/cytology/embryology/metabolism ; Gene Expression Regulation, Developmental ; Mice ; *Models, Biological ; }, abstract = {Understanding how individual cells make fate decisions that lead to the faithful formation and homeostatic maintenance of tissues is a fundamental goal of contemporary developmental and stem cell biology. Seemingly uniform populations of stem cells and multipotent progenitors display a surprising degree of heterogeneity, primarily originating from the inherent stochastic nature of molecular processes underlying gene expression. Despite this heterogeneity, lineage decisions result in tissues of a defined size and with consistent proportions of differentiated cell types. Using the early mouse embryo as a model we review recent developments that have allowed the quantification of molecular intercellular heterogeneity during cell differentiation. We first discuss the relationship between these heterogeneities and developmental cellular potential. We then review recent theoretical approaches that formalize the mechanisms underlying fate decisions in the inner cell mass of the blastocyst stage embryo. These models build on our extensive knowledge of the genetic control of fate decisions in this system and will become essential tools for a rigorous understanding of the connection between noisy molecular processes and reproducible outcomes at the multicellular level. We conclude by suggesting that cell-to-cell communication provides a mechanism to exploit and buffer intercellular variability in a self-organized process that culminates in the reproducible formation of the mature mammalian blastocyst stage embryo that is ready for implantation into the maternal uterus. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Gene Expression and Transcriptional Hierarchies > Quantitative Methods and Models.}, } @article {pmid29688518, year = {2018}, author = {Lee, J and Yang, EC and Graf, L and Yang, JH and Qiu, H and Zelzion, U and Chan, CX and Stephens, TG and Weber, APM and Boo, GH and Boo, SM and Kim, KM and Shin, Y and Jung, M and Lee, SJ and Yim, HS and Lee, JH and Bhattacharya, D and Yoon, HS}, title = {Analysis of the Draft Genome of the Red Seaweed Gracilariopsis chorda Provides Insights into Genome Size Evolution in Rhodophyta.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1869-1886}, doi = {10.1093/molbev/msy081}, pmid = {29688518}, issn = {1537-1719}, mesh = {*Biological Evolution ; DNA Methylation ; *DNA Transposable Elements ; Epigenesis, Genetic ; Gene Duplication ; Gene Expression Regulation ; *Genome Size ; Rhodophyta/*genetics ; }, abstract = {Red algae (Rhodophyta) underwent two phases of large-scale genome reduction during their early evolution. The red seaweeds did not attain genome sizes or gene inventories typical of other multicellular eukaryotes. We generated a high-quality 92.1 Mb draft genome assembly from the red seaweed Gracilariopsis chorda, including methylation and small (s)RNA data. We analyzed these and other Archaeplastida genomes to address three questions: 1) What is the role of repeats and transposable elements (TEs) in explaining Rhodophyta genome size variation, 2) what is the history of genome duplication and gene family expansion/reduction in these taxa, and 3) is there evidence for TE suppression in red algae? We find that the number of predicted genes in red algae is relatively small (4,803-13,125 genes), particularly when compared with land plants, with no evidence of polyploidization. Genome size variation is primarily explained by TE expansion with the red seaweeds having the largest genomes. Long terminal repeat elements and DNA repeats are the major contributors to genome size growth. About 8.3% of the G. chorda genome undergoes cytosine methylation among gene bodies, promoters, and TEs, and 71.5% of TEs contain methylated-DNA with 57% of these regions associated with sRNAs. These latter results suggest a role for TE-associated sRNAs in RNA-dependent DNA methylation to facilitate silencing. We postulate that the evolution of genome size in red algae is the result of the combined action of TE spread and the concomitant emergence of its epigenetic suppression, together with other important factors such as changes in population size.}, } @article {pmid29686411, year = {2018}, author = {Marín, I}, title = {Origin and evolution of fungal HECT ubiquitin ligases.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {6419}, pmid = {29686411}, issn = {2045-2322}, mesh = {Animals ; *Evolution, Molecular ; Genes, Fungal ; Genetic Variation ; Humans ; Saccharomyces cerevisiae/*enzymology ; Ubiquitin-Protein Ligases/genetics/*metabolism ; }, abstract = {Ubiquitin ligases (E3s) are basic components of the eukaryotic ubiquitination system. In this work, the emergence and diversification of fungal HECT ubiquitin ligases is described. Phylogenetic and structural data indicate that six HECT subfamilies (RSP5, TOM1, UFD4, HUL4, HUL4A and HUL5) existed in the common ancestor of all fungi. These six subfamilies have evolved very conservatively, with only occasional losses and duplications in particular fungal lineages. However, an early, drastic reduction in the number of HECT genes occurred in microsporidians, in parallel to the reduction of their genomes. A significant correlation between the total number of genes and the number of HECT-encoding genes present in fungi has been observed. However, transitions from unicellularity to multicellularity or vice versa apparently had no effect on the evolution of this family. Likely orthologs or co-orthologs of all fungal HECT genes have been detected in animals. Four genes are deduced to be present in the common ancestor of fungi, animals and plants. Protein-protein interactions detected in both the yeast Saccharomyces cerevisiae and humans suggest that some ancient functions of HECT proteins have been conserved since the animals/fungi split.}, } @article {pmid29685747, year = {2018}, author = {Miller, WB and Torday, JS}, title = {Four domains: The fundamental unicell and Post-Darwinian Cognition-Based Evolution.}, journal = {Progress in biophysics and molecular biology}, volume = {140}, number = {}, pages = {49-73}, doi = {10.1016/j.pbiomolbio.2018.04.006}, pmid = {29685747}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Cells/*cytology ; *Cognition ; Humans ; Signal Transduction ; }, abstract = {Contemporary research supports the viewpoint that self-referential cognition is the proper definition of life. From that initiating platform, a cohesive alternative evolutionary narrative distinct from standard Neodarwinism can be presented. Cognition-Based Evolution contends that biological variation is a product of a self-reinforcing information cycle that derives from self-referential attachment to biological information space-time with its attendant ambiguities. That information cycle is embodied through obligatory linkages among energy, biological information, and communication. Successive reiterations of the information cycle enact the informational architectures of the basic unicellular forms. From that base, inter-domain and cell-cell communications enable genetic and cellular variations through self-referential natural informational engineering and cellular niche construction. Holobionts are the exclusive endpoints of that self-referential cellular engineering as obligatory multicellular combinations of the essential Four Domains: Prokaryota, Archaea, Eukaryota and the Virome. Therefore, it is advocated that these Four Domains represent the perpetual object of the living circumstance rather than the visible macroorganic forms. In consequence, biology and its evolutionary development can be appraised as the continual defense of instantiated cellular self-reference. As the survival of cells is as dependent upon limitations and boundaries as upon any freedom of action, it is proposed that selection represents only one of many forms of cellular constraint that sustain self-referential integrity.}, } @article {pmid29675836, year = {2018}, author = {Nagy, LG and Kovács, GM and Krizsán, K}, title = {Complex multicellularity in fungi: evolutionary convergence, single origin, or both?.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1778-1794}, doi = {10.1111/brv.12418}, pmid = {29675836}, issn = {1469-185X}, support = {P2014/12//Hungarian Academy of Sciences/International ; ERC_HU Grant #118722//NRDI Office/International ; }, mesh = {*Biological Evolution ; Ecosystem ; Fungi/*cytology/*genetics ; Gene Expression Regulation, Fungal ; Genome, Fungal ; Genomics ; }, abstract = {Complex multicellularity represents the most advanced level of biological organization and it has evolved only a few times: in metazoans, green plants, brown and red algae and fungi. Compared to other lineages, the evolution of multicellularity in fungi follows different principles; both simple and complex multicellularity evolved via unique mechanisms not found in other lineages. Herein we review ecological, palaeontological, developmental and genomic aspects of complex multicellularity in fungi and discuss general principles of the evolution of complex multicellularity in light of its fungal manifestations. Fungi represent the only lineage in which complex multicellularity shows signatures of convergent evolution: it appears 8-11 times in distinct fungal lineages, which show a patchy phylogenetic distribution yet share some of the genetic mechanisms underlying complex multicellular development. To explain the patchy distribution of complex multicellularity across the fungal phylogeny we identify four key observations: the large number of apparently independent complex multicellular clades; the lack of documented phenotypic homology between these clades; the conservation of gene circuits regulating the onset of complex multicellular development; and the existence of clades in which the evolution of complex multicellularity is coupled with limited gene family diversification. We discuss how these patterns and known genetic aspects of fungal development can be reconciled with the genetic theory of convergent evolution to explain the pervasive occurrence of complex multicellularity across the fungal tree of life.}, } @article {pmid29675831, year = {2018}, author = {Kauko, A and Lehto, K}, title = {Eukaryote specific folds: Part of the whole.}, journal = {Proteins}, volume = {86}, number = {8}, pages = {868-881}, doi = {10.1002/prot.25517}, pmid = {29675831}, issn = {1097-0134}, mesh = {Archaea/genetics ; Bacteria/classification ; Biological Evolution ; Databases, Protein ; Eukaryota/*classification ; Eukaryotic Cells/classification ; Evolution, Molecular ; Genes, Bacterial ; Genes, Mitochondrial ; Mitochondria/genetics ; Phylogeny ; Proteins/genetics ; Symbiosis/*genetics ; }, abstract = {The origin of eukaryotes is one of the central transitions in the history of life; without eukaryotes there would be no complex multicellular life. The most accepted scenarios suggest the endosymbiosis of a mitochondrial ancestor with a complex archaeon, even though the details regarding the host and the triggering factors are still being discussed. Accordingly, phylogenetic analyses have demonstrated archaeal affiliations with key informational systems, while metabolic genes are often related to bacteria, mostly to the mitochondrial ancestor. Despite of this, there exists a large number of protein families and folds found only in eukaryotes. In this study, we have analyzed structural superfamilies and folds that probably appeared during eukaryogenesis. These folds typically represent relatively small binding domains of larger multidomain proteins. They are commonly involved in biological processes that are particularly complex in eukaryotes, such as signaling, trafficking/cytoskeleton, ubiquitination, transcription and RNA processing, but according to recent studies, these processes also have prokaryotic roots. Thus the folds originating from an eukaryotic stem seem to represent accessory parts that have contributed in the expansion of several prokaryotic processes to a new level of complexity. This might have taken place as a co-evolutionary process where increasing complexity and fold innovations have supported each other.}, } @article {pmid29663630, year = {2018}, author = {Albuquerque, TAF and Drummond do Val, L and Doherty, A and de Magalhães, JP}, title = {From humans to hydra: patterns of cancer across the tree of life.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1715-1734}, pmid = {29663630}, issn = {1469-185X}, support = {//Wellcome Trust/United Kingdom ; 104978/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Genetic Predisposition to Disease ; Humans ; *Hydra ; *Neoplasms ; Species Specificity ; }, abstract = {Cancer is a disease of multicellularity; it originates when cells become dysregulated due to mutations and grow out of control, invading other tissues and provoking discomfort, disability, and eventually death. Human life expectancy has greatly increased in the last two centuries, and consequently so has the incidence of cancer. However, how cancer patterns in humans compare to those of other species remains largely unknown. In this review, we search for clues about cancer and its evolutionary underpinnings across the tree of life. We discuss data from a wide range of species, drawing comparisons with humans when adequate, and interpret our findings from an evolutionary perspective. We conclude that certain cancers are uniquely common in humans, such as lung, prostate, and testicular cancer; while others are common across many species. Lymphomas appear in almost every animal analysed, including in young animals, which may be related to pathogens imposing selection on the immune system. Cancers unique to humans may be due to our modern environment or may be evolutionary accidents: random events in the evolution of our species. Finally, we find that cancer-resistant animals such as whales and mole-rats have evolved cellular mechanisms that help them avoid neoplasia, and we argue that there are multiple natural routes to cancer resistance.}, } @article {pmid29662839, year = {2018}, author = {Dhakshinamoorthy, R and Bitzhenner, M and Cosson, P and Soldati, T and Leippe, M}, title = {The Saposin-Like Protein AplD Displays Pore-Forming Activity and Participates in Defense Against Bacterial Infection During a Multicellular Stage of Dictyostelium discoideum.}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {73}, pmid = {29662839}, issn = {2235-2988}, mesh = {Animals ; Anti-Infective Agents/metabolism/pharmacology ; Bacillus megaterium/drug effects ; Bacterial Infections/*immunology ; Dictyostelium/genetics/*immunology/metabolism/*microbiology ; Gastropoda/immunology/metabolism/microbiology ; Gene Expression Profiling ; Host-Pathogen Interactions/*immunology ; *Immunity, Innate ; Ion Channels/metabolism/pharmacology ; Klebsiella pneumoniae/drug effects/pathogenicity ; Liposomes/metabolism ; Peptides/genetics/metabolism/pharmacology ; Protozoan Proteins/metabolism/pharmacology ; Recombinant Proteins ; Saposins/genetics/immunology/*metabolism/*pharmacology ; }, abstract = {Due to their archaic life style and microbivor behavior, amoebae may represent a source of antimicrobial peptides and proteins. The amoebic protozoon Dictyostelium discoideum has been a model organism in cell biology for decades and has recently also been used for research on host-pathogen interactions and the evolution of innate immunity. In the genome of D. discoideum, genes can be identified that potentially allow the synthesis of a variety of antimicrobial proteins. However, at the protein level only very few antimicrobial proteins have been characterized that may interact directly with bacteria and help in fighting infection of D. discoideum with potential pathogens. Here, we focus on a large group of gene products that structurally belong to the saposin-like protein (SAPLIP) family and which members we named provisionally Apls (amoebapore-like peptides) according to their similarity to a comprehensively studied antimicrobial and cytotoxic pore-forming protein of the protozoan parasite Entamoeba histolytica. We focused on AplD because it is the only Apl gene that is reported to be primarily transcribed further during the multicellular stages such as the mobile slug stage. Upon knock-out (KO) of the gene, aplD[-] slugs became highly vulnerable to virulent Klebsiella pneumoniae. AplD[-] slugs harbored bacterial clumps in their interior and were unable to slough off the pathogen in their slime sheath. Re-expression of AplD in aplD[-] slugs rescued the susceptibility toward K. pneumoniae. The purified recombinant protein rAplD formed pores in liposomes and was also capable of permeabilizing the membrane of live Bacillus megaterium. We propose that the multifarious Apl family of D. discoideum comprises antimicrobial effector polypeptides that are instrumental to interact with bacteria and their phospholipid membranes. The variety of its members would allow a complementary and synergistic action against a variety of microbes, which the amoeba encounters in its environment.}, } @article {pmid29644800, year = {2018}, author = {Mincarelli, L and Lister, A and Lipscombe, J and Macaulay, IC}, title = {Defining Cell Identity with Single-Cell Omics.}, journal = {Proteomics}, volume = {18}, number = {18}, pages = {e1700312}, pmid = {29644800}, issn = {1615-9861}, mesh = {Animals ; Biomarkers/*analysis ; *Cell Lineage ; Epigenomics/*methods ; Genomics/*methods ; Humans ; Metabolomics/*methods ; Phenotype ; Proteomics/*methods ; Single-Cell Analysis/*methods ; }, abstract = {Cells are a fundamental unit of life, and the ability to study the phenotypes and behaviors of individual cells is crucial to understanding the workings of complex biological systems. Cell phenotypes (epigenomic, transcriptomic, proteomic, and metabolomic) exhibit dramatic heterogeneity between and within the different cell types and states underlying cellular functional diversity. Cell genotypes can also display heterogeneity throughout an organism, in the form of somatic genetic variation-most notably in the emergence and evolution of tumors. Recent technical advances in single-cell isolation and the development of omics approaches sensitive enough to reveal these aspects of cell identity have enabled a revolution in the study of multicellular systems. In this review, we discuss the technologies available to resolve the genomes, epigenomes, transcriptomes, proteomes, and metabolomes of single cells from a wide variety of living systems.}, } @article {pmid29643333, year = {2018}, author = {Ikeda, T and Hikichi, T and Miura, H and Shibata, H and Mitsunaga, K and Yamada, Y and Woltjen, K and Miyamoto, K and Hiratani, I and Yamada, Y and Hotta, A and Yamamoto, T and Okita, K and Masui, S}, title = {Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {1387}, pmid = {29643333}, issn = {2041-1723}, mesh = {Actins/genetics/metabolism ; Animals ; Cell Differentiation ; Cellular Reprogramming/genetics ; Chromatin/*chemistry/metabolism ; Colitis, Ulcerative/*genetics/metabolism/pathology ; Disease Models, Animal ; Female ; Gene Expression Regulation ; Induced Pluripotent Stem Cells/cytology/*metabolism ; Male ; Metaplasia/*genetics/metabolism/pathology ; Mice ; Mice, Transgenic ; Neural Stem Cells/cytology/*metabolism ; Pancreas/*metabolism/pathology ; Serum Response Factor/*genetics/metabolism ; Signal Transduction ; Trans-Activators/genetics/metabolism ; }, abstract = {Multicellular organisms consist of multiple cell types. The identity of these cells is primarily maintained by cell-type-specific gene expression programs; however, mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease β-actin monomer quantity result in the nuclear accumulation of Mkl1 and the activation of Srf, which downregulate cell-type-specific genes and alter the epigenetics of regulatory regions and chromatin organization. Mice overexpressing Srf exhibit various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases.}, } @article {pmid29641448, year = {2018}, author = {Zheng, S and Long, J and Liu, Z and Tao, W and Wang, D}, title = {Identification and Evolution of TGF-β Signaling Pathway Members in Twenty-Four Animal Species and Expression in Tilapia.}, journal = {International journal of molecular sciences}, volume = {19}, number = {4}, pages = {}, pmid = {29641448}, issn = {1422-0067}, mesh = {Activin Receptors, Type I/genetics/metabolism ; Animals ; *Evolution, Molecular ; Fish Proteins/*genetics/metabolism ; Phylogeny ; Receptors, Transforming Growth Factor beta/genetics/metabolism ; *Signal Transduction ; Smad4 Protein/genetics/metabolism ; Tilapia/classification/*genetics/metabolism ; Transforming Growth Factor beta/*genetics/metabolism ; }, abstract = {Transforming growth factor β (TGF-β) signaling controls diverse cellular processes during embryogenesis as well as in mature tissues of multicellular animals. Here we carried out a comprehensive analysis of TGF-β pathway members in 24 representative animal species. The appearance of the TGF-β pathway was intrinsically linked to the emergence of metazoan. The total number of TGF-β ligands, receptors, and smads changed slightly in all invertebrates and jawless vertebrates analyzed. In contrast, expansion of the pathway members, especially ligands, was observed in jawed vertebrates most likely due to the second round of whole genome duplication (2R) and additional rounds in teleosts. Duplications of TGFB2, TGFBR2, ACVR1, SMAD4 and SMAD6, which were resulted from 2R, were first isolated. Type II receptors may be originated from the ACVR2-like ancestor. Interestingly, AMHR2 was not identified in Chimaeriformes and Cypriniformes even though they had the ligand AMH. Based on transcriptome data, TGF-β ligands exhibited a tissue-specific expression especially in the heart and gonads. However, most receptors and smads were expressed in multiple tissues indicating they were shared by different ligands. Spatial and temporal expression profiles of 8 genes in gonads of different developmental stages provided a fundamental clue for understanding their important roles in sex determination and reproduction. Taken together, our findings provided a global insight into the phylogeny and expression patterns of the TGF-β pathway genes, and hence contribute to the greater understanding of their biological roles in the organism especially in teleosts.}, } @article {pmid29632261, year = {2018}, author = {Halatek, J and Brauns, F and Frey, E}, title = {Self-organization principles of intracellular pattern formation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632261}, issn = {1471-2970}, mesh = {Animals ; Caenorhabditis elegans/*genetics ; Caenorhabditis elegans Proteins/genetics ; Escherichia coli/*genetics ; Escherichia coli Proteins/genetics ; *Evolution, Molecular ; Models, Genetic ; Saccharomyces cerevisiae/*genetics ; cdc42 GTP-Binding Protein, Saccharomyces cerevisiae/genetics ; }, abstract = {Dynamic patterning of specific proteins is essential for the spatio-temporal regulation of many important intracellular processes in prokaryotes, eukaryotes and multicellular organisms. The emergence of patterns generated by interactions of diffusing proteins is a paradigmatic example for self-organization. In this article, we review quantitative models for intracellular Min protein patterns in Escherichia coli, Cdc42 polarization in Saccharomyces cerevisiae and the bipolar PAR protein patterns found in Caenorhabditis elegans By analysing the molecular processes driving these systems we derive a theoretical perspective on general principles underlying self-organized pattern formation. We argue that intracellular pattern formation is not captured by concepts such as 'activators', 'inhibitors' or 'substrate depletion'. Instead, intracellular pattern formation is based on the redistribution of proteins by cytosolic diffusion, and the cycling of proteins between distinct conformational states. Therefore, mass-conserving reaction-diffusion equations provide the most appropriate framework to study intracellular pattern formation. We conclude that directed transport, e.g. cytosolic diffusion along an actively maintained cytosolic gradient, is the key process underlying pattern formation. Thus the basic principle of self-organization is the establishment and maintenance of directed transport by intracellular protein dynamics.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632050, year = {2018}, author = {Fidler, AL and Boudko, SP and Rokas, A and Hudson, BG}, title = {The triple helix of collagens - an ancient protein structure that enabled animal multicellularity and tissue evolution.}, journal = {Journal of cell science}, volume = {131}, number = {7}, pages = {}, pmid = {29632050}, issn = {1477-9137}, support = {R01 DK018381/DK/NIDDK NIH HHS/United States ; R37 DK018381/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cellular Microenvironment/genetics ; Collagen Type IV/chemistry/*genetics ; *Evolution, Molecular ; Extracellular Matrix ; Protein Conformation, alpha-Helical/*genetics ; }, abstract = {The cellular microenvironment, characterized by an extracellular matrix (ECM), played an essential role in the transition from unicellularity to multicellularity in animals (metazoans), and in the subsequent evolution of diverse animal tissues and organs. A major ECM component are members of the collagen superfamily -comprising 28 types in vertebrates - that exist in diverse supramolecular assemblies ranging from networks to fibrils. Each assembly is characterized by a hallmark feature, a protein structure called a triple helix. A current gap in knowledge is understanding the mechanisms of how the triple helix encodes and utilizes information in building scaffolds on the outside of cells. Type IV collagen, recently revealed as the evolutionarily most ancient member of the collagen superfamily, serves as an archetype for a fresh view of fundamental structural features of a triple helix that underlie the diversity of biological activities of collagens. In this Opinion, we argue that the triple helix is a protein structure of fundamental importance in building the extracellular matrix, which enabled animal multicellularity and tissue evolution.}, } @article {pmid29625658, year = {2018}, author = {Padder, SA and Prasad, R and Shah, AH}, title = {Quorum sensing: A less known mode of communication among fungi.}, journal = {Microbiological research}, volume = {210}, number = {}, pages = {51-58}, doi = {10.1016/j.micres.2018.03.007}, pmid = {29625658}, issn = {1618-0623}, mesh = {Anti-Infective Agents/pharmacology ; Bacteria/drug effects/genetics ; Bacterial Physiological Phenomena ; Candida albicans/physiology ; Drug Resistance, Multiple/genetics ; Farnesol/metabolism ; Fungi/*drug effects/*physiology ; Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Fungal ; Phenylethyl Alcohol/analogs & derivatives/metabolism ; Pheromones/metabolism ; Quorum Sensing/*drug effects/genetics/*physiology ; Virulence/genetics ; Volatile Organic Compounds/metabolism ; }, abstract = {Quorum sensing (QS), a density-dependent signaling mechanism of microbial cells, involves an exchange and sense of low molecular weight signaling compounds called autoinducers. With the increase in population density, the autoinducers accumulate in the extracellular environment and once their concentration reaches a threshold, many genes are either expressed or repressed. This cell density-dependent signaling mechanism enables single cells to behave as multicellular organisms and regulates different microbial behaviors like morphogenesis, pathogenesis, competence, biofilm formation, bioluminescence, etc guided by environmental cues. Initially, QS was regarded to be a specialized system of certain bacteria. The discovery of filamentation control in pathogenic polymorphic fungus Candida albicans by farnesol revealed the phenomenon of QS in fungi as well. Pathogenic microorganisms primarily regulate the expression of virulence genes using QS systems. The indirect role of QS in the emergence of multiple drug resistance (MDR) in microbial pathogens necessitates the finding of alternative antimicrobial therapies that target QS and inhibit the same. A related phenomenon of quorum sensing inhibition (QSI) performed by small inhibitor molecules called quorum sensing inhibitors (QSIs) has an ability for efficient reduction of gene expression regulated by quorum sensing. In the present review, recent advancements in the study of different fungal quorum sensing molecules (QSMs) and quorum sensing inhibitors (QSIs) of fungal origin along with their mechanism of action and/or role/s are discussed.}, } @article {pmid29616867, year = {2018}, author = {Gaiti, F and Degnan, BM and Tanurdžić, M}, title = {Long non-coding regulatory RNAs in sponges and insights into the origin of animal multicellularity.}, journal = {RNA biology}, volume = {15}, number = {6}, pages = {696-702}, pmid = {29616867}, issn = {1555-8584}, mesh = {Animals ; *Evolution, Molecular ; *Genome ; Porifera/cytology/genetics/*metabolism ; RNA, Long Noncoding/genetics/*metabolism ; }, abstract = {How animals evolved from a single-celled ancestor over 700 million years ago is poorly understood. Recent transcriptomic and chromatin analyses in the sponge Amphimedon queenslandica, a morphologically-simple representative of one of the oldest animal phyletic lineages, have shed light on what innovations in the genome and its regulation underlie the emergence of animal multicellularity. Comparisons of the regulatory genome of this sponge with those of more complex bilaterian model species and even simpler unicellular relatives have revealed that fundamental changes in genome regulatory complexity accompanied the evolution of animal multicellularity. Here, we review and discuss the results of these recent investigations by specifically focusing on the contribution of long non-coding RNAs to the evolution of the animal regulatory genome.}, } @article {pmid29614268, year = {2018}, author = {Park, B and Kim, H and Jeon, TJ}, title = {Loss of RapC causes defects in cytokinesis, cell migration, and multicellular development of Dictyostelium.}, journal = {Biochemical and biophysical research communications}, volume = {499}, number = {4}, pages = {783-789}, doi = {10.1016/j.bbrc.2018.03.223}, pmid = {29614268}, issn = {1090-2104}, mesh = {Cell Adhesion ; *Cell Movement ; Cell Shape ; *Cytokinesis ; Dictyostelium/*cytology/*growth & development/metabolism ; Phenotype ; Phylogeny ; Protozoan Proteins/chemistry/*metabolism ; Sequence Homology, Amino Acid ; rap1 GTP-Binding Proteins/chemistry ; }, abstract = {The small GTPase Ras proteins are involved in diverse cellular processes. We investigated the functions of RapC, one of 15 Ras subfamily GTPases in Dictyostelium. Loss of RapC resulted in a spread shape of cells; severe defects in cytokinesis leading to multinucleation; decrease of migration speed in chemoattractant-mediated cell migration, likely through increased cell adhesion; and aberrations in multicellular development producing abnormal multiple tips from one mound and multi-branched developmental structures. Defects in cells lacking RapC were rescued by expressing GFP-RapC in rapC null cells. Our results demonstrate that RapC, despite its high sequence homology with Rap1, plays a negative role in cell spreading and cell adhesion, in contrast to Rap1, which is a key regulator of cell adhesion and cytoskeleton rearrangement. In addition, RapC appears to have a unique function in multicellular development and is involved in tip formation from mounds. This study contributes to the understanding of Ras-mediated cellular processes.}, } @article {pmid29610072, year = {2018}, author = {Loewke, NO and Pai, S and Cordeiro, C and Black, D and King, BL and Contag, CH and Chen, B and Baer, TM and Solgaard, O}, title = {Automated Cell Segmentation for Quantitative Phase Microscopy.}, journal = {IEEE transactions on medical imaging}, volume = {37}, number = {4}, pages = {929-940}, pmid = {29610072}, issn = {1558-254X}, support = {R01 CA172895/CA/NCI NIH HHS/United States ; R01 CA182043/CA/NCI NIH HHS/United States ; T32 EB009653/EB/NIBIB NIH HHS/United States ; }, mesh = {*Algorithms ; Cell Line ; Cells, Cultured ; Cytological Techniques/*methods ; Humans ; Image Processing, Computer-Assisted/*methods ; Microscopy/*methods ; }, abstract = {Automated cell segmentation and tracking is essential for dynamic studies of cellular morphology, movement, and interactions as well as other cellular behaviors. However, accurate, automated, and easy-to-use cell segmentation remains a challenge, especially in cases of high cell densities, where discrete boundaries are not easily discernable. Here, we present a fully automated segmentation algorithm that iteratively segments cells based on the observed distribution of optical cell volumes measured by quantitative phase microscopy. By fitting these distributions to known probability density functions, we are able to converge on volumetric thresholds that enable valid segmentation cuts. Since each threshold is determined from the observed data itself, virtually no input is needed from the user. We demonstrate the effectiveness of this approach over time using six cell types that display a range of morphologies, and evaluate these cultures over a range of confluencies. Facile dynamic measures of cell mobility and function revealed unique cellular behaviors that relate to tissue origins, state of differentiation, and real-time signaling. These will improve our understanding of multicellular communication and organization.}, } @article {pmid29608173, year = {2018}, author = {Clarke, EK and Rivera Gomez, KA and Mustachi, Z and Murph, MC and Schvarzstein, M}, title = {Manipulation of Ploidy in Caenorhabditis elegans.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {133}, pages = {}, pmid = {29608173}, issn = {1940-087X}, support = {P40 OD010440/OD/NIH HHS/United States ; R25 GM062981/GM/NIGMS NIH HHS/United States ; SC2 GM118275/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*genetics ; Male ; *Ploidies ; }, abstract = {Mechanisms that involve whole genome polyploidy play important roles in development and evolution; also, an abnormal generation of tetraploid cells has been associated with both the progression of cancer and the development of drug resistance. Until now, it has not been feasible to easily manipulate the ploidy of a multicellular animal without generating mostly sterile progeny. Presented here is a simple and rapid protocol for generating tetraploid Caenorhabditis elegans animals from any diploid strain. This method allows the user to create a bias in chromosome segregation during meiosis, ultimately increasing ploidy in C. elegans. This strategy relies on the transient reduction of expression of the rec-8 gene to generate diploid gametes. A rec-8 mutant produces diploid gametes that can potentially produce tetraploids upon fertilization. This tractable scheme has been used to generate tetraploid strains carrying mutations and chromosome rearrangements to gain insight into chromosomal dynamics and interactions during pairing and synapsis in meiosis. This method is efficient for generating stable tetraploid strains without genetic markers, can be applied to any diploid strain, and can be used to derive triploid C. elegans. This straightforward method is useful for investigating other fundamental biological questions relevant to genome instability, gene dosage, biological scaling, extracellular signaling, adaptation to stress, development of resistance to drugs, and mechanisms of speciation.}, } @article {pmid29606595, year = {2018}, author = {Lherminier, P}, title = {[Informative predation: Towards a new species concept].}, journal = {Comptes rendus biologies}, volume = {341}, number = {4}, pages = {209-218}, doi = {10.1016/j.crvi.2018.02.004}, pmid = {29606595}, issn = {1768-3238}, mesh = {*Adaptation, Physiological ; Animals ; Biological Evolution ; Child ; Courtship ; Diploidy ; Female ; Fertility ; Genome ; Humans ; Male ; *Predatory Behavior ; Pregnancy ; Reproduction/genetics ; *Selection, Genetic ; }, abstract = {We distinguish two types of predations: the predation of matter-energy equals the food chain, and the informative predation is the capture of the information brought by the sexual partners. The cell or parent consumes energy and matter to grow, multiply and produce offspring. A fixed amount of resources is divided by the number of organisms, so individual growth and numerical multiplication are limited by depletion resources of the environment. Inversely, fertilization does not destroy information, but instead produces news. The information is multiplied by the number of partners and children, since each fertilization gives rise to a new genome following a combinatorial process that continues without exhaustion. The egg does not swallow the sperm to feed, but exchange good food for quality information. With the discovery of sex, that is, 1.5 Ga ago, life added soft predation to hard predation, i.e. information production within each species to matter-energy flow between species. Replicative and informative structures are subject to two competing biological constraints: replicative fidelity promotes proliferation, but limits adaptive evolution. On the contrary, the offspring of a couple obviously cannot be a copy of both partners, they are a new production, a re-production. Sexual recombination allows the exponential enrichment of the genetic diversity, thus promoting indefinite adaptive and evolutionary capacities. Evolutionary history illustrates this: the bacteria proliferate but have remained at the first purely nutritive stage in which most of the sensory functions, mobility, defense, and feeding have experienced almost no significant novelty in three billion years. Another world appeared with the sexual management of information. Sexual reproduction actually combines two functions: multiplicative by "vertical transfer" and informative by "horizontal transfer". This distinction is very common: polypus - medusa alternations, parasite multiplication cycles, the lytochal and deuterotochal parthenogenesis of aphids, and the innumerable para- and pseudo-sexual strategies of plants opportunistically combine the two modes of asexual replication and sexual combination. However, for the majority of animals and multicellular plants that produce many gametes, numerical proliferation by descendants and informative diversity by sexuality are mutually implicated, for example in the seed. The true discovery of eukaryotes may not be the "true nucleus", as their name implies, but an orderly informative function. The field of recombinations circumscribes a class of partners genetically compatible with each other, each simultaneously prey and predator of the DNA of the other. The mythical Maxwell demon capable of tracing entropy by sorting molecules according to their state does exist: each mate is the other's Maxwell's demon. While a sexless bacterium is simply divided into two cells, two sexual parents work together to produce a single offspring a time. Added to this are the burdens involved in meiosis and crossing-over, cellular diploidy, and mating. Sex produces an information gain that is paid for by a cost of energy-material, and this barter must be fair to survive. The domains of sexual intercourse are very diverse: uniparental reproduction, alternation of asexual proliferation and sexual information, self-fertilization, endogamy, exogamy, panmixis, diffuse or structured polymorphism, fertile or sterile hybridization, horizontal transfers. Each species is a recombination field between two domains, cloning and hybridization. Multiplicative descent and informative fertilization are organically distinct, but selectively associated: the information produced by the parents' sexuality favors the predation of matter-energy and therefore the proliferation of offspring, and this proliferation in turn favors the sexed producers of information. The equation specific to each species is: enough energy to proliferate, enough information to diversify. Alternatively, two other reproductive modes obtain or transmit less information at lower cost: not enough recombinations=repetitive clonal proliferation, and too many recombinations=disordered hybridization. But these marginal modes have poor prospects, as the model of the species is successfully attractive. Better discriminate to better inform. In bacteria, the exchanged and incorporated DNA segments are directly identified by the parity of the complementary strands, which determines simultaneously the similarity, the offspring, and the pairing. In eukaryotes, on the contrary, somatic growth and germinal information are segregated. During speciation, adaptive information is compacted, delocalized, codified and published to inform the species about its own state: the prezygotic relationship governs viable mating. Under the effect of sexual selection, the runaway and the reinforcement of the characters related to courtship testifies to their identifying function, which explains the paradox of the singularity and luxuriance of the sexual hypertrophies. The speciation discretizes a balanced recombination field and validates the informative relations. The species is without degree. Mates of a species recognize each other quickly and well because the logic of coding disengages from the ecological game of adaptations. The system of mate recognition has a function of cohesion and its regularity allows the adaptations of the less regular being, it is neither elitist nor normative, it is subjected neither to a level of aptitudes, nor to sexual performances, but permissive; it protects the variability and polymorphism. Two mutually irreducible relationships triggered the debate between the taxonomists who support the phyletic definition of the species by the descendance, and the proponents of the definition by interfertility. Such a taxonomic disagreement is not insurmountable, but the issue is deeper than taxonomic concepts, because these concepts relate to two different modes of evolution. According to the phyletic model, each species is a lineage passively isolated by external circumstances; on the contrary, in the sexual model each species is actively produced by an internal process of adjustment between replicative costs and informative gains. Each species develops a solution of the equation that matches material-energy expenditures with informative gains. A species concept based on a lasting relationship between these two quantities or on the limits of certain values or their equilibrium is therefore legitimate. It is this equilibrium that all couples resolve, without our formulation being as clearly as biology desires and as physics demands. Energy expenditures and informative gains in sexuality are almost impossible to measure, yet observation and experience allow an approximate ranking of the energy/information ratio. For example, endogamy is more economical, but less diversifying than exogamy, polymorphism increases information, the reinforcement of sexual isolation limits the rate of unproductive fertilization, between neighboring species hybridization allows certain genetic contributions, etc. A closed species evolves naturally towards another just as closed. On the contrary, the artificial transfer of DNA opens the species. The natural boundaries that isolate the species are easily trespassed as energy costs and constraints of sexual recognition are easily controlled; and the perspectives of manipulations are visible, whereas natural selection never anticipates and thus works blindly. Informative, artificially directed predation stimulates the evolution of species.}, } @article {pmid29602367, year = {2018}, author = {Shingleton, AW and Frankino, WA}, title = {The (ongoing) problem of relative growth.}, journal = {Current opinion in insect science}, volume = {25}, number = {}, pages = {9-19}, doi = {10.1016/j.cois.2017.10.001}, pmid = {29602367}, issn = {2214-5753}, mesh = {Animals ; Biological Evolution ; Endocrine System/physiology ; Imaginal Discs/growth & development ; Insecta/anatomy & histology/*growth & development/physiology ; Morphogenesis/*physiology ; Phenotype ; Signal Transduction ; }, abstract = {Differential growth, the phenomenon where parts of the body grow at different rates, is necessary to generate the complex morphologies of most multicellular organisms. Despite this central importance, how differential growth is regulated remains largely unknown. Recent discoveries, particularly in insects, have started to uncover the molecular-genetic and physiological mechanisms that coordinate growth among different tissues throughout the body and regulate relative growth. These discoveries suggest that growth is coordinated by a network of signals that emanate from growing tissues and central endocrine organs. Here we review these findings and discuss their implications for understanding the regulation of relative growth and the evolution of morphology.}, } @article {pmid29599012, year = {2018}, author = {Bang, C and Dagan, T and Deines, P and Dubilier, N and Duschl, WJ and Fraune, S and Hentschel, U and Hirt, H and Hülter, N and Lachnit, T and Picazo, D and Pita, L and Pogoreutz, C and Rädecker, N and Saad, MM and Schmitz, RA and Schulenburg, H and Voolstra, CR and Weiland-Bräuer, N and Ziegler, M and Bosch, TCG}, title = {Metaorganisms in extreme environments: do microbes play a role in organismal adaptation?.}, journal = {Zoology (Jena, Germany)}, volume = {127}, number = {}, pages = {1-19}, doi = {10.1016/j.zool.2018.02.004}, pmid = {29599012}, issn = {1873-2720}, mesh = {*Adaptation, Physiological/physiology ; Animals ; Ecosystem ; *Extreme Environments ; Microbiota/genetics/*physiology ; Phylogeny ; Symbiosis/physiology ; }, abstract = {From protists to humans, all animals and plants are inhabited by microbial organisms. There is an increasing appreciation that these resident microbes influence the fitness of their plant and animal hosts, ultimately forming a metaorganism consisting of a uni- or multicellular host and a community of associated microorganisms. Research on host-microbe interactions has become an emerging cross-disciplinary field. In both vertebrates and invertebrates a complex microbiome confers immunological, metabolic and behavioural benefits; conversely, its disturbance can contribute to the development of disease states. However, the molecular and cellular mechanisms controlling the interactions within a metaorganism are poorly understood and many key interactions between the associated organisms remain unknown. In this perspective article, we outline some of the issues in interspecies interactions and in particular address the question of how metaorganisms react and adapt to inputs from extreme environments such as deserts, the intertidal zone, oligothrophic seas, and hydrothermal vents.}, } @article {pmid29597064, year = {2018}, author = {Presting, GG}, title = {Centromeric retrotransposons and centromere function.}, journal = {Current opinion in genetics & development}, volume = {49}, number = {}, pages = {79-84}, doi = {10.1016/j.gde.2018.03.004}, pmid = {29597064}, issn = {1879-0380}, mesh = {Centromere/*genetics ; DNA Breaks, Double-Stranded ; Eukaryota/genetics ; *Evolution, Molecular ; Retroelements/*genetics ; Tandem Repeat Sequences/*genetics ; }, abstract = {The centromeric DNA of most multicellular eukaryotes consists of tandem repeats (TR) that bind centromere-specific proteins and act as a substrate for the efficient repair of frequent double-stranded DNA breaks. Some retrotransposons target active centromeres during integration with such specificity that they can be used to deduce current and historic centromere positions. The roles of transposons in centromere function remain incompletely understood but appear to include maintaining centromere size and increasing the repeat content of neocentromeres that lack TR. Retrotransposons are known to give rise to TR. Centromere-targeting elements thus have the potential to replace centromeric TR essentially in situ, providing a mechanism to explain the centromere paradox, that is, the presence of unrelated centromeric TRs in closely related species.}, } @article {pmid29590089, year = {2018}, author = {Alemany, A and Florescu, M and Baron, CS and Peterson-Maduro, J and van Oudenaarden, A}, title = {Whole-organism clone tracing using single-cell sequencing.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {108-112}, pmid = {29590089}, issn = {1476-4687}, mesh = {Animal Fins/cytology ; Animals ; Brain/cytology ; CRISPR-Cas Systems/genetics ; *Cell Lineage/genetics ; Cell Tracking/*methods ; Clone Cells/*cytology/*metabolism ; Embryonic Stem Cells/cytology/metabolism ; Eye/cytology ; Female ; Genes, Reporter/genetics ; Hematopoietic Stem Cells/cytology/metabolism ; Male ; Multipotent Stem Cells/cytology/metabolism ; Organ Specificity ; Regeneration ; Sequence Analysis/*methods ; *Single-Cell Analysis ; Transcriptome ; Whole Body Imaging ; Zebrafish/*anatomy & histology/embryology/genetics ; }, abstract = {Embryonic development is a crucial period in the life of a multicellular organism, during which limited sets of embryonic progenitors produce all cells in the adult body. Determining which fate these progenitors acquire in adult tissues requires the simultaneous measurement of clonal history and cell identity at single-cell resolution, which has been a major challenge. Clonal history has traditionally been investigated by microscopically tracking cells during development, monitoring the heritable expression of genetically encoded fluorescent proteins and, more recently, using next-generation sequencing technologies that exploit somatic mutations, microsatellite instability, transposon tagging, viral barcoding, CRISPR-Cas9 genome editing and Cre-loxP recombination. Single-cell transcriptomics provides a powerful platform for unbiased cell-type classification. Here we present ScarTrace, a single-cell sequencing strategy that enables the simultaneous quantification of clonal history and cell type for thousands of cells obtained from different organs of the adult zebrafish. Using ScarTrace, we show that a small set of multipotent embryonic progenitors generate all haematopoietic cells in the kidney marrow, and that many progenitors produce specific cell types in the eyes and brain. In addition, we study when embryonic progenitors commit to the left or right eye. ScarTrace reveals that epidermal and mesenchymal cells in the caudal fin arise from the same progenitors, and that osteoblast-restricted precursors can produce mesenchymal cells during regeneration. Furthermore, we identify resident immune cells in the fin with a distinct clonal origin from other blood cell types. We envision that similar approaches will have major applications in other experimental systems, in which the matching of embryonic clonal origin to adult cell type will ultimately allow reconstruction of how the adult body is built from a single cell.}, } @article {pmid29589089, year = {2018}, author = {Huang, C and Fu, C and Wren, JD and Wang, X and Zhang, F and Zhang, YH and Connel, SA and Chen, T and Zhang, XA}, title = {Tetraspanin-enriched microdomains regulate digitation junctions.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {75}, number = {18}, pages = {3423-3439}, pmid = {29589089}, issn = {1420-9071}, support = {CA096991/NH/NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; 13GRNT17040028//American Heart Association/International ; R01 HL137819/HL/NHLBI NIH HHS/United States ; R01 CA096991/CA/NCI NIH HHS/United States ; R01 HL132553/HL/NHLBI NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/drug effects ; Actins/metabolism ; Animals ; Antigens, CD/genetics/metabolism ; Cell Adhesion Molecules/metabolism ; Cell Line ; Cytochalasin D/pharmacology ; Dogs ; Humans ; Intercellular Junctions/*metabolism ; Madin Darby Canine Kidney Cells ; Membrane Microdomains/metabolism ; Membrane Proteins/antagonists & inhibitors/genetics/metabolism ; Microscopy, Confocal ; Tetraspanins/chemistry/*metabolism ; }, abstract = {Tetraspanins co-emerged with multi-cellular organisms during evolution and are typically localized at the cell–cell interface, [corrected] and form tetraspanin-enriched microdomains (TEMs) by associating with each other and other membrane molecules. Tetraspanins affect various biological functions, but how tetraspanins engage in multi-faceted functions at the cellular level is largely unknown. When cells interact, the membrane microextrusions at the cell-cell interfaces form dynamic, digit-like structures between cells, which we term digitation junctions (DJs). We found that (1) tetraspanins CD9, CD81, and CD82 and (2) TEM-associated molecules integrin α3β1, CD44, EWI2/PGRL, and PI-4P are present in DJs of epithelial, endothelial, and cancer cells. Tetraspanins and their associated molecules also regulate the formation and development of DJs. Moreover, (1) actin cytoskeleton, RhoA, and actomyosin activities and (2) growth factor receptor-Src-MAP kinase signaling, but not PI-3 kinase, regulate DJs. Finally, we showed that DJs consist of various forms in different cells. Thus, DJs are common, interactive structures between cells, and likely affect cell adhesion, migration, and communication. TEMs probably modulate various cell functions through DJs. Our findings highlight that DJ morphogenesis reflects the transition between cell-matrix adhesion and cell-cell adhesion and involves both cell-cell and cell-matrix adhesion molecules.}, } @article {pmid29587819, year = {2018}, author = {Dickson, LB and Ghozlane, A and Volant, S and Bouchier, C and Ma, L and Vega-Rúa, A and Dusfour, I and Jiolle, D and Paupy, C and Mayanja, MN and Kohl, A and Lutwama, JJ and Duong, V and Lambrechts, L}, title = {Diverse laboratory colonies of Aedes aegypti harbor the same adult midgut bacterial microbiome.}, journal = {Parasites & vectors}, volume = {11}, number = {1}, pages = {207}, pmid = {29587819}, issn = {1756-3305}, support = {ANR-10-LABX-62-IBEID//Investissement d'Avenir program Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases/International ; ANR-16-CE35-0004-01//Agence Nationale de la Recherche/International ; ANR-17-ERC2-0016-01//Agence Nationale de la Recherche/International ; 734584//European Union's Horizon 2020 research and innovation programme under ZikaPLAN/International ; MC_UU_12014/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/8/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/MRC_/Medical Research Council/United Kingdom ; ANR10-INBS-09-08//France Génomique consortium/International ; 2015-FED-192//Programme Opérationnel FEDER-Guadeloupe-Conseil Régional/International ; }, mesh = {Aedes/*microbiology ; Animals ; Bacteria/*classification/*genetics ; Cluster Analysis ; DNA, Ribosomal/chemistry/genetics ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Metagenomics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Host-associated microbes, collectively known as the microbiota, play an important role in the biology of multicellular organisms. In mosquito vectors of human pathogens, the gut bacterial microbiota influences vectorial capacity and has become the subject of intense study. In laboratory studies of vector biology, genetic effects are often inferred from differences between geographically and genetically diverse colonies of mosquitoes that are reared in the same insectary. It is unclear, however, to what extent genetic effects can be confounded by uncontrolled differences in the microbiota composition among mosquito colonies. To address this question, we used 16S metagenomics to compare the midgut bacterial microbiome of six laboratory colonies of Aedes aegypti recently derived from wild populations representing the geographical range and genetic diversity of the species.

RESULTS: We found that the diversity, abundance, and community structure of the midgut bacterial microbiome was remarkably similar among the six different colonies of Ae. aegypti, regardless of their geographical origin. We also confirmed the relatively low complexity of bacterial communities inhabiting the mosquito midgut.

CONCLUSIONS: Our finding that geographically diverse colonies of Ae. aegypti reared in the same insectary harbor a similar gut bacterial microbiome supports the conclusion that the gut microbiota of adult mosquitoes is environmentally determined regardless of the host genotype. Thus, uncontrolled differences in microbiota composition are unlikely to represent a significant confounding factor in genetic studies of vector biology.}, } @article {pmid29579574, year = {2018}, author = {Lower, SS and McGurk, MP and Clark, AG and Barbash, DA}, title = {Satellite DNA evolution: old ideas, new approaches.}, journal = {Current opinion in genetics & development}, volume = {49}, number = {}, pages = {70-78}, pmid = {29579574}, issn = {1879-0380}, support = {F32 GM126736/GM/NIGMS NIH HHS/United States ; R01 GM119125/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence/*genetics ; Chromosome Segregation/genetics ; DNA, Satellite/*genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; Genome/genetics ; Reproductive Isolation ; }, abstract = {A substantial portion of the genomes of most multicellular eukaryotes consists of large arrays of tandemly repeated sequence, collectively called satellite DNA. The processes generating and maintaining different satellite DNA abundances across lineages are important to understand as satellites have been linked to chromosome mis-segregation, disease phenotypes, and reproductive isolation between species. While much theory has been developed to describe satellite evolution, empirical tests of these models have fallen short because of the challenges in assessing satellite repeat regions of the genome. Advances in computational tools and sequencing technologies now enable identification and quantification of satellite sequences genome-wide. Here, we describe some of these tools and how their applications are furthering our knowledge of satellite evolution and function.}, } @article {pmid29575407, year = {2018}, author = {Radzvilavicius, AL and Blackstone, NW}, title = {The evolution of individuality revisited.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1620-1633}, doi = {10.1111/brv.12412}, pmid = {29575407}, issn = {1469-185X}, mesh = {Animals ; *Biological Evolution ; Eukaryota ; Genetic Variation ; *Individuality ; *Models, Biological ; }, abstract = {Evolutionary theory is formulated in terms of individuals that carry heritable information and are subject to selective pressures. However, individuality itself is a trait that had to evolve - an individual is not an indivisible entity, but a result of evolutionary processes that necessarily begin at the lower level of hierarchical organisation. Traditional approaches to biological individuality focus on cooperation and relatedness within a group, division of labour, policing mechanisms and strong selection at the higher level. Nevertheless, despite considerable theoretical progress in these areas, a full dynamical first-principles account of how new types of individuals arise is missing. To the extent that individuality is an emergent trait, the problem can be approached by recognising the importance of individuating mechanisms that are present from the very beginning of the transition, when only lower-level selection is acting. Here we review some of the most influential theoretical work on the role of individuating mechanisms in these transitions, and demonstrate how a lower-level, bottom-up evolutionary framework can be used to understand biological complexity involved in the origin of cellular life, early eukaryotic evolution, sexual life cycles and multicellular development. Some of these mechanisms inevitably stem from environmental constraints, population structure and ancestral life cycles. Others are unique to specific transitions - features of the natural history and biochemistry that are co-opted into conflict mediation. Identifying mechanisms of individuation that provide a coarse-grained description of the system's evolutionary dynamics is an important step towards understanding how biological complexity and hierarchical organisation evolves. In this way, individuality can be reconceptualised as an approximate model that with varying degrees of precision applies to a wide range of biological systems.}, } @article {pmid29575018, year = {2018}, author = {Revilla-I-Domingo, R and Simakov, O}, title = {The Diversification of Early Emerging Metazoans: A Window into the Evolution of Animal Multicellularity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {40}, number = {5}, pages = {e1800029}, doi = {10.1002/bies.201800029}, pmid = {29575018}, issn = {1521-1878}, mesh = {Animals ; *Biological Evolution ; Cnidaria/classification ; Ctenophora/classification ; Evolution, Molecular ; Germany ; Phylogeny ; Placozoa/classification ; Porifera/classification ; }, abstract = {The biannual international workshop entitled "The diversification of early emerging metazoans: A window into animal evolution?" took place at the Evangelische Akademie Tutzing, Germany, 11-14. September 2017. It was organized by Thomas Bosch (Kiel), Thomas Holstein (Heidelberg), and Ulrich Technau (Vienna), and it was sponsored by the Deutsche Forschungsgemeinschaft (DFG). The meeting gathered over 140 researchers to discuss the contribution of non-bilaterian metazoan models (Porifera, Ctenophora, Placozoa, and Cnidaria) to our understanding of: a. The evolution of metazoan developmental processes; b. Fundamental molecular mechanisms underlying metazoan features; and c. The complex interactions that animals establish with their environment.}, } @article {pmid29573204, year = {2018}, author = {Preisner, H and Habicht, J and Garg, SG and Gould, SB}, title = {Intermediate filament protein evolution and protists.}, journal = {Cytoskeleton (Hoboken, N.J.)}, volume = {75}, number = {6}, pages = {231-243}, doi = {10.1002/cm.21443}, pmid = {29573204}, issn = {1949-3592}, mesh = {Animals ; *Biological Evolution ; Eukaryotic Cells/*cytology ; *Intermediate Filaments ; Prokaryotic Cells/*cytology ; }, abstract = {Metazoans evolved from a single protist lineage. While all eukaryotes share a conserved actin and tubulin-based cytoskeleton, it is commonly perceived that intermediate filaments (IFs), including lamin, vimentin or keratin among many others, are restricted to metazoans. Actin and tubulin proteins are conserved enough to be detectable across all eukaryotic genomes using standard phylogenetic methods, but IF proteins, in contrast, are notoriously difficult to identify by such means. Since the 1950s, dozens of cytoskeletal proteins in protists have been identified that seemingly do not belong to any of the IF families described for metazoans, yet, from a structural and functional perspective fit criteria that define metazoan IF proteins. Here, we briefly review IF protein discovery in metazoans and the implications this had for the definition of this protein family. We argue that the many cytoskeletal and filament-forming proteins of protists should be incorporated into a more comprehensive picture of IF evolution by aligning it with the recent identification of lamins across the phylogenetic diversity of eukaryotic supergroups. This then brings forth the question of how the diversity of IF proteins has unfolded. The evolution of IF proteins likely represents an example of convergent evolution, which, in combination with the speed with which these cytoskeletal proteins are evolving, generated their current diversity. IF proteins did not first emerge in metazoa, but in protists. Only the emergence of cytosolic IF proteins that appear to stem from a nuclear lamin is unique to animals and coincided with the emergence of true animal multicellularity.}, } @article {pmid29559848, year = {2018}, author = {Shabardina, V and Kischka, T and Kmita, H and Suzuki, Y and Makałowski, W}, title = {Environmental adaptation of Acanthamoeba castellanii and Entamoeba histolytica at genome level as seen by comparative genomic analysis.}, journal = {International journal of biological sciences}, volume = {14}, number = {3}, pages = {306-320}, pmid = {29559848}, issn = {1449-2288}, mesh = {Acanthamoeba castellanii/*genetics/*physiology ; Actins/genetics ; *Adaptation, Physiological ; *Comparative Genomic Hybridization ; Entamoeba histolytica/*genetics/*physiology ; Gene Expression ; Genes, Protozoan ; Sequence Analysis, RNA ; Transcriptome ; }, abstract = {Amoebozoans are in many aspects interesting research objects, as they combine features of single-cell organisms with complex signaling and defense systems, comparable to multicellular organisms. Acanthamoeba castellanii is a cosmopolitan species and developed diverged feeding abilities and strong anti-bacterial resistance; Entamoeba histolytica is a parasitic amoeba, who underwent massive gene loss and its genome is almost twice smaller than that of A. castellanii. Nevertheless, both species prosper, demonstrating fitness to their specific environments. Here we compare transcriptomes of A. castellanii and E. histolytica with application of orthologs' search and gene ontology to learn how different life strategies influence genome evolution and restructuring of physiology. A. castellanii demonstrates great metabolic activity and plasticity, while E. histolytica reveals several interesting features in its translational machinery, cytoskeleton, antioxidant protection, and nutritional behavior. In addition, we suggest new features in E. histolytica physiology that may explain its successful colonization of human colon and may facilitate medical research.}, } @article {pmid29557480, year = {2018}, author = {Gonçalves, DPN and Park, DM and Schmidt, TL and Werner, C}, title = {Modular peptide-functionalized gold nanorods for effective glioblastoma multicellular tumor spheroid targeting.}, journal = {Biomaterials science}, volume = {6}, number = {5}, pages = {1140-1146}, doi = {10.1039/C7BM01107E}, pmid = {29557480}, issn = {2047-4849}, mesh = {Antineoplastic Agents/*chemistry/pharmacology ; Apoptosis ; Endocytosis ; Glioblastoma/metabolism ; Gold/*chemistry ; Humans ; Metal Nanoparticles/*chemistry ; Nanotubes/*chemistry ; Neoplastic Stem Cells/*drug effects ; Nestin/chemistry ; Polyethylene Glycols/chemistry ; Spheroids, Cellular/drug effects ; Tumor Cells, Cultured ; }, abstract = {Glioblastoma multiforme (GBM) contains a population of tumor initiating stem-like cells, termed cancer stem cells (CSCs). These CSCs, which are resistant to chemo- and radiotherapy, are thought to persist after treatment and drive tumor recurrence. Thus, it is believed that the elimination of CSCs can lead to GBM remission. GBM CSCs express Nestin on their surface, and can be therefore targeted via this protein. Gold nanorods (AuNRs) functionalized with an engineered, modular peptide that recognizes Nestin (NesPEG-AuNRs) were used to target the models of solid tumors originated from human GBM CSC multicellular tumor spheroids (MCTS). In our study, we show that NesPEG-AuNRs have low cytotoxicity, are efficiently taken up by MCTS, and distribute uniformly throughout our tumor models, not only at the periphery as often seen in other nanoparticle systems. NesPEG-AuNR uptake by MCTS appears to be mediated by an energy/caveolae endocytic mechanism. Moreover, plasmon excitation of AuNRs in the near-infrared (NIR) region results in the production of localized heat. Consequently, NesPEG-AuNR cytotoxicity is only observed during NIR-irradiation in MCTS with a high intracellular AuNR content. The intracellular accumulation/diffusion of NesPEG-AuNRs and NIR-irradiation result in photothermally induced GBM CSC apoptosis and MCTS growth inhibition. In summary, these data suggest that the combination of the Nestin recognizing peptide with AuNRs contributes to better tumor accumulation/penetration, and thus in GBM CSC elimination. Moreover, due to the modularity of our peptide design, the Nestin-binding peptide sequence can be exchanged for peptides targeting other surface markers for the treatment of various types of tumors.}, } @article {pmid29547664, year = {2018}, author = {Zielich, J and Tzima, E and Schröder, EA and Jemel, F and Conradt, B and Lambie, EJ}, title = {Overlapping expression patterns and functions of three paralogous P5B ATPases in Caenorhabditis elegans.}, journal = {PloS one}, volume = {13}, number = {3}, pages = {e0194451}, pmid = {29547664}, issn = {1932-6203}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/classification/*genetics/metabolism ; Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/cytology/enzymology/*genetics ; Caenorhabditis elegans Proteins/*genetics/metabolism ; Cell Movement/genetics ; *Gene Expression Profiling ; *Gene Expression Regulation, Enzymologic ; Luminescent Proteins/genetics/metabolism ; Membrane Proteins/genetics/metabolism ; Mutation ; Organelles/enzymology ; Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {P5B ATPases are present in the genomes of diverse unicellular and multicellular eukaryotes, indicating that they have an ancient origin, and that they are important for cellular fitness. Inactivation of ATP13A2, one of the four human P5B ATPases, leads to early-onset Parkinson's disease (Kufor-Rakeb Syndrome). The presence of an invariant PPALP motif within the putative substrate interaction pocket of transmembrane segment M4 suggests that all P5B ATPases might have similar transport specificity; however, the identity of the transport substrate(s) remains unknown. Nematodes of the genus Caenorhabditis possess three paralogous P5B ATPase genes, catp-5, catp-6 and catp-7, which probably originated from a single ancestral gene around the time of origin of the Caenorhabditid clade. By using CRISPR/Cas9, we have systematically investigated the expression patterns, subcellular localization and biological functions of each of the P5B ATPases of C. elegans. We find that each gene has a unique expression pattern, and that some tissues express more than one P5B. In some tissues where their expression patterns overlap, different P5Bs are targeted to different subcellular compartments (e.g., early endosomes vs. plasma membrane), whereas in other tissues they localize to the same compartment (plasma membrane). We observed lysosomal co-localization between CATP-6::GFP and LMP-1::RFP in transgenic animals; however, this was an artifact of the tagged LMP-1 protein, since anti-LMP-1 antibody staining of native protein revealed that LMP-1 and CATP-6::GFP occupy different compartments. The nematode P5Bs are at least partially redundant, since we observed synthetic sterility in catp-5(0); catp-6(0) and catp-6(0) catp-7(0) double mutants. The double mutants exhibit defects in distal tip cell migration that resemble those of ina-1 (alpha integrin ortholog) and vab-3 (Pax6 ortholog) mutants, suggesting that the nematode P5Bs are required for ina-1and/or vab-3 function. This is potentially a conserved regulatory interaction, since mammalian ATP13A2, alpha integrin and Pax6 are all required for proper dopaminergic neuron function.}, } @article {pmid29546464, year = {2018}, author = {Zhang, H and Yang, X and Feng, X and Xu, H and Yang, Q and Zou, L and Yan, M and Liu, D and Su, X and Jiao, B}, title = {Chromosome-wide gene dosage rebalance may benefit tumor progression.}, journal = {Molecular genetics and genomics : MGG}, volume = {293}, number = {4}, pages = {895-906}, pmid = {29546464}, issn = {1617-4623}, support = {XDB13030400//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; No.2016FB038//Applied Basic Research Foundation of Yunnan Province/ ; No.31371502//National Natural Science Foundation of China/ ; No. GREKF15-11//Open Project from state Key Laboratory of Genetic Resources and Evolution/ ; No.GREKF14-05//Open Project from State Key Laboratory of Genetic Resources and Evolution/ ; }, mesh = {Breast Neoplasms/*genetics ; Chromosomes, Human, X/*genetics ; Female ; *Gene Dosage ; *Gene Expression Regulation, Neoplastic ; *Gene Ontology ; Humans ; MCF-7 Cells ; }, abstract = {The high-risk of tumor initiation in patients with Turner syndrome (TS) characterized by X chromosome monosomy in women has been well established and aneuploidy, defined as an abnormal number of chromosomes, is a common feature in human cancer. However, the underlying mechanisms of X chromosome aneuploidy promoting tumorigenesis remain obscure. We propose that chromosome-wide gene dosage imbalance (CDI) may serve as an important mechanism. Here, we assess the relative expression ratios of X chromosome and autosomes (expression ratios of X:AA) between tumor samples and adjacent normal samples across 16 tumor types using expression datasets from The Cancer Genome Atlas (TCGA) project. Our results show that the expression ratios of X:AA in tumor samples are frequently rebalanced to a lower level compared to those in adjacent normal samples, which is termed chromosome-wide gene dosage rebalance (CDR) thereafter. Gene ontology (GO) analysis of differentially expression genes from X chromosome reveals that downregulation of multicellularity-related genes and upregulation of unicellularity-related genes in tumors form a distinctive feature and enrichment analysis shows that downregulated genes are enriched in tumor suppressor genes, which indicate that CDR benefits tumor progression. Further experimental results prove that disturbance of X chromosome expression by knocking down of XIST in breast cancer cells, which functions in initiation phase of X chromosome inactivation (XCI), inhibits tumor progression. Our results demonstrate that the prevalent CDRs across tumor types serve as an important mechanism in promoting tumor progression, which partially explains the high risk of tumor in patients with TS and also provides a new cancer therapy from the CDR perspective.}, } @article {pmid29546391, year = {2018}, author = {Kritzer, JA and Freyzon, Y and Lindquist, S}, title = {Yeast can accommodate phosphotyrosine: v-Src toxicity in yeast arises from a single disrupted pathway.}, journal = {FEMS yeast research}, volume = {18}, number = {3}, pages = {}, pmid = {29546391}, issn = {1567-1364}, support = {F32 NS055492/NS/NINDS NIH HHS/United States ; }, mesh = {*Genes, src ; Mitogen-Activated Protein Kinases/genetics ; Peptides, Cyclic/genetics ; Phosphorylation ; Phosphotyrosine/*metabolism ; Protein-Tyrosine Kinases/genetics ; Saccharomyces cerevisiae/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Signal Transduction ; Tyrosine/metabolism ; }, abstract = {Tyrosine phosphorylation is a key biochemical signal that controls growth and differentiation in multicellular organisms. Saccharomyces cerevisiae and nearly all other unicellular eukaryotes lack intact phosphotyrosine signaling pathways. However, many of these organisms have primitive phosphotyrosine-binding proteins and tyrosine phosphatases, leading to the assumption that the major barrier for emergence of phosphotyrosine signaling was the negative consequences of promiscuous tyrosine kinase activity. In this work, we reveal that the classic oncogene v-Src, which phosphorylates many dozens of proteins in yeast, is toxic because it disrupts a specific spore wall remodeling pathway. Using genetic selections, we find that expression of a specific cyclic peptide, or overexpression of SMK1, a MAP kinase that controls spore wall assembly, both lead to robust growth despite a continuous high level of phosphotyrosine in the yeast proteome. Thus, minimal genetic manipulations allow yeast to tolerate high levels of phosphotyrosine. These results indicate that the introduction of tyrosine kinases within single-celled organisms may not have been a major obstacle to the evolution of phosphotyrosine signaling.}, } @article {pmid29545531, year = {2018}, author = {Moroni, M and Servin-Vences, MR and Fleischer, R and Sánchez-Carranza, O and Lewin, GR}, title = {Voltage gating of mechanosensitive PIEZO channels.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {1096}, pmid = {29545531}, issn = {2041-1723}, mesh = {Animals ; Cell Line ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Evolution, Molecular ; Humans ; Ion Channels/genetics/*metabolism ; *Mechanotransduction, Cellular ; Mice ; Mutation, Missense ; Patch-Clamp Techniques ; Zebrafish ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage-gated mode. Mutations that cause human diseases, such as xerocytosis, profoundly shift voltage sensitivity of PIEZO1 channels toward the resting membrane potential and strongly promote voltage gating. Voltage modulation may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Older invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive, but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.}, } @article {pmid29545511, year = {2018}, author = {Rosenberg, AB and Roco, CM and Muscat, RA and Kuchina, A and Sample, P and Yao, Z and Graybuck, LT and Peeler, DJ and Mukherjee, S and Chen, W and Pun, SH and Sellers, DL and Tasic, B and Seelig, G}, title = {Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {176-182}, pmid = {29545511}, issn = {1095-9203}, support = {R01 CA207029/CA/NCI NIH HHS/United States ; R01 NS064404/NS/NINDS NIH HHS/United States ; R21 NS086500/NS/NINDS NIH HHS/United States ; TL1 TR002318/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Brain/*growth & development ; Cell Nucleus/genetics ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Developmental ; HEK293 Cells ; Humans ; Mice ; NIH 3T3 Cells ; Neurons/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis/*methods ; Spinal Cord/*growth & development ; *Transcriptome ; }, abstract = {To facilitate scalable profiling of single cells, we developed split-pool ligation-based transcriptome sequencing (SPLiT-seq), a single-cell RNA-seq (scRNA-seq) method that labels the cellular origin of RNA through combinatorial barcoding. SPLiT-seq is compatible with fixed cells or nuclei, allows efficient sample multiplexing, and requires no customized equipment. We used SPLiT-seq to analyze 156,049 single-nucleus transcriptomes from postnatal day 2 and 11 mouse brains and spinal cords. More than 100 cell types were identified, with gene expression patterns corresponding to cellular function, regional specificity, and stage of differentiation. Pseudotime analysis revealed transcriptional programs driving four developmental lineages, providing a snapshot of early postnatal development in the murine central nervous system. SPLiT-seq provides a path toward comprehensive single-cell transcriptomic analysis of other similarly complex multicellular systems.}, } @article {pmid29535324, year = {2018}, author = {Mukherjee, I and Large, RR and Corkrey, R and Danyushevsky, LV}, title = {The Boring Billion, a slingshot for Complex Life on Earth.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {4432}, pmid = {29535324}, issn = {2045-2322}, mesh = {Animals ; Biological Evolution ; Geologic Sediments/*chemistry ; Oceans and Seas ; Oxygen/metabolism ; Seawater/*chemistry ; Trace Elements/*analysis ; }, abstract = {The period 1800 to 800 Ma ("Boring Billion") is believed to mark a delay in the evolution of complex life, primarily due to low levels of oxygen in the atmosphere. Earlier studies highlight the remarkably flat C, Cr isotopes and low trace element trends during the so-called stasis, caused by prolonged nutrient, climatic, atmospheric and tectonic stability. In contrast, we suggest a first-order variability of bio-essential trace element availability in the oceans by combining systematic sampling of the Proterozoic rock record with sensitive geochemical analyses of marine pyrite by LA-ICP-MS technique. We also recall that several critical biological evolutionary events, such as the appearance of eukaryotes, origin of multicellularity & sexual reproduction, and the first major diversification of eukaryotes (crown group) occurred during this period. Therefore, it appears possible that the period of low nutrient trace elements (1800-1400 Ma) caused evolutionary pressures which became an essential trigger for promoting biological innovations in the eukaryotic domain. Later periods of stress-free conditions, with relatively high nutrient trace element concentration, facilitated diversification. We propose that the "Boring Billion" was a period of sequential stepwise evolution and diversification of complex eukaryotes, triggering evolutionary pathways that made possible the later rise of micro-metazoans and their macroscopic counterparts.}, } @article {pmid29524586, year = {2018}, author = {Heber-Katz, E and Messersmith, P}, title = {Drug delivery and epimorphic salamander-type mouse regeneration: A full parts and labor plan.}, journal = {Advanced drug delivery reviews}, volume = {129}, number = {}, pages = {254-261}, pmid = {29524586}, issn = {1872-8294}, support = {R01 CA180070/CA/NCI NIH HHS/United States ; R01 DE021104/DE/NIDCR NIH HHS/United States ; R01 DE021215/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; *Drug Delivery Systems ; Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors/metabolism ; Mice ; Mice, Inbred MRL lpr ; Prolyl-Hydroxylase Inhibitors/chemistry/*pharmacology ; Regeneration/*drug effects ; Caudata/*metabolism ; }, abstract = {The capacity to regenerate entire body parts, tissues, and organs had generally been thought to be lost in evolution with very few exceptions (e.g. the liver) surviving in mammals. The discovery of the MRL mouse and the elucidation of the underlying molecular pathway centering around hypoxia inducible factor, HIF-1α, has allowed a drug and materials approach to regeneration in mice and hopefully humans. The HIF-1α pathway is ancient and permitted the transition from unicellular to multicellular organisms. Furthermore, HIF-1α and its regulation by PHDs, important oxygen sensors in the cell, provides a perfect drug target. We review the historical background of regeneration biology, the discovery of the MRL mouse, and its underlying biology, and novel approaches to drugs, targets, and delivery systems (see Fig. 1).}, } @article {pmid29520890, year = {2018}, author = {Deevi, RK and Javadi, A and McClements, J and Vohhodina, J and Savage, K and Loughrey, MB and Evergren, E and Campbell, FC}, title = {Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.}, journal = {The Journal of pathology}, volume = {244}, number = {4}, pages = {445-459}, pmid = {29520890}, issn = {1096-9896}, support = {15342/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Caco-2 Cells ; Cell Proliferation ; Cell Shape ; Centrosome/*enzymology ; Chromosomal Instability ; Colorectal Neoplasms/*enzymology/genetics/pathology ; Cytoskeletal Proteins/genetics/metabolism ; Humans ; *Interphase ; Neoplasm Grading ; Phenotype ; Phosphoproteins/genetics/metabolism ; Protein Kinase C/genetics/*metabolism ; Signal Transduction ; Sodium-Hydrogen Exchangers/genetics/metabolism ; }, abstract = {Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring. PKCz regulates interdependent processes that control centrosome positioning. Among these, interaction between the cytoskeletal linker protein ezrin and its binding partner NHERF1 promotes the formation of a localized cue for anchoring interphase centrosomes to the cell cortex. Perturbation of these phenomena induced different outcomes in cells with single or extra centrosomes. Defective anchoring of a single centrosome promoted bipolar spindle misorientation, multi-lumen formation, and aberrant epithelial stratification. Collectively, these disturbances induce cribriform multicellular morphology that is typical of some categories of low-grade CRC. By contrast, defective anchoring of extra centrosomes promoted multipolar spindle formation, chromosomal instability (CIN), disruption of glandular morphology, and cell outgrowth across the extracellular matrix interface characteristic of aggressive, high-grade CRC. Because PKCz enhances apical NHERF1 intensity in 3D epithelial cultures, we used an immunohistochemical (IHC) assay of apical NHERF1 intensity as an indirect readout of PKCz activity in translational studies. We show that apical NHERF1 IHC intensity is inversely associated with multipolar spindle frequency and high-grade morphology in formalin-fixed human CRC samples. To conclude, defective PKCz control of interphase centrosome anchoring may underlie distinct categories of mitotic slippage that shape the development of low- or high-grade CRC phenotypes. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.}, } @article {pmid29512128, year = {2018}, author = {Flamier, A and Singh, S and Rasmussen, TP}, title = {Use of Human Embryoid Bodies for Teratology.}, journal = {Current protocols in toxicology}, volume = {75}, number = {}, pages = {13.13.1-13.13.14}, doi = {10.1002/cptx.38}, pmid = {29512128}, issn = {1934-9262}, mesh = {Embryoid Bodies/*drug effects ; Embryonic Stem Cells/drug effects ; Humans ; Pluripotent Stem Cells/drug effects ; Teratology/*methods ; Toxicity Tests/methods ; }, abstract = {Human birth defects are relatively common and can be caused by exposure to environmental teratogens or to pharmaceuticals with teratogenic activities. Human embryonic stem cells (hESCs), by virtue of their pluripotent nature, provide an excellent cellular platform for teratogen detection and risk assessment. This unit describes detailed protocols for the preparation and validation of highly pluripotent hESCs, the production of large quantities of aggregated multicellular spheroids composed of hESCs, and these spheroids' differentiation into embryoid bodies (EBs). EBs contain a variety of cells of endodermal, ectodermal, and mesodermal origin and can be subjected to compound exposure in vitro. Hence, they are useful for the detection of chemicals with teratogenic activities. Beyond describing protocols to assemble and culture EBs, this unit details methods to exploit the EB system for teratological assessment. In addition, strategies to distinguish compounds with bona fide teratogenic activity versus simple toxicity are discussed. © 2018 by John Wiley & Sons, Inc.}, } @article {pmid29500366, year = {2018}, author = {Langford, MB and Outhwaite, JE and Hughes, M and Natale, DRC and Simmons, DG}, title = {Deletion of the Syncytin A receptor Ly6e impairs syncytiotrophoblast fusion and placental morphogenesis causing embryonic lethality in mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {3961}, pmid = {29500366}, issn = {2045-2322}, mesh = {Animals ; Antigens, Surface/*genetics ; *Cell Fusion ; Cell Proliferation/genetics ; Cells, Cultured ; Female ; GPI-Linked Proteins/*genetics ; *Genes, Lethal ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Morphogenesis ; Neovascularization, Physiologic ; Placenta/blood supply/*cytology ; Pregnancy ; Trophoblasts/*cytology ; }, abstract = {Fetal growth and survival is dependent on the elaboration and propinquity of the fetal and maternal circulations within the placenta. Central to this is the formation of the interhaemal membrane, a multi-cellular lamina facilitating exchange of oxygen, nutrients and metabolic waste products between the mother and fetus. In rodents, this cellular barrier contains two transporting layers of syncytiotrophoblast, which are multinucleated cells that form by cell-cell fusion. Previously, we reported the expression of the GPI-linked cell surface protein LY6E by the syncytial layer closest to the maternal sinusoids of the mouse placenta (syncytiotrophoblast layer I). LY6E has since been shown to be a putative receptor for the fusogenic protein responsible for fusion of syncytiotrophoblast layer I, Syncytin A. In this report, we demonstrate that LY6E is essential for the normal fusion of syncytiotrophoblast layer I, and for the proper morphogenesis of both fetal and maternal vasculatures within the placenta. Furthermore, specific inactivation of Ly6e in the epiblast, but not in placenta, is compatible with embryonic development, indicating the embryonic lethality reported for Ly6e[-/-] embryos is most likely placental in origin.}, } @article {pmid29499253, year = {2018}, author = {Wood, KE and Komarova, NL}, title = {Cooperation-based branching as a mechanism of evolutionary speciation.}, journal = {Journal of theoretical biology}, volume = {445}, number = {}, pages = {166-186}, doi = {10.1016/j.jtbi.2018.02.033}, pmid = {29499253}, issn = {1095-8541}, support = {U01 CA187956/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*physiology ; *Biological Evolution ; Insecta/*physiology ; *Models, Biological ; *Social Behavior ; }, abstract = {When performing complex tasks, coexistence of organisms in a shared environment can be achieved by means of different strategies. For example, individuals can evolve to complete all parts of the complex task, choosing self-sufficiency over cooperation. On the other hand, they may choose to split parts of the task and share the products for mutual benefit, such that distinct groups of the organisms specialize on a subset of elementary tasks. In contrast to the existing theory of specialization and task sharing for cells in multicellular organisms (or colonies of social insects), here we describe a mechanism of evolutionary branching which is based on cooperation and division of labor, and where selection happens at the individual level. Using a class of mathematical models and the methodology of adaptive dynamics, we investigate the conditions for such branching into distinct cooperating subgroups to occur. We show that, as long as performing multiple tasks is associated with additional cost, branching occurs for a wide parameter range, and this scenario is stable against the invasion of cheaters. We hypothesize that over time, this can lead to evolutionary speciation. Examples from bacterial evolution and the connection with the Black Queen Hypothesis are discussed. It is our hope that the theory of diversification rooted in cooperation may inspire further ecological research to identify more evolutionary examples consistent with this speciation mechanism.}, } @article {pmid29487180, year = {2018}, author = {Cardon, ZG and Peredo, EL and Dohnalkova, AC and Gershone, HL and Bezanilla, M}, title = {A model suite of green algae within the Scenedesmaceae for investigating contrasting desiccation tolerance and morphology.}, journal = {Journal of cell science}, volume = {131}, number = {7}, pages = {}, doi = {10.1242/jcs.212233}, pmid = {29487180}, issn = {1477-9137}, mesh = {Cell Nucleus/chemistry/genetics/ultrastructure ; Chlorophyceae/classification/*genetics/growth & development ; Chlorophyta/*genetics/growth & development/ultrastructure ; Cytokinesis/genetics ; Ecosystem ; Golgi Apparatus/chemistry/ultrastructure ; Light ; Photosynthesis/*genetics ; *Phylogeny ; Reactive Oxygen Species/metabolism ; Time-Lapse Imaging ; }, abstract = {Microscopic green algae inhabiting desert microbiotic crusts are remarkably diverse phylogenetically, and many desert lineages have independently evolved from aquatic ancestors. Here we worked with five desert and aquatic species within the family Scenedesmaceae to examine mechanisms that underlie desiccation tolerance and release of unicellular versus multicellular progeny. Live cell staining and time-lapse confocal imaging coupled with transmission electron microscopy established that the desert and aquatic species all divide by multiple (rather than binary) fission, although progeny were unicellular in three species and multicellular (joined in a sheet-like coenobium) in two. During division, Golgi complexes were localized near nuclei, and all species exhibited dynamic rotation of the daughter cell mass within the mother cell wall at cytokinesis. Differential desiccation tolerance across the five species, assessed from photosynthetic efficiency during desiccation/rehydration cycles, was accompanied by differential accumulation of intracellular reactive oxygen species (ROS) detected using a dye sensitive to intracellular ROS. Further comparative investigation will aim to understand the genetic, ultrastructural and physiological characteristics supporting unicellular versus multicellular coenobial morphology, and the ability of representatives in the Scenedesmaceae to colonize ecologically diverse, even extreme, habitats.}, } @article {pmid29475741, year = {2018}, author = {Thomas, F and Kareva, I and Raven, N and Hamede, R and Pujol, P and Roche, B and Ujvari, B}, title = {Evolved Dependence in Response to Cancer.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {269-276}, doi = {10.1016/j.tree.2018.01.012}, pmid = {29475741}, issn = {1872-8383}, mesh = {*Biological Evolution ; Eukaryota/*genetics ; Evolution, Molecular ; Neoplasms/*genetics/prevention & control/therapy ; *Selection, Genetic ; }, abstract = {Evolved dependence is a process through which one species becomes 'dependent' on another following a long evolutionary history of interaction. This happens when adaptations selected in the first species for interacting lead to fitness costs when the second species is not encountered. Evolved dependence is frequent in host-parasite interactions, where hosts may achieve a higher fitness in the presence of the parasite than in its absence. Since oncogenic manifestations are (i) ubiquitous across multicellular life, (ii) involved in parasitic-like interactions with their hosts, and (iii) have effectively driven the selection of numerous adaptations, it is possible that multicellular organisms display evolved dependence in response to oncogenic processes. We provide a comprehensive overview of the topic, including the implications for cancer prevention and treatment.}, } @article {pmid29461501, year = {2018}, author = {Żółtowska-Aksamitowska, S and Shaala, LA and Youssef, DTA and Elhady, SS and Tsurkan, MV and Petrenko, I and Wysokowski, M and Tabachnick, K and Meissner, H and Ivanenko, VN and Bechmann, N and Joseph, Y and Jesionowski, T and Ehrlich, H}, title = {First Report on Chitin in a Non-Verongiid Marine Demosponge: The Mycale euplectellioides Case.}, journal = {Marine drugs}, volume = {16}, number = {2}, pages = {}, pmid = {29461501}, issn = {1660-3397}, mesh = {Animals ; Aquatic Organisms/chemistry/*metabolism ; Biocompatible Materials/chemistry ; Biomimetics/methods ; Chitin/*chemistry/*metabolism ; Chitinases/metabolism ; Microscopy, Electron, Scanning/methods ; Porifera/*chemistry/*metabolism ; Skeleton/chemistry/metabolism ; Spectroscopy, Fourier Transform Infrared/methods ; Spectrum Analysis, Raman/methods ; Tissue Engineering/methods ; }, abstract = {Sponges (Porifera) are recognized as aquatic multicellular organisms which developed an effective biochemical pathway over millions of years of evolution to produce both biologically active secondary metabolites and biopolymer-based skeletal structures. Among marine demosponges, only representatives of the Verongiida order are known to synthetize biologically active substances as well as skeletons made of structural polysaccharide chitin. The unique three-dimensional (3D) architecture of such chitinous skeletons opens the widow for their recent applications as adsorbents, as well as scaffolds for tissue engineering and biomimetics. This study has the ambitious goal of monitoring other orders beyond Verongiida demosponges and finding alternative sources of naturally prestructured chitinous scaffolds; especially in those demosponge species which can be cultivated at large scales using marine farming conditions. Special attention has been paid to the demosponge Mycale euplectellioides(Heteroscleromorpha: Poecilosclerida: Mycalidae) collected in the Red Sea. For the first time, we present here a detailed study of the isolation of chitin from the skeleton of this sponge, as well as its identification using diverse bioanalytical tools. Calcofluor white staining, Fourier-transform Infrared Spcetcroscopy (FTIR), electrospray ionization mass spectrometry (ESI-MS), scanning electron microscopy (SEM), and fluorescence microscopy, as well as a chitinase digestion assay were applied in order to confirm with strong evidence the finding of a-chitin in the skeleton of M. euplectellioides. We suggest that the discovery of chitin within representatives of the Mycale genus is a promising step in their evaluation of these globally distributed sponges as new renewable sources for both biologically active metabolites and chitin, which are of prospective use for pharmacology and biomaterials oriented biomedicine, respectively.}, } @article {pmid29442314, year = {2018}, author = {Aruga, J and Hatayama, M}, title = {Comparative Genomics of the Zic Family Genes.}, journal = {Advances in experimental medicine and biology}, volume = {1046}, number = {}, pages = {3-26}, doi = {10.1007/978-981-10-7311-3_1}, pmid = {29442314}, issn = {0065-2598}, mesh = {Animals ; *Evolution, Molecular ; Humans ; Multigene Family/*physiology ; *Phylogeny ; Protein Domains ; Species Specificity ; *Transcription Factors/genetics/metabolism ; Zinc Fingers/*physiology ; }, abstract = {Zic family genes encode five C2H2-type zinc finger domain-containing proteins that have many roles in animal development and maintenance. Recent phylogenetic analyses showed that Zic family genes are distributed in metazoans (multicellular animals), except Porifera (sponges) and Ctenophora (comb jellies). The sequence comparisons revealed that the zinc finger domains were absolutely conserved among the Zic family genes. Zic zinc finger domains are similar to, but distinct from those of the Gli, Glis, and Nkl gene family, and these zinc finger protein families are proposed to have been derived from a common ancestor gene. The Gli-Glis-Nkl-Zic superfamily and some other eukaryotic zinc finger proteins share a tandem CWCH2 (tCWCH2) motif, a hallmark for inter-zinc finger interaction between two adjacent C2H2 zinc fingers. In Zic family proteins, there exist additional evolutionally conserved domains known as ZOC and ZFNC, both of which may have appeared before cnidarian-bilaterian divergence. Comparison of the exon-intron boundaries in the Zic zinc finger domains revealed an intron (A-intron) that was absolutely conserved in bilaterians (metazoans with bilateral symmetry) and a placozoan (a simple nonparasitic metazoan). In vertebrates, there are five to seven Zic paralogs among which Zic1, Zic2, and Zic3 are generated through a tandem gene duplication and carboxy-terminal truncation in a vertebrate common ancestor, sharing a conserved carboxy-terminal sequence. Several hypotheses have been proposed to explain the Zic family phylogeny, including their origin, unique features in the first and second zinc finger motif, evolution of the nuclear localization signal, significance of the animal taxa-selective degeneration, gene multiplication in the vertebrate lineage, and involvement in the evolutionary alteration of the animal body plan.}, } @article {pmid29440299, year = {2018}, author = {Simonini, S and Stephenson, P and Østergaard, L}, title = {A molecular framework controlling style morphology in Brassicaceae.}, journal = {Development (Cambridge, England)}, volume = {145}, number = {5}, pages = {}, pmid = {29440299}, issn = {1477-9129}, support = {BBS/E/J/000PR9788/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M004112/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/J/000PR9773/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/J/00000613/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004588/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P013511/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Brassicaceae/*genetics/*growth & development ; Flowers/anatomy & histology/*genetics/*growth & development ; Gene Expression Regulation, Developmental/drug effects ; Gene Expression Regulation, Plant/drug effects ; Indoleacetic Acids/pharmacology ; Phenotype ; Plant Development/drug effects/*genetics ; Plant Growth Regulators/pharmacology ; Plants, Genetically Modified ; Transcription Factors/physiology ; }, abstract = {Organ formation in multicellular organisms depends on the coordinated activities of regulatory components that integrate developmental and hormonal cues to control gene expression and mediate cell-type specification. For example, development of the Arabidopsis gynoecium is tightly controlled by distribution and synthesis of the plant hormone auxin. The functions of several transcription factors (TFs) have been linked with auxin dynamics during gynoecium development; yet how their activities are coordinated is not known. Here, we show that five such TFs function together to ensure polarity establishment at the gynoecium apex. The auxin response factor ETTIN (ARF3; herein, ETT) is a central component of this framework. Interaction of ETT with TF partners is sensitive to the presence of auxin and our results suggest that ETT forms part of a repressive gene-regulatory complex. We show that this function is conserved between members of the Brassicaceae family and that variation in an ETT subdomain affects interaction strengths and gynoecium morphology. These results suggest that variation in affinities between conserved TFs can lead to morphological differences and thus contribute to the evolution of diverse organ shapes.}, } @article {pmid29439203, year = {2018}, author = {Mori, T and Cahn, JKB and Wilson, MC and Meoded, RA and Wiebach, V and Martinez, AFC and Helfrich, EJN and Albersmeier, A and Wibberg, D and Dätwyler, S and Keren, R and Lavy, A and Rückert, C and Ilan, M and Kalinowski, J and Matsunaga, S and Takeyama, H and Piel, J}, title = {Single-bacterial genomics validates rich and varied specialized metabolism of uncultivated Entotheonella sponge symbionts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1718-1723}, pmid = {29439203}, issn = {1091-6490}, mesh = {Animals ; Bacteria/chemistry/genetics/isolation & purification ; *Bacterial Physiological Phenomena ; Bacterial Proteins/genetics/metabolism ; Genome, Bacterial ; Genomics ; Polyketides/metabolism ; *Symbiosis ; Theonella/chemistry/*microbiology/physiology ; }, abstract = {Marine sponges are prolific sources of unique bioactive natural products. The sponge Theonella swinhoei is represented by several distinct variants with largely nonoverlapping chemistry. For the Japanese chemotype Y harboring diverse complex polyketides and peptides, we previously provided genomic and functional evidence that a single symbiont, the filamentous, multicellular organism "Candidatus Entotheonella factor," produces almost all of these compounds. To obtain further insights into the chemistry of "Entotheonella," we investigated another phylotype, "Candidatus Entotheonella serta," present in the T. swinhoei WA sponge chemotype, a source of theonellamide- and misakinolide-type compounds. Unexpectedly, considering the lower chemical diversity, sequencing of individual bacterial filaments revealed an even larger number of biosynthetic gene regions than for Ca E. factor, with virtually no overlap. These included genes for misakinolide and theonellamide biosynthesis, the latter assigned by comparative genomic and metabolic analysis of a T. swinhoei chemotype from Israel, and by biochemical studies. The data suggest that both compound families, which were among the earliest model substances to study bacterial producers in sponges, originate from the same bacterium in T. swinhoei WA. They also add evidence that metabolic richness and variability could be a more general feature of Entotheonella symbionts.}, } @article {pmid29436502, year = {2018}, author = {Hörandl, E and Speijer, D}, title = {How oxygen gave rise to eukaryotic sex.}, journal = {Proceedings. Biological sciences}, volume = {285}, number = {1872}, pages = {}, pmid = {29436502}, issn = {1471-2954}, mesh = {*Biological Evolution ; Eukaryota/*physiology ; Oxygen/*metabolism ; Reactive Oxygen Species/metabolism ; *Sex ; Symbiosis/physiology ; }, abstract = {How did full meiotic eukaryotic sex evolve and what was the immediate advantage allowing it to develop? We propose that the crucial determinant can be found in internal reactive oxygen species (ROS) formation at the start of eukaryotic evolution approximately 2 × 10[9] years ago. The large amount of ROS coming from a bacterial endosymbiont gave rise to DNA damage and vast increases in host genome mutation rates. Eukaryogenesis and chromosome evolution represent adaptations to oxidative stress. The host, an archaeon, most probably already had repair mechanisms based on DNA pairing and recombination, and possibly some kind of primitive cell fusion mechanism. The detrimental effects of internal ROS formation on host genome integrity set the stage allowing evolution of meiotic sex from these humble beginnings. Basic meiotic mechanisms thus probably evolved in response to endogenous ROS production by the 'pre-mitochondrion'. This alternative to mitosis is crucial under novel, ROS-producing stress situations, like extensive motility or phagotrophy in heterotrophs and endosymbiontic photosynthesis in autotrophs. In multicellular eukaryotes with a germline-soma differentiation, meiotic sex with diploid-haploid cycles improved efficient purging of deleterious mutations. Constant pressure of endogenous ROS explains the ubiquitous maintenance of meiotic sex in practically all eukaryotic kingdoms. Here, we discuss the relevant observations underpinning this model.}, } @article {pmid29432421, year = {2018}, author = {Exposito-Alonso, M and Becker, C and Schuenemann, VJ and Reiter, E and Setzer, C and Slovak, R and Brachi, B and Hagmann, J and Grimm, DG and Chen, J and Busch, W and Bergelson, J and Ness, RW and Krause, J and Burbano, HA and Weigel, D}, title = {The rate and potential relevance of new mutations in a colonizing plant lineage.}, journal = {PLoS genetics}, volume = {14}, number = {2}, pages = {e1007155}, pmid = {29432421}, issn = {1553-7404}, mesh = {Arabidopsis/genetics/growth & development ; Crosses, Genetic ; Directed Molecular Evolution ; Evolution, Molecular ; Gene Flow/physiology ; *Genome, Plant ; Introduced Species ; Mutation/*physiology ; *Mutation Rate ; Phenotype ; Phylogeny ; Plant Development/*genetics ; Plant Weeds/genetics/growth & development ; Selection, Genetic ; Sequence Analysis, DNA ; }, abstract = {By following the evolution of populations that are initially genetically homogeneous, much can be learned about core biological principles. For example, it allows for detailed studies of the rate of emergence of de novo mutations and their change in frequency due to drift and selection. Unfortunately, in multicellular organisms with generation times of months or years, it is difficult to set up and carry out such experiments over many generations. An alternative is provided by "natural evolution experiments" that started from colonizations or invasions of new habitats by selfing lineages. With limited or missing gene flow from other lineages, new mutations and their effects can be easily detected. North America has been colonized in historic times by the plant Arabidopsis thaliana, and although multiple intercrossing lineages are found today, many of the individuals belong to a single lineage, HPG1. To determine in this lineage the rate of substitutions-the subset of mutations that survived natural selection and drift-, we have sequenced genomes from plants collected between 1863 and 2006. We identified 73 modern and 27 herbarium specimens that belonged to HPG1. Using the estimated substitution rate, we infer that the last common HPG1 ancestor lived in the early 17th century, when it was most likely introduced by chance from Europe. Mutations in coding regions are depleted in frequency compared to those in other portions of the genome, consistent with purifying selection. Nevertheless, a handful of mutations is found at high frequency in present-day populations. We link these to detectable phenotypic variance in traits of known ecological importance, life history and growth, which could reflect their adaptive value. Our work showcases how, by applying genomics methods to a combination of modern and historic samples from colonizing lineages, we can directly study new mutations and their potential evolutionary relevance.}, } @article {pmid29432146, year = {2018}, author = {Simonet, P and Gaget, K and Balmand, S and Ribeiro Lopes, M and Parisot, N and Buhler, K and Duport, G and Vulsteke, V and Febvay, G and Heddi, A and Charles, H and Callaerts, P and Calevro, F}, title = {Bacteriocyte cell death in the pea aphid/Buchnera symbiotic system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1819-E1828}, pmid = {29432146}, issn = {1091-6490}, mesh = {Animals ; Aphids/*microbiology ; Buchnera/*physiology ; Cell Death ; Lysosomes ; Symbiosis/*physiology ; }, abstract = {Symbiotic associations play a pivotal role in multicellular life by facilitating acquisition of new traits and expanding the ecological capabilities of organisms. In insects that are obligatorily dependent on intracellular bacterial symbionts, novel host cells (bacteriocytes) or organs (bacteriomes) have evolved for harboring beneficial microbial partners. The processes regulating the cellular life cycle of these endosymbiont-bearing cells, such as the cell-death mechanisms controlling their fate and elimination in response to host physiology, are fundamental questions in the biology of symbiosis. Here we report the discovery of a cell-death process involved in the degeneration of bacteriocytes in the hemipteran insect Acyrthosiphon pisum This process is activated progressively throughout aphid adulthood and exhibits morphological features distinct from known cell-death pathways. By combining electron microscopy, immunohistochemistry, and molecular analyses, we demonstrated that the initial event of bacteriocyte cell death is the cytoplasmic accumulation of nonautophagic vacuoles, followed by a sequence of cellular stress responses including the formation of autophagosomes in intervacuolar spaces, activation of reactive oxygen species, and Buchnera endosymbiont degradation by the lysosomal system. We showed that this multistep cell-death process originates from the endoplasmic reticulum, an organelle exhibiting a unique reticular network organization spread throughout the entire cytoplasm and surrounding Buchnera aphidicola endosymbionts. Our findings provide insights into the cellular and molecular processes that coordinate eukaryotic host and endosymbiont homeostasis and death in a symbiotic system and shed light on previously unknown aspects of bacteriocyte biological functioning.}, } @article {pmid29427837, year = {2018}, author = {Baldauf, SL and Romeralo, M and Fiz-Palacios, O and Heidari, N}, title = {A Deep Hidden Diversity of Dictyostelia.}, journal = {Protist}, volume = {169}, number = {1}, pages = {64-78}, doi = {10.1016/j.protis.2017.12.005}, pmid = {29427837}, issn = {1618-0941}, mesh = {*Biodiversity ; DNA Primers/genetics ; DNA, Protozoan/genetics ; DNA, Ribosomal/genetics ; Dictyostelium/classification/*genetics/isolation & purification ; Phylogeny ; Polymerase Chain Reaction ; }, abstract = {Dictyostelia is a monophyletic group of transiently multicellular (sorocarpic) amoebae, whose study is currently limited to laboratory culture. This tends to favour faster growing species with robust sorocarps, while species with smaller more delicate sorocarps constitute most of the group's taxonomic breadth. The number of known species is also small (∼150) given Dictyostelia's molecular depth and apparent antiquity (>600 myr). Nonetheless, dictyostelid sequences are rarely recovered in culture independent sampling (ciPCR) surveys. We developed ciPCR primers to specifically target dictyostelid small subunit (SSU or 18S) rDNA and tested them on total DNAs extracted from a wide range of soils from five continents. The resulting clone libraries show mostly dictyostelid sequences (∼90%), and phylogenetic analyses of these sequences indicate novel lineages in all four dictyostelid families and most genera. This is especially true for the species-rich Heterostelium and Dictyosteliaceae but also the less species-rich Raperosteliaceae. However, the most novel deep branches are found in two very species-poor taxa, including the deepest branch yet seen in the highly divergent Cavenderiaceae. These results confirm a deep hidden diversity of Dictyostelia, potentially including novel morphologies and developmental schemes. The primers and protocols presented here should also enable more comprehensive studies of dictyostelid ecology.}, } @article {pmid29425731, year = {2018}, author = {Israel, MR and Morgan, M and Tay, B and Deuis, JR}, title = {Toxins as tools: Fingerprinting neuronal pharmacology.}, journal = {Neuroscience letters}, volume = {679}, number = {}, pages = {4-14}, doi = {10.1016/j.neulet.2018.02.001}, pmid = {29425731}, issn = {1872-7972}, mesh = {Animals ; Behavior Rating Scale ; Electrophysiology/methods ; Humans ; Ion Channel Gating/drug effects ; Ion Channels/chemistry/metabolism/pharmacology ; Models, Animal ; Neurons/*drug effects/physiology ; Neuropharmacology/*methods ; Neurotoxins/*pharmacology/*therapeutic use ; Sensory Receptor Cells/chemistry/*metabolism ; }, abstract = {Toxins have been used as tools for decades to study the structure and function of neuronal ion channels and receptors. The biological origin of these toxins varies from single cell organisms, including bacteria and algae, to complex multicellular organisms, including a wide variety of plants and venomous animals. Toxins are a structurally and functionally diverse group of compounds that often modulate neuronal function by interacting with an ion channel or receptor. Many of these toxins display high affinity and exquisite selectivity, making them valuable tools to probe the structure and function of neuronal ion channels and receptors. This review article provides an overview of the experimental techniques used to assess the effects that toxins have on neuronal function, as well as discussion on toxins that have been used as tools, with a focus on toxins that target voltage-gated and ligand-gated ion channels.}, } @article {pmid29424391, year = {2018}, author = {Cipriano, JLD and Cruz, ACF and Mancini, KC and Schmildt, ER and Lopes, JC and Otoni, WC and Alexandre, RS}, title = {Somatic embryogenesis in Carica papaya as affected by auxins and explants, and morphoanatomical-related aspects.}, journal = {Anais da Academia Brasileira de Ciencias}, volume = {90}, number = {1}, pages = {385-400}, doi = {10.1590/0001-3765201820160252}, pmid = {29424391}, issn = {1678-2690}, mesh = {Abscisic Acid/pharmacology ; Carica/anatomy & histology/drug effects/*embryology/*physiology ; Culture Media ; Germination/drug effects/physiology ; Indoleacetic Acids/*analysis ; Microscopy, Electron, Scanning ; Plant Growth Regulators/pharmacology ; Plant Leaves/drug effects/physiology ; Plant Shoots/drug effects/*physiology ; Plant Somatic Embryogenesis Techniques/*methods ; Reference Values ; Reproducibility of Results ; Time Factors ; }, abstract = {The aim of this study was to evaluate somatic embryogenesis in juvenile explants of the THB papaya cultivar. Apical shoots and cotyledonary leaves were inoculated in an induction medium composed of different concentrations of 2,4-D (6, 9, 12, 15 and 18 µM) or 4-CPA (19, 22, 25, 28 and 31 µM). The embryogenic calluses were transferred to a maturation medium for 30 days. Histological analysis were done during the induction and scanning electron microscopy after maturing. For both types of auxin, embryogenesis was achieved at higher frequencies with cotyledonary leaves incubated in induction medium than with apical shoots; except for callogenesis. The early-stage embryos (e.g., globular or heart-shape) predominated. Among the auxins, best results were observed in cotyledonary leaves induced with 4-CPA (25 µM). Histological analyses of the cotyledonary leaf-derived calluses confirmed that the somatic embryos (SEs) formed from parenchyma cells, predominantly differentiated via indirect and multicellular origin and infrequently via synchronized embryogenesis. The secondary embryogenesis was observed during induction and maturation phases in papaya THB cultivar. The combination of ABA (0.5 µM) and AC (15 g L-1) in maturation medium resulted in the highest somatic embryogenesis induction frequency (70 SEs callus-1) and the lowest percentage of early germination (4%).}, } @article {pmid29422410, year = {2018}, author = {Potjewyd, G and Moxon, S and Wang, T and Domingos, M and Hooper, NM}, title = {Tissue Engineering 3D Neurovascular Units: A Biomaterials and Bioprinting Perspective.}, journal = {Trends in biotechnology}, volume = {36}, number = {4}, pages = {457-472}, doi = {10.1016/j.tibtech.2018.01.003}, pmid = {29422410}, issn = {1879-3096}, support = {MR/L023784/1/MRC_/Medical Research Council/United Kingdom ; NC/K001744/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; PG/12/31/29527/BHF_/British Heart Foundation/United Kingdom ; MR/L023784/2/MRC_/Medical Research Council/United Kingdom ; MC_PC_16033/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Biocompatible Materials/*chemistry ; *Bioprinting ; Brain Diseases/therapy ; Extracellular Matrix/chemistry ; Humans ; Hydrogels/chemistry ; Models, Animal ; Neuroglia/chemistry ; Neurons/chemistry ; *Printing, Three-Dimensional ; *Tissue Engineering ; }, abstract = {Neurovascular dysfunction is a central process in the pathogenesis of stroke and most neurodegenerative diseases, including Alzheimer's disease. The multicellular neurovascular unit (NVU) combines the neural, vascular and extracellular matrix (ECM) components in an important interface whose correct functioning is critical to maintain brain health. Tissue engineering is now offering new tools and insights to advance our understanding of NVU function. Here, we review how the use of novel biomaterials to mimic the mechanical and functional cues of the ECM, coupled with precisely layered deposition of the different cells of the NVU through 3D bioprinting, is revolutionising the study of neurovascular function and dysfunction.}, } @article {pmid29415511, year = {2018}, author = {Henderson, SW and Wege, S and Gilliham, M}, title = {Plant Cation-Chloride Cotransporters (CCC): Evolutionary Origins and Functional Insights.}, journal = {International journal of molecular sciences}, volume = {19}, number = {2}, pages = {}, pmid = {29415511}, issn = {1422-0067}, mesh = {Biological Evolution ; Gene Expression ; Homeostasis ; Ions/metabolism ; Phenotype ; Plant Development/genetics ; Plant Proteins/genetics/*metabolism ; Plants/classification/drug effects/genetics/*metabolism ; Sodium-Potassium-Chloride Symporters/genetics/*metabolism ; Water/metabolism ; }, abstract = {Genomes of unicellular and multicellular green algae, mosses, grasses and dicots harbor genes encoding cation-chloride cotransporters (CCC). CCC proteins from the plant kingdom have been comparatively less well investigated than their animal counterparts, but proteins from both plants and animals have been shown to mediate ion fluxes, and are involved in regulation of osmotic processes. In this review, we show that CCC proteins from plants form two distinct phylogenetic clades (CCC1 and CCC2). Some lycophytes and bryophytes possess members from each clade, most land plants only have members of the CCC1 clade, and green algae possess only the CCC2 clade. It is currently unknown whether CCC1 and CCC2 proteins have similar or distinct functions, however they are both more closely related to animal KCC proteins compared to NKCCs. Existing heterologous expression systems that have been used to functionally characterize plant CCC proteins, namely yeast and Xenopus laevis oocytes, have limitations that are discussed. Studies from plants exposed to chemical inhibitors of animal CCC protein function are reviewed for their potential to discern CCC function in planta. Thus far, mutations in plant CCC genes have been evaluated only in two species of angiosperms, and such mutations cause a diverse array of phenotypes-seemingly more than could simply be explained by localized disruption of ion transport alone. We evaluate the putative roles of plant CCC proteins and suggest areas for future investigation.}, } @article {pmid29413517, year = {2018}, author = {Gavish, M and Veenman, L}, title = {Regulation of Mitochondrial, Cellular, and Organismal Functions by TSPO.}, journal = {Advances in pharmacology (San Diego, Calif.)}, volume = {82}, number = {}, pages = {103-136}, doi = {10.1016/bs.apha.2017.09.004}, pmid = {29413517}, issn = {1557-8925}, mesh = {Animals ; Evolution, Molecular ; Genes, Essential ; Homeostasis ; Humans ; Mitochondria/*metabolism ; Reactive Oxygen Species/metabolism ; Receptors, GABA/*metabolism ; }, abstract = {In 1999, the enigma of the 18kDa mitochondrial translocator protein (TSPO), also known as the peripheral-type benzodiazepine receptor, was the seeming disparity of the many functions attributed to TSPO, ranging from the potential of TSPO acting as a housekeeping gene at molecular biological levels to adaptations to stress, and even involvement in higher emotional and cognitive functioning, such as anxiety and depression. In the years since then, knowledge regarding the many functions modulated by TSPO has expanded, and understanding has deepened. In addition, new functions could be firmly associated with TSPO, such as regulation of programmed cell death and modulation of gene expression. Interestingly, control by the mitochondrial TSPO over both of these life and death functions appears to include Ca[++] homeostasis, generation of reactive oxygen species (ROS), and ATP production. Other mitochondrial functions under TSPO control are considered to be steroidogenesis and tetrapyrrole metabolism. As TSPO effects on gene expression and on programmed cell death can be related to the wide range of functions that can be associated with TSPO, several of these five elements of Ca[++], ROS, ATP, steroids, and tetrapyrroles may indeed form the basis of TSPO's capability to operate as a multifunctional housekeeping gene to maintain homeostasis of the cell and of the whole multicellular organism.}, } @article {pmid29411901, year = {2018}, author = {Taverne, YJ and Merkus, D and Bogers, AJ and Halliwell, B and Duncker, DJ and Lyons, TW}, title = {Reactive Oxygen Species: Radical Factors in the Evolution of Animal Life: A molecular timescale from Earth's earliest history to the rise of complex life.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {40}, number = {3}, pages = {}, doi = {10.1002/bies.201700158}, pmid = {29411901}, issn = {1521-1878}, mesh = {Animals ; Atmosphere/analysis ; Bacteria/chemistry/metabolism ; *Biological Evolution ; Earth, Planet ; Electron Transport ; Energy Metabolism ; *Origin of Life ; Oxidation-Reduction ; Oxygen/chemistry/*metabolism ; Photosynthesis/*physiology ; Plants/chemistry/*metabolism ; Reactive Oxygen Species/chemistry/*metabolism ; Time Factors ; }, abstract = {Introduction of O2 to Earth's early biosphere stimulated remarkable evolutionary adaptations, and a wide range of electron acceptors allowed diverse, energy-yielding metabolic pathways. Enzymatic reduction of O2 yielded a several-fold increase in energy production, enabling evolution of multi-cellular animal life. However, utilization of O2 also presented major challenges as O2 and many of its derived reactive oxygen species (ROS) are highly toxic, possibly impeding multicellular evolution after the Great Oxidation Event. Remarkably, ROS, and especially hydrogen peroxide, seem to play a major part in early diversification and further development of cellular respiration and other oxygenic pathways, thus becoming an intricate part of evolution of complex life. Hence, although harnessing of chemical and thermo-dynamic properties of O2 for aerobic metabolism is generally considered to be an evolutionary milestone, the ability to use ROS for cell signaling and regulation may have been the first true breakthrough in development of complex life.}, } @article {pmid29405978, year = {2018}, author = {Wechman, SL and Pradhan, AK and DeSalle, R and Das, SK and Emdad, L and Sarkar, D and Fisher, PB}, title = {New Insights Into Beclin-1: Evolution and Pan-Malignancy Inhibitor Activity.}, journal = {Advances in cancer research}, volume = {137}, number = {}, pages = {77-114}, pmid = {29405978}, issn = {2162-5557}, support = {K12 GM093857/GM/NIGMS NIH HHS/United States ; P30 CA016059/CA/NCI NIH HHS/United States ; R01 CA097318/CA/NCI NIH HHS/United States ; R01 CA168517/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*therapeutic use ; Beclin-1/*metabolism ; *Evolution, Molecular ; Genes, Tumor Suppressor ; Humans ; *Molecular Targeted Therapy ; Neoplasms/*drug therapy/*metabolism/pathology ; }, abstract = {Autophagy is a functionally conserved self-degradation process that facilitates the survival of eukaryotic life via the management of cellular bioenergetics and maintenance of the fidelity of genomic DNA. The first known autophagy inducer was Beclin-1. Beclin-1 is expressed in multicellular eukaryotes ranging throughout plants to animals, comprising a nonmonophyllic group, as shown in this report via aggressive BLAST searches. In humans, Beclin-1 is a haploinsuffient tumor suppressor as biallelic deletions have not been observed in patient tumors clinically. Therefore, Beclin-1 fails the Knudson hypothesis, implicating expression of at least one Beclin-1 allele is essential for cancer cell survival. However, Beclin-1 is frequently monoallelically deleted in advanced human cancers and the expression of two Beclin-1 allelles is associated with greater anticancer effects. Overall, experimental evidence suggests that Beclin-1 inhibits tumor formation, angiogenesis, and metastasis alone and in cooperation with the tumor suppressive molecules UVRAG, Bif-1, Ambra1, and MDA-7/IL-24 via diverse mechanisms of action. Conversely, Beclin-1 is upregulated in cancer stem cells (CSCs), portending a role in cancer recurrence, and highlighting this molecule as an intriguing molecular target for the treatment of CSCs. Many aspects of Beclin-1's biological effects remain to be studied. The consequences of these BLAST searches on the molecular evolution of Beclin-1, and the eukaryotic branches of the tree of life, are discussed here in greater detail with future inquiry focused upon protist taxa. Also in this review, the effects of Beclin-1 on tumor suppression and cancer malignancy are discussed. Beclin-1 holds significant promise for the development of novel targeted cancer therapeutics and is anticipated to lead to a many advances in our understanding of eukaryotic evolution, multicellularity, and even the treatment of CSCs in the coming decades.}, } @article {pmid29400699, year = {2018}, author = {Ćetković, H and Bosnar, MH and Perina, D and Mikoč, A and Deželjin, M and Belužić, R and Bilandžija, H and Ruiz-Trillo, I and Harcet, M}, title = {Characterization of a group I Nme protein of Capsaspora owczarzaki-a close unicellular relative of animals.}, journal = {Laboratory investigation; a journal of technical methods and pathology}, volume = {98}, number = {3}, pages = {304-314}, pmid = {29400699}, issn = {1530-0307}, mesh = {Amino Acid Sequence ; Cell Migration Assays ; *Cell Movement ; Eukaryota/*enzymology/genetics ; Evolution, Molecular ; HeLa Cells ; Humans ; NM23 Nucleoside Diphosphate Kinases/chemistry/genetics/*metabolism ; }, abstract = {Nucleoside diphosphate kinases are enzymes present in all domains of life. In animals, they are called Nme or Nm23 proteins, and are divided into group I and II. Human Nme1 was the first protein identified as a metastasis suppressor. Because of its medical importance, it has been extensively studied. In spite of the large research effort, the exact mechanism of metastasis suppression remains unclear. It is unknown which of the biochemical properties or biological functions are responsible for the antimetastatic role of the mammalian Nme1. Furthermore, it is not clear at which point in the evolution of life group I Nme proteins acquired the potential to suppress metastasis, a process that is usually associated with complex animals. In this study we performed a series of tests and assays on a group I Nme protein from filasterean Capsaspora owczarzaki, a close unicellular relative of animals. The aim was to compare the protein to the well-known human Nme1 and Nme2 homologs, as well as with the homolog from a simple animal-sponge (Porifera), in order to see how the proteins changed with the transition to multicellularity, and subsequently in the evolution of complex animals. We found that premetazoan-type protein is highly similar to the homologs from sponge and human, in terms of biochemical characteristics and potential biological functions. Like the human Nme1 and Nme2, it is able to diminish the migratory potential of human cancer cells in culture.}, } @article {pmid29395928, year = {2018}, author = {Yamaoka, S and Nishihama, R and Yoshitake, Y and Ishida, S and Inoue, K and Saito, M and Okahashi, K and Bao, H and Nishida, H and Yamaguchi, K and Shigenobu, S and Ishizaki, K and Yamato, KT and Kohchi, T}, title = {Generative Cell Specification Requires Transcription Factors Evolutionarily Conserved in Land Plants.}, journal = {Current biology : CB}, volume = {28}, number = {3}, pages = {479-486.e5}, doi = {10.1016/j.cub.2017.12.053}, pmid = {29395928}, issn = {1879-0445}, mesh = {Basic Helix-Loop-Helix Transcription Factors/*genetics/metabolism ; *Cell Differentiation ; *Evolution, Molecular ; Germ Cells, Plant/*growth & development/metabolism ; Marchantia/genetics/*physiology ; Phylogeny ; Plant Proteins/*genetics/metabolism ; }, abstract = {Land plants differentiate germ cells in the haploid gametophyte. In flowering plants, a generative cell is specified as a precursor that subsequently divides into two sperm cells in the developing male gametophyte, pollen. Generative cell specification requires cell-cycle control and microtubule-dependent nuclear relocation (reviewed in [1-3]). However, the generative cell fate determinant and its evolutionary origin are still unknown. In bryophytes, gametophytes produce eggs and sperm in multicellular reproductive organs called archegonia and antheridia, respectively, or collectively called gametangia. Given the monophyletic origin of land plants [4-6], evolutionarily conserved mechanisms may play key roles in these diverse reproductive processes. Here, we showed that a single member of the subfamily VIIIa of basic helix-loop-helix (bHLH) transcription factors in the liverwort Marchantia polymorpha primarily accumulated in the initial cells and controlled their development into gametangia. We then demonstrated that an Arabidopsis thaliana VIIIa bHLH transiently accumulated in the smaller daughter cell after an asymmetric division of the meiosis-derived microspore and was required for generative cell specification redundantly with its paralog. Furthermore, these A. thaliana VIIIa bHLHs were functionally replaceable by the M. polymorpha VIIIa bHLH. These findings suggest the VIIIa bHLH proteins as core regulators for reproductive development, including germ cell differentiation, since an early stage of land plant evolution.}, } @article {pmid29394379, year = {2018}, author = {Niklas, KJ and Dunker, AK and Yruela, I}, title = {The evolutionary origins of cell type diversification and the role of intrinsically disordered proteins.}, journal = {Journal of experimental botany}, volume = {69}, number = {7}, pages = {1437-1446}, doi = {10.1093/jxb/erx493}, pmid = {29394379}, issn = {1460-2431}, mesh = {*Alternative Splicing ; Cell Proliferation ; Eukaryotic Cells/*cytology/metabolism ; *Evolution, Molecular ; Gene Regulatory Networks/*physiology ; Genes, Plant ; Intrinsically Disordered Proteins/genetics/*metabolism ; Plant Proteins/genetics/*metabolism ; *Protein Processing, Post-Translational ; RNA, Messenger/genetics/metabolism ; }, abstract = {The evolution of complex multicellular life forms occurred multiple times and was attended by cell type specialization. We review seven lines of evidence indicating that intrinsically disordered/ductile proteins (IDPs) played a significant role in the evolution of multicellularity and cell type specification: (i) most eukaryotic transcription factors (TFs) and multifunctional enzymes contain disproportionately long IDP sequences (≥30 residues in length), whereas highly conserved enzymes are normally IDP region poor; (ii) ~80% of the proteome involved in development are IDPs; (iii) the majority of proteins undergoing alternative splicing (AS) of pre-mRNA contain significant IDP regions; (iv) proteins encoded by DNA regions flanking crossing-over 'hot spots' are significantly enriched in IDP regions; (v) IDP regions are disproportionately subject to combinatorial post-translational modifications (PTMs) as well as AS; (vi) proteins involved in transcription and RNA processing are enriched in IDP regions; and (vii) a strong positive correlation exists between the number of different cell types and the IDP proteome fraction across a broad spectrum of uni- and multicellular algae, plants, and animals. We argue that the multifunctionalities conferred by IDPs and the disproportionate involvement of IDPs with AS and PTMs provided a IDP-AS-PTM 'motif' that significantly contributed to the evolution of multicellularity in all major eukaryotic lineages.}, } @article {pmid29385672, year = {2018}, author = {Park, B and Shin, DY and Jeon, TJ}, title = {CBP7 Interferes with the Multicellular Development of Dictyostelium Cells by Inhibiting Chemoattractant-Mediated Cell Aggregation.}, journal = {Molecules and cells}, volume = {41}, number = {2}, pages = {103-109}, pmid = {29385672}, issn = {0219-1032}, mesh = {Calcium/metabolism ; Calcium-Binding Proteins/classification/genetics/*metabolism ; Chemotactic Factors/genetics/metabolism ; *Chemotaxis ; Cyclic AMP/metabolism ; Dictyostelium/cytology/genetics/*metabolism ; Movement ; Phylogeny ; *Signal Transduction ; }, abstract = {Calcium ions are involved in the regulation of diverse cellular processes. Fourteen genes encoding calcium binding proteins have been identified in Dictyostelium. CBP7, one of the 14 CBPs, is composed of 169 amino acids and contains four EF-hand motifs. Here, we investigated the roles of CBP7 in the development and cell migration of Dictyostelium cells and found that high levels of CBP7 exerted a negative effect on cells aggregation during development, possibly by inhibiting chemoattractant-directed cell migration. While cells lacking CBP7 exhibited normal development and chemotaxis similar that of wild-type cells, CBP7 overexpressing cells completely lost their chemotactic abilities to move toward increasing cAMP concentrations. This resulted in inhibition of cellular aggregation, a process required for forming multicellular organisms during development. Low levels of cytosolic free calcium were observed in CBP7 overexpressing cells, which was likely the underlying cause of their lack of chemotaxis. Our results demonstrate that CBP7 plays an important role in cell spreading and cell-substrate adhesion. cbp7 null cells showed decreased cell size and cell-substrate adhesion. The present study contributes to further understanding the role of calcium signaling in regulation of cell migration and development.}, } @article {pmid31162574, year = {2018}, author = {McGrath, C}, title = {Highlight: Origins of Multicellularity Revealed by Single-Celled Amoebae.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {705-706}, pmid = {31162574}, issn = {1759-6653}, mesh = {*Amoeba ; Biological Evolution ; Phylogeny ; }, } @article {pmid29381766, year = {2018}, author = {Boyd, M and Rosenzweig, F and Herron, MD}, title = {Analysis of motility in multicellular Chlamydomonas reinhardtii evolved under predation.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0192184}, pmid = {29381766}, issn = {1932-6203}, mesh = {Animals ; *Biological Evolution ; Chlamydomonas reinhardtii/*physiology ; *Predatory Behavior ; }, abstract = {The advent of multicellularity was a watershed event in the history of life, yet the transition from unicellularity to multicellularity is not well understood. Multicellularity opens up opportunities for innovations in intercellular communication, cooperation, and specialization, which can provide selective advantages under certain ecological conditions. The unicellular alga Chlamydomonas reinhardtii has never had a multicellular ancestor yet it is closely related to the volvocine algae, a clade containing taxa that range from simple unicells to large, specialized multicellular colonies. Simple multicellular structures have been observed to evolve in C. reinhardtii in response to predation or to settling rate-based selection. Structures formed in response to predation consist of individual cells confined within a shared transparent extracellular matrix. Evolved isolates form such structures obligately under culture conditions in which their wild type ancestors do not, indicating that newly-evolved multicellularity is heritable. C. reinhardtii is capable of photosynthesis, and possesses an eyespot and two flagella with which it moves towards or away from light in order to optimize input of radiant energy. Motility contributes to C. reinhardtii fitness because it allows cells or colonies to achieve this optimum. Utilizing phototaxis to assay motility, we determined that newly evolved multicellular strains do not exhibit significant directional movement, even though the flagellae of their constituent unicells are present and active. In C. reinhardtii the first steps towards multicellularity in response to predation appear to result in a trade-off between motility and differential survivorship, a trade-off that must be overcome by further genetic change to ensure long-term success of the new multicellular organism.}, } @article {pmid29381236, year = {2018}, author = {Li, Y and Zuo, S and Zhang, Z and Li, Z and Han, J and Chu, Z and Hasterok, R and Wang, K}, title = {Centromeric DNA characterization in the model grass Brachypodium distachyon provides insights on the evolution of the genus.}, journal = {The Plant journal : for cell and molecular biology}, volume = {93}, number = {6}, pages = {1088-1101}, doi = {10.1111/tpj.13832}, pmid = {29381236}, issn = {1365-313X}, mesh = {Amino Acid Sequence ; Brachypodium/classification/*genetics/metabolism ; Centromere/*genetics/metabolism ; Chromosomes, Plant/genetics/metabolism ; DNA, Plant/*genetics/metabolism ; Evolution, Molecular ; Genome, Plant/*genetics ; Histones/genetics/metabolism ; In Situ Hybridization, Fluorescence ; Nucleosomes/genetics/metabolism ; Phylogeny ; Plant Proteins/genetics/metabolism ; Polyploidy ; Protein Binding ; Sequence Homology, Amino Acid ; }, abstract = {Brachypodium distachyon is a well-established model monocot plant, and its small and compact genome has been used as an accurate reference for the much larger and often polyploid genomes of cereals such as Avena sativa (oats), Hordeum vulgare (barley) and Triticum aestivum (wheat). Centromeres are indispensable functional units of chromosomes and they play a core role in genome polyploidization events during evolution. As the Brachypodium genus contains about 20 species that differ significantly in terms of their basic chromosome numbers, genome size, ploidy levels and life strategies, studying their centromeres may provide important insight into the structure and evolution of the genome in this interesting and important genus. In this study, we isolated the centromeric DNA of the B. distachyon reference line Bd21 and characterized its composition via the chromatin immunoprecipitation of the nucleosomes that contain the centromere-specific histone CENH3. We revealed that the centromeres of Bd21 have the features of typical multicellular eukaryotic centromeres. Strikingly, these centromeres contain relatively few centromeric satellite DNAs; in particular, the centromere of chromosome 5 (Bd5) consists of only ~40 kb. Moreover, the centromeric retrotransposons in B. distachyon (CRBds) are evolutionarily young. These transposable elements are located both within and adjacent to the CENH3 binding domains, and have similar compositions. Moreover, based on the presence of CRBds in the centromeres, the species in this study can be grouped into two distinct lineages. This may provide new evidence regarding the phylogenetic relationships within the Brachypodium genus.}, } @article {pmid29378020, year = {2018}, author = {Hillmann, F and Forbes, G and Novohradská, S and Ferling, I and Riege, K and Groth, M and Westermann, M and Marz, M and Spaller, T and Winckler, T and Schaap, P and Glöckner, G}, title = {Multiple Roots of Fruiting Body Formation in Amoebozoa.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {591-606}, pmid = {29378020}, issn = {1759-6653}, mesh = {Amoebozoa/cytology/*genetics/*growth & development ; Cell Communication ; Dictyostelium/cytology/genetics/growth & development ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Phylogeny ; Protozoan Proteins/genetics ; Transcriptome ; }, abstract = {Establishment of multicellularity represents a major transition in eukaryote evolution. A subgroup of Amoebozoa, the dictyosteliids, has evolved a relatively simple aggregative multicellular stage resulting in a fruiting body supported by a stalk. Protosteloid amoeba, which are scattered throughout the amoebozoan tree, differ by producing only one or few single stalked spores. Thus, one obvious difference in the developmental cycle of protosteliids and dictyosteliids seems to be the establishment of multicellularity. To separate spore development from multicellular interactions, we compared the genome and transcriptome of a Protostelium species (Protostelium aurantium var. fungivorum) with those of social and solitary members of the Amoebozoa. During fruiting body formation nearly 4,000 genes, corresponding to specific pathways required for differentiation processes, are upregulated. A comparison with genes involved in the development of dictyosteliids revealed conservation of >500 genes, but most of them are also present in Acanthamoeba castellanii for which fruiting bodies have not been documented. Moreover, expression regulation of those genes differs between P. aurantium and Dictyostelium discoideum. Within Amoebozoa differentiation to fruiting bodies is common, but our current genome analysis suggests that protosteliids and dictyosteliids used different routes to achieve this. Most remarkable is both the large repertoire and diversity between species in genes that mediate environmental sensing and signal processing. This likely reflects an immense adaptability of the single cell stage to varying environmental conditions. We surmise that this signaling repertoire provided sufficient building blocks to accommodate the relatively simple demands for cell-cell communication in the early multicellular forms.}, } @article {pmid29373067, year = {2017}, author = {Lindström, JB and Pierce, NT and Latz, MI}, title = {Role of TRP Channels in Dinoflagellate Mechanotransduction.}, journal = {The Biological bulletin}, volume = {233}, number = {2}, pages = {151-167}, doi = {10.1086/695421}, pmid = {29373067}, issn = {1939-8697}, mesh = {Biological Evolution ; Dinoflagellida/classification/genetics/*physiology ; Signal Transduction/genetics ; Transient Receptor Potential Channels/genetics/*metabolism ; }, abstract = {Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences. In a phylogenetic tree including all mammalian TRP subfamilies and TRP channel sequences from unicellular and multicellular organisms, the L. polyedra sequences grouped with the TRPM, TPPML, and TRPP clades. In pharmacological experiments, we used the intrinsic bioluminescence of L. polyedra as a reporter of mechanoresponsivity. Capsaicin and RN1734, agonists of mammalian TRPV, and arachidonic acid, an agonist of mammalian TRPV, TRPA, TRPM, and Drosophila TRP, all stimulated bioluminescence in L. polyedra. Mechanical stimulation of bioluminescence, but not capsaicin-stimulated bioluminescence, was inhibited by gadolinium (Gd[3+]), a general inhibitor of mechanosensitive ion channels, and the phospholipase C (PLC) inhibitor U73122. These pharmacological results are consistent with the involvement of TRP-like channels in mechanosensing by L. polyedra. The TRP channels do not appear to be mechanoreceptors but rather are components of the mechanotransduction signaling pathway and may be activated via a PLC-dependent mechanism. The presence and function of TRP channels in a dinoflagellate emphasize the evolutionary conservation of both the channel structures and their functions.}, } @article {pmid29361519, year = {2018}, author = {Cocorocchio, M and Baldwin, AJ and Stewart, B and Kim, L and Harwood, AJ and Thompson, CRL and Andrews, PLR and Williams, RSB}, title = {Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum.}, journal = {Disease models & mechanisms}, volume = {11}, number = {1}, pages = {}, pmid = {29361519}, issn = {1754-8411}, support = {/WT_/Wellcome Trust/United Kingdom ; BB/M007146/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; NC/M001504/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; 101582Z/13/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Antioxidants/pharmacology ; Curcumin/analogs & derivatives/chemistry/*pharmacology ; Dictyostelium/drug effects/growth & development/*metabolism ; Ligands ; Molecular Docking Simulation ; Presenilin-1/*metabolism ; Protein Phosphatase 2/*metabolism ; *Sequence Homology, Amino Acid ; }, abstract = {Natural compounds often have complex molecular structures and unknown molecular targets. These characteristics make them difficult to analyse using a classical pharmacological approach. Curcumin, the main curcuminoid of turmeric, is a complex molecule possessing wide-ranging biological activities, cellular mechanisms and roles in potential therapeutic treatment, including Alzheimer's disease and cancer. Here, we investigate the physiological effects and molecular targets of curcumin in Dictyostelium discoideum We show that curcumin exerts acute effects on cell behaviour, reduces cell growth and slows multicellular development. We employed a range of structurally related compounds to show the distinct role of different structural groups in curcumin's effects on cell behaviour, growth and development, highlighting active moieties in cell function, and showing that these cellular effects are unrelated to the well-known antioxidant activity of curcumin. Molecular mechanisms underlying the effect of curcumin and one synthetic analogue (EF24) were then investigated to identify a curcumin-resistant mutant lacking the protein phosphatase 2A regulatory subunit (PsrA) and an EF24-resistant mutant lacking the presenilin 1 orthologue (PsenB). Using in silico docking analysis, we then showed that curcumin might function through direct binding to a key regulatory region of PsrA. These findings reveal novel cellular and molecular mechanisms for the function of curcumin and related compounds.}, } @article {pmid29348641, year = {2018}, author = {Hammarlund, EU and von Stedingk, K and Påhlman, S}, title = {Refined control of cell stemness allowed animal evolution in the oxic realm.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {220-228}, doi = {10.1038/s41559-017-0410-5}, pmid = {29348641}, issn = {2397-334X}, mesh = {Anaerobiosis ; Animals ; *Biological Evolution ; Cell Hypoxia/*physiology ; Oxygen/*physiology ; Stem Cells/*physiology ; }, abstract = {Animal diversification on Earth has long been presumed to be associated with the increasing extent of oxic niches. Here, we challenge that view. We start with the fact that hypoxia (<1-3% O2) maintains cellular immaturity (stemness), whereas adult stem cells continuously-and paradoxically-regenerate animal tissue in oxygenated settings. Novel insights from tumour biology illuminate how cell stemness nevertheless can be achieved through the action of oxygen-sensing transcription factors in oxygenated, regenerating tissue. We suggest that these hypoxia-inducible transcription factors provided animals with unprecedented control over cell stemness that allowed them to cope with fluctuating oxygen concentrations. Thus, a refinement of the cellular hypoxia-response machinery enabled cell stemness at oxic conditions and, then, animals to evolve into the oxic realm. This view on the onset of animal diversification is consistent with geological evidence and provides a new perspective on the challenges and evolution of multicellular life.}, } @article {pmid29340409, year = {2018}, author = {Ray, A and Morford, RK and Ghaderi, N and Odde, DJ and Provenzano, PP}, title = {Dynamics of 3D carcinoma cell invasion into aligned collagen.}, journal = {Integrative biology : quantitative biosciences from nano to macro}, volume = {10}, number = {2}, pages = {100-112}, pmid = {29340409}, issn = {1757-9708}, support = {R01 CA172986/CA/NCI NIH HHS/United States ; R01 CA181385/CA/NCI NIH HHS/United States ; U54 CA210190/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/metabolism/pathology ; Carcinoma/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement/physiology ; Collagen/metabolism ; Extracellular Matrix/metabolism/pathology ; Female ; Humans ; Imaging, Three-Dimensional ; Microscopy, Fluorescence, Multiphoton ; Models, Biological ; Neoplasm Invasiveness/*pathology/physiopathology ; Systems Biology ; }, abstract = {Carcinoma cells frequently expand and invade from a confined lesion, or multicellular clusters, into and through the stroma on the path to metastasis, often with an efficiency dictated by the architecture and composition of the microenvironment. Specifically, in desmoplastic carcinomas such as those of the breast, aligned collagen tracks provide contact guidance cues for directed cancer cell invasion. Yet, the evolving dynamics of this process of invasion remains poorly understood, in part due to difficulties in continuously capturing both spatial and temporal heterogeneity and progression to invasion in experimental systems. Therefore, to study the local invasion process from cell dense clusters into aligned collagen architectures found in solid tumors, we developed a novel engineered 3D invasion platform that integrates an aligned collagen matrix with a cell dense tumor-like plug. Using multiphoton microscopy and quantitative analysis of cell motility, we track the invasion of cancer cells from cell-dense bulk clusters into the pre-aligned 3D matrix, and define the temporal evolution of the advancing invasion fronts over several days. This enables us to identify and probe cell dynamics in key regions of interest: behind, at, and beyond the edge of the invading lesion at distinct time points. Analysis of single cell migration identifies significant spatial heterogeneity in migration behavior between cells in the highly cell-dense region behind the leading edge of the invasion front and cells at and beyond the leading edge. Moreover, temporal variations in motility and directionality are also observed between cells within the cell-dense tumor-like plug and the leading invasive edge as its boundary extends into the anisotropic collagen over time. Furthermore, experimental results combined with mathematical modeling demonstrate that in addition to contact guidance, physical crowding of cells is a key regulating factor orchestrating variability in single cell migration during invasion into anisotropic ECM. Thus, our novel platform enables us to capture spatio-temporal dynamics of cell behavior behind, at, and beyond the invasive front and reveals heterogeneous, local interactions that lead to the emergence and maintenance of the advancing front.}, } @article {pmid29337961, year = {2018}, author = {Trigos, AS and Pearson, RB and Papenfuss, AT and Goode, DL}, title = {How the evolution of multicellularity set the stage for cancer.}, journal = {British journal of cancer}, volume = {118}, number = {2}, pages = {145-152}, pmid = {29337961}, issn = {1532-1827}, mesh = {Animals ; Biological Evolution ; Gene Regulatory Networks ; Humans ; Neoplasms/*genetics/*pathology ; }, abstract = {Neoplastic growth and many of the hallmark properties of cancer are driven by the disruption of molecular networks established during the emergence of multicellularity. Regulatory pathways and molecules that evolved to impose regulatory constraints upon networks established in earlier unicellular organisms enabled greater communication and coordination between the diverse cell types required for multicellularity, but also created liabilities in the form of points of vulnerability in the network that when mutated or dysregulated facilitate the development of cancer. These factors are usually overlooked in genomic analyses of cancer, but understanding where vulnerabilities to cancer lie in the networks of multicellular species would provide important new insights into how core molecular processes and gene regulation change during tumourigenesis. We describe how the evolutionary origins of genes influence their roles in cancer, and how connections formed between unicellular and multicellular genes that act as key regulatory hubs for normal tissue homeostasis can also contribute to malignant transformation when disrupted. Tumours in general are characterised by increased dependence on unicellular processes for survival, and major dysregulation of the control structures imposed on these processes during the evolution of multicellularity. Mounting molecular evidence suggests altered interactions at the interface between unicellular and multicellular genes play key roles in the initiation and progression of cancer. Furthermore, unicellular network regions activated in cancer show high degrees of robustness and plasticity, conferring increased adaptability to tumour cells by supporting effective responses to environmental pressures such as drug exposure. Examining how the links between multicellular and unicellular regions get disrupted in tumours has great potential to identify novel drivers of cancer, and to guide improvements to cancer treatment by identifying more effective therapeutic strategies. Recent successes in targeting unicellular processes by novel compounds underscore the logic of such approaches. Further gains could come from identifying genes at the interface between unicellular and multicellular processes and manipulating the communication between network regions of different evolutionary ages.}, } @article {pmid29322818, year = {2018}, author = {Baig, AM and Zohaib, R and Tariq, S and Ahmad, HR}, title = {Evolution of pH buffers and water homeostasis in eukaryotes: homology between humans and Acanthamoeba proteins.}, journal = {Future microbiology}, volume = {13}, number = {}, pages = {195-207}, doi = {10.2217/fmb-2017-0116}, pmid = {29322818}, issn = {1746-0921}, mesh = {Acanthamoeba castellanii/*genetics/*physiology ; Amino Acid Sequence ; Carbonic Anhydrases/chemistry/genetics ; Computational Biology ; *Evolution, Molecular ; Homeostasis/*genetics ; Humans ; Hydrogen-Ion Concentration ; Membrane Transport Proteins/chemistry/genetics ; Models, Molecular ; Molecular Sequence Data ; Protozoan Proteins/chemistry/*genetics ; Sequence Homology, Amino Acid ; Water ; }, abstract = {AIM: This study intended to trace the evolution of acid-base buffers and water homeostasis in eukaryotes. Acanthamoeba castellanii was selected as a model unicellular eukaryote for this purpose. Homologies of proteins involved in pH and water regulatory mechanisms at cellular levels were compared between humans and A. castellanii.

MATERIALS & METHODS: Amino acid sequence homology, structural homology, 3D modeling and docking prediction were done to show the extent of similarities between carbonic anhydrase 1 (CA1), aquaporin (AQP), band-3 protein and H[+] pump. Experimental assays were done with acetazolamide (AZM), brinzolamide and mannitol to observe their effects on the trophozoites of  A. castellanii.

RESULTS: The human CA1, AQP, band-3 protein and H[+]-transport proteins revealed similar proteins in Acanthamoeba. Docking showed the binding of AZM on amoebal AQP-like proteins.  Acanthamoeba showed transient shape changes and encystation at differential doses of brinzolamide, mannitol and AZM.  Conclusion: Water and pH regulating adapter proteins in Acanthamoeba and humans show significant homology, these mechanisms evolved early in the primitive unicellular eukaryotes and have remained conserved in multicellular eukaryotes.}, } @article {pmid29322437, year = {2018}, author = {Jakobi, T and Dieterich, C}, title = {Deep Computational Circular RNA Analytics from RNA-seq Data.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1724}, number = {}, pages = {9-25}, doi = {10.1007/978-1-4939-7562-4_2}, pmid = {29322437}, issn = {1940-6029}, mesh = {Computational Biology/*methods ; *Gene Expression Regulation ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; RNA/*genetics ; RNA, Circular ; Sequence Analysis, RNA/*methods ; *Transcriptome ; }, abstract = {Circular RNAs (circRNAs) have been first described as "scrambled exons" in the 1990s. CircRNAs originate from back splicing or exon skipping of linear RNA templates and have continuously gained attention in recent years due to the availability of high-throughput whole-transcriptome sequencing methods. Numerous manuscripts describe thousands of circRNAs throughout uni- and multicellular eukaryote species and demonstrated that they are conserved, stable, and abundant in specific tissues or conditions. This manuscript provides a walk-through of our bioinformatics toolbox, which covers all aspects of in silico circRNA analysis, starting from raw sequencing data and back-splicing junction discovery to circRNA quantitation and reconstruction of internal the circRNA structure.}, } @article {pmid29320478, year = {2018}, author = {Smakowska-Luzan, E and Mott, GA and Parys, K and Stegmann, M and Howton, TC and Layeghifard, M and Neuhold, J and Lehner, A and Kong, J and Grünwald, K and Weinberger, N and Satbhai, SB and Mayer, D and Busch, W and Madalinski, M and Stolt-Bergner, P and Provart, NJ and Mukhtar, MS and Zipfel, C and Desveaux, D and Guttman, DS and Belkhadir, Y}, title = {An extracellular network of Arabidopsis leucine-rich repeat receptor kinases.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {342-346}, pmid = {29320478}, issn = {1476-4687}, support = {T 947/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Arabidopsis/cytology/*enzymology/immunology/microbiology ; Arabidopsis Proteins/*chemistry/*metabolism ; Leucine/*metabolism ; Protein Binding ; Protein Domains ; Protein Kinases/*chemistry/*metabolism ; Protein Serine-Threonine Kinases/chemistry/metabolism ; Receptors, Cell Surface/chemistry/metabolism ; Reproducibility of Results ; Signal Transduction ; }, abstract = {The cells of multicellular organisms receive extracellular signals using surface receptors. The extracellular domains (ECDs) of cell surface receptors function as interaction platforms, and as regulatory modules of receptor activation. Understanding how interactions between ECDs produce signal-competent receptor complexes is challenging because of their low biochemical tractability. In plants, the discovery of ECD interactions is complicated by the massive expansion of receptor families, which creates tremendous potential for changeover in receptor interactions. The largest of these families in Arabidopsis thaliana consists of 225 evolutionarily related leucine-rich repeat receptor kinases (LRR-RKs), which function in the sensing of microorganisms, cell expansion, stomata development and stem-cell maintenance. Although the principles that govern LRR-RK signalling activation are emerging, the systems-level organization of this family of proteins is unknown. Here, to address this, we investigated 40,000 potential ECD interactions using a sensitized high-throughput interaction assay, and produced an LRR-based cell surface interaction network (CSI[LRR]) that consists of 567 interactions. To demonstrate the power of CSI[LRR] for detecting biologically relevant interactions, we predicted and validated the functions of uncharacterized LRR-RKs in plant growth and immunity. In addition, we show that CSI[LRR] operates as a unified regulatory network in which the LRR-RKs most crucial for its overall structure are required to prevent the aberrant signalling of receptors that are several network-steps away. Thus, plants have evolved LRR-RK networks to process extracellular signals into carefully balanced responses.}, } @article {pmid29320389, year = {2018}, author = {Ćetković, H and Halasz, M and Herak Bosnar, M}, title = {Sponges: A Reservoir of Genes Implicated in Human Cancer.}, journal = {Marine drugs}, volume = {16}, number = {1}, pages = {}, pmid = {29320389}, issn = {1660-3397}, mesh = {Animals ; Evolution, Molecular ; Genome/genetics ; Humans ; Neoplasms/*genetics ; Porifera/*genetics ; Proteome/genetics ; Signal Transduction/genetics ; }, abstract = {Recently, it was shown that the majority of genes linked to human diseases, such as cancer genes, evolved in two major evolutionary transitions-the emergence of unicellular organisms and the transition to multicellularity. Therefore, it has been widely accepted that the majority of disease-related genes has already been present in species distantly related to humans. An original way of studying human diseases relies on analyzing genes and proteins that cause a certain disease using model organisms that belong to the evolutionary level at which these genes have emerged. This kind of approach is supported by the simplicity of the genome/proteome, body plan, and physiology of such model organisms. It has been established for quite some time that sponges are an ideal model system for such studies, having a vast variety of genes known to be engaged in sophisticated processes and signalling pathways associated with higher animals. Sponges are considered to be the simplest multicellular animals and have changed little during evolution. Therefore, they provide an insight into the metazoan ancestor genome/proteome features. This review compiles current knowledge of cancer-related genes/proteins in marine sponges.}, } @article {pmid29301490, year = {2018}, author = {Strader, ME and Aglyamova, GV and Matz, MV}, title = {Molecular characterization of larval development from fertilization to metamorphosis in a reef-building coral.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {17}, pmid = {29301490}, issn = {1471-2164}, support = {DEB-1501463//National Science Foundation/International ; }, mesh = {Animals ; Anthozoa/anatomy & histology/embryology/*genetics/*growth & development ; Behavior, Animal/drug effects ; Fertilization ; Larva/genetics/growth & development/metabolism ; Luminescent Proteins/metabolism ; Metamorphosis, Biological/genetics ; Transcriptome ; }, abstract = {BACKGROUND: Molecular mechanisms underlying coral larval competence, the ability of larvae to respond to settlement cues, determine their dispersal potential and are potential targets of natural selection. Here, we profiled competence, fluorescence and genome-wide gene expression in embryos and larvae of the reef-building coral Acropora millepora daily throughout 12 days post-fertilization.

RESULTS: Gene expression associated with competence was positively correlated with transcriptomic response to the natural settlement cue, confirming that mature coral larvae are "primed" for settlement. Rise of competence through development was accompanied by up-regulation of sensory and signal transduction genes such as ion channels, genes involved in neuropeptide signaling, and G-protein coupled receptor (GPCRs). A drug screen targeting components of GPCR signaling pathways confirmed a role in larval settlement behavior and metamorphosis.

CONCLUSIONS: These results gives insight into the molecular complexity underlying these transitions and reveals receptors and pathways that, if altered by changing environments, could affect dispersal capabilities of reef-building corals. In addition, this dataset provides a toolkit for asking broad questions about sensory capacity in multicellular animals and the evolution of development.}, } @article {pmid29294063, year = {2018}, author = {Featherston, J and Arakaki, Y and Hanschen, ER and Ferris, PJ and Michod, RE and Olson, BJSC and Nozaki, H and Durand, PM}, title = {The 4-Celled Tetrabaena socialis Nuclear Genome Reveals the Essential Components for Genetic Control of Cell Number at the Origin of Multicellularity in the Volvocine Lineage.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {855-870}, doi = {10.1093/molbev/msx332}, pmid = {29294063}, issn = {1537-1719}, mesh = {*Biological Evolution ; Chlorophyta/*genetics ; Cyclins/genetics ; Genes, Retinoblastoma ; *Genes, cdc ; *Genome Components ; Multigene Family ; Proteasome Endopeptidase Complex/genetics ; Selection, Genetic ; Transcriptome ; Ubiquitin/genetics ; }, abstract = {Multicellularity is the premier example of a major evolutionary transition in individuality and was a foundational event in the evolution of macroscopic biodiversity. The volvocine chlorophyte lineage is well suited for studying this process. Extant members span unicellular, simple colonial, and obligate multicellular taxa with germ-soma differentiation. Here, we report the nuclear genome sequence of one of the most morphologically simple organisms in this lineage-the 4-celled colonial Tetrabaena socialis and compare this to the three other complete volvocine nuclear genomes. Using conservative estimates of gene family expansions a minimal set of expanded gene families was identified that associate with the origin of multicellularity. These families are rich in genes related to developmental processes. A subset of these families is lineage specific, which suggests that at a genomic level the evolution of multicellularity also includes lineage-specific molecular developments. Multiple points of evidence associate modifications to the ubiquitin proteasomal pathway (UPP) with the beginning of coloniality. Genes undergoing positive or accelerating selection in the multicellular volvocines were found to be enriched in components of the UPP and gene families gained at the origin of multicellularity include components of the UPP. A defining feature of colonial/multicellular life cycles is the genetic control of cell number. The genomic data presented here, which includes diversification of cell cycle genes and modifications to the UPP, align the genetic components with the evolution of this trait.}, } @article {pmid29292130, year = {2018}, author = {López, JL and Alvarez, F and Príncipe, A and Salas, ME and Lozano, MJ and Draghi, WO and Jofré, E and Lagares, A}, title = {Isolation, taxonomic analysis, and phenotypic characterization of bacterial endophytes present in alfalfa (Medicago sativa) seeds.}, journal = {Journal of biotechnology}, volume = {267}, number = {}, pages = {55-62}, doi = {10.1016/j.jbiotec.2017.12.020}, pmid = {29292130}, issn = {1873-4863}, mesh = {Actinobacteria/genetics/isolation & purification ; Bacteroidetes/genetics/isolation & purification ; Endophytes/classification/*genetics ; Firmicutes/genetics/isolation & purification ; Medicago sativa/genetics/*microbiology ; Microbiota/*genetics ; *Phylogeny ; Proteobacteria/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Seedlings/microbiology ; Seeds/microbiology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {A growing body of evidence has reinforced the central role of microbiomes in the life of sound multicellular eukaryotes, thus more properly described as true holobionts. Though soil was considered a main source of plant microbiomes, seeds have been shown to be endophytically colonized by microorganisms thus representing natural carriers of a selected microbial inoculum to the young seedlings. In this work we have investigated the type of culturable endophytic bacteria that are carried within surface-sterilized alfalfa seeds. MALDI-TOF analysis revealed the presence of bacteria that belonged to 40 separate genera, distributed within four taxa (Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes). Nonsymbiotic members of the Rhizobiaceae family were also found. The evaluation of nine different in-vitro biochemical activities demonstrated isolates with complex combinations of traits that, upon a Principal-Component-Analysis, could be classified into four phenotypic groups. That isolates from nearly half of the genera identified had been able to colonize alfalfa plants grown under axenic conditions was remarkable. Further analyses should be addressed to investigating the colonization mechanisms of the alfalfa seeds, the evolutionary significance of the alfalfa-seed endophytes, and also how after germination the seed microbiome competes with spermospheric and rhizospheric soil bacteria to colonize newly emerging seedlings.}, } @article {pmid29288005, year = {2018}, author = {Yoshida, T and Kates, M and Sopko, NA and Liu, X and Singh, AK and Bishai, WR and Joice, G and McConkey, DJ and Bivalacqua, TJ}, title = {Ex vivo culture of tumor cells from N-methyl-N-nitrosourea-induced bladder cancer in rats: Development of organoids and an immortalized cell line.}, journal = {Urologic oncology}, volume = {36}, number = {4}, pages = {160.e23-160.e32}, doi = {10.1016/j.urolonc.2017.11.024}, pmid = {29288005}, issn = {1873-2496}, mesh = {Animals ; Carcinoma, Transitional Cell/chemically induced/*pathology ; Cell Differentiation ; Cell Line, Tumor ; Coculture Techniques ; Female ; Fibroblasts ; Humans ; Methylnitrosourea/toxicity ; Mice ; Organoids/*pathology ; Primary Cell Culture ; Rats ; Rats, Inbred F344 ; Spheroids, Cellular ; Urinary Bladder/*cytology ; Urinary Bladder Neoplasms/chemically induced/*pathology ; }, abstract = {OBJECTIVE: We ex vivo cultured primary tumor cells from N-methyl-N-nitrosourea (MNU)-induced bladder tumors in rats and established an immortalized cell line from them.

MATERIALS AND METHODS: Bladder tumors in rats were induced by instillation of MNU into the murine bladder. Primary tumor cells were prepared by the cancer-tissue originated spheroid method. An immortalized cell line was established by co-culture with fibroblasts. The cultured tumor cells were molecularly and functionally characterized by quantitative real-time polymerase chain reaction, Western blot, growth assay, and transwell migration assay.

RESULTS: Primary tumor cells were successfully prepared as multicellular spheroids from MNU-induced bladder tumors. The differentiation marker expression patterns observed in the original tumors were largely retained in the spheroids. We succeeded in establishing a cell line from the spheroids and named it T-MNU-1. Although basal markers (CK14 and CK5) were enriched in T-MNU-1 compared to the spheroids, T-MNU-1 expressed both luminal and basal markers. T-MNU-1 was able to migrate through a transwell.

CONCLUSIONS: Tumor cells in MNU-induced bladder tumors were successfully cultured ex vivo as organoids, and an immortalized cell line was also established from them. The ex vivo models offer a platform that enables analysis of intrinsic characteristics of tumor cells excluding influence of microenvironment in MNU-induced bladder tumors.}, } @article {pmid29283188, year = {2018}, author = {Peccoud, J and Cordaux, R and Gilbert, C}, title = {Analyzing Horizontal Transfer of Transposable Elements on a Large Scale: Challenges and Prospects.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {40}, number = {2}, pages = {}, doi = {10.1002/bies.201700177}, pmid = {29283188}, issn = {1521-1878}, mesh = {Animals ; DNA Transposable Elements/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome ; Sequence Analysis/methods ; }, abstract = {Whoever compares the genomes of distantly related species might find aberrantly high sequence similarity at certain loci. Such anomaly can only be explained by genetic material being transferred through other means than reproduction, that is, a horizontal transfer (HT). Between multicellular organisms, the transferred material will likely turn out to be a transposable element (TE). Because TEs can move between loci and invade chromosomes by replicating themselves, HT of TEs (HTT) profoundly impacts genome evolution. Yet, very few studies have quantified HTT at large taxonomic scales. Indeed, this task currently faces difficulties that range from the variable quality of available genome sequences to limitations of analytical procedures, some of which have been overlooked. Here we review the many challenges that an extensive analysis of HTT must overcome, we expose biases and limits of current methods, suggest solutions or workarounds, and reflect upon approaches that could be developed to better quantify this phenomenon.}, } @article {pmid29279310, year = {2018}, author = {Hesp, ZC and Yoseph, RY and Suzuki, R and Jukkola, P and Wilson, C and Nishiyama, A and McTigue, DM}, title = {Proliferating NG2-Cell-Dependent Angiogenesis and Scar Formation Alter Axon Growth and Functional Recovery After Spinal Cord Injury in Mice.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {38}, number = {6}, pages = {1366-1382}, pmid = {29279310}, issn = {1529-2401}, support = {R01 NS074870/NS/NINDS NIH HHS/United States ; P30 NS045758/NS/NINDS NIH HHS/United States ; F31 NS095606/NS/NINDS NIH HHS/United States ; P30 NS104177/NS/NINDS NIH HHS/United States ; R01 NS073425/NS/NINDS NIH HHS/United States ; R01 NS049267/NS/NINDS NIH HHS/United States ; R01 NS043246/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Antigens/*genetics ; Astrocytes/pathology ; Axons/*pathology ; Cell Proliferation/drug effects ; Cicatrix/*genetics/pathology ; Fibrosis/pathology ; Glial Fibrillary Acidic Protein/biosynthesis/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neovascularization, Pathologic/*genetics/pathology ; Neuroglia/metabolism/pathology ; Pericytes/metabolism/pathology ; Proteoglycans/*genetics ; Recovery of Function/genetics ; Spinal Cord Injuries/*genetics/*pathology ; }, abstract = {Spinal cord injury (SCI) induces a centralized fibrotic scar surrounded by a reactive glial scar at the lesion site. The origin of these scars is thought to be perivascular cells entering lesions on ingrowing blood vessels and reactive astrocytes, respectively. However, two NG2-expressing cell populations, pericytes and glia, may also influence scar formation. In the periphery, new blood vessel growth requires proliferating NG2[+] pericytes; if this were also true in the CNS, then the fibrotic scar would depend on dividing NG2[+] pericytes. NG2[+] glial cells (also called oligodendrocyte progenitors or polydendrocytes) also proliferate after SCI and accumulate in large numbers among astrocytes in the glial scar. Their effect there, if any, is unknown. We show that proliferating NG2[+] pericytes and glia largely segregate into the fibrotic and glial scars, respectively; therefore, we used a thymidine kinase/ganciclovir paradigm to ablate both dividing NG2[+] cell populations to determine whether either scar was altered. Results reveal that loss of proliferating NG2[+] pericytes in the lesion prevented intralesion angiogenesis and completely abolished the fibrotic scar. The glial scar was also altered in the absence of acutely dividing NG2[+] cells, displaying discontinuous borders and significantly reduced GFAP density. Collectively, these changes enhanced edema, prolonged hemorrhage, and impaired forelimb functional recovery. Interestingly, after halting GCV at 14 d postinjury, scar elements and vessels entered the lesions over the next 7 d, as did large numbers of axons that were not present in controls. Collectively, these data reveal that acutely dividing NG2[+] pericytes and glia play fundamental roles in post-SCI tissue remodeling.SIGNIFICANCE STATEMENT Spinal cord injury (SCI) is characterized by formation of astrocytic and fibrotic scars, both of which are necessary for lesion repair. NG2[+] cells may influence both scar-forming processes. This study used a novel transgenic mouse paradigm to ablate proliferating NG2[+] cells after SCI to better understand their role in repair. For the first time, our data show that dividing NG2[+] pericytes are required for post-SCI angiogenesis, which in turn is needed for fibrotic scar formation. Moreover, loss of cycling NG2[+] glia and pericytes caused significant multicellular tissue changes, including altered astrocyte responses and impaired functional recovery. This work reveals previously unknown ways in which proliferating NG2[+] cells contribute to endogenous repair after SCI.}, } @article {pmid29260254, year = {2018}, author = {Böttcher, T}, title = {From Molecules to Life: Quantifying the Complexity of Chemical and Biological Systems in the Universe.}, journal = {Journal of molecular evolution}, volume = {86}, number = {1}, pages = {1-10}, pmid = {29260254}, issn = {1432-1432}, support = {Emmy Noether//DFG/International ; Marie Curie Zukunftskolleg Incoming Fellowship//EU FP7/International ; }, mesh = {*Biological Evolution ; Earth, Planet ; Eukaryotic Cells ; *Evolution, Chemical ; Evolution, Molecular ; Life ; Models, Biological ; Models, Statistical ; *Origin of Life ; Prokaryotic Cells ; }, abstract = {Life is a complex phenomenon and much research has been devoted to both understanding its origins from prebiotic chemistry and discovering life beyond Earth. Yet, it has remained elusive how to quantify this complexity and how to compare chemical and biological units on one common scale. Here, a mathematical description of molecular complexity was applied allowing to quantitatively assess complexity of chemical structures. This in combination with the orthogonal measure of information complexity resulted in a two-dimensional complexity space ranging over the entire spectrum from molecules to organisms. Entities with a certain level of information complexity directly require a functionally complex mechanism for their production or replication and are hence indicative for life-like systems. In order to describe entities combining molecular and information complexity, the term biogenic unit was introduced. Exemplified biogenic unit complexities were calculated for ribozymes, protein enzymes, multimeric protein complexes, and even an entire virus particle. Complexities of prokaryotic and eukaryotic cells, as well as multicellular organisms, were estimated. Thereby distinct evolutionary stages in complexity space were identified. The here developed approach to compare the complexity of biogenic units allows for the first time to address the gradual characteristics of prebiotic and life-like systems without the need for a definition of life. This operational concept may guide our search for life in the Universe, and it may direct the investigations of prebiotic trajectories that lead towards the evolution of complexity at the origins of life.}, } @article {pmid29251593, year = {2017}, author = {Molaro, A and Malik, HS}, title = {Culture shock.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {29251593}, issn = {2050-084X}, mesh = {Cell Line ; *Dosage Compensation, Genetic ; Humans ; *Sex Chromosomes ; }, abstract = {Many different human cell lines, including both normal and cancer cells, appear to converge to a state that contains an unusual number of chromosomes when they are grown in culture.}, } @article {pmid29251591, year = {2017}, author = {Xu, J and Peng, X and Chen, Y and Zhang, Y and Ma, Q and Liang, L and Carter, AC and Lu, X and Wu, CI}, title = {Free-living human cells reconfigure their chromosomes in the evolution back to uni-cellularity.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {29251591}, issn = {2050-084X}, mesh = {*Adaptation, Biological ; Cell Line, Tumor ; *Cell Proliferation ; *Chromosomes, Human ; Evolution, Molecular ; Humans ; Karyotype ; *Sex Chromosomes ; }, abstract = {Cells of multi-cellular organisms evolve toward uni-cellularity in the form of cancer and, if humans intervene, continue to evolve in cell culture. During this process, gene dosage relationships may evolve in novel ways to cope with the new environment and may regress back to the ancestral uni-cellular state. In this context, the evolution of sex chromosomes vis-a-vis autosomes is of particular interest. Here, we report the chromosomal evolution in ~ 600 cancer cell lines. Many of them jettisoned either Y or the inactive X; thus, free-living male and female cells converge by becoming 'de-sexualized'. Surprisingly, the active X often doubled, accompanied by the addition of one haploid complement of autosomes, leading to an X:A ratio of 2:3 from the extant ratio of 1:2. Theoretical modeling of the frequency distribution of X:A karyotypes suggests that the 2:3 ratio confers a higher fitness and may reflect aspects of sex chromosome evolution.}, } @article {pmid29245010, year = {2017}, author = {Kundu, P and Blacher, E and Elinav, E and Pettersson, S}, title = {Our Gut Microbiome: The Evolving Inner Self.}, journal = {Cell}, volume = {171}, number = {7}, pages = {1481-1493}, doi = {10.1016/j.cell.2017.11.024}, pmid = {29245010}, issn = {1097-4172}, mesh = {Aging ; Animals ; Bacteria/classification/*growth & development/metabolism ; Biological Evolution ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; Organ Specificity ; Puberty ; Symbiosis ; }, abstract = {The "holobiont" concept, defined as the collective contribution of the eukaryotic and prokaryotic counterparts to the multicellular organism, introduces a complex definition of individuality enabling a new comprehensive view of human evolution and personalized characteristics. Here, we provide snapshots of the evolving microbial-host associations and relations during distinct milestones across the lifespan of a human being. We discuss the current knowledge of biological symbiosis between the microbiome and its host and portray the challenges in understanding these interactions and their potential effects on human physiology, including microbiome-nervous system inter-relationship and its relevance to human variation and individuality.}, } @article {pmid29225309, year = {2017}, author = {Jong, LW and Fujiwara, T and Nozaki, H and Miyagishima, SY}, title = {Cell size for commitment to cell division and number of successive cell divisions in multicellular volvocine green algae Tetrabaena socialis and Gonium pectorale.}, journal = {Proceedings of the Japan Academy. Series B, Physical and biological sciences}, volume = {93}, number = {10}, pages = {832-840}, pmid = {29225309}, issn = {1349-2896}, mesh = {Cell Count/methods ; Cell Culture Techniques/methods ; Cell Division ; Cell Size ; Chlorophyta/*cytology ; Electrophoresis, Polyacrylamide Gel/methods ; }, abstract = {Volvocine algae constitute a green algal lineage comprising unicellular Chlamydomonas, four-celled Tetrabaena, eight to 32-celled Gonium, and others up to Volvox spp., which consist of up to 50,000 cells. These algae proliferate by multiple fissions with cellular growth up to several fold in size and subsequent successive cell divisions. Chlamydomonas reinhardtii cells produce two to 32 daughter cells by one to five divisions, depending on cellular growth in the G1 phase. By contrast, in this study, we found that Tetrabaena socialis and Gonium pectorale cells mostly produced four and eight daughter cells by two and three successive divisions, respectively. In contrast to C. reinhardtii, which is committed to cell division when the cell has grown two-fold, T. socialis and G. pectorale are committed only when the cells have grown four- and eight-fold, respectively. Thus, our results suggest that evolutionary changes in cellular size for commitment largely contributes to the emergence and evolution of multicellularity in volvocine algae.}, } @article {pmid29212441, year = {2017}, author = {Arakaki, Y and Fujiwara, T and Kawai-Toyooka, H and Kawafune, K and Featherston, J and Durand, PM and Miyagishima, SY and Nozaki, H}, title = {Evolution of cytokinesis-related protein localization during the emergence of multicellularity in volvocine green algae.}, journal = {BMC evolutionary biology}, volume = {17}, number = {1}, pages = {243}, pmid = {29212441}, issn = {1471-2148}, support = {2016-B//NIG-JOINT/International ; 25-9234//Japan Society for the Promotion of Science/International ; 16H02518//Japan Society for the Promotion of Science/International ; RA151217156515//National Research Foundation/International ; }, mesh = {Algal Proteins/*genetics ; Cytokinesis/*genetics ; *Evolution, Molecular ; Likelihood Functions ; Models, Biological ; Phylogeny ; Protein Transport ; Species Specificity ; Subcellular Fractions/metabolism ; Volvox/*cytology/*genetics ; }, abstract = {BACKGROUND: The volvocine lineage, containing unicellular Chlamydomonas reinhardtii and differentiated multicellular Volvox carteri, is a powerful model for comparative studies aiming at understanding emergence of multicellularity. Tetrabaena socialis is the simplest multicellular volvocine alga and belongs to the family Tetrabaenaceae that is sister to more complex multicellular volvocine families, Goniaceae and Volvocaceae. Thus, T. socialis is a key species to elucidate the initial steps in the evolution of multicellularity. In the asexual life cycle of C. reinhardtii and multicellular volvocine species, reproductive cells form daughter cells/colonies by multiple fission. In embryogenesis of the multicellular species, daughter protoplasts are connected to one another by cytoplasmic bridges formed by incomplete cytokinesis during multiple fission. These bridges are important for arranging the daughter protoplasts in appropriate positions such that species-specific integrated multicellular individuals are shaped. Detailed comparative studies of cytokinesis between unicellular and simple multicellular volvocine species will help to elucidate the emergence of multicellularity from the unicellular ancestor. However, the cytokinesis-related genes between closely related unicellular and multicellular species have not been subjected to a comparative analysis.

RESULTS: Here we focused on dynamin-related protein 1 (DRP1), which is known for its role in cytokinesis in land plants. Immunofluorescence microscopy using an antibody against T. socialis DRP1 revealed that volvocine DRP1 was localized to division planes during cytokinesis in unicellular C. reinhardtii and two simple multicellular volvocine species T. socialis and Gonium pectorale. DRP1 signals were mainly observed in the newly formed division planes of unicellular C. reinhardtii during multiple fission, whereas in multicellular T. socialis and G. pectorale, DRP1 signals were observed in all division planes during embryogenesis.

CONCLUSIONS: These results indicate that the molecular mechanisms of cytokinesis may be different in unicellular and multicellular volvocine algae. The localization of DRP1 during multiple fission might have been modified in the common ancestor of multicellular volvocine algae. This modification may have been essential for the re-orientation of cells and shaping colonies during the emergence of multicellularity in this lineage.}, } @article {pmid29208647, year = {2018}, author = {Matt, GY and Umen, JG}, title = {Cell-Type Transcriptomes of the Multicellular Green Alga Volvox carteri Yield Insights into the Evolutionary Origins of Germ and Somatic Differentiation Programs.}, journal = {G3 (Bethesda, Md.)}, volume = {8}, number = {2}, pages = {531-550}, pmid = {29208647}, issn = {2160-1836}, support = {P30 CA091842/CA/NCI NIH HHS/United States ; R01 GM078376/GM/NIGMS NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Algal Proteins/classification/genetics ; Cell Differentiation/*genetics ; Energy Metabolism/genetics ; *Evolution, Molecular ; *Gene Expression Profiling ; Gene Ontology ; Light-Harvesting Protein Complexes/classification/genetics ; Phylogeny ; Volvox/cytology/*genetics/metabolism ; }, abstract = {Germ-soma differentiation is a hallmark of complex multicellular organisms, yet its origins are not well understood. Volvox carteri is a simple multicellular green alga that has recently evolved a simple germ-soma dichotomy with only two cell-types: large germ cells called gonidia and small terminally differentiated somatic cells. Here, we provide a comprehensive characterization of the gonidial and somatic transcriptomes of V. carteri to uncover fundamental differences between the molecular and metabolic programming of these cell-types. We found extensive transcriptome differentiation between cell-types, with somatic cells expressing a more specialized program overrepresented in younger, lineage-specific genes, and gonidial cells expressing a more generalist program overrepresented in more ancient genes that shared striking overlap with stem cell-specific genes from animals and land plants. Directed analyses of different pathways revealed a strong dichotomy between cell-types with gonidial cells expressing growth-related genes and somatic cells expressing an altruistic metabolic program geared toward the assembly of flagella, which support organismal motility, and the conversion of storage carbon to sugars, which act as donors for production of extracellular matrix (ECM) glycoproteins whose secretion enables massive organismal expansion. V. carteri orthologs of diurnally controlled genes from C. reinhardtii, a single-celled relative, were analyzed for cell-type distribution and found to be strongly partitioned, with expression of dark-phase genes overrepresented in somatic cells and light-phase genes overrepresented in gonidial cells- a result that is consistent with cell-type programs in V. carteri arising by cooption of temporal regulons in a unicellular ancestor. Together, our findings reveal fundamental molecular, metabolic, and evolutionary mechanisms that underlie the origins of germ-soma differentiation in V. carteri and provide a template for understanding the acquisition of germ-soma differentiation in other multicellular lineages.}, } @article {pmid29198427, year = {2018}, author = {Kenny, NJ and de Goeij, JM and de Bakker, DM and Whalen, CG and Berezikov, E and Riesgo, A}, title = {Towards the identification of ancestrally shared regenerative mechanisms across the Metazoa: A Transcriptomic case study in the Demosponge Halisarca caerulea.}, journal = {Marine genomics}, volume = {37}, number = {}, pages = {135-147}, doi = {10.1016/j.margen.2017.11.001}, pmid = {29198427}, issn = {1876-7478}, mesh = {Animals ; *Evolution, Molecular ; Porifera/genetics/*physiology ; Regeneration/*genetics ; Time Factors ; *Transcriptome ; }, abstract = {Regeneration is an essential process for all multicellular organisms, allowing them to recover effectively from internal and external injury. This process has been studied extensively in a medical context in vertebrates, with pathways often investigated mechanistically, both to derive increased understanding and as potential drug targets for therapy. Several species from other parts of the metazoan tree of life, including Hydra, planarians and echinoderms, noted for their regenerative capabilities, have previously been targeted for study. Less well-documented for their regenerative abilities are sponges. This is surprising, as they are both one of the earliest-branching extant metazoan phyla on Earth, and are rapidly able to respond to injury. Their sessile lifestyle, lack of an external protective layer, inability to respond to predation and filter-feeding strategy all mean that regeneration is often required. In particular the demosponge genus Halisarca has been noted for its fast cell turnover and ability to quickly adjust its cell kinetic properties to repair damage through regeneration. However, while the rate and structure of regeneration in sponges has begun to be investigated, the molecular mechanisms behind this ability are yet to be catalogued. Here we describe the assembly of a reference transcriptome for Halisarca caerulea, along with additional transcriptomes noting response to injury before, shortly following (2h post-), and 12h after trauma. RNAseq reads were assembled using Trinity, annotated, and samples compared, to allow initial insight into the transcriptomic basis of sponge regenerative processes. These resources are deep, with our reference assembly containing >92.6% of the BUSCO Metazoa set of genes, and well-assembled (N50s of 836, 957, 1688 and 2032 for untreated, 2h, 12h and reference transcriptomes respectively), and therefore represent excellent qualitative resources as a bedrock for future study. The generation of transcriptomic resources from sponges before and following deliberate damage has allowed us to study particular pathways within this species responsible for repairing damage. We note particularly the involvement of the Wnt cascades in this process in this species, and detail the contents of this cascade, along with cell cycle, extracellular matrix and apoptosis-linked genes in this work. This resource represents an initial starting point for the continued development of this knowledge, given H. caerulea's ability to regenerate and position as an outgroup for comparing the process of regeneration across metazoan lineages. With this resource in place, we can begin to infer the regenerative capacity of the common ancestor of all extant animal life, and unravel the elements of regeneration in an often-overlooked clade.}, } @article {pmid29191225, year = {2017}, author = {Sanfilippo, P and Wen, J and Lai, EC}, title = {Landscape and evolution of tissue-specific alternative polyadenylation across Drosophila species.}, journal = {Genome biology}, volume = {18}, number = {1}, pages = {229}, pmid = {29191225}, issn = {1474-760X}, support = {R01-GM083300/GM/NIGMS NIH HHS/United States ; P30-CA008748/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 NS083833/NS/NINDS NIH HHS/United States ; R01-NS083833/NS/NINDS NIH HHS/United States ; R01 GM083300/GM/NIGMS NIH HHS/United States ; }, mesh = {*3' Untranslated Regions ; Animals ; Cell Line ; Computational Biology/methods ; Drosophila/embryology/*genetics ; Drosophila melanogaster/genetics ; *Evolution, Molecular ; Molecular Sequence Annotation ; Organ Specificity/genetics ; *Poly A ; Polyadenylation ; RNA Isoforms ; RNA-Binding Proteins/metabolism ; Species Specificity ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Drosophila melanogaster has one of best-described transcriptomes of any multicellular organism. Nevertheless, the paucity of 3'-sequencing data in this species precludes comprehensive assessment of alternative polyadenylation (APA), which is subject to broad tissue-specific control.

RESULTS: Here, we generate deep 3'-sequencing data from 23 developmental stages, tissues, and cell lines of D. melanogaster, yielding a comprehensive atlas of ~ 62,000 polyadenylated ends. These data broadly extend the annotated transcriptome, identify ~ 40,000 novel 3' termini, and reveal that two-thirds of Drosophila genes are subject to APA. Furthermore, we dramatically expand the numbers of genes known to be subject to tissue-specific APA, such as 3' untranslated region (UTR) lengthening in head and 3' UTR shortening in testis, and characterize new tissue and developmental 3' UTR patterns. Our thorough 3' UTR annotations permit reassessment of post-transcriptional regulatory networks, via conserved miRNA and RNA binding protein sites. To evaluate the evolutionary conservation and divergence of APA patterns, we generate developmental and tissue-specific 3'-seq libraries from Drosophila yakuba and Drosophila virilis. We document broadly analogous tissue-specific APA trends in these species, but also observe significant alterations in 3' end usage across orthologs. We exploit the population of functionally evolving poly(A) sites to gain clear evidence that evolutionary divergence in core polyadenylation signal (PAS) and downstream sequence element (DSE) motifs drive broad alterations in 3' UTR isoform expression across the Drosophila phylogeny.

CONCLUSIONS: These data provide a critical resource for the Drosophila community and offer many insights into the complex control of alternative tissue-specific 3' UTR formation and its consequences for post-transcriptional regulatory networks.}, } @article {pmid29179763, year = {2017}, author = {Klein, B and Wibberg, D and Hallmann, A}, title = {Whole transcriptome RNA-Seq analysis reveals extensive cell type-specific compartmentalization in Volvox carteri.}, journal = {BMC biology}, volume = {15}, number = {1}, pages = {111}, pmid = {29179763}, issn = {1741-7007}, mesh = {*Biological Evolution ; Computational Biology ; Gene Expression Profiling ; *Genome ; Sequence Analysis, RNA ; *Transcriptome ; Volvox/*genetics ; }, abstract = {BACKGROUND: One of evolution's most important achievements is the development and radiation of multicellular organisms with different types of cells. Complex multicellularity has evolved several times in eukaryotes; yet, in most lineages, an investigation of its molecular background is considerably challenging since the transition occurred too far in the past and, in addition, these lineages evolved a large number of cell types. However, for volvocine green algae, such as Volvox carteri, multicellularity is a relatively recent innovation. Furthermore, V. carteri shows a complete division of labor between only two cell types - small, flagellated somatic cells and large, immotile reproductive cells. Thus, V. carteri provides a unique opportunity to study multicellularity and cellular differentiation at the molecular level.

RESULTS: This study provides a whole transcriptome RNA-Seq analysis of separated cell types of the multicellular green alga V. carteri f. nagariensis to reveal cell type-specific components and functions. To this end, 246 million quality filtered reads were mapped to the genome and valid expression data were obtained for 93% of the 14,247 gene loci. In the subsequent search for protein domains with assigned molecular function, we identified 9435 previously classified domains in 44% of all gene loci. Furthermore, in 43% of all gene loci we identified 15,254 domains that are involved in biological processes. All identified domains were investigated regarding cell type-specific expression. Moreover, we provide further insight into the expression pattern of previously described gene families (e.g., pherophorin, extracellular matrix metalloprotease, and VARL families). Our results demonstrate an extensive compartmentalization of the transcriptome between cell types: More than half of all genes show a clear difference in expression between somatic and reproductive cells.

CONCLUSIONS: This study constitutes the first transcriptome-wide RNA-Seq analysis of separated cell types of V. carteri focusing on gene expression. The high degree of differential expression indicates a strong differentiation of cell types despite the fact that V. carteri diverged relatively recently from its unicellular relatives. Our expression dataset and the bioinformatic analyses provide the opportunity to further investigate and understand the mechanisms of cell type-specific expression and its transcriptional regulation.}, } @article {pmid29175233, year = {2018}, author = {Miller, WB}, title = {Biological information systems: Evolution as cognition-based information management.}, journal = {Progress in biophysics and molecular biology}, volume = {134}, number = {}, pages = {1-26}, doi = {10.1016/j.pbiomolbio.2017.11.005}, pmid = {29175233}, issn = {1873-1732}, mesh = {Animals ; *Biological Evolution ; Cells/cytology/metabolism ; Cognition ; Humans ; }, abstract = {An alternative biological synthesis is presented that conceptualizes evolutionary biology as an epiphenomenon of integrated self-referential information management. Since all biological information has inherent ambiguity, the systematic assessment of information is required by living organisms to maintain self-identity and homeostatic equipoise in confrontation with environmental challenges. Through their self-referential attachment to information space, cells are the cornerstone of biological action. That individualized assessment of information space permits self-referential, self-organizing niche construction. That deployment of information and its subsequent selection enacted the dominant stable unicellular informational architectures whose biological expressions are the prokaryotic, archaeal, and eukaryotic unicellular forms. Multicellularity represents the collective appraisal of equivocal environmental information through a shared information space. This concerted action can be viewed as systematized information management to improve information quality for the maintenance of preferred homeostatic boundaries among the varied participants. When reiterated in successive scales, this same collaborative exchange of information yields macroscopic organisms as obligatory multicellular holobionts. Cognition-Based Evolution (CBE) upholds that assessment of information precedes biological action, and the deployment of information through integrative self-referential niche construction and natural cellular engineering antecedes selection. Therefore, evolutionary biology can be framed as a complex reciprocating interactome that consists of the assessment, communication, deployment and management of information by self-referential organisms at multiple scales in continuous confrontation with environmental stresses.}, } @article {pmid29170260, year = {2018}, author = {Swafford, AJM and Oakley, TH}, title = {Multimodal sensorimotor system in unicellular zoospores of a fungus.}, journal = {The Journal of experimental biology}, volume = {221}, number = {Pt 2}, pages = {}, doi = {10.1242/jeb.163196}, pmid = {29170260}, issn = {1477-9145}, mesh = {Allomyces/*physiology ; *Chemotaxis ; *Phototaxis ; Sensation ; Spores, Fungal/*physiology ; }, abstract = {Complex sensory systems often underlie critical behaviors, including avoiding predators and locating prey, mates and shelter. Multisensory systems that control motor behavior even appear in unicellular eukaryotes, such as Chlamydomonas, which are important laboratory models for sensory biology. However, we know of no unicellular opisthokonts that control motor behavior using a multimodal sensory system. Therefore, existing single-celled models for multimodal sensorimotor integration are very distantly related to animals. Here, we describe a multisensory system that controls the motor function of unicellular fungal zoospores. We found that zoospores of Allomyces arbusculus exhibit both phototaxis and chemotaxis. Furthermore, we report that closely related Allomyces species respond to either the chemical or the light stimuli presented in this study, not both, and likely do not share this multisensory system. This diversity of sensory systems within Allomyces provides a rare example of a comparative framework that can be used to examine the evolution of sensory systems following the gain/loss of available sensory modalities. The tractability of Allomyces and related fungi as laboratory organisms will facilitate detailed mechanistic investigations into the genetic underpinnings of novel photosensory systems, and how multisensory systems may have functioned in early opisthokonts before multicellularity allowed for the evolution of specialized cell types.}, } @article {pmid29166656, year = {2017}, author = {Pichugin, Y and Peña, J and Rainey, PB and Traulsen, A}, title = {Fragmentation modes and the evolution of life cycles.}, journal = {PLoS computational biology}, volume = {13}, number = {11}, pages = {e1005860}, pmid = {29166656}, issn = {1553-7358}, mesh = {Animals ; Bacteria/cytology ; *Biological Evolution ; Cell Physiological Phenomena/*physiology ; Computational Biology ; Life Cycle Stages/*physiology ; *Models, Biological ; Reproduction/physiology ; }, abstract = {Reproduction is a defining feature of living systems. To reproduce, aggregates of biological units (e.g., multicellular organisms or colonial bacteria) must fragment into smaller parts. Fragmentation modes in nature range from binary fission in bacteria to collective-level fragmentation and the production of unicellular propagules in multicellular organisms. Despite this apparent ubiquity, the adaptive significance of fragmentation modes has received little attention. Here, we develop a model in which groups arise from the division of single cells that do not separate but stay together until the moment of group fragmentation. We allow for all possible fragmentation patterns and calculate the population growth rate of each associated life cycle. Fragmentation modes that maximise growth rate comprise a restrictive set of patterns that include production of unicellular propagules and division into two similar size groups. Life cycles marked by single-cell bottlenecks maximise population growth rate under a wide range of conditions. This surprising result offers a new evolutionary explanation for the widespread occurrence of this mode of reproduction. All in all, our model provides a framework for exploring the adaptive significance of fragmentation modes and their associated life cycles.}, } @article {pmid29149403, year = {2017}, author = {Xoconostle-Cázares, B and Ruiz-Medrano, R}, title = {Structure-Function Relationship of TCTP.}, journal = {Results and problems in cell differentiation}, volume = {64}, number = {}, pages = {47-68}, doi = {10.1007/978-3-319-67591-6_3}, pmid = {29149403}, issn = {0080-1844}, mesh = {Agriculture ; Amino Acid Sequence ; Animals ; Arabidopsis Proteins/*chemistry/genetics/*metabolism ; Biomarkers, Tumor/*chemistry/genetics/*metabolism ; Biomedical Research ; Humans ; Microtubule-Associated Proteins/*chemistry/genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; Structure-Activity Relationship ; Tumor Protein, Translationally-Controlled 1 ; }, abstract = {The translationally controlled tumor protein (TCTP) is a small, multifunctional protein found in most, if not all, eukaryotic lineages, involved in a myriad of key regulatory processes. Among these, the control of proliferation and inhibition of cell death, as well as differentiation, are the most important, and it is probable that other responses are derived from the ability of TCTP to influence them in both unicellular and multicellular organisms. In the latter, an additional function for TCTP stems from its capacity to be secreted via a nonclassical pathway and function in a non-cell autonomous (paracrine) manner, thus affecting the responses of neighboring or distant cells to developmental or environmental stimuli (as in the case of serum TCTP/histamine-releasing factor in mammals and phloem TCTP in Arabidopsis). The additional ability to traverse membranes without a requirement for transmembrane receptors adds to its functional flexibility. The long-distance transport of TCTP mRNA and protein in plants via the vascular system supports the notion that an important aspect of TCTP function is its ability to influence the response of neighboring and distant cells to endogenous and exogenous signals in a supracellular manner. The predicted tridimensional structure of TCTPs indicates a high degree of conservation, more than its amino acid sequence similarity could suggest. However, subtle differences in structure could lead to different activities, as evidenced by TCTPs secreted by Plasmodium spp. Similar structural variations in animal and plant TCTPs, likely the result of convergent evolution, could lead to deviations from the canonical function of this group of proteins, which could have an impact from a biomedical and agricultural perspectives.}, } @article {pmid29147724, year = {2018}, author = {Zhu, H and Sun, X and Zhang, Q and Song, P and Hu, Q and Zhang, X and Li, X and Hu, J and Pan, J and Sun, S and Weng, Y and Yang, L}, title = {GLABROUS (CmGL) encodes a HD-ZIP IV transcription factor playing roles in multicellular trichome initiation in melon.}, journal = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik}, volume = {131}, number = {3}, pages = {569-579}, pmid = {29147724}, issn = {1432-2242}, support = {31601776//National Natural Science Foundation of China/ ; }, mesh = {Chromosome Mapping ; Cucumis melo/*genetics/growth & development ; Genes, Plant ; Genetic Linkage ; Genetic Markers ; *Leucine Zippers ; Plant Proteins/*genetics ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Transcription Factors/*genetics ; Trichomes/*growth & development ; }, abstract = {Map-based cloning identified CmGL that encodes a HD-ZIP type IV transcription factor that controls multicellular trichome initiation in melon. Trichomes are small hairs covering the aerial parts of plants that originate from the epidermal cells, which can protect plants against the damage by insects and pathogens. The regulatory pathway of unicellular trichomes has been well studied in the model plant Arabidopsis. Little is known about the genetic control and regulation of trichome development in melon (Cucumis melo L.) which has multicellular trichomes. In this study, we identified a melon mutant, cmgl, which showed completely glabrous on all aerial organs. A bulked segregant analysis was conducted to identify polymorphic markers for linkage analysis in a population with 256 F2 plants, which allowed to locate the cmgl locus in melon chromosome VIII. Next-generation sequencing-aided marker discovery and fine mapping in a large population with 1536 F2 plants narrowed the candidate gene region to 12 kb that harbored only one candidate gene for cmgl, which encoded a class IV homeodomain-associated leucine zipper transcription factor. Four SNPs in the coding region of the CmGL gene were identified between the two parental lines; a single base substitution from C to A resulted in a premature termination codon and a truncated protein in the cmgl. The SNP was converted into a dCAPS marker, which showed co-segregation in the F2 population and 564 melon accessions. Result of this study will be helpful for better understanding of genetic control of trichome development in melon and marker-assisted selection in developing new cultivars.}, } @article {pmid29141015, year = {2017}, author = {Bozler, J and Kacsoh, BZ and Bosco, G}, title = {Nematocytes: Discovery and characterization of a novel anculeate hemocyte in Drosophila falleni and Drosophila phalerata.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0188133}, pmid = {29141015}, issn = {1932-6203}, support = {DP1 MH110234/MH/NIMH NIH HHS/United States ; P30 CA023108/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Drosophila/*classification/immunology ; *Hemocytes ; Immunity, Innate ; Microscopy, Fluorescence ; Phylogeny ; Species Specificity ; }, abstract = {Immune challenges, such as parasitism, can be so pervasive and deleterious that they constitute an existential threat to a species' survival. In response to these ecological pressures, organisms have developed a wide array of novel behavioral, cellular, and molecular adaptations. Research into these immune defenses in model systems has resulted in a revolutionary understanding of evolution and functional biology. As the field has expanded beyond the limited number of model organisms our appreciation of evolutionary innovation and unique biology has widened as well. With this in mind, we have surveyed the hemolymph of several non-model species of Drosophila. Here we identify and describe a novel hemocyte, type-II nematocytes, found in larval stages of numerous Drosophila species. Examined in detail in Drosophila falleni and Drosophila phalerata, we find that these remarkable cells are distinct from previously described hemocytes due to their anucleate state (lacking a nucleus) and unusual morphology. Type-II nematocytes are long, narrow cells with spindle-like projections extending from a cell body with high densities of mitochondria and microtubules, and exhibit the ability to synthesize proteins. These properties are unexpected for enucleated cells, and together with our additional characterization, we demonstrate that these type-II nematocytes represent a biological novelty. Surprisingly, despite the absence of a nucleus, we observe through live cell imaging that these cells remain motile with a highly dynamic cellular shape. Furthermore, these cells demonstrate the ability to form multicellular structures, which we suggest may be a component of the innate immune response to macro-parasites. In addition, live cell imaging points to a large nucleated hemocyte, type-I nematocyte, as the progenitor cell, leading to enucleation through a budding or asymmetrical division process rather than nuclear ejection: This study is the first to report such a process of enucleation. Here we describe these cells in detail for the first time and examine their evolutionary history in Drosophila.}, } @article {pmid29133828, year = {2017}, author = {Schenkelaars, Q and Pratlong, M and Kodjabachian, L and Fierro-Constain, L and Vacelet, J and Le Bivic, A and Renard, E and Borchiellini, C}, title = {Animal multicellularity and polarity without Wnt signaling.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {15383}, pmid = {29133828}, issn = {2045-2322}, mesh = {Animals ; *Models, Biological ; Morphogenesis/*physiology ; *Porifera/cytology/physiology ; Transforming Growth Factor beta/*metabolism ; Wnt Proteins/metabolism ; *Wnt Signaling Pathway ; }, abstract = {Acquisition of multicellularity is a central event in the evolution of Eukaryota. Strikingly, animal multicellularity coincides with the emergence of three intercellular communication pathways - Notch, TGF-β and Wnt - all considered as hallmarks of metazoan development. By investigating Oopsacas minuta and Aphrocallistes vastus, we show here that the emergence of a syncytium and plugged junctions in glass sponges coincides with the loss of essential components of the Wnt signaling (i.e. Wntless, Wnt ligands and Disheveled), whereas core components of the TGF-β and Notch modules appear unaffected. This suggests that Wnt signaling is not essential for cell differentiation, polarity and morphogenesis in glass sponges. Beyond providing a comparative study of key developmental toolkits, we define here the first case of a metazoan phylum that maintained a level of complexity similar to its relatives despite molecular degeneration of Wnt pathways.}, } @article {pmid29133443, year = {2017}, author = {Kempes, CP and Wolpert, D and Cohen, Z and Pérez-Mercader, J}, title = {The thermodynamic efficiency of computations made in cells across the range of life.}, journal = {Philosophical transactions. Series A, Mathematical, physical, and engineering sciences}, volume = {375}, number = {2109}, pages = {}, pmid = {29133443}, issn = {1471-2962}, mesh = {Biological Evolution ; Cells/*metabolism ; *Life ; Protein Biosynthesis ; Thermodynamics ; }, abstract = {Biological organisms must perform computation as they grow, reproduce and evolve. Moreover, ever since Landauer's bound was proposed, it has been known that all computation has some thermodynamic cost-and that the same computation can be achieved with greater or smaller thermodynamic cost depending on how it is implemented. Accordingly an important issue concerning the evolution of life is assessing the thermodynamic efficiency of the computations performed by organisms. This issue is interesting both from the perspective of how close life has come to maximally efficient computation (presumably under the pressure of natural selection), and from the practical perspective of what efficiencies we might hope that engineered biological computers might achieve, especially in comparison with current computational systems. Here we show that the computational efficiency of translation, defined as free energy expended per amino acid operation, outperforms the best supercomputers by several orders of magnitude, and is only about an order of magnitude worse than the Landauer bound. However, this efficiency depends strongly on the size and architecture of the cell in question. In particular, we show that the useful efficiency of an amino acid operation, defined as the bulk energy per amino acid polymerization, decreases for increasing bacterial size and converges to the polymerization cost of the ribosome. This cost of the largest bacteria does not change in cells as we progress through the major evolutionary shifts to both single- and multicellular eukaryotes. However, the rates of total computation per unit mass are non-monotonic in bacteria with increasing cell size, and also change across different biological architectures, including the shift from unicellular to multicellular eukaryotes.This article is part of the themed issue 'Reconceptualizing the origins of life'.}, } @article {pmid29129605, year = {2018}, author = {Pogozheva, ID and Lomize, AL}, title = {Evolution and adaptation of single-pass transmembrane proteins.}, journal = {Biochimica et biophysica acta. Biomembranes}, volume = {1860}, number = {2}, pages = {364-377}, doi = {10.1016/j.bbamem.2017.11.002}, pmid = {29129605}, issn = {0005-2736}, mesh = {*Adaptation, Physiological ; Arabidopsis/genetics/metabolism ; Cell Membrane/*metabolism ; Databases, Protein ; Dictyostelium/genetics/metabolism ; Escherichia coli/genetics/metabolism ; *Evolution, Molecular ; Humans ; Membrane Proteins/chemistry/genetics/*metabolism ; Methanocaldococcus/genetics/metabolism ; Protein Conformation, alpha-Helical ; Protein Multimerization ; Proteome/chemistry/genetics/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Species Specificity ; }, abstract = {A comparative analysis of 6039 single-pass (bitopic) membrane proteins from six evolutionarily distant organisms was performed based on data from the Membranome database. The observed repertoire of bitopic proteins is significantly enlarged in eukaryotic cells and especially in multicellular organisms due to the diversification of enzymes, emergence of proteins involved in vesicular trafficking, and expansion of receptors, structural, and adhesion proteins. The majority of bitopic proteins in multicellular organisms are located in the plasma membrane (PM) and involved in cell communication. Bitopic proteins from different membranes significantly diverge in terms of their biological functions, size, topology, domain architecture, physical properties of transmembrane (TM) helices and propensity to form homodimers. Most proteins from eukaryotic PM and endoplasmic reticulum (ER) have the N-out topology. The predicted lengths of TM helices and hydrophobic thicknesses, stabilities and hydrophobicities of TM α-helices are the highest for proteins from eukaryotic PM, intermediate for proteins from prokaryotic cells, ER and Golgi apparatus, and lowest for proteins from mitochondria, chloroplasts, and peroxisomes. Tyr and Phe residues accumulate at the cytoplasmic leaflet of PM and at the outer leaflet of membranes of bacteria, Golgi apparatus, and nucleus. The propensity for dimerization increases from unicellular to multicellular eukaryotes, from enzymes to receptors, and from intracellular membrane proteins to PM proteins. More than half of PM proteins form homodimers with a 2:1 ratio of right-handed to left-handed helix packing arrangements. The inverse ratio (1:2) was observed for dimers from the ER, Golgi and vesicles.}, } @article {pmid29128405, year = {2018}, author = {Soni, B and Saha, B and Singh, S}, title = {Systems cues governing IL6 signaling in leishmaniasis.}, journal = {Cytokine}, volume = {106}, number = {}, pages = {169-175}, doi = {10.1016/j.cyto.2017.11.001}, pmid = {29128405}, issn = {1096-0023}, mesh = {Animals ; Computer Simulation ; Interleukin-6/*metabolism ; Leishmaniasis/*metabolism ; Mice ; Models, Biological ; Phylogeny ; Principal Component Analysis ; *Signal Transduction ; *Systems Biology ; Toll-Like Receptors/metabolism ; }, abstract = {IL-6 has been proposed to favor the development of Th2 responses and play an important role in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation, differentiation and act as key player during inflammation and immune response. Th2 cytokines play an immunoregulatory role in early infection. Literature says in mice infected with L. major, IL-6 may promote the development of both Th1 and Th2 responses. IL-4 is also considered to be the signature cytokine of Th-2 response. IL-10 was initially characterized as a Th2 cytokine but later on it was proved to be a pleiotropic cytokine, secreted from different cell types including the macrophages. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches may be used to tackle this challenge in an iterative process of quantitative mathematical analysis. In this study, we created an in silico model of IL6 mediated macrophage activation which suffers from an excessive impact of the negative feedback loop involving SOCS3. The strategy adopted in this framework may help to reduce the complexity of the leishmanial IL6 model analysis and also laydown various physiological or pathological conditions of IL6 signaling in future.}, } @article {pmid29121339, year = {2017}, author = {Polychronopoulos, D and King, JWD and Nash, AJ and Tan, G and Lenhard, B}, title = {Conserved non-coding elements: developmental gene regulation meets genome organization.}, journal = {Nucleic acids research}, volume = {45}, number = {22}, pages = {12611-12624}, pmid = {29121339}, issn = {1362-4962}, support = {MC_UP_1102/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Base Sequence ; Conserved Sequence/*genetics ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Genes, Developmental/genetics ; Genome/*genetics ; Humans ; Regulatory Sequences, Nucleic Acid/*genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {Comparative genomics has revealed a class of non-protein-coding genomic sequences that display an extraordinary degree of conservation between two or more organisms, regularly exceeding that found within protein-coding exons. These elements, collectively referred to as conserved non-coding elements (CNEs), are non-randomly distributed across chromosomes and tend to cluster in the vicinity of genes with regulatory roles in multicellular development and differentiation. CNEs are organized into functional ensembles called genomic regulatory blocks-dense clusters of elements that collectively coordinate the expression of shared target genes, and whose span in many cases coincides with topologically associated domains. CNEs display sequence properties that set them apart from other sequences under constraint, and have recently been proposed as useful markers for the reconstruction of the evolutionary history of organisms. Disruption of several of these elements is known to contribute to diseases linked with development, and cancer. The emergence, evolutionary dynamics and functions of CNEs still remain poorly understood, and new approaches are required to enable comprehensive CNE identification and characterization. Here, we review current knowledge and identify challenges that need to be tackled to resolve the impasse in understanding extreme non-coding conservation.}, } @article {pmid29119267, year = {2018}, author = {Li, L and Aslam, M and Rabbi, F and Vanderwel, MC and Ashton, NW and Suh, DY}, title = {PpORS, an ancient type III polyketide synthase, is required for integrity of leaf cuticle and resistance to dehydration in the moss, Physcomitrella patens.}, journal = {Planta}, volume = {247}, number = {2}, pages = {527-541}, pmid = {29119267}, issn = {1432-2048}, support = {262038-2013//Natural Sciences and Engineering Research Council of Canada/ ; 2982-2008//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Acyltransferases/genetics/*metabolism ; Biological Evolution ; Bryopsida/*enzymology/genetics/physiology ; Dehydration ; Gene Knockout Techniques ; Mutation ; Phenotype ; Phylogeny ; Plant Leaves/enzymology/genetics/physiology ; Plant Proteins/genetics/metabolism ; Water/physiology ; }, abstract = {PpORS knockout mutants produced abnormal leaves with increased dye permeability and were more susceptible to dehydration, consistent with PpORS products being constituents of a cuticular structure in the moss. Type III polyketide synthases (PKSs) have co-evolved with terrestrial plants such that each taxon can generate a characteristic collection of polyketides, fine-tuned to its needs. 2'-Oxoalkylresorcinol synthase from Physcomitrella patens (PpORS) is basal to all plant type III PKSs in phylogenetic trees and may closely resemble their most recent common ancestor. To gain insight into the roles that ancestral plant type III PKSs might have played during early land plant evolution, we constructed and phenotypically characterized targeted knockouts of PpORS. Ors gametophores, unless submerged in water while they were developing, displayed various leaf malformations that included grossly misshapen leaves, missing or abnormal midribs, multicellular protuberances and localized necrosis. Ors leaves, particularly abnormal ones, showed increased permeability to the hydrophilic dye, toluidine blue. Ors gametophores lost water faster and were more susceptible to dehydration than those of the control strain. Our findings are consistent with ors leaves possessing a partially defective cuticle and implicate PpORS in synthesis of the intact cuticle. PpORS orthologs are present in a few moss species but have not been found in other plants. However, conceivably an ancestral ORS in early land plants may have contributed to their protection from dehydration.}, } @article {pmid29118134, year = {2017}, author = {Berger, D and Stångberg, J and Grieshop, K and Martinossi-Allibert, I and Arnqvist, G}, title = {Temperature effects on life-history trade-offs, germline maintenance and mutation rate under simulated climate warming.}, journal = {Proceedings. Biological sciences}, volume = {284}, number = {1866}, pages = {}, pmid = {29118134}, issn = {1471-2954}, mesh = {Acclimatization ; Animals ; Climate Change ; Coleoptera/*physiology ; Female ; *Germ-Line Mutation ; *Life History Traits ; Longevity ; Male ; *Mutation Rate ; Reproduction ; }, abstract = {Mutation has a fundamental influence over evolutionary processes, but how evolutionary processes shape mutation rate remains less clear. In asexual unicellular organism, increased mutation rates have been observed in stressful environments and the reigning paradigm ascribes this increase to selection for evolvability. However, this explanation does not apply in sexually reproducing species, where little is known about how the environment affects mutation rate. Here we challenged experimental lines of seed beetle, evolved at ancestral temperature or under simulated climate warming, to repair induced mutations at ancestral and stressful temperature. Results show that temperature stress causes individuals to pass on a greater mutation load to their grand-offspring. This suggests that stress-induced mutation rates, in unicellular and multicellular organisms alike, can result from compromised germline DNA repair in low condition individuals. Moreover, lines adapted to simulated climate warming had evolved increased longevity at the cost of reproduction, and this allocation decision improved germline repair. These results suggest that mutation rates can be modulated by resource allocation trade-offs encompassing life-history traits and the germline and have important implications for rates of adaptation and extinction as well as our understanding of genetic diversity in multicellular organisms.}, } @article {pmid29114025, year = {2017}, author = {Hajjar, C and Cherrier, MV and Dias Mirandela, G and Petit-Hartlein, I and Stasia, MJ and Fontecilla-Camps, JC and Fieschi, F and Dupuy, J}, title = {The NOX Family of Proteins Is Also Present in Bacteria.}, journal = {mBio}, volume = {8}, number = {6}, pages = {}, pmid = {29114025}, issn = {2150-7511}, mesh = {Algorithms ; Bacterial Proteins/chemistry/*genetics/isolation & purification/*metabolism ; Databases, Genetic ; Electron Transport ; Humans ; NADPH Oxidase 2/chemistry/genetics ; NADPH Oxidases/chemistry/*genetics/isolation & purification/*metabolism ; Oxidation-Reduction ; Oxidative Stress ; Phagocytes/enzymology ; Phylogeny ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Streptococcus pneumoniae/enzymology/*genetics ; }, abstract = {Transmembrane NADPH oxidase (NOX) enzymes have been so far only characterized in eukaryotes. In most of these organisms, they reduce molecular oxygen to superoxide and, depending on the presence of additional domains, are called NOX or dual oxidases (DUOX). Reactive oxygen species (ROS), including superoxide, have been traditionally considered accidental toxic by-products of aerobic metabolism. However, during the last decade it has become evident that both O2[•-] and H2O2 are key players in complex signaling networks and defense. A well-studied example is the production of O2[•-] during the bactericidal respiratory burst of phagocytes; this production is catalyzed by NOX2. Here, we devised and applied a novel algorithm to search for additional NOX genes in genomic databases. This procedure allowed us to discover approximately 23% new sequences from bacteria (in relation to the number of NOX-related sequences identified by the authors) that we have added to the existing eukaryotic NOX family and have used to build an expanded phylogenetic tree. We cloned and overexpressed the identified nox gene from Streptococcus pneumoniae and confirmed that it codes for an NADPH oxidase. The membrane of the S. pneumoniae NOX protein (SpNOX) shares many properties with its eukaryotic counterparts, such as affinity for NADPH and flavin adenine dinucleotide, superoxide dismutase and diphenylene iodonium inhibition, cyanide resistance, oxygen consumption, and superoxide production. Traditionally, NOX enzymes in eukaryotes are related to functions linked to multicellularity. Thus, the discovery of a large family of NOX-related enzymes in the bacterial world brings up fascinating questions regarding their role in this new biological context.IMPORTANCE NADPH oxidase (NOX) enzymes have not yet been reported in bacteria. Here, we carried out computational and experimental studies to provide the first characterization of a prokaryotic NOX. Out of 996 prokaryotic proteins showing NOX signatures, we initially selected, cloned, and overexpressed four of them. Subsequently, and based on preliminary testing, we concentrated our efforts on Streptococcus SpNOX, which shares many biochemical characteristics with NOX2, the referent model of NOX enzymes. Our work makes possible, for the first time, the study of pure forms of this important family of enzymes, allowing for biophysical and molecular characterization in an unprecedented way. Similar advances regarding other membrane protein families have led to new structures, further mechanistic studies, and the improvement of inhibitors. In addition, biological functions of these newly described bacterial enzymes will be certainly discovered in the near future.}, } @article {pmid29109290, year = {2017}, author = {Brennan, JJ and Messerschmidt, JL and Williams, LM and Matthews, BJ and Reynoso, M and Gilmore, TD}, title = {Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-κB signal transduction, and development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {47}, pages = {E10122-E10131}, pmid = {29109290}, issn = {1091-6490}, mesh = {Animals ; Cell Line ; Chickens ; Embryo, Nonmammalian ; Fibroblasts/drug effects/immunology/microbiology ; Flagellin/pharmacology ; Gene Expression Regulation, Developmental/*immunology ; HEK293 Cells ; Hot Temperature ; Humans ; Immunity, Innate ; Morpholinos/genetics/metabolism ; Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics/immunology ; Myeloid Differentiation Factor 88/genetics/immunology ; NF-kappa B/genetics/*immunology ; Protein Binding ; Sea Anemones/genetics/growth & development/*immunology/microbiology ; Signal Transduction ; Toll-Like Receptors/antagonists & inhibitors/genetics/*immunology ; Vibrio/pathogenicity/physiology ; }, abstract = {In organisms from insects to vertebrates, Toll-like receptors (TLRs) are primary pathogen detectors that activate downstream pathways, specifically those that direct expression of innate immune effector genes. TLRs also have roles in development in many species. The sea anemone Nematostella vectensis is a useful cnidarian model to study the origins of TLR signaling because its genome encodes a single TLR and homologs of many downstream signaling components, including the NF-κB pathway. We have characterized the single N. vectensis TLR (Nv-TLR) and demonstrated that it can activate canonical NF-κB signaling in human cells. Furthermore, we show that the intracellular Toll/IL-1 receptor (TIR) domain of Nv-TLR can interact with the human TLR adapter proteins MAL and MYD88. We demonstrate that the coral pathogen Vibrio coralliilyticus causes a rapidly lethal disease in N. vectensis and that heat-inactivated V. coralliilyticus and bacterial flagellin can activate a reconstituted Nv-TLR-to-NF-κB pathway in human cells. By immunostaining of anemones, we show that Nv-TLR is expressed in a subset of cnidocytes and that many of these Nv-TLR-expressing cells also express Nv-NF-κB. Additionally, the nematosome, which is a Nematostella-specific multicellular structure, expresses Nv-TLR and many innate immune pathway homologs and can engulf V. coralliilyticus Morpholino knockdown indicates that Nv-TLR also has an essential role during early embryonic development. Our characterization of this primitive TLR and identification of a bacterial pathogen for N. vectensis reveal ancient TLR functions and provide a model for studying the molecular basis of cnidarian disease and immunity.}, } @article {pmid29109219, year = {2017}, author = {Stapley, J and Feulner, PGD and Johnston, SE and Santure, AW and Smadja, CM}, title = {Variation in recombination frequency and distribution across eukaryotes: patterns and processes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1736}, pages = {}, pmid = {29109219}, issn = {1471-2970}, mesh = {Chromosome Mapping ; Eukaryota/*genetics ; *Genetic Linkage ; *Genome ; Recombination, Genetic/*genetics ; }, abstract = {Recombination, the exchange of DNA between maternal and paternal chromosomes during meiosis, is an essential feature of sexual reproduction in nearly all multicellular organisms. While the role of recombination in the evolution of sex has received theoretical and empirical attention, less is known about how recombination rate itself evolves and what influence this has on evolutionary processes within sexually reproducing organisms. Here, we explore the patterns of, and processes governing recombination in eukaryotes. We summarize patterns of variation, integrating current knowledge with an analysis of linkage map data in 353 organisms. We then discuss proximate and ultimate processes governing recombination rate variation and consider how these influence evolutionary processes. Genome-wide recombination rates (cM/Mb) can vary more than tenfold across eukaryotes, and there is large variation in the distribution of recombination events across closely related taxa, populations and individuals. We discuss how variation in rate and distribution relates to genome architecture, genetic and epigenetic mechanisms, sex, environmental perturbations and variable selective pressures. There has been great progress in determining the molecular mechanisms governing recombination, and with the continued development of new modelling and empirical approaches, there is now also great opportunity to further our understanding of how and why recombination rate varies.This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'.}, } @article {pmid29101312, year = {2017}, author = {Björnfot Holmström, S and Clark, R and Zwicker, S and Bureik, D and Kvedaraite, E and Bernasconi, E and Nguyen Hoang, AT and Johannsen, G and Marsland, BJ and Boström, EA and Svensson, M}, title = {Gingival Tissue Inflammation Promotes Increased Matrix Metalloproteinase-12 Production by CD200R[low] Monocyte-Derived Cells in Periodontitis.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {199}, number = {12}, pages = {4023-4035}, doi = {10.4049/jimmunol.1700672}, pmid = {29101312}, issn = {1550-6606}, mesh = {Adult ; Antigens, Surface/biosynthesis/genetics/*physiology ; Cell Division ; Cells, Cultured ; Coculture Techniques ; Cyclooxygenase Inhibitors/pharmacology ; Epithelial Cells/metabolism ; Fibroblasts/metabolism ; Flow Cytometry ; Gene Expression Regulation ; Gingiva/*enzymology/pathology ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Inflammation ; Keratinocytes/metabolism ; Matrix Metalloproteinase 12/biosynthesis/genetics/*physiology ; Monocytes/*enzymology/pathology ; Orexin Receptors ; Periodontitis/*enzymology/pathology ; Pyrazoles/pharmacology ; Real-Time Polymerase Chain Reaction ; Receptors, Cell Surface/biosynthesis/genetics/*physiology ; }, abstract = {Irreversible tissue recession in chronic inflammatory diseases is associated with dysregulated immune activation and production of tissue degradative enzymes. In this study, we identified elevated levels of matrix metalloproteinase (MMP)-12 in gingival tissue of patients with the chronic inflammatory disease periodontitis (PD). The source of MMP12 was cells of monocyte origin as determined by the expression of CD14, CD68, and CD64. These MMP12-producing cells showed reduced surface levels of the coinhibitory molecule CD200R. Similarly, establishing a multicellular three-dimensional model of human oral mucosa with induced inflammation promoted MMP12 production and reduced CD200R surface expression by monocyte-derived cells. MMP12 production by monocyte-derived cells was induced by CSF2 rather than the cyclooxygenase-2 pathway, and treatment of monocyte-derived cells with a CD200R ligand reduced CSF2-induced MMP12 production. Further, MMP12-mediated degradation of the extracellular matrix proteins tropoelastin and fibronectin in the tissue model coincided with a loss of Ki-67, a protein strictly associated with cell proliferation. Reduced amounts of tropoelastin were confirmed in gingival tissue from PD patients. Thus, this novel association of the CD200/CD200R pathway with MMP12 production by monocyte-derived cells may play a key role in PD progression and will be important to take into consideration in the development of future strategies to diagnose, treat, and prevent PD.}, } @article {pmid29099481, year = {2018}, author = {Strasser, A and Vaux, DL}, title = {Viewing BCL2 and cell death control from an evolutionary perspective.}, journal = {Cell death and differentiation}, volume = {25}, number = {1}, pages = {13-20}, pmid = {29099481}, issn = {1476-5403}, mesh = {Animals ; *Apoptosis ; Biological Evolution ; Caenorhabditis elegans/genetics ; Humans ; Inflammation ; Neoplasms/drug therapy ; Proto-Oncogene Proteins c-bcl-2/genetics/*physiology ; Stress, Physiological ; }, abstract = {The last 30 years of studying BCL2 have brought cell death research into the molecular era, and revealed its relevance to human pathophysiology. Most, if not all metazoans use an evolutionarily conserved process for cellular self destruction that is controlled and implemented by proteins related to BCL2. We propose the anti-apoptotic BCL2-like and pro-apoptotic BH3-only members of the family arose through duplication and modification of genes for the pro-apoptotic multi-BH domain family members, such as BAX and BAK1. In that way, a cell suicide process that initially evolved as a mechanism for defense against intracellular parasites was then also used in multicellular organisms for morphogenesis and to maintain the correct number of cells in adults by balancing cell production by mitosis.}, } @article {pmid29085064, year = {2017}, author = {Sipos, G and Prasanna, AN and Walter, MC and O'Connor, E and Bálint, B and Krizsán, K and Kiss, B and Hess, J and Varga, T and Slot, J and Riley, R and Bóka, B and Rigling, D and Barry, K and Lee, J and Mihaltcheva, S and LaButti, K and Lipzen, A and Waldron, R and Moloney, NM and Sperisen, C and Kredics, L and Vágvölgyi, C and Patrignani, A and Fitzpatrick, D and Nagy, I and Doyle, S and Anderson, JB and Grigoriev, IV and Güldener, U and Münsterkötter, M and Nagy, LG}, title = {Genome expansion and lineage-specific genetic innovations in the forest pathogenic fungi Armillaria.}, journal = {Nature ecology & evolution}, volume = {1}, number = {12}, pages = {1931-1941}, doi = {10.1038/s41559-017-0347-8}, pmid = {29085064}, issn = {2397-334X}, mesh = {Armillaria/*genetics ; Fungal Proteins/*genetics ; *Genome, Fungal ; Proteomics ; Sequence Analysis, RNA ; Species Specificity ; Transcriptome ; }, abstract = {Armillaria species are both devastating forest pathogens and some of the largest terrestrial organisms on Earth. They forage for hosts and achieve immense colony sizes via rhizomorphs, root-like multicellular structures of clonal dispersal. Here, we sequenced and analysed the genomes of four Armillaria species and performed RNA sequencing and quantitative proteomic analysis on the invasive and reproductive developmental stages of A. ostoyae. Comparison with 22 related fungi revealed a significant genome expansion in Armillaria, affecting several pathogenicity-related genes, lignocellulose-degrading enzymes and lineage-specific genes expressed during rhizomorph development. Rhizomorphs express an evolutionarily young transcriptome that shares features with the transcriptomes of both fruiting bodies and vegetative mycelia. Several genes show concomitant upregulation in rhizomorphs and fruiting bodies and share cis-regulatory signatures in their promoters, providing genetic and regulatory insights into complex multicellularity in fungi. Our results suggest that the evolution of the unique dispersal and pathogenicity mechanisms of Armillaria might have drawn upon ancestral genetic toolkits for wood-decay, morphogenesis and complex multicellularity.}, } @article {pmid29070590, year = {2017}, author = {de Wiljes, OO and van Elburg, RAJ and Keijzer, FA}, title = {Modelling the effects of short and random proto-neural elongations.}, journal = {Journal of the Royal Society, Interface}, volume = {14}, number = {135}, pages = {}, pmid = {29070590}, issn = {1742-5662}, mesh = {Animals ; Axons/*physiology ; *Computer Simulation ; Dendrites/*physiology ; *Models, Biological ; }, abstract = {To understand how neurons and nervous systems first evolved, we need an account of the origins of neural elongations: why did neural elongations (axons and dendrites) first originate, such that they could become the central component of both neurons and nervous systems? Two contrasting conceptual accounts provide different answers to this question. Braitenberg's vehicles provide the iconic illustration of the dominant input-output (IO) view. Here, the basic role of neural elongations is to connect sensors to effectors, both situated at different positions within the body. For this function, neural elongations are thought of as comparatively long and specific connections, which require an articulated body involving substantial developmental processes to build. Internal coordination (IC) models stress a different function for early nervous systems. Here, the coordination of activity across extended parts of a multicellular body is held central, in particular, for the contractions of (muscle) tissue. An IC perspective allows the hypothesis that the earliest proto-neural elongations could have been functional even when they were initially simple, short and random connections, as long as they enhanced the patterning of contractile activity across a multicellular surface. The present computational study provides a proof of concept that such short and random neural elongations can play this role. While an excitable epithelium can generate basic forms of patterning for small body configurations, adding elongations allows such patterning to scale up to larger bodies. This result supports a new, more gradual evolutionary route towards the origins of the very first neurons and nervous systems.}, } @article {pmid29069493, year = {2018}, author = {Gao, D and Chu, Y and Xia, H and Xu, C and Heyduk, K and Abernathy, B and Ozias-Akins, P and Leebens-Mack, JH and Jackson, SA}, title = {Horizontal Transfer of Non-LTR Retrotransposons from Arthropods to Flowering Plants.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {354-364}, pmid = {29069493}, issn = {1537-1719}, mesh = {Animals ; Arachis/*genetics ; Arthropods/*genetics ; Base Sequence ; *Gene Transfer, Horizontal ; Genome, Plant ; Phylogeny ; *Retroelements ; Sequence Homology, Nucleic Acid ; }, abstract = {Even though lateral movements of transposons across families and even phyla within multicellular eukaryotic kingdoms have been found, little is known about transposon transfer between the kingdoms Animalia and Plantae. We discovered a novel non-LTR retrotransposon, AdLINE3, in a wild peanut species. Sequence comparisons and phylogenetic analyses indicated that AdLINE3 is a member of the RTE clade, originally identified in a nematode and rarely reported in plants. We identified RTE elements in 82 plants, spanning angiosperms to algae, including recently active elements in some flowering plants. RTE elements in flowering plants were likely derived from a single family we refer to as An-RTE. Interestingly, An-RTEs show significant DNA sequence identity with non-LTR retroelements from 42 animals belonging to four phyla. Moreover, the sequence identity of RTEs between two arthropods and two plants was higher than that of homologous genes. Phylogenetic and evolutionary analyses of RTEs from both animals and plants suggest that the An-RTE family was likely transferred horizontally into angiosperms from an ancient aphid(s) or ancestral arthropod(s). Notably, some An-RTEs were recruited as coding sequences of functional genes participating in metabolic or other biochemical processes in plants. This is the first potential example of horizontal transfer of transposons between animals and flowering plants. Our findings help to understand exchanges of genetic material between the kingdom Animalia and Plantae and suggest arthropods likely impacted on plant genome evolution.}, } @article {pmid29065305, year = {2017}, author = {Brunet, T and King, N}, title = {The Origin of Animal Multicellularity and Cell Differentiation.}, journal = {Developmental cell}, volume = {43}, number = {2}, pages = {124-140}, pmid = {29065305}, issn = {1878-1551}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 GM089977/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Lineage ; }, abstract = {Over 600 million years ago, animals evolved from a unicellular or colonial organism whose cell(s) captured bacteria with a collar complex, a flagellum surrounded by a microvillar collar. Using principles from evolutionary cell biology, we reason that the transition to multicellularity required modification of pre-existing mechanisms for extracellular matrix synthesis and cytokinesis. We discuss two hypotheses for the origin of animal cell types: division of labor from ancient plurifunctional cells and conversion of temporally alternating phenotypes into spatially juxtaposed cell types. Mechanistic studies in diverse animals and their relatives promise to deepen our understanding of animal origins and cell biology.}, } @article {pmid29061899, year = {2017}, author = {Dukas, R}, title = {Cognitive innovations and the evolutionary biology of expertise.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1735}, pages = {}, pmid = {29061899}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; *Cognition ; *Learning ; Social Learning ; }, abstract = {Animal life can be perceived as the selective use of information for maximizing survival and reproduction. All organisms including bacteria and protists rely on genetic networks to build and modulate sophisticated structures and biochemical mechanisms for perceiving information and responding to environmental changes. Animals, however, have gone through a series of innovations that dramatically increased their capacity to acquire, retain and act upon information. Multicellularity was associated with the evolution of the nervous system, which took over many tasks of internal communication and coordination. This paved the way for the evolution of learning, initially based on individual experience and later also via social interactions. The increased importance of social learning also led to the evolution of language in a single lineage. Individuals' ability to dramatically increase performance via learning may have led to an evolutionary cycle of increased lifespan and greater investment in cognitive abilities, as well as in the time necessary for the development and refinement of expertise. We still know little, however, about the evolutionary biology, genetics and neurobiological mechanisms that underlie such expertise and its development.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.}, } @article {pmid29061894, year = {2017}, author = {Aktipis, A and Maley, CC}, title = {Cooperation and cheating as innovation: insights from cellular societies.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1735}, pages = {}, pmid = {29061894}, issn = {1471-2970}, support = {P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cooperative Behavior ; *Eukaryota ; Microbial Interactions ; *Microbiota ; Models, Biological ; }, abstract = {The capacity to innovate is often considered a defining feature of human societies, but it is not a capacity that is unique to human societies: innovation occurs in cellular societies as well. Cellular societies such as multicellular bodies and microbial communities, including the human microbiome, are capable of innovation in response to novel opportunities and threats. Multicellularity represents a suite of innovations for cellular cooperation, but multicellularity also opened up novel opportunities for cells to cheat, exploiting the infrastructure and resources of the body. Multicellular bodies evolve less quickly than the cells within them, leaving them vulnerable to cellular innovations that can lead to cancer and infections. In order to counter these threats, multicellular bodies deploy additional innovations including the adaptive immune system and the development of partnerships with preferred microbial partners. What can we learn from examining these innovations in cooperation and cheating in cellular societies? First, innovation in social systems involves a constant tension between novel mechanisms that enable greater size and complexity of cooperative entities and novel ways of cheating. Second, cultivating cooperation with partners who can rapidly and effectively innovate (such as microbes) is important for large entities including multicellular bodies. And third, multicellularity enabled cells to manage risk socially, allowing organisms to survive in challenging environments where life would otherwise be impossible. Throughout, we ask how insights from cellular societies might be translated into new innovations in human health and medicine, promoting and protecting the cellular cooperation that makes us viable multicellular organisms.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.}, } @article {pmid29061893, year = {2017}, author = {Ratcliff, WC and Herron, M and Conlin, PL and Libby, E}, title = {Nascent life cycles and the emergence of higher-level individuality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1735}, pages = {}, pmid = {29061893}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Individuality ; *Life Cycle Stages ; *Life History Traits ; Models, Genetic ; Mutation ; }, abstract = {Evolutionary transitions in individuality (ETIs) occur when formerly autonomous organisms evolve to become parts of a new, 'higher-level' organism. One of the first major hurdles that must be overcome during an ETI is the emergence of Darwinian evolvability in the higher-level entity (e.g. a multicellular group), and the loss of Darwinian autonomy in the lower-level units (e.g. individual cells). Here, we examine how simple higher-level life cycles are a key innovation during an ETI, allowing this transfer of fitness to occur 'for free'. Specifically, we show how novel life cycles can arise and lead to the origin of higher-level individuals by (i) mitigating conflicts between levels of selection, (ii) engendering the expression of heritable higher-level traits and (iii) allowing selection to efficiently act on these emergent higher-level traits. Further, we compute how canonical early life cycles vary in their ability to fix beneficial mutations via mathematical modelling. Life cycles that lack a persistent lower-level stage and develop clonally are far more likely to fix 'ratcheting' mutations that limit evolutionary reversion to the pre-ETI state. By stabilizing the fragile first steps of an evolutionary transition in individuality, nascent higher-level life cycles may play a crucial role in the origin of complex life.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.}, } @article {pmid29050666, year = {2017}, author = {Fortier, LC}, title = {The Contribution of Bacteriophages to the Biology and Virulence of Pathogenic Clostridia.}, journal = {Advances in applied microbiology}, volume = {101}, number = {}, pages = {169-200}, doi = {10.1016/bs.aambs.2017.05.002}, pmid = {29050666}, issn = {0065-2164}, mesh = {Bacteriophages/*physiology ; Clostridioides difficile/pathogenicity/physiology/*virology ; Humans ; Prophages ; Virulence ; }, abstract = {Bacteriophages are key players in the evolution of most bacteria. Temperate phages have been associated with virulence of some of the deadliest pathogenic bacteria. Among the most notorious cases, the genes encoding the botulinum neurotoxin produced by Clostridium botulinum types C and D and the α-toxin (TcnA) produced by Clostridium novyi are both encoded within prophage genomes. Clostridium difficile is another important human pathogen and the recent identification of a complete binary toxin locus (CdtLoc) carried on a C. difficile prophage raises the potential for horizontal transfer of toxin genes by mobile genetic elements. Although the TcdA and TcdB toxins produced by C. difficile have never been found outside the pathogenicity locus (PaLoc), some prophages can still influence their production. Prophages can alter the expression of several metabolic and regulatory genes in C. difficile, as well as cell surface proteins such as CwpV, which confers phage resistance. Homologs of an Agr-like quorum sensing system have been identified in a C. difficile prophage, suggesting that it could possibly participate in cell-cell communication. Yet, other C. difficile prophages contain riboswitches predicted to recognize the secondary messenger molecule c-di-GMP involved in bacterial multicellular behaviors. Altogether, recent findings on clostridial phages underline the diversity of mechanisms and intricate relationship linking phages with their host. Here, milestone discoveries linking phages and virulence of some of the most pathogenic clostridial species will be retraced, with a focus on C. botulinum, C. novyi, C. difficile, and Clostridium perfringens phages, for which evidences are mostly available.}, } @article {pmid29046735, year = {2017}, author = {Luebeck, EG and Curtius, K and Hazelton, WD and Maden, S and Yu, M and Thota, PN and Patil, DT and Chak, A and Willis, JE and Grady, WM}, title = {Identification of a key role of widespread epigenetic drift in Barrett's esophagus and esophageal adenocarcinoma.}, journal = {Clinical epigenetics}, volume = {9}, number = {}, pages = {113}, pmid = {29046735}, issn = {1868-7083}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; P50 CA150964/CA/NCI NIH HHS/United States ; U01 CA086402/CA/NCI NIH HHS/United States ; U01 CA182940/CA/NCI NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; U01 CA152756/CA/NCI NIH HHS/United States ; U54 CA163060/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/*genetics ; Aged ; Barrett Esophagus/*genetics ; CpG Islands ; *DNA Methylation ; Databases, Genetic ; Disease Progression ; Epigenesis, Genetic ; Esophageal Neoplasms/*genetics ; Female ; Gene Expression Regulation, Neoplastic ; *Genetic Drift ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Models, Genetic ; }, abstract = {BACKGROUND: Recent studies have identified age-related changes in DNA methylation patterns in normal and cancer tissues in a process that is called epigenetic drift. However, the evolving patterns, functional consequences, and dynamics of epigenetic drift during carcinogenesis remain largely unexplored. Here we analyze the evolution of epigenetic drift patterns during progression from normal squamous esophagus tissue to Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) using 173 tissue samples from 100 (nonfamilial) BE patients, along with publically available datasets including The Cancer Genome Atlas (TCGA).

RESULTS: Our analysis reveals extensive methylomic drift between normal squamous esophagus and BE tissues in nonprogressed BE patients, with differential drift affecting 4024 (24%) of 16,984 normally hypomethylated cytosine-guanine dinucleotides (CpGs) occurring in CpG islands. The majority (63%) of islands that include drift CpGs are associated with gene promoter regions. Island CpGs that drift have stronger pairwise correlations than static islands, reflecting collective drift consistent with processive DNA methylation maintenance. Individual BE tissues are extremely heterogeneous in their distribution of methylomic drift and encompass unimodal low-drift to bimodal high-drift patterns, reflective of differences in BE tissue age. Further analysis of longitudinally collected biopsy samples from 20 BE patients confirm the time-dependent evolution of these drift patterns. Drift patterns in EAC are similar to those in BE, but frequently exhibit enhanced bimodality and advanced mode drift. To better understand the observed drift patterns, we developed a multicellular stochastic model at the CpG island level. Importantly, we find that nonlinear feedback in the model between mean island methylation and CpG methylation rates is able to explain the widely heterogeneous collective drift patterns. Using matched gene expression and DNA methylation data in EAC from TCGA and other publically available data, we also find that advanced methylomic drift is correlated with significant transcriptional repression of ~ 200 genes in important regulatory and developmental pathways, including several checkpoint and tumor suppressor-like genes.

CONCLUSIONS: Taken together, our findings suggest that epigenetic drift evolution acts to significantly reduce the expression of developmental genes that may alter tissue characteristics and improve functional adaptation during BE to EAC progression.}, } @article {pmid29021161, year = {2017}, author = {Jackson, MDB and Duran-Nebreda, S and Bassel, GW}, title = {Network-based approaches to quantify multicellular development.}, journal = {Journal of the Royal Society, Interface}, volume = {14}, number = {135}, pages = {}, pmid = {29021161}, issn = {1742-5662}, support = {BB/M01116X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L010232/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N009754/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Humans ; *Models, Biological ; }, abstract = {Multicellularity and cellular cooperation confer novel functions on organs following a structure-function relationship. How regulated cell migration, division and differentiation events generate cellular arrangements has been investigated, providing insight into the regulation of genetically encoded patterning processes. Much less is known about the higher-order properties of cellular organization within organs, and how their functional coordination through global spatial relations shape and constrain organ function. Key questions to be addressed include: why are cells organized in the way they are? What is the significance of the patterns of cellular organization selected for by evolution? What other configurations are possible? These may be addressed through a combination of global cellular interaction mapping and network science to uncover the relationship between organ structure and function. Using this approach, global cellular organization can be discretized and analysed, providing a quantitative framework to explore developmental processes. Each of the local and global properties of integrated multicellular systems can be analysed and compared across different tissues and models in discrete terms. Advances in high-resolution microscopy and image analysis continue to make cellular interaction mapping possible in an increasing variety of biological systems and tissues, broadening the further potential application of this approach. Understanding the higher-order properties of complex cellular assemblies provides the opportunity to explore the evolution and constraints of cell organization, establishing structure-function relationships that can guide future organ design.}, } @article {pmid28988859, year = {2017}, author = {Vermeij, GJ}, title = {How the Land Became the Locus of Major Evolutionary Innovations.}, journal = {Current biology : CB}, volume = {27}, number = {20}, pages = {3178-3182.e1}, doi = {10.1016/j.cub.2017.08.076}, pmid = {28988859}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; *Embryophyta/anatomy & histology/physiology ; *Environment ; *Invertebrates/anatomy & histology/physiology ; *Vertebrates/anatomy & histology/physiology ; }, abstract = {Life originated in the sea and evolved its early metabolic pathways in water [1, 2]. Nevertheless, activities of organisms on land have influenced and enriched marine ecosystems with oxygen and nutrients for billions of years [3-7]. In contrast to the history of species diversity in the sea and on land [8-10] and the flows of resources within and between these two realms [11], little is known about the times and places of origin of major metabolic and ecological innovations during the Phanerozoic. Many innovations among multicellular organisms originated in the sea during or before the Cambrian, including predation and most of its variations, biomineralization, colonial or clonal growth, bioerosion, deposit feeding, bioturbation by animals, communication at a distance by vision and olfaction, photosymbiosis, chemosymbiosis, suspension feeding, osmotrophy, internal fertilization, jet propulsion, undulatory locomotion, and appendages for movement. Activity is less constrained in air than in the denser, more viscous medium of water [9, 12-14]. I therefore predict that high-performance metabolic and ecological innovations should predominantly originate on land after the Ordovician once organisms had conquered the challenges of life away from water and later appeared in the sea, either in marine-colonizing clades or by arising separately in clades that never left the sea. In support of this hypothesis, I show that 11 of 13 major post-Ordovician innovations appeared first or only on land. This terrestrial locus of innovation cannot be explained by the Cretaceous to recent expansion of diversity on land. It reveals one of several irreversible shifts in the history of life.}, } @article {pmid28985561, year = {2017}, author = {Bowman, JL and Kohchi, T and Yamato, KT and Jenkins, J and Shu, S and Ishizaki, K and Yamaoka, S and Nishihama, R and Nakamura, Y and Berger, F and Adam, C and Aki, SS and Althoff, F and Araki, T and Arteaga-Vazquez, MA and Balasubrmanian, S and Barry, K and Bauer, D and Boehm, CR and Briginshaw, L and Caballero-Perez, J and Catarino, B and Chen, F and Chiyoda, S and Chovatia, M and Davies, KM and Delmans, M and Demura, T and Dierschke, T and Dolan, L and Dorantes-Acosta, AE and Eklund, DM and Florent, SN and Flores-Sandoval, E and Fujiyama, A and Fukuzawa, H and Galik, B and Grimanelli, D and Grimwood, J and Grossniklaus, U and Hamada, T and Haseloff, J and Hetherington, AJ and Higo, A and Hirakawa, Y and Hundley, HN and Ikeda, Y and Inoue, K and Inoue, SI and Ishida, S and Jia, Q and Kakita, M and Kanazawa, T and Kawai, Y and Kawashima, T and Kennedy, M and Kinose, K and Kinoshita, T and Kohara, Y and Koide, E and Komatsu, K and Kopischke, S and Kubo, M and Kyozuka, J and Lagercrantz, U and Lin, SS and Lindquist, E and Lipzen, AM and Lu, CW and De Luna, E and Martienssen, RA and Minamino, N and Mizutani, M and Mizutani, M and Mochizuki, N and Monte, I and Mosher, R and Nagasaki, H and Nakagami, H and Naramoto, S and Nishitani, K and Ohtani, M and Okamoto, T and Okumura, M and Phillips, J and Pollak, B and Reinders, A and Rövekamp, M and Sano, R and Sawa, S and Schmid, MW and Shirakawa, M and Solano, R and Spunde, A and Suetsugu, N and Sugano, S and Sugiyama, A and Sun, R and Suzuki, Y and Takenaka, M and Takezawa, D and Tomogane, H and Tsuzuki, M and Ueda, T and Umeda, M and Ward, JM and Watanabe, Y and Yazaki, K and Yokoyama, R and Yoshitake, Y and Yotsui, I and Zachgo, S and Schmutz, J}, title = {Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.}, journal = {Cell}, volume = {171}, number = {2}, pages = {287-304.e15}, doi = {10.1016/j.cell.2017.09.030}, pmid = {28985561}, issn = {1097-4172}, support = {BB/L014130/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; P 28320/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adaptation, Biological ; *Biological Evolution ; Embryophyta/*genetics/physiology ; Gene Expression Regulation, Plant ; *Genome, Plant ; Marchantia/*genetics/physiology ; Molecular Sequence Annotation ; Signal Transduction ; Transcription, Genetic ; }, abstract = {The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.}, } @article {pmid28968519, year = {2017}, author = {Crocker, J and Ilsley, GR}, title = {Using synthetic biology to study gene regulatory evolution.}, journal = {Current opinion in genetics & development}, volume = {47}, number = {}, pages = {91-101}, doi = {10.1016/j.gde.2017.09.001}, pmid = {28968519}, issn = {1879-0380}, mesh = {Binding Sites ; Drosophila Proteins/genetics ; *Enhancer Elements, Genetic ; *Evolution, Molecular ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/*genetics ; Protein Binding ; *Synthetic Biology ; Transcription, Genetic ; }, abstract = {Transcriptional enhancers specify the precise time, level, and location of gene expression. Disentangling and characterizing the components of enhancer activity in multicellular eukaryotic development has proven challenging because enhancers contain activator and repressor binding sites for multiple factors that each exert nuanced, context-dependent control of enhancer activity. Recent advances in synthetic biology provide an almost unlimited ability to create and modify regulatory elements and networks, offering unprecedented power to study gene regulation. Here we review several studies demonstrating the utility of synthetic biology for studying enhancer function during development and evolution. These studies clearly show that synthetic biology can provide a way to reverse-engineer and reengineer transcriptional regulation in animal genomes with enormous potential for understanding evolution.}, } @article {pmid28961459, year = {2018}, author = {Deb, J and Bland, HM and Østergaard, L}, title = {Developmental cartography: coordination via hormonal and genetic interactions during gynoecium formation.}, journal = {Current opinion in plant biology}, volume = {41}, number = {}, pages = {54-60}, doi = {10.1016/j.pbi.2017.09.004}, pmid = {28961459}, issn = {1879-0356}, support = {BBS/E/J/000PR9788/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M004112/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/J/000PR9773/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/J/00000613/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004588/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P013511/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/genetics/growth & development/*physiology ; Cytokinins/metabolism ; Evolution, Molecular ; Flowers/genetics/growth & development/*physiology ; Indoleacetic Acids/metabolism ; Plant Growth Regulators/*metabolism ; Plant Leaves/genetics/growth & development/physiology ; }, abstract = {Development in multicellular organisms requires the establishment of tissue identity through polarity cues. The Arabidopsis gynoecium presents an excellent model to study this coordination, as it comprises a complex tissue structure which is established through multiple polarity systems. The gynoecium is derived from the fusion of two carpels and forms in the centre of the flower. Many regulators of carpel development also have roles in leaf development, emphasizing the evolutionary origin of carpels as modified leaves. The gynoecium can therefore be considered as having evolved from a simple setup followed by adjustment in tissue polarity to facilitate efficient reproduction. Here, we discuss concepts to understand how hormonal and genetic systems interact to pattern the gynoecium.}, } @article {pmid28959054, year = {2017}, author = {Attwood, MM and Krishnan, A and Almén, MS and Schiöth, HB}, title = {Highly diversified expansions shaped the evolution of membrane bound proteins in metazoans.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {12387}, pmid = {28959054}, issn = {2045-2322}, mesh = {Animals ; *Biodiversity ; Datasets as Topic ; Enzymes/genetics ; *Evolution, Molecular ; Membrane Proteins/*genetics ; Phylogeny ; Proteome/*genetics ; }, abstract = {The dramatic increase in membrane proteome complexity is arguably one of the most pivotal evolutionary events that underpins the origin of multicellular animals. However, the origin of a significant number of membrane families involved in metazoan development has not been clarified. In this study, we have manually curated the membrane proteomes of 22 metazoan and 2 unicellular holozoan species. We identify 123,014 membrane proteins in these 24 eukaryotic species and classify 86% of the dataset. We determine 604 functional clusters that are present from the last holozoan common ancestor (LHCA) through many metazoan species. Intriguingly, we show that more than 70% of the metazoan membrane protein families have a premetazoan origin. The data show that enzymes are more highly represented in the LHCA and expand less than threefold throughout metazoan species; in contrast to receptors that are relatively few in the LHCA but expand nearly eight fold within metazoans. Expansions related to cell adhesion, communication, immune defence, and developmental processes are shown in conjunction with emerging biological systems, such as neuronal development, cytoskeleton organization, and the adaptive immune response. This study defines the possible LHCA membrane proteome and describes the fundamental functional clusters that underlie metazoan diversity and innovation.}, } @article {pmid28938124, year = {2017}, author = {Hinshaw, SM and Makrantoni, V and Harrison, SC and Marston, AL}, title = {The Kinetochore Receptor for the Cohesin Loading Complex.}, journal = {Cell}, volume = {171}, number = {1}, pages = {72-84.e13}, pmid = {28938124}, issn = {1097-4172}, support = {/WT_/Wellcome Trust/United Kingdom ; 107827/WT_/Wellcome Trust/United Kingdom ; P41 GM103403/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Cycle Proteins/*metabolism ; Centromere/metabolism ; Chromosomal Proteins, Non-Histone/*metabolism ; Cytoskeletal Proteins/metabolism ; Kinetochores/*metabolism ; Multiprotein Complexes/metabolism ; Phosphorylation ; Phylogeny ; Saccharomyces cerevisiae/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; X-Ray Diffraction ; Cohesins ; }, abstract = {The ring-shaped cohesin complex brings together distant DNA domains to maintain, express, and segregate the genome. Establishing specific chromosomal linkages depends on cohesin recruitment to defined loci. One such locus is the budding yeast centromere, which is a paradigm for targeted cohesin loading. The kinetochore, a multiprotein complex that connects centromeres to microtubules, drives the recruitment of high levels of cohesin to link sister chromatids together. We have exploited this system to determine the mechanism of specific cohesin recruitment. We show that phosphorylation of the Ctf19 kinetochore protein by a conserved kinase, DDK, provides a binding site for the Scc2/4 cohesin loading complex, thereby directing cohesin loading to centromeres. A similar mechanism targets cohesin to chromosomes in vertebrates. These findings represent a complete molecular description of targeted cohesin loading, a phenomenon with wide-ranging importance in chromosome segregation and, in multicellular organisms, transcription regulation.}, } @article {pmid28936730, year = {2017}, author = {Conigliaro, A and Fontana, S and Raimondo, S and Alessandro, R}, title = {Exosomes: Nanocarriers of Biological Messages.}, journal = {Advances in experimental medicine and biology}, volume = {998}, number = {}, pages = {23-43}, doi = {10.1007/978-981-10-4397-0_2}, pmid = {28936730}, issn = {0065-2598}, mesh = {Animals ; Exosomes/genetics/*metabolism/ultrastructure ; Humans ; Intracellular Signaling Peptides and Proteins/*metabolism ; *Lipid Metabolism ; *Nanoparticles ; Nucleic Acids/*metabolism ; Organelle Size ; Protein Transport ; *Signal Transduction ; }, abstract = {Cell-cell communication is crucial to maintain homeostasis in multicellular organism. Cells communicate each other by direct contact or by releasing factors that, soluble or packaged in membrane vesicles, can reach different regions of the organism. To date numerous studies highlighted the existence of several types of extracellular vesicles that, differing for dimension, origin and contents, play a role in physiological and/or pathological processes. Among extracellular vesicles, exosomes are emerging as efficient players to modulate target cells phenotype and as new non-invasive diagnostic and prognostic tools in multiple diseases. They, in fact, strictly reflect the type and functional status of the producing cells and are able to deliver their contents even over a long distance. The results accumulated in the last two decades and collected in this chapter, indicated that exosomes, can carry RNAs, microRNAs, long non-coding RNAs, DNA, lipids, metabolites and proteins; a deeper understanding of their contents is therefore needed to get the most from this incredible cell product.}, } @article {pmid28923586, year = {2017}, author = {Dennis, JW}, title = {Genetic code asymmetry supports diversity through experimentation with posttranslational modifications.}, journal = {Current opinion in chemical biology}, volume = {41}, number = {}, pages = {1-11}, doi = {10.1016/j.cbpa.2017.08.012}, pmid = {28923586}, issn = {1879-0402}, mesh = {Animals ; Evolution, Molecular ; *Genetic Code ; Humans ; Protein Processing, Post-Translational/*genetics ; Proteins/*genetics/*metabolism ; Selection, Genetic ; }, abstract = {Protein N-glycosylation has been identified in all three domains of life presumably conserved for its early role in glycoprotein folding. However, the N-glycans added to proteins in the secretory pathway of multicellular organisms are remodeling in the Golgi, increasing structural diversity exponentially and adding new layers of functionality in immunity, metabolism and other systems. The branching and elongation of N-glycan chains found on cell surface receptors generates a gradation of affinities for carbohydrate-binding proteins, the galectin, selectin and siglec families. These interactions adapt cellular responsiveness to environmental conditions, but their complexity presents a daunting challenge to drug design. To gain further insight, I review how N-glycans biosynthesis and biophysical properties provide a selective advantage in the form of tunable and ultrasensitive stimulus-response relationships. In addition, the N-glycosylation motif favors step-wise mutational experimentation with sites. Glycoproteins display accelerated evolution during vertebrate radiation, and the encoding asymmetry of NXS/T(X≠P) has left behind phylogenetic evidence suggesting that the genetic code may have been selected to optimize diversity in part through emerging posttranslational modifications.}, } @article {pmid28916791, year = {2017}, author = {Yamazaki, T and Ichihara, K and Suzuki, R and Oshima, K and Miyamura, S and Kuwano, K and Toyoda, A and Suzuki, Y and Sugano, S and Hattori, M and Kawano, S}, title = {Genomic structure and evolution of the mating type locus in the green seaweed Ulva partita.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {11679}, pmid = {28916791}, issn = {2045-2322}, mesh = {Chromosomes ; Computational Biology ; DNA, Algal/genetics ; *Evolution, Molecular ; *Gene Order ; *Genetic Loci ; *Genomics ; High-Throughput Nucleotide Sequencing ; Seaweed/*genetics ; Ulva/*genetics ; }, abstract = {The evolution of sex chromosomes and mating loci in organisms with UV systems of sex/mating type determination in haploid phases via genes on UV chromosomes is not well understood. We report the structure of the mating type (MT) locus and its evolutionary history in the green seaweed Ulva partita, which is a multicellular organism with an isomorphic haploid-diploid life cycle and mating type determination in the haploid phase. Comprehensive comparison of a total of 12.0 and 16.6 Gb of genomic next-generation sequencing data for mt[-] and mt[+] strains identified highly rearranged MT loci of 1.0 and 1.5 Mb in size and containing 46 and 67 genes, respectively, including 23 gametologs. Molecular evolutionary analyses suggested that the MT loci diverged over a prolonged period in the individual mating types after their establishment in an ancestor. A gene encoding an RWP-RK domain-containing protein was found in the mt[-] MT locus but was not an ortholog of the chlorophycean mating type determination gene MID. Taken together, our results suggest that the genomic structure and its evolutionary history in the U. partita MT locus are similar to those on other UV chromosomes and that the MT locus genes are quite different from those of Chlorophyceae.}, } @article {pmid28916376, year = {2017}, author = {Peng, L and Wang, L and Yang, YF and Zou, MM and He, WY and Wang, Y and Wang, Q and Vasseur, L and You, MS}, title = {Transcriptome profiling of the Plutella xylostella (Lepidoptera: Plutellidae) ovary reveals genes involved in oogenesis.}, journal = {Gene}, volume = {637}, number = {}, pages = {90-99}, doi = {10.1016/j.gene.2017.09.020}, pmid = {28916376}, issn = {1879-0038}, mesh = {Animals ; Female ; Gene Expression Profiling/*methods ; Gene Regulatory Networks ; Insect Proteins/*genetics/metabolism ; Insecticide Resistance/*genetics ; Moths/*genetics/growth & development/metabolism ; *Oogenesis ; Ovary/growth & development/*metabolism ; Phylogeny ; Reproduction ; *Transcriptome ; }, abstract = {BACKGROUND: As a specialized organ, the insect ovary performs valuable functions by ensuring fecundity and population survival. Oogenesis is the complex physiological process resulting in the production of mature eggs, which are involved in epigenetic programming, germ cell behavior, cell cycle regulation, etc. Identification of the genes involved in ovary development and oogenesis is critical to better understand the reproductive biology and screening for the potential molecular targets in Plutella xylostella, a worldwide destructive pest of economically major crops.

RESULTS: Based on transcriptome sequencing, a total of 7.88Gb clean nucleotides was obtained, with 19,934 genes and 1861 new transcripts being identified. Expression profiling indicated that 61.7% of the genes were expressed (FPKM≥1) in the P. xylostella ovary. GO annotation showed that the pathways of multicellular organism reproduction and multicellular organism reproduction process, as well as gamete generation and chorion were significantly enriched. Processes that were most likely relevant to reproduction included the spliceosome, ubiquitin mediated proteolysis, endocytosis, PI3K-Akt signaling pathway, insulin signaling pathway, cAMP signaling pathway, and focal adhesion were identified in the top 20 'highly represented' KEGG pathways. Functional genes involved in oogenesis were further analyzed and validated by qRT-PCR to show their potential predominant roles in P. xylostella reproduction.

CONCLUSIONS: Our newly developed P. xylostella ovary transcriptome provides an overview of the gene expression profiling in this specialized tissue and the functional gene network closely related to the ovary development and oogenesis. This is the first genome-wide transcriptome dataset of P. xylostella ovary that includes a subset of functionally activated genes. This global approach will be the basis for further studies on molecular mechanisms of P. xylostella reproduction aimed at screening potential molecular targets for integrated pest management.}, } @article {pmid28904210, year = {2017}, author = {Willy, NM and Ferguson, JP and Huber, SD and Heidotting, SP and Aygün, E and Wurm, SA and Johnston-Halperin, E and Poirier, MG and Kural, C}, title = {Membrane mechanics govern spatiotemporal heterogeneity of endocytic clathrin coat dynamics.}, journal = {Molecular biology of the cell}, volume = {28}, number = {24}, pages = {3480-3488}, pmid = {28904210}, issn = {1939-4586}, support = {R01 AI121124/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Biomechanical Phenomena ; Cell Line, Tumor ; Cell Membrane/metabolism/physiology ; Cells, Cultured ; Chlorocebus aethiops ; Clathrin/metabolism ; Clathrin-Coated Vesicles/metabolism/*physiology ; Coated Pits, Cell-Membrane/metabolism/physiology ; Cytoplasm/metabolism ; Drosophila ; Endocytosis/physiology ; Humans ; Spatio-Temporal Analysis ; }, abstract = {Dynamics of endocytic clathrin-coated structures can be remarkably divergent across different cell types, cells within the same culture, or even distinct surfaces of the same cell. The origin of this astounding heterogeneity remains to be elucidated. Here we show that cellular processes associated with changes in effective plasma membrane tension induce significant spatiotemporal alterations in endocytic clathrin coat dynamics. Spatiotemporal heterogeneity of clathrin coat dynamics is also observed during morphological changes taking place within developing multicellular organisms. These findings suggest that tension gradients can lead to patterning and differentiation of tissues through mechanoregulation of clathrin-mediated endocytosis.}, } @article {pmid28904062, year = {2017}, author = {Huang, Y and Wang, S and Guo, Q and Kessel, S and Rubinoff, I and Chan, LL and Li, P and Liu, Y and Qiu, J and Zhou, C}, title = {Optical Coherence Tomography Detects Necrotic Regions and Volumetrically Quantifies Multicellular Tumor Spheroids.}, journal = {Cancer research}, volume = {77}, number = {21}, pages = {6011-6020}, pmid = {28904062}, issn = {1538-7445}, support = {R15 EB019704/EB/NIBIB NIH HHS/United States ; R21 EY026380/EY/NEI NIH HHS/United States ; }, mesh = {Cell Culture Techniques/methods ; Cell Line, Tumor ; Cell Survival ; HCT116 Cells ; Humans ; Imaging, Three-Dimensional/*methods ; Necrosis ; Neoplasms/*diagnostic imaging ; Reproducibility of Results ; Spheroids, Cellular/*pathology ; Time Factors ; Tomography, Optical Coherence/*methods ; }, abstract = {Three-dimensional (3D) tumor spheroid models have gained increased recognition as important tools in cancer research and anticancer drug development. However, currently available imaging approaches used in high-throughput screening drug discovery platforms, for example, bright-field, phase contrast, and fluorescence microscopies, are unable to resolve 3D structures deep inside (>50 μm) tumor spheroids. In this study, we established a label-free, noninvasive optical coherence tomography (OCT) imaging platform to characterize 3D morphologic and physiologic information of multicellular tumor spheroids (MCTS) growing from approximately 250 to 600 μm in height over 21 days. In particular, tumor spheroids of two cell lines, glioblastoma (U-87MG) and colorectal carcinoma (HCT116), exhibited distinctive evolutions in their geometric shapes at late growth stages. Volumes of MCTS were accurately quantified using a voxel-based approach without presumptions of their geometries. In contrast, conventional diameter-based volume calculations assuming perfect spherical shape resulted in large quantification errors. Furthermore, we successfully detected necrotic regions within these tumor spheroids based on increased intrinsic optical attenuation, suggesting a promising alternative of label-free viability tests in tumor spheroids. Therefore, OCT can serve as a promising imaging modality to characterize morphologic and physiologic features of MCTS, showing great potential for high-throughput drug screening. Cancer Res; 77(21); 6011-20. ©2017 AACR.}, } @article {pmid28899581, year = {2017}, author = {Kennedy, P and Baron, G and Qiu, B and Freitak, D and Helanterä, H and Hunt, ER and Manfredini, F and O'Shea-Wheller, T and Patalano, S and Pull, CD and Sasaki, T and Taylor, D and Wyatt, CDR and Sumner, S}, title = {Deconstructing Superorganisms and Societies to Address Big Questions in Biology.}, journal = {Trends in ecology & evolution}, volume = {32}, number = {11}, pages = {861-872}, doi = {10.1016/j.tree.2017.08.004}, pmid = {28899581}, issn = {1872-8383}, mesh = {Animals ; *Behavior, Animal ; Biological Evolution ; Hymenoptera/*physiology ; Isoptera/*physiology ; *Social Behavior ; }, abstract = {Social insect societies are long-standing models for understanding social behaviour and evolution. Unlike other advanced biological societies (such as the multicellular body), the component parts of social insect societies can be easily deconstructed and manipulated. Recent methodological and theoretical innovations have exploited this trait to address an expanded range of biological questions. We illustrate the broadening range of biological insight coming from social insect biology with four examples. These new frontiers promote open-minded, interdisciplinary exploration of one of the richest and most complex of biological phenomena: sociality.}, } @article {pmid28898926, year = {2018}, author = {Mosaffa, P and Rodríguez-Ferran, A and Muñoz, JJ}, title = {Hybrid cell-centred/vertex model for multicellular systems with equilibrium-preserving remodelling.}, journal = {International journal for numerical methods in biomedical engineering}, volume = {34}, number = {3}, pages = {}, doi = {10.1002/cnm.2928}, pmid = {28898926}, issn = {2040-7947}, mesh = {*Biomechanical Phenomena ; Humans ; Models, Biological ; }, abstract = {We present a hybrid cell-centred/vertex model for mechanically simulating planar cellular monolayers undergoing cell reorganisation. Cell centres are represented by a triangular nodal network, while the cell boundaries are formed by an associated vertex network. The two networks are coupled through a kinematic constraint which we allow to relax progressively. Special attention is paid to the change of cell-cell connectivity due to cell reorganisation or remodelling events. We handle these situations by using a variable resting length and applying an Equilibrium-Preserving Mapping on the new connectivity, which computes a new set of resting lengths that preserve nodal and vertex equilibrium. We illustrate the properties of the model by simulating monolayers subjected to imposed extension and during a wound healing process. The evolution of forces and the Equilibrium-Preserving Mapping are analysed during the remodelling events. As a by-product, the proposed technique enables to recover fully vertex or fully cell-centred models in a seamless manner by modifying a numerical parameter of the model.}, } @article {pmid28898640, year = {2017}, author = {Ferrer-Bonet, M and Ruiz-Trillo, I}, title = {Capsaspora owczarzaki.}, journal = {Current biology : CB}, volume = {27}, number = {17}, pages = {R829-R830}, doi = {10.1016/j.cub.2017.05.074}, pmid = {28898640}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; Eukaryota/*classification/*cytology/genetics ; Genome ; Phylogeny ; }, abstract = {Capsaspora owczarzaki is a unicellular eukaryote that is becoming pivotal to understanding the origin of animal multicellularity.}, } @article {pmid28893859, year = {2018}, author = {Rübsam, M and Broussard, JA and Wickström, SA and Nekrasova, O and Green, KJ and Niessen, CM}, title = {Adherens Junctions and Desmosomes Coordinate Mechanics and Signaling to Orchestrate Tissue Morphogenesis and Function: An Evolutionary Perspective.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, pmid = {28893859}, issn = {1943-0264}, support = {R01 AR043380/AR/NIAMS NIH HHS/United States ; T32 AR007593/AR/NIAMS NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; R01 CA122151/CA/NCI NIH HHS/United States ; R01 AR041836/AR/NIAMS NIH HHS/United States ; R01 CA228196/CA/NCI NIH HHS/United States ; P30 AR057216/AR/NIAMS NIH HHS/United States ; R37 AR043380/AR/NIAMS NIH HHS/United States ; }, mesh = {Adherens Junctions/genetics/*physiology ; Animals ; *Biological Evolution ; Cell Polarity ; Desmosomes/genetics/*physiology ; Epithelial Cells/physiology ; Signal Transduction/*physiology ; }, abstract = {Cadherin-based adherens junctions (AJs) and desmosomes are crucial to couple intercellular adhesion to the actin or intermediate filament cytoskeletons, respectively. As such, these intercellular junctions are essential to provide not only integrity to epithelia and other tissues but also the mechanical machinery necessary to execute complex morphogenetic and homeostatic intercellular rearrangements. Moreover, these spatially defined junctions serve as signaling hubs that integrate mechanical and chemical pathways to coordinate tissue architecture with behavior. This review takes an evolutionary perspective on how the emergence of these two essential intercellular junctions at key points during the evolution of multicellular animals afforded metazoans with new opportunities to integrate adhesion, cytoskeletal dynamics, and signaling. We discuss known literature on cross-talk between the two junctions and, using the skin epidermis as an example, provide a model for how these two junctions function in concert to orchestrate tissue organization and function.}, } @article {pmid28889384, year = {2018}, author = {Yoshida, T and Okuyama, H and Endo, H and Inoue, M}, title = {Spheroid Cultures of Primary Urothelial Cancer Cells: Cancer Tissue-Originated Spheroid (CTOS) Method.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1655}, number = {}, pages = {145-153}, doi = {10.1007/978-1-4939-7234-0_12}, pmid = {28889384}, issn = {1940-6029}, mesh = {Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Separation/methods ; Drug Resistance, Neoplasm ; Humans ; *Primary Cell Culture/methods ; *Spheroids, Cellular ; *Tumor Cells, Cultured ; Urinary Bladder Neoplasms/*pathology ; }, abstract = {Increasingly, it has been recognized that studying cancer samples from individual patients is important for the development of effective therapeutic strategies and in endeavors to overcome therapy resistance. Primary cultures of cancer cells acutely dissected from individual patients can provide a platform that enables the study and characterization of individual tumors. To that end, we have developed a method for preparing cancer cells in the form of multi-cellular spheroids. The cells can be derived from patient tumors (primary cells), from patient-derived xenografts, or from genetically- or chemically induced animal tumors. This method of culturing spheroids composed of cells derived from cancer tissues can be applied to various types of cancer, including urothelial cancer. The method is based on the principle of retaining cell-cell contact throughout cancer cell preparation and culturing. The first step is a partial digestion of the tumor specimen into small fragments; these fragments spontaneously form spheroidal shapes within several hours. The spheroid is referred to as a cancer tissue-originated spheroid (CTOS). The advantage of the CTOS method is that it allows one to prepare pure cancer cells at high yield. CTOSs can be stably cultured in serum-free conditions. The CTOS method can be applied to drug sensitivity assays, drug screening, and analyses of intracellular signaling. Moreover, the CTOS method provides a platform for studying the nature of cancer cell clusters.}, } @article {pmid28889015, year = {2017}, author = {He, HH and Chi, YM and Yuan, K and Li, XY and Weng, SP and He, JG and Chen, YH}, title = {Functional characterization of a reactive oxygen species modulator 1 gene in Litopenaeus vannamei.}, journal = {Fish & shellfish immunology}, volume = {70}, number = {}, pages = {270-279}, doi = {10.1016/j.fsi.2017.09.024}, pmid = {28889015}, issn = {1095-9947}, mesh = {Amino Acid Sequence ; Animals ; Arthropod Proteins/*genetics/*immunology ; Base Sequence ; Cell Line ; Drosophila melanogaster ; Gene Expression Regulation ; *Immunity, Innate ; Penaeidae/*genetics/*immunology ; Phylogeny ; Reactive Oxygen Species/*metabolism ; Sequence Alignment ; Vibrio alginolyticus/physiology ; White spot syndrome virus 1/physiology ; }, abstract = {Reactive oxygen species (ROS) imparts a dual effect on multicellular organisms, wherein high levels are usually harmful, and low levels could facilitate in combating pathogenic microorganisms; therefore, the regulation of ROS production is critical. Previous studies have suggested that ROS contributes to resistance to the white spot syndrome virus (WSSV) or Vibrio alginolyticus in Litopenaeus vannamei. However, the regulation of ROS metabolism in L. vannamei remains elusive. In the present study, we proved that the overexpression of L. vannamei reactive oxygen species modulator 1 (LvROMO1) increases ROS production in Drosophila Schneider 2 (S2) cells. Real-time RT-PCR analysis indicated that LvROMO1 is induced by WSSV or V. alginolyticus infection and β-glucan or microcystin (MC-LR) injection. Further investigation showed that LvROMO1 responding to MC-LR, thereby inducing hemocytes to undergo apoptosis, and ultimately resulting in hepatopancreatic damage. And LvROMO1 downregulation induced an increase in the cumulative mortality of WSSV-infected shrimp by reducing ROS production and suppressing the expression of antimicrobial peptides genes. The findings of present study suggest that LvROMO1 plays an important role in ROS production in L. vannamei and is involved in innate immunity.}, } @article {pmid28866006, year = {2017}, author = {Witting, L}, title = {The natural selection of metabolism and mass selects allometric transitions from prokaryotes to mammals.}, journal = {Theoretical population biology}, volume = {117}, number = {}, pages = {23-42}, doi = {10.1016/j.tpb.2017.08.005}, pmid = {28866006}, issn = {1096-0325}, mesh = {Animals ; Basal Metabolism ; Biological Evolution ; Body Size ; Ecology ; Mammals/*metabolism ; Models, Biological ; Prokaryotic Cells/*metabolism ; Selection, Genetic/*physiology ; }, abstract = {The exponents of inter-specific allometries for several life history (metabolism, lifespan, reproductive rate, survival) and ecological (population density, home range) traits may evolve from the spatial dimensionality (d) of the intra-specific interactive competition that selects net assimilated energy into mass, with 1∕4 exponents being the two-dimensional (2D) case of the more general 1∕2d (Witting, 1995). While the exponents for mass-specific metabolism cluster around the predicted -1/4 and -1/6 in terrestrial and pelagic vertebrates, the allometries of mobile organisms are more diverse than the prediction. An exponent around zero has been reported for protists and protozoa (Makarieva et al., 2005, 2008), and the exponent appears to be strongly positive in prokaryotes with a value of about 5/6 (DeLong et al., 2010). I show that the natural selection of metabolism and mass is sufficient to explain exponents for mass-specific metabolism that decline from 5/6 over zero to -1∕6 in 3D, and from 3/4 over zero to -1∕4 in 2D. These results suggest that mass-specific metabolism is selected as the pace of the resource handling that generates net energy for self-replication and the selection of mass, with the decline in the metabolic exponent following from a decline in the importance of mass-specific metabolism for the selection of mass. The body mass variation in prokaryotes is found to be selected from primary variation in mass-specific metabolism, while the variation in multicellular animals is selected from primary variation in the handling and/or densities of the underlying resources, with protists and protozoa being selected as an intermediate lifeform.}, } @article {pmid28864113, year = {2017}, author = {Li, DD and Luo, Z and Chen, GH and Song, YF and Wei, CC and Pan, YX}, title = {Identification of apoptosis-related genes Bcl2 and Bax from yellow catfish Pelteobagrus fulvidraco and their transcriptional responses to waterborne and dietborne zinc exposure.}, journal = {Gene}, volume = {633}, number = {}, pages = {1-8}, doi = {10.1016/j.gene.2017.08.029}, pmid = {28864113}, issn = {1879-0038}, mesh = {Animals ; Apoptosis/*genetics/physiology ; Catfishes/*genetics/metabolism ; DNA, Complementary/genetics ; Down-Regulation ; Environmental Exposure ; Fish Proteins/classification/*genetics/physiology ; Lipid Metabolism/genetics ; Liver/metabolism ; Phylogeny ; RNA, Messenger/genetics/metabolism ; *Transcription, Genetic ; Up-Regulation ; Water/chemistry ; Zinc/analysis/*metabolism ; bcl-2-Associated X Protein/classification/*genetics/physiology ; bcl-Associated Death Protein/classification/*genetics/physiology ; }, abstract = {Apoptosis plays a key role in the physiology of multicellular organisms, and has been well studied in mammals, but not in teleosts. Zinc (Zn) has been shown to be an important regulator of apoptosis and apoptosis involves in the regulation of lipid metabolism. Moreover, our recent study indicated that waterborne and dietborne Zn exposure differently influenced lipid metabolism in Pelteobagrus fulvidraco, but further mechanism remained unknown. The hypothesis of the present study is that apoptosis mediated the Zn-induced changes of lipid metabolism of P. fulvidraco subjected to different exposure pathways. To this end, we cloned full-length cDNA sequences of Bcl2 and three Bax subtypes involved in apoptosis in P. fulvidraco, explored their mRNA expressions in responses to different Zn exposure pathways. Bcl2 and three Bax subtypes shared similar domain structure as typical pro- and anti-apoptotic Bcl2 family members. Their mRNAs were widely expressed among various tissues, but at variable levels. Waterborne Zn exposure down-regulated mRNA levels of Baxg and ratios of Baxa/Bcl2, and Baxg/Bcl2, but showed no significant effects on mRNA abundances of Bcl2, Baxa and Baxb, and the ratio of Baxb/Bcl2. In contrast, dietborne Zn exposure up-regulated mRNA levels of Bcl2, Baxa, Baxb and Baxg, but reduced the ratios of Baxa/Bcl2, Baxb/Bcl2, and Baxg/Bcl2. Considering their important roles of these genes in apoptosis induced by Zn, apoptosis may mediate the Zn-induced changes of hepatic lipid metabolism of Pelteobagrus fulvidraco under different Zn exposure pathways. For the first time, we characterized the full-length cDNA sequences of Bcl2 and three Bax subtypes, determined their expression profiles and transcriptional responses to different Zn exposure pathways, which would contribute to our understanding of the molecular basis of apoptosis, and also provide new insights into physiological responses to different Zn exposure pathways.}, } @article {pmid28862769, year = {2018}, author = {Yuan, H and Silberstein, SD}, title = {Histamine and Migraine.}, journal = {Headache}, volume = {58}, number = {1}, pages = {184-193}, doi = {10.1111/head.13164}, pmid = {28862769}, issn = {1526-4610}, mesh = {Central Nervous System/*metabolism ; Histamine/*metabolism ; Homeostasis ; Humans ; Migraine Disorders/*metabolism/*pathology ; Neurotransmitter Agents/physiology ; }, abstract = {BACKGROUND: Histamine is an ancient "tissue amine" preceding multicellular organisms. In the central nervous system (CNS), its fibers originate solely from the tuberomammillary nucleus and travel throughout the brain. It is mainly responsible for wakefulness, energy homeostasis, and memory consolidation. Recently, several studies suggest a potential role of histamine in migraine pathogenesis and management.

METHODS: Narrative review of current literature regarding histamine and migraine.

RESULTS: Histamine plays a crucial role in migraine pathogenesis: sustaining the neurogenic inflammation pathway. Interaction between mast cells (MC) and calcitonin-gene related protein (CGRP) results in sensitization of trigeminal afferents and trigeminal ganglia (TG). Histamine binds with differing affinities to four different histaminergic G-protein coupled receptors, activating protein kinases, or triggering calcium release with subsequent mode of actions. Histamine 1 receptor (H1 R) and histamine 2 receptor (H2 R) antagonists are frequently used for the treatment of allergy and gastric acid secretion, respectively, but their antagonism is probably ineffective for migraine. Histamine 3 receptor (H3 R) and histamine 4 receptor (H4 R) have a threefold higher affinity than H1 R/H2 R for histamine and are found almost exclusively on neurons and immune tissues, respectively. H3 R acts as an autoreceptor or as a heteroreceptor, lowering the release of histamine and other neurotransmitters. This is a potential target for anti-nociception and anti-neurogenic inflammation. To date, several small clinical trials using low dose histamine or N[α] -methylhistamine have demonstrated migraine prophylactic efficacy, probably via H3 R or other undetermined pathways.

CONCLUSION: The histamine system interacts with multiple regions in the CNS and may hypothetically modulate the migraine response. Low dose histamine may be a promising option for migraine prevention.}, } @article {pmid28859623, year = {2017}, author = {Patel, VD and Capra, JA}, title = {Ancient human miRNAs are more likely to have broad functions and disease associations than young miRNAs.}, journal = {BMC genomics}, volume = {18}, number = {1}, pages = {672}, pmid = {28859623}, issn = {1471-2164}, mesh = {Animals ; Disease/*genetics ; *Evolution, Molecular ; Humans ; MicroRNAs/*genetics ; Phylogeny ; Transcriptome ; }, abstract = {BACKGROUND: microRNAs (miRNAs) are essential to the regulation of gene expression in eukaryotes, and improper expression of miRNAs contributes to hundreds of diseases. Despite the essential functions of miRNAs, the evolutionary dynamics of how they are integrated into existing gene regulatory and functional networks is not well understood. Knowledge of the origin and evolutionary history a gene has proven informative about its functions and disease associations; we hypothesize that incorporating the evolutionary origins of miRNAs into analyses will help resolve differences in their functional dynamics and how they influence disease.

RESULTS: We computed the phylogenetic age of miRNAs across 146 species and quantified the relationship between human miRNA age and several functional attributes. Older miRNAs are significantly more likely to be associated with disease than younger miRNAs, and the number of associated diseases increases with age. As has been observed for genes, the miRNAs associated with different diseases have different age profiles. For example, human miRNAs implicated in cancer are enriched for origins near the dawn of animal multicellularity. Consistent with the increasing contribution of miRNAs to disease with age, older miRNAs target more genes than younger miRNAs, and older miRNAs are expressed in significantly more tissues. Furthermore, miRNAs of all ages exhibit a strong preference to target older genes; 93% of validated miRNA gene targets were in existence at the origin of the targeting miRNA. Finally, we find that human miRNAs in evolutionarily related families are more similar in their targets and expression profiles than unrelated miRNAs.

CONCLUSIONS: Considering the evolutionary origin and history of a miRNA provides useful context for the analysis of its function. Consistent with recent work in Drosophila, our results support a model in which miRNAs increase their expression and functional regulatory interactions over evolutionary time, and thus older miRNAs have increased potential to cause disease. We anticipate that these patterns hold across mammalian species; however, comprehensively evaluating them will require refining miRNA annotations across species and collecting functional data in non-human systems.}, } @article {pmid28859501, year = {2017}, author = {Csaba, G}, title = {Is there a hormonal regulation of phagocytosis at unicellular and multicellular levels? A critical review.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {64}, number = {4}, pages = {357-372}, doi = {10.1556/030.64.2017.024}, pmid = {28859501}, issn = {1217-8950}, mesh = {Animals ; Hormones/*immunology ; Humans ; Macrophages/cytology/*immunology ; *Phagocytosis ; }, abstract = {Phagocytosis is an ancient cell function, which is similar at unicellular and multicellular levels. Unicells synthesize, store, and secrete multicellular (mammalian) hormones, which influence their phagocytosis. Amino acid hormones, such as histamine, serotonin, epinephrine, and melatonin stimulate phagocytosis, whereas peptide hormones, such as adrenocorticotropic hormone (ACTH), insulin, opioids, arginine vasopressin, and atrial natriuretic peptide decreased it, independently on their chemical structure or function in multicellulars. Macrophage phagocytosis of multicellulars is also stimulated by amino acid hormones, such as histamine, epinephrine, melatonin, and thyroid hormones, however, the effect of peptide hormones is not uniform: prolactin, insulin, glucagon, somatostatin, and leptin have positive effects, whereas ACTH, human chorionic gonadotropin, opioids, and ghrelin have negative ones. Steroid hormones, such as estrogen, hydrocortisone, and dexamethasone are stimulating macrophage phagocytosis, whereas progesterone, aldosterone, and testosterone are depressing it. Considering the data and observations there is not a specific phagocytosis hormone, or a hormonal regulation of phagocytosis neither unicellular, nor multicellular level, however, hormones having specific functions in multicellulars also influence phagocytosis at both levels universally (in unicellulars) or individually (in macrophages). Nevertheless, the hormonal influence cannot be neglected, as phagocytosis (as a function) is rather sensitive to minute dose of hormones and endocrine disruptors. The hormonal influence of phagocytosis by macrophages can be deduced to the events at unicellular level.}, } @article {pmid28856734, year = {2017}, author = {Deines, P and Lachnit, T and Bosch, TCG}, title = {Competing forces maintain the Hydra metaorganism.}, journal = {Immunological reviews}, volume = {279}, number = {1}, pages = {123-136}, doi = {10.1111/imr.12564}, pmid = {28856734}, issn = {1600-065X}, mesh = {Animals ; *Biological Evolution ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Hydra/*physiology ; *Immunity, Innate ; Symbiosis ; }, abstract = {Our conventional view of multicellular organisms often overlooks the fact that they are metaorganisms. They consist of a host, which is comprised of both a community of self-replicating cells that can compete as well as cooperate and a community of associated microorganisms. This newly discovered complexity raises a profound challenge: How to maintain such a multicellular association that includes independently replicating units and even different genotypes? Here, we identify competing forces acting at the host tissue level, the host-microbe interface, and within the microbial community as key factors to maintain the metaorganism Hydra. Maintenance of host tissue integrity, as well as proper regulation and management of the multiorganismic interactions are fundamental to organismal survival and health. Findings derived from the in vivo context of the Hydra model may provide one of the simplest possible systems to address questions on how a metaorganism is established and remains in balance over time.}, } @article {pmid28846170, year = {2017}, author = {Votaw, HR and Ostrowski, EA}, title = {Stalk size and altruism investment within and among populations of the social amoeba.}, journal = {Journal of evolutionary biology}, volume = {30}, number = {11}, pages = {2017-2030}, doi = {10.1111/jeb.13172}, pmid = {28846170}, issn = {1420-9101}, mesh = {Altruism ; Dictyostelium/*cytology/genetics/*physiology ; Epistasis, Genetic ; Genotype ; Reproduction ; }, abstract = {Reproductive division of labour is common in many societies, including those of eusocial insects, cooperatively breeding vertebrates, and most forms of multicellularity. However, conflict over what is best for the individual vs. the group can prevent an optimal division of labour from being achieved. In the social amoeba Dictyostelium discoideum, cells aggregate to become multicellular and a fraction behaves altruistically, forming a dead stalk that supports the rest. Theory suggests that intra-organismal conflict over spore-stalk cell fate can drive rapid evolutionary change in allocation traits, leading to polymorphisms within populations or rapid divergence between them. Here, we assess several proxies for stalk size and spore-stalk allocation as metrics of altruism investment among strains and across geographic regions. We observe geographic divergence in stalk height that can be partly explained by differences in multicellular size, as well as variation among strains in clonal spore-stalk allocation, suggesting within-population variation in altruism investment. Analyses of chimeras comprised of strains from the same vs. different populations indicated genotype-by-genotype epistasis, where the morphology of the chimeras deviated significantly from the average morphology of the strains developed clonally. The significantly negative epistasis observed for allopatric pairings suggests that populations are diverging in their spore-stalk allocation behaviours, generating incompatibilities when they encounter one another. Our results demonstrate divergence in microbial social traits across geographically separated populations and demonstrate how quantification of genotype-by-genotype interactions can elucidate the trajectory of social trait evolution in nature.}, } @article {pmid28839913, year = {2017}, author = {Shapiro, JA}, title = {Biological action in Read-Write genome evolution.}, journal = {Interface focus}, volume = {7}, number = {5}, pages = {20160115}, pmid = {28839913}, issn = {2042-8898}, abstract = {Many of the most important evolutionary variations that generated phenotypic adaptations and originated novel taxa resulted from complex cellular activities affecting genome content and expression. These activities included (i) the symbiogenetic cell merger that produced the mitochondrion-bearing ancestor of all extant eukaryotes, (ii) symbiogenetic cell mergers that produced chloroplast-bearing ancestors of photosynthetic eukaryotes, and (iii) interspecific hybridizations and genome doublings that generated new species and adaptive radiations of higher plants and animals. Adaptive variations also involved horizontal DNA transfers and natural genetic engineering by mobile DNA elements to rewire regulatory networks, such as those essential to viviparous reproduction in mammals. In the most highly evolved multicellular organisms, biological complexity scales with 'non-coding' DNA content rather than with protein-coding capacity in the genome. Coincidentally, 'non-coding' RNAs rich in repetitive mobile DNA sequences function as key regulators of complex adaptive phenotypes, such as stem cell pluripotency. The intersections of cell fusion activities, horizontal DNA transfers and natural genetic engineering of Read-Write genomes provide a rich molecular and biological foundation for understanding how ecological disruptions can stimulate productive, often abrupt, evolutionary transformations.}, } @article {pmid28839200, year = {2017}, author = {Fickentscher, R and Weiss, M}, title = {Physical determinants of asymmetric cell divisions in the early development of Caenorhabditis elegans.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {9369}, pmid = {28839200}, issn = {2045-2322}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; *Asymmetric Cell Division ; Biomarkers ; Caenorhabditis elegans/*embryology ; Cell Size ; *Embryonic Development ; Gastrulation ; Germ Cells ; Models, Biological ; Spindle Apparatus/metabolism ; }, abstract = {Asymmetric cell divisions are of fundamental importance for the development of multicellular organisms, e.g. for the generation of founder cells. Prime examples are asymmetric cell divisions in germline precursors during the early embryogenesis of the transparent roundworm Caenorhabditis elegans, one of the major developmental model organisms. However, due to a lack of quantitative data it has remained unclear how frequent unequal daughter cell sizes emerge in the worm's early embryogenesis, and whether these originate from sterical or biochemical cues. Using quantitative light-sheet microscopy, we have found that about 40% of all cell divisions in C. elegans until gastrulation generate daughter cells with significantly different volumes. Removing the embryo's rigid eggshell revealed asymmetric divisions in somatic cells to be primarily induced by steric effects. Division asymmetries in the germline remained unaltered and were correctly reproduced by a model based on a cell-size independent, eccentric displacement of the metaphase plate. Our data suggest that asymmetric cell divisions, imposed by physical determinants, are essential for establishing important cell-cell interactions that eventually fuel a successful embryogenesis.}, } @article {pmid28827358, year = {2017}, author = {Larsen, NB and Liberti, SE and Vogel, I and Jørgensen, SW and Hickson, ID and Mankouri, HW}, title = {Stalled replication forks generate a distinct mutational signature in yeast.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {36}, pages = {9665-9670}, pmid = {28827358}, issn = {1091-6490}, mesh = {DNA Replication/*genetics ; DNA, Fungal/genetics/metabolism ; DNA, Single-Stranded/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Escherichia coli/genetics/metabolism ; Escherichia coli Proteins/genetics/metabolism ; Exodeoxyribonucleases/genetics/metabolism ; Genes, Reporter ; Genetic Engineering ; Humans ; Models, Biological ; Mutagenesis ; Mutation ; Nuclear Proteins/genetics/metabolism ; RecQ Helicases/genetics/metabolism ; Recombinant Proteins/genetics/metabolism ; Recombinational DNA Repair ; Replication Origin ; Saccharomyces cerevisiae/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; }, abstract = {Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells.}, } @article {pmid28825126, year = {2018}, author = {Chi, S and Liu, T and Wang, X and Wang, R and Wang, S and Wang, G and Shan, G and Liu, C}, title = {Functional genomics analysis reveals the biosynthesis pathways of important cellular components (alginate and fucoidan) of Saccharina.}, journal = {Current genetics}, volume = {64}, number = {1}, pages = {259-273}, pmid = {28825126}, issn = {1432-0983}, support = {41376143//National Natural Science Foundation of China/ ; 14-2-4-104-jch//Qingdao applied basic research project/ ; }, mesh = {Alginates/*metabolism ; *Biosynthetic Pathways/genetics ; Computational Biology/methods ; Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Transfer, Horizontal ; *Genome ; *Genomics/methods ; Glucuronic Acid/metabolism ; Hexuronic Acids/metabolism ; High-Throughput Nucleotide Sequencing ; Phaeophyceae/classification/*genetics/*metabolism ; Phylogeny ; Polysaccharides/*metabolism ; Symbiosis/genetics ; Transcriptome ; }, abstract = {Although alginate and fucoidan are unique cellular components and have important biological significance in brown algae, and many possible involved genes are present in brown algal genomes, their functions and regulatory mechanisms have not been fully revealed. Both polysaccharides may play important roles in the evolution of multicellular brown algae, but specific and in-depth studies are still limited. In this study, a functional genomics analysis of alginate and fucoidan biosynthesis routes was conducted in Saccharina, and the key events in these pathways in brown algae were identified. First, genes from different sources, including eukaryotic hosts via endosymbiotic gene transfer and bacteria via horizontal gene transfer, were combined to build a complete pathway framework. Then, a critical event occurred to drive these pathways to have real function: one of the mannose-6-phosphate isomerase homologs that arose by gene duplication subsequently adopted the function of the mannose-1-phosphate guanylyltransferase (MGP) gene, which was absent in algal genomes. Further, downstream pathway genes proceeded with gene expansions and complex transcriptional mechanisms, which may be conducive to the synthesis of alginate and fucoidan with diverse structures and contents depending on the developmental stage, tissue structure, and environmental conditions. This study revealed the alginate and fucoidan synthesis pathways and all included genes from separate phylogenetic sources in brown algae. Enzyme assays confirmed the function of key genes and led to the determination of a substitute for the missing MPG. All gene families had constitutively expressed member(s) to maintain the basic synthesis; and the gene function differentiation, enzyme characterization and gene expression regulation differences separated brown algae from other algae lineages and were considered to be the major driving forces for sophisticated system evolution of brown algae.}, } @article {pmid28820125, year = {2017}, author = {Stajich, JE}, title = {Fungal Genomes and Insights into the Evolution of the Kingdom.}, journal = {Microbiology spectrum}, volume = {5}, number = {4}, pages = {}, pmid = {28820125}, issn = {2165-0497}, support = {S10 OD016290/OD/NIH HHS/United States ; }, mesh = {Evolution, Molecular ; Fungi/*genetics ; Genes, Fungal/*genetics ; Genome, Fungal/*genetics ; }, abstract = {The kingdom Fungi comprises species that inhabit nearly all ecosystems. Fungi exist as both free-living and symbiotic unicellular and multicellular organisms with diverse morphologies. The genomes of fungi encode genes that enable them to thrive in diverse environments, invade plant and animal cells, and participate in nutrient cycling in terrestrial and aquatic ecosystems. The continuously expanding databases of fungal genome sequences have been generated by individual and large-scale efforts such as Génolevures, Broad Institute's Fungal Genome Initiative, and the 1000 Fungal Genomes Project (http://1000.fungalgenomes.org). These efforts have produced a catalog of fungal genes and genomic organization. The genomic datasets can be utilized to better understand how fungi have adapted to their lifestyles and ecological niches. Large datasets of fungal genomic and transcriptomic data have enabled the use of novel methodologies and improved the study of fungal evolution from a molecular sequence perspective. Combined with microscopes, petri dishes, and woodland forays, genome sequencing supports bioinformatics and comparative genomics approaches as important tools in the study of the biology and evolution of fungi.}, } @article {pmid28820115, year = {2017}, author = {Nagy, LG and Tóth, R and Kiss, E and Slot, J and Gácser, A and Kovács, GM}, title = {Six Key Traits of Fungi: Their Evolutionary Origins and Genetic Bases.}, journal = {Microbiology spectrum}, volume = {5}, number = {4}, pages = {}, pmid = {28820115}, issn = {2165-0497}, mesh = {*Biological Evolution ; Cell Lineage/genetics ; Evolution, Molecular ; Fruiting Bodies, Fungal/*growth & development ; Fungi/*genetics/*growth & development ; Hyphae/*growth & development ; Mycorrhizae/physiology ; Phylogeny ; Plants/microbiology ; }, abstract = {The fungal lineage is one of the three large eukaryotic lineages that dominate terrestrial ecosystems. They share a common ancestor with animals in the eukaryotic supergroup Opisthokonta and have a deeper common ancestry with plants, yet several phenotypes, such as morphological, physiological, or nutritional traits, make them unique among all living organisms. This article provides an overview of some of the most important fungal traits, how they evolve, and what major genes and gene families contribute to their development. The traits highlighted here represent just a sample of the characteristics that have evolved in fungi, including polarized multicellular growth, fruiting body development, dimorphism, secondary metabolism, wood decay, and mycorrhizae. However, a great number of other important traits also underlie the evolution of the taxonomically and phenotypically hyperdiverse fungal kingdom, which could fill up a volume on its own. After reviewing the evolution of these six well-studied traits in fungi, we discuss how the recurrent evolution of phenotypic similarity, that is, convergent evolution in the broad sense, has shaped their phylogenetic distribution in extant species.}, } @article {pmid28819830, year = {2017}, author = {Liu, A and He, F and Gu, X}, title = {Identification and characterization of tyrosine kinases in anole lizard indicate the conserved tyrosine kinase repertoire in vertebrates.}, journal = {Molecular genetics and genomics : MGG}, volume = {292}, number = {6}, pages = {1405-1418}, pmid = {28819830}, issn = {1617-4623}, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence ; Lizards/classification/genetics/*metabolism ; Phylogeny ; Protein-Tyrosine Kinases/chemistry/*genetics ; }, abstract = {The tyrosine kinases (TKs) play principal roles in regulation of multicellular aspects of the organism and are implicated in many cancer types and congenital disorders. The anole lizard has recently been introduced as a model organism for laboratory-based studies of organismal function and field studies of ecology and evolution. However, the TK family of anole lizard has not been systematically identified and characterized yet. In this study, we identified 82 TK-encoding genes in the anole lizard genome and classified them into 28 subfamilies through phylogenetic analysis, with no member from ROS and STYK1 subfamilies identified. Although TK domain sequences and domain organization in each subfamily were conserved, the total number of TKs in different species was much variable. In addition, extensive evolutionary analysis in metazoans indicated that TK repertoire in vertebrates tends to be remarkably stable. Phylogenetic analysis of Eph subfamily indicated that the divergence of EphA and EphB occurred prior to the whole genome duplication (WGD) but after the split of Urochordates and vertebrates. Moreover, the expression pattern analysis of lizard TK genes among 9 different tissues showed that 14 TK genes exhibited tissue-specific expression and 6 TK genes were widely expressed. Comparative analysis of TK expression suggested that the tissue specifically expressed genes showed different expression pattern but the widely expressed genes showed similar pattern between anole lizard and human. These results may provide insights into the evolutionary diversification of animal TK genes and would aid future studies on TK protein regulation of key growth and developmental processes.}, } @article {pmid28804953, year = {2017}, author = {Gyoja, F}, title = {Basic helix-loop-helix transcription factors in evolution: Roles in development of mesoderm and neural tissues.}, journal = {Genesis (New York, N.Y. : 2000)}, volume = {55}, number = {9}, pages = {}, doi = {10.1002/dvg.23051}, pmid = {28804953}, issn = {1526-968X}, mesh = {Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/chemistry/*genetics/metabolism ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Mesoderm/growth & development/*metabolism ; Nervous System/growth & development/*metabolism ; }, abstract = {Basic helix-loop-helix (bHLH) transcription factors have attracted the attention of developmental and evolutionary biologists for decades because of their conserved functions in mesodermal and neural tissue formation in both vertebrates and fruit flies. Their evolutionary history is of special interest because it will likely provide insights into developmental processes and refinement of metazoan-specific traits. This review briefly considers advances in developmental biological studies on bHLHs/HLHs. I also discuss recent genome-wide surveys and molecular phylogenetic analyses of these factors in a wide range of metazoans. I hypothesize that interactions between metazoan-specific Group A, D, and E bHLH/HLH factors enabled a sophisticated transition system from cell proliferation to differentiation in multicellular development. This control mechanism probably emerged initially to organize a multicellular animal body and was subsequently recruited to form evolutionarily novel tissues, which differentiated during a later ontogenetic phase.}, } @article {pmid28802203, year = {2017}, author = {Campbell, S and Aswad, A and Katzourakis, A}, title = {Disentangling the origins of virophages and polintons.}, journal = {Current opinion in virology}, volume = {25}, number = {}, pages = {59-65}, doi = {10.1016/j.coviro.2017.07.011}, pmid = {28802203}, issn = {1879-6265}, mesh = {DNA Transposable Elements/*genetics ; DNA, Viral/genetics ; Eukaryota/*virology ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genome, Viral ; Giant Viruses/*genetics/physiology ; Phylogeny ; Virophages/*genetics ; Virus Diseases/genetics/transmission ; }, abstract = {Virophages and polintons are part of a complex system that also involves eukaryotes, giant viruses, as well as other viruses and transposable elements. Virophages are cosmopolitan, being found in environments ranging from the Amazon River to Antarctic hypersaline lakes, while polintons are found in many single celled and multicellular eukaryotes. Virophages and polintons have a shared ancestry, but their exact origins are unknown and obscured by antiquity and extensive horizontal gene transfer (HGT). Paleovirology can help disentangle the complicated gene flow between these two, as well as their giant viral and eukaryotic hosts. We outline the evidence and theoretical support for polintons being descended from viruses and not vice versa. In order to disentangle the natural history of polintons and virophages, we suggest that there is much to be gained by embracing rigorous metagenomics and evolutionary analyses. Methods from paleovirology will play a pivotal role in unravelling ancient relationships, HGT and patterns of cross-species transmission.}, } @article {pmid28774341, year = {2017}, author = {Riffle, S and Hegde, RS}, title = {Modeling tumor cell adaptations to hypoxia in multicellular tumor spheroids.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {36}, number = {1}, pages = {102}, pmid = {28774341}, issn = {1756-9966}, support = {R01 CA207068/CA/NCI NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; Cell Proliferation/*drug effects ; Humans ; Spheroids, Cellular/*metabolism ; }, abstract = {Under hypoxic conditions, tumor cells undergo a series of adaptations that promote evolution of a more aggressive tumor phenotype including the activation of DNA damage repair proteins, altered metabolism, and decreased proliferation. Together these changes mitigate the negative impact of oxygen deprivation and allow preservation of genomic integrity and proliferative capacity, thus contributing to tumor growth and metastasis. As a result the presence of a hypoxic microenvironment is considered a negative clinical feature of many solid tumors. Hypoxic niches in tumors also represent a therapeutically privileged environment in which chemo- and radiation therapy is less effective. Although the negative impact of tumor hypoxia has been well established, the precise effect of oxygen deprivation on tumor cell behavior, and the molecular signals that allow a tumor cell to survive in vivo are poorly understood. Multicellular tumor spheroids (MCTS) have been used as an in vitro model for the avascular tumor niche, capable of more accurately recreating tumor genomic profiles and predicting therapeutic response. However, relatively few studies have used MCTS to study the molecular mechanisms driving tumor cell adaptations within the hypoxic tumor environment. Here we will review what is known about cell proliferation, DNA damage repair, and metabolic pathways as modeled in MCTS in comparison to observations made in solid tumors. A more precise definition of the cell populations present within 3D tumor models in vitro could better inform our understanding of the heterogeneity within tumors as well as provide a more representative platform for the testing of therapeutic strategies.}, } @article {pmid28768887, year = {2017}, author = {Tong, K and Wang, Y and Su, Z}, title = {Phosphotyrosine signalling and the origin of animal multicellularity.}, journal = {Proceedings. Biological sciences}, volume = {284}, number = {1860}, pages = {}, pmid = {28768887}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; *Cell Communication ; Eukaryota/enzymology/*genetics ; Phosphotyrosine/*metabolism ; Protein-Tyrosine Kinases/*metabolism ; *Signal Transduction ; }, abstract = {The evolution of multicellular animals (i.e. metazoans) from a unicellular ancestor is one of the most important yet least understood evolutionary transitions. Historically, given its indispensable functions in intercellular communication and exclusive presence in metazoans, phosphotyrosine (pTyr) signalling was considered a metazoan-specific evolutionary innovation that might have contributed to the origin of metazoan multicellularity. However, recent studies have led to a new understanding of pTyr signalling evolution and its role in the metazoan origin. Sequence analyses have unravelled a much earlier emergence of pTyr signalling in eukaryotic evolution. Even so, several distinct properties of holozoan pTyr signalling may have paved the way for a hypothesized functional transition of pTyr signalling at the multicellular origin, from environmental sensing to intercellular communication, and for it to evolve as a powerful intercellular signalling system for multicellularity. Biochemical analyses of premetazoan pTyr signalling components have further revealed the premetazoan origin of many key features of metazoan pTyr signalling, and the metazoan establishment of others, including the Csk-mediated negative regulation of the activity of Src, a conserved tyrosine kinase in the Holozoa. Finally, potential future directions are discussed, with a stress on the biological functions of premetazoan pTyr signalling via newly developed gene manipulation tools in non-animal holozoans.}, } @article {pmid28762573, year = {2017}, author = {Zanchi, C and Johnston, PR and Rolff, J}, title = {Evolution of defence cocktails: Antimicrobial peptide combinations reduce mortality and persistent infection.}, journal = {Molecular ecology}, volume = {26}, number = {19}, pages = {5334-5343}, doi = {10.1111/mec.14267}, pmid = {28762573}, issn = {1365-294X}, mesh = {Animals ; Bacterial Load ; Gene Knockdown Techniques ; Host-Pathogen Interactions ; *Immunity, Innate ; Insect Proteins/genetics/*immunology ; RNA Interference ; Staphylococcal Infections/*immunology ; Staphylococcus aureus ; Tenebrio/*immunology ; }, abstract = {The simultaneous expression of costly immune effectors such as multiple antimicrobial peptides is a hallmark of innate immunity of multicellular organisms, yet the adaptive advantage remains unresolved. Here, we test current hypotheses on the evolution of such defence cocktails. We use RNAi gene knock-down to explore, the effects of three highly expressed antimicrobial peptides, displaying different degrees of activity in vitro against Staphylococcus aureus, during an infection in the beetle Tenebrio molitor. We find that a defensin confers no survival benefit but reduces bacterial loads. A coleoptericin contributes to host survival without affecting bacterial loads. An attacin has no individual effect. Simultaneous knock-down of the defensin with the other AMPs results in increased mortality and elevated bacterial loads. Contrary to common expectations, the effects on host survival and bacterial load can be independent. The expression of multiple AMPs increases host survival and contributes to the control of persisting infections and tolerance. This is an emerging property that explains the adaptive benefit of defence cocktails.}, } @article {pmid28761011, year = {2017}, author = {Borges, RM}, title = {Co-niche construction between hosts and symbionts: ideas and evidence.}, journal = {Journal of genetics}, volume = {96}, number = {3}, pages = {483-489}, pmid = {28761011}, issn = {0973-7731}, mesh = {Animals ; Biological Evolution ; *Ecosystem ; Gene Transfer, Horizontal ; Genome/genetics ; Host Specificity/*genetics ; *Inheritance Patterns ; Phenotype ; Symbiosis/*genetics ; }, abstract = {Symbiosis is a process that can generate evolutionary novelties and can extend the phenotypic niche space of organisms. Symbionts can act together with their hosts to co-construct host organs, within which symbionts are housed. Once established within hosts, symbionts can also influence various aspects of host phenotype, such as resource acquisition, protection from predation by acquisition of toxicity, as well as behaviour. Once symbiosis is established, its fidelity between generations must be ensured. Hosts evolve various mechanisms to screen unwanted symbionts and to facilitate faithful transmission of mutualistic partners between generations. Microbes are the most important symbionts that have influenced plant and animal phenotypes; multicellular organisms engage in developmental symbioses with microbes at many stages in ontogeny. The co-construction of niches may result in composite organisms that are physically nested within each other. While it has been advocated that these composite organisms need new evolutionary theories and perspectives to describe their properties and evolutionary trajectories, it appears that standard evolutionary theories are adequate to explore selection pressures on their composite or individual traits. Recent advances in our understanding of composite organisms open up many important questions regarding the stability and transmission of these units.}, } @article {pmid28755343, year = {2017}, author = {Abdelbar, OH}, title = {Histological Analysis of the Developmental Stages of Direct Somatic Embryogenesis Induced from In Vitro Leaf Explants of Date Palm.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1637}, number = {}, pages = {145-162}, doi = {10.1007/978-1-4939-7156-5_13}, pmid = {28755343}, issn = {1940-6029}, mesh = {Culture Media/chemistry ; Germination ; In Vitro Techniques ; Inflorescence/*cytology ; Phoeniceae/cytology/*growth & development ; Plant Leaves/growth & development ; Plant Somatic Embryogenesis Techniques/*methods ; Regeneration ; Seeds/growth & development ; }, abstract = {Somatic embryogenesis is an ideal technique for the micropropagation of date palm using different explant tissue; however, histological studies describing the ontogenesis of plant regeneration are limited. This chapter provides a simple protocol for the histological analysis of the successive developmental stages of direct somatic embryogenesis induced from in vitro leaf explants. Direct somatic embryos are obtained from Murashige and Skoog (MS) medium containing 2 mg/L 6-benzylaminopurine. In order to observe the different developmental stages, histological analysis is carried out on samples at 15-day intervals for 60 days. Samples are fixed in formalin acetic alcohol and embedded in paraffin wax. Stain serial transverse and longitudinal sections, 8 μm thick, are stained with safranin-Fast Green. After 15 days on the induction medium, somatic embryos exhibit multicellular origin directly from the procambium cells, whereas the mesophyll and the epidermal cells are not involved in this process. After 2 months, several developmental stages (pre-globular, globular, early bipolar, bipolar, and cotyledonary-shaped) are observed. These embryos germinate after transferring to MS medium without plant growth regulators and rooting on 2 mg/L NAA-containing medium resulting in complete plantlets.}, } @article {pmid28749982, year = {2017}, author = {Yoshida, Y and Koutsovoulos, G and Laetsch, DR and Stevens, L and Kumar, S and Horikawa, DD and Ishino, K and Komine, S and Kunieda, T and Tomita, M and Blaxter, M and Arakawa, K}, title = {Comparative genomics of the tardigrades Hypsibius dujardini and Ramazzottius varieornatus.}, journal = {PLoS biology}, volume = {15}, number = {7}, pages = {e2002266}, pmid = {28749982}, issn = {1545-7885}, mesh = {Animals ; Base Sequence ; Chromosome Mapping/veterinary ; DNA/chemistry/metabolism ; Desiccation ; Extremophiles/*genetics/growth & development/physiology ; Gene Expression Profiling/veterinary ; *Gene Expression Regulation ; Gene Transfer, Horizontal ; Genetic Linkage ; Genome Size ; Genome-Wide Association Study/veterinary ; Genomic Library ; High-Throughput Nucleotide Sequencing/veterinary ; Multigene Family ; Phylogeny ; Proteome/genetics/*metabolism ; Reproducibility of Results ; Species Specificity ; Tardigrada/*genetics/growth & development/physiology ; }, abstract = {Tardigrada, a phylum of meiofaunal organisms, have been at the center of discussions of the evolution of Metazoa, the biology of survival in extreme environments, and the role of horizontal gene transfer in animal evolution. Tardigrada are placed as sisters to Arthropoda and Onychophora (velvet worms) in the superphylum Panarthropoda by morphological analyses, but many molecular phylogenies fail to recover this relationship. This tension between molecular and morphological understanding may be very revealing of the mode and patterns of evolution of major groups. Limnoterrestrial tardigrades display extreme cryptobiotic abilities, including anhydrobiosis and cryobiosis, as do bdelloid rotifers, nematodes, and other animals of the water film. These extremophile behaviors challenge understanding of normal, aqueous physiology: how does a multicellular organism avoid lethal cellular collapse in the absence of liquid water? Meiofaunal species have been reported to have elevated levels of horizontal gene transfer (HGT) events, but how important this is in evolution, and particularly in the evolution of extremophile physiology, is unclear. To address these questions, we resequenced and reassembled the genome of H. dujardini, a limnoterrestrial tardigrade that can undergo anhydrobiosis only after extensive pre-exposure to drying conditions, and compared it to the genome of R. varieornatus, a related species with tolerance to rapid desiccation. The 2 species had contrasting gene expression responses to anhydrobiosis, with major transcriptional change in H. dujardini but limited regulation in R. varieornatus. We identified few horizontally transferred genes, but some of these were shown to be involved in entry into anhydrobiosis. Whole-genome molecular phylogenies supported a Tardigrada+Nematoda relationship over Tardigrada+Arthropoda, but rare genomic changes tended to support Tardigrada+Arthropoda.}, } @article {pmid28745003, year = {2018}, author = {Müller, V and de Boer, RJ and Bonhoeffer, S and Szathmáry, E}, title = {An evolutionary perspective on the systems of adaptive immunity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {505-528}, doi = {10.1111/brv.12355}, pmid = {28745003}, issn = {1469-185X}, mesh = {Adaptive Immunity/*genetics ; Animals ; *Biological Evolution ; Genetic Fitness ; Vertebrates/*genetics/*immunology ; }, abstract = {We propose an evolutionary perspective to classify and characterize the diverse systems of adaptive immunity that have been discovered across all major domains of life. We put forward a new function-based classification according to the way information is acquired by the immune systems: Darwinian immunity (currently known from, but not necessarily limited to, vertebrates) relies on the Darwinian process of clonal selection to 'learn' by cumulative trial-and-error feedback; Lamarckian immunity uses templated targeting (guided adaptation) to internalize heritable information on potential threats; finally, shotgun immunity operates through somatic mechanisms of variable targeting without feedback. We argue that the origin of Darwinian (but not Lamarckian or shotgun) immunity represents a radical innovation in the evolution of individuality and complexity, and propose to add it to the list of major evolutionary transitions. While transitions to higher-level units entail the suppression of selection at lower levels, Darwinian immunity re-opens cell-level selection within the multicellular organism, under the control of mechanisms that direct, rather than suppress, cell-level evolution for the benefit of the individual. From a conceptual point of view, the origin of Darwinian immunity can be regarded as the most radical transition in the history of life, in which evolution by natural selection has literally re-invented itself. Furthermore, the combination of clonal selection and somatic receptor diversity enabled a transition from limited to practically unlimited capacity to store information about the antigenic environment. The origin of Darwinian immunity therefore comprises both a transition in individuality and the emergence of a new information system - the two hallmarks of major evolutionary transitions. Finally, we present an evolutionary scenario for the origin of Darwinian immunity in vertebrates. We propose a revival of the concept of the 'Big Bang' of vertebrate immunity, arguing that its origin involved a 'difficult' (i.e. low-probability) evolutionary transition that might have occurred only once, in a common ancestor of all vertebrates. In contrast to the original concept, we argue that the limiting innovation was not the generation of somatic diversity, but the regulatory circuitry needed for the safe operation of amplifiable immune responses with somatically acquired targeting. Regulatory complexity increased abruptly by genomic duplications at the root of the vertebrate lineage, creating a rare opportunity to establish such circuitry. We discuss the selection forces that might have acted at the origin of the transition, and in the subsequent stepwise evolution leading to the modern immune systems of extant vertebrates.}, } @article {pmid28741966, year = {2017}, author = {Bryja, V and Červenka, I and Čajánek, L}, title = {The connections of Wnt pathway components with cell cycle and centrosome: side effects or a hidden logic?.}, journal = {Critical reviews in biochemistry and molecular biology}, volume = {52}, number = {6}, pages = {614-637}, pmid = {28741966}, issn = {1549-7798}, support = {166533/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Animals ; Cell Communication ; *Cell Cycle ; Cell Polarity ; Centrosome/*metabolism ; Humans ; *Wnt Signaling Pathway ; }, abstract = {Wnt signaling cascade has developed together with multicellularity to orchestrate the development and homeostasis of complex structures. Wnt pathway components - such as β-catenin, Dishevelled (DVL), Lrp6, and Axin-- are often dedicated proteins that emerged in evolution together with the Wnt signaling cascade and are believed to function primarily in the Wnt cascade. It is interesting to see that in recent literature many of these proteins are connected with cellular functions that are more ancient and not limited to multicellular organisms - such as cell cycle regulation, centrosome biology, or cell division. In this review, we summarize the recent literature describing this crosstalk. Specifically, we attempt to find the answers to the following questions: Is the response to Wnt ligands regulated by the cell cycle? Is the centrosome and/or cilium required to activate the Wnt pathway? How do Wnt pathway components regulate the centrosomal cycle and cilia formation and function? We critically review the evidence that describes how these connections are regulated and how they help to integrate cell-to-cell communication with the cell and the centrosomal cycle in order to achieve a fine-tuned, physiological response.}, } @article {pmid28736221, year = {2017}, author = {Paris, M and Götz, A and Hettrich, I and Bidan, CM and Dunlop, JWC and Razi, H and Zizak, I and Hutmacher, DW and Fratzl, P and Duda, GN and Wagermaier, W and Cipitria, A}, title = {Scaffold curvature-mediated novel biomineralization process originates a continuous soft tissue-to-bone interface.}, journal = {Acta biomaterialia}, volume = {60}, number = {}, pages = {64-80}, doi = {10.1016/j.actbio.2017.07.029}, pmid = {28736221}, issn = {1878-7568}, mesh = {Animals ; *Calcification, Physiologic ; Cartilage/*metabolism/pathology ; *Osteogenesis ; Sheep ; *Stress, Mechanical ; Tissue Scaffolds/*chemistry ; }, abstract = {UNLABELLED: A myriad of shapes are found in biological tissues, often naturally evolved to fulfill a particular function. In the field of tissue engineering, substrate geometry influences cell behavior and tissue formation in vitro, yet little is known how this translates to an in vivo scenario. Here we investigate scaffold curvature-induced tissue growth, without additional growth factors or cells, in an ovine animal model. We show that soft tissue formation follows a curvature-driven tissue growth model. The highly organized endogenous soft matrix, potentially under mechanical strain, leads to a non-standard form of biomineralization, whereby the pre-existing organic matrix is mineralized without collagen remodeling and without an intermediate cartilage ossification phase. Micro- and nanoscale characterization of the tissue microstructure using histology, backscattered electron (BSE) and second-harmonic generation (SHG) imaging and synchrotron small angle X-ray scattering (SAXS) revealed (i) continuous collagen fibers across the soft-hard tissue interface on the tip of mineralized cones, and (ii) bone remodeling by basic multicellular units (BMUs) in regions adjacent to the native cortical bone. Thus, features of soft tissue-to-bone interface resembling the insertion sites of ligaments and tendons into bone were created, using a scaffold that did not mimic the structural or biological gradients across such a complex interface at its mature state. This study provides fundamental knowledge for biomimetic scaffold design in the fields of bone regeneration and soft tissue-to-bone interface tissue engineering.

STATEMENT OF SIGNIFICANCE: Geometry influences cell behavior and tissue formation in vitro. However, little is known how this translates to an in vivo scenario. Here we investigate the influence of scaffold mean surface curvature on in vivo tissue growth using an ovine animal model. Based on a multiscale tissue microstructure characterization, we show a seamless integration of soft tissue into newly formed bone, resembling the insertion sites of ligaments and tendons into bone. This interface was created using a scaffold without additional growth factors or cells that did not recapitulate the structural or biological gradients across such a complex tissue interface at its mature state. These findings have important implications for biomimetic scaffold design for bone regeneration and soft tissue-to-bone interface tissue engineering.}, } @article {pmid28726632, year = {2017}, author = {Grau-Bové, X and Torruella, G and Donachie, S and Suga, H and Leonard, G and Richards, TA and Ruiz-Trillo, I}, title = {Dynamics of genomic innovation in the unicellular ancestry of animals.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {28726632}, issn = {2050-084X}, support = {616960/ERC_/European Research Council/International ; }, mesh = {Eukaryota/*genetics ; *Evolution, Molecular ; *Genome, Protozoan ; Genomics ; }, abstract = {Which genomic innovations underpinned the origin of multicellular animals is still an open debate. Here, we investigate this question by reconstructing the genome architecture and gene family diversity of ancestral premetazoans, aiming to date the emergence of animal-like traits. Our comparative analysis involves genomes from animals and their closest unicellular relatives (the Holozoa), including four new genomes: three Ichthyosporea and Corallochytrium limacisporum. Here, we show that the earliest animals were shaped by dynamic changes in genome architecture before the emergence of multicellularity: an early burst of gene diversity in the ancestor of Holozoa, enriched in transcription factors and cell adhesion machinery, was followed by multiple and differently-timed episodes of synteny disruption, intron gain and genome expansions. Thus, the foundations of animal genome architecture were laid before the origin of complex multicellularity - highlighting the necessity of a unicellular perspective to understand early animal evolution.}, } @article {pmid28719054, year = {2018}, author = {Plattner, H}, title = {Evolutionary Cell Biology of Proteins from Protists to Humans and Plants.}, journal = {The Journal of eukaryotic microbiology}, volume = {65}, number = {2}, pages = {255-289}, doi = {10.1111/jeu.12449}, pmid = {28719054}, issn = {1550-7408}, mesh = {*Biological Evolution ; *Cell Biology ; Eukaryotic Cells/*metabolism ; *Genetic Variation ; Phylogeny ; Plastids/genetics ; }, abstract = {During evolution, the cell as a fine-tuned machine had to undergo permanent adjustments to match changes in its environment, while "closed for repair work" was not possible. Evolution from protists (protozoa and unicellular algae) to multicellular organisms may have occurred in basically two lineages, Unikonta and Bikonta, culminating in mammals and angiosperms (flowering plants), respectively. Unicellular models for unikont evolution are myxamoebae (Dictyostelium) and increasingly also choanoflagellates, whereas for bikonts, ciliates are preferred models. Information accumulating from combined molecular database search and experimental verification allows new insights into evolutionary diversification and maintenance of genes/proteins from protozoa on, eventually with orthologs in bacteria. However, proteins have rarely been followed up systematically for maintenance or change of function or intracellular localization, acquirement of new domains, partial deletion (e.g. of subunits), and refunctionalization, etc. These aspects are discussed in this review, envisaging "evolutionary cell biology." Protozoan heritage is found for most important cellular structures and functions up to humans and flowering plants. Examples discussed include refunctionalization of voltage-dependent Ca[2+] channels in cilia and replacement by other types during evolution. Altogether components serving Ca[2+] signaling are very flexible throughout evolution, calmodulin being a most conservative example, in contrast to calcineurin whose catalytic subunit is lost in plants, whereas both subunits are maintained up to mammals for complex functions (immune defense and learning). Domain structure of R-type SNAREs differs in mono- and bikonta, as do Ca[2+] -dependent protein kinases. Unprecedented selective expansion of the subunit a which connects multimeric base piece and head parts (V0, V1) of H[+] -ATPase/pump may well reflect the intriguing vesicle trafficking system in ciliates, specifically in Paramecium. One of the most flexible proteins is centrin when its intracellular localization and function throughout evolution is traced. There are many more examples documenting evolutionary flexibility of translation products depending on requirements and potential for implantation within the actual cellular context at different levels of evolution. From estimates of gene and protein numbers per organism, it appears that much of the basic inventory of protozoan precursors could be transmitted to highest eukaryotic levels, with some losses and also with important additional "inventions."}, } @article {pmid28716924, year = {2017}, author = {Brawley, SH and Blouin, NA and Ficko-Blean, E and Wheeler, GL and Lohr, M and Goodson, HV and Jenkins, JW and Blaby-Haas, CE and Helliwell, KE and Chan, CX and Marriage, TN and Bhattacharya, D and Klein, AS and Badis, Y and Brodie, J and Cao, Y and Collén, J and Dittami, SM and Gachon, CMM and Green, BR and Karpowicz, SJ and Kim, JW and Kudahl, UJ and Lin, S and Michel, G and Mittag, M and Olson, BJSC and Pangilinan, JL and Peng, Y and Qiu, H and Shu, S and Singer, JT and Smith, AG and Sprecher, BN and Wagner, V and Wang, W and Wang, ZY and Yan, J and Yarish, C and Zäuner-Riek, S and Zhuang, Y and Zou, Y and Lindquist, EA and Grimwood, J and Barry, KW and Rokhsar, DS and Schmutz, J and Stiller, JW and Grossman, AR and Prochnik, SE}, title = {Insights into the red algae and eukaryotic evolution from the genome of Porphyra umbilicalis (Bangiophyceae, Rhodophyta).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {31}, pages = {E6361-E6370}, pmid = {28716924}, issn = {1091-6490}, support = {P20 GM103418/GM/NIGMS NIH HHS/United States ; P20 GM103638/GM/NIGMS NIH HHS/United States ; BB/1013164/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Actins/genetics ; Calcium Signaling/genetics ; Cell Cycle/genetics ; Cell Wall/genetics/metabolism ; Chromatin/genetics ; Cytoskeleton/*genetics ; *Evolution, Molecular ; Genome, Plant/*genetics ; Kinesins/genetics ; Phylogeny ; Porphyra/*cytology/*genetics ; }, abstract = {Porphyra umbilicalis (laver) belongs to an ancient group of red algae (Bangiophyceae), is harvested for human food, and thrives in the harsh conditions of the upper intertidal zone. Here we present the 87.7-Mbp haploid Porphyra genome (65.8% G + C content, 13,125 gene loci) and elucidate traits that inform our understanding of the biology of red algae as one of the few multicellular eukaryotic lineages. Novel features of the Porphyra genome shared by other red algae relate to the cytoskeleton, calcium signaling, the cell cycle, and stress-tolerance mechanisms including photoprotection. Cytoskeletal motor proteins in Porphyra are restricted to a small set of kinesins that appear to be the only universal cytoskeletal motors within the red algae. Dynein motors are absent, and most red algae, including Porphyra, lack myosin. This surprisingly minimal cytoskeleton offers a potential explanation for why red algal cells and multicellular structures are more limited in size than in most multicellular lineages. Additional discoveries further relating to the stress tolerance of bangiophytes include ancestral enzymes for sulfation of the hydrophilic galactan-rich cell wall, evidence for mannan synthesis that originated before the divergence of green and red algae, and a high capacity for nutrient uptake. Our analyses provide a comprehensive understanding of the red algae, which are both commercially important and have played a major role in the evolution of other algal groups through secondary endosymbioses.}, } @article {pmid28714591, year = {2017}, author = {Kloesener, MH and Bose, J and Schulte, RD}, title = {Experimental evolution with a multicellular host causes diversification within and between microbial parasite populations-Differences in emerging phenotypes of two different parasite strains.}, journal = {Evolution; international journal of organic evolution}, volume = {71}, number = {9}, pages = {2194-2205}, doi = {10.1111/evo.13306}, pmid = {28714591}, issn = {1558-5646}, mesh = {Animals ; *Bacillus thuringiensis ; Biological Evolution ; Caenorhabditis elegans/parasitology ; Genotype ; *Host-Parasite Interactions ; Parasites ; Phenotype ; Selection, Genetic ; }, abstract = {Host-parasite coevolution is predicted to have complex evolutionary consequences, potentially leading to the emergence of genetic and phenotypic diversity for both antagonists. However, little is known about variation in phenotypic responses to coevolution between different parasite strains exposed to the same experimental conditions. We infected Caenorhabditis elegans with one of two strains of Bacillus thuringiensis and either allowed the host and the parasite to experimentally coevolve (coevolution treatment) or allowed only the parasite to adapt to the host (one-sided parasite adaptation). By isolating single parasite clones from evolved populations, we found phenotypic diversification of the ancestral strain into distinct clones, which varied in virulence toward ancestral hosts and competitive ability against other parasite genotypes. Parasite phenotypes differed remarkably not only between the two strains, but also between and within different replicate populations, indicating diversification of the clonal population caused by selection. This study highlights that the evolutionary selection pressure mediated by a multicellular host causes phenotypic diversification, but not necessarily with the same phenotypic outcome for different parasite strains.}, } @article {pmid28713421, year = {2017}, author = {Mohanta, TK and Bae, H}, title = {Analyses of Genomic tRNA Reveal Presence of Novel tRNAs in Oryza sativa.}, journal = {Frontiers in genetics}, volume = {8}, number = {}, pages = {90}, pmid = {28713421}, issn = {1664-8021}, abstract = {Transfer rRNAs are important molecules responsible for the translation event during protein synthesis. tRNAs are widespread found in unicellular to multi-cellular organisms. Analysis of tRNA gene family members in Oryza sativa revealed the presence of 750 tRNA genes distributed unevenly in different chromosomes. The length of O. sativa tRNAs genes were ranged from 66 to 91 nucleotides encoding 52 isoacceptor in total. tRNA[Ser] found in chromosome 8 of O. sativa encoded only 66 nucleotides which is the smallest tRNA of O. sativa and to our knowledge, this is the smallest gene of eukaryotic lineage reported so far. Analyses revealed the presence of several novel/pseudo tRNA genes in O. sativa which are reported for the first time. Multiple sequence alignment of tRNAs revealed the presence of family specific conserved consensus sequences. Functional study of these novel tRNA and family specific conserved consensus sequences will be crucial to decipher their importance in biological events. The rate of transition of O. sativa tRNA was found to be higher than the rate of transversion. Evolutionary study revealed, O. sativa tRNAs were evolved from the lineages of multiple common ancestors. Duplication and loss study of tRNAs genes revealed, majority of the O. sativa tRNA were duplicated and 17 of them were found to be undergone loss during the evolution. Orthology and paralogy study showed, the majority of O. sativa tRNA were paralogous and only a few of tRNA[Ser] were found to contain orthologous tRNAs.}, } @article {pmid28711427, year = {2017}, author = {Hinnant, TD and Alvarez, AA and Ables, ET}, title = {Temporal remodeling of the cell cycle accompanies differentiation in the Drosophila germline.}, journal = {Developmental biology}, volume = {429}, number = {1}, pages = {118-131}, pmid = {28711427}, issn = {1095-564X}, support = {R15 GM117502/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biomarkers/metabolism ; *Cell Cycle/genetics ; *Cell Differentiation/genetics ; Cell Proliferation/genetics ; Cell Self Renewal/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*cytology/genetics ; Female ; Fluorescence ; Genes, Reporter ; Germ Cells/*cytology ; Mitosis/genetics ; Morphogenesis/genetics ; Ovary/cytology ; Proteolysis ; Stem Cells/cytology/metabolism ; Time Factors ; Ubiquitin/metabolism ; Up-Regulation/genetics ; }, abstract = {Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell. Further, germline stem cells (GSCs) and their differentiating progeny remain in a predominantly linear arrangement as oogenesis proceeds. The ability to visualize the stepwise events of differentiation within the context of a single tissue make the Drosophila ovary an exceptional model for study of cell cycle remodeling. To describe how the cell cycle is remodeled in germ cells as they differentiate in situ, we used the Drosophila Fluorescence Ubiquitin-based Cell Cycle Indicator (Fly-FUCCI) system, in which degradable versions of GFP::E2f1 and RFP::CycB fluorescently label cells in each phase of the cell cycle. We found that the lengths of the G1, S, and G2 phases of the cell cycle change dramatically over the course of differentiation, and identified the 4/8-cell cyst as a key developmental transition state in which cells prepare for specialized cell cycles. Our data suggest that the transcriptional activator E2f1, which controls the transition from G1 to S phase, is a key regulator of mitotic divisions in the early germline. Our data support the model that E2f1 is necessary for proper GSC proliferation, self-renewal, and daughter cell development. In contrast, while E2f1 degradation by the Cullin 4 (Cul4)-containing ubiquitin E3 ligase (CRL4) is essential for developmental transitions in the early germline, our data do not support a role for E2f1 degradation as a mechanism to limit GSC proliferation or self-renewal. Taken together, these findings provide further insight into the regulation of cell proliferation and the acquisition of differentiated cell fate, with broad implications across developing tissues.}, } @article {pmid28704372, year = {2017}, author = {Trail, F and Wang, Z and Stefanko, K and Cubba, C and Townsend, JP}, title = {The ancestral levels of transcription and the evolution of sexual phenotypes in filamentous fungi.}, journal = {PLoS genetics}, volume = {13}, number = {7}, pages = {e1006867}, pmid = {28704372}, issn = {1553-7404}, mesh = {Bayes Theorem ; *Biological Evolution ; Fruiting Bodies, Fungal/genetics ; Fungi/genetics ; Gene Expression Regulation, Fungal/genetics ; Gene Knockout Techniques ; Genome, Fungal/*genetics ; Neurospora crassa/genetics ; Phenotype ; Phylogeny ; Sex Differentiation/*genetics ; Sordariales/genetics/growth & development ; Transcriptome/*genetics ; }, abstract = {Changes in gene expression have been hypothesized to play an important role in the evolution of divergent morphologies. To test this hypothesis in a model system, we examined differences in fruiting body morphology of five filamentous fungi in the Sordariomycetes, culturing them in a common garden environment and profiling genome-wide gene expression at five developmental stages. We reconstructed ancestral gene expression phenotypes, identifying genes with the largest evolved increases in gene expression across development. Conducting knockouts and performing phenotypic analysis in two divergent species typically demonstrated altered fruiting body development in the species that had evolved increased expression. Our evolutionary approach to finding relevant genes proved far more efficient than other gene deletion studies targeting whole genomes or gene families. Combining gene expression measurements with knockout phenotypes facilitated the refinement of Bayesian networks of the genes underlying fruiting body development, regulation of which is one of the least understood processes of multicellular development.}, } @article {pmid28700638, year = {2017}, author = {Ashrafi, S and Helaly, S and Schroers, HJ and Stadler, M and Richert-Poeggeler, KR and Dababat, AA and Maier, W}, title = {Ijuhya vitellina sp. nov., a novel source for chaetoglobosin A, is a destructive parasite of the cereal cyst nematode Heterodera filipjevi.}, journal = {PloS one}, volume = {12}, number = {7}, pages = {e0180032}, pmid = {28700638}, issn = {1932-6203}, mesh = {Animals ; Hyphae/growth & development ; Hypocreales/classification/genetics/metabolism/*pathogenicity ; Indole Alkaloids/*metabolism ; Oocytes/microbiology ; Phylogeny ; Tylenchoidea/growth & development/microbiology ; }, abstract = {Cyst nematodes are globally important pathogens in agriculture. Their sedentary lifestyle and long-term association with the roots of host plants render cyst nematodes especially good targets for attack by parasitic fungi. In this context fungi were specifically isolated from nematode eggs of the cereal cyst nematode Heterodera filipjevi. Here, Ijuhya vitellina (Ascomycota, Hypocreales, Bionectriaceae), encountered in wheat fields in Turkey, is newly described on the basis of phylogenetic analyses, morphological characters and life-style related inferences. The species destructively parasitises eggs inside cysts of H. filipjevi. The parasitism was reproduced in in vitro studies. Infected eggs were found to harbour microsclerotia produced by I. vitellina that resemble long-term survival structures also known from other ascomycetes. Microsclerotia were also formed by this species in pure cultures obtained from both, solitarily isolated infected eggs obtained from fields and artificially infected eggs. Hyphae penetrating the eggshell colonised the interior of eggs and became transformed into multicellular, chlamydospore-like structures that developed into microsclerotia. When isolated on artificial media, microsclerotia germinated to produce multiple emerging hyphae. The specific nature of morphological structures produced by I. vitellina inside nematode eggs is interpreted as a unique mode of interaction allowing long-term survival of the fungus inside nematode cysts that are known to survive periods of drought or other harsh environmental conditions. Generic classification of the new species is based on molecular phylogenetic inferences using five different gene regions. I. vitellina is the only species of the genus known to parasitise nematodes and produce microsclerotia. Metabolomic analyses revealed that within the Ijuhya species studied here, only I. vitellina produces chaetoglobosin A and its derivate 19-O-acetylchaetoglobosin A. Nematicidal and nematode-inhibiting activities of these compounds have been demonstrated suggesting that the production of these compounds may represent an adaptation to nematode parasitism.}, } @article {pmid28687715, year = {2017}, author = {Goelzer, A and Fromion, V}, title = {Resource allocation in living organisms.}, journal = {Biochemical Society transactions}, volume = {45}, number = {4}, pages = {945-952}, doi = {10.1042/BST20160436}, pmid = {28687715}, issn = {1470-8752}, mesh = {Animals ; Calibration ; *Energy Metabolism ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; *Genome ; Genomics/methods/trends ; Humans ; *Models, Biological ; Species Specificity ; Systems Biology/methods/trends ; Validation Studies as Topic ; }, abstract = {Quantitative prediction of resource allocation for living systems has been an intensive area of research in the field of biology. Resource allocation was initially investigated in higher organisms by using empirical mathematical models based on mass distribution. A challenge is now to go a step further by reconciling the cellular scale to the individual scale. In the present paper, we review the foundations of modelling of resource allocation, particularly at the cellular scale: from small macro-molecular models to genome-scale cellular models. We enlighten how the combination of omic measurements and computational advances together with systems biology has contributed to dramatic progresses in the current understanding and prediction of cellular resource allocation. Accurate genome-wide predictive methods of resource allocation based on the resource balance analysis (RBA) framework have been developed and ensure a good trade-off between the complexity/tractability and the prediction capability of the model. The RBA framework shows promise for a wide range of applications in metabolic engineering and synthetic biology, and for pursuing investigations of the design principles of cellular and multi-cellular organisms.}, } @article {pmid28687624, year = {2018}, author = {Tejos, R and Rodriguez-Furlán, C and Adamowski, M and Sauer, M and Norambuena, L and Friml, J}, title = {PATELLINS are regulators of auxin-mediated PIN1 relocation and plant development in Arabidopsis thaliana.}, journal = {Journal of cell science}, volume = {131}, number = {2}, pages = {}, doi = {10.1242/jcs.204198}, pmid = {28687624}, issn = {1477-9137}, mesh = {Arabidopsis/drug effects/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Body Patterning/drug effects ; Gene Expression Regulation, Plant/drug effects ; Indoleacetic Acids/pharmacology ; Membrane Transport Proteins/genetics/*metabolism ; Mutation/genetics ; Phenotype ; Phylogeny ; *Plant Development/drug effects ; Plant Epidermis/cytology ; Plant Roots/drug effects/genetics/growth & development/metabolism ; Seedlings/drug effects/metabolism ; Seeds/drug effects/genetics ; }, abstract = {Coordinated cell polarization in developing tissues is a recurrent theme in multicellular organisms. In plants, a directional distribution of the plant hormone auxin is at the core of many developmental programs. A feedback regulation of auxin on the polarized localization of PIN auxin transporters in individual cells has been proposed as a self-organizing mechanism for coordinated tissue polarization, but the molecular mechanisms linking auxin signalling to PIN-dependent auxin transport remain unknown. We used a microarray-based approach to find regulators of the auxin-induced PIN relocation in Arabidopsis thaliana root, and identified a subset of a family of phosphatidylinositol transfer proteins (PITPs), the PATELLINs (PATLs). Here, we show that PATLs are expressed in partially overlapping cell types in different tissues going through mitosis or initiating differentiation programs. PATLs are plasma membrane-associated proteins accumulated in Arabidopsis embryos, primary roots, lateral root primordia and developing stomata. Higher order patl mutants display reduced PIN1 repolarization in response to auxin, shorter root apical meristem, and drastic defects in embryo and seedling development. This suggests that PATLs play a redundant and crucial role in polarity and patterning in Arabidopsis.}, } @article {pmid28683136, year = {2017}, author = {Ballinger, MJ and Perlman, SJ}, title = {Generality of toxins in defensive symbiosis: Ribosome-inactivating proteins and defense against parasitic wasps in Drosophila.}, journal = {PLoS pathogens}, volume = {13}, number = {7}, pages = {e1006431}, pmid = {28683136}, issn = {1553-7374}, mesh = {Animals ; Bacterial Proteins/genetics/metabolism/*toxicity ; Bacterial Toxins/genetics/metabolism/*toxicity ; Biological Evolution ; Drosophila/genetics/*microbiology/*parasitology/physiology ; Larva/genetics/microbiology/parasitology/physiology ; Ribosome Inactivating Proteins/genetics/metabolism/*toxicity ; Spiroplasma/genetics/*metabolism ; *Symbiosis ; Wasps/*drug effects/physiology ; }, abstract = {While it has become increasingly clear that multicellular organisms often harbor microbial symbionts that protect their hosts against natural enemies, the mechanistic underpinnings underlying most defensive symbioses are largely unknown. Spiroplasma bacteria are widespread associates of terrestrial arthropods, and include strains that protect diverse Drosophila flies against parasitic wasps and nematodes. Recent work implicated a ribosome-inactivating protein (RIP) encoded by Spiroplasma, and related to Shiga-like toxins in enterohemorrhagic Escherichia coli, in defense against a virulent parasitic nematode in the woodland fly, Drosophila neotestacea. Here we test the generality of RIP-mediated protection by examining whether Spiroplasma RIPs also play a role in wasp protection, in D. melanogaster and D. neotestacea. We find strong evidence for a major role of RIPs, with ribosomal RNA (rRNA) from the larval endoparasitic wasps, Leptopilina heterotoma and Leptopilina boulardi, exhibiting the hallmarks of RIP activity. In Spiroplasma-containing hosts, parasitic wasp ribosomes show abundant site-specific depurination in the α-sarcin/ricin loop of the 28S rRNA, with depurination occurring soon after wasp eggs hatch inside fly larvae. Interestingly, we found that the pupal ectoparasitic wasp, Pachycrepoideus vindemmiae, escapes protection by Spiroplasma, and its ribosomes do not show high levels of depurination. We also show that fly ribosomes show little evidence of targeting by RIPs. Finally, we find that the genome of D. neotestacea's defensive Spiroplasma encodes a diverse repertoire of RIP genes, which are differ in abundance. This work suggests that specificity of defensive symbionts against different natural enemies may be driven by the evolution of toxin repertoires, and that toxin diversity may play a role in shaping host-symbiont-enemy interactions.}, } @article {pmid28682226, year = {2017}, author = {El Kafsi, H and Gorochov, G and Larsen, M}, title = {[Not Available].}, journal = {Biologie aujourd'hui}, volume = {211}, number = {1}, pages = {39-49}, doi = {10.1051/jbio/2017010}, pmid = {28682226}, issn = {2105-0686}, mesh = {Animals ; Gastrointestinal Microbiome/*genetics/*immunology ; Host-Pathogen Interactions/genetics/immunology ; Humans ; Immune System/metabolism/*physiology ; Immunity, Cellular/physiology ; Immunity, Humoral/physiology ; Immunoglobulin A, Secretory/physiology ; Inheritance Patterns ; Symbiosis/*genetics/*immunology ; }, abstract = {Genetic evolution of multicellular organisms occurred as a response to environmental challenges, in particular competition for nutrients, climatic change, physical and chemical stressors and pathogens. However organism fitness depends on both the efficiency of its defences and its capacities for benefiting from its symbiotic organisms. Indeed microbes not only engender pathogenies, but enable efficient uptake of host non-self biodegradable nutriments. Furthermore, microbes play an important role in the development of host immunity. We shall review here the associations between some specific genes of the host, microbiota and the immune system. Recent genome-wide association studies disclose that symbiosis between host and microbiota results from a stringent genetic co-evolution. On the other hand, a microbe subset isolated from murine and human microbiotes has been identified on the basis of its interaction with both the host genetics and immunity. Remarkably, microbes which have two such connections are taxonomically related. The best performing bacterial genuses in these two perspectives are Bifidobacterium, Lactobacillus and Akkermansia. We conclude that future therapies targeting microbiota within the framework of chronic inflammatory diseases must consider together host immune and genetic characters associated with microbiota homeostasis.}, } @article {pmid28681487, year = {2017}, author = {Wloch-Salamon, DM and Fisher, RM and Regenberg, B}, title = {Division of labour in the yeast: Saccharomyces cerevisiae.}, journal = {Yeast (Chichester, England)}, volume = {34}, number = {10}, pages = {399-406}, doi = {10.1002/yea.3241}, pmid = {28681487}, issn = {1097-0061}, mesh = {Adaptation, Physiological ; Apoptosis ; Biofilms/growth & development ; Biological Evolution ; Phenotype ; Resting Phase, Cell Cycle ; Saccharomyces cerevisiae/genetics/*physiology ; }, abstract = {Division of labour between different specialized cell types is a central part of how we describe complexity in multicellular organisms. However, it is increasingly being recognized that division of labour also plays an important role in the lives of predominantly unicellular organisms. Saccharomyces cerevisiae displays several phenotypes that could be considered a division of labour, including quiescence, apoptosis and biofilm formation, but they have not been explicitly treated as such. We discuss each of these examples, using a definition of division of labour that involves phenotypic variation between cells within a population, cooperation between cells performing different tasks and maximization of the inclusive fitness of all cells involved. We then propose future research directions and possible experimental tests using S. cerevisiae as a model organism for understanding the genetic mechanisms and selective pressures that can lead to the evolution of the very first stages of a division of labour. Copyright © 2017 John Wiley & Sons, Ltd.}, } @article {pmid28673540, year = {2017}, author = {Song, Y and Botvinnik, OB and Lovci, MT and Kakaradov, B and Liu, P and Xu, JL and Yeo, GW}, title = {Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation.}, journal = {Molecular cell}, volume = {67}, number = {1}, pages = {148-161.e5}, pmid = {28673540}, issn = {1097-4164}, support = {R01 AI095277/AI/NIAID NIH HHS/United States ; R01 AI123202/AI/NIAID NIH HHS/United States ; P30 NS047101/NS/NINDS NIH HHS/United States ; R01 HG004659/HG/NHGRI NIH HHS/United States ; U19 MH107367/MH/NIMH NIH HHS/United States ; R01 HD085902/HD/NICHD NIH HHS/United States ; R01 NS075449/NS/NINDS NIH HHS/United States ; }, mesh = {Algorithms ; *Alternative Splicing ; Bayes Theorem ; Cell Line ; Computer Simulation ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Humans ; Kinetics ; Male ; Models, Genetic ; Nerve Tissue Proteins/*biosynthesis/genetics ; Neural Stem Cells/*metabolism ; *Neurogenesis ; Neurons/*metabolism ; Phenotype ; Pluripotent Stem Cells/*metabolism ; RNA, Messenger/genetics/*metabolism ; *Single-Cell Analysis ; }, abstract = {Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational framework consisting of outrigger, a de novo splice graph transversal algorithm to detect AS; anchor, a Bayesian approach to assign modalities; and bonvoyage, a visualization tool using non-negative matrix factorization to display modality changes. Applying Expedition to single pluripotent stem cells undergoing neuronal differentiation, we discover that up to 20% of AS exons exhibit bimodality. Bimodal exons are flanked by more conserved intronic sequences harboring distinct cis-regulatory motifs, constitute much of cell-type-specific splicing, are highly dynamic during cellular transitions, preserve reading frame, and reveal intricacy of cell states invisible to conventional gene expression analysis. Systematic AS characterization in single cells redefines our understanding of AS complexity in cell biology.}, } @article {pmid28669817, year = {2017}, author = {Timoshevskiy, VA and Lampman, RT and Hess, JE and Porter, LL and Smith, JJ}, title = {Deep ancestry of programmed genome rearrangement in lampreys.}, journal = {Developmental biology}, volume = {429}, number = {1}, pages = {31-34}, pmid = {28669817}, issn = {1095-564X}, support = {R01 GM104123/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA/metabolism ; Gene Rearrangement/*genetics ; *Genome ; Germ Cells/metabolism ; Lampreys/*genetics ; *Phylogeny ; }, abstract = {In most multicellular organisms, the structure and content of the genome is rigorously maintained over the course of development. However some species have evolved genome biologies that permit, or require, developmentally regulated changes in the physical structure and content of the genome (programmed genome rearrangement: PGR). Relatively few vertebrates are known to undergo PGR, although all agnathans surveyed to date (several hagfish and one lamprey: Petromyzon marinus) show evidence of large scale PGR. To further resolve the ancestry of PGR within vertebrates, we developed probes that allow simultaneous tracking of nearly all sequences eliminated by PGR in P. marinus and a second lamprey species (Entosphenus tridentatus). These comparative analyses reveal conserved subcellular structures (lagging chromatin and micronuclei) associated with PGR and provide the first comparative embryological evidence in support of the idea that PGR represents an ancient and evolutionarily stable strategy for regulating inherent developmental/genetic conflicts between germline and soma.}, } @article {pmid28663071, year = {2017}, author = {Rosa-Fernandes, L and Maselli, LMF and Maeda, NY and Palmisano, G and Bydlowski, SP}, title = {Outside-in, inside-out: Proteomic analysis of endothelial stress mediated by 7-ketocholesterol.}, journal = {Chemistry and physics of lipids}, volume = {207}, number = {Pt B}, pages = {231-238}, doi = {10.1016/j.chemphyslip.2017.06.008}, pmid = {28663071}, issn = {1873-2941}, mesh = {Cell Survival/drug effects ; Cells, Cultured ; Computational Biology ; Dose-Response Relationship, Drug ; Human Umbilical Vein Endothelial Cells/*drug effects ; Humans ; Ketocholesterols/*pharmacology ; Mass Spectrometry ; Oxidative Stress/*drug effects ; Platelet Aggregation/drug effects ; *Proteomics ; Structure-Activity Relationship ; }, abstract = {Oxysterols are cholesterol oxidation products formed through enzymatic or autoxidation mechanisms. 7-ketocholeterol (7KC) is one of most abundant oxysterols found in atherosclerotic lesions. Its role in atherosclerosis pathogenesis has been broadly studied in a variety of models. The arterial microenvironment is a multicellular dynamic compartment that, among other systemic factors, is continuously stimulated by 7KC. Endothelial cells have a key role on that environment, being in intimate contact with both the blood stream and the vessel wall, the site of disease origin. 7KC has been shown to promote endothelial cell death and/or dysfunction, depending on its concentration. However, its contribution to the cell microenvironment through cell stimulation has not received much attention. Here we applied mass spectrometry-based proteomics followed by bioinformatics workflow to analyze the effect of a non-toxic 7KC concentration on endothelial cell protein expression and secretion in vitro. Trypsin digests were prepared from the secretome of the endothelial cells and from the total cell pellet after 24h exposure to 7KC. All samples were analyzed by high resolution and accurate mass nano-LC MS/MS. After database search and statistical analysis, differentially expressed proteins were selected for further studies. Our workflow identified 1805 secreted proteins and 2203 intracellular proteins, and of these, 48 and 53, respectively, were regulated. Regulated proteins upon 7KC exposure are involved in unfolded protein response, vascular homeostasis, and reduced control of angiogenesis. Moreover, blood coagulation was another main pathway regulated through Tissue Factor Pathway Inhibitor (TFPI), an antithrombotic agent associated with coronary disease that we found to be more than 2 times downregulated. Taken together, these data show differential endothelial protein regulation and secretion upon 7KC exposure for short time periods under non-toxic conditions. Herewith, these data support the role of 7KC in atherosclerosis pathophysiology and thus reinforce the deleterious effect of endothelial cells stress in the arterial microenvironment.}, } @article {pmid28648822, year = {2017}, author = {Hehenberger, E and Tikhonenkov, DV and Kolisko, M and Del Campo, J and Esaulov, AS and Mylnikov, AP and Keeling, PJ}, title = {Novel Predators Reshape Holozoan Phylogeny and Reveal the Presence of a Two-Component Signaling System in the Ancestor of Animals.}, journal = {Current biology : CB}, volume = {27}, number = {13}, pages = {2043-2050.e6}, doi = {10.1016/j.cub.2017.06.006}, pmid = {28648822}, issn = {1879-0445}, mesh = {Animals ; *Biological Evolution ; Eukaryota/*classification/genetics/*physiology ; Evolution, Molecular ; Fetal Proteins/genetics/metabolism ; *Predatory Behavior ; RNA, Ribosomal, 18S/genetics ; *Signal Transduction ; T-Box Domain Proteins/genetics/metabolism ; Brachyury Protein ; }, abstract = {Our understanding of the origin of animals has been transformed by characterizing their most closely related, unicellular sisters: the choanoflagellates, filastereans, and ichthyosporeans. Together with animals, these lineages make up the Holozoa [1, 2]. Many traits previously considered "animal specific" were subsequently found in other holozoans [3, 4], showing that they evolved before animals, although exactly when is currently uncertain because several key relationships remain unresolved [2, 5]. Here we report the morphology and transcriptome sequencing from three novel unicellular holozoans: Pigoraptor vietnamica and Pigoraptor chileana, which are related to filastereans, and Syssomonas multiformis, which forms a new lineage with Corallochytrium in phylogenomic analyses. All three species are predatory flagellates that feed on large eukaryotic prey, and all three also appear to exhibit complex life histories with several distinct stages, including multicellular clusters. Examination of genes associated with multicellularity in animals showed that the new filastereans contain a cell-adhesion gene repertoire similar to those of other species in this group. Syssomonas multiformis possessed a smaller complement overall but does encode genes absent from the earlier-branching ichthyosporeans. Analysis of the T-box transcription factor domain showed expansion of T-box transcription factors based on combination with a non-T-box domain (a receiver domain), which has not been described outside of vertebrates. This domain and other domains we identified in all unicellular holozoans are part of the two-component signaling system that has been lost in animals, suggesting the continued use of this system in the closest relatives of animals and emphasizing the importance of studying loss of function as well as gain in major evolutionary transitions.}, } @article {pmid28644721, year = {2019}, author = {Rivero, C and Traubenik, S and Zanetti, ME and Blanco, FA}, title = {Small GTPases in plant biotic interactions.}, journal = {Small GTPases}, volume = {10}, number = {5}, pages = {350-360}, pmid = {28644721}, issn = {2154-1256}, mesh = {Biological Transport, Active/physiology ; Cell Membrane/*enzymology ; GTP Phosphohydrolases/*metabolism ; Plant Proteins/*metabolism ; Plants/*enzymology ; Signal Transduction/*physiology ; }, abstract = {The superfamily of small monomeric GTPases originated in a common ancestor of eukaryotic multicellular organisms and, since then, it has evolved independently in each lineage to cope with the environmental challenges imposed by their different life styles. Members of the small GTPase family function in the control of vesicle trafficking, cytoskeleton rearrangements and signaling during crucial biological processes, such as cell growth and responses to environmental cues. In this review, we discuss the emerging roles of these small GTPases in the pathogenic and symbiotic interactions established by plants with microorganisms present in their nearest environment, in which membrane trafficking is crucial along the different steps of the interaction, from recognition and signal transduction to nutrient exchange.}, } @article {pmid28637850, year = {2017}, author = {Heim, NA and Payne, JL and Finnegan, S and Knope, ML and Kowalewski, M and Lyons, SK and McShea, DW and Novack-Gottshall, PM and Smith, FA and Wang, SC}, title = {Hierarchical complexity and the size limits of life.}, journal = {Proceedings. Biological sciences}, volume = {284}, number = {1857}, pages = {}, pmid = {28637850}, issn = {1471-2954}, mesh = {*Biological Evolution ; Earth, Planet ; *Eukaryota ; *Prokaryotic Cells ; }, abstract = {Over the past 3.8 billion years, the maximum size of life has increased by approximately 18 orders of magnitude. Much of this increase is associated with two major evolutionary innovations: the evolution of eukaryotes from prokaryotic cells approximately 1.9 billion years ago (Ga), and multicellular life diversifying from unicellular ancestors approximately 0.6 Ga. However, the quantitative relationship between organismal size and structural complexity remains poorly documented. We assessed this relationship using a comprehensive dataset that includes organismal size and level of biological complexity for 11 172 extant genera. We find that the distributions of sizes within complexity levels are unimodal, whereas the aggregate distribution is multimodal. Moreover, both the mean size and the range of size occupied increases with each additional level of complexity. Increases in size range are non-symmetric: the maximum organismal size increases more than the minimum. The majority of the observed increase in organismal size over the history of life on the Earth is accounted for by two discrete jumps in complexity rather than evolutionary trends within levels of complexity. Our results provide quantitative support for an evolutionary expansion away from a minimal size constraint and suggest a fundamental rescaling of the constraints on minimal and maximal size as biological complexity increases.}, } @article {pmid28637420, year = {2017}, author = {Baig, AM and Rana, Z and Tariq, SS and Ahmad, HR}, title = {Bioinformatic Insights on Target Receptors of Amiodarone in Human and Acanthamoeba castellanii.}, journal = {Infectious disorders drug targets}, volume = {17}, number = {3}, pages = {160-177}, doi = {10.2174/1871526517666170622075154}, pmid = {28637420}, issn = {2212-3989}, mesh = {Acanthamoeba castellanii/chemistry/*drug effects/metabolism ; Amiodarone/*metabolism/*pharmacology ; Calcium Channels/*chemistry/genetics ; *Computational Biology ; Cytochrome P-450 CYP3A/*chemistry/genetics ; Humans ; Intramolecular Transferases/chemistry/genetics ; Ligands ; Models, Molecular ; Protein Binding ; Protozoan Proteins/*chemistry/metabolism ; Sequence Homology, Amino Acid ; Trypanosoma cruzi/chemistry/drug effects/genetics ; }, abstract = {BACKGROUND: Amiodarone is prescribed for certain cardiac arrhythmias in current medical practice. The drug targets and inhibits voltage dependent sodium (Na+ v), calcium (Ca+2 v), potassium (K+ v) channels, enzymes like cytochrome P450 and oxidosqualene cyclase. Past studies have shown that amiodarone exerts antiparasitic effects against Trypanosoma cruzi and Acanthamoeba castellanii.

OBJECTIVES: The presence of aforementioned targets and the type of cell death induced by amiodarone in pathogenic eukaryotes like Acanthamoeba castellanii remains to be established. We inferred the presence of homologous targets of amiodarone in A. castellanii compared with humans.

METHODS: This study used bioinformatics exploration for amino acid sequence homology, ligand binding attribute predictions, 3D structural model development, and experimental assays that highlight similarity between certain target proteins in Acanthamoeba as compared to humans.

RESULTS: The sequence identity scores for amino acids and 3D models show that A. castellanii expresses similar types of targets of amiodarone like Na+ v - K+1 v channels, cytochrome P450 3A4, and lanosterol synthase (oxidosqualene cyclase). We show that even though human like L-type and two pore Ca+2 channels are present in A. castellanii, there was no evidence of the expression of T-type voltage dependent Ca+2 channels. Growth assays showed amoebicidal and amoebistatic effects at doses of 40-80μg/ml.

CONCLUSION: The existing bioinformatics tools, ligand binding attribute prediction, and model building offer a specific method to establish homology of proteins, discover drug targets, and facilitate the investigation of the evolution of several types of cardinal ion channels from unicellular eukaryotes to multicellular species as humans.}, } @article {pmid28633034, year = {2017}, author = {Nagy, LG}, title = {Evolution: Complex Multicellular Life with 5,500 Genes.}, journal = {Current biology : CB}, volume = {27}, number = {12}, pages = {R609-R612}, doi = {10.1016/j.cub.2017.04.032}, pmid = {28633034}, issn = {1879-0445}, mesh = {*Ascomycota ; Genomics ; }, abstract = {The origin of complex multicellularity was a major transition in evolution and is generally associated with higher genomic complexity. However, some complex multicellular fungi defy this principle, having small genomes that resemble those of unicellular yeasts rather than those of other complex multicellular organisms.}, } @article {pmid28631149, year = {2017}, author = {Krsmanovic, P}, title = {Vigor of survival determinism: subtle evolutionary gradualism interspersed with robust phylogenetic leaping.}, journal = {Theory in biosciences = Theorie in den Biowissenschaften}, volume = {136}, number = {3-4}, pages = {141-151}, pmid = {28631149}, issn = {1611-7530}, mesh = {Animals ; *Biological Evolution ; Caenorhabditis elegans ; Cell Lineage ; Drosophila melanogaster ; Female ; Genetic Drift ; Genetic Variation ; Genetics, Population ; Genomics ; Male ; Models, Genetic ; Mutagenesis ; Mutation ; *Phylogeny ; Saccharomyces cerevisiae ; *Selection, Genetic ; Stochastic Processes ; }, abstract = {Discussions of the survival determinism concept have previously focused on its primary role in the evolution of early unicellular organisms in the light of findings which have been reported on a number of diseases. The rationale for such parallel was in the view according to which multicellular organisms could be regarded as sophisticated colonies of semi-autonomous, single-celled entities, whereby various diseases were described as conditions arising upon the activation of the respective survival mechanisms in a milieu unsuitable for such robust stress response. The cellular mechanisms that were discussed in these contexts have been known to play various roles in other biological processes. The proposed notion could thereby be further extended to discussion on mechanisms for the implementation of the respective survival pathways in the development of metazoa, considering that they would have been propagated in their evolution for so long. This manuscript first presents a concise overview of the model previously discussed, followed by the discussion on the role of respective mechanism(s) in origins and development of metazoa. Finally, a reflection on the concept in relation to the prominent evolutionary models is put forward to illustrate a broader context of what is being discussed.}, } @article {pmid28630027, year = {2017}, author = {Sapir, L and Tzlil, S}, title = {Talking over the extracellular matrix: How do cells communicate mechanically?.}, journal = {Seminars in cell & developmental biology}, volume = {71}, number = {}, pages = {99-105}, doi = {10.1016/j.semcdb.2017.06.010}, pmid = {28630027}, issn = {1096-3634}, mesh = {Animals ; Biomechanical Phenomena ; Cell Communication ; Cell Movement ; *Extracellular Matrix ; Humans ; Myocardium/cytology ; }, abstract = {Communication between cells enables them to coordinate their activity and is crucial for the differentiation, development, and function of tissues and multicellular organisms. Cell-cell communication is discussed almost exclusively as having a chemical or electrical origin. Only recently, a new mode of cell communication was elucidated: mechanical communication through the extracellular matrix (ECM). Cells can communicate mechanically by responding either to mechanical deformations generated by their neighbors or to a change in the mechanical properties of the ECM induced by a neighboring cell. This newly resolved mode of communication possesses unique features that complement the cellular ability to receive and share information, and to consequently act in a cooperative way with surrounding cells. Herein, we review several examples of mechanical communication, discuss their unique properties, and comment on the major challenges facing the field.}, } @article {pmid28629791, year = {2017}, author = {Xie, N and Ruprich-Robert, G and Chapeland-Leclerc, F and Coppin, E and Lalucque, H and Brun, S and Debuchy, R and Silar, P}, title = {Inositol-phosphate signaling as mediator for growth and sexual reproduction in Podospora anserina.}, journal = {Developmental biology}, volume = {429}, number = {1}, pages = {285-305}, doi = {10.1016/j.ydbio.2017.06.017}, pmid = {28629791}, issn = {1095-564X}, mesh = {Amino Acid Sequence ; Cell Nucleus/metabolism ; Fertility ; Fruiting Bodies, Fungal/metabolism ; Fungal Proteins/chemistry/metabolism ; Genes, Fungal ; Green Fluorescent Proteins/metabolism ; Inositol/metabolism ; Inositol Phosphates/*metabolism ; MAP Kinase Signaling System ; Mosaicism ; Mutation/genetics ; Phenotype ; Pigments, Biological/metabolism ; Podospora/enzymology/genetics/*growth & development/*metabolism ; Protein Transport ; Reproduction ; *Signal Transduction ; Sordariales/metabolism ; Spores, Fungal/metabolism ; Temperature ; Zygote/metabolism ; }, abstract = {The molecular pathways involved in the development of multicellular fruiting bodies in fungi are still not well known. Especially, the interplay between the mycelium, the female tissues and the zygotic tissues of the fruiting bodies is poorly documented. Here, we describe PM154, a new strain of the model ascomycetes Podospora anserina able to mate with itself and that enabled the easy recovery of new mutants affected in fruiting body development. By complete genome sequencing of spod1, one of the new mutants, we identified an inositol phosphate polykinase gene as essential, especially for fruiting body development. A factor present in the wild type and diffusible in mutant hyphae was able to induce the development of the maternal tissues of the fruiting body in spod1, but failed to promote complete development of the zygotic ones. Addition of myo-inositol in the growth medium was able to increase the number of developing fruiting bodies in the wild type, but not in spod1. Overall, the data indicated that inositol and inositol polyphosphates were involved in promoting fruiting body maturation, but also in regulating the number of fruiting bodies that developed after fertilization. The same effect of inositol was seen in two other fungi, Sordaria macrospora and Chaetomium globosum. Key role of the inositol polyphosphate pathway during fruiting body maturation appears thus conserved during the evolution of Sordariales fungi.}, } @article {pmid28627239, year = {2017}, author = {Csaba, G}, title = {Complex multicellular functions at a unicellular eukaryote level: Learning, memory, and immunity.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {64}, number = {2}, pages = {105-120}, doi = {10.1556/030.64.2017.013}, pmid = {28627239}, issn = {1217-8950}, mesh = {Animals ; Eukaryota/genetics/*immunology/*physiology ; Humans ; Learning ; Memory ; }, abstract = {According to experimental data, eukaryote unicellulars are able to learn, have immunity and memory. Learning is carried out in a very primitive form, and the memory is not neural but an epigenetic one. However, this epigenetic memory, which is well justified by the presence and manifestation of hormonal imprinting, is strong and permanent in the life of cell and also in its progenies. This memory is epigenetically executed by the alteration and fixation of methylation pattern of genes without changes in base sequences. The immunity of unicellulars is based on self/non-self discrimination, which leads to the destruction of non-self invaders and utilization of them as nourishment (by phagocytosis). The tools of learning, memory, and immunity of unicellulars are uniformly found in plasma membrane receptors, which formed under the effect of dynamic receptor pattern generation, suggested by Koch et al., and this is the basis of hormonal imprinting, by which the encounter between a chemical substance and the cell is specifically memorized. The receptors and imprinting are also used in the later steps of evolution up to mammals (including man) in each mentioned functions. This means that learning, memory, and immunity can be deduced to a unicellular eukaryote level.}, } @article {pmid28610890, year = {2017}, author = {Brodie, J and Chan, CX and De Clerck, O and Cock, JM and Coelho, SM and Gachon, C and Grossman, AR and Mock, T and Raven, JA and Smith, AG and Yoon, HS and Bhattacharya, D}, title = {The Algal Revolution.}, journal = {Trends in plant science}, volume = {22}, number = {8}, pages = {726-738}, doi = {10.1016/j.tplants.2017.05.005}, pmid = {28610890}, issn = {1878-4372}, support = {BB/L014130/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Biodiversity ; Biological Evolution ; Biotechnology ; Ecology ; Gene Transfer, Horizontal ; *Photosynthesis ; Stramenopiles/*genetics/physiology ; Symbiosis ; }, abstract = {Algae are (mostly) photosynthetic eukaryotes that occupy multiple branches of the tree of life, and are vital for planet function and health. In this review, we highlight a transformative period in studies of the evolution and functioning of this extraordinary group of organisms and their potential for novel applications, wrought by high-throughput 'omic' and reverse genetic methods. We cover the origin and diversification of algal groups, explore advances in understanding the link between phenotype and genotype, consider algal sex determination, and review progress in understanding the roots of algal multicellularity. Experimental evolution studies to determine how algae evolve in changing environments are highlighted, as is their potential as production platforms for compounds of commercial interest, such as biofuel precursors, nutraceuticals, or therapeutics.}, } @article {pmid28605523, year = {2017}, author = {Vergara, Z and Sequeira-Mendes, J and Morata, J and Peiró, R and Hénaff, E and Costas, C and Casacuberta, JM and Gutierrez, C}, title = {Retrotransposons are specified as DNA replication origins in the gene-poor regions of Arabidopsis heterochromatin.}, journal = {Nucleic acids research}, volume = {45}, number = {14}, pages = {8358-8368}, pmid = {28605523}, issn = {1362-4962}, mesh = {Arabidopsis/cytology/*genetics/metabolism ; Cell Line ; Chromatin/genetics/metabolism ; Chromosome Mapping ; *DNA Replication ; DNA, Plant/genetics/metabolism ; GC Rich Sequence/genetics ; Genome, Plant/genetics ; Heterochromatin/*genetics/metabolism ; Histones/metabolism ; Lysine/metabolism ; Methylation ; Microscopy, Confocal ; Replication Origin/*genetics ; Retroelements/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription, Genetic ; }, abstract = {Genomic stability depends on faithful genome replication. This is achieved by the concerted activity of thousands of DNA replication origins (ORIs) scattered throughout the genome. The DNA and chromatin features determining ORI specification are not presently known. We have generated a high-resolution genome-wide map of 3230 ORIs in cultured Arabidopsis thaliana cells. Here, we focused on defining the features associated with ORIs in heterochromatin. In pericentromeric gene-poor domains ORIs associate almost exclusively with the retrotransposon class of transposable elements (TEs), in particular of the Gypsy family. ORI activity in retrotransposons occurs independently of TE expression and while maintaining high levels of H3K9me2 and H3K27me1, typical marks of repressed heterochromatin. ORI-TEs largely colocalize with chromatin signatures defining GC-rich heterochromatin. Importantly, TEs with active ORIs contain a local GC content higher than the TEs lacking them. Our results lead us to conclude that ORI colocalization with retrotransposons is determined by their transposition mechanism based on transcription, and a specific chromatin landscape. Our detailed analysis of ORIs responsible for heterochromatin replication has implications on the mechanisms of ORI specification in other multicellular organisms in which retrotransposons are major components of heterochromatin and of the entire genome.}, } @article {pmid28603898, year = {2019}, author = {Dhouailly, D and Godefroit, P and Martin, T and Nonchev, S and Caraguel, F and Oftedal, O}, title = {Getting to the root of scales, feather and hair: As deep as odontodes?.}, journal = {Experimental dermatology}, volume = {28}, number = {4}, pages = {503-508}, doi = {10.1111/exd.13391}, pmid = {28603898}, issn = {1600-0625}, mesh = {Adaptation, Physiological ; Animal Scales/*embryology ; Animals ; *Biological Evolution ; Feathers/*embryology ; *Fossils ; Hair/*embryology ; }, abstract = {While every jawed vertebrate, or its recent ancestor, possesses teeth, skin appendages are characteristic of the living clades: skin denticles (odontodes) in chondrichthyans, dermal scales in teleosts, ducted multicellular glands in amphibians, epidermal scales in squamates, feathers in birds and hair-gland complexes in mammals, all of them showing a dense periodic patterning. While the odontode origin of teleost scales is generally accepted, the origin of both feather and hair is still debated. They appear long before mammals and birds, at least in the Jurassic in mammaliaforms and in ornithodires (pterosaurs and dinosaurs), and are contemporary to scales of early squamates. Epidermal scales might have appeared several times in evolution, and basal amniotes could not have developed a scaled dry integument, as the function of hair follicle requires its association with glands. In areas such as amnion, cornea or plantar pads, the formation of feather and hair is prevented early in embryogenesis, but can be easily reverted by playing with the Wnt/BMP/Shh pathways, which both imply the plasticity and the default competence of ectoderm. Conserved ectodermal/mesenchymal signalling pathways lead to placode formation, while later the crosstalk differs, as well as the final performing tissue(s): both epidermis and dermis for teeth and odontodes, mostly dermis for teleosts scales and only epidermis for squamate scale, feather and hair. We therefore suggest that tooth, dermal scale, epidermal scale, feather and hair evolved in parallel from a shared placode/dermal cell unit, which was present in a common ancestor, an early vertebrate gnathostome with odontodes, ca. 420 million years ago.}, } @article {pmid28592899, year = {2017}, author = {Nan, F and Feng, J and Lv, J and Liu, Q and Fang, K and Gong, C and Xie, S}, title = {Origin and evolutionary history of freshwater Rhodophyta: further insights based on phylogenomic evidence.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {2934}, pmid = {28592899}, issn = {2045-2322}, mesh = {*Biological Evolution ; Evolution, Molecular ; *Fresh Water ; Genes, Plant ; Genetic Variation ; Genome, Chloroplast ; Genome, Mitochondrial ; Genomics/methods ; Phylogeny ; Rhodophyta/*classification/*genetics ; }, abstract = {Freshwater representatives of Rhodophyta were sampled and the complete chloroplast and mitochondrial genomes were determined. Characteristics of the chloroplast and mitochondrial genomes were analyzed and phylogenetic relationship of marine and freshwater Rhodophyta were reconstructed based on the organelle genomes. The freshwater member Compsopogon caeruleus was determined for the largest chloroplast genome among multicellular Rhodophyta up to now. Expansion and subsequent reduction of both the genome size and GC content were observed in the Rhodophyta except for the freshwater Compsopogon caeruleus. It was inferred that the freshwater members of Rhodophyta occurred through diverse origins based on evidence of genome size, GC-content, phylogenomic analysis and divergence time estimation. The freshwater species Compsopogon caeruleus and Hildenbrandia rivularis originated and evolved independently at the inland water, whereas the Bangia atropurpurea, Batrachospermum arcuatum and Thorea hispida are derived from the marine relatives. The typical freshwater representatives Thoreales and Batrachospermales are probably derived from the marine relative Palmaria palmata at approximately 415-484 MYA. The origin and evolutionary history of freshwater Rhodophyta needs to be testified with more organelle genome sequences and wider global sampling.}, } @article {pmid28588313, year = {2017}, author = {Salmeán, AA and Duffieux, D and Harholt, J and Qin, F and Michel, G and Czjzek, M and Willats, WGT and Hervé, C}, title = {Insoluble (1 → 3), (1 → 4)-β-D-glucan is a component of cell walls in brown algae (Phaeophyceae) and is masked by alginates in tissues.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {2880}, pmid = {28588313}, issn = {2045-2322}, mesh = {Alginates/*metabolism ; Cell Wall/*chemistry/*metabolism ; Chromatography, High Pressure Liquid ; Fluorescent Antibody Technique ; Glucans/*chemistry/*metabolism ; Immunohistochemistry ; Organ Specificity ; Phaeophyceae/classification/genetics/*metabolism ; Solubility ; }, abstract = {Brown algae are photosynthetic multicellular marine organisms. They belong to the phylum of Stramenopiles, which are not closely related to land plants and green algae. Brown algae share common evolutionary features with other photosynthetic and multicellular organisms, including a carbohydrate-rich cell-wall. Brown algal cell walls are composed predominantly of the polyanionic polysaccharides alginates and fucose-containing sulfated polysaccharides. These polymers are prevalent over neutral and crystalline components, which are believed to be mostly, if not exclusively, cellulose. In an attempt to better understand brown algal cell walls, we performed an extensive glycan array analysis of a wide range of brown algal species. Here we provide the first demonstration that mixed-linkage (1 → 3), (1 → 4)-β-D-glucan (MLG) is common in brown algal cell walls. Ultra-Performance Liquid Chromatography analyses indicate that MLG in brown algae solely consists of trisaccharide units of contiguous (1 → 4)-β-linked glucose residues joined by (1 → 3)-β-linkages. This regular conformation may allow long stretches of the molecule to align and to form well-structured microfibrils. At the tissue level, immunofluorescence studies indicate that MLG epitopes in brown algae are unmasked by a pre-treatment with alginate lyases to remove alginates. These findings are further discussed in terms of the origin and evolution of MLG in the Stramenopile lineage.}, } @article {pmid28584082, year = {2017}, author = {Vergara, HM and Bertucci, PY and Hantz, P and Tosches, MA and Achim, K and Vopalensky, P and Arendt, D}, title = {Whole-organism cellular gene-expression atlas reveals conserved cell types in the ventral nerve cord of Platynereis dumerilii.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {23}, pages = {5878-5885}, pmid = {28584082}, issn = {1091-6490}, mesh = {Algorithms ; Animals ; *Biological Evolution ; Body Patterning/genetics ; Cell Differentiation ; Gene Expression Profiling/methods ; Gene Expression Regulation, Developmental ; Models, Biological ; Neurons/cytology ; Polychaeta/cytology/*genetics ; }, abstract = {The comparative study of cell types is a powerful approach toward deciphering animal evolution. To avoid selection biases, however, comparisons ideally involve all cell types present in a multicellular organism. Here, we use image registration and a newly developed "Profiling by Signal Probability Mapping" algorithm to generate a cellular resolution 3D expression atlas for an entire animal. We investigate three-segmented young worms of the marine annelid Platynereis dumerilii, with a rich diversity of differentiated cells present in relatively low number. Starting from whole-mount expression images for close to 100 neural specification and differentiation genes, our atlas identifies and molecularly characterizes 605 bilateral pairs of neurons at specific locations in the ventral nerve cord. Among these pairs, we identify sets of neurons expressing similar combinations of transcription factors, located at spatially coherent anterior-posterior, dorsal-ventral, and medial-lateral coordinates that we interpret as cell types. Comparison with motor and interneuron types in the vertebrate neural tube indicates conserved combinations, for example, of cell types cospecified by Gata1/2/3 and Tal transcription factors. These include V2b interneurons and the central spinal fluid-contacting Kolmer-Agduhr cells in the vertebrates, and several neuron types in the intermediate ventral ganglionic mass in the annelid. We propose that Kolmer-Agduhr cell-like mechanosensory neurons formed part of the mucociliary sole in protostome-deuterostome ancestors and diversified independently into several neuron types in annelid and vertebrate descendants.}, } @article {pmid28580966, year = {2017}, author = {Driscoll, WW and Travisano, M}, title = {Synergistic cooperation promotes multicellular performance and unicellular free-rider persistence.}, journal = {Nature communications}, volume = {8}, number = {}, pages = {15707}, pmid = {28580966}, issn = {2041-1723}, mesh = {Biological Evolution ; Cluster Analysis ; *Ecology ; Flocculation ; Genotype ; Green Fluorescent Proteins/metabolism ; Kluyveromyces/genetics/*physiology ; Microscopy, Confocal ; Phenotype ; Saccharomyces cerevisiae/genetics/*physiology ; Species Specificity ; Video Recording ; }, abstract = {The evolution of multicellular life requires cooperation among cells, which can be undermined by intra-group selection for selfishness. Theory predicts that selection to avoid non-cooperators limits social interactions among non-relatives, yet previous evolution experiments suggest that intra-group conflict is an outcome, rather than a driver, of incipient multicellular life cycles. Here we report the evolution of multicellularity via two distinct mechanisms of group formation in the unicellular budding yeast Kluyveromyces lactis. Cells remain permanently attached following mitosis, giving rise to clonal clusters (staying together); clusters then reversibly assemble into social groups (coming together). Coming together amplifies the benefits of multicellularity and allows social clusters to collectively outperform solitary clusters. However, cooperation among non-relatives also permits fast-growing unicellular lineages to 'free-ride' during selection for increased size. Cooperation and competition for the benefits of multicellularity promote the stable coexistence of unicellular and multicellular genotypes, underscoring the importance of social and ecological context during the transition to multicellularity.}, } @article {pmid28571799, year = {2017}, author = {Salerian, AJ}, title = {Human body may produce bacteria.}, journal = {Medical hypotheses}, volume = {103}, number = {}, pages = {131-132}, doi = {10.1016/j.mehy.2017.05.005}, pmid = {28571799}, issn = {1532-2777}, mesh = {Animals ; *Bacteria ; *Bacterial Physiological Phenomena ; Fermentation ; *Human Body ; Humans ; Models, Theoretical ; Muscles/physiology ; Origin of Life ; }, abstract = {"Human body may produce bacteria" proposes that human body may produce bacteria and represent an independent source of infections contrary to the current paradigm of infectious disorders proposed by Louis Pasteur in 1880. The following observations are consistent with this hypothesis: A. Bidirectional transformations of both living and nonliving things have been commonly observed in nature. B. Complex multicellular organisms harbor the necessary properties to produce bacteria (water, nitrogen and oxygen). C. Physical laws suggest any previously observed phenomenon or action will occur again (life began on earth; a non living thing). D. Animal muscle cells may generate energy (fermentation). E. Sterilized food products (i.e. boiled eggs), may produce bacteria and fungus under special conditions and without any exposure to foreign living cells. "Human body may produce bacteria" may challenge the current medical paradigm that views human infectious disorders as the exclusive causative byproducts of invading foreign cells. It may also introduce new avenues to treat infectious disorders.}, } @article {pmid28560344, year = {2017}, author = {Knoll, AH and Nowak, MA}, title = {The timetable of evolution.}, journal = {Science advances}, volume = {3}, number = {5}, pages = {e1603076}, pmid = {28560344}, issn = {2375-2548}, mesh = {*Biological Evolution ; *Ecosystem ; *Models, Biological ; }, abstract = {The integration of fossils, phylogeny, and geochronology has resulted in an increasingly well-resolved timetable of evolution. Life appears to have taken root before the earliest known minimally metamorphosed sedimentary rocks were deposited, but for a billion years or more, evolution played out beneath an essentially anoxic atmosphere. Oxygen concentrations in the atmosphere and surface oceans first rose in the Great Oxygenation Event (GOE) 2.4 billion years ago, and a second increase beginning in the later Neoproterozoic Era [Neoproterozoic Oxygenation Event (NOE)] established the redox profile of modern oceans. The GOE facilitated the emergence of eukaryotes, whereas the NOE is associated with large and complex multicellular organisms. Thus, the GOE and NOE are fundamental pacemakers for evolution. On the time scale of Earth's entire 4 billion-year history, the evolutionary dynamics of the planet's biosphere appears to be fast, and the pace of evolution is largely determined by physical changes of the planet. However, in Phanerozoic ecosystems, interactions between new functions enabled by the accumulation of characters in a complex regulatory environment and changing biological components of effective environments appear to have an important influence on the timing of evolutionary innovations. On the much shorter time scale of transient environmental perturbations, such as those associated with mass extinctions, rates of genetic accommodation may have been limiting for life.}, } @article {pmid28551499, year = {2017}, author = {Shakiba, N and Zandstra, PW}, title = {Engineering cell fitness: lessons for regenerative medicine.}, journal = {Current opinion in biotechnology}, volume = {47}, number = {}, pages = {7-15}, doi = {10.1016/j.copbio.2017.05.005}, pmid = {28551499}, issn = {1879-0429}, support = {MOP 57885//CIHR/Canada ; }, mesh = {Animals ; Cell Engineering/*methods ; Humans ; Models, Biological ; Regenerative Medicine/*methods ; Tissue Engineering ; }, abstract = {Cell competition results in the loss of weaker cells and the dominance of stronger cells. So-called 'loser' cells are either removed by active elimination or by limiting their access to survival factors. Recently, competition has been shown to serve as a surveillance mechanism against emerging aberrant cells in both the developing and adult organism, contributing to overall organism fitness and survival. Here, we explore the origins and implications of cell competition in development, tissue homeostasis, and in vitro culture. We also provide a forward look on the use of cell competition to interpret multicellular dynamics while offering a perspective on harnessing competition to engineer cells with optimized and controllable fitness characteristics for regenerative medicine applications.}, } @article {pmid28550046, year = {2017}, author = {Vijg, J and Dong, X and Milholland, B and Zhang, L}, title = {Genome instability: a conserved mechanism of ageing?.}, journal = {Essays in biochemistry}, volume = {61}, number = {3}, pages = {305-315}, pmid = {28550046}, issn = {1744-1358}, support = {P01 AG017242/AG/NIA NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; P30 AG038072/AG/NIA NIH HHS/United States ; R01 CA180126/CA/NCI NIH HHS/United States ; }, mesh = {Aging/genetics/*physiology ; Animals ; DNA Repair/genetics/physiology ; Genomic Instability/genetics/*physiology ; Humans ; Mutation/genetics ; }, abstract = {DNA is the carrier of genetic information and the primary template from which all cellular information is ultimately derived. Changes in the DNA information content through mutation generate diversity for evolution through natural selection but are also a source of deleterious effects. It has since long been hypothesized that mutation accumulation in somatic cells of multicellular organisms could causally contribute to age-related cellular degeneration and death. Assays to detect different types of mutations, from base substitutions to large chromosomal aberrations, have been developed and show unequivocally that mutations accumulate in different tissues and cell types of ageing humans and animals. More recently, next-generation sequencing-based methods have been developed to accurately determine the complete landscape of base substitution mutations in single cells. The first results show that the somatic mutation rate is much higher than the germline mutation rate and that base substitution loads in somatic cells are high enough to potentially affect cellular function.}, } @article {pmid28529980, year = {2017}, author = {Moran, Y and Agron, M and Praher, D and Technau, U}, title = {The evolutionary origin of plant and animal microRNAs.}, journal = {Nature ecology & evolution}, volume = {1}, number = {3}, pages = {27}, pmid = {28529980}, issn = {2397-334X}, support = {637456/ERC_/European Research Council/International ; P 22618/FWF_/Austrian Science Fund FWF/Austria ; }, abstract = {microRNAs (miRNAs) are a unique class of short endogenous RNAs that became known in the last few decades as major players in gene regulation at the post-transcriptional level. Their regulatory roles make miRNAs crucial for normal development and physiology in several distinct groups of eukaryotes including plants and animals. The common notion in the field is that miRNAs have evolved independently in those distinct lineages, but recent evidence from non-bilaterian metazoans, plants, as well as various algae raise the possibility that already the last common ancestor of these lineages might have employed a miRNA pathway for post-transcriptional regulation. In this review we present the commonalities and differences of the miRNA pathways in various eukaryotes and discuss the contrasting scenarios of their possible evolutionary origin and their proposed link to organismal complexity and multicellularity.}, } @article {pmid28525299, year = {2017}, author = {Berbee, ML and James, TY and Strullu-Derrien, C}, title = {Early Diverging Fungi: Diversity and Impact at the Dawn of Terrestrial Life.}, journal = {Annual review of microbiology}, volume = {71}, number = {}, pages = {41-60}, doi = {10.1146/annurev-micro-030117-020324}, pmid = {28525299}, issn = {1545-3251}, mesh = {*Evolution, Molecular ; Fungi/*classification/*genetics ; *Genetic Variation ; }, abstract = {As decomposers or plant pathogens, fungi deploy invasive growth and powerful carbohydrate active enzymes to reduce multicellular plant tissues to humus and simple sugars. Fungi are perhaps also the most important mutualistic symbionts in modern ecosystems, transporting poorly soluble mineral nutrients to plants and thus enhancing the growth of vegetation. However, at their origin over a billion years ago, fungi, like plants and animals, were unicellular marine microbes. Like the other multicellular kingdoms, Fungi evolved increased size, complexity, and metabolic functioning. Interactions of fungi with plants changed terrestrial ecology and geology and modified the Earth's atmosphere. In this review, we discuss the diversification and ecological roles of the fungi over their first 600 million years, from their origin through their colonization of land, drawing on phylogenomic evidence for their relationships and metabolic capabilities and on molecular dating, fossils, and modeling of Earth's paleoclimate.}, } @article {pmid28509401, year = {2017}, author = {Dittami, SM and Heesch, S and Olsen, JL and Collén, J}, title = {Transitions between marine and freshwater environments provide new clues about the origins of multicellular plants and algae.}, journal = {Journal of phycology}, volume = {53}, number = {4}, pages = {731-745}, doi = {10.1111/jpy.12547}, pmid = {28509401}, issn = {1529-8817}, mesh = {Adaptation, Biological ; *Biological Evolution ; *Ecosystem ; Fresh Water ; *Phaeophyceae ; *Plants ; Seawater ; }, abstract = {Marine-freshwater and freshwater-marine transitions have been key events in the evolution of life, and most major groups of organisms have independently undergone such events at least once in their history. Here, we first compile an inventory of bidirectional freshwater and marine transitions in multicellular photosynthetic eukaryotes. While green and red algae have mastered multiple transitions in both directions, brown algae have colonized freshwater on a maximum of six known occasions, and angiosperms have made the transition to marine environments only two or three times. Next, we review the early evolutionary events leading to the colonization of current habitats. It is commonly assumed that the conquest of land proceeded in a sequence from marine to freshwater habitats. However, recent evidence suggests that early photosynthetic eukaryotes may have arisen in subaerial or freshwater environments and only later colonized marine environments as hypersaline oceans were diluted to the contemporary level. Although this hypothesis remains speculative, it is important to keep these alternative scenarios in mind when interpreting the current habitat distribution of plants and algae. Finally, we discuss the roles of structural and functional adaptations of the cell wall, reactive oxygen species scavengers, osmoregulation, and reproduction. These are central for acclimatization to freshwater or to marine environments. We observe that successful transitions appear to have occurred more frequently in morphologically simple forms and conclude that, in addition to physiological studies of euryhaline species, comparative studies of closely related species fully adapted to one or the other environment are necessary to better understand the adaptive processes.}, } @article {pmid28508537, year = {2018}, author = {Boomsma, JJ and Gawne, R}, title = {Superorganismality and caste differentiation as points of no return: how the major evolutionary transitions were lost in translation.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {28-54}, doi = {10.1111/brv.12330}, pmid = {28508537}, issn = {1469-185X}, mesh = {Animals ; *Behavior, Animal ; *Biological Evolution ; Insecta/*genetics/*physiology ; Selection, Genetic ; *Social Behavior ; }, abstract = {More than a century ago, William Morton Wheeler proposed that social insect colonies can be regarded as superorganisms when they have morphologically differentiated reproductive and nursing castes that are analogous to the metazoan germ-line and soma. Following the rise of sociobiology in the 1970s, Wheeler's insights were largely neglected, and we were left with multiple new superorganism concepts that are mutually inconsistent and uninformative on how superorganismality originated. These difficulties can be traced to the broadened sociobiological concept of eusociality, which denies that physical queen-worker caste differentiation is a universal hallmark of superorganismal colonies. Unlike early evolutionary naturalists and geneticists such as Weismann, Huxley, Fisher and Haldane, who set out to explain the acquisition of an unmated worker caste, the goal of sociobiology was to understand the evolution of eusociality, a broad-brush convenience category that covers most forms of cooperative breeding. By lumping a diverse spectrum of social systems into a single category, and drawing attention away from the evolution of distinct quantifiable traits, the sociobiological tradition has impeded straightforward connections between inclusive fitness theory and the major evolutionary transitions paradigm for understanding irreversible shifts to higher organizational complexity. We evaluate the history by which these inconsistencies accumulated, develop a common-cause approach for understanding the origins of all major transitions in eukaryote hierarchical complexity, and use Hamilton's rule to argue that they are directly comparable. We show that only Wheeler's original definition of superorganismality can be unambiguously linked to irreversible evolutionary transitions from context-dependent reproductive altruism to unconditional differentiation of permanently unmated castes in the ants, corbiculate bees, vespine wasps and higher termites. We argue that strictly monogamous parents were a necessary, albeit not sufficient condition for all transitions to superorganismality, analogous to single-zygote bottlenecking being a necessary but not sufficient condition for the convergent origins of complex soma across multicellular eukaryotes. We infer that conflict reduction was not a necessary condition for the origin of any of these major transitions, and conclude that controversies over the status of inclusive fitness theory primarily emanate from the arbitrarily defined sociobiological concepts of superorganismality and eusociality, not from the theory itself.}, } @article {pmid28506208, year = {2017}, author = {Labocha, MK and Yuan, W and Aleman-Meza, B and Zhong, W}, title = {A strategy to apply quantitative epistasis analysis on developmental traits.}, journal = {BMC genetics}, volume = {18}, number = {1}, pages = {42}, pmid = {28506208}, issn = {1471-2156}, support = {K99 HG004724/HG/NHGRI NIH HHS/United States ; R00 HG004724/HG/NHGRI NIH HHS/United States ; R01 DA018341/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*genetics/*growth & development ; Caenorhabditis elegans Proteins/genetics ; *Epistasis, Genetic ; High-Throughput Nucleotide Sequencing/methods ; Models, Genetic ; *Quantitative Trait Loci ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Genetic interactions are keys to understand complex traits and evolution. Epistasis analysis is an effective method to map genetic interactions. Large-scale quantitative epistasis analysis has been well established for single cells. However, there is a substantial lack of such studies in multicellular organisms and their complex phenotypes such as development. Here we present a method to extend quantitative epistasis analysis to developmental traits.

METHODS: In the nematode Caenorhabditis elegans, we applied RNA interference on mutants to inactivate two genes, used an imaging system to quantitatively measure phenotypes, and developed a set of statistical methods to extract genetic interactions from phenotypic measurement.

RESULTS: Using two different C. elegans developmental phenotypes, body length and sex ratio, as examples, we showed that this method could accommodate various metazoan phenotypes with performances comparable to those methods in single cell growth studies. Comparing with qualitative observations, this method of quantitative epistasis enabled detection of new interactions involving subtle phenotypes. For example, several sex-ratio genes were found to interact with brc-1 and brd-1, the orthologs of the human breast cancer genes BRCA1 and BARD1, respectively. We confirmed the brc-1 interactions with the following genes in DNA damage response: C34F6.1, him-3 (ortholog of HORMAD1, HORMAD2), sdc-1, and set-2 (ortholog of SETD1A, SETD1B, KMT2C, KMT2D), validating the effectiveness of our method in detecting genetic interactions.

CONCLUSIONS: We developed a reliable, high-throughput method for quantitative epistasis analysis of developmental phenotypes.}, } @article {pmid28505429, year = {2017}, author = {Siu, KH and Chen, W}, title = {Control of the Yeast Mating Pathway by Reconstitution of Functional α-Factor Using Split Intein-Catalyzed Reactions.}, journal = {ACS synthetic biology}, volume = {6}, number = {8}, pages = {1453-1460}, doi = {10.1021/acssynbio.7b00078}, pmid = {28505429}, issn = {2161-5063}, mesh = {Catalysis ; Gene Expression Regulation, Fungal/*genetics ; Genes, Mating Type, Fungal/*genetics ; Inteins/*genetics ; Metabolic Engineering/*methods ; Metabolic Networks and Pathways/*genetics ; Models, Genetic ; Pheromones/*genetics ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Signal Transduction/genetics ; }, abstract = {Synthetic control strategies using signaling peptides to regulate and coordinate cellular behaviors in multicellular organisms and synthetic consortia remain largely underdeveloped because of the complexities necessitated by heterologous peptide expression. Using recombinant proteins that exploit split intein-mediated reactions, we presented here a new strategy for reconstituting functional signaling peptides capable of eliciting desired cellular responses in S. cerevisiae. These designs can potentially be tailored to any signaling peptides to be reconstituted, as the split inteins are promiscuous and both the peptides and the reactions are amenable to changes by directed evolution and other protein engineering tools, thereby offering a general strategy to implement synthetic control strategies in a large variety of applications.}, } @article {pmid28498101, year = {2017}, author = {Hinman, V and Cary, G}, title = {The evolution of gene regulation.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {28498101}, issn = {2050-084X}, mesh = {Animals ; *Gene Expression Regulation ; *Histone Code ; Protein Processing, Post-Translational ; }, abstract = {The gene regulation mechanisms necessary for the development of complex multicellular animals have been found in sponges.}, } @article {pmid28485371, year = {2017}, author = {Milholland, B and Dong, X and Zhang, L and Hao, X and Suh, Y and Vijg, J}, title = {Differences between germline and somatic mutation rates in humans and mice.}, journal = {Nature communications}, volume = {8}, number = {}, pages = {15183}, pmid = {28485371}, issn = {2041-1723}, support = {P01 AG017242/AG/NIA NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Child ; Genome ; Germ-Line Mutation/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mice, Inbred C57BL ; *Mutation Rate ; }, abstract = {The germline mutation rate has been extensively studied and has been found to vary greatly between species, but much less is known about the somatic mutation rate in multicellular organisms, which remains very difficult to determine. Here, we present data on somatic mutation rates in mice and humans, obtained by sequencing single cells and clones derived from primary fibroblasts, which allows us to make the first direct comparison with germline mutation rates in these two species. The results indicate that the somatic mutation rate is almost two orders of magnitude higher than the germline mutation rate and that both mutation rates are significantly higher in mice than in humans. Our findings demonstrate both the privileged status of germline genome integrity and species-specific differences in genome maintenance.}, } @article {pmid28484005, year = {2017}, author = {Trigos, AS and Pearson, RB and Papenfuss, AT and Goode, DL}, title = {Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {24}, pages = {6406-6411}, pmid = {28484005}, issn = {1091-6490}, mesh = {Animals ; Carcinogenesis/genetics ; Cell Transformation, Neoplastic/genetics ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genome, Human ; Humans ; Models, Genetic ; Neoplasms/etiology/*genetics ; Oncogenes ; Phenotype ; Stress, Physiological/genetics ; Systems Biology ; }, abstract = {Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer.}, } @article {pmid28481398, year = {2017}, author = {Lei, Y and Anders, HJ}, title = {Evolutionary trade-offs in kidney injury and repair.}, journal = {Histology and histopathology}, volume = {32}, number = {11}, pages = {1099-1113}, doi = {10.14670/HH-11-900}, pmid = {28481398}, issn = {1699-5848}, mesh = {Animals ; *Biological Evolution ; Humans ; Kidney/*injuries ; *Regeneration ; }, abstract = {Evolutionary medicine has proven helpful to understand the origin of human disease, e.g. in identifying causal roles of recent environmental changes impacting on human physiology (environment-phenotype mismatch). In contrast, diseases affecting only a limited number of members of a species often originate from evolutionary trade-offs for usually physiologic adaptations assuring reproductive success in the context of extrinsic threats. For example, the G1 and G2 variants of the APOL1 gene supporting control of Trypanosoma infection come with the trade-off that they promote the progression of kidney disease. In this review we extend the concept of evolutionary nephrology by discussing how the physiologic adaptations (danger responses) to tissue injury create evolutionary trade-offs that drive histopathological changes underlying acute and chronic kidney diseases. The evolution of multicellular organisms positively selected a number of danger response programs for their overwhelming benefits in assuring survival such as clotting, inflammation, epithelial healing and mesenchymal healing, i.e. fibrosis and sclerosis. Upon kidney injury these danger programs often present as pathomechanisms driving persistent nephron loss and renal failure. We explore how classic kidney disease entities involve insufficient or overshooting activation of these danger response programs for which the underlying genetic basis remains largely to be defined. Dissecting the causative and hierarchical relationships between danger programs should help to identify molecular targets to control kidney injury and to improve disease outcomes.}, } @article {pmid28479598, year = {2017}, author = {Sebé-Pedrós, A and Degnan, BM and Ruiz-Trillo, I}, title = {The origin of Metazoa: a unicellular perspective.}, journal = {Nature reviews. Genetics}, volume = {18}, number = {8}, pages = {498-512}, pmid = {28479598}, issn = {1471-0064}, mesh = {Animals ; *Biological Evolution ; Eukaryota/classification/cytology/*genetics ; Humans ; Phylogeny ; }, abstract = {The first animals evolved from an unknown single-celled ancestor in the Precambrian period. Recently, the identification and characterization of the genomic and cellular traits of the protists most closely related to animals have shed light on the origin of animals. Comparisons of animals with these unicellular relatives allow us to reconstruct the first evolutionary steps towards animal multicellularity. Here, we review the results of these investigations and discuss their implications for understanding the earliest stages of animal evolution, including the origin of metazoan genes and genome function.}, } @article {pmid28459980, year = {2017}, author = {Fares, MA and Sabater-Muñoz, B and Toft, C}, title = {Genome Mutational and Transcriptional Hotspots Are Traps for Duplicated Genes and Sources of Adaptations.}, journal = {Genome biology and evolution}, volume = {9}, number = {5}, pages = {1229-1240}, pmid = {28459980}, issn = {1759-6653}, mesh = {Adaptation, Biological ; *Gene Duplication ; *Mutation ; Mutation Rate ; Promoter Regions, Genetic ; Saccharomyces cerevisiae/*genetics/*physiology ; Stress, Physiological ; *Transcription, Genetic ; }, abstract = {Gene duplication generates new genetic material, which has been shown to lead to major innovations in unicellular and multicellular organisms. A whole-genome duplication occurred in the ancestor of Saccharomyces yeast species but 92% of duplicates returned to single-copy genes shortly after duplication. The persisting duplicated genes in Saccharomyces led to the origin of major metabolic innovations, which have been the source of the unique biotechnological capabilities in the Baker's yeast Saccharomyces cerevisiae. What factors have determined the fate of duplicated genes remains unknown. Here, we report the first demonstration that the local genome mutation and transcription rates determine the fate of duplicates. We show, for the first time, a preferential location of duplicated genes in the mutational and transcriptional hotspots of S. cerevisiae genome. The mechanism of duplication matters, with whole-genome duplicates exhibiting different preservation trends compared to small-scale duplicates. Genome mutational and transcriptional hotspots are rich in duplicates with large repetitive promoter elements. Saccharomyces cerevisiae shows more tolerance to deleterious mutations in duplicates with repetitive promoter elements, which in turn exhibit higher transcriptional plasticity against environmental perturbations. Our data demonstrate that the genome traps duplicates through the accelerated regulatory and functional divergence of their gene copies providing a source of novel adaptations in yeast.}, } @article {pmid28457024, year = {2017}, author = {Golstein, P}, title = {Conserved nucleolar stress at the onset of cell death.}, journal = {The FEBS journal}, volume = {284}, number = {22}, pages = {3791-3800}, doi = {10.1111/febs.14095}, pmid = {28457024}, issn = {1742-4658}, mesh = {Animals ; *Cell Death ; Cell Nucleolus/metabolism/*pathology ; Humans ; Nuclear Proteins/*metabolism ; *Stress, Physiological ; }, abstract = {Cell death pervasiveness among multicellular eukaryotes suggested that some core steps of cell death may be conserved. This could be addressed by comparing the course of cell death in organisms belonging to distinct eukaryotic kingdoms. A search for early cell death events in a protist revealed nucleolar disorganization similar to the nucleolar stress often reported in dying animal cells. This indicated a conserved role for the nucleolus at the onset of eukaryotic cell death and leads one to consider the course of cell death as a succession of unequally conserved modules.}, } @article {pmid28453786, year = {2017}, author = {Porath, HT and Schaffer, AA and Kaniewska, P and Alon, S and Eisenberg, E and Rosenthal, J and Levanon, EY and Levy, O}, title = {A-to-I RNA Editing in the Earliest-Diverging Eumetazoan Phyla.}, journal = {Molecular biology and evolution}, volume = {34}, number = {8}, pages = {1890-1901}, pmid = {28453786}, issn = {1537-1719}, support = {311257/ERC_/European Research Council/International ; }, mesh = {Adenosine Deaminase/*genetics/metabolism ; Animals ; Anthozoa/*genetics/metabolism ; Base Sequence ; Evolution, Molecular ; Genome ; Genomics ; Humans ; Mammals/genetics ; Phylogeny ; RNA ; RNA Editing/*genetics ; RNA, Messenger/genetics ; RNA-Binding Proteins/genetics ; }, abstract = {The highly conserved ADAR enzymes, found in all multicellular metazoans, catalyze the editing of mRNA transcripts by the deamination of adenosines to inosines. This type of editing has two general outcomes: site specific editing, which frequently leads to recoding, and clustered editing, which is usually found in transcribed genomic repeats. Here, for the first time, we looked for both editing of isolated sites and clustered, non-specific sites in a basal metazoan, the coral Acropora millepora during spawning event, in order to reveal its editing pattern. We found that the coral editome resembles the mammalian one: it contains more than 500,000 sites, virtually all of which are clustered in non-coding regions that are enriched for predicted dsRNA structures. RNA editing levels were increased during spawning and increased further still in newly released gametes. This may suggest that editing plays a role in introducing variability in coral gametes.}, } @article {pmid28450045, year = {2017}, author = {Wang, X and Junior, JCB and Mishra, B and Lushnikova, T and Epand, RM and Wang, G}, title = {Arginine-lysine positional swap of the LL-37 peptides reveals evolutional advantages of the native sequence and leads to bacterial probes.}, journal = {Biochimica et biophysica acta. Biomembranes}, volume = {1859}, number = {8}, pages = {1350-1361}, pmid = {28450045}, issn = {0005-2736}, support = {R01 AI105147/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Anti-Bacterial Agents/*pharmacology ; Antimicrobial Cationic Peptides/*pharmacology ; Arginine/*chemistry ; Cardiolipins/chemistry/isolation & purification ; Cell Membrane/chemistry/*drug effects ; Cell Membrane Permeability/drug effects ; Escherichia coli/chemistry/drug effects/growth & development ; Humans ; Hydrogen-Ion Concentration ; Klebsiella pneumoniae/chemistry/drug effects/growth & development ; Lysine/*chemistry ; Microbial Sensitivity Tests ; Models, Molecular ; Peptides/pharmacology ; Phosphatidylethanolamines/chemistry/isolation & purification ; Phosphatidylglycerols/chemistry/isolation & purification ; Pseudomonas aeruginosa/chemistry/drug effects/growth & development ; Species Specificity ; Staphylococcus aureus/chemistry/drug effects/growth & development ; Structure-Activity Relationship ; Cathelicidins ; }, abstract = {Antimicrobial peptides are essential components of the innate immune system of multicellular organisms. Although cationic and hydrophobic amino acids are known determinants of these amphipathic molecules for bacterial killing, it is not clear how lysine-arginine (K-R) positional swaps influence peptide structure and activity. This study addresses this question by investigating two groups of peptides (GF-17 and 17BIPHE2) derived from human cathelicidin LL-37. K-R positional swap showed little effect on minimal inhibitory concentrations of the peptides. However, there are clear differences in bacterial killing kinetics. The membrane permeation patterns vary with peptide and bacterial types, but not changes in fluorescent dyes, salts or pH. In general, the original peptide is more efficient in bacterial killing, but less toxic to human cells, than the K-R swapped peptides, revealing the evolutionary significance of the native sequence for host defense. The characteristic membrane permeation patterns for different bacteria suggest a possible application of these K-R positional-swapped peptides as molecular probes for the type of bacteria. Such differences are related to bacterial membrane compositions: minimal for Gram-positive Staphylococcus aureus with essentially all anionic lipids (cardiolipin and phosphatidylglycerol), but evident for Gram-negative Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli with a mixture of phosphatidylethanolamine and phosphatidylglycerol. Biophysical characterization found similar structures and binding affinities for these peptides in vesicle systems mimicking E. coli and S. aureus. It seems that interfacial arginines of GF-17 are preferred over lysines in bacterial membrane permeation. Our study sheds new light on the design of cationic amphipathic peptides.}, } @article {pmid28441401, year = {2017}, author = {Cisneros, L and Bussey, KJ and Orr, AJ and Miočević, M and Lineweaver, CH and Davies, P}, title = {Ancient genes establish stress-induced mutation as a hallmark of cancer.}, journal = {PloS one}, volume = {12}, number = {4}, pages = {e0176258}, pmid = {28441401}, issn = {1932-6203}, mesh = {Animals ; Cell Cycle/genetics ; DNA Repair/genetics ; Databases, Genetic ; Humans ; *Mutation ; Neoplasms/*genetics ; *Oncogenes ; Phenotype ; Phylogeny ; }, abstract = {Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cancer and whose mutations are functionally important for the emergence of the cancer phenotype evolved within the past 1000 million years, and thus would exhibit an age distribution that is skewed to younger genes. In order to investigate these hypotheses we estimated the evolutionary ages of all human genes and then studied the probability of mutation and their biological function in relation to their age and genomic location for both normal germline and cancer contexts. We observed that under a model of uniform random mutation across the genome, controlled for gene size, genes less than 500 MY were more frequently mutated in both cases. Paradoxically, causal genes, defined in the COSMIC Cancer Gene Census, were depleted in this age group. When we used functional enrichment analysis to explain this unexpected result we discovered that COSMIC genes with recessive disease phenotypes were enriched for DNA repair and cell cycle control. The non-mutated genes in these pathways are orthologous to those underlying stress-induced mutation in bacteria, which results in the clustering of single nucleotide variations. COSMIC genes were less common in regions where the probability of observing mutational clusters is high, although they are approximately 2-fold more likely to harbor mutational clusters compared to other human genes. Our results suggest this ancient mutational response to stress that evolved among prokaryotes was co-opted to maintain diversity in the germline and immune system, while the original phenotype is restored in cancer. Reversion to a stress-induced mutational response is a hallmark of cancer that allows for effectively searching "protected" genome space where genes causally implicated in cancer are located and underlies the high adaptive potential and concomitant therapeutic resistance that is characteristic of cancer.}, } @article {pmid28427949, year = {2017}, author = {Freese, JM and Lane, CE}, title = {Parasitism finds many solutions to the same problems in red algae (Florideophyceae, Rhodophyta).}, journal = {Molecular and biochemical parasitology}, volume = {214}, number = {}, pages = {105-111}, doi = {10.1016/j.molbiopara.2017.04.006}, pmid = {28427949}, issn = {1872-9428}, mesh = {*Biological Evolution ; *Host-Parasite Interactions ; Microscopy ; Phylogeny ; Rhodophyta/classification/cytology/*genetics/*physiology ; }, abstract = {Parasitic red algae evolve from a common ancestor with their hosts, parasitizing cousins using familiar cellular mechanisms. They have independently evolved over one hundred times within the exclusively multicellular red algal class Florideophyceae. Reduced morphology, a lack of pigmentation, and direct cell-cell connections with their hosts are markers of red algal parasitism. With so many potential evolutionary pathways, red algal parasite diversity offers a unique test case to understand the earliest stages of this lifestyle transition. Molecular and morphological investigations led to the categorization of these parasites based on their relationship to their host. "Adelphoparasites" are phylogenetically close to their hosts, often infecting a sister species, whereas "alloparasites" are more distantly related to their hosts. The differentiation of these parasites, based on their phylogenetic relationship to their host, has resulted in a simplified classification of these parasites that may not reflect the many evolutionary pathways they take to arrive at a similar endpoint. Accordingly, many parasites fall into a gray area between adelphoparasite and alloparasite definitions, challenging the established features we use to classify them. Molecular phylogenetic research has been essential in identifying gaps in knowledge, but microscopy needs to be reincorporated in order to address red algal parasite developmental variation to establish a new paradigm. The joint utilization of molecular and microscopic methods will be critical in identifying the genomic and physiological traits of both nascent and well-established parasites.}, } @article {pmid28427501, year = {2017}, author = {Fonseca, NA and Cruz, AF and Moura, V and Simões, S and Moreira, JN}, title = {The cancer stem cell phenotype as a determinant factor of the heterotypic nature of breast tumors.}, journal = {Critical reviews in oncology/hematology}, volume = {113}, number = {}, pages = {111-121}, doi = {10.1016/j.critrevonc.2017.03.016}, pmid = {28427501}, issn = {1879-0461}, mesh = {Breast Neoplasms/metabolism/pathology/*physiopathology ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Neoplastic Stem Cells/*metabolism/physiology ; Neovascularization, Pathologic ; *Phosphoproteins ; *RNA-Binding Proteins ; *Signal Transduction ; *Tumor Microenvironment ; Nucleolin ; }, abstract = {Gathering evidence supports the existence of a population of cells with stem-like characteristics, named cancer stem cells (CSC), which is involved not only in tumor recurrence but also in tumorigenicity, metastization and drug resistance. Several markers have been used to identify putative CSC sub-populations in different cancers. Notwithstanding, it has been acknowledged that breast CSC may originate from non-stem cancer cells (non-SCC), interconverting through an epithelial-to-mesenchymal transition-mediated process, and presenting several deregulated canonical and developmental signaling pathways. These support the heterogeneity that, directly or indirectly, influences fundamental biological features supporting breast tumor development. Accordingly, CSC have increasingly become highly relevant cellular targets. In this review, we will address the stemness concept in cancer, setting the perspective on CSC and their origin, by exploring their relation and regulation within the tumor microenvironment, in the context of emerging therapeutic targets. Within this framework, we will discuss nucleolin, a protein that has been associated with angiogenesis and, more recently, with the stemness phenotype, becoming a common denominator between CSC and non-SCC for multicellular targeting.}, } @article {pmid28425150, year = {2017}, author = {Grochau-Wright, ZI and Hanschen, ER and Ferris, PJ and Hamaji, T and Nozaki, H and Olson, BJSC and Michod, RE}, title = {Genetic basis for soma is present in undifferentiated volvocine green algae.}, journal = {Journal of evolutionary biology}, volume = {30}, number = {6}, pages = {1205-1218}, pmid = {28425150}, issn = {1420-9101}, support = {NNX13AH41G//NASA/United States ; T32 GM084905/GM/NIGMS NIH HHS/United States ; NNX13AH41G//NASA/ ; }, mesh = {Adaptation, Physiological ; *Biological Evolution ; Chlorophyta ; *Phylogeny ; Stress, Physiological ; *Volvox ; }, abstract = {Somatic cellular differentiation plays a critical role in the transition from unicellular to multicellular life, but the evolution of its genetic basis remains poorly understood. By definition, somatic cells do not reproduce to pass on genes and so constitute an extreme form of altruistic behaviour. The volvocine green algae provide an excellent model system to study the evolution of multicellularity and somatic differentiation. In Volvox carteri, somatic cell differentiation is controlled by the regA gene, which is part of a tandem duplication of genes known as the reg cluster. Although previous work found the reg cluster in divergent Volvox species, its origin and distribution in the broader group of volvocine algae has not been known. Here, we show that the reg cluster is present in many species without somatic cells and determine that the genetic basis for soma arose before the phenotype at the origin of the family Volvocaceae approximately 200 million years ago. We hypothesize that the ancestral function was involved in regulating reproduction in response to stress and that this function was later co-opted to produce soma. Determining that the reg cluster was co-opted to control somatic cell development provides insight into how cellular differentiation, and with it greater levels of complexity and individuality, evolves.}, } @article {pmid28424311, year = {2017}, author = {Deora, T and Gundiah, N and Sane, SP}, title = {Mechanics of the thorax in flies.}, journal = {The Journal of experimental biology}, volume = {220}, number = {Pt 8}, pages = {1382-1395}, doi = {10.1242/jeb.128363}, pmid = {28424311}, issn = {1477-9145}, mesh = {Animals ; Biomechanical Phenomena ; Body Size ; Diptera/anatomy & histology/*physiology ; *Flight, Animal ; Wings, Animal/anatomy & histology/*physiology ; }, abstract = {Insects represent more than 60% of all multicellular life forms, and are easily among the most diverse and abundant organisms on earth. They evolved functional wings and the ability to fly, which enabled them to occupy diverse niches. Insects of the hyper-diverse orders show extreme miniaturization of their body size. The reduced body size, however, imposes steep constraints on flight ability, as their wings must flap faster to generate sufficient forces to stay aloft. Here, we discuss the various physiological and biomechanical adaptations of the thorax in flies which enabled them to overcome the myriad constraints of small body size, while ensuring very precise control of their wing motion. One such adaptation is the evolution of specialized myogenic or asynchronous muscles that power the high-frequency wing motion, in combination with neurogenic or synchronous steering muscles that control higher-order wing kinematic patterns. Additionally, passive cuticular linkages within the thorax coordinate fast and yet precise bilateral wing movement, in combination with an actively controlled clutch and gear system that enables flexible flight patterns. Thus, the study of thoracic biomechanics, along with the underlying sensory-motor processing, is central in understanding how the insect body form is adapted for flight.}, } @article {pmid28418331, year = {2017}, author = {Fidler, AL and Darris, CE and Chetyrkin, SV and Pedchenko, VK and Boudko, SP and Brown, KL and Gray Jerome, W and Hudson, JK and Rokas, A and Hudson, BG}, title = {Collagen IV and basement membrane at the evolutionary dawn of metazoan tissues.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {28418331}, issn = {2050-084X}, support = {T32 DK007569/DK/NIDDK NIH HHS/United States ; R24 DK103067/DK/NIDDK NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; R37 DK018381/DK/NIDDK NIH HHS/United States ; P30 DK114809/DK/NIDDK NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; R01 DK018381/DK/NIDDK NIH HHS/United States ; U2C DK059637/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Basement Membrane/*chemistry ; Collagen Type IV/*analysis/*genetics ; Ctenophora/cytology/genetics/metabolism/*physiology ; Evolution, Molecular ; Extracellular Matrix/*chemistry ; }, abstract = {The role of the cellular microenvironment in enabling metazoan tissue genesis remains obscure. Ctenophora has recently emerged as one of the earliest-branching extant animal phyla, providing a unique opportunity to explore the evolutionary role of the cellular microenvironment in tissue genesis. Here, we characterized the extracellular matrix (ECM), with a focus on collagen IV and its variant, spongin short-chain collagens, of non-bilaterian animal phyla. We identified basement membrane (BM) and collagen IV in Ctenophora, and show that the structural and genomic features of collagen IV are homologous to those of non-bilaterian animal phyla and Bilateria. Yet, ctenophore features are more diverse and distinct, expressing up to twenty genes compared to six in vertebrates. Moreover, collagen IV is absent in unicellular sister-groups. Collectively, we conclude that collagen IV and its variant, spongin, are primordial components of the extracellular microenvironment, and as a component of BM, collagen IV enabled the assembly of a fundamental architectural unit for multicellular tissue genesis.}, } @article {pmid28409312, year = {2017}, author = {Garcin, CL and Habib, SJ}, title = {A Comparative Perspective on Wnt/β-Catenin Signalling in Cell Fate Determination.}, journal = {Results and problems in cell differentiation}, volume = {61}, number = {}, pages = {323-350}, doi = {10.1007/978-3-319-53150-2_15}, pmid = {28409312}, issn = {0080-1844}, mesh = {Animals ; Body Patterning/physiology ; Cell Differentiation/*physiology ; Embryonic Development/*physiology ; Humans ; Wnt Signaling Pathway/*physiology ; }, abstract = {The Wnt/β-catenin pathway is an ancient and highly conserved signalling pathway that plays fundamental roles in the regulation of embryonic development and adult homeostasis. This pathway has been implicated in numerous cellular processes, including cell proliferation, differentiation, migration, morphological changes and apoptosis. In this chapter, we aim to illustrate with specific examples the involvement of Wnt/β-catenin signalling in cell fate determination. We discuss the roles of the Wnt/β-catenin pathway in specifying cell fate throughout evolution, how its function in patterning during development is often reactivated during regeneration and how perturbation of this pathway has negative consequences for the control of cell fate.The origin of all life was a single cell that had the capacity to respond to cues from the environment. With evolution, multicellular organisms emerged, and as a result, subsets of cells arose to form tissues able to respond to specific instructive signals and perform specialised functions. This complexity and specialisation required two types of messages to direct cell fate: intra- and intercellular. A fundamental question in developmental biology is to understand the underlying mechanisms of cell fate choice. Amongst the numerous external cues involved in the generation of cellular diversity, a prominent pathway is the Wnt signalling pathway in all its forms.}, } @article {pmid28406446, year = {2017}, author = {Breviario, D}, title = {Is There any Alternative to Canonical DNA Barcoding of Multicellular Eukaryotic Species? A Case for the Tubulin Gene Family.}, journal = {International journal of molecular sciences}, volume = {18}, number = {4}, pages = {}, pmid = {28406446}, issn = {1422-0067}, mesh = {DNA/chemistry/metabolism ; *DNA Barcoding, Taxonomic ; Eukaryota/*genetics ; Polymorphism, Genetic ; Sequence Analysis, DNA ; Tubulin/*genetics ; }, abstract = {Modern taxonomy is largely relying on DNA barcoding, a nucleotide sequence-based approach that provides automated species identification using short orthologous DNA regions, mainly of organellar origin when applied to multicellular Eukaryotic species. Target DNA loci have been selected that contain a minimal amount of nucleotide sequence variation within species while diverging among species. This strategy is quite effective for the identification of vertebrates and other animal lineages but poses a problem in plants where different combinations of two or three loci are constantly used. Even so, species discrimination in such plant categories as ornamentals and herbals remain problematic as well as the confident identification of subspecies, ecotypes, and closely related or recently evolved species. All these limitations may be successfully solved by the application of a different strategy, based on the use of a multi-locus, ubiquitous, nuclear marker, that is tubulin. In fact, the tubulin-based polymorphism method can release specific genomic profiles to any plant species independently from its taxonomic group. This offers the rare possibility of an effective yet generic genomic fingerprint. In a more general context, the issue is raised about the possibility that approaches alternative to systematic DNA sequencing may still provide useful and simple solutions.}, } @article {pmid28405374, year = {2017}, author = {Pratlong, M and Haguenauer, A and Chenesseau, S and Brener, K and Mitta, G and Toulza, E and Bonabaud, M and Rialle, S and Aurelle, D and Pontarotti, P}, title = {Evidence for a genetic sex determination in Cnidaria, the Mediterranean red coral (Corallium rubrum).}, journal = {Royal Society open science}, volume = {4}, number = {3}, pages = {160880}, pmid = {28405374}, issn = {2054-5703}, abstract = {Sexual reproduction is widespread among eukaryotes, and the sex-determining processes vary greatly among species. While genetic sex determination (GSD) has been intensively described in bilaterian species, no example has yet been recorded among non-bilaterians. However, the quasi-ubiquitous repartition of GSD among multicellular species suggests that similar evolutionary forces can promote this system, and that these forces could occur also in non-bilaterians. Studying sex determination across the range of Metazoan diversity is indeed important to understand better the evolution of this mechanism and its lability. We tested the existence of sex-linked genes in the gonochoric red coral (Corallium rubrum, Cnidaria) using restriction site-associated DNA sequencing. We analysed 27 461 single nucleotide polymorphisms (SNPs) in 354 individuals from 12 populations including 53 that were morphologically sexed. We found a strong association between the allele frequencies of 472 SNPs and the sex of individuals, suggesting an XX/XY sex-determination system. This result was confirmed by the identification of 435 male-specific loci. An independent test confirmed that the amplification of these loci enabled us to identify males with absolute certainty. This is the first demonstration of a GSD system among non-bilaterian species and a new example of its convergence in multicellular eukaryotes.}, } @article {pmid28398223, year = {2017}, author = {Cao, TJ and Huang, XQ and Qu, YY and Zhuang, Z and Deng, YY and Lu, S}, title = {Cloning and Functional Characterization of a Lycopene β-Cyclase from Macrophytic Red Alga Bangia fuscopurpurea.}, journal = {Marine drugs}, volume = {15}, number = {4}, pages = {}, pmid = {28398223}, issn = {1660-3397}, mesh = {Amino Acid Sequence ; Base Sequence ; Carotenoids/*genetics/*metabolism ; Cloning, Molecular/methods ; Escherichia coli/genetics ; Intramolecular Lyases/*genetics/*metabolism ; Lycopene ; Photosynthesis/physiology ; Phylogeny ; Rhodophyta/*genetics/*metabolism ; Zeaxanthins/genetics/metabolism ; beta Carotene/genetics/metabolism ; }, abstract = {Lycopene cyclases cyclize the open ends of acyclic lycopene (ψ,ψ-carotene) into β- or ε-ionone rings in the crucial bifurcation step of carotenoid biosynthesis. Among all carotenoid constituents, β-carotene (β,β-carotene) is found in all photosynthetic organisms, except for purple bacteria and heliobacteria, suggesting a ubiquitous distribution of lycopene β-cyclase activity in these organisms. In this work, we isolated a gene (BfLCYB) encoding a lycopene β-cyclase from Bangia fuscopurpurea, a red alga that is considered to be one of the primitive multicellular eukaryotic photosynthetic organisms and accumulates carotenoid constituents with both β- and ε-rings, including β-carotene, zeaxanthin, α-carotene (β,ε-carotene) and lutein. Functional complementation in Escherichia coli demonstrated that BfLCYB is able to catalyze cyclization of lycopene into monocyclic γ-carotene (β,ψ-carotene) and bicyclic β-carotene, and cyclization of the open end of monocyclic δ-carotene (ε,ψ-carotene) to produce α-carotene. No ε-cyclization activity was identified for BfLCYB. Sequence comparison showed that BfLCYB shares conserved domains with other functionally characterized lycopene cyclases from different organisms and belongs to a group of ancient lycopene cyclases. Although B. fuscopurpurea also synthesizes α-carotene and lutein, its enzyme-catalyzing ε-cyclization is still unknown.}, } @article {pmid28395144, year = {2017}, author = {Gaiti, F and Jindrich, K and Fernandez-Valverde, SL and Roper, KE and Degnan, BM and Tanurdžić, M}, title = {Landscape of histone modifications in a sponge reveals the origin of animal cis-regulatory complexity.}, journal = {eLife}, volume = {6}, number = {}, pages = {}, pmid = {28395144}, issn = {2050-084X}, mesh = {Animals ; *Biological Evolution ; *Gene Expression Regulation ; *Histone Code ; Porifera/*genetics ; }, abstract = {Combinatorial patterns of histone modifications regulate developmental and cell type-specific gene expression and underpin animal complexity, but it is unclear when this regulatory system evolved. By analysing histone modifications in a morphologically-simple, early branching animal, the sponge Amphimedonqueenslandica, we show that the regulatory landscape used by complex bilaterians was already in place at the dawn of animal multicellularity. This includes distal enhancers, repressive chromatin and transcriptional units marked by H3K4me3 that vary with levels of developmental regulation. Strikingly, Amphimedon enhancers are enriched in metazoan-specific microsyntenic units, suggesting that their genomic location is extremely ancient and likely to place constraints on the evolution of surrounding genes. These results suggest that the regulatory foundation for spatiotemporal gene expression evolved prior to the divergence of sponges and eumetazoans, and was necessary for the evolution of animal multicellularity.}, } @article {pmid28392224, year = {2017}, author = {Schiffmann, Y}, title = {The non-equilibrium basis of Turing Instability and localised biological work.}, journal = {Progress in biophysics and molecular biology}, volume = {127}, number = {}, pages = {12-32}, doi = {10.1016/j.pbiomolbio.2017.04.002}, pmid = {28392224}, issn = {1873-1732}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; *Biological Evolution ; Humans ; Hydrolysis ; *Models, Biological ; }, abstract = {Turing's theory for biological pattern formation is based on the instability of the homogeneous state, which occurs if certain key criteria are met. The problem of how chemical energy is converted to localised biological work requires one to understand not only the basis of localised power generation, but also the age-old puzzle of how organisms decrease their entropy; these problems can only be solved by the identification of the Turing Instability. At the heart of this is how natural selection, not chemistry, has fashioned the large non-equilibrium overall affinity (ΔG is a large negative quantity) for the oxidation of the fuel molecules. Natural selection has also resulted in the homeostasis at non-equilibrium values of the hydrolysis of molecules like ATP, GTP, which are the energy links between the overall oxidation of the fuel and biological work. The conditions for such homeostasis are central requirements for the Turing Instability and are the essence of being alive. The Turing-Child (TC) patterns are the spontaneous primary spatial cause not only of localised biological work in multicellular systems (especially those in patterning and development) but also of intracellular patterns including the mitotic spindle and the contractile ring. The Turing picture comprises the nonuniform distribution of the concentrations of the Turing morphogens, cAMP and ATP, and the Child picture is the resulting nonuniform distribution of the metabolic rate and of power. The TC pattern is shaped as the dominant eigenfunction in the combination of eigenfunctions which provides the spatial pattern of the Turing morphogens. The TC patterns and the bifurcation parameter manifest quantisation and symmetry as in music and in applications of quantum mechanics. The notion of correlation diagrams is also introduced.}, } @article {pmid28384293, year = {2017}, author = {Olariu, V and Nilsson, J and Jönsson, H and Peterson, C}, title = {Different reprogramming propensities in plants and mammals: Are small variations in the core network wirings responsible?.}, journal = {PloS one}, volume = {12}, number = {4}, pages = {e0175251}, pmid = {28384293}, issn = {1932-6203}, mesh = {Animals ; Mammals/*physiology ; Mice ; *Plant Physiological Phenomena ; }, abstract = {Although the plant and animal kingdoms were separated more than 1,6 billion years ago, multicellular development is for both guided by similar transcriptional, epigenetic and posttranscriptional machinery. One may ask to what extent there are similarities and differences in the gene regulation circuits and their dynamics when it comes to important processes like stem cell regulation. The key players in mouse embryonic stem cells governing pluripotency versus differentiation are Oct4, Sox2 and Nanog. Correspondingly, the WUSCHEL and CLAVATA3 genes represent a core in the Shoot Apical Meristem regulation for plants. In addition, both systems have designated genes that turn on differentiation. There is very little molecular homology between mammals and plants for these core regulators. Here, we focus on functional homologies by performing a comparison between the circuitry connecting these players in plants and animals and find striking similarities, suggesting that comparable regulatory logics have been evolved for stem cell regulation in both kingdoms. From in silico simulations we find similar differentiation dynamics. Further when in the differentiated state, the cells are capable of regaining the stem cell state. We find that the propensity for this is higher for plants as compared to mammalians. Our investigation suggests that, despite similarity in core regulatory networks, the dynamics of these can contribute to plant cells being more plastic than mammalian cells, i.e. capable to reorganize from single differentiated cells to whole plants-reprogramming. The presence of an incoherent feed-forward loop in the mammalian core circuitry could be the origin of the different reprogramming behaviour.}, } @article {pmid28383827, year = {2017}, author = {Palazzo, L and Mikoč, A and Ahel, I}, title = {ADP-ribosylation: new facets of an ancient modification.}, journal = {The FEBS journal}, volume = {284}, number = {18}, pages = {2932-2946}, pmid = {28383827}, issn = {1742-4658}, support = {281739/ERC_/European Research Council/International ; /WT_/Wellcome Trust/United Kingdom ; 22284/CRUK_/Cancer Research UK/United Kingdom ; 101794/WT_/Wellcome Trust/United Kingdom ; C35050/A22284/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {ADP Ribose Transferases/*genetics/metabolism ; Aging/genetics/*metabolism ; Animals ; Archaea/genetics/metabolism ; Bacteria/genetics/metabolism ; Biological Evolution ; DNA Damage ; *DNA Repair ; DNA Replication ; Gene Expression ; Humans ; Isoenzymes/genetics/metabolism ; Phosphoric Diester Hydrolases/genetics/metabolism ; Poly Adenosine Diphosphate Ribose/*metabolism ; *Protein Processing, Post-Translational ; Pyrophosphatases/genetics/metabolism ; Signal Transduction ; Viruses/genetics/metabolism ; Nudix Hydrolases ; }, abstract = {Rapid response to environmental changes is achieved by uni- and multicellular organisms through a series of molecular events, often involving modification of macromolecules, including proteins, nucleic acids and lipids. Amongst these, ADP-ribosylation is of emerging interest because of its ability to modify different macromolecules in the cells, and its association with many key biological processes, such as DNA-damage repair, DNA replication, transcription, cell division, signal transduction, stress and infection responses, microbial pathogenicity and aging. In this review, we provide an update on novel pathways and mechanisms regulated by ADP-ribosylation in organisms coming from all kingdoms of life.}, } @article {pmid28368386, year = {2017}, author = {Barber, J}, title = {A mechanism for water splitting and oxygen production in photosynthesis.}, journal = {Nature plants}, volume = {3}, number = {}, pages = {17041}, doi = {10.1038/nplants.2017.41}, pmid = {28368386}, issn = {2055-0278}, mesh = {Biological Evolution ; Models, Biological ; Oxidation-Reduction ; Oxygen/*metabolism ; *Photosynthesis ; Photosystem II Protein Complex/*chemistry ; Plants/*metabolism ; Water/*metabolism ; }, abstract = {Sunlight is absorbed and converted to chemical energy by photosynthetic organisms. At the heart of this process is the most fundamental reaction on Earth, the light-driven splitting of water into its elemental constituents. In this way molecular oxygen is released, maintaining an aerobic atmosphere and creating the ozone layer. The hydrogen that is released is used to convert carbon dioxide into the organic molecules that constitute life and were the origin of fossil fuels. Oxidation of these organic molecules, either by respiration or combustion, leads to the recombination of the stored hydrogen with oxygen, releasing energy and reforming water. This water splitting is achieved by the enzyme photosystem II (PSII). Its appearance at least 3 billion years ago, and linkage through an electron transfer chain to photosystem I, directly led to the emergence of eukaryotic and multicellular organisms. Before this, biological organisms had been dependent on hydrogen/electron donors, such as H2S, NH3, organic acids and Fe[2+], that were in limited supply compared with the oceans of liquid water. However, it is likely that water was also used as a hydrogen source before the emergence of PSII, as found today in anaerobic prokaryotic organisms that use carbon monoxide as an energy source to split water. The enzyme that catalyses this reaction is carbon monoxide dehydrogenase (CODH). Similarities between PSII and the iron- and nickel-containing form of this enzyme (Fe-Ni CODH) suggest a possible mechanism for the photosynthetic O-O bond formation.}, } @article {pmid28359330, year = {2017}, author = {Szafranski, P}, title = {Evolutionarily recent, insertional fission of mitochondrial cox2 into complementary genes in bilaterian Metazoa.}, journal = {BMC genomics}, volume = {18}, number = {1}, pages = {269}, pmid = {28359330}, issn = {1471-2164}, mesh = {Animals ; Electron Transport Complex IV/chemistry/*genetics ; *Evolution, Molecular ; Gene Expression Regulation ; *Genes, Mitochondrial ; Genome, Mitochondrial ; Hydrophobic and Hydrophilic Interactions ; Mitochondrial Dynamics/*genetics ; *Mutagenesis, Insertional ; Phylogeny ; Polyadenylation ; }, abstract = {BACKGROUND: Mitochondrial genomes (mtDNA) of multicellular animals (Metazoa) with bilateral symmetry (Bilateria) are compact and usually carry 13 protein-coding genes for subunits of three respiratory complexes and ATP synthase. However, occasionally reported exceptions to this typical mtDNA organization prompted speculation that, as in protists and plants, some bilaterian mitogenomes may continue to lose their canonical genes, or may even acquire new genes. To shed more light on this phenomenon, a PCR-based screen was conducted to assess fast-evolving mtDNAs of apocritan Hymenoptera (Arthropoda, Insecta) for genomic rearrangements that might be associated with the modification of mitochondrial gene content.

RESULTS: Sequencing of segmental inversions, identified in the screen, revealed that the cytochrome oxidase subunit II gene (cox2) of Campsomeris (Dielis) (Scoliidae) was split into two genes coding for COXIIA and COXIIB. The COXII-derived complementary polypeptides apparently form a heterodimer, have reduced hydrophobicity compared with the majority of mitogenome-encoded COX subunits, and one of them, COXIIB, features increased content of Cys residues. Analogous cox2 fragmentation is known only in two clades of protists (chlorophycean algae and alveolates), where it has been associated with piecewise relocation of this gene into the nucleus. In Campsomeris mtDNA, cox2a and cox2b loci are separated by a 3-kb large cluster of several antiparallel overlapping ORFs, one of which, qnu, seems to encode a nuclease that may have played a role in cox2 fission.

CONCLUSIONS: Although discontinuous mitochondrial protein genes encoding fragmented, complementary polypeptides are known in protists and some plants, split cox2 of Campsomeris is the first case of such a gene arrangement found in animals. The reported data also indicate that bilaterian animal mitogenomes may be carrying lineage-specific genes more often than previously thought, and suggest a homing endonuclease-based mechanism for insertional mitochondrial gene fission.}, } @article {pmid28357395, year = {2017}, author = {Mignot, T and Nöllmann, M}, title = {New insights into the function of a versatile class of membrane molecular motors from studies of Myxococcus xanthus surface (gliding) motility.}, journal = {Microbial cell (Graz, Austria)}, volume = {4}, number = {3}, pages = {98-100}, doi = {10.15698/mic2017.03.563}, pmid = {28357395}, issn = {2311-2638}, abstract = {Cell motility is a central function of living cells, as it empowers colonization of new environmental niches, cooperation, and development of multicellular organisms. This process is achieved by complex yet precise energy-consuming machineries in both eukaryotes and bacteria. Bacteria move on surfaces using extracellular appendages such as flagella and pili but also by a less-understood process called gliding motility. During this process, rod-shaped bacteria move smoothly along their long axis without any visible morphological changes besides occasional bending. For this reason, the molecular mechanism of gliding motility and its origin have long remained a complete mystery. An important breakthrough in the understanding of gliding motility came from single cell and genetic studies in the delta-proteobacterium Myxococcus xanthus. These early studies revealed, for the first time, the existence of bacterial Focal Adhesion complexes (FA). FAs are formed at the bacterial pole and rapidly move towards the opposite cell pole. Their attachment to the underlying surface is linked to cell propulsion, in a process similar to the rearward translocation of actomyosin complexes in Apicomplexans. The protein machinery that forms at FAs was shown to contain up to seventeen proteins predicted to localize in all layers of the bacterial cell envelope, the cytosolic face, the inner membrane (IM), the periplasmic space and the outer membrane (OM). Among these proteins, a proton-gated channel at the inner membrane was identified as the molecular motor. Thus, thrust generation requires the transduction of traction forces generated at the inner membrane through the cell envelope beyond the rigid barrier of the bacterial peptidoglycan.}, } @article {pmid28355288, year = {2017}, author = {Werfel, J and Ingber, DE and Bar-Yam, Y}, title = {Theory and associated phenomenology for intrinsic mortality arising from natural selection.}, journal = {PloS one}, volume = {12}, number = {3}, pages = {e0173677}, pmid = {28355288}, issn = {1932-6203}, mesh = {Aging/*physiology ; Animals ; Biological Evolution ; Herbivory/physiology ; Host-Pathogen Interactions ; Longevity/*physiology ; *Models, Biological ; *Models, Statistical ; Plants ; Poaceae/physiology ; Predatory Behavior/physiology ; Reproduction/physiology ; Selection, Genetic/*physiology ; }, abstract = {Standard evolutionary theories of aging and mortality, implicitly based on assumptions of spatial averaging, hold that natural selection cannot favor shorter lifespan without direct compensating benefit to individual reproductive success. However, a number of empirical observations appear as exceptions to or are difficult to reconcile with this view, suggesting explicit lifespan control or programmed death mechanisms inconsistent with the classic understanding. Moreover, evolutionary models that take into account the spatial distributions of populations have been shown to exhibit a variety of self-limiting behaviors, maintained through environmental feedback. Here we extend recent work on spatial modeling of lifespan evolution, showing that both theory and phenomenology are consistent with programmed death. Spatial models show that self-limited lifespan robustly results in long-term benefit to a lineage; longer-lived variants may have a reproductive advantage for many generations, but shorter lifespan ultimately confers long-term reproductive advantage through environmental feedback acting on much longer time scales. Numerous model variations produce the same qualitative result, demonstrating insensitivity to detailed assumptions; the key conditions under which self-limited lifespan is favored are spatial extent and locally exhaustible resources. Factors including lower resource availability, higher consumption, and lower dispersal range are associated with evolution of shorter lifespan. A variety of empirical observations can parsimoniously be explained in terms of long-term selective advantage for intrinsic mortality. Classically anomalous empirical data on natural lifespans and intrinsic mortality, including observations of longer lifespan associated with increased predation, and evidence of programmed death in both unicellular and multicellular organisms, are consistent with specific model predictions. The generic nature of the spatial model conditions under which intrinsic mortality is favored suggests a firm theoretical basis for the idea that evolution can quite generally select for shorter lifespan directly.}, } @article {pmid28342854, year = {2017}, author = {Holzer, G and Roux, N and Laudet, V}, title = {Evolution of ligands, receptors and metabolizing enzymes of thyroid signaling.}, journal = {Molecular and cellular endocrinology}, volume = {459}, number = {}, pages = {5-13}, doi = {10.1016/j.mce.2017.03.021}, pmid = {28342854}, issn = {1872-8057}, mesh = {Animals ; Biological Evolution ; Cnidaria/anatomy & histology/physiology ; Gene Expression Regulation, Developmental ; Humans ; Insecta/anatomy & histology/physiology ; Iodide Peroxidase/genetics/*metabolism ; Ligands ; Phylogeny ; Receptors, Thyroid Hormone/genetics/*metabolism ; Signal Transduction/*physiology ; Species Specificity ; Thyroid Gland/*physiology ; Thyroxine/genetics/*metabolism ; Triiodothyronine/analogs & derivatives/genetics/*metabolism ; }, abstract = {Thyroid hormones (THs) play important roles in vertebrates such as the control of the metabolism, development and seasonality. Given the pleiotropic effects of thyroid disorders (developmental delay, mood disorder, tachycardia, etc), THs signaling is highly investigated, specially using mammalian models. In addition, the critical role of TH in controlling frog metamorphosis has led to the use of Xenopus as another prominent model to study THs action. Nevertheless, animals regarded as non-model species can also improve our understanding of THs signaling. For instance, studies in amphioxus highlighted the role of Triac as a bona fide thyroid hormone receptor (TR) ligand. In this review, we discuss our current understanding of the THs signaling in the different taxa forming the metazoans (multicellular animals) group. We mainly focus on three actors of the THs signaling: the ligand, the receptor and the deiodinases, enzymes playing a critical role in THs metabolism. By doing so, we also pinpoint many key questions that remain unanswered. How can THs accelerate metamorphosis in tunicates and echinoderms while their TRs have not been yet demonstrated as functional THs receptors in these species? Do THs have a biological effect in insects and cnidarians even though they do not have any TR? What is the basic function of THs in invertebrate protostomia? These questions can appear disconnected from pharmacological issues and human applications, but the investigation of THs signaling at the metazoans scale can greatly improve our understanding of this major endocrinological pathway.}, } @article {pmid28324731, year = {2017}, author = {Jayadev, R and Sherwood, DR}, title = {Basement membranes.}, journal = {Current biology : CB}, volume = {27}, number = {6}, pages = {R207-R211}, doi = {10.1016/j.cub.2017.02.006}, pmid = {28324731}, issn = {1879-0445}, support = {R01 GM079320/GM/NIGMS NIH HHS/United States ; R01 GM100083/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Basement Membrane/*physiology ; Caenorhabditis elegans/growth & development/*physiology ; Disease Susceptibility/*physiopathology ; Drosophila/growth & development/*physiology ; Growth/physiology ; Homeostasis/physiology ; Humans ; Mice ; }, abstract = {Basement membranes (BMs) are thin, dense sheets of specialized, self-assembled extracellular matrix that surround most animal tissues (Figure 1, top). The emergence of BMs coincided with the origin of multicellularity in animals, suggesting that they were essential for the formation of tissues. Their sheet-like structure derives from two independent polymeric networks - one of laminin and one of type IV collagen (Figure 1, bottom). These independent collagen and laminin networks are thought to be linked by several additional extracellular matrix proteins, including nidogen and perlecan (Figure 1, bottom). BMs are usually associated with cells and are anchored to cell surfaces through interactions with adhesion receptors and sulfated glycolipids (Figure 1, bottom). Various combinations of other proteins, glycoproteins, and proteoglycans - including fibulin, hemicentin, SPARC, agrin, and type XVIII collagen - are present in BMs, creating biochemically and biophysically distinct structures that serve a wide variety of functions. BMs have traditionally been viewed as static protein assemblies that provide structural support to tissues. However, recent studies have begun to uncover dynamic, active roles for BMs in many developmental processes. Here, we discuss established and emerging roles of BMs in development, tissue construction, and tissue homeostasis. We also explore how cells traverse BM barriers, the roles of BMs in human diseases, and future directions for the field.}, } @article {pmid28317949, year = {2017}, author = {Rudd, TR and Preston, MD and Yates, EA}, title = {The nature of the conserved basic amino acid sequences found among 437 heparin binding proteins determined by network analysis.}, journal = {Molecular bioSystems}, volume = {13}, number = {5}, pages = {852-865}, doi = {10.1039/c6mb00857g}, pmid = {28317949}, issn = {1742-2051}, mesh = {Amino Acid Sequence ; Binding Sites ; Computational Biology/methods ; Conserved Sequence ; Heparin/*metabolism ; Heparitin Sulfate/*metabolism ; Humans ; Models, Molecular ; Protein Binding ; Protein Interaction Maps ; Proteins/*chemistry/*metabolism ; }, abstract = {In multicellular organisms, a large number of proteins interact with the polyanionic polysaccharides heparan sulphate (HS) and heparin. These interactions are usually assumed to be dominated by charge-charge interactions between the anionic carboxylate and/or sulfate groups of the polysaccharide and cationic amino acids of the protein. A major question is whether there exist conserved amino acid sequences for HS/heparin binding among these diverse proteins. Potentially conserved HS/heparin binding sequences were sought amongst 437 HS/heparin binding proteins. Amino acid sequences were extracted and compared using a Levenshtein distance metric. The resultant similarity matrices were visualised as graphs, enabling extraction of strongly conserved sequences from highly variable primary sequences while excluding short, core regions. This approach did not reveal extensive, conserved HS/heparin binding sequences, rather a number of shorter, more widely spaced sequences that may work in unison to form heparin-binding sites on protein surfaces, arguing for convergent evolution. Thus, it is the three-dimensional arrangement of these conserved motifs on the protein surface, rather than the primary sequence per se, which are the evolutionary elements.}, } @article {pmid28294448, year = {2017}, author = {Inglis, RF and Ryu, E and Asikhia, O and Strassmann, JE and Queller, DC}, title = {Does high relatedness promote cheater-free multicellularity in synthetic lifecycles?.}, journal = {Journal of evolutionary biology}, volume = {30}, number = {5}, pages = {985-993}, doi = {10.1111/jeb.13067}, pmid = {28294448}, issn = {1420-9101}, mesh = {*Biological Evolution ; Dictyostelium/*growth & development ; *Life Cycle Stages ; }, abstract = {The evolution of multicellularity is one of the key transitions in evolution and requires extreme levels of cooperation between cells. However, even when cells are genetically identical, noncooperative cheating mutants can arise that cause a breakdown in cooperation. How then, do multicellular organisms maintain cooperation between cells? A number of mechanisms that increase relatedness amongst cooperative cells have been implicated in the maintenance of cooperative multicellularity including single-cell bottlenecks and kin recognition. In this study, we explore how relatively simple biological processes such as growth and dispersal can act to increase relatedness and promote multicellular cooperation. Using experimental populations of pseudo-organisms, we found that manipulating growth and dispersal of clones of a social amoeba to create high levels of relatedness was sufficient to prevent the spread of cheating mutants. By contrast, cheaters were able to spread under low-relatedness conditions. Most surprisingly, we saw the largest increase in cheating mutants under an experimental treatment that should create intermediate levels of relatedness. This is because one of the factors raising relatedness, structured growth, also causes high vulnerability to growth rate cheaters.}, } @article {pmid28291791, year = {2017}, author = {Bengtson, S and Sallstedt, T and Belivanova, V and Whitehouse, M}, title = {Three-dimensional preservation of cellular and subcellular structures suggests 1.6 billion-year-old crown-group red algae.}, journal = {PLoS biology}, volume = {15}, number = {3}, pages = {e2000735}, pmid = {28291791}, issn = {1545-7885}, mesh = {*Fossils ; Geologic Sediments ; *Geological Phenomena ; India ; Phylogeny ; Radiometry ; Rhodophyta/*cytology/ultrastructure ; Subcellular Fractions/metabolism ; Time Factors ; }, abstract = {The ~1.6 Ga Tirohan Dolomite of the Lower Vindhyan in central India contains phosphatized stromatolitic microbialites. We report from there uniquely well-preserved fossils interpreted as probable crown-group rhodophytes (red algae). The filamentous form Rafatazmia chitrakootensis n. gen, n. sp. has uniserial rows of large cells and grows through diffusely distributed septation. Each cell has a centrally suspended, conspicuous rhomboidal disk interpreted as a pyrenoid. The septa between the cells have central structures that may represent pit connections and pit plugs. Another filamentous form, Denaricion mendax n. gen., n. sp., has coin-like cells reminiscent of those in large sulfur-oxidizing bacteria but much more recalcitrant than the liquid-vacuole-filled cells of the latter. There are also resemblances with oscillatoriacean cyanobacteria, although cell volumes in the latter are much smaller. The wider affinities of Denaricion are uncertain. Ramathallus lobatus n. gen., n. sp. is a lobate sessile alga with pseudoparenchymatous thallus, "cell fountains," and apical growth, suggesting florideophycean affinity. If these inferences are correct, Rafatazmia and Ramathallus represent crown-group multicellular rhodophytes, antedating the oldest previously accepted red alga in the fossil record by about 400 million years.}, } @article {pmid28284906, year = {2017}, author = {Lochab, AK and Extavour, CG}, title = {Bone Morphogenetic Protein (BMP) signaling in animal reproductive system development and function.}, journal = {Developmental biology}, volume = {427}, number = {2}, pages = {258-269}, doi = {10.1016/j.ydbio.2017.03.002}, pmid = {28284906}, issn = {1095-564X}, mesh = {Animals ; *Biological Evolution ; Bone Morphogenetic Proteins/*metabolism ; Cell Lineage ; Genitalia/embryology/*metabolism ; *Germ Cells/metabolism ; Humans ; Reproduction ; Signal Transduction ; }, abstract = {In multicellular organisms, the specification, maintenance, and transmission of the germ cell lineage to subsequent generations are critical processes that ensure species survival. A number of studies suggest that the Bone Morphogenetic Protein (BMP) pathway plays multiple roles in this cell lineage. We wished to use a comparative framework to examine the role of BMP signaling in regulating these processes, to determine if patterns would emerge that might shed light on the evolution of molecular mechanisms that may play germ cell-specific or other reproductive roles across species. To this end, here we review evidence to date from the literature supporting a role for BMP signaling in reproductive processes across Metazoa. We focus on germ line-specific processes, and separately consider somatic reproductive processes. We find that from primordial germ cell (PGC) induction to maintenance of PGC identity and gametogenesis, BMP signaling regulates these processes throughout embryonic development and adult life in multiple deuterostome and protostome clades. In well-studied model organisms, functional genetic evidence suggests that BMP signaling is required in the germ line across all life stages, with the exception of PGC specification in species that do not use inductive signaling to induce germ cell formation. The current evidence is consistent with the hypothesis that BMP signaling is ancestral in bilaterian inductive PGC specification. While BMP4 appears to be the most broadly employed ligand for the reproductive processes considered herein, we also noted evidence for sex-specific usage of different BMP ligands. In gametogenesis, BMP6 and BMP15 seem to have roles restricted to oogenesis, while BMP8 is restricted to spermatogenesis. We hypothesize that a BMP-based mechanism may have been recruited early in metazoan evolution to specify the germ line, and was subsequently co-opted for use in other germ line-specific and somatic reproductive processes. We suggest that if future studies assessing the function of the BMP pathway across extant species were to include a reproductive focus, that we would be likely to find continued evidence in favor of an ancient association between BMP signaling and the reproductive cell lineage in animals.}, } @article {pmid28258564, year = {2017}, author = {Ishibashi, K and Morishita, Y and Tanaka, Y}, title = {The Evolutionary Aspects of Aquaporin Family.}, journal = {Advances in experimental medicine and biology}, volume = {969}, number = {}, pages = {35-50}, doi = {10.1007/978-94-024-1057-0_2}, pmid = {28258564}, issn = {0065-2598}, mesh = {Amino Acid Sequence ; Animals ; Aquaporins/chemistry/classification/*genetics/metabolism ; Biological Evolution ; Biological Transport ; Conserved Sequence ; Fungi/classification/*genetics/metabolism ; Gene Duplication ; Gene Expression ; Gene Transfer, Horizontal ; Invertebrates/classification/*genetics/metabolism ; Phylogeny ; Plants/classification/*genetics/metabolism ; Prokaryotic Cells/classification/*metabolism ; Protein Domains ; Vertebrates/classification/*genetics/metabolism ; }, abstract = {Aquaporins (AQPs) are a family of transmembrane proteins present in almost all species including virus. They are grossly divided into three subfamilies based on the sequence around a highly conserved pore-forming NPA motif: (1) classical water -selective AQP (CAQP), (2) glycerol -permeable aquaglyceroporin (AQGP) and (3) AQP super-gene channel, superaquaporin (SAQP). AQP is composed of two tandem repeats of conserved three transmembrane domains and a NPA motif. AQP ancestors probably started in prokaryotes by the duplication of half AQP genes to be diversified into CAQPs or AQGPs by evolving a subfamily-specific carboxyl-terminal NPA motif. Both AQP subfamilies may have been carried over to unicellular eukaryotic ancestors, protists and further to multicellular organisms. Although fungus lineage has kept both AQP subfamilies, the plant lineage has lost AQGP after algal ancestors with extensive diversifications of CAQPs into PIP, TIP, SIP, XIP, HIP and LIP with a possible horizontal transfer of NIP from bacteria. Interestingly, the animal lineage has obtained new SAQP subfamily with highly deviated NPA motifs, especially at the amino-terminal halves in both prostomial and deuterostomial animals. The prostomial lineage has lost AQGP after hymenoptera, while the deuterostomial lineage has kept all three subfamilies up to the vertebrate with diversified CAQPs (AQP0, 1, 2, 4, 5, 6, 8) and AQGPs (AQP3, 7, 9, 10) with limited SAQPs (AQP11, 12) in mammals. Whole-genome duplications, local gene duplications and horizontal gene transfers may have produced the AQP diversity with adaptive selections and functional alternations in response to environment changes. With the above evolutionary perspective in mind, the function of each AQP could be speculated by comparison among species to get new insights into physiological roles of AQPs . This evolutionary guidance in AQP research will lead to deeper understandings of water and solute homeostasis.}, } @article {pmid28253955, year = {2017}, author = {López-Otín, C and Mariño, G}, title = {Tagged ATG8-Coding Constructs for the In Vitro and In Vivo Assessment of ATG4 Activity.}, journal = {Methods in enzymology}, volume = {587}, number = {}, pages = {189-205}, doi = {10.1016/bs.mie.2016.11.001}, pmid = {28253955}, issn = {1557-7988}, mesh = {Animals ; Autophagy ; Autophagy-Related Protein 8 Family/*genetics/metabolism ; Autophagy-Related Proteins/genetics/metabolism ; Cells, Cultured ; Cysteine Endopeptidases/analysis/genetics/*metabolism ; Genetic Vectors ; Humans ; Mammals/genetics ; Mice ; Molecular Biology/*methods ; Recombinant Proteins/genetics/metabolism ; Transfection ; }, abstract = {Autophagy is a catabolic pathway, which mediates the degradation of cytoplasmic components and sustains many essential cellular functions. More than 30 genes have been involved in different aspects of this essential process in simple eukaryotes as yeast. Among these genes, those coding for members of the Atg4-Atg8 proteolytic system have acquired a high degree of complexity throughout evolution. Contrasting with the situation in unicellular eukaryotes, in which the system is composed by just a single protease (Atg4) and a single substrate (Atg8), evolution has led to the presence of several members for both Atg4 and Atg8 families in multicellular organisms. In human cells, there are four Atg4 proteases and six Atg8 substrates, which have probably evolved to cope with specific requirements for autophagic pathway in more complex scenarios. Despite these considerations, the reasons for the evolutionarily acquired complexity of this proteolytic system are still not completely understood. In this work, we describe two different applications of a relatively simple but useful technique to analyze protease-substrate specificity of this system in mammalian cells. By using the described technique, it is possible to determine the cellular efficiency in the initial cleavage for each of the Atg8 family members in diverse experimental settings both in cultured cells and live laboratory mice.}, } @article {pmid28250339, year = {2017}, author = {Cahill, MA}, title = {The evolutionary appearance of signaling motifs in PGRMC1.}, journal = {Bioscience trends}, volume = {11}, number = {2}, pages = {179-192}, doi = {10.5582/bst.2017.01009}, pmid = {28250339}, issn = {1881-7823}, mesh = {Animals ; Humans ; Membrane Proteins/genetics/*metabolism ; Receptors, Progesterone/genetics/*metabolism ; Signal Transduction/genetics/physiology ; }, abstract = {A complex PGRMC1-centred regulatory system controls multiple cell functions. Although PGRMC1 is phosphorylated at several positions, we do not understand the mechanisms regulating its function. PGRMC1 is the archetypal member of the membrane associated progesterone receptor (MAPR) family. Phylogentic comparison of MAPR proteins suggests that the ancestral metazoan "PGRMC-like" MAPR gene resembled PGRMC1/PGRMC2, containing the equivalents of PGRMC1 Y139 and Y180 SH2 target motifs. It later acquired a CK2 site with phosphoacceptor at S181. Separate PGRMC1 and PGRMC2 genes with this "PGRMC-like" structure diverged after the separation of vertebrates from protochordates. Terrestrial tetrapods possess a novel proline-rich PGRMC1 SH3 target motif centred on P64 which in mammals is augmented by a phosphoacceptor at PGRMC1 S54, and in primates by an additional S57 CK2 site. All of these phosphoacceptors are phosphorylated in vivo. This study suggests that an increasingly sophisticated system of PGRMC1-modulated multicellular functional regulation has characterised animal evolution since Precambrian times.}, } @article {pmid28247585, year = {2017}, author = {Frenk, S and Pizza, G and Walker, RV and Houseley, J}, title = {Aging yeast gain a competitive advantage on non-optimal carbon sources.}, journal = {Aging cell}, volume = {16}, number = {3}, pages = {602-604}, pmid = {28247585}, issn = {1474-9726}, support = {088335/WT_/Wellcome Trust/United Kingdom ; BBS/E/B/0000H247/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /MRC_/Medical Research Council/United Kingdom ; 088335/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Acetic Acid/metabolism/pharmacology ; Adaptation, Physiological/*genetics ; Carbon/*metabolism ; Cell Division ; Fermentation ; Galactose/metabolism/pharmacology ; Glucose/metabolism/pharmacology ; Metabolic Networks and Pathways/*genetics ; Raffinose/metabolism/pharmacology ; Saccharomyces cerevisiae/*drug effects/genetics/growth & development/*metabolism ; }, abstract = {Animals, plants and fungi undergo an aging process with remarkable physiological and molecular similarities, suggesting that aging has long been a fact of life for eukaryotes and one to which our unicellular ancestors were subject. Key biochemical pathways that impact longevity evolved prior to multicellularity, and the interactions between these pathways and the aging process therefore emerged in ancient single-celled eukaryotes. Nevertheless, we do not fully understand how aging impacts the fitness of unicellular organisms, and whether such cells gain a benefit from modulating rather than simply suppressing the aging process. We hypothesized that age-related loss of fitness in single-celled eukaryotes may be counterbalanced, partly or wholly, by a transition from a specialist to a generalist life-history strategy that enhances adaptability to other environments. We tested this hypothesis in budding yeast using competition assays and found that while young cells are more successful in glucose, highly aged cells outcompete young cells on other carbon sources such as galactose. This occurs because aged yeast divide faster than young cells in galactose, reversing the normal association between age and fitness. The impact of aging on single-celled organisms is therefore complex and may be regulated in ways that anticipate changing nutrient availability. We propose that pathways connecting nutrient availability with aging arose in unicellular eukaryotes to capitalize on age-linked diversity in growth strategy and that individual cells in higher eukaryotes may similarly diversify during aging to the detriment of the organism as a whole.}, } @article {pmid28241893, year = {2017}, author = {Zemková, M and Zahradník, D and Mokrejš, M and Flegr, J}, title = {Parasitism as the main factor shaping peptide vocabularies in current organisms.}, journal = {Parasitology}, volume = {144}, number = {7}, pages = {975-983}, doi = {10.1017/S0031182017000191}, pmid = {28241893}, issn = {1469-8161}, mesh = {Animals ; *Biological Evolution ; Helminth Proteins/*analysis ; *Host-Parasite Interactions ; Peptides/*analysis ; *Proteome ; Protozoan Proteins/*analysis ; }, abstract = {Self/non-self-discrimination by vertebrate immune systems is based on the recognition of the presence of peptides in proteins of a parasite that are not contained in the proteins of a host. Therefore, a reduction of the number of 'words' in its own peptide vocabulary could be an efficient evolutionary strategy of parasites for escaping recognition. Here, we compared peptide vocabularies of 30 endoparasitic and 17 free-living unicellular organisms and also eight multicellular parasitic and 16 multicellular free-living organisms. We found that both unicellular and multicellular parasites used a significantly lower number of different pentapeptides than free-living controls. Impoverished pentapeptide vocabularies in parasites were observed across all five clades that contain both the parasitic and free-living species. The effect of parasitism on a number of peptides used in an organism's proteins is larger than effects of all other studied factors, including the size of a proteome, the number of encoded proteins, etc. This decrease of pentapeptide diversity was partly compensated for by an increased number of hexapeptides. Our results support the hypothesis of parasitism-associated reduction of peptide vocabulary and suggest that T-cell receptors mostly recognize the five amino acids-long part of peptides that are presented in the groove of major histocompatibility complex molecules.}, } @article {pmid28222679, year = {2017}, author = {Skippington, E and Barkman, TJ and Rice, DW and Palmer, JD}, title = {Comparative mitogenomics indicates respiratory competence in parasitic Viscum despite loss of complex I and extreme sequence divergence, and reveals horizontal gene transfer and remarkable variation in genome size.}, journal = {BMC plant biology}, volume = {17}, number = {1}, pages = {49}, pmid = {28222679}, issn = {1471-2229}, mesh = {DNA, Plant ; Electron Transport Chain Complex Proteins/genetics ; Electron Transport Complex I/*genetics/metabolism ; *Evolution, Molecular ; Gene Deletion ; *Gene Transfer, Horizontal ; Genes, Plant ; *Genetic Variation ; Genome, Mitochondrial ; *Genome, Plant ; Molecular Sequence Annotation ; Plant Proteins/genetics ; RNA, Plant ; RNA, Ribosomal ; Sequence Analysis, DNA ; Species Specificity ; Viscum/*genetics/metabolism ; Viscum album/genetics/metabolism ; }, abstract = {BACKGROUND: Aerobically respiring eukaryotes usually contain four respiratory-chain complexes (complexes I-IV) and an ATP synthase (complex V). In several lineages of aerobic microbial eukaryotes, complex I has been lost, with an alternative, nuclear-encoded NADH dehydrogenase shown in certain cases to bypass complex I and oxidize NADH without proton translocation. The first loss of complex I in any multicellular eukaryote was recently reported in two studies; one sequenced the complete mitogenome of the hemiparasitic aerial mistletoe, Viscum scurruloideum, and the other sequenced the V. album mitogenome. The V. scurruloideum study reported no significant additional loss of mitochondrial genes or genetic function, but the V. album study postulated that mitochondrial genes encoding all ribosomal RNAs and proteins of all respiratory complexes are either absent or pseudogenes, thus raising questions as to whether the mitogenome and oxidative respiration are functional in this plant.

RESULTS: To determine whether these opposing conclusions about the two Viscum mitogenomes reflect a greater degree of reductive/degenerative evolution in V. album or instead result from interpretative and analytical differences, we reannotated and reanalyzed the V. album mitogenome and compared it with the V. scurruloideum mitogenome. We find that the two genomes share a complete complement of mitochondrial rRNA genes and a typical complement of genes encoding respiratory complexes II-V. Most Viscum mitochondrial protein genes exhibit very high levels of divergence yet are evolving under purifying, albeit relaxed selection. We discover two cases of horizontal gene transfer in V. album and show that the two Viscum mitogenomes differ by 8.6-fold in size (66 kb in V. scurruloideum; 565 kb in V. album).

CONCLUSIONS: Viscum mitogenomes are extraordinary compared to other plant mitogenomes in terms of their wide size range, high rates of synonymous substitutions, degree of relaxed selection, and unprecedented loss of respiratory complex I. However, contrary to the initial conclusions regarding V. album, both Viscum mitogenomes possess conventional sets of rRNA and, excepting complex I, respiratory genes. Both plants should therefore be able to carry out aerobic respiration. Moreover, with respect to size, the V. scurruloideum mitogenome has experienced a greater level of reductive evolution.}, } @article {pmid28214944, year = {2017}, author = {Basile, A and Fambrini, M and Pugliesi, C}, title = {The vascular plants: open system of growth.}, journal = {Development genes and evolution}, volume = {227}, number = {2}, pages = {129-157}, pmid = {28214944}, issn = {1432-041X}, mesh = {*Evolution, Molecular ; Magnoliopsida/*genetics/growth & development/metabolism ; Meristem/*genetics/growth & development/metabolism ; Plant Growth Regulators/metabolism ; Plant Proteins/genetics/metabolism ; }, abstract = {What is fascinating in plants (true also in sessile animals such as corals and hydroids) is definitely their open and indeterminate growth, as a result of meristematic activity. Plants as well as animals are characterized by a multicellular organization, with which they share a common set of genes inherited from a common eukaryotic ancestor; nevertheless, circa 1.5 billion years of evolutionary history made the two kingdoms very different in their own developmental biology. Flowering plants, also known as angiosperms, arose during the Cretaceous Period (145-65 million years ago), and up to date, they count around 235,000 species, representing the largest and most diverse group within the plant kingdom. One of the foundations of their success relies on the plant-pollinator relationship, essentially unique to angiosperms that pushed large speciation in both plants and insects and on the presence of the carpel, the structure devoted to seed enclosure. A seed represents the main organ preserving the genetic information of a plant; during embryogenesis, the primary axis of development is established by two groups of pluripotent cells: the shoot apical meristem (SAM), responsible for gene rating all aboveground organs, and the root apical meristem (RAM), responsible for producing all underground organs. During postembryonic shoot development, axillary meristem (AM) initiation and outgrowth are responsible for producing all secondary axes of growth including inflorescence branches or flowers. The production of AMs is tightly linked to the production of leaves and their separation from SAM. As leaf primordia are formed on the flanks of the SAM, a region between the apex and the developing organ is established and referred to as boundary zone. Interaction between hormones and the gene network in the boundary zone is fundamental for AM initiation. AMs only develop at the adaxial base of the leaf; thus, AM initiation is also strictly associated with leaf polarity. AMs function as new SAMs: form axillary buds with a few leaves and then the buds can either stay dormant or develop into shoot branches to define a plant architecture, which in turn affects assimilate production and reproductive efficiency. Therefore, the radiation of angiosperms was accompanied by a huge diversification in growth forms that determine an enormous morphological plasticity helping plants to environmental changes. In this review, we focused on the developmental processes of AM initiation and outgrowth. In particular, we summarized the primary growth of SAM, the key role of positional signals for AM initiation, and the dissection of molecular players involved in AM initiation and outgrowth. Finally, the interaction between phytohormone signals and gene regulatory network controlling AM development was discussed.}, } @article {pmid28207760, year = {2017}, author = {Neeb, ZT and Hogan, DJ and Katzman, S and Zahler, AM}, title = {Preferential expression of scores of functionally and evolutionarily diverse DNA and RNA-binding proteins during Oxytricha trifallax macronuclear development.}, journal = {PloS one}, volume = {12}, number = {2}, pages = {e0170870}, pmid = {28207760}, issn = {1932-6203}, support = {T32 GM008646/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA, Protozoan/*genetics ; *Evolution, Molecular ; *Gene Expression Profiling ; Gene Expression Regulation ; High-Throughput Nucleotide Sequencing ; Macronucleus/genetics/*metabolism ; Oxytricha/genetics/growth & development/*metabolism ; Phylogeny ; Protozoan Proteins/genetics/*metabolism ; RNA-Binding Proteins/genetics/*metabolism ; }, abstract = {During its sexual reproduction, the stichotrichous ciliate Oxytricha trifallax orchestrates a remarkable transformation of one of the newly formed germline micronuclear genomes. Hundreds of thousands of gene pieces are stitched together, excised from chromosomes, and replicated dozens of times to yield a functional somatic macronuclear genome composed of ~16,000 distinct DNA molecules that typically encode a single gene. Little is known about the proteins that carry out this process. We profiled mRNA expression as a function of macronuclear development and identified hundreds of mRNAs preferentially expressed at specific times during the program. We find that a disproportionate number of these mRNAs encode proteins that are involved in DNA and RNA functions. Many mRNAs preferentially expressed during macronuclear development have paralogs that are either expressed constitutively or are expressed at different times during macronuclear development, including many components of the RNA polymerase II machinery and homologous recombination complexes. Hundreds of macronuclear development-specific genes encode proteins that are well-conserved among multicellular eukaryotes, including many with links to germline functions or development. Our work implicates dozens of DNA and RNA-binding proteins with diverse evolutionary trajectories in macronuclear development in O. trifallax. It suggests functional connections between the process of macronuclear development in unicellular ciliates and germline specialization and differentiation in multicellular organisms, and argues that gene duplication is a key source of evolutionary innovation in this process.}, } @article {pmid28204813, year = {2017}, author = {Agnati, LF and Marcoli, M and Leo, G and Maura, G and Guidolin, D}, title = {Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review).}, journal = {International journal of molecular medicine}, volume = {39}, number = {3}, pages = {487-497}, pmid = {28204813}, issn = {1791-244X}, mesh = {Animals ; Biological Evolution ; Body Temperature Regulation ; Brain/*physiology ; Cerebrospinal Fluid/metabolism ; Extracellular Fluid/*metabolism ; Feedback, Physiological ; *Homeostasis ; Humans ; Kidney/physiology ; Sodium/metabolism ; }, abstract = {In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. However, the new concept of a hierarchic role of ISF of the various organs is introduced. Additionally, it is suggested that particularly for some chemico‑physical parameters, oscillatory rhythms within their proper set‑ranges should be considered a fundamental component of homeostasis. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio‑pathological states. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Furthermore, the evolutionary links between brain and kidney and their synergistic role in H2O/Na balance and brain temperature control are discussed. Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis.}, } @article {pmid28189637, year = {2017}, author = {Sieber, KB and Bromley, RE and Dunning Hotopp, JC}, title = {Lateral gene transfer between prokaryotes and eukaryotes.}, journal = {Experimental cell research}, volume = {358}, number = {2}, pages = {421-426}, pmid = {28189637}, issn = {1090-2422}, support = {DP2 OD007372/OD/NIH HHS/United States ; R01 CA206188/CA/NCI NIH HHS/United States ; T32 DK067872/DK/NIDDK NIH HHS/United States ; 1-R01-CA206188/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics/physiology ; Humans ; Mitochondria/metabolism ; Prokaryotic Cells/*cytology ; }, abstract = {Lateral gene transfer (LGT) is an all-encompassing term for the movement of DNA between diverse organisms. LGT is synonymous with horizontal gene transfer, and the terms are used interchangeably throughout the scientific literature. While LGT has been recognized within the bacteria domain of life for decades, inter-domain LGTs are being increasingly described. LGTs between bacteria and complex multicellular organisms are of interest because they challenge the long-held dogma that such transfers could only occur in closely-related, single-celled organisms. Scientists will continue to challenge our understanding of LGT as we sequence more, diverse organisms, as we sequence more endosymbiont-colonized arthropods, and as we continue to appreciate LGT events, both young and old.}, } @article {pmid28188480, year = {2017}, author = {Sekimoto, H}, title = {Sexual reproduction and sex determination in green algae.}, journal = {Journal of plant research}, volume = {130}, number = {3}, pages = {423-431}, pmid = {28188480}, issn = {1618-0860}, mesh = {Biological Evolution ; Cell Adhesion/physiology ; Cell Fusion ; Chlamydomonas reinhardtii/genetics/growth & development ; Chlorophyta/*genetics/growth & development/*physiology ; Closterium/genetics/growth & development ; Fresh Water ; Life Cycle Stages/genetics/physiology ; Membrane Fusion/physiology ; Reproduction/*genetics/*physiology ; Sex Determination Processes/*genetics/*physiology ; Volvox/genetics/growth & development ; }, abstract = {The sexual reproductive processes of some representative freshwater green algae are reviewed. Chlamydomonas reinhardtii is a unicellular volvocine alga having two mating types: mating type plus (mt[+]) and mating type minus (mt[-]), which are controlled by a single, complex mating-type locus. Sexual adhesion between the gametes is mediated by sex-specific agglutinin molecules on their flagellar membranes. Cell fusion is initiated by an adhesive interaction between the mt[+] and mt[-] mating structures, followed by localized membrane fusion. The loci of sex-limited genes and the conformation of sex-determining regions have been rearranged during the evolution of volvocine algae; however, the essential function of the sex-determining genes of the isogamous unicellular Chlamydomonas reinhardtii is conserved in the multicellular oogamous Volvox carteri. The sexual reproduction of the unicellular charophycean alga, Closterium peracerosum-strigosum-littorale complex, is also focused on here. The sexual reproductive processes of heterothallic strains are controlled by two multifunctional sex pheromones, PR-IP and PR-IP Inducer, which independently promote multiple steps in conjugation at the appropriate times through different induction mechanisms. The molecules involved in sexual reproduction and sex determination have also been characterized.}, } @article {pmid28188197, year = {2017}, author = {Drumm, BT and Baker, SA}, title = {Teaching a changing paradigm in physiology: a historical perspective on gut interstitial cells.}, journal = {Advances in physiology education}, volume = {41}, number = {1}, pages = {100-109}, doi = {10.1152/advan.00154.2016}, pmid = {28188197}, issn = {1522-1229}, mesh = {Animals ; Gastrointestinal Motility/*physiology ; Gastrointestinal Tract/*cytology/*physiology ; Humans ; Muscle, Smooth/cytology/physiology ; Physiology/*education ; Teaching/*trends ; }, abstract = {The study and teaching of gastrointestinal (GI) physiology necessitates an understanding of the cellular basis of contractile and electrical coupling behaviors in the muscle layers that comprise the gut wall. Our knowledge of the cellular origin of GI motility has drastically changed over the last 100 yr. While the pacing and coordination of GI contraction was once thought to be solely attributable to smooth muscle cells, it is now widely accepted that the motility patterns observed in the GI tract exist as a result of a multicellular system, consisting of not only smooth muscle cells but also enteric neurons and distinct populations of specialized interstitial cells that all work in concert to ensure proper GI functions. In this historical perspective, we focus on the emerging role of interstitial cells in GI motility and examine the key discoveries and experiments that led to a major shift in a paradigm of GI physiology regarding the role of interstitial cells in modulating GI contractile patterns. A review of these now classic experiments and papers will enable students and educators to fully appreciate the complex, multicellular nature of GI muscles as well as impart lessons on how shifting paradigms in physiology are fueled by new technologies that lead to new emerging discoveries.}, } @article {pmid28179656, year = {2017}, author = {Hotamisligil, GS}, title = {Inflammation, metaflammation and immunometabolic disorders.}, journal = {Nature}, volume = {542}, number = {7640}, pages = {177-185}, pmid = {28179656}, issn = {1476-4687}, support = {R01 DK052539/DK/NIDDK NIH HHS/United States ; R01 HL125753/HL/NHLBI NIH HHS/United States ; R01 AI116901/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptive Immunity/genetics ; Animals ; Clinical Trials as Topic ; Cytokines/metabolism ; Evolution, Molecular ; Genome-Wide Association Study ; Hormones/metabolism ; Humans ; Inflammation/complications/genetics/*immunology/*metabolism ; Invertebrates/immunology/metabolism ; Metabolic Diseases/complications/genetics/*immunology/*metabolism ; Obesity/complications/genetics/immunology/metabolism ; Organelles/metabolism ; Signal Transduction ; }, abstract = {Proper regulation and management of energy, substrate diversity and quantity, as well as macromolecular synthesis and breakdown processes, are fundamental to cellular and organismal survival and are paramount to health. Cellular and multicellular organization are defended by the immune response, a robust and critical system through which self is distinguished from non-self, pathogenic signals are recognized and eliminated, and tissue homeostasis is safeguarded. Many layers of evolutionarily conserved interactions occur between immune response and metabolism. Proper maintenance of this delicate balance is crucial for health and has important implications for many pathological states such as obesity, diabetes, and other chronic non-communicable diseases.}, } @article {pmid28176784, year = {2017}, author = {Nguyen, TA and Cissé, OH and Yun Wong, J and Zheng, P and Hewitt, D and Nowrousian, M and Stajich, JE and Jedd, G}, title = {Innovation and constraint leading to complex multicellularity in the Ascomycota.}, journal = {Nature communications}, volume = {8}, number = {}, pages = {14444}, pmid = {28176784}, issn = {2041-1723}, support = {P01 GM068087/GM/NIGMS NIH HHS/United States ; }, mesh = {Ascomycota/*cytology/genetics ; Biodiversity ; Biological Transport/physiology ; Computational Biology ; DNA, Fungal/*genetics ; Evolution, Molecular ; Fungal Proteins/*physiology ; Genome, Fungal/*physiology ; Phylogeny ; Sequence Alignment ; Whole Genome Sequencing ; }, abstract = {The advent of complex multicellularity (CM) was a pivotal event in the evolution of animals, plants and fungi. In the fungal Ascomycota, CM is based on hyphal filaments and arose in the Pezizomycotina. The genus Neolecta defines an enigma: phylogenetically placed in a related group containing mostly yeasts, Neolecta nevertheless possesses Pezizomycotina-like CM. Here we sequence the Neolecta irregularis genome and identify CM-associated functions by searching for genes conserved in Neolecta and the Pezizomycotina, which are absent or divergent in budding or fission yeasts. This group of 1,050 genes is enriched for functions related to diverse endomembrane systems and their organization. Remarkably, most show evidence for divergence in both yeasts. Using functional genomics, we identify new genes involved in fungal complexification. Together, these data show that rudimentary multicellularity is deeply rooted in the Ascomycota. Extensive parallel gene divergence during simplification and constraint leading to CM suggest a deterministic process where shared modes of cellular organization select for similarly configured organelle- and transport-related machineries.}, } @article {pmid28174248, year = {2017}, author = {Jones, VA and Dolan, L}, title = {MpWIP regulates air pore complex development in the liverwort Marchantia polymorpha.}, journal = {Development (Cambridge, England)}, volume = {144}, number = {8}, pages = {1472-1476}, pmid = {28174248}, issn = {1477-9129}, mesh = {Marchantia/anatomy & histology/*embryology/*metabolism/ultrastructure ; Mutation/genetics ; Plant Epidermis/cytology/*embryology/ultrastructure ; Plant Proteins/genetics/*metabolism ; Promoter Regions, Genetic/genetics ; Repressor Proteins/metabolism ; Transcription, Genetic ; }, abstract = {The colonisation of the land by plants was accompanied by the evolution of complex tissues and multicellular structures comprising different cell types as morphological adaptations to the terrestrial environment. Here, we show that the single WIP protein in the early-diverging land plant Marchantia polymorpha L. is required for the development of the multicellular gas exchange structure: the air pore complex. This 16-cell barrel-shaped structure surrounds an opening between epidermal cells that facilitates the exchange of gases between the chamber containing the photosynthetic cells inside the plant and the air outside. MpWIP is expressed in cells of the developing air pore complex and the morphogenesis of the complex is defective in plants with reduced MpWIP function. The role of WIP proteins in the control of different multicellular structures in M. polymorpha and the flowering plant Arabidopsis thaliana suggests that these proteins controlled the development of multicellular structures in the common ancestor of land plants. We hypothesise that WIP genes were subsequently co-opted in the control of morphogenesis of novel multicellular structures that evolved during the diversification of land plants.}, } @article {pmid28173090, year = {2017}, author = {Gallagher, MD and Macqueen, DJ}, title = {Evolution and Expression of Tissue Globins in Ray-Finned Fishes.}, journal = {Genome biology and evolution}, volume = {9}, number = {1}, pages = {32-47}, pmid = {28173090}, issn = {1759-6653}, support = {BB/J01446X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Biological Evolution ; *Evolution, Molecular ; Fish Proteins/*genetics ; Fishes/*classification/*genetics ; Globins/*genetics ; Phylogeny ; }, abstract = {The globin gene family encodes oxygen-binding hemeproteins conserved across the major branches of multicellular life. The origins and evolutionary histories of complete globin repertoires have been established for many vertebrates, but there remain major knowledge gaps for ray-finned fish. Therefore, we used phylogenetic, comparative genomic and gene expression analyses to discover and characterize canonical “non-blood” globin family members (i.e., myoglobin, cytoglobin, neuroglobin, globin-X, and globin-Y) across multiple ray-finned fish lineages, revealing novel gene duplicates (paralogs) conserved from whole genome duplication (WGD) and small-scale duplication events. Our key findings were that: (1) globin-X paralogs in teleosts have been retained from the teleost-specific WGD, (2) functional paralogs of cytoglobin, neuroglobin, and globin-X, but not myoglobin, have been conserved from the salmonid-specific WGD, (3) triplicate lineage-specific myoglobin paralogs are conserved in arowanas (Osteoglossiformes), which arose by tandem duplication and diverged under positive selection, (4) globin-Y is retained in multiple early branching fish lineages that diverged before teleosts, and (5) marked variation in tissue-specific expression of globin gene repertoires exists across ray-finned fish evolution, including several previously uncharacterized sites of expression. In this respect, our data provide an interesting link between myoglobin expression and the evolution of air breathing in teleosts. Together, our findings demonstrate great-unrecognized diversity in the repertoire and expression of nonblood globins that has arisen during ray-finned fish evolution.}, } @article {pmid28168289, year = {2017}, author = {Paulet, D and David, A and Rivals, E}, title = {Ribo-seq enlightens codon usage bias.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {24}, number = {3}, pages = {303-210}, pmid = {28168289}, issn = {1756-1663}, mesh = {Animals ; Codon/analysis/*genetics ; Eukaryota/genetics ; Evolution, Molecular ; Genomics/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; *Protein Biosynthesis ; RNA, Messenger ; Ribosomes ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {Codon usage is biased between lowly and highly expressed genes in a genome-specific manner. This universal bias has been well assessed in some unicellular species, but remains problematic to assess in more complex species. We propose a new method to compute codon usage bias based on genome wide translational data. A new technique based on sequencing of ribosome protected mRNA fragments (Ribo-seq) allowed us to rank genes and compute codon usage bias with high precision for a great variety of species, including mammals. Genes ranking using Ribo-Seq data confirms the influence of the tRNA pool on codon usage bias and shows a decreasing bias in multicellular species. Ribo-Seq analysis also makes possible to detect preferred codons without information on genes function.}, } @article {pmid28161621, year = {2017}, author = {Tollis, M and Schiffman, JD and Boddy, AM}, title = {Evolution of cancer suppression as revealed by mammalian comparative genomics.}, journal = {Current opinion in genetics & development}, volume = {42}, number = {}, pages = {40-47}, doi = {10.1016/j.gde.2016.12.004}, pmid = {28161621}, issn = {1879-0380}, mesh = {Animals ; Carcinogenesis/*genetics ; Conserved Sequence/genetics ; DNA Damage/genetics ; DNA Repair/genetics ; *Evolution, Molecular ; *Genomics ; Humans ; Mammals ; Neoplasms/*genetics/pathology ; }, abstract = {Cancer suppression is an important feature in the evolution of large and long-lived animals. While some tumor suppression pathways are conserved among all multicellular organisms, others mechanisms of cancer resistance are uniquely lineage specific. Comparative genomics has become a powerful tool to discover these unique and shared molecular adaptations in respect to cancer suppression. These findings may one day be translated to human patients through evolutionary medicine. Here, we will review theory and methods of comparative cancer genomics and highlight major findings of cancer suppression across mammals. Our current knowledge of cancer genomics suggests that more efficient DNA repair and higher sensitivity to DNA damage may be the key to tumor suppression in large or long-lived mammals.}, } @article {pmid28158973, year = {2017}, author = {Mohanta, TK and Kumar, P and Bae, H}, title = {Genomics and evolutionary aspect of calcium signaling event in calmodulin and calmodulin-like proteins in plants.}, journal = {BMC plant biology}, volume = {17}, number = {1}, pages = {38}, pmid = {28158973}, issn = {1471-2229}, mesh = {Amino Acid Sequence ; *Biological Evolution ; Calcium/metabolism ; *Calcium Signaling ; Calmodulin/chemistry/*genetics/metabolism ; Genomics ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Plants/chemistry/classification/*genetics/metabolism ; Sequence Alignment ; }, abstract = {BACKGROUND: Ca[2+] ion is a versatile second messenger that operate in a wide ranges of cellular processes that impact nearly every aspect of life. Ca[2+] regulates gene expression and biotic and abiotic stress responses in organisms ranging from unicellular algae to multi-cellular higher plants through the cascades of calcium signaling processes.

RESULTS: In this study, we deciphered the genomics and evolutionary aspects of calcium signaling event of calmodulin (CaM) and calmodulin like- (CML) proteins. We studied the CaM and CML gene family of 41 different species across the plant lineages. Genomic analysis showed that plant encodes more calmodulin like-protein than calmodulins. Further analyses showed, the majority of CMLs were intronless, while CaMs were intron rich. Multiple sequence alignment showed, the EF-hand domain of CaM contains four conserved D-x-D motifs, one in each EF-hand while CMLs contain only one D-x-D-x-D motif in the fourth EF-hand. Phylogenetic analysis revealed that, the CMLs were evolved earlier than CaM and later diversified. Gene expression analysis demonstrated that different CaM and CMLs genes were express differentially in different tissues in a spatio-temporal manner.

CONCLUSION: In this study we provided in detailed genome-wide identifications and characterization of CaM and CML protein family, phylogenetic relationships, and domain structure. Expression study of CaM and CML genes were conducted in Glycine max and Phaseolus vulgaris. Our study provides a strong foundation for future functional research in CaM and CML gene family in plant kingdom.}, } @article {pmid28148211, year = {2017}, author = {Buonanno, F and Anesi, A and Giuseppe, GD and Guella, G and Ortenzi, C}, title = {Chemical Defense by Erythrolactones in the Euryhaline Ciliated Protist, Pseudokeronopsis erythrina.}, journal = {Zoological science}, volume = {34}, number = {1}, pages = {42-51}, doi = {10.2108/zs160123}, pmid = {28148211}, issn = {0289-0003}, mesh = {Animals ; Ciliophora/genetics/*metabolism ; Invertebrates ; Lactones/*chemistry/metabolism/*toxicity ; Molecular Structure ; Phylogeny ; Predatory Behavior ; }, abstract = {Pseudokeronopsis erythrina produces three new secondary metabolites, erythrolactones A2, B2 and C2, and their respective sulfate esters (A1, B1, C1), the structures of which have been recently elucidated on the basis of NMR spectroscopic data coupled to high resolution mass measurements (HR-MALDI-TOF). An analysis of the discharge of the protozoan pigment granules revealed that the non-sulfonated erythrolactones are exclusively stored in these cortical organelles, which are commonly used by a number of ciliates as chemical weapons in offense/defense interactions with prey and predators. We evaluated the toxic activity of pigment granule discharge on a panel of free-living ciliates and micro-invertebrates, and the activity of each single purified erythrolactone on three ciliate species. We also observed predator-prey interactions of P. erythrina with unicellular and multicellular predators. Experimental results confirm that only P. erythrina cells with discharged pigment granules were preferentially or exclusively hunted and eaten by at least some of its predators, whereas almost all intact (fully pigmented) cells remained alive. Our results indicate that erythrolactones are very effective as a chemical defense in P. erythrina.}, } @article {pmid28131316, year = {2017}, author = {Tompitak, M and Vaillant, C and Schiessel, H}, title = {Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions.}, journal = {Biophysical journal}, volume = {112}, number = {3}, pages = {505-511}, pmid = {28131316}, issn = {1542-0086}, mesh = {Animals ; Base Sequence ; DNA/genetics/metabolism ; *Evolution, Molecular ; Genome, Human/*genetics ; Humans ; Nucleosomes/genetics/*metabolism ; *Promoter Regions, Genetic ; Saccharomyces cerevisiae/genetics ; }, abstract = {Sequences that influence nucleosome positioning in promoter regions, and their relation to gene regulation, have been the topic of much research over the last decade. In yeast, significant nucleosome-depleted regions are found, which facilitate transcription. With the arrival of nucleosome positioning maps for the human genome, it was discovered that in our genome, unlike in that of yeast, promoters encode for high nucleosome occupancy. In this work, we look at the genomes of a range of different organisms, to provide a catalog of nucleosome positioning signals in promoters across the tree of life. We utilize a computational model of the nucleosome, based on crystallographic analyses of the structure and elasticity of the nucleosome, to predict the nucleosome positioning signals in promoter regions. To be able to apply our model to large genomic datasets, we introduce an approximative scheme that makes use of the limited range of correlations in nucleosomal sequence preferences to create a computationally efficient approximation of the full biophysical model. Our predictions show that a clear distinction between unicellular and multicellular life is visible in the intrinsically encoded nucleosome affinity. Furthermore, the strength of the nucleosome positioning signals correlates with the complexity of the organism. We conclude that encoding for high nucleosome occupancy, as in the human genome, is in fact a universal feature of multicellular life.}, } @article {pmid28116828, year = {2017}, author = {Arenas-Mena, C}, title = {The origins of developmental gene regulation.}, journal = {Evolution & development}, volume = {19}, number = {2}, pages = {96-107}, doi = {10.1111/ede.12217}, pmid = {28116828}, issn = {1525-142X}, mesh = {Animals ; *Biological Evolution ; Enhancer Elements, Genetic ; Eukaryota/cytology/genetics ; *Gene Expression Regulation, Developmental ; Prokaryotic Cells/metabolism ; Promoter Regions, Genetic ; }, abstract = {The leap from simple unicellularity to complex multicellularity remains one of life's major enigmas. The origins of metazoan developmental gene regulatory mechanisms are sought by analyzing gene regulation in extant eumetazoans, sponges, and unicellular organisms. The main hypothesis of this manuscript is that, developmental enhancers evolved from unicellular inducible promoters that diversified the expression of regulatory genes during metazoan evolution. Promoters and enhancers are functionally similar; both can regulate the transcription of distal promoters and both direct local transcription. Additionally, enhancers have experimentally characterized structural features that reveal their origin from inducible promoters. The distal co-operative regulation among promoters identified in unicellular opisthokonts possibly represents the precursor of distal regulation of promoters by enhancers. During metazoan evolution, constitutive-type promoters of regulatory genes would have acquired novel receptivity to distal regulatory inputs from promoters of inducible genes that eventually specialized as enhancers. The novel regulatory interactions would have caused constitutively expressed genes controlling differential gene expression in unicellular organisms to become themselves differentially expressed. The consequence of the novel regulatory interactions was that regulatory pathways of unicellular organisms became interlaced and ultimately evolved into the intricate developmental gene regulatory networks (GRNs) of extant metazoans.}, } @article {pmid28115992, year = {2017}, author = {Navratilova, P and Danks, GB and Long, A and Butcher, S and Manak, JR and Thompson, EM}, title = {Sex-specific chromatin landscapes in an ultra-compact chordate genome.}, journal = {Epigenetics & chromatin}, volume = {10}, number = {}, pages = {3}, pmid = {28115992}, issn = {1756-8935}, mesh = {Animals ; Chromatin/genetics/*metabolism ; Chromatin Immunoprecipitation ; DNA Methylation ; DNA Transposable Elements/genetics ; Female ; *Genome ; Histones/chemistry/genetics/metabolism ; Male ; Ovary/metabolism ; Promoter Regions, Genetic ; Protein Processing, Post-Translational ; RNA Polymerase II/genetics/metabolism ; Testis/metabolism ; Urochordata/*genetics ; }, abstract = {BACKGROUND: In multicellular organisms, epigenome dynamics are associated with transitions in the cell cycle, development, germline specification, gametogenesis and inheritance. Evolutionarily, regulatory space has increased in complex metazoans to accommodate these functions. In tunicates, the sister lineage to vertebrates, we examine epigenome adaptations to strong secondary genome compaction, sex chromosome evolution and cell cycle modes.

RESULTS: Across the 70 MB Oikopleura dioica genome, we profiled 19 histone modifications, and RNA polymerase II, CTCF and p300 occupancies, to define chromatin states within two homogeneous tissues with distinct cell cycle modes: ovarian endocycling nurse nuclei and mitotically proliferating germ nuclei in testes. Nurse nuclei had active chromatin states similar to other metazoan epigenomes, with large domains of operon-associated transcription, a general lack of heterochromatin, and a possible role of Polycomb PRC2 in dosage compensation. Testis chromatin states reflected transcriptional activity linked to spermatogenesis and epigenetic marks that have been associated with establishment of transgenerational inheritance in other organisms. We also uncovered an unusual chromatin state specific to the Y-chromosome, which combined active and heterochromatic histone modifications on specific transposable elements classes, perhaps involved in regulating their activity.

CONCLUSIONS: Compacted regulatory space in this tunicate genome is accompanied by reduced heterochromatin and chromatin state domain widths. Enhancers, promoters and protein-coding genes have conserved epigenomic features, with adaptations to the organization of a proportion of genes in operon units. We further identified features specific to sex chromosomes, cell cycle modes, germline identity and dosage compensation, and unusual combinations of histone PTMs with opposing consensus functions.}, } @article {pmid28112403, year = {2018}, author = {Torday, JS and Miller, WB}, title = {A systems approach to physiologic evolution: From micelles to consciousness.}, journal = {Journal of cellular physiology}, volume = {233}, number = {1}, pages = {162-167}, doi = {10.1002/jcp.25820}, pmid = {28112403}, issn = {1097-4652}, mesh = {Adaptation, Physiological ; Animals ; *Biological Evolution ; Body Temperature Regulation ; Homeostasis ; Humans ; Lung/physiology ; Physiology/*methods ; Pulmonary Ventilation ; *Systems Biology ; *Systems Integration ; Time Factors ; }, abstract = {A systems approach to evolutionary biology offers the promise of an improved understanding of the fundamental principles of life through the effective integration of many biologic disciplines. It is presented that any critical integrative approach to evolutionary development involves a paradigmatic shift in perspective, more than just the engagement of a large number of disciplines. Critical to this differing viewpoint is the recognition that all biological processes originate from the unicellular state and remain permanently anchored to that phase throughout evolutionary development despite their macroscopic appearances. Multicellular eukaryotic development can, therefore, be viewed as a series of connected responses to epiphenomena that proceeds from that base in continuous iterative maintenance of collective cellular homeostatic equipoise juxtaposed against an ever-changing and challenging environment. By following this trajectory of multicellular eukaryotic evolution from within unicellular First Principles of Physiology forward, the mechanistic nature of complex physiology can be identified through a step-wise analysis of a continuous arc of vertebrate evolution based upon serial exaptations.}, } @article {pmid28106309, year = {2017}, author = {Wang, D and Qu, Z and Yang, L and Zhang, Q and Liu, ZH and Do, T and Adelson, DL and Wang, ZY and Searle, I and Zhu, JK}, title = {Transposable elements (TEs) contribute to stress-related long intergenic noncoding RNAs in plants.}, journal = {The Plant journal : for cell and molecular biology}, volume = {90}, number = {1}, pages = {133-146}, pmid = {28106309}, issn = {1365-313X}, support = {R01 GM059138/GM/NIGMS NIH HHS/United States ; R01 GM070795/GM/NIGMS NIH HHS/United States ; }, mesh = {Abscisic Acid/pharmacology ; Arabidopsis/drug effects/genetics ; Cold Temperature ; DNA Transposable Elements/*genetics ; Gene Expression Profiling ; Gene Expression Regulation, Plant/drug effects/genetics ; Oryza/drug effects/genetics ; RNA, Long Noncoding/*genetics ; RNA, Plant/*genetics ; Sodium Chloride/pharmacology ; Zea mays/drug effects/genetics ; }, abstract = {Noncoding RNAs have been extensively described in plant and animal transcriptomes by using high-throughput sequencing technology. Of these noncoding RNAs, a growing number of long intergenic noncoding RNAs (lincRNAs) have been described in multicellular organisms, however the origins and functions of many lincRNAs remain to be explored. In many eukaryotic genomes, transposable elements (TEs) are widely distributed and often account for large fractions of plant and animal genomes yet the contribution of TEs to lincRNAs is largely unknown. By using strand-specific RNA-sequencing, we profiled the expression patterns of lincRNAs in Arabidopsis, rice and maize, and identified 47 611 and 398 TE-associated lincRNAs (TE-lincRNAs), respectively. TE-lincRNAs were more often derived from retrotransposons than DNA transposons and as retrotransposon copy number in both rice and maize genomes so did TE-lincRNAs. We validated the expression of these TE-lincRNAs by strand-specific RT-PCR and also demonstrated tissue-specific transcription and stress-induced TE-lincRNAs either after salt, abscisic acid (ABA) or cold treatments. For Arabidopsis TE-lincRNA11195, mutants had reduced sensitivity to ABA as demonstrated by longer roots and higher shoot biomass when compared to wild-type. Finally, by altering the chromatin state in the Arabidopsis chromatin remodelling mutant ddm1, unique lincRNAs including TE-lincRNAs were generated from the preceding untranscribed regions and interestingly inherited in a wild-type background in subsequent generations. Our findings not only demonstrate that TE-associated lincRNAs play important roles in plant abiotic stress responses but lincRNAs and TE-lincRNAs might act as an adaptive reservoir in eukaryotes.}, } @article {pmid28096354, year = {2017}, author = {Xing, S and Mehlhorn, DG and Wallmeroth, N and Asseck, LY and Kar, R and Voss, A and Denninger, P and Schmidt, VA and Schwarzländer, M and Stierhof, YD and Grossmann, G and Grefen, C}, title = {Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {8}, pages = {E1544-E1553}, pmid = {28096354}, issn = {1091-6490}, mesh = {Adenosine Triphosphatases/metabolism ; Animals ; Arabidopsis/*physiology ; Arabidopsis Proteins/*metabolism ; Cell Membrane/*metabolism ; Cytosol/metabolism ; Endoplasmic Reticulum/metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Homeostasis/physiology ; Mammals/physiology ; Membrane Fusion/physiology ; Molecular Chaperones/metabolism ; Phylogeny ; Plant Roots/*growth & development/metabolism ; Plants, Genetically Modified ; SNARE Proteins/genetics/*metabolism ; Saccharomyces cerevisiae/physiology ; Saccharomyces cerevisiae Proteins/metabolism ; Signal Transduction/*physiology ; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins ; }, abstract = {Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the Guided Entry of Tail-anchored proteins (GET) pathway was described in mammalian and yeast cells that serve as a blueprint of TA protein insertion [Schuldiner M, et al. (2008) Cell 134(4):634-645; Stefanovic S, Hegde RS (2007) Cell 128(6):1147-1159]. This pathway consists of six proteins, with the cytosolic ATPase GET3 chaperoning the newly synthesized TA protein posttranslationally from the ribosome to the endoplasmic reticulum (ER) membrane. Structural and biochemical insights confirmed the potential of pathway components to facilitate membrane insertion, but the physiological significance in multicellular organisms remains to be resolved. Our phylogenetic analysis of 37 GET3 orthologs from 18 different species revealed the presence of two different GET3 clades. We identified and analyzed GET pathway components in Arabidopsis thaliana and found reduced root hair elongation in Atget lines, possibly as a result of reduced SNARE biogenesis. Overexpression of AtGET3a in a receptor knockout (KO) results in severe growth defects, suggesting presence of alternative insertion pathways while highlighting an intricate involvement for the GET pathway in cellular homeostasis of plants.}, } @article {pmid28094816, year = {2017}, author = {Cramer, JM and Pohlmann, D and Gomez, F and Mark, L and Kornegay, B and Hall, C and Siraliev-Perez, E and Walavalkar, NM and Sperlazza, MJ and Bilinovich, S and Prokop, JW and Hill, AL and Williams, DC}, title = {Methylation specific targeting of a chromatin remodeling complex from sponges to humans.}, journal = {Scientific reports}, volume = {7}, number = {}, pages = {40674}, pmid = {28094816}, issn = {2045-2322}, support = {K01 ES025435/ES/NIEHS NIH HHS/United States ; R01 GM098264/GM/NIGMS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Amino Acid Sequence ; Animals ; *Chromatin Assembly and Disassembly ; DNA/chemistry/metabolism ; *DNA Methylation ; DNA-Binding Proteins/chemistry/genetics/metabolism ; Gene Knockdown Techniques ; Humans ; Models, Molecular ; Nucleic Acid Conformation ; Phenotype ; Porifera/*genetics/metabolism ; Protein Conformation ; }, abstract = {DNA cytosine methylation and methyl-cytosine binding domain (MBD) containing proteins are found throughout all vertebrate species studied to date. However, both the presence of DNA methylation and pattern of methylation varies among invertebrate species. Invertebrates generally have only a single MBD protein, MBD2/3, that does not always contain appropriate residues for selectively binding methylated DNA. Therefore, we sought to determine whether sponges, one of the most ancient extant metazoan lineages, possess an MBD2/3 capable of recognizing methylated DNA and recruiting the associated nucleosome remodeling and deacetylase (NuRD) complex. We find that Ephydatia muelleri has genes for each of the NuRD core components including an EmMBD2/3 that selectively binds methylated DNA. NMR analyses reveal a remarkably conserved binding mode, showing almost identical chemical shift changes between binding to methylated and unmethylated CpG dinucleotides. In addition, we find that EmMBD2/3 and EmGATAD2A/B proteins form a coiled-coil interaction known to be critical for the formation of NuRD. Finally, we show that knockdown of EmMBD2/3 expression disrupts normal cellular architecture and development of E. muelleri. These data support a model in which the MBD2/3 methylation-dependent functional role emerged with the earliest multicellular organisms and has been maintained to varying degrees across animal evolution.}, } @article {pmid28088333, year = {2017}, author = {Baffy, G}, title = {Mitochondrial uncoupling in cancer cells: Liabilities and opportunities.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1858}, number = {8}, pages = {655-664}, doi = {10.1016/j.bbabio.2017.01.005}, pmid = {28088333}, issn = {0005-2728}, mesh = {Animals ; Antineoplastic Agents/pharmacokinetics ; Cell Hypoxia ; Cell Line, Tumor ; Cellular Reprogramming ; Drug Resistance, Neoplasm/physiology ; Drug Synergism ; Energy Metabolism ; Humans ; Mitochondria/drug effects/*metabolism ; Mitochondrial Uncoupling Proteins/*physiology ; Models, Biological ; Neoplasm Proteins/physiology ; Neoplasms/drug therapy/*metabolism ; Oxidative Phosphorylation/drug effects ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Symbiosis ; Uncoupling Agents/pharmacology/therapeutic use ; }, abstract = {Acquisition of the endosymbiotic ancestor of mitochondria was a critical event in eukaryote evolution. Mitochondria offered an unparalleled source of metabolic energy through oxidative phosphorylation and allowed the development of multicellular life. However, as molecular oxygen had become the terminal electron acceptor in most eukaryotic cells, the electron transport chain proved to be the largest intracellular source of superoxide, contributing to macromolecular injury, aging, and cancer. Hence, the 'contract of endosymbiosis' represents a compromise between the possibilities and perils of multicellular life. Uncoupling proteins (UCPs), a group of the solute carrier family of transporters, may remove some of the physiologic constraints that link mitochondrial respiration and ATP synthesis by mediating inducible proton leak and limiting oxidative cell injury. This important property makes UCPs an ancient partner in the metabolic adaptation of cancer cells. Efforts are underway to explore the therapeutic opportunities stemming from the intriguing relationship of UCPs and cancer. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.}, } @article {pmid28078674, year = {2017}, author = {Bustamante, DE and Won, BY and Miller, KA and Cho, TO}, title = {Wilsonosiphonia gen. nov. (Rhodomelaceae, Rhodophyta) based on molecular and morpho-anatomical characters.}, journal = {Journal of phycology}, volume = {53}, number = {2}, pages = {368-380}, doi = {10.1111/jpy.12512}, pmid = {28078674}, issn = {1529-8817}, mesh = {DNA, Ribosomal ; Phylogeny ; Rhodophyta/classification/*genetics ; Sequence Analysis, DNA ; }, abstract = {Morphological, anatomical, and molecular sequence data were used to assess the establishment and phylogenetic position of the genus Wilsonosiphonia gen. nov. Phylogenies based on rbcL and concatenated rbcL and cox1 loci support recognition of Wilsonosiphonia gen. nov., sister to Herposiphonia. Diagnostic features for Wilsonosiphonia are rhizoids located at distal ends of pericentral cells and taproot-shaped multicellular tips of rhizoids. Wilsonosiphonia includes three species with diagnostic rbcL and cox1 sequences, Wilsonosiphonia fujiae sp. nov. (the generitype), W. howei comb. nov., and W. indica sp. nov. These three species resemble each other in external morphology, but W. fujiae is distinguished by having two tetrasporangia per segment rather than one, W. indica by having abundant and persistent trichoblasts, and W. howei by having few and deciduous trichoblasts.}, } @article {pmid28063828, year = {2017}, author = {Terauchi, M and Yamagishi, T and Hanyuda, T and Kawai, H}, title = {Genome-wide computational analysis of the secretome of brown algae (Phaeophyceae).}, journal = {Marine genomics}, volume = {32}, number = {}, pages = {49-59}, doi = {10.1016/j.margen.2016.12.002}, pmid = {28063828}, issn = {1876-7478}, mesh = {Amino Acid Sequence ; *Genome ; Genome-Wide Association Study ; Phaeophyceae/*genetics ; Sequence Alignment ; }, abstract = {Brown algae have evolved complex multicellularity in the heterokont lineage. They are phylogenetically distant to land plants, fungi and animals. Especially, the members of Laminariales (so-called kelps) have developed highly differentiated tissues. Extracellular matrix (ECM) plays pivotal roles in a number of essential processes in multicellular organisms, such as cell adhesion, cell and tissue differentiations, cell-to-cell communication, and responses to environmental stimuli. In these processes, a set of extracellular secreted proteins called the secretome operates remodeling of the physicochemical nature of ECM and signal transduction by interacting with cell surface proteins and signaling molecules. Characterization of the secretome is a critical step to clarify the contributions of ECM to the multicellularity of brown algae. However, the identity of the brown algal secretome has been poorly understood. In order to reveal the repertory of the brown algal secretome and its involvement in the evolution of Laminariales, we conducted a genome-wide analysis of the brown algal secretome utilizing the published complete genome data of Ectocarpus siliculosus and Saccharina japonica as well as newly obtained RNA-seq data of seven laminarialean species (Agarum clathratum, Alaria crassifolia, Aureophycus aleuticus, Costaria costata, Pseudochorda nagaii, Saccharina angustata and Undaria pinnatifida) largely covering the laminarialean families. We established the in silico pipeline to systematically and accurately detect the secretome by combining multiple prediction algorithms for the N-terminal signal peptide and transmembrane domain within the protein sequence. From 16,189 proteins of E. siliculosus and 18,733 proteins of S. japonica, 552 and 964 proteins respectively were predicted to be classified as the secretome. Conserved domain analysis showed that the domain repertory were very similar to each other, and that of the brown algal secretome was partially common with that of the secretome of other multicellular organisms (land plants, fungi and animals). In the laminarialean species, it was estimated that the gene abundance and the domain architecture of putative ECM remodeling-related proteins were altered compared with those of E. siliculosus, and that the alteration started from the basal group of Laminariales. These results suggested that brown algae have developed their own secretome, and its functions became more elaborated in the more derived members in Laminariales.}, } @article {pmid28058671, year = {2017}, author = {Sommese, L and Zullo, A and Schiano, C and Mancini, FP and Napoli, C}, title = {Possible Muscle Repair in the Human Cardiovascular System.}, journal = {Stem cell reviews and reports}, volume = {13}, number = {2}, pages = {170-191}, pmid = {28058671}, issn = {2629-3277}, mesh = {Animals ; Cardiovascular Diseases/genetics/physiopathology/therapy ; Cardiovascular System/injuries/*metabolism/*physiopathology ; Cell Differentiation/genetics ; Cell Proliferation/genetics ; *Cellular Reprogramming ; Humans ; Myocardium/*metabolism/pathology ; Regeneration/genetics ; Regenerative Medicine/methods ; }, abstract = {The regenerative potential of tissues and organs could promote survival, extended lifespan and healthy life in multicellular organisms. Niches of adult stemness are widely distributed and lead to the anatomical and functional regeneration of the damaged organ. Conversely, muscular regeneration in mammals, and humans in particular, is very limited and not a single piece of muscle can fully regrow after a severe injury. Therefore, muscle repair after myocardial infarction is still a chimera. Recently, it has been recognized that epigenetics could play a role in tissue regrowth since it guarantees the maintenance of cellular identity in differentiated cells and, therefore, the stability of organs and tissues. The removal of these locks can shift a specific cell identity back to the stem-like one. Given the gradual loss of tissue renewal potential in the course of evolution, in the last few years many different attempts to retrieve such potential by means of cell therapy approaches have been performed in experimental models. Here we review pathways and mechanisms involved in the in vivo repair of cardiovascular muscle tissues in humans. Moreover, we address the ongoing research on mammalian cardiac muscle repair based on adult stem cell transplantation and pro-regenerative factor delivery. This latter issue, involving genetic manipulations of adult cells, paves the way for developing possible therapeutic strategies in the field of cardiovascular muscle repair.}, } @article {pmid28057261, year = {2017}, author = {Sebé-Pedrós, A and Ruiz-Trillo, I}, title = {Evolution and Classification of the T-Box Transcription Factor Family.}, journal = {Current topics in developmental biology}, volume = {122}, number = {}, pages = {1-26}, doi = {10.1016/bs.ctdb.2016.06.004}, pmid = {28057261}, issn = {1557-8933}, mesh = {Animals ; Base Sequence ; Conserved Sequence ; *Evolution, Molecular ; Fetal Proteins/chemistry/genetics ; Humans ; Morphogenesis ; Phylogeny ; T-Box Domain Proteins/chemistry/*classification/*genetics ; Brachyury Protein ; }, abstract = {T-box proteins are key developmental transcription factors in Metazoa. Until recently they were thought to be animal specific and many T-box classes were considered bilaterian specific. Recent genome data from both early-branching animals and their closest unicellular relatives have radically changed this scenario. Thus, we now know that T-box genes originated in premetazoans, being present in the genomes of some extant early-branching fungi and unicellular holozoans. Here, we update the evolutionary classification of T-box families and review the evolution of T-box function in early-branching animals (sponges, ctenophores, placozoans, and cnidarians) and nonmodel bilaterians. We show that concomitant with the origin of Metazoa, the T-box family radiated into the major known T-box classes. On the other hand, while functional studies are still missing for many T-box classes, the emerging picture is that T-box genes have key roles in multiple aspects of development and in adult terminal cell-type differentiation in different animal lineages. A paradigmatic example is that of Brachyury, the founding member of the T-box family, for which several studies indicate a widely conserved role in regulating cell motility in different animal lineages and probably even before the advent of animal multicellularity. Overall, we here review the evolutionary history of T-box genes from holozoans to animals and discuss both their functional diversity and conservation.}, } @article {pmid28049657, year = {2017}, author = {Macaisne, N and Liu, F and Scornet, D and Peters, AF and Lipinska, A and Perrineau, MM and Henry, A and Strittmatter, M and Coelho, SM and Cock, JM}, title = {The Ectocarpus IMMEDIATE UPRIGHT gene encodes a member of a novel family of cysteine-rich proteins with an unusual distribution across the eukaryotes.}, journal = {Development (Cambridge, England)}, volume = {144}, number = {3}, pages = {409-418}, doi = {10.1242/dev.141523}, pmid = {28049657}, issn = {1477-9129}, support = {638240/ERC_/European Research Council/International ; }, mesh = {Algal Proteins/antagonists & inhibitors/chemistry/*genetics ; Amino Acid Sequence ; Cloning, Molecular ; Cysteine/chemistry ; Evolution, Molecular ; Gene Expression Profiling ; Gene Transfer, Horizontal ; Models, Genetic ; Multigene Family ; Mutation ; Phaeophyceae/*genetics/growth & development/virology ; Phylogeny ; RNA Interference ; Sequence Homology, Amino Acid ; Viral Proteins/chemistry/genetics ; }, abstract = {The sporophyte generation of the brown alga Ectocarpus sp. exhibits an unusual pattern of development compared with the majority of brown algae. The first cell division is symmetrical and the apical-basal axis is established late in development. In the immediate upright (imm) mutant, the initial cell undergoes an asymmetric division to immediately establish the apical-basal axis. We provide evidence which suggests that this phenotype corresponds to the ancestral state of the sporophyte. The IMM gene encodes a protein of unknown function that contains a repeated motif also found in the EsV-1-7 gene of the Ectocarpus virus EsV-1. Brown algae possess large families of EsV-1-7 domain genes but these genes are rare in other stramenopiles, suggesting that the expansion of this family might have been linked with the emergence of multicellular complexity. EsV-1-7 domain genes have a patchy distribution across eukaryotic supergroups and occur in several viral genomes, suggesting possible horizontal transfer during eukaryote evolution.}, } @article {pmid28048969, year = {2017}, author = {Veloso, FA}, title = {On the developmental self-regulatory dynamics and evolution of individuated multicellular organisms.}, journal = {Journal of theoretical biology}, volume = {417}, number = {}, pages = {84-99}, doi = {10.1016/j.jtbi.2016.12.025}, pmid = {28048969}, issn = {1095-8541}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation/*genetics ; Cell Line ; Computational Biology ; Drosophila melanogaster ; *Epigenesis, Genetic ; *Gene Expression Regulation ; Histones/metabolism ; Humans ; Mice ; Protein Processing, Post-Translational ; RNA, Messenger/analysis ; Transcription Initiation Site ; }, abstract = {Changes in gene expression are thought to regulate the cell differentiation process intrinsically through complex epigenetic mechanisms. In fundamental terms, however, this assumed regulation refers only to the intricate propagation of changes in gene expression or else leads to non-explanatory regresses. The developmental self-regulatory dynamics and evolution of individuated multicellular organisms also lack a unified and falsifiable description. To fill this gap, I computationally analyzed publicly available high-throughput data of histone H3 post-translational modifications and mRNA abundance for different Homo sapiens, Mus musculus, and Drosophila melanogaster cell-type/developmental-period samples. My analysis of genomic regions adjacent to transcription start sites generated a profile from pairwise partial correlations between histone modifications controlling for the respective mRNA levels for each cell-type/developmental-period dataset. I found that these profiles, while explicitly uncorrelated with the respective transcriptional "identities" by construction, associate strongly with cell differentiation states. This association is not expected if cell differentiation is, in effect, regulated by epigenetic mechanisms. Based on these results, I propose a general, falsifiable theory of individuated multicellularity, which relies on the synergistic coupling across the extracellular space of two explicitly uncorrelated "self-organizing" systems constraining histone modification states at the same sites. This theory describes how the simplest multicellular individual-understood as an intrinsic, higher-order constraint-emerges from proliferating undifferentiated cells, and could explain the intrinsic regulation of gene transcriptional changes for cell differentiation and the evolution of individuated multicellular organisms.}, } @article {pmid29687830, year = {2017}, author = {Cazzolla Gatti, R}, title = {Adaptation, Evolution And Reproduction Of Gaia By The Means Of Our Species.}, journal = {Theoretical biology forum}, volume = {110}, number = {1-2}, pages = {25-45}, doi = {10.19272/201711402003}, pmid = {29687830}, issn = {2282-2593}, mesh = {*Adaptation, Physiological ; Animals ; Atmosphere ; *Biological Evolution ; *Earth, Planet ; *Ecosystem ; *Evolution, Planetary ; Humans ; *Models, Biological ; *Reproduction ; Symbiosis ; }, abstract = {Nowadays, the idea that life affects the development of the planetary environment, and can, in turn, affect the future evolution of itself (in a coevolutionary way) is well-accepted. However, since the proposal of the Gaia hypothesis, there has been widespread criticism. Most of it is related to teleology, the absence of natural selection at a universal scale, and the lack of planetary reproduction. Some of the problems concerning the 'internal' logic of the idea have been resolved. Nevertheless, it is not sure whether Earth can be considered a unit of selection and (therefore) Gaia can adapt according to Darwinian evolution. After Lovelock and Margulis, Gaia has been considered a symbiotic planet composed of biotic (the biosphere) and abiotic (the geosphere-atmosphere) interacting with and coevolving elements. Here I propose why and suggest how a Gaian system should be considered alive in any evolutionary sense. I take into consideration the three principal criticisms and I analyse them following a logic-inductive reasoning. I use thought experiments and analogical arguments to analyse the rationale and the mechanisms by which Gaia evolves and may reproduce. This reasoning could allow rejecting the aforementioned criticisms as outdated and insufficient to discredit the main idea. I argue that without invoking teleology - so without any foresight or planning - a Gaian planet can be considered a coevolutionary system analogous to a multicellular body: a super-unit of selection. I describe different situations according to which Gaia is able to reproduce and transfer her planetary genome to other uninhabited or inhabited planets. Then I suggest that Gaia can face exclusion- competition-coexistence states depending on the fitness of her biota compared to those of the other reproducing biospheres. This demonstrates that Gaia can reproduce and evolve in competition-cooperation with other planets. Some deep implications arise from this evidence, also in light of the recent discovery of a new solar system with Earth-like planets by NASA.}, } @article {pmid28039083, year = {2017}, author = {Filippopoulou, K and Papaevgeniou, N and Lefaki, M and Paraskevopoulou, A and Biedermann, D and Křen, V and Chondrogianni, N}, title = {2,3-Dehydrosilybin A/B as a pro-longevity and anti-aggregation compound.}, journal = {Free radical biology & medicine}, volume = {103}, number = {}, pages = {256-267}, doi = {10.1016/j.freeradbiomed.2016.12.042}, pmid = {28039083}, issn = {1873-4596}, mesh = {Animals ; CHO Cells ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/metabolism ; Cell Line ; Cell Survival/drug effects ; Cricetinae ; Cricetulus ; Drug Evaluation, Preclinical ; Glucose Transport Proteins, Facilitative/metabolism ; Humans ; Longevity/*drug effects ; Oxidative Stress ; Protective Agents/*pharmacology ; Protein Aggregation, Pathological/*prevention & control ; Silybin ; Silymarin/*pharmacology ; }, abstract = {Aging is an unavoidable process characterized by gradual failure of homeostasis that constitutes a critical risk factor for several age-related disorders. It has been unveiled that manipulation of various key pathways may decelerate the aging progression and the triggering of age-related diseases. As a consequence, the identification of compounds, preferably natural-occurring, administered through diet, with lifespan-extending, anti-aggregation and anti-oxidation properties that in parallel exhibit negligible side-effects is the main goal in the battle against aging. Here we analyze the role of 2,3-dehydrosilybin A/B (DHS A/B), a minor component of silymarin used in a plethora of dietary supplements. This flavonolignan is well-known for its anti-oxidative and neuroprotective properties, among others. We demonstrate that DHS A/B confers oxidative stress resistance not only in human primary cells but also in the context of a multi-cellular aging model, namely Caenorhabditis elegans (C. elegans) where it also promotes lifespan extension. We reveal that these DHS A/B outcomes are FGT-1 and DAF-16 dependent. We additionally demonstrate the anti-aggregation properties of DHS A/B in human cells of nervous origin but also in nematode models of Alzheimer's disease (AD), eventually leading to decelerated progression of AD phenotype. Our results identify DHS A/B as the active component of silymarin extract and propose DHS A/B as a candidate anti-aging and anti-aggregation compound.}, } @article {pmid28036012, year = {2016}, author = {Pauzaite, T and Thacker, U and Tollitt, J and Copeland, NA}, title = {Emerging Roles for Ciz1 in Cell Cycle Regulation and as a Driver of Tumorigenesis.}, journal = {Biomolecules}, volume = {7}, number = {1}, pages = {}, pmid = {28036012}, issn = {2218-273X}, mesh = {Animals ; Antineoplastic Agents/therapeutic use ; Carcinogenesis/*drug effects ; Cell Cycle ; *Cell Cycle Checkpoints ; Cell Transformation, Neoplastic ; Chromatin/metabolism ; Cyclin-Dependent Kinase 2/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; *DNA Replication ; Humans ; Mice ; Nuclear Proteins/*metabolism ; }, abstract = {Precise duplication of the genome is a prerequisite for the health and longevity of multicellular organisms. The temporal regulation of origin specification, replication licensing, and firing at replication origins is mediated by the cyclin-dependent kinases. Here the role of Cip1 interacting Zinc finger protein 1 (Ciz1) in regulation of cell cycle progression is discussed. Ciz1 contributes to regulation of the G1/S transition in mammalian cells. Ciz1 contacts the pre-replication complex (pre-RC) through cell division cycle 6 (Cdc6) interactions and aids localization of cyclin A- cyclin-dependent kinase 2 (CDK2) activity to chromatin and the nuclear matrix during initiation of DNA replication. We discuss evidence that Ciz1 serves as a kinase sensor that regulates both initiation of DNA replication and prevention of re-replication. Finally, the emerging role for Ciz1 in cancer biology is discussed. Ciz1 is overexpressed in common tumors and tumor growth is dependent on Ciz1 expression, suggesting that Ciz1 is a driver of tumor growth. We present evidence that Ciz1 may contribute to deregulation of the cell cycle due to its ability to alter the CDK activity thresholds that are permissive for initiation of DNA replication. We propose that Ciz1 may contribute to oncogenesis by induction of DNA replication stress and that Ciz1 may be a multifaceted target in cancer therapy.}, } @article {pmid28013230, year = {2017}, author = {Ohtani, M and Akiyoshi, N and Takenaka, Y and Sano, R and Demura, T}, title = {Evolution of plant conducting cells: perspectives from key regulators of vascular cell differentiation.}, journal = {Journal of experimental botany}, volume = {68}, number = {1}, pages = {17-26}, doi = {10.1093/jxb/erw473}, pmid = {28013230}, issn = {1460-2431}, mesh = {Biological Evolution ; Cell Differentiation/*physiology ; Embryophyta/cytology/growth & development/physiology ; Gene Expression Regulation, Developmental/physiology ; Gene Expression Regulation, Plant/physiology ; Phloem/*cytology/growth & development/physiology ; Xylem/*cytology/growth & development/physiology ; }, abstract = {One crucial problem that plants faced during their evolution, particularly during the transition to growth on land, was how to transport water, nutrients, metabolites, and small signaling molecules within a large, multicellular body. As a solution to this problem, land plants developed specific tissues for conducting molecules, called water-conducting cells (WCCs) and food-conducting cells (FCCs). The well-developed WCCs and FCCs in extant plants are the tracheary elements and sieve elements, respectively, which are found in vascular plants. Recent molecular genetic studies revealed that transcriptional networks regulate the differentiation of tracheary and sieve elements, and that the networks governing WCC differentiation are largely conserved among land plant species. In this review, we discuss the molecular evolution of plant conducting cells. By focusing on the evolution of the key transcription factors that regulate vascular cell differentiation, the NAC transcription factor VASCULAR-RELATED NAC-DOMAIN for WCCs and the MYB-coiled-coil (CC)-type transcription factor ALTERED PHLOEM DEVELOPMENT for sieve elements, we describe how land plants evolved molecular systems to produce the specialized cells that function as WCCs and FCCs.}, } @article {pmid28007886, year = {2017}, author = {Cleard, F and Wolle, D and Taverner, AM and Aoki, T and Deshpande, G and Andolfatto, P and Karch, F and Schedl, P}, title = {Different Evolutionary Strategies To Conserve Chromatin Boundary Function in the Bithorax Complex.}, journal = {Genetics}, volume = {205}, number = {2}, pages = {589-603}, pmid = {28007886}, issn = {1943-2631}, support = {R01 GM043432/GM/NIGMS NIH HHS/United States ; R01 GM083228/GM/NIGMS NIH HHS/United States ; R56 GM043432/GM/NIGMS NIH HHS/United States ; T32 HG003284/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Chromatin/*genetics ; Conserved Sequence ; Drosophila/*genetics ; Drosophila Proteins/genetics/metabolism ; *Evolution, Molecular ; *Insulator Elements ; Transcription Factors/genetics/metabolism ; }, abstract = {Chromatin boundary elements subdivide chromosomes in multicellular organisms into physically independent domains. In addition to this architectural function, these elements also play a critical role in gene regulation. Here we investigated the evolution of a Drosophila Bithorax complex boundary element called Fab-7, which is required for the proper parasegment specific expression of the homeotic Abd-B gene. Using a "gene" replacement strategy, we show that Fab-7 boundaries from two closely related species, D. erecta and D. yakuba, and a more distant species, D. pseudoobscura, are able to substitute for the melanogaster boundary. Consistent with this functional conservation, the two known Fab-7 boundary factors, Elba and LBC, have recognition sequences in the boundaries from all species. However, the strategies used for maintaining binding and function in the face of sequence divergence is different. The first is conventional, and depends upon conservation of the 8 bp Elba recognition sequence. The second is unconventional, and takes advantage of the unusually large and flexible sequence recognition properties of the LBC boundary factor, and the deployment of multiple LBC recognition elements in each boundary. In the former case, binding is lost when the recognition sequence is altered. In the latter case, sequence divergence is accompanied by changes in the number, relative affinity, and location of the LBC recognition elements.}, } @article {pmid27998811, year = {2016}, author = {Ramírez-Sánchez, O and Pérez-Rodríguez, P and Delaye, L and Tiessen, A}, title = {Plant Proteins Are Smaller Because They Are Encoded by Fewer Exons than Animal Proteins.}, journal = {Genomics, proteomics & bioinformatics}, volume = {14}, number = {6}, pages = {357-370}, pmid = {27998811}, issn = {2210-3244}, mesh = {Animals ; Bacteria/classification/genetics/metabolism ; Bacterial Proteins/chemistry/genetics/metabolism ; Eukaryota/classification/genetics/metabolism ; Evolution, Molecular ; Exons ; Genes, Plant ; Humans ; Linear Models ; Phylogeny ; Plant Proteins/*chemistry/genetics/metabolism ; Plants/classification/genetics/*metabolism ; Proteins/*chemistry/genetics/metabolism ; Symbiosis ; }, abstract = {Protein size is an important biochemical feature since longer proteins can harbor more domains and therefore can display more biological functionalities than shorter proteins. We found remarkable differences in protein length, exon structure, and domain count among different phylogenetic lineages. While eukaryotic proteins have an average size of 472 amino acid residues (aa), average protein sizes in plant genomes are smaller than those of animals and fungi. Proteins unique to plants are ∼81aa shorter than plant proteins conserved among other eukaryotic lineages. The smaller average size of plant proteins could neither be explained by endosymbiosis nor subcellular compartmentation nor exon size, but rather due to exon number. Metazoan proteins are encoded on average by ∼10 exons of small size [∼176 nucleotides (nt)]. Streptophyta have on average only ∼5.7 exons of medium size (∼230nt). Multicellular species code for large proteins by increasing the exon number, while most unicellular organisms employ rather larger exons (>400nt). Among subcellular compartments, membrane proteins are the largest (∼520aa), whereas the smallest proteins correspond to the gene ontology group of ribosome (∼240aa). Plant genes are encoded by half the number of exons and also contain fewer domains than animal proteins on average. Interestingly, endosymbiotic proteins that migrated to the plant nucleus became larger than their cyanobacterial orthologs. We thus conclude that plants have proteins larger than bacteria but smaller than animals or fungi. Compared to the average of eukaryotic species, plants have ∼34% more but ∼20% smaller proteins. This suggests that photosynthetic organisms are unique and deserve therefore special attention with regard to the evolutionary forces acting on their genomes and proteomes.}, } @article {pmid27994131, year = {2017}, author = {Jill Harrison, C}, title = {Development and genetics in the evolution of land plant body plans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1713}, pages = {}, pmid = {27994131}, issn = {1471-2970}, support = {BB/L00224811//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Embryophyta/*genetics/*growth & development ; *Genes, Plant ; Germ Cells, Plant/growth & development ; }, abstract = {The colonization of land by plants shaped the terrestrial biosphere, the geosphere and global climates. The nature of morphological and molecular innovation driving land plant evolution has been an enigma for over 200 years. Recent phylogenetic and palaeobotanical advances jointly demonstrate that land plants evolved from freshwater algae and pinpoint key morphological innovations in plant evolution. In the haploid gametophyte phase of the plant life cycle, these include the innovation of mulitcellular forms with apical growth and multiple growth axes. In the diploid phase of the life cycle, multicellular axial sporophytes were an early innovation priming subsequent diversification of indeterminate branched forms with leaves and roots. Reverse and forward genetic approaches in newly emerging model systems are starting to identify the genetic basis of such innovations. The data place plant evo-devo research at the cusp of discovering the developmental and genetic changes driving the radiation of land plant body plans.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.}, } @article {pmid27994119, year = {2017}, author = {Cavalier-Smith, T}, title = {Origin of animal multicellularity: precursors, causes, consequences-the choanoflagellate/sponge transition, neurogenesis and the Cambrian explosion.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1713}, pages = {}, pmid = {27994119}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Choanoflagellata/growth & development/physiology ; Evolution, Molecular ; Invertebrates/growth & development/*physiology ; *Neurogenesis ; Porifera/growth & development/physiology ; }, abstract = {Evolving multicellularity is easy, especially in phototrophs and osmotrophs whose multicells feed like unicells. Evolving animals was much harder and unique; probably only one pathway via benthic 'zoophytes' with pelagic ciliated larvae allowed trophic continuity from phagocytic protozoa to gut-endowed animals. Choanoflagellate protozoa produced sponges. Converting sponge flask cells mediating larval settling to synaptically controlled nematocysts arguably made Cnidaria. I replace Haeckel's gastraea theory by a sponge/coelenterate/bilaterian pathway: Placozoa, hydrozoan diploblasty and ctenophores were secondary; stem anthozoan developmental mutations arguably independently generated coelomate bilateria and ctenophores. I emphasize animal origin's conceptual aspects (selective, developmental) related to feeding modes, cell structure, phylogeny of related protozoa, sequence evidence, ecology and palaeontology. Epithelia and connective tissue could evolve only by compensating for dramatically lower feeding efficiency that differentiation into non-choanocytes entails. Consequentially, larger bodies enabled filtering more water for bacterial food and harbouring photosynthetic bacteria, together adding more food than cell differentiation sacrificed. A hypothetical presponge of sessile triploblastic sheets (connective tissue sandwiched between two choanocyte epithelia) evolved oogamy through selection for larger dispersive ciliated larvae to accelerate benthic trophic competence and overgrowing protozoan competitors. Extinct Vendozoa might be elaborations of this organismal grade with choanocyte-bearing epithelia, before poriferan water channels and cnidarian gut/nematocysts/synapses evolved.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.}, } @article {pmid27994117, year = {2017}, author = {Bush, SJ and Chen, L and Tovar-Corona, JM and Urrutia, AO}, title = {Alternative splicing and the evolution of phenotypic novelty.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1713}, pages = {}, pmid = {27994117}, issn = {1471-2970}, mesh = {*Alternative Splicing ; Animals ; *Biological Evolution ; Evolution, Molecular ; Gene Duplication ; *Phenotype ; Transcriptome ; }, abstract = {Alternative splicing, a mechanism of post-transcriptional RNA processing whereby a single gene can encode multiple distinct transcripts, has been proposed to underlie morphological innovations in multicellular organisms. Genes with developmental functions are enriched for alternative splicing events, suggestive of a contribution of alternative splicing to developmental programmes. The role of alternative splicing as a source of transcript diversification has previously been compared to that of gene duplication, with the relationship between the two extensively explored. Alternative splicing is reduced following gene duplication with the retention of duplicate copies higher for genes which were alternatively spliced prior to duplication. Furthermore, and unlike the case for overall gene number, the proportion of alternatively spliced genes has also increased in line with the evolutionary diversification of cell types, suggesting alternative splicing may contribute to the complexity of developmental programmes. Together these observations suggest a prominent role for alternative splicing as a source of functional innovation. However, it is unknown whether the proliferation of alternative splicing events indeed reflects a functional expansion of the transcriptome or instead results from weaker selection acting on larger species, which tend to have a higher number of cell types and lower population sizes.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.}, } @article {pmid27984033, year = {2017}, author = {Malagoli, D and Ottaviani, E}, title = {Cross-talk among immune and neuroendocrine systems in molluscs and other invertebrate models.}, journal = {Hormones and behavior}, volume = {88}, number = {}, pages = {41-44}, doi = {10.1016/j.yhbeh.2016.10.015}, pmid = {27984033}, issn = {1095-6867}, mesh = {Animals ; *Biological Evolution ; Cell Transdifferentiation/physiology ; Homeostasis/physiology ; Immune System/immunology/*metabolism ; Invertebrates/immunology/*metabolism ; Mollusca/immunology/*metabolism ; Neurosecretory Systems/immunology/*metabolism ; }, abstract = {The comparison between immune and neuroendocrine systems in vertebrates and invertebrates suggest an ancient origin and a high degree of conservation for the mechanisms underlying the integration between immune and stress responses. This suggests that in both vertebrates and invertebrates the stress response involves the integrated network of soluble mediators (e.g., neurotransmitters, hormones and cytokines) and cell functions (e.g., chemotaxis and phagocytosis), that interact with a common objective, i.e., the maintenance of body homeostasis. During evolution, several changes observed in the stress response of more complex taxa could be the result of new roles of ancestral molecules, such as ancient immune mediators may have been recruited as neurotransmitters and hormones, or vice versa. We review older and recent evidence suggesting that immune and neuro-endocrine functions during the stress response were deeply intertwined already at the dawn of multicellular organisms. These observations found relevant reflections in the demonstration that immune cells can transdifferentiate in olfactory neurons in crayfish and the recently re-proposed neural transdifferentiation in humans.}, } @article {pmid27980068, year = {2017}, author = {Ihara, S and Nakayama, S and Murakami, Y and Suzuki, E and Asakawa, M and Kinoshita, T and Sawa, H}, title = {PIGN prevents protein aggregation in the endoplasmic reticulum independently of its function in the GPI synthesis.}, journal = {Journal of cell science}, volume = {130}, number = {3}, pages = {602-613}, doi = {10.1242/jcs.196717}, pmid = {27980068}, issn = {1477-9137}, mesh = {Animals ; Caenorhabditis elegans/cytology/*metabolism/ultrastructure ; Caenorhabditis elegans Proteins/*metabolism ; Conserved Sequence ; Endoplasmic Reticulum/*metabolism/ultrastructure ; Evolution, Molecular ; Glycosylphosphatidylinositols/*metabolism ; HEK293 Cells ; Humans ; Intracellular Membranes/metabolism ; Intracellular Space/metabolism ; Mutation/genetics ; Phosphotransferases/chemistry/*metabolism ; *Protein Aggregates ; Sequence Homology, Amino Acid ; }, abstract = {Quality control of proteins in the endoplasmic reticulum (ER) is essential for ensuring the integrity of secretory proteins before their release into the extracellular space. Secretory proteins that fail to pass quality control form aggregates. Here we show the PIGN-1/PIGN is required for quality control in Caenorhabditis elegans and in mammalian cells. In C. elegans pign-1 mutants, several proteins fail to be secreted and instead form abnormal aggregation. PIGN-knockout HEK293 cells also showed similar protein aggregation. Although PIGN-1/PIGN is responsible for glycosylphosphatidylinositol (GPI)-anchor biosynthesis in the ER, certain mutations in C. elegans pign-1 caused protein aggregation in the ER without affecting GPI-anchor biosynthesis. These results show that PIGN-1/PIGN has a conserved and non-canonical function to prevent deleterious protein aggregation in the ER independently of the GPI-anchor biosynthesis. PIGN is a causative gene for some human diseases including multiple congenital seizure-related syndrome (MCAHS1). Two pign-1 mutations created by CRISPR/Cas9 that correspond to MCAHS1 also cause protein aggregation in the ER, implying that the dysfunction of the PIGN non-canonical function might affect symptoms of MCAHS1 and potentially those of other diseases.}, } @article {pmid27979655, year = {2017}, author = {Lalucque, H and Malagnac, F and Green, K and Gautier, V and Grognet, P and Chan Ho Tong, L and Scott, B and Silar, P}, title = {IDC2 and IDC3, two genes involved in cell non-autonomous signaling of fruiting body development in the model fungus Podospora anserina.}, journal = {Developmental biology}, volume = {421}, number = {2}, pages = {126-138}, doi = {10.1016/j.ydbio.2016.12.016}, pmid = {27979655}, issn = {1095-564X}, mesh = {Amino Acid Sequence ; Blotting, Western ; Cellulose/pharmacology ; Conserved Sequence ; Cysteine/metabolism ; Evolution, Molecular ; Fruiting Bodies, Fungal/*genetics/*growth & development ; Fungal Proteins/chemistry/*genetics/metabolism ; Gene Deletion ; *Genes, Fungal ; Genetic Complementation Test ; Green Fluorescent Proteins/metabolism ; Mosaicism ; Mycelium/metabolism ; Phenotype ; Phosphorylation/drug effects ; Podospora/*genetics/*growth & development ; Signal Transduction/*genetics ; Subcellular Fractions/metabolism ; Vacuoles/metabolism ; }, abstract = {Filamentous ascomycetes produce complex multicellular structures during sexual reproduction. Little is known about the genetic pathways enabling the construction of such structures. Here, with a combination of classical and reverse genetic methods, as well as genetic mosaic and graft analyses, we identify and provide evidence for key roles for two genes during the formation of perithecia, the sexual fruiting bodies, of the filamentous fungus Podospora anserina. Data indicate that the proteins coded by these two genes function cell-non-autonomously and that their activity depends upon conserved cysteines, making them good candidate for being involved in the transmission of a reactive oxygen species (ROS) signal generated by the PaNox1 NADPH oxidase inside the maturing fruiting body towards the PaMpk1 MAP kinase, which is located inside the underlying mycelium, in which nutrients are stored. These data provide important new insights to our understanding of how fungi build multicellular structures.}, } @article {pmid27967109, year = {2016}, author = {Kirkegaard, JB and Goldstein, RE}, title = {Filter-feeding, near-field flows, and the morphologies of colonial choanoflagellates.}, journal = {Physical review. E}, volume = {94}, number = {5-1}, pages = {052401}, pmid = {27967109}, issn = {2470-0053}, support = {//Wellcome Trust/United Kingdom ; 097855//Wellcome Trust/United Kingdom ; }, mesh = {Choanoflagellata/*cytology/*physiology ; Feeding Behavior/*physiology ; *Water Movements ; }, abstract = {Efficient uptake of prey and nutrients from the environment is an important component in the fitness of all microorganisms, and its dependence on size may reveal clues to the origins of evolutionary transitions to multicellularity. Because potential benefits in uptake rates must be viewed in the context of other costs and benefits of size, such as varying predation rates and the increased metabolic costs associated with larger and more complex body plans, the uptake rate itself is not necessarily that which is optimized by evolution. Uptake rates can be strongly dependent on local organism geometry and its swimming speed, providing selective pressure for particular arrangements. Here we examine these issues for choanoflagellates, filter-feeding microorganisms that are the closest relatives of the animals. We explore the different morphological variations of the choanoflagellate Salpingoeca rosetta, which can exist as a swimming cell, as a sessile thecate cell, and as colonies of cells in various shapes. In the absence of other requirements and in a homogeneously nutritious environment, we find that the optimal strategy to maximize filter-feeding by the collar of microvilli is to swim fast, which favors swimming unicells. In large external flows, the sessile thecate cell becomes advantageous. Effects of prey diffusion are discussed and also found to be to the advantage of the swimming unicell.}, } @article {pmid27965457, year = {2017}, author = {Däster, S and Amatruda, N and Calabrese, D and Ivanek, R and Turrini, E and Droeser, RA and Zajac, P and Fimognari, C and Spagnoli, GC and Iezzi, G and Mele, V and Muraro, MG}, title = {Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment.}, journal = {Oncotarget}, volume = {8}, number = {1}, pages = {1725-1736}, pmid = {27965457}, issn = {1949-2553}, mesh = {Animals ; Antimetabolites, Antineoplastic/*pharmacology ; Cell Hypoxia/*physiology ; Colorectal Neoplasms/drug therapy/*pathology ; Drug Resistance, Neoplasm/*physiology ; Fluorouracil/*pharmacology ; Gene Expression Profiling ; HCT116 Cells ; HT29 Cells ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Necrosis/*pathology ; Oxygen/metabolism ; Spheroids, Cellular/*physiology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Culture of cancerous cells in standard monolayer conditions poorly mirrors growth in three-dimensional architectures typically observed in a wide majority of cancers of different histological origin. Multicellular tumor spheroid (MCTS) culture models were developed to mimic these features. However, in vivo tumor growth is also characterized by the presence of ischemic and necrotic areas generated by oxygenation gradients and differential access to nutrients. Hypoxia and necrosis play key roles in tumor progression and resistance to treatment. To provide in vitro models recapitulating these events in highly controlled and standardized conditions, we have generated colorectal cancer (CRC) cell spheroids of different sizes and analyzed their gene expression profiles and sensitivity to treatment with 5FU, currently used in therapeutic protocols. Here we identify three MCTS stages, corresponding to defined spheroid sizes, characterized by normoxia, hypoxia, and hypoxia plus necrosis, respectively. Importantly, we show that MCTS including both hypoxic and necrotic areas most closely mimic gene expression profiles of in vivo-developing tumors and display the highest resistance to 5FU. Taken together, our data indicate that MCTS may mimic in vitro generation of ischemic and necrotic areas in highly standardized and controlled conditions, thereby qualifying as relevant models for drug screening purposes.}, } @article {pmid27939723, year = {2017}, author = {Lu, X and Xiang, Y and Yang, G and Zhang, L and Wang, H and Zhong, S}, title = {Transcriptomic characterization of zebrafish larvae in response to mercury exposure.}, journal = {Comparative biochemistry and physiology. Toxicology & pharmacology : CBP}, volume = {192}, number = {}, pages = {40-49}, doi = {10.1016/j.cbpc.2016.12.006}, pmid = {27939723}, issn = {1532-0456}, mesh = {ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/metabolism ; Animals ; Biological Transport ; Computational Biology ; Databases, Genetic ; Gene Expression Profiling/methods ; Gene Expression Regulation, Developmental/*drug effects ; Gene Regulatory Networks ; High-Throughput Nucleotide Sequencing ; LLC-PK1 Cells ; Larva/*drug effects/genetics ; Mercuric Chloride/metabolism/*toxicity ; Swine ; Time Factors ; Transcription, Genetic/*drug effects ; Transfection ; Water Pollutants, Chemical/metabolism/*toxicity ; Zebrafish/*genetics/metabolism ; Zebrafish Proteins/*genetics/metabolism ; }, abstract = {Mercury is a widespread toxicant in aquatic environment that can cause deleterious effects on fish. Although a number of mercury-regulated genes have been investigated in adult fish, the transcriptional responses of fish larvae to acute mercury exposure are not well understood. In this study, RNA sequencing was used to examine the transcriptional changes in developing zebrafish larvae under a low concentration of mercuric chloride exposure from 24 to 120hpf. Our initial results showed that a total of 142.59 million raw reads were obtained from sequencing libraries and about 86% of the processed reads were mapped to the reference genome of zebrafish. Differential expression analysis identified 391 up- and 87 down-regulated genes. Gene ontology enrichment analysis revealed that most of the differential expressed genes are closely related to the regulation of cellular process, metabolic process, multicellular organismal process, biological regulation, pigmentation, and response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that antigen processing and presentation was the most significantly enriched pathway. Moreover, we characterized a novel and sensitive mercury-induced ABCB (ATP- binding cassette B subfamily) transporter gene - abcb5. This gene is localized on zebrafish chromosome 16 and contains a 4014bp open-reading frame. The deduced polypeptide is composed of 1337 amino acids and possesses most of functional domains and critical residues defined in human and mouse ABCB5/Abcb5. Functional analysis in vitro demonstrated that overexpression of zebrafish abcb5 gene can significantly decrease the cytotoxicity of mercury in LLC-PK1 cells, implying it is a potential efflux transporter of mercury. Thus, these findings provide useful insights to help further understand the transcriptional response and detoxification ability of zebrafish larvae following acute exposure to mercury.}, } @article {pmid27936291, year = {2017}, author = {Hughes, KA and Leips, J}, title = {Pleiotropy, constraint, and modularity in the evolution of life histories: insights from genomic analyses.}, journal = {Annals of the New York Academy of Sciences}, volume = {1389}, number = {1}, pages = {76-91}, pmid = {27936291}, issn = {1749-6632}, support = {F32 GM016990/GM/NIGMS NIH HHS/United States ; R01 DK084219/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Drosophila melanogaster ; *Genetic Pleiotropy ; *Genetic Variation ; *Genetics, Population ; Genome ; Genome-Wide Association Study ; *Genomics ; Humans ; Plants ; Quantitative Trait Loci ; Selection, Genetic ; }, abstract = {Multicellular organisms display an enormous range of life history (LH) strategies and present an evolutionary conundrum; despite strong natural selection, LH traits are characterized by high levels of genetic variation. To understand the evolution of life histories and maintenance of this variation, the specific phenotypic effects of segregating alleles and the genetic networks in which they act need to be elucidated. In particular, the extent to which LH evolution is constrained by the pleiotropy of alleles contributing to LH variation is generally unknown. Here, we review recent empirical results that shed light on this question, with an emphasis on studies employing genomic analyses. While genome-scale analyses are increasingly practical and affordable, they face limitations of genetic resolution and statistical power. We describe new research approaches that we believe can produce new insights and evaluate their promise and applicability to different kinds of organisms. Two approaches seem particularly promising: experiments that manipulate selection in multiple dimensions and measure phenotypic and genomic response and analytical approaches that take into account genome-wide associations between markers and phenotypes, rather than applying a traditional marker-by-marker approach.}, } @article {pmid27934708, year = {2016}, author = {Jones, JD and Vance, RE and Dangl, JL}, title = {Intracellular innate immune surveillance devices in plants and animals.}, journal = {Science (New York, N.Y.)}, volume = {354}, number = {6316}, pages = {}, doi = {10.1126/science.aaf6395}, pmid = {27934708}, issn = {1095-9203}, support = {BB/K003550/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M003809/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M008193/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Evolution, Molecular ; Host-Pathogen Interactions ; *Immunity, Innate ; *Immunologic Surveillance ; NLR Proteins/chemistry/genetics/*immunology ; Plant Diseases/immunology/microbiology ; Plants/*immunology/*microbiology ; Protein Domains ; }, abstract = {Multicellular eukaryotes coevolve with microbial pathogens, which exert strong selective pressure on the immune systems of their hosts. Plants and animals use intracellular proteins of the nucleotide-binding domain, leucine-rich repeat (NLR) superfamily to detect many types of microbial pathogens. The NLR domain architecture likely evolved independently and convergently in each kingdom, and the molecular mechanisms of pathogen detection by plant and animal NLRs have long been considered to be distinct. However, microbial recognition mechanisms overlap, and it is now possible to discern important key trans-kingdom principles of NLR-dependent immune function. Here, we attempt to articulate these principles. We propose that the NLR architecture has evolved for pathogen-sensing in diverse organisms because of its utility as a tightly folded "hair trigger" device into which a virtually limitless number of microbial detection platforms can be integrated. Recent findings suggest means to rationally design novel recognition capabilities to counter disease.}, } @article {pmid27917322, year = {2016}, author = {Grishaeva, TM and Kulichenko, D and Bogdanov, YF}, title = {Bioinformatical analysis of eukaryotic shugoshins reveals meiosis-specific features of vertebrate shugoshins.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e2736}, pmid = {27917322}, issn = {2167-8359}, abstract = {BACKGROUND: Shugoshins (SGOs) are proteins that protect cohesins located at the centromeres of sister chromatids from their early cleavage during mitosis and meiosis in plants, fungi, and animals. Their function is to prevent premature sister-chromatid disjunction and segregation. The study focused on the structural differences among SGOs acting during mitosis and meiosis that cause differences in chromosome behavior in these two types of cell division in different organisms.

METHODS: A bioinformatical analysis of protein domains, conserved amino acid motifs, and physicochemical properties of 32 proteins from 25 species of plants, fungi, and animals was performed.

RESULTS: We identified a C-terminal amino acid motif that is highly evolutionarily conserved among the SGOs protecting centromere cohesion of sister chromatids in meiotic anaphase I, but not among mitotic SGOs. This meiotic motif is arginine-rich in vertebrates. SGOs differ in different eukaryotic kingdoms by the sets and locations of amino acid motifs and the number of α-helical regions in the protein molecule.

DISCUSSION: These structural differences between meiotic and mitotic SGOs probably could be responsible for the prolonged SGOs resistance to degradation during meiotic metaphase I and anaphase I. We suggest that the "arginine comb" in C-end meiotic motifs is capable of interaction by hydrogen bonds with guanine bases in the minor groove of DNA helix, thus protecting SGOs from hydrolysis. Our findings support independent evolution of meiosis in different lineages of multicellular organisms.}, } @article {pmid27913751, year = {2017}, author = {Wu, Y and Gao, B and Zhu, S}, title = {New fungal defensin-like peptides provide evidence for fold change of proteins in evolution.}, journal = {Bioscience reports}, volume = {37}, number = {1}, pages = {}, pmid = {27913751}, issn = {1573-4935}, mesh = {Amino Acid Sequence ; Ascomycota/*chemistry/genetics ; Cysteine/chemistry/genetics ; Defensins/*chemistry/genetics ; Evolution, Molecular ; Fungal Proteins/*chemistry/genetics ; Genes, Fungal ; Models, Molecular ; Protein Conformation, alpha-Helical ; Protein Conformation, beta-Strand ; Protein Folding ; Sequence Alignment ; }, abstract = {Defensins containing a consensus cystine framework, Cys[1]…Cys[2]X3Cys[3]…Cys[4]… Cys[5]X1Cys[6] (X, any amino acid except Cys; …, variable residue numbers), are extensively distributed in a variety of multicellular organisms (plants, fungi and invertebrates) and essentially involved in immunity as microbicidal agents. This framework is a prerequisite for forming the cysteine-stabilized α-helix and β-sheet (CSαβ) fold, in which the two invariant motifs, Cys[2]X3Cys[3]/Cys[5]X1Cys[6], are key determinants of fold formation. By using a computational genomics approach, we identified a large superfamily of fungal defensin-like peptides (fDLPs) in the phytopathogenic fungal genus - Zymoseptoria, which includes 132 structurally typical and 63 atypical members. These atypical fDLPs exhibit an altered cystine framework and accompanying fold change associated with their secondary structure elements and disulfide bridge patterns, as identified by protein structure modelling. Despite this, they definitely are homologous with the typical fDLPs in view of their precise gene structure conservation and identical precursor organization. Sequence and structural analyses combined with functional data suggest that most of Zymoseptoria fDLPs might have lost their antimicrobial activity. The present study provides a clear example of fold change in the evolution of proteins and is valuable in establishing remote homology among peptide superfamily members with different folds.}, } @article {pmid27903631, year = {2017}, author = {Dettman, JR and Rodrigue, N and Schoustra, SE and Kassen, R}, title = {Genomics of Compensatory Adaptation in Experimental Populations of Aspergillus nidulans.}, journal = {G3 (Bethesda, Md.)}, volume = {7}, number = {2}, pages = {427-436}, pmid = {27903631}, issn = {2160-1836}, support = {//CIHR/Canada ; }, mesh = {Adaptation, Physiological/*genetics ; Aspergillus nidulans/drug effects/*genetics/growth & development ; Dioxoles/pharmacology ; Drug Resistance, Fungal ; *Evolution, Molecular ; *Genetic Fitness ; Genome, Fungal ; Genomics ; Osmotic Pressure/physiology ; Pyrroles/pharmacology ; }, abstract = {Knowledge of the number and nature of genetic changes responsible for adaptation is essential for understanding and predicting evolutionary trajectories. Here, we study the genomic basis of compensatory adaptation to the fitness cost of fungicide resistance in experimentally evolved strains of the filamentous fungus Aspergillus nidulans The original selection experiment tracked the fitness recovery of lines founded by an ancestral strain that was resistant to fludioxonil, but paid a fitness cost in the absence of the fungicide. We obtained whole-genome sequence data for the ancestral A. nidulans strain and eight experimentally evolved strains. We find that fludioxonil resistance in the ancestor was likely conferred by a mutation in histidine kinase nikA, part of the two-component signal transduction system of the high-osmolarity glycerol (HOG) stress response pathway. To compensate for the pleiotropic negative effects of the resistance mutation, the subsequent fitness gains observed in the evolved lines were likely caused by secondary modification of HOG pathway activity. Candidate genes for the compensatory fitness increases were significantly overrepresented by stress response functions, and some were specifically associated with the HOG pathway itself. Parallel evolution at the gene level was rare among evolved lines. There was a positive relationship between the predicted number of adaptive steps, estimated from fitness data, and the number of genomic mutations, determined by whole-genome sequencing. However, the number of genomic mutations was, on average, 8.45 times greater than the number of adaptive steps inferred from fitness data. This research expands our understanding of the genetic basis of adaptation in multicellular eukaryotes and lays out a framework for future work on the genomics of compensatory adaptation in A. nidulans.}, } @article {pmid27888167, year = {2017}, author = {Liao, BK and Oates, AC}, title = {Delta-Notch signalling in segmentation.}, journal = {Arthropod structure & development}, volume = {46}, number = {3}, pages = {429-447}, pmid = {27888167}, issn = {1873-5495}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Body Patterning/genetics/*physiology ; Gene Expression Regulation, Developmental ; Phylogeny ; Receptors, Notch/genetics/*metabolism ; *Signal Transduction ; }, abstract = {Modular body organization is found widely across multicellular organisms, and some of them form repetitive modular structures via the process of segmentation. It's vastly interesting to understand how these regularly repeated structures are robustly generated from the underlying noise in biomolecular interactions. Recent studies from arthropods reveal similarities in segmentation mechanisms with vertebrates, and raise the possibility that the three phylogenetic clades, annelids, arthropods and chordates, might share homology in this process from a bilaterian ancestor. Here, we discuss vertebrate segmentation with particular emphasis on the role of the Notch intercellular signalling pathway. We introduce vertebrate segmentation and Notch signalling, pointing out historical milestones, then describe existing models for the Notch pathway in the synchronization of noisy neighbouring oscillators, and a new role in the modulation of gene expression wave patterns. We ask what functions Notch signalling may have in arthropod segmentation and explore the relationship between Notch-mediated lateral inhibition and synchronization. Finally, we propose open questions and technical challenges to guide future investigations into Notch signalling in segmentation.}, } @article {pmid27886385, year = {2017}, author = {Frangedakis, E and Saint-Marcoux, D and Moody, LA and Rabbinowitsch, E and Langdale, JA}, title = {Nonreciprocal complementation of KNOX gene function in land plants.}, journal = {The New phytologist}, volume = {216}, number = {2}, pages = {591-604}, pmid = {27886385}, issn = {1469-8137}, mesh = {Bayes Theorem ; Embryophyta/*genetics ; Evolution, Molecular ; Gene Duplication ; *Genes, Plant ; *Genetic Complementation Test ; Likelihood Functions ; Loss of Function Mutation/genetics ; Phylogeny ; Plant Proteins/genetics/metabolism ; Plants, Genetically Modified ; Species Specificity ; Transgenes ; }, abstract = {Class I KNOTTED-LIKE HOMEOBOX (KNOX) proteins regulate development of the multicellular diploid sporophyte in both mosses and flowering plants; however, the morphological context in which they function differs. In order to determine how Class I KNOX function was modified as land plants evolved, phylogenetic analyses and cross-species complementation assays were performed. Our data reveal that a duplication within the charophyte sister group to land plants led to distinct Class I and Class II KNOX gene families. Subsequently, Class I sequences diverged substantially in the nonvascular bryophyte groups (liverworts, mosses and hornworts), with moss sequences being most similar to those in vascular plants. Despite this similarity, moss mutants were not complemented by vascular plant KNOX genes. Conversely, the Arabidopsis brevipedicellus (bp-9) mutant was complemented by the PpMKN2 gene from the moss Physcomitrella patens. Lycophyte KNOX genes also complemented bp-9 whereas fern genes only partially complemented the mutant. This lycophyte/fern distinction is mirrored in the phylogeny of KNOX-interacting BELL proteins, in that a gene duplication occurred after divergence of the two groups. Together, our results imply that the moss MKN2 protein can function in a broader developmental context than vascular plant KNOX proteins, the narrower scope having evolved progressively as lycophytes, ferns and flowering plants diverged.}, } @article {pmid27882869, year = {2016}, author = {Kirkegaard, JB and Bouillant, A and Marron, AO and Leptos, KC and Goldstein, RE}, title = {Aerotaxis in the closest relatives of animals.}, journal = {eLife}, volume = {5}, number = {}, pages = {}, pmid = {27882869}, issn = {2050-084X}, support = {097855/WT_/Wellcome Trust/United Kingdom ; 247333/ERC_/European Research Council/International ; 097855/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Chemotaxis ; Choanoflagellata/*drug effects/*physiology ; Lab-On-A-Chip Devices ; Oxygen/*metabolism ; }, abstract = {As the closest unicellular relatives of animals, choanoflagellates serve as useful model organisms for understanding the evolution of animal multicellularity. An important factor in animal evolution was the increasing ocean oxygen levels in the Precambrian, which are thought to have influenced the emergence of complex multicellular life. As a first step in addressing these conditions, we study here the response of the colony-forming choanoflagellate Salpingoeca rosetta to oxygen gradients. Using a microfluidic device that allows spatio-temporal variations in oxygen concentrations, we report the discovery that S. rosetta displays positive aerotaxis. Analysis of the spatial population distributions provides evidence for logarithmic sensing of oxygen, which enhances sensing in low oxygen neighborhoods. Analysis of search strategy models on the experimental colony trajectories finds that choanoflagellate aerotaxis is consistent with stochastic navigation, the statistics of which are captured using an effective continuous version based on classical run-and-tumble chemotaxis.}, } @article {pmid27880891, year = {2017}, author = {Guzman, A and Sánchez Alemany, V and Nguyen, Y and Zhang, CR and Kaufman, LJ}, title = {A novel 3D in vitro metastasis model elucidates differential invasive strategies during and after breaching basement membrane.}, journal = {Biomaterials}, volume = {115}, number = {}, pages = {19-29}, doi = {10.1016/j.biomaterials.2016.11.014}, pmid = {27880891}, issn = {1878-5905}, mesh = {Batch Cell Culture Techniques/*methods ; Cell Line, Tumor ; Cell Membrane/metabolism/*pathology ; Extracellular Matrix/metabolism/pathology ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms, Experimental/metabolism/*pathology/*secondary ; *Printing, Three-Dimensional ; *Tissue Scaffolds ; }, abstract = {Invasive breast cancer and other tumors of epithelial origin must breach a layer of basement membrane (BM) that surrounds the primary tumor before invading into the adjacent extracellular matrix. To analyze invasive strategies of breast cancer cells during BM breaching and subsequent invasion into a collagen I-rich extracellular matrix (ECM), we developed a physiologically relevant 3D in vitro model that recreates the architecture of a solid tumor with an intact, degradable, cell-assembled BM layer embedded in a collagen I environment. Using this model we demonstrate that while the BM layer fully prevents dissemination of non-malignant cells, cancer cells are capable of breaching it and invading into the surrounding collagen, indicating that the developed system recreates a hallmark of invasive disease. We demonstrate that cancer cells exhibiting individual invasion in collagen matrices preferentially adopt a specific mode of collective invasion when transmigrating a cell-assembled BM that is not observed in any other tested fibrillar, non-fibrillar, or composite ECM. Matrix-degrading enzymes are found to be crucial during BM breaching but not during subsequent invasion in the collagen matrix. It is further shown that multicellular transmigration of the BM is less susceptible to pharmacological MMP inhibition than multicellular invasion in composite collagen/basement membrane extract matrices. The newly developed in vitro model of metastasis allows 3D cancer cell invasion to be studied not only as a function of a particular tumor's genetics but also as a function of its heterogeneous environment and the different stages of invasion. As such, this model is a valuable new tool with which to dissect basic mechanisms of invasion and metastasis and develop new therapeutic approaches in a physiologically relevant, yet inexpensive and highly tunable, in vitro setting.}, } @article {pmid27880868, year = {2017}, author = {Gaiti, F and Calcino, AD and Tanurdžić, M and Degnan, BM}, title = {Origin and evolution of the metazoan non-coding regulatory genome.}, journal = {Developmental biology}, volume = {427}, number = {2}, pages = {193-202}, doi = {10.1016/j.ydbio.2016.11.013}, pmid = {27880868}, issn = {1095-564X}, mesh = {Animals ; *Biological Evolution ; *Gene Expression Regulation ; *Genome ; Humans ; Regulatory Sequences, Nucleic Acid ; }, abstract = {Animals rely on genomic regulatory systems to direct the dynamic spatiotemporal and cell-type specific gene expression that is essential for the development and maintenance of a multicellular lifestyle. Although it is widely appreciated that these systems ultimately evolved from genomic regulatory mechanisms present in single-celled stem metazoans, it remains unclear how this occurred. Here, we focus on the contribution of the non-coding portion of the genome to the evolution of animal gene regulation, specifically on recent insights from non-bilaterian metazoan lineages, and unicellular and colonial holozoan sister taxa. High-throughput next-generation sequencing, largely in bilaterian model species, has led to the discovery of tens of thousands of non-coding RNA genes (ncRNAs), including short, long and circular forms, and uncovered the central roles they play in development. Based on the analysis of non-bilaterian metazoan, unicellular holozoan and fungal genomes, the evolution of some ncRNAs, such as Piwi-interacting RNAs, correlates with the emergence of metazoan multicellularity, while others, including microRNAs, long non-coding RNAs and circular RNAs, appear to be more ancient. Analysis of non-coding regulatory DNA and histone post-translational modifications have revealed that some cis-regulatory mechanisms, such as those associated with proximal promoters, are present in non-animal holozoans, while others appear to be metazoan innovations, most notably distal enhancers. In contrast, the cohesin-CTCF system for regulating higher-order chromatin structure and enhancer-promoter long-range interactions appears to be restricted to bilaterians. Taken together, most bilaterian non-coding regulatory mechanisms appear to have originated before the divergence of crown metazoans. However, differential expansion of non-coding RNA and cis-regulatory DNA repertoires in bilaterians may account for their increased regulatory and morphological complexity relative to non-bilaterians.}, } @article {pmid27876853, year = {2016}, author = {Rodriguez-Pascual, F and Slatter, DA}, title = {Collagen cross-linking: insights on the evolution of metazoan extracellular matrix.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {37374}, pmid = {27876853}, issn = {2045-2322}, mesh = {Amino Acid Sequence ; Animals ; Collagen/classification/genetics/*metabolism ; Evolution, Molecular ; Extracellular Matrix/*metabolism ; Fibrillar Collagens/chemistry/genetics/*metabolism ; Humans ; Invertebrates/genetics/metabolism ; Models, Molecular ; Phylogeny ; Protein Structure, Secondary ; Protein-Lysine 6-Oxidase/*metabolism ; Sequence Homology, Amino Acid ; Vertebrates/genetics/metabolism ; }, abstract = {Collagens constitute a large family of extracellular matrix (ECM) proteins that play a fundamental role in supporting the structure of various tissues in multicellular animals. The mechanical strength of fibrillar collagens is highly dependent on the formation of covalent cross-links between individual fibrils, a process initiated by the enzymatic action of members of the lysyl oxidase (LOX) family. Fibrillar collagens are present in a wide variety of animals, therefore often being associated with metazoan evolution, where the emergence of an ancestral collagen chain has been proposed to lead to the formation of different clades. While LOX-generated collagen cross-linking metabolites have been detected in different metazoan families, there is limited information about when and how collagen acquired this particular modification. By analyzing telopeptide and helical sequences, we identified highly conserved, potential cross-linking sites throughout the metazoan tree of life. Based on this analysis, we propose that they have importantly contributed to the formation and further expansion of fibrillar collagens.}, } @article {pmid27871856, year = {2017}, author = {Pianca, N and Zaglia, T and Mongillo, M}, title = {Will cardiac optogenetics find the way through the obscure angles of heart physiology?.}, journal = {Biochemical and biophysical research communications}, volume = {482}, number = {4}, pages = {515-523}, doi = {10.1016/j.bbrc.2016.11.104}, pmid = {27871856}, issn = {1090-2104}, mesh = {Animals ; Arrhythmias, Cardiac/genetics/pathology/physiopathology/therapy ; Channelrhodopsins ; Equipment Design ; Heart/*physiology/physiopathology ; Humans ; Myocardium/metabolism/pathology ; Optogenetics/instrumentation/*methods ; }, abstract = {Optogenetics is a technique exploded in the last 10 years, which revolutionized several areas of biological research. The brightest side of this technology is the use of light to modulate non-invasively, with high spatial resolution and millisecond time scale, excitable cells genetically modified to express light-sensitive microbial ion channels (opsins). Neuroscience has first benefited from such fascinating strategy, in intact organisms. By shining light to specific neuronal subpopulations, optogenetics allowed unearth the mechanisms involved in cell-to-cell communication within the context of intact organs, such as the brain, formed by complex neuronal circuits. More recently, scientists looked at optogenetics as a tool to answer some of the questions, remained in the dark, of cardiovascular physiology. In this review, we focus on the application of optogenetics in the study of the heart, a complex multicellular organ, homing different populations of excitable cells, spatially and functionally interconnected. Moving from the first proof-of-principle works, published in 2010, to the present time, we discuss the in vitro and in vivo applications of optogenetics for the study of electrophysiology of the different cardiac cell types, and for the dissection of cellular mechanisms underlying arrhythmias. We also present how molecular biology and technology foster the evolution of cardiac optogenetics, with the aim to further our understanding of fundamental questions in cardiac physiology and pathology. Finally, we confer about the therapeutic potential of such biotechnological strategy for the treatment of heart rhythm disturbances (e.g. cardiac pacing, cardioversion).}, } @article {pmid27870211, year = {2016}, author = {Cunningham, JA and Vargas, K and Marone, F and Bengtson, S and Donoghue, PC}, title = {A multicellular organism with embedded cell clusters from the Ediacaran Weng'an biota (Doushantuo Formation, South China).}, journal = {Evolution & development}, volume = {18}, number = {5-6}, pages = {308-316}, pmid = {27870211}, issn = {1525-142X}, mesh = {*Biological Evolution ; China ; Eukaryota/ultrastructure ; Fossils/*anatomy & histology/ultrastructure ; Microscopy, Electron, Scanning ; }, abstract = {Three-dimensional analyses of the early Ediacaran microfossils from the Weng'an biota (Doushantuo Formation) have focused predominantly on multicellular forms that have been interpreted as embryos, and yet they have defied phylogenetic interpretation principally because of absence of evidence from other stages in their life cycle. It is therefore unfortunate that the affinities of the various other Doushantuo microfossils have been neglected. A new conical fossil that is preserved at a cellular level is described here. The fossil contains distinct cell clusters that are characterized and analysed in three dimensions. These clusters are often exposed at the specimen surface, and the fossil preserves many hemispherical craters that are interpreted as positions where clusters have left the organism. The cell clusters may be either reproductive propagules or infesting organisms. Similar clusters are found in a variety of Doushantuo organisms including putative animal embryos and algae.}, } @article {pmid27863931, year = {2016}, author = {Filyk, HA and Osborne, LC}, title = {The Multibiome: The Intestinal Ecosystem's Influence on Immune Homeostasis, Health, and Disease.}, journal = {EBioMedicine}, volume = {13}, number = {}, pages = {46-54}, pmid = {27863931}, issn = {2352-3964}, mesh = {Animals ; Disease Susceptibility ; Ecosystem ; *Gastrointestinal Microbiome ; *Homeostasis ; Host-Parasite Interactions/genetics/immunology ; Host-Pathogen Interactions/genetics/immunology ; Humans ; Immunity, Mucosal ; Immunomodulation ; Intestinal Mucosa/immunology/metabolism/microbiology ; Intestines/*physiology ; }, abstract = {Mammalian evolution has occurred in the presence of mutualistic, commensal, and pathogenic micro- and macro-organisms for millennia. The presence of these organisms during mammalian evolution has allowed for intimate crosstalk between these colonizing species and the host immune system. In this review, we introduce the concept of the 'multibiome' to holistically refer to the biodiverse collection of bacteria, viruses, fungi and multicellular helminthic worms colonizing the mammalian intestine. Furthermore, we discuss new insights into multibiome-host interactions in the context of host-protective immunity and immune-mediated diseases, including inflammatory bowel disease and multiple sclerosis. Finally, we provide reasons to account for the multibiome in experimental design, analysis and in therapeutic applications.}, } @article {pmid27855631, year = {2016}, author = {Singh, R and Schilde, C and Schaap, P}, title = {A core phylogeny of Dictyostelia inferred from genomes representative of the eight major and minor taxonomic divisions of the group.}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {251}, pmid = {27855631}, issn = {1471-2148}, support = {BB/K000799/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 100293/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Base Sequence ; Computational Biology ; Consensus Sequence ; Dictyostelium/*classification/*genetics ; *Genome, Protozoan ; *Phylogeny ; Protozoan Proteins/chemistry/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Dictyostelia are a well-studied group of organisms with colonial multicellularity, which are members of the mostly unicellular Amoebozoa. A phylogeny based on SSU rDNA data subdivided all Dictyostelia into four major groups, but left the position of the root and of six group-intermediate taxa unresolved. Recent phylogenies inferred from 30 or 213 proteins from sequenced genomes, positioned the root between two branches, each containing two major groups, but lacked data to position the group-intermediate taxa. Since the positions of these early diverging taxa are crucial for understanding the evolution of phenotypic complexity in Dictyostelia, we sequenced six representative genomes of early diverging taxa.

RESULTS: We retrieved orthologs of 47 housekeeping proteins with an average size of 890 amino acids from six newly sequenced and eight published genomes of Dictyostelia and unicellular Amoebozoa and inferred phylogenies from single and concatenated protein sequence alignments. Concatenated alignments of all 47 proteins, and four out of five subsets of nine concatenated proteins all produced the same consensus phylogeny with 100% statistical support. Trees inferred from just two out of the 47 proteins, individually reproduced the consensus phylogeny, highlighting that single gene phylogenies will rarely reflect correct species relationships. However, sets of two or three concatenated proteins again reproduced the consensus phylogeny, indicating that a small selection of genes suffices for low cost classification of as yet unincorporated or newly discovered dictyostelid and amoebozoan taxa by gene amplification.

CONCLUSIONS: The multi-locus consensus phylogeny shows that groups 1 and 2 are sister clades in branch I, with the group-intermediate taxon D. polycarpum positioned as outgroup to group 2. Branch II consists of groups 3 and 4, with the group-intermediate taxon Polysphondylium violaceum positioned as sister to group 4, and the group-intermediate taxon Dictyostelium polycephalum branching at the base of that whole clade. Given the data, the approximately unbiased test rejects all alternative topologies favoured by SSU rDNA and individual proteins with high statistical support. The test also rejects monophyletic origins for the genera Acytostelium, Polysphondylium and Dictyostelium. The current position of Acytostelium ellipticum in the consensus phylogeny indicates that somatic cells were lost twice in Dictyostelia.}, } @article {pmid27845495, year = {2016}, author = {Romero, D}, title = {Unicellular but not asocial. Life in community of a bacterium.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {19}, number = {2}, pages = {81-90}, doi = {10.2436/20.1501.01.266}, pmid = {27845495}, issn = {1139-6709}, mesh = {Bacillus/physiology ; Bacteria/*cytology ; Biological Evolution ; *Microbial Consortia ; }, abstract = {All living organisms have acquired the outstanding ability to overcome the limitations imposed by changeable environments through the gain of genetic traits over years of evolution and the tendency of individuals to associate in communities. The complementation of a singular weakness, the deployment of reinforcement for the good of the community, the better use of resources, or effective defense against external aggression are advantages gained by this communal behavior. Communication has been the cohesive element prompting the global responses that promote efficiency in two features of any community: specialization in differentiated labor and the spatio-temporal organization of the environment. These principles illustrate that what we call human ecology also applies to the cellular world and is exemplified in eukaryotic organisms, where sophisticated cell-to-cell communication networks coordinate cell differentiation and the specialization of multiple tissues consisting of numerous cells embedded in a multifunctional extracellular matrix. This sophisticated molecular machinery appears, however, to be invented by the "simple" but still fascinating bacteria. What I will try to expand in the following sections are notions of how "single prokaryotic cells" organize a multicellular community. [Int Microbiol 19(2):81-90 (2016)].}, } @article {pmid27829356, year = {2016}, author = {Yamashita, S and Arakaki, Y and Kawai-Toyooka, H and Noga, A and Hirono, M and Nozaki, H}, title = {Alternative evolution of a spheroidal colony in volvocine algae: developmental analysis of embryogenesis in Astrephomene (Volvocales, Chlorophyta).}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {243}, pmid = {27829356}, issn = {1471-2148}, mesh = {Basal Bodies/metabolism ; *Biological Evolution ; Cell Division ; Cell Lineage ; Cell Nucleus/metabolism ; Chlorophyta/*embryology/*genetics ; Fluorescent Antibody Technique, Indirect ; Phylogeny ; Protoplasts/metabolism ; Time-Lapse Imaging ; }, abstract = {BACKGROUND: Volvocine algae, which range from the unicellular Chlamydomonas to the multicellular Volvox with a germ-soma division of labor, are a model for the evolution of multicellularity. Within this group, the spheroidal colony might have evolved in two independent lineages: Volvocaceae and the goniacean Astrephomene. Astrephomene produces spheroidal colonies with posterior somatic cells. The feature that distinguishes Astrephomene from the volvocacean algae is lack of inversion during embryogenesis; the volvocacean embryo undergoes inversion after successive divisions to orient flagella toward the outside. The mechanisms of inversion at the molecular and cellular levels in volvocacean algae have been assessed in detail, particularly in Volvox carteri. However, embryogenesis in Astrephomene has not been subjected to such investigations.

RESULTS: This study relied on light microscopy time-lapse imaging using an actively growing culture of a newly established strain to conduct a developmental analysis of Astrephomene as well as to perform a comparison with the similar spheroidal volvocacean Eudorina. During the successive divisions involved in Astrephomene embryogenesis, gradual rotation of daughter protoplasts resulted in movement of their apical portions toward the embryonic posterior, forming a convex-to-spheroidal cell sheet with the apical ends of protoplasts on the outside. Differentiation of the posterior somatic cells from the embryo periphery was traced based on cell lineages during embryogenesis. In contrast, in Eudorina, the rotation of daughter protoplasts did not occur during successive cell divisions; however, inversion occurred after such divisions, and a spheroidal embryo was formed. Indirect immunofluorescence microscopy of basal bodies and nuclei verified this difference between Astrephomene and Eudorina in the movement of embryonic protoplasts.

CONCLUSIONS: These results suggest different tactics for spheroidal colony formation between the two lineages: rotation of daughter protoplasts during successive cell divisions in Astrephomene, and inversion after cell divisions in Eudorina. This study will facilitate further research into the molecular and genetic mechanisms of the parallel evolution of the spheroidal colony in volvocine algae.}, } @article {pmid27818507, year = {2016}, author = {Arendt, D and Musser, JM and Baker, CVH and Bergman, A and Cepko, C and Erwin, DH and Pavlicev, M and Schlosser, G and Widder, S and Laubichler, MD and Wagner, GP}, title = {The origin and evolution of cell types.}, journal = {Nature reviews. Genetics}, volume = {17}, number = {12}, pages = {744-757}, pmid = {27818507}, issn = {1471-0064}, mesh = {Animals ; *Biological Evolution ; *Cell Differentiation ; *Cell Lineage ; Cells/classification/*cytology ; *Gene Regulatory Networks ; Humans ; Phylogeny ; }, abstract = {Cell types are the basic building blocks of multicellular organisms and are extensively diversified in animals. Despite recent advances in characterizing cell types, classification schemes remain ambiguous. We propose an evolutionary definition of a cell type that allows cell types to be delineated and compared within and between species. Key to cell type identity are evolutionary changes in the 'core regulatory complex' (CoRC) of transcription factors, that make emergent sister cell types distinct, enable their independent evolution and regulate cell type-specific traits termed apomeres. We discuss the distinction between developmental and evolutionary lineages, and present a roadmap for future research.}, } @article {pmid27818249, year = {2017}, author = {Currais, A}, title = {The origin of life at the origin of ageing?.}, journal = {Ageing research reviews}, volume = {35}, number = {}, pages = {297-300}, doi = {10.1016/j.arr.2016.10.007}, pmid = {27818249}, issn = {1872-9649}, mesh = {Aging/*physiology ; Animals ; Cell Survival/physiology ; Humans ; *Origin of Life ; }, abstract = {At first glance, the ageing of unicellular organisms would appear to be different from the ageing of complex, multicellular organisms. In an attempt to describe the nature of ageing in diverse organisms, the intimate links between the origins of life and ageing are examined. Departing from Leslie Orgel's initial ideas on why organisms age, it is then discussed how the potentially detrimental events characteristic of ageing are continuous, cell-autonomous and universal to all organisms. The manifestation of these alterations relies on the balance between their production and cellular renewal. Renewal is achieved not only by repair and maintenance mechanisms but, importantly, by the process of cell division such that every time cells divide ageing-associated effects are diluted.}, } @article {pmid27816674, year = {2017}, author = {Shelton, DE and Leslie, MP and Michod, RE}, title = {Models of cell division initiation in Chlamydomonas: A challenge to the consensus view.}, journal = {Journal of theoretical biology}, volume = {412}, number = {}, pages = {186-197}, doi = {10.1016/j.jtbi.2016.10.018}, pmid = {27816674}, issn = {1095-8541}, mesh = {Cell Division/*physiology ; Chlamydomonas reinhardtii/*physiology ; *Models, Biological ; }, abstract = {We develop and compare two models for division initiation in cells of the unicellular green alga Chlamydomonas reinhardtii, a topic that has remained controversial in spite of years of empirical work. Achieving a better understanding of C. reinhardtii cell cycle regulation is important because this species is used in studies of fundamental eukaryotic cell features and in studies of the evolution of multicellularity. C. reinhardtii proliferates asexually by multiple fission, interspersing rapid rounds of symmetric division with prolonged periods of growth. Our Model 1 reflects major elements of the current consensus view on C. reinhardtii division initiation, with cells first growing to a specific size, then waiting for a particular time prior to division initiation. In Model 2, our proposed alternative, growing cells divide when they have reached a growth-rate-dependent target size. The two models imply a number of different empirical patterns. We highlight these differences alongside published data, which currently fall short of unequivocally distinguishing these differences in predicted cell behavior. Nevertheless, several lines of evidence are suggestive of more Model 2-like behavior than Model 1-like behavior. Our specification of these models adds rigor to issues that have too often been worked out in relation to loose, verbal models and is directly relevant to future development of informative experiments.}, } @article {pmid27815194, year = {2017}, author = {Fletcher, E and Feizi, A and Bisschops, MMM and Hallström, BM and Khoomrung, S and Siewers, V and Nielsen, J}, title = {Evolutionary engineering reveals divergent paths when yeast is adapted to different acidic environments.}, journal = {Metabolic engineering}, volume = {39}, number = {}, pages = {19-28}, doi = {10.1016/j.ymben.2016.10.010}, pmid = {27815194}, issn = {1096-7184}, mesh = {Acids/*chemistry ; Adaptation, Physiological/*genetics ; Directed Molecular Evolution/*methods ; Gene Expression Regulation, Fungal/genetics ; Genetic Enhancement/methods ; *Hydrogen-Ion Concentration ; Saccharomyces cerevisiae/*chemistry/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Stress, Physiological/*genetics ; }, abstract = {Tolerance of yeast to acid stress is important for many industrial processes including organic acid production. Therefore, elucidating the molecular basis of long term adaptation to acidic environments will be beneficial for engineering production strains to thrive under such harsh conditions. Previous studies using gene expression analysis have suggested that both organic and inorganic acids display similar responses during short term exposure to acidic conditions. However, biological mechanisms that will lead to long term adaptation of yeast to acidic conditions remains unknown and whether these mechanisms will be similar for tolerance to both organic and inorganic acids is yet to be explored. We therefore evolved Saccharomyces cerevisiae to acquire tolerance to HCl (inorganic acid) and to 0.3M L-lactic acid (organic acid) at pH 2.8 and then isolated several low pH tolerant strains. Whole genome sequencing and RNA-seq analysis of the evolved strains revealed different sets of genome alterations suggesting a divergence in adaptation to these two acids. An altered sterol composition and impaired iron uptake contributed to HCl tolerance whereas the formation of a multicellular morphology and rapid lactate degradation was crucial for tolerance to high concentrations of lactic acid. Our findings highlight the contribution of both the selection pressure and nature of the acid as a driver for directing the evolutionary path towards tolerance to low pH. The choice of carbon source was also an important factor in the evolutionary process since cells evolved on two different carbon sources (raffinose and glucose) generated a different set of mutations in response to the presence of lactic acid. Therefore, different strategies are required for a rational design of low pH tolerant strains depending on the acid of interest.}, } @article {pmid27814692, year = {2016}, author = {Schilde, C and Lawal, HM and Noegel, AA and Eichinger, L and Schaap, P and Glöckner, G}, title = {A set of genes conserved in sequence and expression traces back the establishment of multicellularity in social amoebae.}, journal = {BMC genomics}, volume = {17}, number = {1}, pages = {871}, pmid = {27814692}, issn = {1471-2164}, mesh = {Amoeba/classification/*genetics ; Conserved Sequence ; *Evolution, Molecular ; *Gene Expression ; Gene Expression Profiling ; Gene Knockout Techniques ; Gene Ontology ; Genome ; Mutation ; Phylogeny ; }, abstract = {BACKGROUND: The developmental cycle of Dictyostelid amoebae represents an early form of multicellularity with cell type differentiation. Mutant studies in the model Dictyostelium discoideum revealed that its developmental program integrates the actions of genes involved in signal transduction, adhesion, motility, autophagy and cell wall and matrix biosynthesis. However, due to functional redundancy and fail safe options not required in the laboratory, this single organism approach cannot capture all essential genes. To understand how multicellular organisms evolved, it is essential to recognize both the conserved core features of their developmental programs and the gene modifications that instigated phenotypic innovation. For complex organisms, such as animals, this is not within easy reach, but it is feasible for less complex forms, such as the Dictyostelid social amoebas.

RESULTS: We compared global profiles of gene expression during the development of four social amoebae species that represent 600 mya of Dictyostelia evolution, and identified orthologous conserved genes with similar developmental up-regulation of expression using three different methods. For validation, we disrupted five genes of this core set and examined the phenotypic consequences.

CONCLUSION: At least 71 of the developmentally regulated genes that were identified with all methods were likely to be already present in the last ancestor of all Dictyostelia. The lack of phenotypic changes in null mutants indicates that even highly conserved genes either participate in functionally redundant pathways or are necessary for developmental progression under adverse, non-standard laboratory conditions. Both mechanisms provide robustness to the developmental program, but impose a limit on the information that can be obtained from deleting single genes.}, } @article {pmid27809783, year = {2016}, author = {Pauli, T and Vedder, L and Dowling, D and Petersen, M and Meusemann, K and Donath, A and Peters, RS and Podsiadlowski, L and Mayer, C and Liu, S and Zhou, X and Heger, P and Wiehe, T and Hering, L and Mayer, G and Misof, B and Niehuis, O}, title = {Transcriptomic data from panarthropods shed new light on the evolution of insulator binding proteins in insects : Insect insulator proteins.}, journal = {BMC genomics}, volume = {17}, number = {1}, pages = {861}, pmid = {27809783}, issn = {1471-2164}, mesh = {Animals ; Arthropods/*genetics ; DNA-Binding Proteins/*genetics ; Drosophila melanogaster/genetics ; Enhancer Elements, Genetic ; *Evolution, Molecular ; Gene Expression Profiling ; *Insulator Elements ; Phylogeny ; *Transcriptome ; }, abstract = {BACKGROUND: Body plan development in multi-cellular organisms is largely determined by homeotic genes. Expression of homeotic genes, in turn, is partially regulated by insulator binding proteins (IBPs). While only a few enhancer blocking IBPs have been identified in vertebrates, the common fruit fly Drosophila melanogaster harbors at least twelve different enhancer blocking IBPs. We screened recently compiled insect transcriptomes from the 1KITE project and genomic and transcriptomic data from public databases, aiming to trace the origin of IBPs in insects and other arthropods.

RESULTS: Our study shows that the last common ancestor of insects (Hexapoda) already possessed a substantial number of IBPs. Specifically, of the known twelve insect IBPs, at least three (i.e., CP190, Su(Hw), and CTCF) already existed prior to the evolution of insects. Furthermore we found GAF orthologs in early branching insect orders, including Zygentoma (silverfish and firebrats) and Diplura (two-pronged bristletails). Mod(mdg4) is most likely a derived feature of Neoptera, while Pita is likely an evolutionary novelty of holometabolous insects. Zw5 appears to be restricted to schizophoran flies, whereas BEAF-32, ZIPIC and the Elba complex, are probably unique to the genus Drosophila. Selection models indicate that insect IBPs evolved under neutral or purifying selection.

CONCLUSIONS: Our results suggest that a substantial number of IBPs either pre-date the evolution of insects or evolved early during insect evolution. This suggests an evolutionary history of insulator binding proteins in insects different to that previously thought. Moreover, our study demonstrates the versatility of the 1KITE transcriptomic data for comparative analyses in insects and other arthropods.}, } @article {pmid27809776, year = {2016}, author = {Liu, Z and Ji, Z and Wang, G and Chao, T and Hou, L and Wang, J}, title = {Genome-wide analysis reveals signatures of selection for important traits in domestic sheep from different ecoregions.}, journal = {BMC genomics}, volume = {17}, number = {1}, pages = {863}, pmid = {27809776}, issn = {1471-2164}, mesh = {Animals ; Breeding ; Evolution, Molecular ; Gene Ontology ; Genetics, Population ; *Genome ; *Genome-Wide Association Study ; *Genomics/methods ; High-Throughput Nucleotide Sequencing ; Mutation ; Phenotype ; Polymorphism, Single Nucleotide ; *Quantitative Trait, Heritable ; Reproduction/genetics ; *Selection, Genetic ; Sheep, Domestic/*genetics ; }, abstract = {BACKGROUND: Throughout a long period of adaptation and selection, sheep have thrived in a diverse range of ecological environments. Mongolian sheep is the common ancestor of the Chinese short fat-tailed sheep. Migration to different ecoregions leads to changes in selection pressures and results in microevolution. Mongolian sheep and its subspecies differ in a number of important traits, especially reproductive traits. Genome-wide intraspecific variation is required to dissect the genetic basis of these traits.

RESULTS: This research resequenced 3 short fat-tailed sheep breeds with a 43.2-fold coverage of the sheep genome. We report more than 17 million single nucleotide polymorphisms and 2.9 million indels and identify 143 genomic regions with reduced pooled heterozygosity or increased genetic distance to each other breed that represent likely targets for selection during the migration. These regions harbor genes related to developmental processes, cellular processes, multicellular organismal processes, biological regulation, metabolic processes, reproduction, localization, growth and various components of the stress responses. Furthermore, we examined the haplotype diversity of 3 genomic regions involved in reproduction and found significant differences in TSHR and PRL gene regions among 8 sheep breeds.

CONCLUSIONS: Our results provide useful genomic information for identifying genes or causal mutations associated with important economic traits in sheep and for understanding the genetic basis of adaptation to different ecological environments.}, } @article {pmid27807261, year = {2016}, author = {Regenberg, B and Hanghøj, KE and Andersen, KS and Boomsma, JJ}, title = {Clonal yeast biofilms can reap competitive advantages through cell differentiation without being obligatorily multicellular.}, journal = {Proceedings. Biological sciences}, volume = {283}, number = {1842}, pages = {}, pmid = {27807261}, issn = {1471-2954}, mesh = {*Biofilms ; *Cell Differentiation ; Membrane Glycoproteins/*physiology ; Saccharomyces cerevisiae/*cytology/growth & development ; Saccharomyces cerevisiae Proteins/*physiology ; }, abstract = {How differentiation between cell types evolved is a fundamental question in biology, but few studies have explored single-gene phenotypes that mediate first steps towards division of labour with selective advantage for groups of cells. Here, we show that differential expression of the FLO11 gene produces stable fractions of Flo11[+] and Flo11[-] cells in clonal Saccharomyces cerevisiae biofilm colonies on medium with intermediate viscosity. Differentiated Flo11[+/-] colonies, consisting of adhesive and non-adhesive cells, obtain a fourfold growth advantage over undifferentiated colonies by overgrowing glucose resources before depleting them, rather than depleting them while they grow as undifferentiated Flo11[-] colonies do. Flo11[+/-] colonies maintain their structure and differentiated state by switching non-adhesive cells to adhesive cells with predictable probability. Mixtures of Flo11[+] and Flo11[-] cells from mutant strains that are unable to use this epigenetic switch mechanism produced neither integrated colonies nor growth advantages, so the condition-dependent selective advantages of differentiated FLO11 expression can only be reaped by clone-mate cells. Our results show that selection for cell differentiation in clonal eukaryotes can evolve before the establishment of obligate undifferentiated multicellularity, and without necessarily leading to more advanced organizational complexity.}, } @article {pmid27806710, year = {2016}, author = {Dueck, A and Evers, M and Henz, SR and Unger, K and Eichner, N and Merkl, R and Berezikov, E and Engelmann, JC and Weigel, D and Wenzl, S and Meister, G}, title = {Gene silencing pathways found in the green alga Volvox carteri reveal insights into evolution and origins of small RNA systems in plants.}, journal = {BMC genomics}, volume = {17}, number = {1}, pages = {853}, pmid = {27806710}, issn = {1471-2164}, mesh = {Argonaute Proteins/metabolism ; Base Sequence ; Binding Sites ; Computational Biology/methods ; DNA Transposable Elements ; *Evolution, Molecular ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Gene Silencing ; MicroRNAs/genetics ; Molecular Sequence Annotation ; Nucleotide Motifs ; Protein Binding ; RNA, Small Untranslated/*genetics ; Reproducibility of Results ; Transcriptome ; Volvox/*genetics ; }, abstract = {BACKGROUND: Volvox carteri (V. carteri) is a multicellular green alga used as model system for the evolution of multicellularity. So far, the contribution of small RNA pathways to these phenomena is not understood. Thus, we have sequenced V. carteri Argonaute 3 (VcAGO3)-associated small RNAs from different developmental stages.

RESULTS: Using this functional approach, we define the Volvox microRNA (miRNA) repertoire and show that miRNAs are not conserved in the closely related unicellular alga Chlamydomonas reinhardtii. Furthermore, we find that miRNAs are differentially expressed during different life stages of V. carteri. In addition to miRNAs, transposon-associated small RNAs or phased siRNA loci, which are common in higher land plants, are highly abundant in Volvox as well. Transposons not only give rise to miRNAs and other small RNAs, they are also targets of small RNAs.

CONCLUSION: Our analyses reveal a surprisingly complex small RNA network in Volvox as elaborate as in higher land plants. At least the identified VcAGO3-associated miRNAs are not conserved in C. reinhardtii suggesting fast evolution of small RNA systems. Thus, distinct small RNAs may contribute to multicellularity and also division of labor in reproductive and somatic cells.}, } @article {pmid27796199, year = {2016}, author = {Trecartin, A and Danopoulos, S and Spurrier, R and Knaneh-Monem, H and Hiatt, M and Driscoll, B and Hochstim, C and Al-Alam, D and Grikscheit, TC}, title = {Establishing Proximal and Distal Regional Identities in Murine and Human Tissue-Engineered Lung and Trachea.}, journal = {Tissue engineering. Part C, Methods}, volume = {22}, number = {11}, pages = {1049-1057}, pmid = {27796199}, issn = {1937-3392}, mesh = {Animals ; *Cell Lineage ; *Cell Proliferation ; Cells, Cultured ; Humans ; Lung/*cytology/physiology ; Lung Transplantation ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Tissue Engineering/*methods ; Trachea/cytology/*metabolism ; *Wound Healing ; }, abstract = {The cellular and molecular mechanisms that underpin regeneration of the human lung are unknown, and the study of lung repair has been impeded by the necessity for reductionist models that may exclude key components. We hypothesized that multicellular epithelial and mesenchymal cell clusters or lung organoid units (LuOU) could be transplanted to recapitulate proximal and distal cellular structures of the native lung and airways. Transplantation of LuOU resulted in the growth of tissue-engineered lung (TELu) that contained the necessary cell types consistent with native adult lung tissue and demonstrated proliferative cells at 2 and 4 weeks. This technique recapitulated important elements of both mouse and human lungs featuring key components of both the proximal and distal lung regions. When LuOU were generated from whole lung, TELu contained key epithelial and mesenchymal cell types, and the origin of the cells was traced from both Actin[GFP] and SPC[GFP] donors to indicate that the cells in TELu were derived from the transplanted LuOU. Alveolar epithelial type 2 cells (AEC2s), club cells, ciliated cells marked by beta-tubulin IV, alveolar epithelial type I cells, Sox-2-positive proximal airway progenitors, p63-positive basal cells, and CGRP-positive pulmonary neuroendocrine cells were identified in the TELu. The mesenchymal components of peribronchial smooth muscle and nerve were identified with a CD31-positive donor endothelial cell contribution to TELu vasculature. TELu successfully grew from postnatal tissues from whole murine and human lung, distal murine lung, as well as murine and human trachea. These data support a model of postnatal lung regeneration containing the diverse cell types present in the entirety of the respiratory tract.}, } @article {pmid27790999, year = {2016}, author = {Chen, X and Köllner, TG and Jia, Q and Norris, A and Santhanam, B and Rabe, P and Dickschat, JS and Shaulsky, G and Gershenzon, J and Chen, F}, title = {Terpene synthase genes in eukaryotes beyond plants and fungi: Occurrence in social amoebae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {43}, pages = {12132-12137}, pmid = {27790999}, issn = {1091-6490}, support = {P01 HD039691/HD/NICHD NIH HHS/United States ; R35 GM118016/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Alkyl and Aryl Transferases/classification/*genetics/metabolism ; Biological Evolution ; Cloning, Molecular ; Dictyostelium/classification/enzymology/*genetics ; Escherichia coli/genetics/metabolism ; Gene Expression ; Gene Expression Regulation, Developmental ; *Genome, Protozoan ; Isoenzymes/classification/genetics/metabolism ; Multigene Family ; *Phylogeny ; Protozoan Proteins/classification/*genetics/metabolism ; Recombinant Proteins/genetics/metabolism ; Terpenes/*metabolism ; Volatilization ; }, abstract = {Terpenes are structurally diverse natural products involved in many ecological interactions. The pivotal enzymes for terpene biosynthesis, terpene synthases (TPSs), had been described only in plants and fungi in the eukaryotic domain. In this report, we systematically analyzed the genome sequences of a broad range of nonplant/nonfungus eukaryotes and identified putative TPS genes in six species of amoebae, five of which are multicellular social amoebae from the order of Dictyosteliida. A phylogenetic analysis revealed that amoebal TPSs are evolutionarily more closely related to fungal TPSs than to bacterial TPSs. The social amoeba Dictyostelium discoideum was selected for functional study of the identified TPSs. D. discoideum grows as a unicellular organism when food is abundant and switches from vegetative growth to multicellular development upon starvation. We found that expression of most D. discoideum TPS genes was induced during development. Upon heterologous expression, all nine TPSs from D. discoideum showed sesquiterpene synthase activities. Some also exhibited monoterpene and/or diterpene synthase activities. Direct measurement of volatile terpenes in cultures of D. discoideum revealed essentially no emission at an early stage of development. In contrast, a bouquet of terpenes, dominated by sesquiterpenes including β-barbatene and (E,E)-α-farnesene, was detected at the middle and late stages of development, suggesting a development-specific function of volatile terpenes in D. discoideum. The patchy distribution of TPS genes in the eukaryotic domain and the evidence for TPS function in D. discoideum indicate that the TPS genes mediate lineage-specific adaptations.}, } @article {pmid27782327, year = {2016}, author = {Elvington, M and Liszewski, MK and Atkinson, JP}, title = {Evolution of the complement system: from defense of the single cell to guardian of the intravascular space.}, journal = {Immunological reviews}, volume = {274}, number = {1}, pages = {9-15}, pmid = {27782327}, issn = {1600-065X}, support = {T32 AR007279/AR/NIAMS NIH HHS/United States ; R01 GM099111/GM/NIGMS NIH HHS/United States ; P30 AR048335/AR/NIAMS NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; R01 AI041592/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Blood Vessels/*physiology ; Cell Membrane/metabolism ; Complement Activation ; Complement C3/*immunology ; Extracellular Space ; Humans ; Immunity ; Inflammation/*immunology ; Intracellular Space ; Liver/*physiology ; Models, Immunological ; }, abstract = {The complement system is an evolutionarily ancient component of immunity that revolves around the central component C3. With the recent description of intracellular C3 stores in many types of human cells, our view of the complement system has expanded. In this article, we hypothesize that a primitive version of C3 comprised the first element of the original complement system and initially functioned intracellularly and on the membrane of single-celled organisms. With increasing specialization and multicellularity, C3 evolved a secretory capacity that allowed it to play a protective role in the interstitial space. Upon development of a pumped circulatory system, C3 was synthesized in large amounts and secreted by the liver to protect the intravascular space. Recent discoveries of intracellular C3 activation, a C3-based recycling pathway and C3 being a driver and programmer of cell metabolism suggest that the complement system utilizes C3 to guard not only extracellular but also the intracellular environment. We predict that the major functions of C3 in all four locations (i.e. intracellular, membrane, interstitium and circulation) are similar: opsonization, membrane perturbation, triggering inflammation, and metabolic reprogramming.}, } @article {pmid27782144, year = {2016}, author = {Balla, KM and Luallen, RJ and Bakowski, MA and Troemel, ER}, title = {Cell-to-cell spread of microsporidia causes Caenorhabditis elegans organs to form syncytia.}, journal = {Nature microbiology}, volume = {1}, number = {11}, pages = {16144}, pmid = {27782144}, issn = {2058-5276}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 GM114139/GM/NIGMS NIH HHS/United States ; T32 GM007240/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/cytology/*microbiology/physiology ; Cytoplasm/microbiology ; Giant Cells/*microbiology ; *Host-Pathogen Interactions ; Intestines/microbiology ; Microsporidia/classification/growth & development/*physiology ; Muscles/microbiology ; Phylogeny ; }, abstract = {The growth of pathogens is dictated by their interactions with the host environment[1]. Obligate intracellular pathogens undergo several cellular decisions as they progress through their life cycles inside host cells[2]. We have studied this process for microsporidian species in the genus Nematocida as they grew and developed inside their co-evolved animal host, Caenorhabditis elegans[3-5]. We found that microsporidia can restructure multicellular host tissues into a single contiguous multinucleate cell. In particular, we found that all three Nematocida species we studied were able to spread across the cells of C. elegans tissues before forming spores, with two species causing syncytial formation in the intestine and one species causing syncytial formation in the muscle. We also found that the decision to switch from replication to differentiation in Nematocida parisii was altered by the density of infection, suggesting that environmental cues influence the dynamics of the pathogen life cycle. These findings show how microsporidia can maximize the use of host space for growth and that environmental cues in the host can regulate a developmental switch in the pathogen.}, } @article {pmid27746046, year = {2016}, author = {Sebé-Pedrós, A and Peña, MI and Capella-Gutiérrez, S and Antó, M and Gabaldón, T and Ruiz-Trillo, I and Sabidó, E}, title = {High-Throughput Proteomics Reveals the Unicellular Roots of Animal Phosphosignaling and Cell Differentiation.}, journal = {Developmental cell}, volume = {39}, number = {2}, pages = {186-197}, doi = {10.1016/j.devcel.2016.09.019}, pmid = {27746046}, issn = {1878-1551}, support = {ERC-2012-CO-616960//European Research Council/International ; }, mesh = {Animals ; *Cell Differentiation ; Eukaryota/cytology/metabolism ; Evolution, Molecular ; Phosphorylation ; Phylogeny ; Protein Kinases/metabolism ; Proteome/metabolism ; Proteomics/*methods ; RNA, Messenger/genetics/metabolism ; *Signal Transduction ; Time Factors ; Transcription Factors/metabolism ; }, abstract = {Cell-specific regulation of protein levels and activity is essential for the distribution of functions among multiple cell types in animals. The finding that many genes involved in these regulatory processes have a premetazoan origin raises the intriguing possibility that the mechanisms required for spatially regulated cell differentiation evolved prior to the appearance of animals. Here, we use high-throughput proteomics in Capsaspora owczarzaki, a close unicellular relative of animals, to characterize the dynamic proteome and phosphoproteome profiles of three temporally distinct cell types in this premetazoan species. We show that life-cycle transitions are linked to extensive proteome and phosphoproteome remodeling and that they affect key genes involved in animal multicellularity, such as transcription factors and tyrosine kinases. The observation of shared features between Capsaspora and metazoans indicates that elaborate and conserved phosphosignaling and proteome regulation supported temporal cell-type differentiation in the unicellular ancestor of animals.}, } @article {pmid27775817, year = {2017}, author = {Goldring, C and Antoine, DJ and Bonner, F and Crozier, J and Denning, C and Fontana, RJ and Hanley, NA and Hay, DC and Ingelman-Sundberg, M and Juhila, S and Kitteringham, N and Silva-Lima, B and Norris, A and Pridgeon, C and Ross, JA and Young, RS and Tagle, D and Tornesi, B and van de Water, B and Weaver, RJ and Zhang, F and Park, BK}, title = {Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury.}, journal = {Hepatology (Baltimore, Md.)}, volume = {65}, number = {2}, pages = {710-721}, pmid = {27775817}, issn = {1527-3350}, support = {G0700654/MRC_/Medical Research Council/United Kingdom ; MR/K017047/1/MRC_/Medical Research Council/United Kingdom ; SP/15/9/31605/BHF_/British Heart Foundation/United Kingdom ; PG/09/027/27141/BHF_/British Heart Foundation/United Kingdom ; NC/C013105/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; PG/14/59/31000/BHF_/British Heart Foundation/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; BB/E006159/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; NC/C013202/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; MR/K026666/1/MRC_/Medical Research Council/United Kingdom ; NC/K000225/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; BBS/B/06164/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/L006758/1/MRC_/Medical Research Council/United Kingdom ; MR/L022974/1/MRC_/Medical Research Council/United Kingdom ; G0801098/MRC_/Medical Research Council/United Kingdom ; BB/G021821/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; G113/30/MRC_/Medical Research Council/United Kingdom ; U01 DK065184/DK/NIDDK NIH HHS/United States ; }, mesh = {Cells, Cultured/drug effects ; Chemical and Drug Induced Liver Injury/*diagnosis ; Drug-Related Side Effects and Adverse Reactions/*diagnosis ; Hepatocytes/*drug effects/metabolism ; Humans ; In Vitro Techniques ; Pluripotent Stem Cells/*drug effects/metabolism ; Predictive Value of Tests ; Sensitivity and Specificity ; *Toxicity Tests ; }, abstract = {Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug-induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalized toxicology to determine interindividual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug-induced liver injury means that no current single-cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human drug-induced liver injury. Nevertheless, a single-cell model of a human hepatocyte which emulates key features of a hepatocyte is likely to be valuable in assessing potential chemical risk; furthermore, understanding how to generate a relevant hepatocyte will also be critical to efforts to build complex multicellular models of the liver. Currently, hepatocyte-like cells differentiated from stem cells still fall short of recapitulating the full mature hepatocellular phenotype. Therefore, we convened a number of experts from the areas of preclinical and clinical hepatotoxicity and safety assessment, from industry, academia, and regulatory bodies, to specifically explore the application of stem cells in hepatotoxicity safety assessment and to make recommendations for the way forward. In this short review, we particularly discuss the importance of benchmarking stem cell-derived hepatocyte-like cells to their terminally differentiated human counterparts using defined phenotyping, to make sure the cells are relevant and comparable between labs, and outline why this process is essential before the cells are introduced into chemical safety assessment. (Hepatology 2017;65:710-721).}, } @article {pmid27751905, year = {2017}, author = {Woyda-Ploszczyca, AM and Jarmuszkiewicz, W}, title = {The conserved regulation of mitochondrial uncoupling proteins: From unicellular eukaryotes to mammals.}, journal = {Biochimica et biophysica acta. Bioenergetics}, volume = {1858}, number = {1}, pages = {21-33}, doi = {10.1016/j.bbabio.2016.10.003}, pmid = {27751905}, issn = {0005-2728}, mesh = {Aldehydes/*metabolism ; Animals ; Eukaryota/*metabolism ; Fatty Acids, Nonesterified/*metabolism ; Mammals/*metabolism ; Mitochondrial Uncoupling Proteins/*metabolism ; Purine Nucleotides/*metabolism ; Ubiquinone/*metabolism ; }, abstract = {Uncoupling proteins (UCPs) belong to the mitochondrial anion carrier protein family and mediate regulated proton leak across the inner mitochondrial membrane. Free fatty acids, aldehydes such as hydroxynonenal, and retinoids activate UCPs. However, there are some controversies about the effective action of retinoids and aldehydes alone; thus, only free fatty acids are commonly accepted positive effectors of UCPs. Purine nucleotides such as GTP inhibit UCP-mediated mitochondrial proton leak. In turn, membranous coenzyme Q may play a role as a redox state-dependent metabolic sensor that modulates the complete activation/inhibition of UCPs. Such regulation has been observed for UCPs in microorganisms, plant and animal UCP1 homologues, and UCP1 in mammalian brown adipose tissue. The origin of UCPs is still under debate, but UCP homologues have been identified in all systematic groups of eukaryotes. Despite the differing levels of amino acid/DNA sequence similarities, functional studies in unicellular and multicellular organisms, from amoebae to mammals, suggest that the mechanistic regulation of UCP activity is evolutionarily well conserved. This review focuses on the regulatory feedback loops of UCPs involving free fatty acids, aldehydes, retinoids, purine nucleotides, and coenzyme Q (particularly its reduction level), which may derive from the early stages of evolution as UCP first emerged.}, } @article {pmid27663234, year = {2017}, author = {Kadam, AA and Jubin, T and Mir, HA and Begum, R}, title = {Potential role of Apoptosis Inducing Factor in evolutionarily significant eukaryote, Dictyostelium discoideum survival.}, journal = {Biochimica et biophysica acta. General subjects}, volume = {1861}, number = {1 Pt A}, pages = {2942-2955}, doi = {10.1016/j.bbagen.2016.09.021}, pmid = {27663234}, issn = {0304-4165}, mesh = {Adenosine Triphosphate/metabolism ; Annexin A5/metabolism ; Apoptosis Inducing Factor/*metabolism ; *Biological Evolution ; Calcium/metabolism ; Cell Cycle/drug effects ; Cell Death/drug effects ; Cell Shape/drug effects ; Cytosol/drug effects/metabolism ; Dictyostelium/*cytology/growth & development/*metabolism/ultrastructure ; Down-Regulation/drug effects ; Flow Cytometry ; Fluorescein-5-isothiocyanate/metabolism ; Fluorometry ; Glucose/pharmacology ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/drug effects/metabolism ; Models, Biological ; NAD/metabolism ; Oxidative Stress/drug effects ; Propidium/metabolism ; Protein Transport/drug effects ; RNA, Antisense/metabolism ; Reactive Oxygen Species/metabolism ; Staining and Labeling ; }, abstract = {Apoptosis Inducing Factor (AIF), a phylogenetically conserved mitochondrial inter-membrane space flavoprotein has an important role in caspase independent cell death. Nevertheless, AIF is also essential for cell survival. It is required for mitochondrial organization and energy metabolism. Upon apoptotic stimulation, AIF induces DNA fragmentation after its mitochondrio-nuclear translocation. Although it executes critical cellular functions in a coordinated manner, the exact mechanism still remains obscure. The present study aims to understand AIF's role in cell survival, growth and development by its down-regulation in an interesting unicellular eukaryote, D. discoideum which exhibits multicellularity upon starvation. Constitutive AIF down-regulated (dR) cells exhibited slower growth and delayed developmental morphogenesis. Also, constitutive AIF dR cells manifested high intracellular ROS, oxidative DNA damage and calcium levels with lower ATP content. Interestingly, constitutive AIF dR cells showed amelioration in cell growth upon antioxidant treatment, strengthening its role as ROS regulator. Under oxidative stress, AIF dR cells showed early mitochondrial membrane depolarization followed by AIF translocation from mitochondria to nucleus and exhibited necrotic cell death as compared to paraptoptic cell death of control cells. Thus, the results of this study provide an exemplar where AIF is involved in growth and development by regulating ROS levels and maintaining mitochondrial function in D. discoideum, an evolutionarily significant model organism exhibiting caspase independent apoptosis.}, } @article {pmid27718356, year = {2016}, author = {Carmell, MA and Dokshin, GA and Skaletsky, H and Hu, YC and van Wolfswinkel, JC and Igarashi, KJ and Bellott, DW and Nefedov, M and Reddien, PW and Enders, GC and Uversky, VN and Mello, CC and Page, DC}, title = {A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes.}, journal = {eLife}, volume = {5}, number = {}, pages = {}, pmid = {27718356}, issn = {2050-084X}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Antigens, Nuclear/*genetics/metabolism ; Caenorhabditis elegans/genetics/growth & development ; Eukaryota/genetics ; *Evolution, Molecular ; Gene Expression Regulation/genetics ; Genome/genetics ; Genomics ; Germ Cells/growth & development/*metabolism ; Meiosis/genetics ; Phylogeny ; Reproduction/*genetics ; }, abstract = {The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya - either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells of diverse multicellular animals. Studies of Gcna-mutant C. elegans and mice indicate that GCNA has functioned in reproduction for at least 600 million years. Homology to IDR-containing proteins implicated in DNA damage repair suggests that GCNA proteins may protect the genomic integrity of cells carrying a heritable genome.}, } @article {pmid27751769, year = {2016}, author = {Gadahi, JA and Ehsan, M and Wang, S and Zhang, Z and Wang, Y and Yan, R and Song, X and Xu, L and Li, X}, title = {Recombinant protein of Haemonchus contortus 14-3-3 isoform 2 (rHcftt-2) decreased the production of IL-4 and suppressed the proliferation of goat PBMCs in vitro.}, journal = {Experimental parasitology}, volume = {171}, number = {}, pages = {57-66}, doi = {10.1016/j.exppara.2016.10.014}, pmid = {27751769}, issn = {1090-2449}, mesh = {Amino Acid Sequence ; Animals ; Antibodies, Helminth/biosynthesis ; Cell Proliferation/drug effects ; Cloning, Molecular ; DNA, Complementary/metabolism ; DNA, Helminth/metabolism ; Dose-Response Relationship, Drug ; Female ; Goats ; Haemonchus/chemistry/genetics/*immunology ; Helminth Proteins/chemistry/*immunology/pharmacology ; Interleukin-4/*immunology/metabolism ; Neutrophils/*immunology/metabolism ; Nitric Oxide/metabolism ; Phylogeny ; Polymerase Chain Reaction ; Protein Isoforms/immunology/pharmacology ; RNA, Helminth/genetics/isolation & purification ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins/*immunology/pharmacology ; Sequence Alignment ; }, abstract = {14-3-3 proteins have been found to be an excreted/secreted antigen and assumed to be released into the host-parasite interface and described in several unicellular and multicellular parasites. However, little is known about the immunomodulatory effects of H. controtus 14-3-3 protein on host cell. In present study, 14-3-3 isoform 2 gene, designated as Hcftt-2, was amplified by reverse transcription-polymerase chain reaction (RT-PCR) from the adult H. contortus cDNA and cloned into expression plasmid pET32a (+) and expression of the recombinant protein (rHcftt-2) was induced by IPTG. Binding activity of rHcftt-2 to goat peripheral blood mononuclear cells (PBMCs) was confirmed by immunofluorescence assay (IFA) and modulatory effects on cytokine production, cell proliferation, cell migration and nitric oxide (NO) production were observed by co-incubation of rHcftt-2 with goat PBMCs. Sequence analysis showed that it had significant homology with the known 14-3-3 protein isoform 2. Results of IFA revealed that, the rHcftt-2 was bound to the cell surface. We found that, the productions of IL10, IL-17, IFN-γ and cell migration of PBMCs were increased after the cells were incubated with rHCftt-2. However, the productions of IL-4, NO and cell proliferation of the PBMCs were significantly decreased in dose depended manner. Our results showed that the Hcftt-2 played important suppressive regulatory effects on the goat PBMCs.}, } @article {pmid27738200, year = {2016}, author = {Spatafora, JW and Chang, Y and Benny, GL and Lazarus, K and Smith, ME and Berbee, ML and Bonito, G and Corradi, N and Grigoriev, I and Gryganskyi, A and James, TY and O'Donnell, K and Roberson, RW and Taylor, TN and Uehling, J and Vilgalys, R and White, MM and Stajich, JE}, title = {A phylum-level phylogenetic classification of zygomycete fungi based on genome-scale data.}, journal = {Mycologia}, volume = {108}, number = {5}, pages = {1028-1046}, pmid = {27738200}, issn = {0027-5514}, support = {S10 OD016290/OD/NIH HHS/United States ; }, mesh = {Fungi/*classification/*genetics ; *Genome, Fungal ; *Phylogeny ; }, abstract = {Zygomycete fungi were classified as a single phylum, Zygomycota, based on sexual reproduction by zygospores, frequent asexual reproduction by sporangia, absence of multicellular sporocarps, and production of coenocytic hyphae, all with some exceptions. Molecular phylogenies based on one or a few genes did not support the monophyly of the phylum, however, and the phylum was subsequently abandoned. Here we present phylogenetic analyses of a genome-scale data set for 46 taxa, including 25 zygomycetes and 192 proteins, and we demonstrate that zygomycetes comprise two major clades that form a paraphyletic grade. A formal phylogenetic classification is proposed herein and includes two phyla, six subphyla, four classes and 16 orders. On the basis of these results, the phyla Mucoromycota and Zoopagomycota are circumscribed. Zoopagomycota comprises Entomophtoromycotina, Kickxellomycotina and Zoopagomycotina; it constitutes the earliest diverging lineage of zygomycetes and contains species that are primarily parasites and pathogens of small animals (e.g. amoeba, insects, etc.) and other fungi, i.e. mycoparasites. Mucoromycota comprises Glomeromycotina, Mortierellomycotina, and Mucoromycotina and is sister to Dikarya. It is the more derived clade of zygomycetes and mainly consists of mycorrhizal fungi, root endophytes, and decomposers of plant material. Evolution of trophic modes, morphology, and analysis of genome-scale data are discussed.}, } @article {pmid27737633, year = {2016}, author = {Lumsden, AL and Young, RL and Pezos, N and Keating, DJ}, title = {Huntingtin-associated protein 1: Eutherian adaptation from a TRAK-like protein, conserved gene promoter elements, and localization in the human intestine.}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {214}, pmid = {27737633}, issn = {1471-2148}, mesh = {Animals ; Base Sequence ; Binding Sites ; Caenorhabditis elegans/genetics ; Conserved Sequence/*genetics ; Humans ; Intestinal Mucosa/*metabolism ; Mammals/*genetics ; Mitochondria/genetics ; Multigene Family ; Nerve Tissue Proteins/*metabolism ; Nucleotide Motifs/genetics ; Phylogeny ; *Promoter Regions, Genetic ; Protein Binding/genetics ; Protein Domains ; Protein Transport ; Reproducibility of Results ; Sequence Homology, Nucleic Acid ; Serotonin/metabolism ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: Huntingtin-associated Protein 1 (HAP1) is expressed in neurons and endocrine cells, and is critical for postnatal survival in mice. HAP1 shares a conserved "HAP1_N" domain with TRAfficking Kinesin proteins TRAK1 and TRAK2 (vertebrate), Milton (Drosophila) and T27A3.1 (C. elegans). HAP1, TRAK1 and TRAK2 have a degree of common function, particularly regarding intracellular receptor trafficking. However, TRAK1, TRAK2 and Milton (which have a "Milt/TRAK" domain that is absent in human and rodent HAP1) differ in function to HAP1 in that they are mitochondrial transport proteins, while HAP1 has emerging roles in starvation response. We have investigated HAP1 function by examining its evolution, and upstream gene promoter sequences. We performed phylogenetic analyses of the HAP1_N domain family of proteins, incorporating HAP1 orthologues (identified by genomic synteny) from 5 vertebrate classes, and also searched the Dictyostelium proteome for a common ancestor. Computational analyses of mammalian HAP1 gene promoters were performed to identify phylogenetically conserved regulatory motifs.

RESULTS: We found that as recently as marsupials, HAP1 contained a Milt/TRAK domain and was more similar to TRAK1 and TRAK2 than to eutherian HAP1. The Milt/TRAK domain likely arose post multicellularity, as it was absent in the Dictyostelium proteome. It was lost from HAP1 in the eutherian lineage, and also from T27A3.1 in C. elegans. The HAP1 promoter from human, mouse, rat, rabbit, horse, dog, Tasmanian devil and opossum contained common sites for transcription factors involved in cell cycle, growth, differentiation, and stress response. A conserved arrangement of regulatory elements was identified, including sites for caudal-related homeobox transcription factors (CDX1 and CDX2), and myc-associated factor X (MAX) in the region of the TATA box. CDX1 and CDX2 are intestine-enriched factors, prompting investigation of HAP1 protein expression in the human duodenum. HAP1 was localized to singly dispersed mucosal cells, including a subset of serotonin-positive enterochromaffin cells.

CONCLUSION: We have identified eutherian HAP1 as an evolutionarily recent adaptation of a vertebrate TRAK protein-like ancestor, and found conserved CDX1/CDX2 and MAX transcription factor binding sites near the TATA box in mammalian HAP1 gene promoters. We also demonstrated that HAP1 is expressed in endocrine cells of the human gut.}, } @article {pmid27733125, year = {2016}, author = {Höhn, S and Hallmann, A}, title = {Distinct shape-shifting regimes of bowl-shaped cell sheets - embryonic inversion in the multicellular green alga Pleodorina.}, journal = {BMC developmental biology}, volume = {16}, number = {1}, pages = {35}, pmid = {27733125}, issn = {1471-213X}, mesh = {Biological Evolution ; Cell Division ; Chlorophyta/*cytology/*embryology/ultrastructure ; Microscopy, Electron, Transmission ; *Models, Biological ; *Morphogenesis ; Photogrammetry ; Time Factors ; }, abstract = {BACKGROUND: The multicellular volvocine alga Pleodorina is intermediate in organismal complexity between its unicellular relative, Chlamydomonas, and its multicellular relative, Volvox, which shows complete division of labor between different cell types. The volvocine green microalgae form a group of genera closely related to the genus Volvox within the order Volvocales (Chlorophyta). Embryos of multicellular volvocine algae consist of a cellular monolayer that, depending on the species, is either bowl-shaped or comprises a sphere. During embryogenesis, multicellular volvocine embryos turn their cellular monolayer right-side out to expose their flagella. This process is called 'inversion' and serves as simple model for epithelial folding in metazoa. While the development of spherical Volvox embryos has been the subject of detailed studies, the inversion process of bowl-shaped embryos is less well understood. Therefore, it has been unclear how the inversion of a sphere might have evolved from less complicated processes.

RESULTS: In this study we characterized the inversion of initially bowl-shaped embryos of the 64- to 128-celled volvocine species Pleodorina californica. We focused on the movement patterns of the cell sheet, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. The development of living embryos was recorded using time-lapse light microscopy. Moreover, fixed and sectioned embryos throughout inversion and at successive stages of development were analyzed by light and transmission electron microscopy. We generated three-dimensional models of the identified cell shapes including the localization of CBs.

CONCLUSIONS: In contrast to descriptions concerning volvocine embryos with lower cell numbers, the embryonic cells of P. californica undergo non-simultaneous and non-uniform cell shape changes. In P. californica, cell wedging in combination with a relocation of the CBs to the basal cell tips explains the curling of the cell sheet during inversion. In volvocine genera with lower organismal complexity, the cell shape changes and relocation of CBs are less pronounced in comparison to P. californica, while they are more pronounced in all members of the genus Volvox. This finding supports an increasing significance of the temporal and spatial regulation of cell shape changes and CB relocations with both increasing cell number and organismal complexity during evolution of differentiated multicellularity.}, } @article {pmid27697546, year = {2017}, author = {Cai, W and Zhang, K and Li, P and Zhu, L and Xu, J and Yang, B and Hu, X and Lu, Z and Chen, J}, title = {Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: An aging effect.}, journal = {Ageing research reviews}, volume = {34}, number = {}, pages = {77-87}, pmid = {27697546}, issn = {1872-9649}, support = {R01 NS089534/NS/NINDS NIH HHS/United States ; R01 NS095671/NS/NINDS NIH HHS/United States ; I01 BX002495/BX/BLRD VA/United States ; I01 RX000420/RX/RRD VA/United States ; R01 NS036736/NS/NINDS NIH HHS/United States ; R01 NS045048/NS/NINDS NIH HHS/United States ; }, mesh = {Aging/*physiology ; Blood-Brain Barrier ; *Brain/blood supply/pathology/physiopathology ; Humans ; *Neurodegenerative Diseases/pathology/physiopathology ; Neurovascular Coupling/*physiology ; *Stroke/pathology/physiopathology ; }, abstract = {Current understanding on the mechanisms of brain injury and neurodegeneration highlights an appreciation of multicellular interactions within the neurovascular unit (NVU), which include the evolution of blood-brain barrier (BBB) damage, neuronal cell death or degeneration, glial reaction, and immune cell infiltration. Aging is an important factor that influences the integrity of the NVU. The age-related physiological or pathological changes in the cellular components of the NVU have been shown to increase the vulnerability of the NVU to ischemia/reperfusion injury or neurodegeneration, and to result in deteriorated brain damage. This review describes the impacts of aging on each NVU component and discusses the mechanisms by which aging increases NVU sensitivity to stroke and neurodegenerative diseases. Prophylactic or therapeutic perspectives that may delay or diminish aging and thus prevent the incidence of these neurological disorders will also be reviewed.}, } @article {pmid27693864, year = {2016}, author = {Kuburich, NA and Adhikari, N and Hadwiger, JA}, title = {Acanthamoeba and Dictyostelium Use Different Foraging Strategies.}, journal = {Protist}, volume = {167}, number = {6}, pages = {511-525}, pmid = {27693864}, issn = {1618-0941}, support = {R15 GM097717/GM/NIGMS NIH HHS/United States ; }, mesh = {Acanthamoeba/classification/genetics/*physiology ; *Chemotaxis ; Dictyostelium/classification/genetics/*physiology ; Phylogeny ; Protozoan Proteins/genetics ; Signal Transduction ; }, abstract = {Amoeba often use cell movement as a mechanism to find food, such as bacteria, in their environment. The chemotactic movement of the soil amoeba Dictyostelium to folate or other pterin compounds released by bacteria is a well-documented foraging mechanism. Acanthamoeba can also feed on bacteria but relatively little is known about the mechanism(s) by which this amoeba locates bacteria. Acanthamoeba movement in the presence of folate or bacteria was analyzed in above agar assays and compared to that observed for Dictyostelium. The overall mobility of Acanthamoeba was robust like that of Dictyostelium but Acanthamoeba did not display a chemotactic response to folate. In the presence of bacteria, Acanthamoeba only showed a marginal bias in directed movement whereas Dictyostelium displayed a strong chemotactic response. A comparison of genomes revealed that Acanthamoeba and Dictyostelium share some similarities in G protein signaling components but that specific G proteins used in Dictyostelium chemotactic responses were not present in current Acanthamoeba genome sequence data. The results of this study suggest that Acanthamoeba does not use chemotaxis as the primary mechanism to find bacterial food sources and that the chemotactic responses of Dictyostelium to bacteria may have co-evolved with chemotactic responses that facilitate multicellular development.}, } @article {pmid27686422, year = {2017}, author = {Mills, DB and Canfield, DE}, title = {A trophic framework for animal origins.}, journal = {Geobiology}, volume = {15}, number = {2}, pages = {197-210}, doi = {10.1111/gbi.12216}, pmid = {27686422}, issn = {1472-4669}, mesh = {Animals ; *Biological Evolution ; Feeding Behavior ; *Heterotrophic Processes ; Organic Chemicals/*metabolism ; *Phagocytosis ; }, abstract = {Metazoans emerged in a microbial world and play a unique role in the biosphere as the only complex multicellular eukaryotes capable of phagocytosis. While the bodyplan and feeding mode of the last common metazoan ancestor remain unresolved, the earliest multicellular stem-metazoans likely subsisted on picoplankton (planktonic microbes 0.2-2 μm in diameter) and dissolved organic matter (DOM), similarly to modern sponges. Once multicellular stem-metazoans emerged, they conceivably modulated both the local availability of picoplankton, which they preferentially removed from the water column for feeding, and detrital particles 2-100 μm in diameter, which they expelled and deposited into the benthos as waste products. By influencing the availability of these heterotrophic food sources, the earliest multicellular stem-metazoans would have acted as ecosystem engineers, helping create the ecological conditions under which other metazoans, namely detritivores and non-sponge suspension feeders incapable of subsisting on picoplankton and DOM, could emerge and diversify. This early style of metazoan feeding, specifically the phagocytosis of small eukaryotic prey, could have also encouraged the evolution of larger, even multicellular, eukaryotic forms less prone to metazoan consumption. Therefore, the first multicellular stem-metazoans, through their feeding, arguably helped bridge the strictly microbial food webs of the Proterozoic Eon (2.5-0.541 billion years ago) to the more macroscopic, metazoan-sustaining food webs of the Phanerozoic Eon (0.541-0 billion years ago).}, } @article {pmid27686281, year = {2016}, author = {Wu, CI and Wang, HY and Ling, S and Lu, X}, title = {The Ecology and Evolution of Cancer: The Ultra-Microevolutionary Process.}, journal = {Annual review of genetics}, volume = {50}, number = {}, pages = {347-369}, doi = {10.1146/annurev-genet-112414-054842}, pmid = {27686281}, issn = {1545-2948}, mesh = {Animals ; *Biological Evolution ; Ecology ; Genetic Variation ; Genetics, Population ; Genome, Human ; Genotype ; Humans ; Neoplasms/*etiology/genetics ; Phenotype ; Population Growth ; *Selection, Genetic ; }, abstract = {Although tumorigenesis has been accepted as an evolutionary process (20 , 102), many forces may operate differently in cancers than in organisms, as they evolve at vastly different time scales. Among such forces, natural selection, here defined as differential cellular proliferation among distinct somatic cell genotypes, is particularly interesting because its action might be thwarted in multicellular organisms (20 , 29). In this review, selection is analyzed in two stages of cancer evolution: Stage I is the evolution between tumors and normal tissues, and Stage II is the evolution within tumors. The Cancer Genome Atlas (TCGA) data show a low degree of convergent evolution in Stage I, where genetic changes are not extensively shared among cases. An equally important, albeit much less highlighted, discovery using TCGA data is that there is almost no net selection in cancer evolution. Both positive and negative selection are evident but they neatly cancel each other out, rendering total selection ineffective in the absence of recombination. The efficacy of selection is even lower in Stage II, where neutral (non-Darwinian) evolution is increasingly supported by high-density sampling studies (81 , 123). Because natural selection is not a strong deterministic force, cancers usually evolve divergently even in similar tissue environments.}, } @article {pmid27672092, year = {2016}, author = {Noble, LM and Holland, LM and McLauchlan, AJ and Andrianopoulos, A}, title = {A Plastic Vegetative Growth Threshold Governs Reproductive Capacity in Aspergillus nidulans.}, journal = {Genetics}, volume = {204}, number = {3}, pages = {1161-1175}, pmid = {27672092}, issn = {1943-2631}, mesh = {Aspergillus nidulans/*genetics/growth & development ; *Gene Expression Regulation, Fungal ; Gene-Environment Interaction ; Reproduction, Asexual/*genetics ; ras Proteins/genetics/metabolism ; }, abstract = {Ontogenetic phases separating growth from reproduction are a common feature of cellular life. Long recognized for flowering plants and animals, early literature suggests this life-history component may also be prevalent among multicellular fungi. We establish the basis of developmental competence-the capacity to respond to induction of asexual development-in the filamentous saprotroph Aspergillus nidulans, describing environmental influences, including genotype-by-environment interactions among precocious mutants, gene expression associated with wild type and precocious competence acquisition, and the genetics of competence timing. Environmental effects are consistent with a threshold driven by metabolic rate and organism density, with pH playing a particularly strong role in determining competence timing. Gene expression diverges significantly over the competence window, despite a lack of overt morphological change, with differentiation in key metabolic, signaling, and cell trafficking processes. We identify five genes for which mutant alleles advance competence timing, including the conserved GTPase RasB (AN5832) and ambient pH sensor PalH (AN6886). In all cases examined, inheritance of competence timing is complex and non-Mendelian, with F1 progeny showing highly variable transgressive timing and dominant parental effects with a weak contribution from progeny genotype. Competence provides a new model for nutrient-limited life-cycle phases, and their elaboration from unicellular origins. Further work is required to establish the hormonal and bioenergetic basis of the trait across fungi, and underlying mechanisms of variable inheritance.}, } @article {pmid27663838, year = {2017}, author = {Ageitos, JM and Sánchez-Pérez, A and Calo-Mata, P and Villa, TG}, title = {Antimicrobial peptides (AMPs): Ancient compounds that represent novel weapons in the fight against bacteria.}, journal = {Biochemical pharmacology}, volume = {133}, number = {}, pages = {117-138}, doi = {10.1016/j.bcp.2016.09.018}, pmid = {27663838}, issn = {1873-2968}, mesh = {Amino Acid Sequence ; Animals ; Antimicrobial Cationic Peptides/*chemistry/genetics/*pharmacology ; Biological Products/*chemistry/*pharmacology ; Cell Wall/drug effects/physiology ; Drug Resistance, Multiple, Bacterial/*drug effects/physiology ; Humans ; Methicillin-Resistant Staphylococcus aureus/drug effects/physiology ; Microbial Sensitivity Tests/methods ; Protein Structure, Secondary ; }, abstract = {Antimicrobial peptides (AMPs) are short peptidic molecules produced by most living creatures. They help unicellular organisms to successfully compete for nutrients with other organisms sharing their biological niche, while AMPs form part of the immune system of multicellular creatures. Thus, these molecules represent biological weapons that have evolved over millions of years as a result of an escalating arms race for survival among living organisms. All AMPs share common features, such as a small size, with cationic and hydrophobic sequences within a linear or cyclic structure. AMPs can inhibit or kill bacteria at micromolar concentrations, often by non-specific mechanisms; hence the appearance of resistance to these antimicrobials is rare. Moreover, AMPs can kill antibiotic-resistant bacteria, including insidious microbes such as Acinetobacter baumannii and the methicillin-resistant Staphylococcus aureus. This review gives a detailed insight into a selection of the most prominent and interesting AMPs with antibacterial activity. In the near future AMPs, due to their properties and despite their ancient origin, should represent a novel alternative to antibiotics in the struggle to control pathogenic microorganisms and maintain the current human life expectancy.}, } @article {pmid27629030, year = {2016}, author = {Wensink, MJ}, title = {Size, longevity and cancer: age structure.}, journal = {Proceedings. Biological sciences}, volume = {283}, number = {1838}, pages = {}, pmid = {27629030}, issn = {1471-2954}, mesh = {Animals ; *Body Size ; Humans ; *Longevity ; Models, Biological ; *Neoplasms ; Probability ; }, abstract = {There is significant recent interest in Peto's paradox and the related problem of the evolution of large, long-lived organisms in terms of cancer robustness. Peto's paradox refers to the expectation that large, long-lived organisms have a higher lifetime cancer risk, which is not the case: a paradox. This paradox, however, is circular: large, long-lived organisms are large and long-lived because they are cancer robust. Lifetime risk, meanwhile, depends on the age distributions of both cancer and competing risks: if cancer strikes before competing risks, then lifetime risk is high; if not, not. Because no set of competing risks is generally prevalent, it is instructive to temporarily dispose of competing risks and investigate the pure age dynamics of cancer under the multistage model of carcinogenesis. In addition to augmenting earlier results, I show that in terms of cancer-free lifespan large organisms reap greater benefits from an increase in cellular cancer robustness than smaller organisms. Conversely, a higher cellular cancer robustness renders cancer-free lifespan more resilient to an increase in size. This interaction may be an important driver of the evolution of large, cancer-robust organisms.}, } @article {pmid27628442, year = {2016}, author = {Li, S and Hauser, F and Skadborg, SK and Nielsen, SV and Kirketerp-Møller, N and Grimmelikhuijzen, CJ}, title = {Adipokinetic hormones and their G protein-coupled receptors emerged in Lophotrochozoa.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {32789}, pmid = {27628442}, issn = {2045-2322}, mesh = {Adipokines/*metabolism ; Animals ; *Biological Evolution ; CHO Cells ; Cloning, Molecular ; Computational Biology ; Crassostrea/metabolism ; Cricetinae ; Cricetulus ; Drosophila melanogaster ; Gonadotropin-Releasing Hormone/metabolism ; Humans ; Insect Hormones/*metabolism ; Insect Proteins/metabolism ; Insecta ; Invertebrates/*metabolism ; Ligands ; Neuropeptides/metabolism ; Oligopeptides/*metabolism ; Peptides/metabolism ; Phylogeny ; Pyrrolidonecarboxylic Acid/*analogs & derivatives/metabolism ; Receptors, G-Protein-Coupled/*metabolism ; Signal Transduction ; }, abstract = {Most multicellular animals belong to two evolutionary lineages, the Proto- and Deuterostomia, which diverged 640-760 million years (MYR) ago. Neuropeptide signaling is abundant in animals belonging to both lineages, but it is often unclear whether there exist evolutionary relationships between the neuropeptide systems used by proto- or deuterostomes. An exception, however, are members of the gonadotropin-releasing hormone (GnRH) receptor superfamily, which occur in both evolutionary lineages, where GnRHs are the ligands in Deuterostomia and GnRH-like peptides, adipokinetic hormone (AKH), corazonin, and AKH/corazonin-related peptide (ACP) are the ligands in Protostomia. AKH is a well-studied insect neuropeptide that mobilizes lipids and carbohydrates from the insect fat body during flight. In our present paper, we show that AKH is not only widespread in insects, but also in other Ecdysozoa and in Lophotrochozoa. Furthermore, we have cloned and deorphanized two G protein-coupled receptors (GPCRs) from the oyster Crassostrea gigas (Mollusca) that are activated by low nanomolar concentrations of oyster AKH (pQVSFSTNWGSamide). Our discovery of functional AKH receptors in molluscs is especially significant, because it traces the emergence of AKH signaling back to about 550 MYR ago and brings us closer to a more complete understanding of the evolutionary origins of the GnRH receptor superfamily.}, } @article {pmid27619696, year = {2016}, author = {Lehtonen, J and Kokko, H and Parker, GA}, title = {What do isogamous organisms teach us about sex and the two sexes?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1706}, pages = {}, pmid = {27619696}, issn = {1471-2970}, mesh = {*Biological Evolution ; Eukaryota/*physiology ; Germ Cells/*physiology ; Reproduction ; *Sex ; }, abstract = {Isogamy is a reproductive system where all gametes are morphologically similar, especially in terms of size. Its importance goes beyond specific cases: to this day non-anisogamous systems are common outside of multicellular animals and plants, they can be found in all eukaryotic super-groups, and anisogamous organisms appear to have isogamous ancestors. Furthermore, because maleness is synonymous with the production of small gametes, an explanation for the initial origin of males and females is synonymous with understanding the transition from isogamy to anisogamy. As we show here, this transition may also be crucial for understanding why sex itself remains common even in taxa with high costs of male production (the twofold cost of sex). The transition to anisogamy implies the origin of male and female sexes, kickstarts the subsequent evolution of sex roles, and has a major impact on the costliness of sexual reproduction. Finally, we combine some of the consequences of isogamy and anisogamy in a thought experiment on the maintenance of sexual reproduction. We ask what happens if there is a less than twofold benefit to sex (not an unlikely scenario as large short-term benefits have proved difficult to find), and argue that this could lead to a situation where lineages that evolve anisogamy-and thus the highest costs of sex-end up being associated with constraints that make invasion by asexual reproduction unlikely (the 'anisogamy gateway' hypothesis).This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'.}, } @article {pmid27617970, year = {2016}, author = {Bowman, JL and Sakakibara, K and Furumizu, C and Dierschke, T}, title = {Evolution in the Cycles of Life.}, journal = {Annual review of genetics}, volume = {50}, number = {}, pages = {133-154}, doi = {10.1146/annurev-genet-120215-035227}, pmid = {27617970}, issn = {1545-2948}, mesh = {*Biological Evolution ; Bryophyta/genetics ; Chlorophyta/genetics ; Diploidy ; Eukaryota ; Fungi/genetics ; Haploidy ; Homeodomain Proteins/genetics ; Magnoliopsida/genetics ; Phaeophyceae/genetics ; Phylogeny ; Plants/*genetics ; Rhodophyta/genetics ; }, abstract = {The life cycles of eukaryotes alternate between haploid and diploid phases, which are initiated by meiosis and gamete fusion, respectively. In both ascomycete and basidiomycete fungi and chlorophyte algae, the haploid-to-diploid transition is regulated by a pair of paralogous homeodomain protein encoding genes. That a common genetic program controls the haploid-to-diploid transition in phylogenetically disparate eukaryotic lineages suggests this may be the ancestral function for homeodomain proteins. Multicellularity has evolved independently in many eukaryotic lineages in either one or both phases of the life cycle. Organisms, such as land plants, exhibiting a life cycle whereby multicellular bodies develop in both the haploid and diploid phases are often referred to as possessing an alternation of generations. We review recent progress on understanding the genetic basis for the land plant alternation of generations and highlight the roles that homeodomain-encoding genes may have played in the evolution of complex multicellularity in this lineage.}, } @article {pmid27617059, year = {2016}, author = {Robbins, RJ and Krishtalka, L and Wooley, JC}, title = {Advances in biodiversity: metagenomics and the unveiling of biological dark matter.}, journal = {Standards in genomic sciences}, volume = {11}, number = {1}, pages = {69}, pmid = {27617059}, issn = {1944-3277}, abstract = {BACKGROUND: Efforts to harmonize genomic data standards used by the biodiversity and metagenomic research communities have shown that prokaryotic data cannot be understood or represented in a traditional, classical biological context for conceptual reasons, not technical ones.

RESULTS: Biology, like physics, has a fundamental duality-the classical macroscale eukaryotic realm vs. the quantum microscale microbial realm-with the two realms differing profoundly, and counter-intuitively, from one another. Just as classical physics is emergent from and cannot explain the microscale realm of quantum physics, so classical biology is emergent from and cannot explain the microscale realm of prokaryotic life. Classical biology describes the familiar, macroscale realm of multi-cellular eukaryotic organisms, which constitute a highly derived and constrained evolutionary subset of the biosphere, unrepresentative of the vast, mostly unseen, microbial world of prokaryotic life that comprises at least half of the planet's biomass and most of its genetic diversity. The two realms occupy fundamentally different mega-niches: eukaryotes interact primarily mechanically with the environment, prokaryotes primarily physiologically. Further, many foundational tenets of classical biology simply do not apply to prokaryotic biology.

CONCLUSIONS: Classical genetics one held that genes, arranged on chromosomes like beads on a string, were the fundamental units of mutation, recombination, and heredity. Then, molecular analysis showed that there were no fundamental units, no beads, no string. Similarly, classical biology asserts that individual organisms and species are fundamental units of ecology, evolution, and biodiversity, composing an evolutionary history of objectively real, lineage-defined groups in a single-rooted tree of life. Now, metagenomic tools are forcing a recognition that there are no completely objective individuals, no unique lineages, and no one true tree. The newly revealed biosphere of microbial dark matter cannot be understood merely by extending the concepts and methods of eukaryotic macrobiology. The unveiling of biological dark matter is allowing us to see, for the first time, the diversity of the entire biosphere and, to paraphrase Darwin, is providing a new view of life. Advancing and understanding that view will require major revisions to some of the most fundamental concepts and theories in biology.}, } @article {pmid27609894, year = {2016}, author = {Sunyer, R and Conte, V and Escribano, J and Elosegui-Artola, A and Labernadie, A and Valon, L and Navajas, D and García-Aznar, JM and Muñoz, JJ and Roca-Cusachs, P and Trepat, X}, title = {Collective cell durotaxis emerges from long-range intercellular force transmission.}, journal = {Science (New York, N.Y.)}, volume = {353}, number = {6304}, pages = {1157-1161}, doi = {10.1126/science.aaf7119}, pmid = {27609894}, issn = {1095-9203}, mesh = {Cell Line ; Epithelial Cells/*physiology ; *Extracellular Matrix ; Humans ; Intercellular Junctions/physiology ; Microscopy, Phase-Contrast ; Myosins/physiology ; *Taxis Response ; }, abstract = {The ability of cells to follow gradients of extracellular matrix stiffness-durotaxis-has been implicated in development, fibrosis, and cancer. Here, we found multicellular clusters that exhibited durotaxis even if isolated constituent cells did not. This emergent mode of directed collective cell migration applied to a variety of epithelial cell types, required the action of myosin motors, and originated from supracellular transmission of contractile physical forces. To explain the observed phenomenology, we developed a generalized clutch model in which local stick-slip dynamics of cell-matrix adhesions was integrated to the tissue level through cell-cell junctions. Collective durotaxis is far more efficient than single-cell durotaxis; it thus emerges as a robust mechanism to direct cell migration during development, wound healing, and collective cancer cell invasion.}, } @article {pmid27595342, year = {2017}, author = {Ishizaki, K}, title = {Evolution of land plants: insights from molecular studies on basal lineages.}, journal = {Bioscience, biotechnology, and biochemistry}, volume = {81}, number = {1}, pages = {73-80}, doi = {10.1080/09168451.2016.1224641}, pmid = {27595342}, issn = {1347-6947}, mesh = {Embryophyta/*genetics/metabolism ; *Evolution, Molecular ; Introduced Species ; }, abstract = {The invasion of the land by plants, or terrestrialization, was one of the most critical events in the history of the Earth. The evolution of land plants included significant transformations in body plans: the emergence of a multicellular diploid sporophyte, transition from gametophyte-dominant to sporophyte-dominant life histories, and development of many specialized tissues and organs, such as stomata, vascular tissues, roots, leaves, seeds, and flowers. Recent advances in molecular genetics in two model basal plants, bryophytes Physcomitrella patens and Marchantia polymorpha, have begun to provide answers to several key questions regarding land plant evolution. This paper discusses the evolution of the genes and regulatory mechanisms that helped drive such significant morphological innovations among land-based plants.}, } @article {pmid27589960, year = {2016}, author = {Lee, J and Cho, CH and Park, SI and Choi, JW and Song, HS and West, JA and Bhattacharya, D and Yoon, HS}, title = {Parallel evolution of highly conserved plastid genome architecture in red seaweeds and seed plants.}, journal = {BMC biology}, volume = {14}, number = {}, pages = {75}, pmid = {27589960}, issn = {1741-7007}, mesh = {Conserved Sequence/*genetics ; Cycadopsida/*genetics ; *Evolution, Molecular ; Genetic Variation ; *Genome, Plastid ; Magnoliopsida/*genetics ; Multigene Family ; Phylogeny ; Rhodophyta/*genetics ; Seeds/*genetics ; Synteny/genetics ; }, abstract = {BACKGROUND: The red algae (Rhodophyta) diverged from the green algae and plants (Viridiplantae) over one billion years ago within the kingdom Archaeplastida. These photosynthetic lineages provide an ideal model to study plastid genome reduction in deep time. To this end, we assembled a large dataset of the plastid genomes that were available, including 48 from the red algae (17 complete and three partial genomes produced for this analysis) to elucidate the evolutionary history of these organelles.

RESULTS: We found extreme conservation of plastid genome architecture in the major lineages of the multicellular Florideophyceae red algae. Only three minor structural types were detected in this group, which are explained by recombination events of the duplicated rDNA operons. A similar high level of structural conservation (although with different gene content) was found in seed plants. Three major plastid genome architectures were identified in representatives of 46 orders of angiosperms and three orders of gymnosperms.

CONCLUSIONS: Our results provide a comprehensive account of plastid gene loss and rearrangement events involving genome architecture within Archaeplastida and lead to one over-arching conclusion: from an ancestral pool of highly rearranged plastid genomes in red and green algae, the aquatic (Florideophyceae) and terrestrial (seed plants) multicellular lineages display high conservation in plastid genome architecture. This phenomenon correlates with, and could be explained by, the independent and widely divergent (separated by >400 million years) origins of complex sexual cycles and reproductive structures that led to the rapid diversification of these lineages.}, } @article {pmid27579832, year = {2016}, author = {Xu, Y and Yu, XL and Hu, CM and Hao, G}, title = {Morphological and Molecular Phylogenetic Data Reveal a New Species of Primula (Primulaceae) from Hunan, China.}, journal = {PloS one}, volume = {11}, number = {8}, pages = {e0161172}, pmid = {27579832}, issn = {1932-6203}, mesh = {China ; Genetic Markers ; *Phylogeny ; Plant Proteins/*genetics ; *Primula/anatomy & histology/classification/genetics ; }, abstract = {A new species of Primulaceae, Primula undulifolia, is described from the hilly area of Hunan province in south-central China. Its morphology and distributional range suggest that it is allied to P. kwangtungensis, both adapted to subtropical climate, having contiguous distribution and similar habitat, growing on shady and moist cliffs. Petioles, scapes and pedicels of them are densely covered with rusty multicellular hairs, but the new species can be easily distinguished by its smaller flowers and narrowly oblong leaves with undulate margins. Molecular phylogenetic analysis based on four DNA markers (ITS, matK, trnL-F and rps16) confirmed the new species as an independent lineage and constitutes a main clade together with P. kwangtungensis, P. kweichouensis, P. wangii and P. hunanensis of Primula sect. Carolinella.}, } @article {pmid27571751, year = {2016}, author = {Leducq, JB and Nielly-Thibault, L and Charron, G and Eberlein, C and Verta, JP and Samani, P and Sylvester, K and Hittinger, CT and Bell, G and Landry, CR}, title = {Speciation driven by hybridization and chromosomal plasticity in a wild yeast.}, journal = {Nature microbiology}, volume = {1}, number = {}, pages = {15003}, pmid = {27571751}, issn = {2058-5276}, mesh = {*Chromosomes, Fungal ; Forests ; *Genetic Speciation ; *Genetic Variation ; *Hybridization, Genetic ; North America ; *Recombination, Genetic ; Saccharomyces/*classification/*genetics/isolation & purification ; }, abstract = {Hybridization is recognized as a powerful mechanism of speciation and a driving force in generating biodiversity. However, only few multicellular species, limited to a handful of plants and animals, have been shown to fulfil all the criteria of homoploid hybrid speciation. This lack of evidence could lead to the interpretation that speciation by hybridization has a limited role in eukaryotes, particularly in single-celled organisms. Laboratory experiments have revealed that fungi such as budding yeasts can rapidly develop reproductive isolation and novel phenotypes through hybridization, showing that in principle homoploid speciation could occur in nature. Here, we report a case of homoploid hybrid speciation in natural populations of the budding yeast Saccharomyces paradoxus inhabiting the North American forests. We show that the rapid evolution of chromosome architecture and an ecological context that led to secondary contact between nascent species drove the formation of an incipient hybrid species with a potentially unique ecological niche.}, } @article {pmid27559062, year = {2016}, author = {Schoustra, S and Hwang, S and Krug, J and de Visser, JA}, title = {Diminishing-returns epistasis among random beneficial mutations in a multicellular fungus.}, journal = {Proceedings. Biological sciences}, volume = {283}, number = {1837}, pages = {}, pmid = {27559062}, issn = {1471-2954}, mesh = {Aspergillus nidulans/*genetics ; *Epistasis, Genetic ; *Genetic Fitness ; Genotype ; Models, Genetic ; *Mutation ; }, abstract = {Adaptive evolution ultimately is fuelled by mutations generating novel genetic variation. Non-additivity of fitness effects of mutations (called epistasis) may affect the dynamics and repeatability of adaptation. However, understanding the importance and implications of epistasis is hampered by the observation of substantial variation in patterns of epistasis across empirical studies. Interestingly, some recent studies report increasingly smaller benefits of beneficial mutations once genotypes become better adapted (called diminishing-returns epistasis) in unicellular microbes and single genes. Here, we use Fisher's geometric model (FGM) to generate analytical predictions about the relationship between the effect size of mutations and the extent of epistasis. We then test these predictions using the multicellular fungus Aspergillus nidulans by generating a collection of 108 strains in either a poor or a rich nutrient environment that each carry a beneficial mutation and constructing pairwise combinations using sexual crosses. Our results support the predictions from FGM and indicate negative epistasis among beneficial mutations in both environments, which scale with mutational effect size. Hence, our findings show the importance of diminishing-returns epistasis among beneficial mutations also for a multicellular organism, and suggest that this pattern reflects a generic constraint operating at diverse levels of biological organization.}, } @article {pmid27549405, year = {2016}, author = {Rödelsperger, C and Menden, K and Serobyan, V and Witte, H and Baskaran, P}, title = {First insights into the nature and evolution of antisense transcription in nematodes.}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {165}, pmid = {27549405}, issn = {1471-2148}, mesh = {Animals ; Biological Evolution ; Evolution, Molecular ; Gene Expression Regulation ; Gene Library ; Genes, Helminth ; *Introns ; Nematoda/*genetics ; Proteomics ; RNA, Antisense/*genetics ; Synteny ; Transcription, Genetic ; }, abstract = {BACKGROUND: The development of multicellular organisms is coordinated by various gene regulatory mechanisms that ensure correct spatio-temporal patterns of gene expression. Recently, the role of antisense transcription in gene regulation has moved into focus of research. To characterize genome-wide patterns of antisense transcription and to study their evolutionary conservation, we sequenced a strand-specific RNA-seq library of the nematode Pristionchus pacificus.

RESULTS: We identified 1112 antisense configurations of which the largest group represents 465 antisense transcripts (ASTs) that are fully embedded in introns of their host genes. We find that most ASTs show homology to protein-coding genes and are overrepresented in proteomic data. Together with the finding, that expression levels of ASTs and host genes are uncorrelated, this indicates that most ASTs in P. pacificus do not represent non-coding RNAs and do not exhibit regulatory functions on their host genes. We studied the evolution of antisense gene pairs across 20 nematode genomes, showing that the majority of pairs is lineage-specific and even the highly conserved vps-4, ddx-27, and sel-2 loci show abundant structural changes including duplications, deletions, intron gains and loss of antisense transcription. In contrast, host genes in general, are remarkably conserved and encode exceptionally long introns leading to unusually large blocks of conserved synteny.

CONCLUSIONS: Our study has shown that in P. pacificus antisense transcription as such does not define non-coding RNAs but is rather a feature of highly conserved genes with long introns. We hypothesize that the presence of regulatory elements imposes evolutionary constraint on the intron length, but simultaneously, their large size makes them a likely target for translocation of genomic elements including protein-coding genes that eventually end up as ASTs.}, } @article {pmid27534782, year = {2016}, author = {Šmardová, J and Koptíková, J}, title = {[Two Approaches to Cancer Development].}, journal = {Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti}, volume = {29}, number = {4}, pages = {259-266}, doi = {10.14735/amko2016259}, pmid = {27534782}, issn = {0862-495X}, mesh = {Carcinogenesis/*genetics ; Cell Proliferation/*genetics ; Epigenesis, Genetic/genetics ; Humans ; Mutation/*genetics ; Neoplasms/*genetics ; Tumor Microenvironment ; }, abstract = {BACKGROUND: The somatic mutation theory explaining the process of carcinogenesis is generally accepted. The theory postulates that carcinogenesis begins in a first renegade cell that undergoes gradual transformation from a healthy to a fully malignant state through the accumulation of genetic and epigenetic "hits". This theory focuses specifically on mutations and genetic aberrations, and their impact on cells. It considers tumors as populations of sick cells that lose control of their own proliferation. The theory was put forward by Robert Weinberg and Douglas Hanahan, and is the predominant view in current cancer biology. By contrast, the tissue organization field theory proposed by Carlos Sonnenschein and Ana Soto considers loss of physiological structure and function by a tissue as key events in tumor development. According to this theory, tumors arise at a tissue rather than at a cellular level. It is based on a presumption that proliferation status, rather than quiescence, is the default position of cells in multicellular organisms.

AIM: The article aims to provide answers to following questions: Are the views of proponents of the somatic mutation theory (the reductionists) and proponents of the tissue organization field theory (the organicists) incompatible and incommensurable, even when the mainstream of tumor biology has shifted its attention from tumor cells toward the tumor microenvironment? Where to find a third interconnecting systemic approach? Is it useful to be aware of the controversy between reductionists and organicists? What this awareness contributes to? How do these alternative views influence practical oncology and tumor biology in general?

CONCLUSION: Whether the true position is held by reductionists or organicists is unimportant. What is important is to be aware of the existence of these two concepts because this knowledge makes the way we think about tumor origin and development, and how we set up and interpret our experiments, more precise.

KEY WORDS: carcinogenesis - mutation - cell - tissues - cell proliferation - cell quiescenceThis study was supported by grant of Internal Grant Agency of the Czech ministry of Health No. NT/13784-4/2012.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 7. 2015Accepted: 27. 4. 2016.}, } @article {pmid27518838, year = {2016}, author = {El Kafsi, H and Gorochov, G and Larsen, M}, title = {Host genetics affect microbial ecosystems via host immunity.}, journal = {Current opinion in allergy and clinical immunology}, volume = {16}, number = {5}, pages = {413-420}, doi = {10.1097/ACI.0000000000000302}, pmid = {27518838}, issn = {1473-6322}, mesh = {Animals ; Biological Evolution ; Ecosystem ; *Gene-Environment Interaction ; *Genetic Phenomena ; Homeostasis ; *Host-Pathogen Interactions ; Humans ; Immunity/*genetics ; Mice ; *Microbiota ; Symbiosis ; }, abstract = {PURPOSE OF REVIEW: Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity.

RECENT FINDINGS: Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics.

SUMMARY: We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.}, } @article {pmid27512113, year = {2016}, author = {Derelle, R and López-García, P and Timpano, H and Moreira, D}, title = {A Phylogenomic Framework to Study the Diversity and Evolution of Stramenopiles (=Heterokonts).}, journal = {Molecular biology and evolution}, volume = {33}, number = {11}, pages = {2890-2898}, pmid = {27512113}, issn = {1537-1719}, support = {322669/ERC_/European Research Council/International ; }, mesh = {*Biological Evolution ; DNA, Ribosomal/genetics ; Diatoms/genetics ; Evolution, Molecular ; Heterotrophic Processes ; Phylogeny ; Sequence Analysis, DNA/methods ; Stramenopiles/*genetics ; }, abstract = {Stramenopiles or heterokonts constitute one of the most speciose and diverse clades of protists. It includes ecologically important algae (such as diatoms or large multicellular brown seaweeds), as well as heterotrophic (e.g., bicosoecids, MAST groups) and parasitic (e.g., Blastocystis, oomycetes) species. Despite their evolutionary and ecological relevance, deep phylogenetic relationships among stramenopile groups, inferred mostly from small-subunit rDNA phylogenies, remain unresolved, especially for the heterotrophic taxa. Taking advantage of recently released stramenopile transcriptome and genome sequences, as well as data from the genomic assembly of the MAST-3 species Incisomonas marina generated in our laboratory, we have carried out the first extensive phylogenomic analysis of stramenopiles, including representatives of most major lineages. Our analyses, based on a large data set of 339 widely distributed proteins, strongly support a root of stramenopiles lying between two clades, Bigyra and Gyrista (Pseudofungi plus Ochrophyta). Additionally, our analyses challenge the Phaeista-Khakista dichotomy of photosynthetic stramenopiles (ochrophytes) as two groups previously considered to be part of the Phaeista (Pelagophyceae and Dictyochophyceae), branch with strong support with the Khakista (Bolidophyceae and Diatomeae). We propose a new classification of ochrophytes within the two groups Chrysista and Diatomista to reflect the new phylogenomic results. Our stramenopile phylogeny provides a robust phylogenetic framework to investigate the evolution and diversification of this group of ecologically relevant protists.}, } @article {pmid27510329, year = {2017}, author = {Pesce, M and Santoro, R}, title = {Feeling the right force: How to contextualize the cell mechanical behavior in physiologic turnover and pathologic evolution of the cardiovascular system.}, journal = {Pharmacology & therapeutics}, volume = {171}, number = {}, pages = {75-82}, doi = {10.1016/j.pharmthera.2016.08.002}, pmid = {27510329}, issn = {1879-016X}, mesh = {Animals ; Cardiovascular Diseases/*physiopathology ; Cardiovascular System/*cytology/metabolism/physiopathology ; Cell Differentiation/*physiology ; Cell Engineering/methods ; Embryonic Development/physiology ; Gene Expression/physiology ; Humans ; }, abstract = {Although traditionally linked to the physiology of tissues in 'motion', the ability of the cells to transduce external forces into coordinated gene expression programs is emerging as an integral component of the fundamental structural organization of multicellular organisms with consequences for cell differentiation even from the beginning of embryonic development. The ability of the cells to 'feel' the surrounding mechanical environment, even in the absence of tissue motion, is then translated into 'positional' or 'social' sensing that instructs, before the organ renewal, the correct patterning of the embryos. In the present review, we will highlight how these basic concepts, emerging from the employment of novel cell engineering tools, can be linked to pathophysiology of the cardiovascular system, and may contribute to understanding the molecular bases of some of the major cardiovascular diseases like heart failure, heart valve stenosis and failure of the venous aorto-coronary bypass.}, } @article {pmid27501943, year = {2016}, author = {Sojo, V and Dessimoz, C and Pomiankowski, A and Lane, N}, title = {Membrane Proteins Are Dramatically Less Conserved than Water-Soluble Proteins across the Tree of Life.}, journal = {Molecular biology and evolution}, volume = {33}, number = {11}, pages = {2874-2884}, pmid = {27501943}, issn = {1537-1719}, support = {BB/L018241/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adaptation, Biological ; Archaea/genetics ; Bacteria/genetics ; Biological Evolution ; Databases, Protein ; Eukaryota/genetics ; Evolution, Molecular ; Homeostasis ; Membrane Proteins/*genetics/metabolism ; Phylogeny ; Prokaryotic Cells ; Proteins/*genetics/metabolism ; Sequence Analysis, Protein/*methods ; Solubility ; Water/metabolism ; }, abstract = {Membrane proteins are crucial in transport, signaling, bioenergetics, catalysis, and as drug targets. Here, we show that membrane proteins have dramatically fewer detectable orthologs than water-soluble proteins, less than half in most species analyzed. This sparse distribution could reflect rapid divergence or gene loss. We find that both mechanisms operate. First, membrane proteins evolve faster than water-soluble proteins, particularly in their exterior-facing portions. Second, we demonstrate that predicted ancestral membrane proteins are preferentially lost compared with water-soluble proteins in closely related species of archaea and bacteria. These patterns are consistent across the whole tree of life, and in each of the three domains of archaea, bacteria, and eukaryotes. Our findings point to a fundamental evolutionary principle: membrane proteins evolve faster due to stronger adaptive selection in changing environments, whereas cytosolic proteins are under more stringent purifying selection in the homeostatic interior of the cell. This effect should be strongest in prokaryotes, weaker in unicellular eukaryotes (with intracellular membranes), and weakest in multicellular eukaryotes (with extracellular homeostasis). We demonstrate that this is indeed the case. Similarly, we show that extracellular water-soluble proteins exhibit an even stronger pattern of low homology than membrane proteins. These striking differences in conservation of membrane proteins versus water-soluble proteins have important implications for evolution and medicine.}, } @article {pmid27490201, year = {2016}, author = {Denver, DR and Brown, AM and Howe, DK and Peetz, AB and Zasada, IA}, title = {Genome Skimming: A Rapid Approach to Gaining Diverse Biological Insights into Multicellular Pathogens.}, journal = {PLoS pathogens}, volume = {12}, number = {8}, pages = {e1005713}, pmid = {27490201}, issn = {1553-7374}, mesh = {Animals ; Genome ; Humans ; Nematoda/*genetics ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, } @article {pmid27477870, year = {2016}, author = {Chang, ML and Liang, KH and Ku, CL and Lo, CC and Cheng, YT and Hsu, CM and Yeh, CT and Chiu, CT}, title = {Resistin reinforces interferon λ-3 to eliminate hepatitis C virus with fine-tuning from RETN single-nucleotide polymorphisms.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {30799}, pmid = {27477870}, issn = {2045-2322}, mesh = {Adult ; Female ; Hepacivirus/*immunology ; Hepatitis C/*genetics/*immunology/therapy ; Humans ; Interferons ; *Interleukins/genetics/immunology ; Male ; *Polymorphism, Single Nucleotide ; *Resistin/genetics/immunology ; }, abstract = {The effect of resistin (RETN) on the response to anti-HCV therapy remains unclear. A prospective cohort study was performed using 655 consecutive HCV patients, of whom 513 had completed a course of interferon-based therapy. Multivariate and GEE analyses revealed four RETN single-nucleotide polymorphisms (SNPs), rs34861192, rs3219175, rs3745367 and rs1423096, to be synergistically associated with resistin levels. After adjusting for co-factors such as interferon λ-3 (IFNL3)-rs12979860, the resistin level and the hyper-resistinemic genotype at the 4 RETN SNPs were positively and negatively associated with a sustained virological response (SVR), respectively. RETN-rs3745367 was in linkage disequilibrium with IFNL3-rs12979860. Compared to non-SVR patients, SVR patients had higher levels of pre-therapy resistin, primarily originating from intrahepatic lymphocytes, stellate cells, Kupffer cells, hepatic progenitor cells and hepatocytes. This difference diminished over the course of therapy, as only SVR patients exhibited a 24-week post-therapy decrease in resistin. Both resistin and IFNL3 mRNAs were upregulated, but only resistin mRNA was upregulated by recombinant resistin in peripheral blood mononuclear cells with and without hyper-resistinemic genotypes of the 4 RETN SNPs, respectively. Fine-tuned by RETN SNPs, intrahepatic, multi-cellular resistin reinforced IFNL3 in eliminating HCV via immunomodulation to counteract pro-inflammation. These results encourage the development of novel resistin-targeted anti-viral agents.}, } @article {pmid27476447, year = {2017}, author = {Jubin, T and Kadam, A and Gani, AR and Singh, M and Dwivedi, M and Begum, R}, title = {Poly ADP-ribose polymerase-1: Beyond transcription and towards differentiation.}, journal = {Seminars in cell & developmental biology}, volume = {63}, number = {}, pages = {167-179}, doi = {10.1016/j.semcdb.2016.07.027}, pmid = {27476447}, issn = {1096-3634}, mesh = {Animals ; Cell Differentiation/*genetics ; Embryonic Development/genetics ; Gene Expression Regulation ; Humans ; Models, Biological ; Poly(ADP-ribose) Polymerases/*metabolism ; *Transcription, Genetic ; }, abstract = {Gene regulation mediates the processes of cellular development and differentiation leading to the origin of different cell types each having their own signature gene expression profile. However, the compact chromatin structure and the timely recruitment of molecules involved in various signaling pathways are of prime importance for temporal and spatial gene regulation that eventually contribute towards cell type and specificity. Poly (ADP-ribose) polymerase-1 (PARP-1), a 116-kDa nuclear multitasking protein is involved in modulation of chromatin condensation leading to altered gene expression. In response to activation signals, it adds ADP-ribose units to various target proteins including itself, thus regulating various key cellular processes like DNA repair, cell death, transcription, mRNA splicing etc. This review provides insights into the role of PARP-1 in gene regulation, cell differentiation and multicellular morphogenesis. In addition, the review also explores involvement of PARP-1 in immune cells development and therapeutic possibilities to treat various human diseases.}, } @article {pmid27458458, year = {2016}, author = {Zhang, X and Soldati, T}, title = {Of Amoebae and Men: Extracellular DNA Traps as an Ancient Cell-Intrinsic Defense Mechanism.}, journal = {Frontiers in immunology}, volume = {7}, number = {}, pages = {269}, pmid = {27458458}, issn = {1664-3224}, abstract = {Since the discovery of the formation of DNA-based extracellular traps (ETs) by neutrophils as an innate immune defense mechanism (1), hundreds of articles describe the involvement of ETs in physiological and pathological human and animal conditions [reviewed in Ref. (2), and the previous Frontiers Research Topic on NETosis: http://www.frontiersin.org/books/NETosis_At_the_Intersection_of_Cell_Biology_Microbiology_and_Immunology/195]. Interestingly, a few reports reveal that ETs can be formed by immune cells of more ancient organisms, as far back as the common ancestor of vertebrates and invertebrates (3). Recently, we reported that the Sentinel cells of the multicellular slug of the social amoeba Dictyostelium discoideum also produce ETs to trap and kill slug-invading bacteria [see Box 1; and Figure 1 Ref. (4)]. This is a strong evidence that DNA-based cell-intrinsic defense mechanisms emerged much earlier than thought, about 1.3 billion years ago. Amazingly, using extrusion of DNA as a weapon to capture and kill uningestable microbes has its rationale. During the emergence of multicellularity, a primitive innate immune system developed in the form of a dedicated set of specialized phagocytic cells. This professionalization of immunity allowed the evolution of sophisticated defense mechanisms including the sacrifice of a small set of cells by a mechanism related to NETosis. This altruistic behavior likely emerged in steps, starting from the release of "dispensable" mitochondrial DNA by D. discoideum Sentinel cells. Grounded in this realization, one can anticipate that in the near future, many more examples of the invention and fine-tuning of ETs by early metazoan ancestors will be identified. Consequently, it can be expected that this more complete picture of the evolution of ETs will impact our views of the involvement and pathologies linked to ETs in human and animals.}, } @article {pmid27451296, year = {2016}, author = {Matt, G and Umen, J}, title = {Volvox: A simple algal model for embryogenesis, morphogenesis and cellular differentiation.}, journal = {Developmental biology}, volume = {419}, number = {1}, pages = {99-113}, pmid = {27451296}, issn = {1095-564X}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Cycle ; Cell Lineage ; Cell Size ; Cellular Senescence ; *Models, Biological ; Morphogenesis ; Mutation ; Phylogeny ; Reproduction, Asexual ; Seeds ; Volvox/*cytology/genetics/physiology ; }, abstract = {Patterning of a multicellular body plan involves a coordinated set of developmental processes that includes cell division, morphogenesis, and cellular differentiation. These processes have been most intensively studied in animals and land plants; however, deep insight can also be gained by studying development in simpler multicellular organisms. The multicellular green alga Volvox carteri (Volvox) is an excellent model for the investigation of developmental mechanisms and their evolutionary origins. Volvox has a streamlined body plan that contains only a few thousand cells and two distinct cell types: reproductive germ cells and terminally differentiated somatic cells. Patterning of the Volvox body plan is achieved through a stereotyped developmental program that includes embryonic cleavage with asymmetric cell division, morphogenesis, and cell-type differentiation. In this review we provide an overview of how these three developmental processes give rise to the adult form in Volvox and how developmental mutants have provided insights into the mechanisms behind these events. We highlight the accessibility and tractability of Volvox and its relatives that provide a unique opportunity for studying development.}, } @article {pmid27443165, year = {2016}, author = {Punia, K and Bucaro, M and Mancuso, A and Cuttitta, C and Marsillo, A and Bykov, A and L'Amoreaux, W and Raja, KS}, title = {Rediscovering Chemical Gardens: Self-Assembling Cytocompatible Protein-Intercalated Silicate-Phosphate Sponge-Mimetic Tubules.}, journal = {Langmuir : the ACS journal of surfaces and colloids}, volume = {32}, number = {34}, pages = {8748-8758}, doi = {10.1021/acs.langmuir.6b01721}, pmid = {27443165}, issn = {1520-5827}, mesh = {Animals ; Biocompatible Materials/*chemistry/pharmacology ; Biomimetic Materials/*chemistry/pharmacology ; Calcium Chloride/chemistry ; Cell Line ; Cell Survival/drug effects ; Dinoflagellida/drug effects/physiology ; Gelatin/*chemistry ; HeLa Cells ; Humans ; Myoblasts/cytology/drug effects/physiology ; Phosphates/*chemistry ; Porifera/anatomy & histology/chemistry ; Rats ; Silicates/*chemistry ; Tissue Engineering ; *Tissue Scaffolds ; }, abstract = {The classic chemical garden experiment is reconstructed to produce protein-intercalated silicate-phosphate tubules that resemble tubular sponges. The constructs were synthesized by seeding calcium chloride into a solution of sodium silicate-potassium phosphate and gelatin. Sponge-mimetic tubules were fabricated with varying percentages of gelatin (0-15% w/v), in diameters ranging from 200 μm to 2 mm, characterized morphologically and compositionally, functionalized with biomolecules for cell adhesion, and evaluated for cytocompatibility. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy analysis (EDS) experiments showed that the external surface of the tubules was relatively more amorphous in texture and carbon/protein-rich in comparison to the interior surface. Transmission electron microscopy (TEM) images indicate a network composed of gelatin incorporated into the inorganic scaffold. The presence of gelatin in the constructs was confirmed by infrared spectroscopy. Powder X-ray diffraction (XRD) was used to identify inorganic crystalline phases in the scaffolds that are mainly composed of Ca(OH)2, NaCl, and Ca2SiO4 along with a band corresponding to amorphous gelatin. Bioconjugation and coating protocols were developed to program the scaffolds with cues for cell adhesion, and the resulting constructs were employed for 3D cell culture of marine (Pyrocystis lunula) and mammalian (HeLa and H9C2) cell lines. The cytocompatibility of the constructs was demonstrated by live cell assays. We have successfully shown that these biomimetic materials can indeed support life; they serve as scaffolds that facilitate the attachment and assembly of individual cells to form multicellular entities, thereby revisiting the 350-year-old effort to link chemical gardens with the origins of life. Hybrid chemical garden biomaterials are programmable, readily fabricated and could be employed in tissue engineering, biomolecular materials development, 3D mammalian cell culture and by researchers investigating the origins of multicellular life.}, } @article {pmid27431524, year = {2016}, author = {Moses, M and Bezerra, G and Edwards, B and Brown, J and Forrest, S}, title = {Energy and time determine scaling in biological and computer designs.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431524}, issn = {1471-2970}, support = {T32 EB009414/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; *Basal Metabolism ; Biological Evolution ; *Electric Power Supplies ; Mammals/*physiology ; *Microcomputers ; Models, Biological ; Models, Theoretical ; Selection, Genetic ; }, abstract = {Metabolic rate in animals and power consumption in computers are analogous quantities that scale similarly with size. We analyse vascular systems of mammals and on-chip networks of microprocessors, where natural selection and human engineering, respectively, have produced systems that minimize both energy dissipation and delivery times. Using a simple network model that simultaneously minimizes energy and time, our analysis explains empirically observed trends in the scaling of metabolic rate in mammals and power consumption and performance in microprocessors across several orders of magnitude in size. Just as the evolutionary transitions from unicellular to multicellular animals in biology are associated with shifts in metabolic scaling, our model suggests that the scaling of power and performance will change as computer designs transition to decentralized multi-core and distributed cyber-physical systems. More generally, a single energy-time minimization principle may govern the design of many complex systems that process energy, materials and information.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431522, year = {2016}, author = {Libby, E and Conlin, PL and Kerr, B and Ratcliff, WC}, title = {Stabilizing multicellularity through ratcheting.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431522}, issn = {1471-2970}, mesh = {*Adaptation, Biological ; *Biological Evolution ; Eukaryota/genetics/*physiology ; Models, Genetic ; *Selection, Genetic ; }, abstract = {The evolutionary transition to multicellularity probably began with the formation of simple undifferentiated cellular groups. Such groups evolve readily in diverse lineages of extant unicellular taxa, suggesting that there are few genetic barriers to this first key step. This may act as a double-edged sword: labile transitions between unicellular and multicellular states may facilitate the evolution of simple multicellularity, but reversion to a unicellular state may inhibit the evolution of increased complexity. In this paper, we examine how multicellular adaptations can act as evolutionary 'ratchets', limiting the potential for reversion to unicellularity. We consider a nascent multicellular lineage growing in an environment that varies between favouring multicellularity and favouring unicellularity. The first type of ratcheting mutations increase cell-level fitness in a multicellular context but are costly in a single-celled context, reducing the fitness of revertants. The second type of ratcheting mutations directly decrease the probability that a mutation will result in reversion (either as a pleiotropic consequence or via direct modification of switch rates). We show that both types of ratcheting mutations act to stabilize the multicellular state. We also identify synergistic effects between the two types of ratcheting mutations in which the presence of one creates the selective conditions favouring the other. Ratcheting mutations may play a key role in diverse evolutionary transitions in individuality, sustaining selection on the new higher-level organism by constraining evolutionary reversion.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431521, year = {2016}, author = {Newman, SA}, title = {'Biogeneric' developmental processes: drivers of major transitions in animal evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431521}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Evolution, Molecular ; Extremities/anatomy & histology ; Fishes/anatomy & histology/*physiology ; Invertebrates/*physiology ; *Morphogenesis ; }, abstract = {Using three examples drawn from animal systems, I advance the hypothesis that major transitions in multicellular evolution often involved the constitution of new cell-based materials with unprecedented morphogenetic capabilities. I term the materials and formative processes that arise when highly evolved cells are incorporated into mesoscale matter 'biogeneric', to reflect their commonality with, and distinctiveness from, the organizational properties of non-living materials. The first transition arose by the innovation of classical cell-adhesive cadherins with transmembrane linkage to the cytoskeleton and the appearance of the morphogen Wnt, transforming some ancestral unicellular holozoans into 'liquid tissues', and thereby originating the metazoans. The second transition involved the new capabilities, within a basal metazoan population, of producing a mechanically stable basal lamina, and of planar cell polarization. This gave rise to the eumetazoans, initially diploblastic (two-layered) forms, and then with the addition of extracellular matrices promoting epithelial-mesenchymal transformation, three-layered triploblasts. The last example is the fin-to-limb transition. Here, the components of a molecular network that promoted the development of species-idiosyncratic endoskeletal elements in gnathostome ancestors are proposed to have evolved to a dynamical regime in which they constituted a Turing-type reaction-diffusion system capable of organizing the stereotypical arrays of elements of lobe-finned fish and tetrapods. The contrasting implications of the biogeneric materials-based and neo-Darwinian perspectives for understanding major evolutionary transitions are discussed.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431520, year = {2016}, author = {Koonin, EV}, title = {Viruses and mobile elements as drivers of evolutionary transitions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431520}, issn = {1471-2970}, mesh = {*Biological Evolution ; Interspersed Repetitive Sequences/*genetics ; Viruses/*genetics ; }, abstract = {The history of life is punctuated by evolutionary transitions which engender emergence of new levels of biological organization that involves selection acting at increasingly complex ensembles of biological entities. Major evolutionary transitions include the origin of prokaryotic and then eukaryotic cells, multicellular organisms and eusocial animals. All or nearly all cellular life forms are hosts to diverse selfish genetic elements with various levels of autonomy including plasmids, transposons and viruses. I present evidence that, at least up to and including the origin of multicellularity, evolutionary transitions are driven by the coevolution of hosts with these genetic parasites along with sharing of 'public goods'. Selfish elements drive evolutionary transitions at two distinct levels. First, mathematical modelling of evolutionary processes, such as evolution of primitive replicator populations or unicellular organisms, indicates that only increasing organizational complexity, e.g. emergence of multicellular aggregates, can prevent the collapse of the host-parasite system under the pressure of parasites. Second, comparative genomic analysis reveals numerous cases of recruitment of genes with essential functions in cellular life forms, including those that enable evolutionary transitions.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27431519, year = {2016}, author = {Elena, SF}, title = {Evolutionary transitions during RNA virus experimental evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1701}, pages = {}, pmid = {27431519}, issn = {1471-2970}, mesh = {*Biological Evolution ; Coinfection/virology ; Evolution, Molecular ; *Genome, Viral ; *Microbial Interactions ; RNA Viruses/*genetics/physiology ; }, abstract = {In their search to understand the evolution of biological complexity, John Maynard Smith and Eörs Szathmáry put forward the notion of major evolutionary transitions as those in which elementary units get together to generate something new, larger and more complex. The origins of chromosomes, eukaryotic cells, multicellular organisms, colonies and, more recently, language and technological societies are examples that clearly illustrate this notion. However, a transition may be considered as anecdotal or as major depending on the specific level of biological organization under study. In this contribution, I will argue that transitions may also be occurring at a much smaller scale of biological organization: the viral world. Not only that, but also that we can observe in real time how these major transitions take place during experimental evolution. I will review the outcome of recent evolution experiments with viruses that illustrate four major evolutionary transitions: (i) the origin of a new virus that infects an otherwise inaccessible host and completely changes the way it interacts with the host regulatory and metabolic networks, (ii) the incorporation and loss of genes, (iii) the origin of segmented genomes from a non-segmented one, and (iv) the evolution of cooperative behaviour and cheating between different viruses or strains during co-infection of the same host.This article is part of the themed issue 'The major synthetic evolutionary transitions'.}, } @article {pmid27412854, year = {2016}, author = {Smeds, L and Qvarnström, A and Ellegren, H}, title = {Direct estimate of the rate of germline mutation in a bird.}, journal = {Genome research}, volume = {26}, number = {9}, pages = {1211-1218}, pmid = {27412854}, issn = {1549-5469}, mesh = {Animals ; *Evolution, Molecular ; Genome ; Germ-Line Mutation/*genetics ; High-Throughput Nucleotide Sequencing ; Mutation Rate ; Pedigree ; Songbirds/*genetics ; }, abstract = {The fidelity of DNA replication together with repair mechanisms ensure that the genetic material is properly copied from one generation to another. However, on extremely rare occasions when damages to DNA or replication errors are not repaired, germline mutations can be transmitted to the next generation. Because of the rarity of these events, studying the rate at which new mutations arise across organisms has been a great challenge, especially in multicellular nonmodel organisms with large genomes. We sequenced the genomes of 11 birds from a three-generation pedigree of the collared flycatcher (Ficedula albicollis) and used highly stringent bioinformatic criteria for mutation detection and used several procedures to validate mutations, including following the stable inheritance of new mutations to subsequent generations. We identified 55 de novo mutations with a 10-fold enrichment of mutations at CpG sites and with only a modest male mutation bias. The estimated rate of mutation per site per generation was 4.6 × 10(-9), which corresponds to 2.3 × 10(-9) mutations per site per year. Compared to mammals, this is similar to mouse but about half of that reported for humans, which may be due to the higher frequency of male mutations in humans. We confirm that mutation rate scales positively with genome size and that there is a strong negative relationship between mutation rate and effective population size, in line with the drift-barrier hypothesis. Our study illustrates that it should be feasible to obtain direct estimates of the rate of mutation in essentially any organism from which family material can be obtained.}, } @article {pmid27411810, year = {2016}, author = {Cook, LM and Araujo, A and Pow-Sang, JM and Budzevich, MM and Basanta, D and Lynch, CC}, title = {Predictive computational modeling to define effective treatment strategies for bone metastatic prostate cancer.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {29384}, pmid = {27411810}, issn = {2045-2322}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; R01 CA143094/CA/NCI NIH HHS/United States ; U01 CA151924/CA/NCI NIH HHS/United States ; U01 CA202958/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bone Neoplasms/*secondary/*therapy ; Bone and Bones/pathology ; Cell Differentiation ; Cell Survival ; *Computer Simulation ; Humans ; Male ; Mice ; Mice, SCID ; Neoplasm Metastasis ; Osteoblasts/cytology ; Osteoclasts/cytology ; Osteolysis ; Prostate/pathology ; Prostatic Neoplasms/*pathology/*therapy ; Transforming Growth Factor beta1/antagonists & inhibitors/*metabolism ; }, abstract = {The ability to rapidly assess the efficacy of therapeutic strategies for incurable bone metastatic prostate cancer is an urgent need. Pre-clinical in vivo models are limited in their ability to define the temporal effects of therapies on simultaneous multicellular interactions in the cancer-bone microenvironment. Integrating biological and computational modeling approaches can overcome this limitation. Here, we generated a biologically driven discrete hybrid cellular automaton (HCA) model of bone metastatic prostate cancer to identify the optimal therapeutic window for putative targeted therapies. As proof of principle, we focused on TGFβ because of its known pleiotropic cellular effects. HCA simulations predict an optimal effect for TGFβ inhibition in a pre-metastatic setting with quantitative outputs indicating a significant impact on prostate cancer cell viability, osteoclast formation and osteoblast differentiation. In silico predictions were validated in vivo with models of bone metastatic prostate cancer (PAIII and C4-2B). Analysis of human bone metastatic prostate cancer specimens reveals heterogeneous cancer cell use of TGFβ. Patient specific information was seeded into the HCA model to predict the effect of TGFβ inhibitor treatment on disease evolution. Collectively, we demonstrate how an integrated computational/biological approach can rapidly optimize the efficacy of potential targeted therapies on bone metastatic prostate cancer.}, } @article {pmid27402737, year = {2016}, author = {Wahl, ME and Murray, AW}, title = {Multicellularity makes somatic differentiation evolutionarily stable.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {30}, pages = {8362-8367}, pmid = {27402737}, issn = {1091-6490}, support = {P50 GM068763/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; *Cell Differentiation ; Cell Division/genetics ; *Cell Lineage ; Cell Survival/genetics ; Genetic Engineering/methods ; Germ Cells/*cytology/metabolism ; *Models, Biological ; Mutation ; Saccharomyces cerevisiae/cytology/genetics ; }, abstract = {Many multicellular organisms produce two cell lineages: germ cells, whose descendants produce the next generation, and somatic cells, which support, protect, and disperse the germ cells. This germ-soma demarcation has evolved independently in dozens of multicellular taxa but is absent in unicellular species. A common explanation holds that in these organisms, inefficient intercellular nutrient exchange compels the fitness cost of producing nonreproductive somatic cells to outweigh any potential benefits. We propose instead that the absence of unicellular, soma-producing populations reflects their susceptibility to invasion by nondifferentiating mutants that ultimately eradicate the soma-producing lineage. We argue that multicellularity can prevent the victory of such mutants by giving germ cells preferential access to the benefits conferred by somatic cells. The absence of natural unicellular, soma-producing species previously prevented these hypotheses from being directly tested in vivo: to overcome this obstacle, we engineered strains of the budding yeast Saccharomyces cerevisiae that differ only in the presence or absence of multicellularity and somatic differentiation, permitting direct comparisons between organisms with different lifestyles. Our strains implement the essential features of irreversible conversion from germ line to soma, reproductive division of labor, and clonal multicellularity while maintaining sufficient generality to permit broad extension of our conclusions. Our somatic cells can provide fitness benefits that exceed the reproductive costs of their production, even in unicellular strains. We find that nondifferentiating mutants overtake unicellular populations but are outcompeted by multicellular, soma-producing strains, suggesting that multicellularity confers evolutionary stability to somatic differentiation.}, } @article {pmid27401232, year = {2016}, author = {Francois, CM and Duret, L and Simon, L and Mermillod-Blondin, F and Malard, F and Konecny-Dupré, L and Planel, R and Penel, S and Douady, CJ and Lefébure, T}, title = {No Evidence That Nitrogen Limitation Influences the Elemental Composition of Isopod Transcriptomes and Proteomes.}, journal = {Molecular biology and evolution}, volume = {33}, number = {10}, pages = {2605-2620}, doi = {10.1093/molbev/msw131}, pmid = {27401232}, issn = {1537-1719}, mesh = {Amino Acids/genetics/metabolism ; Animals ; Ecosystem ; Isopoda/*genetics/*metabolism ; Nitrogen/*deficiency/*metabolism ; Nucleotides/genetics/metabolism ; Phylogeny ; Proteome ; Selection, Genetic ; Transcriptome ; }, abstract = {The field of stoichiogenomics aims at understanding the influence of nutrient limitations on the elemental composition of the genome, transcriptome, and proteome. The 20 amino acids and the 4 nt differ in the number of nutrients they contain, such as nitrogen (N). Thus, N limitation shall theoretically select for changes in the composition of proteins or RNAs through preferential use of N-poor amino acids or nucleotides, which will decrease the N-budget of an organism. While these N-saving mechanisms have been evidenced in microorganisms, they remain controversial in multicellular eukaryotes. In this study, we used 13 surface and subterranean isopod species pairs that face strongly contrasted N limitations, either in terms of quantity or quality. We combined in situ nutrient quantification and transcriptome sequencing to test if N limitation selected for N-savings through changes in the expression and composition of the transcriptome and proteome. No evidence of N-savings was found in the total N-budget of transcriptomes or proteomes or in the average protein N-cost. Nevertheless, subterranean species evolving in N-depleted habitats displayed lower N-usage at their third codon positions. To test if this convergent compositional change was driven by natural selection, we developed a method to detect the strand-asymmetric signature that stoichiogenomic selection should leave in the substitution pattern. No such signature was evidenced, indicating that the observed stoichiogenomic-like patterns were attributable to nonadaptive processes. The absence of stoichiogenomic signal despite strong N limitation within a powerful phylogenetic framework casts doubt on the existence of stoichiogenomic mechanisms in metazoans.}, } @article {pmid27391808, year = {2016}, author = {Jeong, SY and Lee, JH and Shin, Y and Chung, S and Kuh, HJ}, title = {Co-Culture of Tumor Spheroids and Fibroblasts in a Collagen Matrix-Incorporated Microfluidic Chip Mimics Reciprocal Activation in Solid Tumor Microenvironment.}, journal = {PloS one}, volume = {11}, number = {7}, pages = {e0159013}, pmid = {27391808}, issn = {1932-6203}, mesh = {Coculture Techniques/instrumentation/methods ; Collagen/*chemistry ; Colorectal Neoplasms/*metabolism/pathology ; Extracellular Matrix/chemistry ; Fibroblasts/*metabolism/pathology ; Humans ; *Lab-On-A-Chip Devices ; Spheroids, Cellular/*metabolism/pathology ; *Tumor Microenvironment ; }, abstract = {Multicellular 3D culture and interaction with stromal components are considered essential elements in establishing a 'more clinically relevant' tumor model. Matrix-embedded 3D cultures using a microfluidic chip platform can recapitulate the microscale interaction within tumor microenvironments. As a major component of tumor microenvironment, cancer-associated fibroblasts (CAFs) play a role in cancer progression and drug resistance. Here, we present a microfluidic chip-based tumor tissue culture model that integrates 3D tumor spheroids (TSs) with CAF in proximity within a hydrogel scaffold. HT-29 human colorectal carcinoma cells grew into 3D TSs and the growth was stimulated when co-cultured with fibroblasts as shown by 1.5-folds increase of % changes in diameter over 5 days. TS cultured for 6 days showed a reduced expression of Ki-67 along with increased expression of fibronectin when co-cultured with fibroblasts compared to mono-cultured TSs. Fibroblasts were activated under co-culture conditions, as demonstrated by increases in α-SMA expression and migratory activity. When exposed to paclitaxel, a survival advantage was observed in TSs co-cultured with activated fibroblasts. Overall, we demonstrated the reciprocal interaction between TSs and fibroblasts in our 7-channel microfluidic chip. The co-culture of 3D TS-CAF in a collagen matrix-incorporated microfluidic chip may be useful to study the tumor microenvironment and for evaluation of drug screening and evaluation.}, } @article {pmid27383475, year = {2016}, author = {Baek, SY and Jang, KH and Choi, EH and Ryu, SH and Kim, SK and Lee, JH and Lim, YJ and Lee, J and Jun, J and Kwak, M and Lee, YS and Hwang, JS and Venmathi Maran, BA and Chang, CY and Kim, IH and Hwang, UW}, title = {DNA Barcoding of Metazoan Zooplankton Copepods from South Korea.}, journal = {PloS one}, volume = {11}, number = {7}, pages = {e0157307}, pmid = {27383475}, issn = {1932-6203}, mesh = {Animals ; Copepoda/*genetics ; *DNA Barcoding, Taxonomic ; Electron Transport Complex IV/*genetics ; Genes, Mitochondrial ; Genetic Variation ; Geography ; Phylogeny ; Republic of Korea ; Sequence Analysis, DNA ; Species Specificity ; Zooplankton/*genetics ; }, abstract = {Copepods, small aquatic crustaceans, are the most abundant metazoan zooplankton and outnumber every other group of multicellular animals on earth. In spite of ecological and biological importance in aquatic environment, their morphological plasticity, originated from their various lifestyles and their incomparable capacity to adapt to a variety of environments, has made the identification of species challenging, even for expert taxonomists. Molecular approaches to species identification have allowed rapid detection, discrimination, and identification of cryptic or sibling species based on DNA sequence data. We examined sequence variation of a partial mitochondrial cytochrome C oxidase I gene (COI) from 133 copepod individuals collected from the Korean Peninsula, in order to identify and discriminate 94 copepod species covering six copepod orders of Calanoida, Cyclopoida, Harpacticoida, Monstrilloida, Poecilostomatoida and Siphonostomatoida. The results showed that there exists a clear gap with ca. 20 fold difference between the averages of within-specific sequence divergence (2.42%) and that of between-specific sequence divergence (42.79%) in COI, suggesting the plausible utility of this gene in delimitating copepod species. The results showed, with the COI barcoding data among 94 copepod species, that a copepod species could be distinguished from the others very clearly, only with four exceptions as followings: Mesocyclops dissimilis-Mesocyclops pehpeiensis (0.26% K2P distance in percent) and Oithona davisae-Oithona similis (1.1%) in Cyclopoida, Ostrincola japonica-Pseudomyicola spinosus (1.5%) in Poecilostomatoida, and Hatschekia japonica-Caligus quadratus (5.2%) in Siphonostomatoida. Thus, it strongly indicated that COI may be a useful tool in identifying various copepod species and make an initial progress toward the construction of a comprehensive DNA barcode database for copepods inhabiting the Korean Peninsula.}, } @article {pmid27379901, year = {2016}, author = {Olson, BJ and Nedelcu, AM}, title = {Co-option during the evolution of multicellular and developmental complexity in the volvocine green algae.}, journal = {Current opinion in genetics & development}, volume = {39}, number = {}, pages = {107-115}, doi = {10.1016/j.gde.2016.06.003}, pmid = {27379901}, issn = {1879-0380}, mesh = {Cell Differentiation/*genetics ; Chlamydomonas/classification/genetics/growth & development ; Chlorophyta/classification/*genetics/growth & development ; *Evolution, Molecular ; Germ Cells/growth & development ; *Phylogeny ; Volvox/classification/genetics/growth & development ; }, abstract = {Despite its major impact on the evolution of Life on Earth, the transition to multicellularity remains poorly understood, especially in terms of its genetic basis. The volvocine algae are a group of closely related species that range in morphology from unicellular individuals (Chlamydomonas) to undifferentiated multicellular forms (Gonium) and complex organisms with distinct developmental programs and one (Pleodorina) or two (Volvox) specialized cell types. Modern genetic approaches, complemented by the recent sequencing of genomes from several key species, revealed that co-option of existing genes and pathways is the primary driving force for the evolution of multicellularity in this lineage. The initial transition to undifferentiated multicellularity, as typified by the extant Gonium, was driven primarily by the co-option of cell cycle regulation. Further morphological and developmental innovations in the lineage leading to Volvox resulted from additional co-option events involving genes important for embryonic inversion, asymmetric cell division, somatic and germ cell differentiation and the structure and function of the extracellular matrix. Because of their relatively low but variable levels of morphological and developmental complexity, simple underlying genetics and recent evolutionary history, the volvocine algae are providing significant insight into our understanding of the genetics and evolution of major developmental and morphological traits.}, } @article {pmid27374341, year = {2016}, author = {Mikhailov, KV and Slyusarev, GS and Nikitin, MA and Logacheva, MD and Penin, AA and Aleoshin, VV and Panchin, YV}, title = {The Genome of Intoshia linei Affirms Orthonectids as Highly Simplified Spiralians.}, journal = {Current biology : CB}, volume = {26}, number = {13}, pages = {1768-1774}, doi = {10.1016/j.cub.2016.05.007}, pmid = {27374341}, issn = {1879-0445}, mesh = {Animals ; Female ; *Genome ; Host-Parasite Interactions ; Invertebrates/*classification/genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Orthonectids are rare parasites of marine invertebrates [1] that are commonly treated in textbooks as a taxon of uncertain affinity [2]. Trophic forms of orthonectids reside in the tissues of their hosts as multinucleated plasmodia, generating short-lived, worm-like ciliated female and male organisms that exit into the environment for copulation [3]. These ephemeral males and females are composed of just several hundred somatic cells and are deprived of digestive, circulatory, or excretory systems. Since their discovery in the 19(th) century, the orthonectids were described as organisms with no differentiated cell types and considered as part of Mesozoa, a putative link between multicellular animals and their unicellular relatives. More recently, this view was challenged as the new data suggested that orthonectids are animals that became simplified due to their parasitic way of life [3, 4]. Here, we report the genomic sequence of Intoshia linei, one of about 20 known species of orthonectids. The genomic data confirm recent morphological analysis asserting that orthonectids are members of Spiralia and possess muscular and nervous systems [5]. The 43-Mbp genome of I. linei encodes about 9,000 genes and retains those essential for the development and activity of muscular and nervous systems. The simplification of orthonectid body plan is associated with considerable reduction of metazoan developmental genes, leaving what might be viewed as the minimal gene set necessary to retain critical bilaterian features.}, } @article {pmid29368868, year = {2016}, author = {Zakharov, IA}, title = {[Horizontal gene transfer into the genomes of insects].}, journal = {Genetika}, volume = {52}, number = {7}, pages = {804-809}, pmid = {29368868}, issn = {0016-6758}, mesh = {Animals ; *Evolution, Molecular ; Gene Transfer, Horizontal/*physiology ; Insecta/*genetics ; }, abstract = {Horizontal gene transfer (HGT) is widespread in the world of prokaryotes, but the examples of this phenomenon among multicellular animals, particularly insects, are few. This review examines the transfer of genetic material to the nuclear genomes of insects from the mitochondrial genome (intracellular HGT), as well as from the genomes of viruses, bacteria, fungi, and unrelated insects. In most cases, the mechanisms of this transfer are unknown. Many pro- and eukaryotic genes that moved through the HGT are expressed in the insect genome and in some cases can provide the evolutionary innovations that are considered as aromorphoses.}, } @article {pmid27357338, year = {2016}, author = {Glöckner, G and Lawal, HM and Felder, M and Singh, R and Singer, G and Weijer, CJ and Schaap, P}, title = {The multicellularity genes of dictyostelid social amoebas.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {12085}, pmid = {27357338}, issn = {2041-1723}, support = {//Wellcome Trust/United Kingdom ; BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Cell Differentiation/genetics ; Dictyostelium/*genetics ; Gene Expression Profiling ; Gene Transfer, Horizontal ; *Genes, Essential ; Whole Genome Sequencing ; }, abstract = {The evolution of multicellularity enabled specialization of cells, but required novel signalling mechanisms for regulating cell differentiation. Early multicellular organisms are mostly extinct and the origins of these mechanisms are unknown. Here using comparative genome and transcriptome analysis across eight uni- and multicellular amoebozoan genomes, we find that 80% of proteins essential for the development of multicellular Dictyostelia are already present in their unicellular relatives. This set is enriched in cytosolic and nuclear proteins, and protein kinases. The remaining 20%, unique to Dictyostelia, mostly consists of extracellularly exposed and secreted proteins, with roles in sensing and recognition, while several genes for synthesis of signals that induce cell-type specialization were acquired by lateral gene transfer. Across Dictyostelia, changes in gene expression correspond more strongly with phenotypic innovation than changes in protein functional domains. We conclude that the transition to multicellularity required novel signals and sensors rather than novel signal processing mechanisms.}, } @article {pmid27356975, year = {2016}, author = {Yerramsetty, P and Stata, M and Siford, R and Sage, TL and Sage, RF and Wong, GK and Albert, VA and Berry, JO}, title = {Evolution of RLSB, a nuclear-encoded S1 domain RNA binding protein associated with post-transcriptional regulation of plastid-encoded rbcL mRNA in vascular plants.}, journal = {BMC evolutionary biology}, volume = {16}, number = {1}, pages = {141}, pmid = {27356975}, issn = {1471-2148}, mesh = {Chloroplasts/genetics ; *Evolution, Molecular ; *Gene Expression Regulation, Plant ; Magnoliopsida/*genetics ; Photosynthesis ; Phylogeny ; Plant Leaves/genetics ; Plant Proteins/*genetics/metabolism ; Plastids/*genetics/metabolism ; Poaceae/genetics ; RNA Processing, Post-Transcriptional ; RNA, Messenger/metabolism ; RNA-Binding Proteins/*genetics ; Ribulose-Bisphosphate Carboxylase/*genetics ; Zea mays/genetics ; }, abstract = {BACKGROUND: RLSB, an S-1 domain RNA binding protein of Arabidopsis, selectively binds rbcL mRNA and co-localizes with Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) within chloroplasts of C3 and C4 plants. Previous studies using both Arabidopsis (C3) and maize (C4) suggest RLSB homologs are post-transcriptional regulators of plastid-encoded rbcL mRNA. While RLSB accumulates in all Arabidopsis leaf chlorenchyma cells, in C4 leaves RLSB-like proteins accumulate only within Rubisco-containing bundle sheath chloroplasts of Kranz-type species, and only within central compartment chloroplasts in the single cell C4 plant Bienertia. Our recent evidence implicates this mRNA binding protein as a primary determinant of rbcL expression, cellular localization/compartmentalization, and photosynthetic function in all multicellular green plants. This study addresses the hypothesis that RLSB is a highly conserved Rubisco regulatory factor that occurs in the chloroplasts all higher plants.

RESULTS: Phylogenetic analysis has identified RLSB orthologs and paralogs in all major plant groups, from ancient liverworts to recent angiosperms. RLSB homologs were also identified in algae of the division Charophyta, a lineage closely related to land plants. RLSB-like sequences were not identified in any other algae, suggesting that it may be specific to the evolutionary line leading to land plants. The RLSB family occurs in single copy across most angiosperms, although a few species with two copies were identified, seemingly randomly distributed throughout the various taxa, although perhaps correlating in some cases with known ancient whole genome duplications. Monocots of the order Poales (Poaceae and Cyperaceae) were found to contain two copies, designated here as RLSB-a and RLSB-b, with only RLSB-a implicated in the regulation of rbcL across the maize developmental gradient. Analysis of microsynteny in angiosperms revealed high levels of conservation across eudicot species and for both paralogs in grasses, highlighting the possible importance of maintaining this gene and its surrounding genomic regions.

CONCLUSIONS: Findings presented here indicate that the RLSB family originated as a unique gene in land plant evolution, perhaps in the common ancestor of charophytes and higher plants. Purifying selection has maintained this as a highly conserved single- or two-copy gene across most extant species, with several conserved gene duplications. Together with previous findings, this study suggests that RLSB has been sustained as an important regulatory protein throughout the course of land plant evolution. While only RLSB-a has been directly implicated in rbcL regulation in maize, RLSB-b could have an overlapping function in the co-regulation of rbcL, or may have diverged as a regulator of one or more other plastid-encoded mRNAs. This analysis confirms that RLSB is an important and unique photosynthetic regulatory protein that has been continuously expressed in land plants as they emerged and diversified from their ancient common ancestor.}, } @article {pmid27355941, year = {2016}, author = {Stojković, S and Podolski-Renić, A and Dinić, J and Pavković, Ž and Ayuso, JM and Fernández, LJ and Ochoa, I and Pérez-García, VM and Pešić, V and Pešić, M}, title = {Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells-Characterization of a New in Vivo Model.}, journal = {Molecules (Basel, Switzerland)}, volume = {21}, number = {7}, pages = {}, pmid = {27355941}, issn = {1420-3049}, mesh = {Animals ; Antineoplastic Agents, Alkylating/*pharmacology ; Behavior, Animal/drug effects ; Brain Neoplasms/drug therapy/*genetics/*pathology ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; DNA Damage/*drug effects ; Disease Models, Animal ; *Drug Resistance, Neoplasm ; Glioma/drug therapy/*genetics/*pathology ; Humans ; Motor Activity/drug effects ; Neoplasm Invasiveness ; Rats ; }, abstract = {Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide (TMZ). Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells' invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats' behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells.}, } @article {pmid27339473, year = {2016}, author = {Chisholm, RH and Lorenzi, T and Clairambault, J}, title = {Cell population heterogeneity and evolution towards drug resistance in cancer: Biological and mathematical assessment, theoretical treatment optimisation.}, journal = {Biochimica et biophysica acta}, volume = {1860}, number = {11 Pt B}, pages = {2627-2645}, doi = {10.1016/j.bbagen.2016.06.009}, pmid = {27339473}, issn = {0006-3002}, mesh = {Drug Resistance, Neoplasm/*drug effects ; Humans ; Immunotherapy/methods ; Models, Biological ; Models, Theoretical ; Neoplasms/*drug therapy/*pathology ; Phenotype ; }, abstract = {BACKGROUND: Drug-induced drug resistance in cancer has been attributed to diverse biological mechanisms at the individual cell or cell population scale, relying on stochastically or epigenetically varying expression of phenotypes at the single cell level, and on the adaptability of tumours at the cell population level.

SCOPE OF REVIEW: We focus on intra-tumour heterogeneity, namely between-cell variability within cancer cell populations, to account for drug resistance. To shed light on such heterogeneity, we review evolutionary mechanisms that encompass the great evolution that has designed multicellular organisms, as well as smaller windows of evolution on the time scale of human disease. We also present mathematical models used to predict drug resistance in cancer and optimal control methods that can circumvent it in combined therapeutic strategies.

MAJOR CONCLUSIONS: Plasticity in cancer cells, i.e., partial reversal to a stem-like status in individual cells and resulting adaptability of cancer cell populations, may be viewed as backward evolution making cancer cell populations resistant to drug insult. This reversible plasticity is captured by mathematical models that incorporate between-cell heterogeneity through continuous phenotypic variables. Such models have the benefit of being compatible with optimal control methods for the design of optimised therapeutic protocols involving combinations of cytotoxic and cytostatic treatments with epigenetic drugs and immunotherapies.

GENERAL SIGNIFICANCE: Gathering knowledge from cancer and evolutionary biology with physiologically based mathematical models of cell population dynamics should provide oncologists with a rationale to design optimised therapeutic strategies to circumvent drug resistance, that still remains a major pitfall of cancer therapeutics. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.}, } @article {pmid27338490, year = {2016}, author = {Shapiro, JA}, title = {Nothing in Evolution Makes Sense Except in the Light of Genomics: Read-Write Genome Evolution as an Active Biological Process.}, journal = {Biology}, volume = {5}, number = {2}, pages = {}, pmid = {27338490}, issn = {2079-7737}, abstract = {The 21st century genomics-based analysis of evolutionary variation reveals a number of novel features impossible to predict when Dobzhansky and other evolutionary biologists formulated the neo-Darwinian Modern Synthesis in the middle of the last century. These include three distinct realms of cell evolution; symbiogenetic fusions forming eukaryotic cells with multiple genome compartments; horizontal organelle, virus and DNA transfers; functional organization of proteins as systems of interacting domains subject to rapid evolution by exon shuffling and exonization; distributed genome networks integrated by mobile repetitive regulatory signals; and regulation of multicellular development by non-coding lncRNAs containing repetitive sequence components. Rather than single gene traits, all phenotypes involve coordinated activity by multiple interacting cell molecules. Genomes contain abundant and functional repetitive components in addition to the unique coding sequences envisaged in the early days of molecular biology. Combinatorial coding, plus the biochemical abilities cells possess to rearrange DNA molecules, constitute a powerful toolbox for adaptive genome rewriting. That is, cells possess "Read-Write Genomes" they alter by numerous biochemical processes capable of rapidly restructuring cellular DNA molecules. Rather than viewing genome evolution as a series of accidental modifications, we can now study it as a complex biological process of active self-modification.}, } @article {pmid27320726, year = {2016}, author = {Bao, W and Greenwold, MJ and Sawyer, RH}, title = {Expressed miRNAs target feather related mRNAs involved in cell signaling, cell adhesion and structure during chicken epidermal development.}, journal = {Gene}, volume = {591}, number = {2}, pages = {393-402}, pmid = {27320726}, issn = {1879-0038}, support = {P20 GM103499/GM/NIGMS NIH HHS/United States ; P20 RR016461/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; *Cell Adhesion ; Chickens ; Epidermal Cells ; Epidermis/growth & development/*metabolism ; Evolution, Molecular ; Feathers/*metabolism ; MicroRNAs/*metabolism ; RNA, Messenger/*metabolism ; *Signal Transduction ; Tenascin/metabolism ; Tissue Array Analysis ; }, abstract = {MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Previous studies have shown that miRNA regulation contributes to a diverse set of processes including cellular differentiation and morphogenesis which leads to the creation of different cell types in multicellular organisms and is thus key to animal development. Feathers are one of the most distinctive features of extant birds and are important for multiple functions including flight, thermal regulation, and sexual selection. However, the role of miRNAs in feather development has been woefully understudied despite the identification of cell signaling pathways, cell adhesion molecules and structural genes involved in feather development. In this study, we performed a microarray experiment comparing the expression of miRNAs and mRNAs among three embryonic stages of development and two tissues (scutate scale and feather) of the chicken. We combined this expression data with miRNA target prediction tools and a curated list of feather related genes to produce a set of 19 miRNA-mRNA duplexes. These targeted mRNAs have been previously identified as important cell signaling and cell adhesion genes as well as structural genes involved in feather and scale morphogenesis. Interestingly, the miRNA target site of the cell signaling pathway gene, Aldehyde Dehydrogenase 1 Family, Member A3 (ALDH1A3), is unique to birds indicating a novel role in Aves. The identified miRNA target site of the cell adhesion gene, Tenascin C (TNC), is only found in specific chicken TNC splice variants that are differentially expressed in developing scutate scale and feather tissue indicating an important role of miRNA regulation in epidermal differentiation. Additionally, we found that β-keratins, a major structural component of avian and reptilian epidermal appendages, are targeted by multiple miRNA genes. In conclusion, our work provides quantitative expression data on miRNAs and mRNAs during feather and scale development and has produced a highly diverse, but manageable list of miRNA-mRNA duplexes for future validation experiments.}, } @article {pmid27319135, year = {2016}, author = {Salasa, A and Mercadoc, MI and Zampini, IC and Ponessa, GI and Isla, MI}, title = {Determination of Botanical Origin of Propolis from Monte Region of Argentina by Histological and Chemical Methods.}, journal = {Natural product communications}, volume = {11}, number = {5}, pages = {627-630}, pmid = {27319135}, issn = {1934-578X}, mesh = {Argentina ; Fabaceae/*cytology ; Larrea/cytology ; Propolis/*analysis/chemistry ; }, abstract = {Propolis production by honey bees is the result of a selective harvest of exudates from plants in the neighborhood of the hive. This product is used in Argentina as a food supplement and alternative medicine. The aim of this study was to determine the botanical origin of propolis from the arid regions of Monte of Argentina using rapid histochemical techniques and by comparison of TLC and HPLC-DAD chromatographic profiles with extract profiles obtained from Zuccagnia punctata, Larrea divaricata and Larrea cuneifolia, plant species that grow in the study area as a natural community named "jarillal". Microscopical analysis revealed the presence of several Z. punctata structures, such as multicellular trichomes, leaflets, stems and young leaves. Remarkable was the richness of the propolis in two bioactive chalcones, also present in Z. punctata resin; these compounds can be regarded as possible markers for propolis identification and justify its use as a dietary supplement, functional food and medicinal product. This study indicates that the source of resin used by honey bees to produce propolis in the Monte region of Argentina is only Z. punctata, a native shrub widespread in this phytogeographical region, while other more abundant species (L. divaricata and L. cuneifolia) in the region were not found, indicating that this propolis could be defined as a mono-resin, type-Zuccagnia.}, } @article {pmid27318693, year = {2016}, author = {Hoffmeyer, TT and Burkhardt, P}, title = {Choanoflagellate models - Monosiga brevicollis and Salpingoeca rosetta.}, journal = {Current opinion in genetics & development}, volume = {39}, number = {}, pages = {42-47}, doi = {10.1016/j.gde.2016.05.016}, pmid = {27318693}, issn = {1879-0380}, mesh = {Animals ; Choanoflagellata/*genetics/growth & development ; *Evolution, Molecular ; Genome ; Models, Genetic ; *Phylogeny ; }, abstract = {Choanoflagellates are the closest single-celled relatives of animals and provide fascinating insights into developmental processes in animals. Two species, the choanoflagellates Monosiga brevicollis and Salpingoeca rosetta are emerging as promising model organisms to reveal the evolutionary origin of key animal innovations. In this review, we highlight how choanoflagellates are used to study the origin of multicellularity in animals. The newly available genomic resources and functional techniques provide important insights into the function of choanoflagellate pre- and postsynaptic proteins, cell-cell adhesion and signaling molecules and the evolution of animal filopodia and thus underscore the relevance of choanoflagellate models for evolutionary biology, neurobiology and cell biology research.}, } @article {pmid27318691, year = {2016}, author = {Adamska, M}, title = {Sponges as models to study emergence of complex animals.}, journal = {Current opinion in genetics & development}, volume = {39}, number = {}, pages = {21-28}, doi = {10.1016/j.gde.2016.05.026}, pmid = {27318691}, issn = {1879-0380}, mesh = {Animals ; *Evolution, Molecular ; Gene Regulatory Networks/*genetics ; Genome ; Germ Cells/*growth & development ; Porifera/anatomy & histology/*genetics/growth & development ; Stem Cells/metabolism ; }, abstract = {The emergence of complex animal life forms remains poorly understood despite substantial interest and research in this area. To be informative, the ideal models to study transitions from single-cell organisms to the first animals and then to mammalian-level complexity should be phylogenetically strategically placed and retain ancestral characters. Sponges (Porifera) are likely to be the earliest branching animal phylum. When analysed from morphological, genomic and developmental perspectives, sponges appear to combine features of single-cell eukaryotic organisms and the complex multicellular animals (Eumetazoa). Intriguingly, homologues of components of the eumetazoan regulatory networks specifying the endoderm, the germ-cells and stem cells and (neuro) sensory cells are expressed in sponge choanocytes, archaeocytes and larval sensory cells. Studies using sponges as model systems are already bringing insights into animal evolution, and have opened avenues to further research benefitting from the recent spectacular expansion of genomic technologies.}, } @article {pmid27318097, year = {2016}, author = {Schaap, P}, title = {Evolution of developmental signalling in Dictyostelid social amoebas.}, journal = {Current opinion in genetics & development}, volume = {39}, number = {}, pages = {29-34}, pmid = {27318097}, issn = {1879-0380}, support = {//Wellcome Trust/United Kingdom ; 100293/Z/12/Z//Wellcome Trust/United Kingdom ; BB/K000799/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Cyclic AMP/genetics ; Developmental Biology ; Dictyostelium/*genetics/growth & development ; *Evolution, Molecular ; *Phylogeny ; Signal Transduction/genetics ; Stress, Physiological/*genetics ; }, abstract = {Dictyostelia represent a tractable system to resolve the evolution of cell-type specialization, with some taxa differentiating into spores only, and other taxa with additionally one or up to four somatic cell types. One of the latter forms, Dictyostelium discoideum, is a popular model system for cell biology and developmental biology with key signalling pathways controlling cell-specialization being resolved recently. For the most dominant pathways, evolutionary origins were retraced to a stress response in the unicellular ancestor, while modifications in the ancestral pathway were associated with acquisition of multicellular complexity. This review summarizes our current understanding of developmental signalling in D. discoideum and its evolution.}, } @article {pmid27300174, year = {2016}, author = {De Felici, M}, title = {The Formation and Migration of Primordial Germ Cells in Mouse and Man.}, journal = {Results and problems in cell differentiation}, volume = {58}, number = {}, pages = {23-46}, doi = {10.1007/978-3-319-31973-5_2}, pmid = {27300174}, issn = {0080-1844}, mesh = {Animals ; Epigenesis, Genetic ; Female ; Germ Cells/*cytology ; Gonads/cytology/*growth & development ; Humans ; Male ; Meiosis ; Mice ; Ovary/cytology ; Testis/cytology ; }, abstract = {In most multicellular organisms, including mammals, germ cells are at the origin of new organisms and ensure the continuation of the genetic and epigenetic information across the generations.In the mammalian germ line, the primordial germ cells (PGCs) are the precursors of the primary oocytes and prospermatogonia of fetal ovaries and testes, respectively. In mammals such as the primates, in which the formation of the primary oocytes is largely asynchronous and occurs during a relatively long period, PGCs after the arrival into the XX gonadal ridges are termed oogonia which then become primary oocytes when entering into meiotic prophase I. In the fetal testes, germ cells derived from the PGCs after gonad colonization are termed prospermatogonia or gonocytes.One of the most fascinating aspect of the mammalian germline development is that it is probably the first cell lineage to be established in the embryo by epigenetic mechanisms and that these inductive events happen in extraembryonic tissues much earlier that gonad develop inside the embryo proper. Moreover, such events prepare the germ cells for totipotency through genetic and epigenetic regulations of their genome function. How this occurs remained a mystery until short time ago.In this chapter, I will report and discuss the most recent advances in the cellular and molecular mechanisms underlying the formation in extraembryonic tissues and migration of PGCs toward the gonadal ridges made primarily by studies carried out in the mouse with some perspective in the human. Established concepts about these processes will be only summarized when necessary since they are widely described and discussed in many excellent reviews; most of them are cited in the text below.}, } @article {pmid27298474, year = {2016}, author = {Foley, RA}, title = {Mosaic evolution and the pattern of transitions in the hominin lineage.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1698}, pages = {}, pmid = {27298474}, issn = {1471-2970}, mesh = {*Adaptation, Biological ; Animals ; *Biological Evolution ; Fossils/*anatomy & histology ; Hominidae/*anatomy & histology ; Humans ; }, abstract = {Humans are uniquely unique, in terms of the extreme differences between them and other living organisms, and the impact they are having on the biosphere. The evolution of humans can be seen, as has been proposed, as one of the major transitions in evolution, on a par with the origins of multicellular organisms or the eukaryotic cell (Maynard Smith & Szathmáry 1997 Major transitions in evolution). Major transitions require the evolution of greater complexity and the emergence of new evolutionary levels or processes. Does human evolution meet these conditions? I explore the diversity of evidence on the nature of transitions in human evolution. Four levels of transition are proposed-baseline, novel taxa, novel adaptive zones and major transitions-and the pattern of human evolution considered in the light of these. The primary conclusions are that changes in human evolution occur continuously and cumulatively; that novel taxa and the appearance of new adaptations are not clustered very tightly in particular periods, although there are three broad transitional phases (Pliocene, Plio-Pleistocene and later Quaternary). Each phase is distinctive, with the first based on ranging and energetics, the second on technology and niche expansion, and the third on cognition and cultural processes. I discuss whether this constitutes a 'major transition' in the context of the evolutionary processes more broadly; the role of behaviour in evolution; and the opportunity provided by the rich genetic, phenotypic (fossil morphology) and behavioural (archaeological) record to examine in detail major transitions and the microevolutionary patterns underlying macroevolutionary change. It is suggested that the evolution of the hominin lineage is consistent with a mosaic pattern of change.This article is part of the themed issue 'Major transitions in human evolution'.}, } @article {pmid27282029, year = {2016}, author = {Félix, MA}, title = {Phenotypic Evolution With and Beyond Genome Evolution.}, journal = {Current topics in developmental biology}, volume = {119}, number = {}, pages = {291-347}, doi = {10.1016/bs.ctdb.2016.04.002}, pmid = {27282029}, issn = {1557-8933}, mesh = {Animals ; *Biological Evolution ; Cell Cycle ; DNA ; Environment ; Genes ; Genetic Association Studies ; *Genetic Variation ; *Genome ; Genotype ; Phenotype ; Selection, Genetic ; }, abstract = {DNA does not make phenotypes on its own. In this volume entitled "Genes and Phenotypic Evolution," the present review draws the attention on the process of phenotype construction-including development of multicellular organisms-and the multiple interactions and feedbacks between DNA, organism, and environment at various levels and timescales in the evolutionary process. First, during the construction of an individual's phenotype, DNA is recruited as a template for building blocks within the cellular context and may in addition be involved in dynamical feedback loops that depend on the environmental and organismal context. Second, in the production of phenotypic variation among individuals, stochastic, environmental, genetic, and parental sources of variation act jointly. While in controlled laboratory settings, various genetic and environmental factors can be tested one at a time or in various combinations, they cannot be separated in natural populations because the environment is not controlled and the genotype can rarely be replicated. Third, along generations, genotype and environment each have specific properties concerning the origin of their variation, the hereditary transmission of this variation, and the evolutionary feedbacks. Natural selection acts as a feedback from phenotype and environment to genotype. This review integrates recent results and concrete examples that illustrate these three points. Although some themes are shared with recent calls and claims to a new conceptual framework in evolutionary biology, the viewpoint presented here only means to add flesh to the standard evolutionary synthesis.}, } @article {pmid27273532, year = {2016}, author = {West, JA and Zuccarello, GC and de Goër, SL and Stavrias, LA and Verbruggen, H}, title = {Rhodenigma contortum, an obscure new genus and species of Rhodogorgonales (Rhodophyta) from Western Australia.}, journal = {Journal of phycology}, volume = {52}, number = {3}, pages = {397-403}, doi = {10.1111/jpy.12402}, pmid = {27273532}, issn = {1529-8817}, mesh = {Algal Proteins/genetics/metabolism ; Phylogeny ; RNA, Algal/genetics/metabolism ; Rhodophyta/*anatomy & histology/*classification/genetics ; Sequence Analysis, DNA ; Western Australia ; }, abstract = {An unknown microscopic, branched filamentous red alga was isolated into culture from coral fragments collected in Coral Bay, Western Australia. It grew well unattached or attached to glass with no reproduction other than fragmentation of filaments. Cells of some branch tips became slightly contorted and digitated, possibly as a substrate-contact-response seen at filament tips of various algae. Attached multicellular compact disks on glass had a very different cellular configuration and size than the free filaments. In culture the filaments did not grow on or in coral fragments. Molecular phylogenies based on four markers (rbcL, cox1, 18S, 28S) clearly showed it belongs to the order Rhodogorgonales, as a sister clade of Renouxia. Based on these results, the alga is described as the new genus and species Rhodenigma contortum in the Rhodogorgonaceae. It had no morphological similarity to either of the other genera in Rhodogorgonaceae and illustrates the unknown diversity in cryptic habitats such as tropical coral rubble.}, } @article {pmid27271841, year = {2016}, author = {Greischar, MA and Mideo, N and Read, AF and Bjørnstad, ON}, title = {Predicting optimal transmission investment in malaria parasites.}, journal = {Evolution; international journal of organic evolution}, volume = {70}, number = {7}, pages = {1542-1558}, pmid = {27271841}, issn = {1558-5646}, support = {R01 GM089932/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Culicidae/*parasitology ; Genetic Fitness ; *Host-Parasite Interactions ; Malaria/*transmission ; Models, Biological ; Plasmodium/genetics/*physiology ; Population Dynamics ; Reproduction ; }, abstract = {In vertebrate hosts, malaria parasites face a tradeoff between replicating and the production of transmission stages that can be passed onto mosquitoes. This tradeoff is analogous to growth-reproduction tradeoffs in multicellular organisms. We use a mathematical model tailored to the life cycle and dynamics of malaria parasites to identify allocation strategies that maximize cumulative transmission potential to mosquitoes. We show that plastic strategies can substantially outperform fixed allocation because parasites can achieve greater fitness by investing in proliferation early and delaying the production of transmission stages. Parasites should further benefit from restraining transmission investment later in infection, because such a strategy can help maintain parasite numbers in the face of resource depletion. Early allocation decisions are predicted to have the greatest impact on parasite fitness. If the immune response saturates as parasite numbers increase, parasites should benefit from even longer delays prior to transmission investment. The presence of a competing strain selects for consistently lower levels of transmission investment and dramatically increased exploitation of the red blood cell resource. While we provide a detailed analysis of tradeoffs pertaining to malaria life history, our approach for identifying optimal plastic allocation strategies may be broadly applicable.}, } @article {pmid27265398, year = {2016}, author = {Breuninger, H and Thamm, A and Streubel, S and Sakayama, H and Nishiyama, T and Dolan, L}, title = {Diversification of a Transcription Factor Family Led to the Evolution of Antagonistically Acting Genetic Regulators of Root Hair Growth.}, journal = {Current biology : CB}, volume = {26}, number = {12}, pages = {1622-1628}, pmid = {27265398}, issn = {1879-0445}, mesh = {Basic Helix-Loop-Helix Transcription Factors/*genetics ; *Evolution, Molecular ; Gene Duplication ; Gene Expression ; *Gene Regulatory Networks ; Multigene Family ; Plant Development/*genetics ; Plant Roots/growth & development ; Plants/*genetics ; }, abstract = {Streptophytes colonized the land some time before 470 million years ago [1-3]. The colonization coincided with an increase in morphological and cellular diversity [4-7]. This increase in diversity is correlated with a proliferation in transcription factors encoded in genomes [8-10]. This suggests that gene duplication and subsequent diversification of function was instrumental in the generation of land plant diversity. Here, we investigate the diversification of the streptophyte-specific Lotus japonicus ROOTHAIRLESS LIKE (LRL) transcription factor (TF) [11, 12] subfamily of basic loop helix (bHLH) proteins by comparing gene function in early divergent and derived land plant species. We report that the single Marchantia polymorpha LRL gene acts as a general growth regulator required for rhizoid development, a function that has been partially conserved throughout multicellular streptophytes. In contrast, the five relatively derived Arabidopsis thaliana LRL genes comprise two antagonistically acting groups of differentially expressed genes. The diversification of LRL genes accompanied the evolution of an antagonistic regulatory element controlling root hair development.}, } @article {pmid27263360, year = {2016}, author = {Weissenbach, J}, title = {The rise of genomics.}, journal = {Comptes rendus biologies}, volume = {339}, number = {7-8}, pages = {231-239}, doi = {10.1016/j.crvi.2016.05.002}, pmid = {27263360}, issn = {1768-3238}, mesh = {Animals ; Computational Biology ; DNA/genetics ; Evolution, Molecular ; Genome ; Genomics/*history ; History, 20th Century ; History, 21st Century ; Humans ; }, abstract = {A brief history of the development of genomics is provided. Complete sequencing of genomes of uni- and multicellular organisms is based on important progress in sequencing and bioinformatics. Evolution of these methods is ongoing and has triggered an explosion in data production and analysis. Initial analyses focused on the inventory of genes encoding proteins. Completeness and quality of gene prediction remains crucial. Genome analyses profoundly modified our views on evolution, biodiversity and contributed to the detection of new functions, yet to be fully elucidated, such as those fulfilled by non-coding RNAs. Genomics has become the basis for the study of biology and provides the molecular support for a bunch of large-scale studies, the omics.}, } @article {pmid27252218, year = {2016}, author = {Colley, NJ and Nilsson, DE}, title = {Photoreception in Phytoplankton.}, journal = {Integrative and comparative biology}, volume = {56}, number = {5}, pages = {764-775}, pmid = {27252218}, issn = {1557-7023}, support = {P30 EY016665/EY/NEI NIH HHS/United States ; R01 EY008768/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Light ; Locomotion ; Phytoplankton/*physiology ; Ultraviolet Rays ; }, abstract = {In many species of phytoplankton, simple photoreceptors monitor ambient lighting. Photoreceptors provide a number of selective advantages including the ability to assess the time of day for circadian rhythms, seasonal changes, and the detection of excessive light intensities and harmful UV light. Photoreceptors also serve as depth gauges in the water column for behaviors such as diurnal vertical migration. Photoreceptors can be organized together with screening pigment into visible eyespots. In a wide variety of motile phytoplankton, including Chlamydomonas, Volvox, Euglena, and Kryptoperidinium, eyespots are light-sensitive organelles residing within the cell. Eyespots are composed of photoreceptor proteins and typically red to orange carotenoid screening pigments. This association of photosensory pigment with screening pigment allows for detection of light directionality, needed for light-guided behaviors such as positive and negative phototaxis. In Chlamydomonas, the eyespot is located in the chloroplast and Chlamydomonas expresses a number of photosensory pigments including the microbial channelrhodopsins (ChR1 and ChR2). Dinoflagellates are unicellular protists that are ecologically important constituents of the phytoplankton. They display a great deal of diversity in morphology, nutritional modes and symbioses, and can be photosynthetic or heterotrophic, feeding on smaller phytoplankton. Dinoflagellates, such as Kryptoperidinium foliaceum, have eyespots that are used for light-mediated tasks including phototaxis. Dinoflagellates belonging to the family Warnowiaceae have a more elaborate eye. Their eye-organelle, called an ocelloid, is a large, elaborate structure consisting of a focusing lens, highly ordered retinal membranes, and a shield of dark pigment. This complex eye-organelle is similar to multicellular camera eyes, such as our own. Unraveling the molecular makeup, structure and function of dinoflagellate eyes, as well as light-guided behaviors in phytoplankton can inform us about the selective forces that drove evolution in the important steps from light detection to vision. We show here that the evolution from simple photoreception to vision seems to have independently followed identical paths and principles in phytoplankton and animals, significantly strengthening our understanding of this important biological process.}, } @article {pmid27250874, year = {2016}, author = {Horst, NA and Katz, A and Pereman, I and Decker, EL and Ohad, N and Reski, R}, title = {A single homeobox gene triggers phase transition, embryogenesis and asexual reproduction.}, journal = {Nature plants}, volume = {2}, number = {}, pages = {15209}, doi = {10.1038/nplants.2015.209}, pmid = {27250874}, issn = {2055-0278}, mesh = {Bryopsida/embryology/*genetics/physiology ; Diploidy ; Genes, Homeobox/*genetics ; Germ Cells, Plant/physiology ; Haploidy ; Reproduction, Asexual ; }, abstract = {Plants characteristically alternate between haploid gametophytic and diploid sporophytic stages. Meiosis and fertilization respectively initiate these two different ontogenies(1). Genes triggering ectopic embryo development on vegetative sporophytic tissues are well described(2,3); however, a genetic control of embryo development from gametophytic tissues remains elusive. Here, in the moss Physcomitrella patens we show that ectopic overexpression of the homeobox gene BELL1 induces embryo formation and subsequently reproductive diploid sporophytes from specific gametophytic cells without fertilization. In line with this, BELL1 loss-of-function mutants have a wild-type phenotype, except that their egg cells are bigger and unable to form embryos. Our results identify BELL1 as a master regulator for the gametophyte-to-sporophyte transition in P. patens and provide mechanistic insights into the evolution of embryos that can generate multicellular diploid sporophytes. This developmental innovation facilitated the colonization of land by plants about 500 million years ago(4) and thus shaped our current ecosystems.}, } @article {pmid27248802, year = {2016}, author = {Howe, K and Schiffer, PH and Zielinski, J and Wiehe, T and Laird, GK and Marioni, JC and Soylemez, O and Kondrashov, F and Leptin, M}, title = {Structure and evolutionary history of a large family of NLR proteins in the zebrafish.}, journal = {Open biology}, volume = {6}, number = {4}, pages = {160009}, pmid = {27248802}, issn = {2046-2441}, support = {335980/ERC_/European Research Council/International ; HG002659/HG/NHGRI NIH HHS/United States ; 22231/CRUK_/Cancer Research UK/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 55007424/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence ; *Evolution, Molecular ; Genome ; Multigene Family ; NLR Proteins/*chemistry/*genetics ; Protein Domains ; Time Factors ; Zebrafish/genetics/*metabolism ; Zebrafish Proteins/*chemistry/*genetics ; }, abstract = {Multicellular eukaryotes have evolved a range of mechanisms for immune recognition. A widespread family involved in innate immunity are the NACHT-domain and leucine-rich-repeat-containing (NLR) proteins. Mammals have small numbers of NLR proteins, whereas in some species, mostly those without adaptive immune systems, NLRs have expanded into very large families. We describe a family of nearly 400 NLR proteins encoded in the zebrafish genome. The proteins share a defining overall structure, which arose in fishes after a fusion of the core NLR domains with a B30.2 domain, but can be subdivided into four groups based on their NACHT domains. Gene conversion acting differentially on the NACHT and B30.2 domains has shaped the family and created the groups. Evidence of positive selection in the B30.2 domain indicates that this domain rather than the leucine-rich repeats acts as the pathogen recognition module. In an unusual chromosomal organization, the majority of the genes are located on one chromosome arm, interspersed with other large multigene families, including a new family encoding zinc-finger proteins. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system.}, } @article {pmid27226324, year = {2016}, author = {Hunter, GL and Hadjivasiliou, Z and Bonin, H and He, L and Perrimon, N and Charras, G and Baum, B}, title = {Coordinated control of Notch/Delta signalling and cell cycle progression drives lateral inhibition-mediated tissue patterning.}, journal = {Development (Cambridge, England)}, volume = {143}, number = {13}, pages = {2305-2310}, pmid = {27226324}, issn = {1477-9129}, support = {BB/K009001/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; P40 OD018537/OD/NIH HHS/United States ; BB/J008532/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Animals ; *Body Patterning ; *Cell Cycle ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/cytology/*embryology/*metabolism ; Epithelial Cells/cytology/metabolism ; Intracellular Signaling Peptides and Proteins/*metabolism ; Membrane Proteins/*metabolism ; Receptors, Notch/*metabolism ; Sense Organs/cytology ; *Signal Transduction ; Stem Cells/cytology/metabolism ; Time Factors ; Vibrissae/cytology/embryology ; }, abstract = {Coordinating cell differentiation with cell growth and division is crucial for the successful development, homeostasis and regeneration of multicellular tissues. Here, we use bristle patterning in the fly notum as a model system to explore the regulatory and functional coupling of cell cycle progression and cell fate decision-making. The pattern of bristles and intervening epithelial cells (ECs) becomes established through Notch-mediated lateral inhibition during G2 phase of the cell cycle, as neighbouring cells physically interact with each other via lateral contacts and/or basal protrusions. Since Notch signalling controls cell division timing downstream of Cdc25, ECs in lateral contact with a Delta-expressing cell experience higher levels of Notch signalling and divide first, followed by more distant neighbours, and lastly Delta-expressing cells. Conversely, mitotic entry and cell division makes ECs refractory to lateral inhibition signalling, fixing their fate. Using a combination of experiments and computational modelling, we show that this reciprocal relationship between Notch signalling and cell cycle progression acts like a developmental clock, providing a delimited window of time during which cells decide their fate, ensuring efficient and orderly bristle patterning.}, } @article {pmid27221222, year = {2016}, author = {Steed, E and Faggianelli, N and Roth, S and Ramspacher, C and Concordet, JP and Vermot, J}, title = {klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11646}, pmid = {27221222}, issn = {2041-1723}, mesh = {Animals ; Animals, Genetically Modified ; Extracellular Matrix/metabolism ; Fibronectins/*metabolism ; Gene Expression Profiling ; Heart Valves/*embryology ; Kruppel-Like Transcription Factors/*metabolism ; *Mechanotransduction, Cellular ; Zebrafish ; Zebrafish Proteins/*metabolism ; }, abstract = {The heartbeat and blood flow signal to endocardial cell progenitors through mechanosensitive proteins that modulate the genetic program controlling heart valve morphogenesis. To date, the mechanism by which mechanical forces coordinate tissue morphogenesis is poorly understood. Here we use high-resolution imaging to uncover the coordinated cell behaviours leading to heart valve formation. We find that heart valves originate from progenitors located in the ventricle and atrium that generate the valve leaflets through a coordinated set of endocardial tissue movements. Gene profiling analyses and live imaging reveal that this reorganization is dependent on extracellular matrix proteins, in particular on the expression of fibronectin1b. We show that blood flow and klf2a, a major endocardial flow-responsive gene, control these cell behaviours and fibronectin1b synthesis. Our results uncover a unique multicellular layering process leading to leaflet formation and demonstrate that endocardial mechanotransduction and valve morphogenesis are coupled via cellular rearrangements mediated by fibronectin synthesis.}, } @article {pmid27213462, year = {2016}, author = {Miller, WB}, title = {Cognition, Information Fields and Hologenomic Entanglement: Evolution in Light and Shadow.}, journal = {Biology}, volume = {5}, number = {2}, pages = {}, pmid = {27213462}, issn = {2079-7737}, abstract = {As the prime unification of Darwinism and genetics, the Modern Synthesis continues to epitomize mainstay evolutionary theory. Many decades after its formulation, its anchor assumptions remain fixed: conflict between macro organic organisms and selection at that level represent the near totality of any evolutionary narrative. However, intervening research has revealed a less easily appraised cellular and microbial focus for eukaryotic existence. It is now established that all multicellular eukaryotic organisms are holobionts representing complex collaborations between the co-aligned microbiome of each eukaryote and its innate cells into extensive mixed cellular ecologies. Each of these ecological constituents has demonstrated faculties consistent with basal cognition. Consequently, an alternative hologenomic entanglement model is proposed with cognition at its center and conceptualized as Pervasive Information Fields within a quantum framework. Evolutionary development can then be reconsidered as being continuously based upon communication between self-referential constituencies reiterated at every scope and scale. Immunological reactions support and reinforce self-recognition juxtaposed against external environmental stresses.}, } @article {pmid27208723, year = {2017}, author = {Kim, HY and Jackson, TR and Davidson, LA}, title = {On the role of mechanics in driving mesenchymal-to-epithelial transitions.}, journal = {Seminars in cell & developmental biology}, volume = {67}, number = {}, pages = {113-122}, pmid = {27208723}, issn = {1096-3634}, support = {R01 HD044750/HD/NICHD NIH HHS/United States ; T32 HL076124/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Biomechanical Phenomena ; Cadherins/genetics/metabolism ; Cell Division ; Cell Polarity ; Cellular Reprogramming/genetics ; Drosophila melanogaster/*genetics/growth & development/metabolism ; Embryo, Mammalian ; Embryo, Nonmammalian ; Epithelial Cells/cytology/*metabolism ; Epithelial-Mesenchymal Transition/*genetics ; Extracellular Matrix/chemistry/metabolism ; Humans ; *Mechanotransduction, Cellular ; Mesenchymal Stem Cells/cytology/*metabolism ; Morphogenesis/*genetics ; Vimentin/genetics/metabolism ; }, abstract = {The mesenchymal-to-epithelial transition (MET) is an intrinsically mechanical process describing a multi-step progression where autonomous mesenchymal cells gradually become tightly linked, polarized epithelial cells. METs are fundamental to a wide range of biological processes, including the evolution of multicellular organisms, generation of primary and secondary epithelia during development and organogenesis, and the progression of diseases including cancer. In these cases, there is an interplay between the establishment of cell polarity and the mechanics of neighboring cells and microenvironment. In this review, we highlight a spectrum of METs found in normal development as well as in pathological lesions, and provide insight into the critical role mechanics play at each step. We define MET as an independent process, distinct from a reverse-EMT, and propose questions to further explore the cellular and physical mechanisms of MET.}, } @article {pmid27197218, year = {2016}, author = {Basler, G and Nikoloski, Z and Larhlimi, A and Barabási, AL and Liu, YY}, title = {Control of fluxes in metabolic networks.}, journal = {Genome research}, volume = {26}, number = {7}, pages = {956-968}, pmid = {27197218}, issn = {1549-5469}, support = {P50 HG004233/HG/NHGRI NIH HHS/United States ; R01 HL118455/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/genetics/metabolism ; Computational Biology ; Evolution, Molecular ; Fungi/genetics/metabolism ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; *Metabolic Networks and Pathways ; Models, Biological ; Signal Transduction ; }, abstract = {Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism.}, } @article {pmid27196967, year = {2016}, author = {Lou, Y and Chen, Y}, title = {Simulating the multicellular homeostasis with a cell-based discrete receptor dynamics model: The non-mutational origin of cancer and aging.}, journal = {Journal of theoretical biology}, volume = {404}, number = {}, pages = {15-29}, doi = {10.1016/j.jtbi.2016.04.035}, pmid = {27196967}, issn = {1095-8541}, mesh = {Aging/*genetics ; Animals ; Cell Proliferation ; *Computer Simulation ; *Homeostasis ; Humans ; *Models, Biological ; Mutation/*genetics ; Neoplasms/*genetics ; Phenotype ; Receptors, Cell Surface/*metabolism ; Reproducibility of Results ; Time Factors ; }, abstract = {The purpose of the study is to investigate the multicellular homeostasis in epithelial tissues over very large timescales. Inspired by the receptor dynamics of IBCell model proposed by Rejniak et al. an on-grid agent-based model for multicellular system is constructed. Instead of observing the multicellular architectural morphologies, the diversity of homeostatic states is quantitatively analyzed through a substantial number of simulations by measuring three new order parameters, the phenotypic population structure, the average proliferation age and the relaxation time to stable homeostasis. Nearby the interfaces of distinct homeostatic phases in 3D phase diagrams of the three order parameters, intermediate quasi-stable phases of slow dynamics that features quasi-stability with a large spectrum of relaxation timescales are found. A further exploration on the static and dynamic correlations among the three order parameters reveals that the quasi-stable phases evolve towards two terminations, tumorigenesis and degeneration, which are respectively accompanied by rejuvenation and aging. With the exclusion of the environmental impact and the mutational strategies, the results imply that cancer and aging may share the non-mutational origin in the intrinsic slow dynamics of the multicellular systems.}, } @article {pmid27194700, year = {2016}, author = {Okie, JG and Smith, VH and Martin-Cereceda, M}, title = {Major evolutionary transitions of life, metabolic scaling and the number and size of mitochondria and chloroplasts.}, journal = {Proceedings. Biological sciences}, volume = {283}, number = {1831}, pages = {}, pmid = {27194700}, issn = {1471-2954}, mesh = {*Biological Evolution ; Chloroplasts/*metabolism ; Eukaryota/*physiology ; Mitochondria/*metabolism ; Models, Biological ; *Symbiosis ; }, abstract = {We investigate the effects of trophic lifestyle and two types of major evolutionary transitions in individuality-the endosymbiotic acquisition of organelles and development of multicellularity-on organellar and cellular metabolism and allometry. We develop a quantitative framework linking the size and metabolic scaling of eukaryotic cells to the abundance, size and metabolic scaling of mitochondria and chloroplasts and analyse a newly compiled, unprecedented database representing unicellular and multicellular cells covering diverse phyla and tissues. Irrespective of cellularity, numbers and total volumes of mitochondria scale linearly with cell volume, whereas chloroplasts scale sublinearly and sizes of both organelles remain largely invariant with cell size. Our framework allows us to estimate the metabolic scaling exponents of organelles and cells. Photoautotrophic cells and organelles exhibit photosynthetic scaling exponents always less than one, whereas chemoheterotrophic cells and organelles have steeper respiratory scaling exponents close to one. Multicellularity has no discernible effect on the metabolic scaling of organelles and cells. In contrast, trophic lifestyle has a profound and uniform effect, and our results suggest that endosymbiosis fundamentally altered the metabolic scaling of free-living bacterial ancestors of mitochondria and chloroplasts, from steep ancestral scaling to a shallower scaling in their endosymbiotic descendants.}, } @article {pmid27187178, year = {2016}, author = {Pârvu, O and Gilbert, D}, title = {A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking.}, journal = {PloS one}, volume = {11}, number = {5}, pages = {e0154847}, pmid = {27187178}, issn = {1932-6203}, mesh = {Algorithms ; Animals ; Cell Cycle/physiology ; *Computer Simulation ; Hemodynamics ; Inflammation ; *Models, Biological ; Models, Cardiovascular ; Rats ; *Spatio-Temporal Analysis ; Workflow ; }, abstract = {Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems.}, } @article {pmid27172191, year = {2016}, author = {Paranjape, NP and Calvi, BR}, title = {The Histone Variant H3.3 Is Enriched at Drosophila Amplicon Origins but Does Not Mark Them for Activation.}, journal = {G3 (Bethesda, Md.)}, volume = {6}, number = {6}, pages = {1661-1671}, pmid = {27172191}, issn = {2160-1836}, support = {R01 GM061290/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *DNA Replication ; Drosophila/*genetics/*metabolism ; Drosophila Proteins/genetics/metabolism ; Gene Amplification ; Histones/genetics/*metabolism ; Mitosis/genetics ; Mutation ; Oogenesis/genetics ; *Replication Origin ; Transcription, Genetic ; }, abstract = {Eukaryotic DNA replication begins from multiple origins. The origin recognition complex (ORC) binds origin DNA and scaffolds assembly of a prereplicative complex (pre-RC), which is subsequently activated to initiate DNA replication. In multicellular eukaryotes, origins do not share a strict DNA consensus sequence, and their activity changes in concert with chromatin status during development, but mechanisms are ill-defined. Previous genome-wide analyses in Drosophila and other organisms have revealed a correlation between ORC binding sites and the histone variant H3.3. This correlation suggests that H3.3 may designate origin sites, but this idea has remained untested. To address this question, we examined the enrichment and function of H3.3 at the origins responsible for developmental gene amplification in the somatic follicle cells of the Drosophila ovary. We found that H3.3 is abundant at these amplicon origins. H3.3 levels remained high when replication initiation was blocked, indicating that H3.3 is abundant at the origins before activation of the pre-RC. H3.3 was also enriched at the origins during early oogenesis, raising the possibility that H3.3 bookmarks sites for later amplification. However, flies null mutant for both of the H3.3 genes in Drosophila did not have overt defects in developmental gene amplification or genomic replication, suggesting that H3.3 is not essential for the assembly or activation of the pre-RC at origins. Instead, our results imply that the correlation between H3.3 and ORC sites reflects other chromatin attributes that are important for origin function.}, } @article {pmid27172135, year = {2016}, author = {Kaczanowski, S}, title = {Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging.}, journal = {Physical biology}, volume = {13}, number = {3}, pages = {031001}, doi = {10.1088/1478-3975/13/3/031001}, pmid = {27172135}, issn = {1478-3975}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects/*physiology ; Biological Evolution ; Cell Respiration ; Cellular Senescence/*physiology ; Humans ; Mitochondria/*metabolism/pathology ; Neoplasms/drug therapy/*pathology ; Neurodegenerative Diseases/pathology ; Phylogeny ; }, abstract = {Programmed cell death is a basic cellular mechanism. Apoptotic-like programmed cell death (called apoptosis in animals) occurs in both unicellular and multicellular eukaryotes, and some apoptotic mechanisms are observed in bacteria. Endosymbiosis between mitochondria and eukaryotic cells took place early in the eukaryotic evolution, and some of the apoptotic-like mechanisms of mitochondria that were retained after this event now serve as parts of the eukaryotic apoptotic machinery. Apoptotic mechanisms have several functions in unicellular organisms: they include kin-selected altruistic suicide that controls population size, sharing common goods, and responding to viral infection. Apoptotic factors also have non-apoptotic functions. Apoptosis is involved in the cellular aging of eukaryotes, including humans. In addition, apoptosis is a key part of the innate tumor-suppression mechanism. Several anticancer drugs induce apoptosis, because apoptotic mechanisms are inactivated during oncogenesis. Because of the ancient history of apoptosis, I hypothesize that there is a deep relationship between mitochondrial metabolism, its role in aerobic versus anaerobic respiration, and the connection between apoptosis and cancer. Whereas normal cells rely primarily on oxidative mitochondrial respiration, most cancer cells use anaerobic metabolism. According to the Warburg hypothesis, the remodeling of the metabolism is one of the processes that leads to cancer. Recent studies indicate that anaerobic, non-mitochondrial respiration is particularly active in embryonic cells, stem cells, and aggressive stem-like cancer cells. Mitochondrial respiration is particularly active during the pathological aging of human cells in neurodegenerative diseases. According to the reversed Warburg hypothesis formulated by Demetrius, pathological aging is induced by mitochondrial respiration. Here, I advance the hypothesis that the stimulation of mitochondrial metabolism leads to pathological aging.}, } @article {pmid27160599, year = {2016}, author = {Rolff, J and Schmid-Hempel, P}, title = {Perspectives on the evolutionary ecology of arthropod antimicrobial peptides.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {371}, number = {1695}, pages = {}, pmid = {27160599}, issn = {1471-2970}, support = {260986/ERC_/European Research Council/International ; 268853/ERC_/European Research Council/International ; }, mesh = {Animals ; Anti-Infective Agents/metabolism ; Antimicrobial Cationic Peptides/*genetics ; Arthropods/*genetics/immunology/microbiology ; *Evolution, Molecular ; *Gene Expression ; Host-Pathogen Interactions ; Immunity, Innate ; Insect Proteins/*genetics ; Insecta/genetics/immunology/microbiology ; Selection, Genetic ; }, abstract = {Antimicrobial peptides (AMPs) are important elements of the innate immune defence in multicellular organisms that target and kill microbes. Here, we reflect on the various points that are raised by the authors of the 11 contributions to a special issue of Philosophical Transactions on the 'evolutionary ecology of arthropod antimicrobial peptides'. We see five interesting topics emerging. (i) AMP genes in insects, and perhaps in arthropods more generally, evolve much slower than most other immune genes. One explanation refers to the constraints set by AMPs being part of a finely tuned defence system. A new view argues that AMPs are under strong stabilizing selection. Regardless, this striking observation still invites many more questions than have been answered so far. (ii) AMPs almost always are expressed in combinations and sometimes show expression patterns that are dependent on the infectious agent. While it is often assumed that this can be explained by synergistic interactions, such interactions have rarely been demonstrated and need to be studied further. Moreover, how to define synergy in the first place remains difficult and needs to be addressed. (iii) AMPs play a very important role in mediating the interaction between a host and its mutualistic or commensal microbes. This has only been studied in a very small number of (insect) species. It has become clear that the very same AMPs play different roles in different situations and hence are under concurrent selection. (iv) Different environments shape the physiology of organisms; especially the host-associated microbial communities should impact on the evolution host AMPs. Studies in social insects and some organisms from extreme environments seem to support this notion, but, overall, the evidence for adaptation of AMPs to a given environment is scant. (v) AMPs are considered or already developed as new drugs in medicine. However, bacteria can evolve resistance to AMPs. Therefore, in the light of our limited understanding of AMP evolution in the natural context, and also the very limited understanding of the evolution of resistance against AMPs in bacteria in particular, caution is recommended. What is clear though is that study of the ecology and evolution of AMPs in natural systems could inform many of these outstanding questions, including those related to medical applications and pathogen control.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.}, } @article {pmid27157793, year = {2016}, author = {Leliaert, F and Tronholm, A and Lemieux, C and Turmel, M and DePriest, MS and Bhattacharya, D and Karol, KG and Fredericq, S and Zechman, FW and Lopez-Bautista, JM}, title = {Chloroplast phylogenomic analyses reveal the deepest-branching lineage of the Chlorophyta, Palmophyllophyceae class. nov.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {25367}, pmid = {27157793}, issn = {2045-2322}, mesh = {Base Sequence ; Cell Nucleus/genetics ; Chlorophyta/classification/*genetics ; Chromosome Mapping ; DNA, Chloroplast/genetics ; DNA, Ribosomal/genetics ; Evolution, Molecular ; Genes, Plant ; *Genome, Chloroplast ; *Phylogeny ; }, abstract = {The green plants (Viridiplantae) are an ancient group of eukaryotes comprising two main clades: the Chlorophyta, which includes a wide diversity of green algae, and the Streptophyta, which consists of freshwater green algae and the land plants. The early-diverging lineages of the Viridiplantae comprise unicellular algae, and multicellularity has evolved independently in the two clades. Recent molecular data have revealed an unrecognized early-diverging lineage of green plants, the Palmophyllales, with a unique form of multicellularity, and typically found in deep water. The phylogenetic position of this enigmatic group, however, remained uncertain. Here we elucidate the evolutionary affinity of the Palmophyllales using chloroplast genomic, and nuclear rDNA data. Phylogenetic analyses firmly place the palmophyllalean Verdigellas peltata along with species of Prasinococcales (prasinophyte clade VI) in the deepest-branching clade of the Chlorophyta. The small, compact and intronless chloroplast genome (cpDNA) of V. peltata shows striking similarities in gene content and organization with the cpDNAs of Prasinococcales and the streptophyte Mesostigma viride, indicating that cpDNA architecture has been extremely well conserved in these deep-branching lineages of green plants. The phylogenetic distinctness of the Palmophyllales-Prasinococcales clade, characterized by unique ultrastructural features, warrants recognition of a new class of green plants, Palmophyllophyceae class. nov.}, } @article {pmid27146690, year = {2016}, author = {Pentz, JT and Taylor, BP and Ratcliff, WC}, title = {Apoptosis in snowflake yeast: novel trait, or side effect of toxic waste?.}, journal = {Journal of the Royal Society, Interface}, volume = {13}, number = {118}, pages = {}, pmid = {27146690}, issn = {1742-5662}, mesh = {Apoptosis/*genetics ; *Fungal Proteins/genetics/metabolism ; *Quantitative Trait Loci ; *Transcription Factors/genetics/metabolism ; *Yeasts/genetics/metabolism ; }, abstract = {Recent experiments evolving de novo multicellularity in yeast have found that large cluster-forming genotypes also exhibit higher rates of programmed cell death (apoptosis). This was previously interpreted as the evolution of a simple form of cellular division of labour: apoptosis results in the scission of cell-cell connections, allowing snowflake yeast to produce proportionally smaller, faster-growing propagules. Through spatial simulations, Duran-Nebreda and Solé (J. R. Soc. Interface 12, 20140982 (doi:10.1073/pnas.1115323109)) develop the novel null hypothesis that apoptosis is not an adaptation, per se, but is instead caused by the accumulation of toxic metabolites in large clusters. Here we test this hypothesis by synthetically creating unicellular derivatives of snowflake yeast through functional complementation with the ancestral ACE2 allele. We find that multicellular snowflake yeast with elevated apoptosis exhibit a similar rate of apoptosis when cultured as single cells. We also show that larger snowflake yeast clusters tend to contain a greater fraction of older, senescent cells, which may explain why larger clusters of a given genotype are more apoptotic. Our results show that apoptosis is not caused by side effects of spatial structure, such as starvation or waste product accumulation, and are consistent with the hypothesis that elevated apoptosis is a trait that co-evolves with large cluster size.}, } @article {pmid27145840, year = {2016}, author = {Joerger, AC and Fersht, AR}, title = {The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches.}, journal = {Annual review of biochemistry}, volume = {85}, number = {}, pages = {375-404}, doi = {10.1146/annurev-biochem-060815-014710}, pmid = {27145840}, issn = {1545-4509}, support = {MC_EX_G0901534/MRC_/Medical Research Council/United Kingdom ; MC_UP_A024_1010/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Antineoplastic Agents, Alkylating/chemical synthesis/*therapeutic use ; Cell Cycle Proteins ; Clinical Trials as Topic ; Drug Design ; *Gene Expression Regulation, Neoplastic ; Humans ; Molecular Docking Simulation ; *Molecular Targeted Therapy ; Mutation ; Neoplasms/*drug therapy/genetics/metabolism/pathology ; Nuclear Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Proto-Oncogene Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors/chemistry/genetics/metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/*agonists/chemistry/genetics/metabolism ; }, abstract = {Inactivation of the transcription factor p53, through either direct mutation or aberrations in one of its many regulatory pathways, is a hallmark of virtually every tumor. In recent years, screening for p53 activators and a better understanding of the molecular mechanisms of oncogenic perturbations of p53 function have opened up a host of novel avenues for therapeutic intervention in cancer: from the structure-guided design of chemical chaperones to restore the function of conformationally unstable p53 cancer mutants, to the development of potent antagonists of the negative regulators MDM2 and MDMX and other modulators of the p53 pathway for the treatment of cancers with wild-type p53. Some of these compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, personalized anticancer medicines. We trace the structural evolution of the p53 pathway, from germ-line surveillance in simple multicellular organisms to its pluripotential role in humans.}, } @article {pmid27139940, year = {2016}, author = {Joachimczak, M and Suzuki, R and Arita, T}, title = {Artificial Metamorphosis: Evolutionary Design of Transforming, Soft-Bodied Robots.}, journal = {Artificial life}, volume = {22}, number = {3}, pages = {271-298}, doi = {10.1162/ARTL_a_00207}, pmid = {27139940}, issn = {1064-5462}, mesh = {Animals ; Biological Evolution ; Larva ; Locomotion ; *Metamorphosis, Biological ; *Models, Biological ; *Robotics ; }, abstract = {We show how the concept of metamorphosis, together with a biologically inspired model of multicellular development, can be used to evolve soft-bodied robots that are adapted to two very different tasks, such as being able to move in an aquatic and in a terrestrial environment. Each evolved solution defines two pairs of morphologies and controllers, together with a process of transforming one pair into the other. Animats develop from a single cell and grow through cellular divisions and deaths until they reach an initial larval form adapted to a first environment. To obtain the adult form adapted to a second environment, the larva undergoes metamorphosis, during which new cells are added or removed and its controller is modified. Importantly, our approach assumes nothing about what morphologies or methods of locomotion are preferred. Instead, it successfully searches the vast space of possible designs and comes up with complex, surprising, lifelike solutions that are reminiscent of amphibian metamorphosis. We analyze obtained solutions and investigate whether the morphological changes during metamorphosis are indeed adaptive. We then compare the effectiveness of three different types of selective pressures used to evolve metamorphic individuals. Finally, we investigate potential advantages of using metamorphosis to automatically produce soft-bodied designs by comparing the performance of metamorphic individuals with their specialized counterparts and designs that are robust to both environments.}, } @article {pmid27139112, year = {2016}, author = {Bastiaans, E and Debets, AJ and Aanen, DK}, title = {Experimental evolution reveals that high relatedness protects multicellular cooperation from cheaters.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11435}, pmid = {27139112}, issn = {2041-1723}, mesh = {Cell Proliferation ; *Clonal Evolution ; *Microbial Interactions ; Mutation ; Neurospora crassa/*genetics/growth & development ; Spores, Fungal/genetics/growth & development ; }, abstract = {In multicellular organisms, there is a potential risk that cheating mutants gain access to the germline. Development from a single-celled zygote resets relatedness among cells to its maximum value each generation, which should accomplish segregation of cheating mutants from non-cheaters and thereby protect multicellular cooperation. Here we provide the crucial direct comparison between high- and low-relatedness conditions to test this hypothesis. We allow two variants of the fungus Neurospora crassa to evolve, one with and one without the ability to form chimeras with other individuals, thus generating two relatedness levels. While multicellular cooperation remains high in the high-relatedness lines, it significantly decreases in all replicate low-relatedness lines, resulting in an average threefold decrease in spore yield. This reduction is caused by cheating mutants with reduced investment in somatic functions, but increased competitive success when fusing with non-cheaters. Our experiments demonstrate that high genetic relatedness is crucial to sustain multicellular cooperation.}, } @article {pmid27122563, year = {2016}, author = {Boisseau, RP and Vogel, D and Dussutour, A}, title = {Habituation in non-neural organisms: evidence from slime moulds.}, journal = {Proceedings. Biological sciences}, volume = {283}, number = {1829}, pages = {}, pmid = {27122563}, issn = {1471-2954}, mesh = {Animals ; Biological Evolution ; Caffeine ; Chemotaxis/physiology ; Habituation, Psychophysiologic/*physiology ; Learning/physiology ; Models, Biological ; Phylogeny ; Physarum polycephalum/*physiology ; Quinine ; }, abstract = {Learning, defined as a change in behaviour evoked by experience, has hitherto been investigated almost exclusively in multicellular neural organisms. Evidence for learning in non-neural multicellular organisms is scant, and only a few unequivocal reports of learning have been described in single-celled organisms. Here we demonstrate habituation, an unmistakable form of learning, in the non-neural organism Physarum polycephalum In our experiment, using chemotaxis as the behavioural output and quinine or caffeine as the stimulus, we showed that P. polycephalum learnt to ignore quinine or caffeine when the stimuli were repeated, but responded again when the stimulus was withheld for a certain time. Our results meet the principle criteria that have been used to demonstrate habituation: responsiveness decline and spontaneous recovery. To distinguish habituation from sensory adaptation or motor fatigue, we also show stimulus specificity. Our results point to the diversity of organisms lacking neurons, which likely display a hitherto unrecognized capacity for learning, and suggest that slime moulds may be an ideal model system in which to investigate fundamental mechanisms underlying learning processes. Besides, documenting learning in non-neural organisms such as slime moulds is centrally important to a comprehensive, phylogenetic understanding of when and where in the tree of life the earliest manifestations of learning evolved.}, } @article {pmid27114036, year = {2016}, author = {Sebé-Pedrós, A and Ballaré, C and Parra-Acero, H and Chiva, C and Tena, JJ and Sabidó, E and Gómez-Skarmeta, JL and Di Croce, L and Ruiz-Trillo, I}, title = {The Dynamic Regulatory Genome of Capsaspora and the Origin of Animal Multicellularity.}, journal = {Cell}, volume = {165}, number = {5}, pages = {1224-1237}, pmid = {27114036}, issn = {1097-4172}, support = {616960/ERC_/European Research Council/International ; }, mesh = {Animals ; *Biological Evolution ; Eukaryota/classification/cytology/*genetics ; Gene Regulatory Networks ; Genome ; Histones/metabolism ; Humans ; Protein Processing, Post-Translational ; RNA, Untranslated ; *Regulatory Elements, Transcriptional ; }, abstract = {The unicellular ancestor of animals had a complex repertoire of genes linked to multicellular processes. This suggests that changes in the regulatory genome, rather than in gene innovation, were key to the origin of animals. Here, we carry out multiple functional genomic assays in Capsaspora owczarzaki, the unicellular relative of animals with the largest known gene repertoire for transcriptional regulation. We show that changing chromatin states, differential lincRNA expression, and dynamic cis-regulatory sites are associated with life cycle transitions in Capsaspora. Moreover, we demonstrate conservation of animal developmental transcription-factor networks and extensive network interconnection in this premetazoan organism. In contrast, however, Capsaspora lacks animal promoter types, and its regulatory sites are small, proximal, and lack signatures of animal enhancers. Overall, our results indicate that the emergence of animal multicellularity was linked to a major shift in genome cis-regulatory complexity, most notably the appearance of distal enhancer regulation.}, } @article {pmid27112670, year = {2016}, author = {Obermeier, B and Verma, A and Ransohoff, RM}, title = {The blood-brain barrier.}, journal = {Handbook of clinical neurology}, volume = {133}, number = {}, pages = {39-59}, doi = {10.1016/B978-0-444-63432-0.00003-7}, pmid = {27112670}, issn = {0072-9752}, mesh = {Animals ; Biological Transport/physiology ; Blood-Brain Barrier/anatomy & histology/*physiology ; Cerebrospinal Fluid/physiology ; Endothelial Cells/physiology ; Humans ; Neovascularization, Physiologic/*physiology ; Neuroglia/physiology ; Neurons/physiology ; }, abstract = {In autoimmune neurologic disorders, the blood-brain barrier (BBB) plays a central role in immunopathogenesis, since this vascular interface is an entry path for cells and effector molecules of the peripheral immune system to reach the target organ, the central nervous system (CNS). The BBB's unique anatomic structure and the tightly regulated interplay of its cellular and acellular components allow for maintenance of brain homeostasis, regulation of influx and efflux, and protection from harm; these ensure an optimal environment for the neuronal network to function properly. In both health and disease, the BBB acts as mediator between the periphery and the CNS. For example, immune cell trafficking through the cerebral vasculature is essential to clear microbes or cell debris from neural tissues, while poorly regulated cellular transmigration can underlie or worsen CNS pathology. In this chapter, we focus on the specialized multicellular structure and function of the BBB/neurovascular unit and discuss how BBB breakdown can precede or be a consequence of neuroinflammation. We introduce the blood-cerebrospinal fluid barrier and include a brief aside about evolutionary aspects of barrier formation and refinements. Lastly, since restoration of barrier function is considered key to ameliorate neurologic disease, we speculate about new therapeutic avenues to repair a damaged BBB.}, } @article {pmid27107900, year = {2016}, author = {Akasov, R and Zaytseva-Zotova, D and Burov, S and Leko, M and Dontenwill, M and Chiper, M and Vandamme, T and Markvicheva, E}, title = {Formation of multicellular tumor spheroids induced by cyclic RGD-peptides and use for anticancer drug testing in vitro.}, journal = {International journal of pharmaceutics}, volume = {506}, number = {1-2}, pages = {148-157}, doi = {10.1016/j.ijpharm.2016.04.005}, pmid = {27107900}, issn = {1873-3476}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Culture Techniques/methods ; Cell Line, Tumor ; Chemistry, Pharmaceutical/methods ; Curcumin/pharmacology ; Dacarbazine/analogs & derivatives/pharmacology ; Doxorubicin/pharmacology ; Drug Screening Assays, Antitumor/*methods ; HCT116 Cells ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Oligopeptides/*pharmacology ; Peptides, Cyclic/*pharmacology ; Spheroids, Cellular/*drug effects ; Temozolomide ; }, abstract = {Development of novel anticancer formulations is a priority challenge in biomedicine. However, in vitro models based on monolayer cultures (2D) which are currently used for cytotoxicity tests leave much to be desired. More and more attention is focusing on 3D in vitro systems which can better mimic solid tumors. The aim of the study was to develop a novel one-step highly reproducible technique for multicellular tumor spheroid (MTS) formation using synthetic cyclic RGD-peptides, and to demonstrate availability of the spheroids as 3D in vitro model for antitumor drug testing. Cell self-assembly effect induced by addition of both linear and cyclic RGD-peptides directly to monolayer cultures was studied for 12 cell lines of various origins, including tumor cells (e.i. U-87 MG, MCF-7, M-3, HCT-116) and normal cells, in particular L-929, BNL.CL2, HepG2. Cyclo-RGDfK and its modification with triphenylphosphonium cation (TPP), namely cyclo-RGDfK(TPP) in a range of 10-100μM were found to induce spheroid formation. The obtained spheroids were unimodal with mean sizes in a range of 60-120μm depending on cell line and serum content in culture medium. The spheroids were used as 3D in vitro model, in order to evaluate cytotoxicity effects of antitumor drugs (doxorubicin, curcumin, temozolomide). The developed technique could be proposed as a promising tool for in vitro test of novel antitumor drugs.}, } @article {pmid27102219, year = {2016}, author = {Hanschen, ER and Marriage, TN and Ferris, PJ and Hamaji, T and Toyoda, A and Fujiyama, A and Neme, R and Noguchi, H and Minakuchi, Y and Suzuki, M and Kawai-Toyooka, H and Smith, DR and Sparks, H and Anderson, J and Bakarić, R and Luria, V and Karger, A and Kirschner, MW and Durand, PM and Michod, RE and Nozaki, H and Olson, BJ}, title = {The Gonium pectorale genome demonstrates co-option of cell cycle regulation during the evolution of multicellularity.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {11370}, pmid = {27102219}, issn = {2041-1723}, support = {R01 HD091846/HD/NICHD NIH HHS/United States ; P20 GM103418/GM/NIGMS NIH HHS/United States ; GM103785-02/GM/NIGMS NIH HHS/United States ; P20 GM103638/GM/NIGMS NIH HHS/United States ; R01 GM103785/GM/NIGMS NIH HHS/United States ; P20GM103418/GM/NIGMS NIH HHS/United States ; T32 GM084905/GM/NIGMS NIH HHS/United States ; GM084905/GM/NIGMS NIH HHS/United States ; P20GM103638/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Cycle Checkpoints/*genetics ; Chlamydomonas/cytology/*genetics ; Chlorophyta/classification/cytology/*genetics ; *Gene Expression Regulation, Plant ; Genome Size ; *Genome, Plant ; Phylogeny ; Plant Cells/metabolism ; Plasmids/chemistry/metabolism ; Retinoblastoma Protein/genetics/metabolism ; Transformation, Genetic ; }, abstract = {The transition to multicellularity has occurred numerous times in all domains of life, yet its initial steps are poorly understood. The volvocine green algae are a tractable system for understanding the genetic basis of multicellularity including the initial formation of cooperative cell groups. Here we report the genome sequence of the undifferentiated colonial alga, Gonium pectorale, where group formation evolved by co-option of the retinoblastoma cell cycle regulatory pathway. Significantly, expression of the Gonium retinoblastoma cell cycle regulator in unicellular Chlamydomonas causes it to become colonial. The presence of these changes in undifferentiated Gonium indicates extensive group-level adaptation during the initial step in the evolution of multicellularity. These results emphasize an early and formative step in the evolution of multicellularity, the evolution of cell cycle regulation, one that may shed light on the evolutionary history of other multicellular innovations and evolutionary transitions.}, } @article {pmid27094475, year = {2016}, author = {Horst, NA and Reski, R}, title = {Alternation of generations - unravelling the underlying molecular mechanism of a 165-year-old botanical observation.}, journal = {Plant biology (Stuttgart, Germany)}, volume = {18}, number = {4}, pages = {549-551}, doi = {10.1111/plb.12468}, pmid = {27094475}, issn = {1438-8677}, mesh = {Animals ; Bryopsida/*genetics/growth & development/physiology ; Diploidy ; *Evolution, Molecular ; Germ Cells, Plant ; Haploidy ; *Life Cycle Stages ; Meiosis ; Models, Molecular ; Phylogeny ; Plant Proteins/*genetics ; Reproduction ; Reproduction, Asexual ; }, abstract = {Characteristically, land plants exhibit a life cycle with an 'alternation of generations' and thus alternate between a haploid gametophyte and a diploid sporophyte. At meiosis and fertilisation the transitions between these two ontogenies take place in distinct single stem cells. The evolutionary invention of an embryo, and thus an upright multicellular sporophyte, in the ancestor of land plants formed the basis for the evolution of increasingly complex plant morphologies shaping Earth's ecosystems. Recent research employing the moss Physcomitrella patens revealed the homeotic gene BELL1 as a master regulator of the gametophyte-to-sporophyte transition. Here, we discuss these findings in the context of classical botanical observations.}, } @article {pmid27091969, year = {2016}, author = {Au, SH and Storey, BD and Moore, JC and Tang, Q and Chen, YL and Javaid, S and Sarioglu, AF and Sullivan, R and Madden, MW and O'Keefe, R and Haber, DA and Maheswaran, S and Langenau, DM and Stott, SL and Toner, M}, title = {Clusters of circulating tumor cells traverse capillary-sized vessels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {113}, number = {18}, pages = {4947-4952}, pmid = {27091969}, issn = {1091-6490}, support = {F33 GM109574/GM/NIGMS NIH HHS/United States ; P41 EB002503/EB/NIBIB NIH HHS/United States ; R24 OD016761/OD/NIH HHS/United States ; U01 EB012493/EB/NIBIB NIH HHS/United States ; }, mesh = {Capillaries/*pathology ; *Cell Movement ; Humans ; *Neoplastic Cells, Circulating ; }, abstract = {Multicellular aggregates of circulating tumor cells (CTC clusters) are potent initiators of distant organ metastasis. However, it is currently assumed that CTC clusters are too large to pass through narrow vessels to reach these organs. Here, we present evidence that challenges this assumption through the use of microfluidic devices designed to mimic human capillary constrictions and CTC clusters obtained from patient and cancer cell origins. Over 90% of clusters containing up to 20 cells successfully traversed 5- to 10-μm constrictions even in whole blood. Clusters rapidly and reversibly reorganized into single-file chain-like geometries that substantially reduced their hydrodynamic resistances. Xenotransplantation of human CTC clusters into zebrafish showed similar reorganization and transit through capillary-sized vessels in vivo. Preliminary experiments demonstrated that clusters could be disrupted during transit using drugs that affected cellular interaction energies. These findings suggest that CTC clusters may contribute a greater role to tumor dissemination than previously believed and may point to strategies for combating CTC cluster-initiated metastasis.}, } @article {pmid27086973, year = {2016}, author = {Woolsey, TA}, title = {Re: Woolsey TA, van der Loos H. 1970. The structural organization of layer IV in the somatosensory region (S I) of mouse cerebral cortex. Brain Res. 17: 205-242.}, journal = {Brain research}, volume = {1645}, number = {}, pages = {22-24}, doi = {10.1016/j.brainres.2016.04.029}, pmid = {27086973}, issn = {1872-6240}, mesh = {Animals ; Autoradiography/history ; History, 20th Century ; Mice ; Neuroanatomical Tract-Tracing Techniques/history/methods ; Neuroanatomy/*history/methods ; Somatosensory Cortex/*anatomy & histology ; Vibrissae ; }, abstract = {UNLABELLED: Axoplasmically transported proteins synthesized in neuronal somata labeled by radioactively labeled amino acids (tritium), following local targeted injections for tracing of pathways in the central nervous system using autoradiography. Results from a number of neuronal systems, including: the rat olfactory bulb; cortico-thalamic projections in the mouse; commissural connections of the rat hippocampus; and retinal projections in the monkey and chick are documented. Pathway origins are clear, as the number and distribution of the labeled cells and the normal structure of the injection site is preserved. Light and electron microscopic autoradiography shows that proteins are transported, at two rates: rapid transport (>100mm/day) of fewer proteins accumulating in axon terminals; and, slow transport (1-5mm/day) of the bulk of labeled proteins distributed along the length of axons. Different survival times can be selected to evaluate terminal projection field(s) or pathways from origin to termination. The clarity of autoradiographic labeling of pathways and their terminations is comparable to other techniques (such as the Nauta-Gygax and the Fink-Heimer methods and the electron microscopy of terminal degeneration). Labeled amino acids do not label molecules in fibers of passage and there is no retrograde transport of labeled material from the axon terminals. The functional polarity of fiber pathways can be easily established. We summarize the merits of this technique is based upon an established physiological properties of neurons that are summarized in contrast to currently used techniques dependent upon pathological changes in neurons, axons, or axonal terminals.

ABSTRACT: The cytoarchitecture of layer IV in mouse SmI cerebral cortex was examined in.formalin-fixed, Nissl-stained and Cox-fixed, Golgi-Nissl-stained sections cut coronally and tangentially to the pia, A multicellular cytoarchitectonic unit is described in layer IV, roughly cylindrical, 100-400um in diameter, and perpendicular to the pia. Because of their characteristic shape we call these structures barrels. Each barrel is a ring of neurons, the side, which surrounds a less cellular hollow. The nearly acellular reigion surrounding each barrel and separating adjacent barrels is the septum. Barrels are discussed in relation to observations reported in several earlier papers on the mouse cortex. The barrel field (all barrels) has remarkable constancy by all measures: from one hemisphere to the next and from one specimen to the next. A consistent part of the barrel field is the postero-medial barrel subield (PMBSF). Barrels in the PMBSF are larger, elliptical in shape, organized into five distinct rows and their numbers are constant. It is postulated that each barrel in the PMBSF is the cortical correlate of a contralateral mystacial vibrissa (whisker). On the basis of counts of barrels and of all facial sinus hairs a 'one barrel-one vibrissa' hypothesis is proposed. The general hypothesis is that barrels are the morphological manifestation in layer IV of the functional cortical columns discovered by physiologists. The barrels offer excellent opportunities for integrated studies of sensory cerebral cortex at a degree of resolution previously not possible. This article is part of a Special Issue entitled SI:50th Anniversary Issue.}, } @article {pmid27077531, year = {2016}, author = {Møller, HD and Bojsen, RK and Tachibana, C and Parsons, L and Botstein, D and Regenberg, B}, title = {Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {110}, pages = {e54239 |}, pmid = {27077531}, issn = {1940-087X}, mesh = {DNA, Circular/genetics/*isolation & purification ; DNA, Fungal/genetics/*isolation & purification ; Eukaryotic Cells ; Extrachromosomal Inheritance/*genetics ; Genome ; Genome, Fungal ; Saccharomyces cerevisiae/*genetics ; }, abstract = {Extrachromosomal circular DNAs (eccDNAs) are common genetic elements in Saccharomyces cerevisiae and are reported in other eukaryotes as well. EccDNAs contribute to genetic variation among somatic cells in multicellular organisms and to evolution of unicellular eukaryotes. Sensitive methods for detecting eccDNA are needed to clarify how these elements affect genome stability and how environmental and biological factors induce their formation in eukaryotic cells. This video presents a sensitive eccDNA-purification method called Circle-Seq. The method encompasses column purification of circular DNA, removal of remaining linear chromosomal DNA, rolling-circle amplification of eccDNA, deep sequencing, and mapping. Extensive exonuclease treatment was required for sufficient linear chromosomal DNA degradation. The rolling-circle amplification step by φ29 polymerase enriched for circular DNA over linear DNA. Validation of the Circle-Seq method on three S. cerevisiae CEN.PK populations of 10(10) cells detected hundreds of eccDNA profiles in sizes larger than 1 kilobase. Repeated findings of ASP3-1, COS111, CUP1, RSC30, HXT6, HXT7 genes on circular DNA in both S288c and CEN.PK suggests that DNA circularization is conserved between strains at these loci. In sum, the Circle-Seq method has broad applicability for genome-scale screening for eccDNA in eukaryotes as well as for detecting specific eccDNA types.}, } @article {pmid27044515, year = {2016}, author = {Barth, E and Hübler, R and Baniahmad, A and Marz, M}, title = {The Evolution of COP9 Signalosome in Unicellular and Multicellular Organisms.}, journal = {Genome biology and evolution}, volume = {8}, number = {4}, pages = {1279-1289}, pmid = {27044515}, issn = {1759-6653}, mesh = {Alternative Splicing ; Animals ; COP9 Signalosome Complex ; *Evolution, Molecular ; Exons ; Humans ; Introns ; Multiprotein Complexes/*genetics ; Peptide Hydrolases/*genetics ; Phylogeny ; Protein Subunits/genetics ; }, abstract = {The COP9 signalosome (CSN) is a highly conserved protein complex, recently being crystallized for human. In mammals and plants the COP9 complex consists of nine subunits, CSN 1-8 and CSNAP. The CSN regulates the activity of culling ring E3 ubiquitin and plays central roles in pleiotropy, cell cycle, and defense of pathogens. Despite the interesting and essential functions, a thorough analysis of the CSN subunits in evolutionary comparative perspective is missing. Here we compared 61 eukaryotic genomes including plants, animals, and yeasts genomes and show that the most conserved subunits of eukaryotes among the nine subunits are CSN2 and CSN5. This may indicate a strong evolutionary selection for these two subunits. Despite the strong conservation of the protein sequence, the genomic structures of the intron/exon boundaries indicate no conservation at genomic level. This suggests that the gene structure is exposed to a much less selection compared with the protein sequence. We also show the conservation of important active domains, such as PCI (proteasome lid-CSN-initiation factor) and MPN (MPR1/PAD1 amino-terminal). We identified novel exons and alternative splicing variants for all CSN subunits. This indicates another level of complexity of the CSN. Notably, most COP9-subunits were identified in all multicellular and unicellular eukaryotic organisms analyzed, but not in prokaryotes or archaeas. Thus, genes encoding CSN subunits present in all analyzed eukaryotes indicate the invention of the signalosome at the root of eukaryotes. The identification of alternative splice variants indicates possible "mini-complexes" or COP9 complexes with independent subunits containing potentially novel and not yet identified functions.}, } @article {pmid27040616, year = {2016}, author = {Moody, LA and Saidi, Y and Gibbs, DJ and Choudhary, A and Holloway, D and Vesty, EF and Bansal, KK and Bradshaw, SJ and Coates, JC}, title = {An ancient and conserved function for Armadillo-related proteins in the control of spore and seed germination by abscisic acid.}, journal = {The New phytologist}, volume = {211}, number = {3}, pages = {940-951}, pmid = {27040616}, issn = {1469-8137}, support = {BB/D007550/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Abscisic Acid/*pharmacology ; Arabidopsis/drug effects/*metabolism ; Armadillo Domain Proteins/*metabolism ; Bryopsida/drug effects/*metabolism ; *Conserved Sequence ; *Germination/drug effects ; Mutation/genetics ; Plant Proteins/*metabolism ; Seeds/drug effects/*metabolism ; Selaginellaceae/drug effects/*metabolism ; Sequence Homology, Amino Acid ; Spores/metabolism ; }, abstract = {Armadillo-related proteins regulate development throughout eukaryotic kingdoms. In the flowering plant Arabidopsis thaliana, Armadillo-related ARABIDILLO proteins promote multicellular root branching. ARABIDILLO homologues exist throughout land plants, including early-diverging species lacking true roots, suggesting that early-evolving ARABIDILLOs had additional biological roles. Here we investigated, using molecular genetics, the conservation and diversification of ARABIDILLO protein function in plants separated by c. 450 million years of evolution. We demonstrate that ARABIDILLO homologues in the moss Physcomitrella patens regulate a previously undiscovered inhibitory effect of abscisic acid (ABA) on spore germination. Furthermore, we show that A. thaliana ARABIDILLOs function similarly during seed germination. Early-diverging ARABIDILLO homologues from both P. patens and the lycophyte Selaginella moellendorffii can substitute for ARABIDILLO function during A. thaliana root development and seed germination. We conclude that (1) ABA was co-opted early in plant evolution to regulate functionally analogous processes in spore- and seed-producing plants and (2) plant ARABIDILLO germination functions were co-opted early into both gametophyte and sporophyte, with a specific rooting function evolving later in the land plant lineage.}, } @article {pmid27034283, year = {2016}, author = {Rosenberg, E and Zilber-Rosenberg, I}, title = {Microbes Drive Evolution of Animals and Plants: the Hologenome Concept.}, journal = {mBio}, volume = {7}, number = {2}, pages = {e01395}, pmid = {27034283}, issn = {2150-7511}, mesh = {Adaptation, Biological ; Animals ; *Biological Evolution ; *Biota ; Humans ; *Microbiota ; Plants ; Recombination, Genetic ; Selection, Genetic ; *Symbiosis ; }, abstract = {The hologenome concept of evolution postulates that the holobiont (host plus symbionts) with its hologenome (host genome plus microbiome) is a level of selection in evolution. Multicellular organisms can no longer be considered individuals by the classical definitions of the term. Every natural animal and plant is a holobiont consisting of the host and diverse symbiotic microbes and viruses. Microbial symbionts can be transmitted from parent to offspring by a variety of methods, including via cytoplasmic inheritance, coprophagy, direct contact during and after birth, and the environment. A large number of studies have demonstrated that these symbionts contribute to the anatomy, physiology, development, innate and adaptive immunity, and behavior and finally also to genetic variation and to the origin and evolution of species. Acquisition of microbes and microbial genes is a powerful mechanism for driving the evolution of complexity. Evolution proceeds both via cooperation and competition, working in parallel.}, } @article {pmid27032420, year = {2017}, author = {Huang, Y and Chen, DH and Liu, BY and Shen, WH and Ruan, Y}, title = {Conservation and diversification of polycomb repressive complex 2 (PRC2) proteins in the green lineage.}, journal = {Briefings in functional genomics}, volume = {16}, number = {2}, pages = {106-119}, doi = {10.1093/bfgp/elw007}, pmid = {27032420}, issn = {2041-2657}, mesh = {*Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants/*classification/*metabolism ; Polycomb Repressive Complex 2/genetics/*metabolism ; Protein Interaction Domains and Motifs ; }, abstract = {The polycomb group (PcG) proteins are key epigenetic regulators of gene expression in animals and plants. They act in multiprotein complexes, of which the best characterized is the polycomb repressive complex 2 (PRC2), which catalyses the trimethylation of histone H3 at lysine 27 (H3K27me3) at chromatin targets. In Arabidopsis thaliana, PRC2 proteins are involved in the regulation of diverse developmental processes, including cell fate determination, vegetative growth and development, flowering time control and embryogenesis. Here, we systematically analysed the evolutionary conservation and diversification of PRC2 components in lower and higher plants. We searched for and identified PRC2 homologues from the sequenced genomes of several green lineage species, from the unicellular green alga Ostreococcus lucimarinus to more complicated angiosperms. We found that some PRC2 core components, e.g. E(z), ESC/FIE and MSI/p55, are ancient and have multiplied coincidently with multicellular evolution. For one component, some members are newly formed, especially in the Cruciferae. During evolution, higher plants underwent copy number multiplication of various PRC2 components, which occurred independently for each component, without any obvious co-amplification of PRC2 members. Among the amplified members, usually one was well-conserved and the others were more diversified. Gene amplification occurred at different times for different PcG members during green lineage evolution. Certain PRC2 core components or members of them were highly conserved. Our study provides an insight into the evolutionary conservation and diversification of PcG proteins and may guide future functional characterization of these important epigenetic regulators in plants other than Arabidopsis.}, } @article {pmid27030801, year = {2016}, author = {Panday, A and Grove, A}, title = {The high mobility group protein HMO1 functions as a linker histone in yeast.}, journal = {Epigenetics & chromatin}, volume = {9}, number = {}, pages = {13}, pmid = {27030801}, issn = {1756-8935}, abstract = {BACKGROUND: Eukaryotic chromatin consists of nucleosome core particles connected by linker DNA of variable length. Histone H1 associates with the linker DNA to stabilize the higher-order chromatin structure and to modulate the ability of regulatory factors to access their nucleosomal targets. In Saccharomyces cerevisiae, the protein with greatest sequence similarity to H1 is Hho1p. However, during vegetative growth, hho1∆ cells do not show any discernible cell growth defects or the changes in bulk chromatin structure that are characteristic of chromatin from multicellular eukaryotes in which H1 is depleted. In contrast, the yeast high mobility group (HMGB) protein HMO1 has been reported to compact chromatin, as evidenced by increased nuclease sensitivity in hmo1∆ cells. HMO1 has an unusual domain architecture compared to vertebrate HMGB proteins in that the HMG domains are followed by a lysine-rich extension instead of an acidic domain. We address here the hypothesis that HMO1 serves the role of H1 in terms of chromatin compaction and that this function requires the lysine-rich extension.

RESULTS: We show here that HMO1 fulfills this function of a linker histone. For histone H1, chromatin compaction requires its basic C-terminal domain, and we find that the same pertains to HMO1, as deletion of its C-terminal lysine-rich extension renders chromatin nuclease sensitive. On rDNA, deletion of both HMO1 and Hho1p is required for significantly increased nuclease sensitivity. Expression of human histone H1 completely reverses the nuclease sensitivity characteristic of chromatin isolated from hmo1∆ cells. While chromatin remodeling events associated with repair of DNA double-strand breaks occur faster in the more dynamic chromatin environment created by the hmo1 deletion, expression of human histone H1 results in chromatin remodeling and double-strand break repair similar to that observed in wild-type cells.

CONCLUSION: Our data suggest that S. cerevisiae HMO1 protects linker DNA from nuclease digestion, a property also characteristic of mammalian linker histone H1. Notably, association with HMO1 creates a less dynamic chromatin environment that depends on its lysine-rich domain. That HMO1 has linker histone function has implications for investigations of chromatin structure and function as well as for evolution of proteins with roles in chromatin compaction.}, } @article {pmid27023049, year = {2016}, author = {Roesch, A and Paschen, A and Landsberg, J and Helfrich, I and Becker, JC and Schadendorf, D}, title = {Phenotypic tumour cell plasticity as a resistance mechanism and therapeutic target in melanoma.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {59}, number = {}, pages = {109-112}, doi = {10.1016/j.ejca.2016.02.023}, pmid = {27023049}, issn = {1879-0852}, mesh = {Drug Resistance, Neoplasm/immunology/*physiology ; Epithelial-Mesenchymal Transition/immunology/physiology ; Humans ; Melanoma/*drug therapy/pathology ; Molecular Targeted Therapy/*methods ; Neoplastic Stem Cells/immunology/physiology ; Phenotype ; Tumor Escape/immunology/physiology ; Tumor Microenvironment/immunology/physiology ; }, abstract = {Despite the recent success of MAPK and immune checkpoint inhibitors in advanced melanoma, intrinsic and acquired resistance mechanisms determine the efficacy of these therapeutic approaches. Therapy resistance in melanoma is not solely driven by genetic evolution, but also by epigenetically driven adaptive plasticity. Melanoma cells are shifting between different transcriptional programs, cell cycle states and differentiation phenotypes reflecting a highly dynamic potential to adapt to various exogenous stressors including immune attack or cancer therapies. This review will focus on the dynamic interconversion and overlap between different melanoma cell phenotypes in the context of therapy resistance and a dynamically changing multicellular microenvironment.}, } @article {pmid27021638, year = {2016}, author = {Jubin, T and Kadam, A and Saran, S and Begum, R}, title = {Poly (ADP-ribose) polymerase1 regulates growth and multicellularity in D. discoideum.}, journal = {Differentiation; research in biological diversity}, volume = {92}, number = {1-2}, pages = {10-23}, doi = {10.1016/j.diff.2016.03.002}, pmid = {27021638}, issn = {1432-0436}, mesh = {ADP Ribose Transferases/genetics/*metabolism ; Amino Acid Sequence ; Animals ; Apoptosis ; Blotting, Western ; Cell Cycle ; *Cell Differentiation ; Cells, Cultured ; Dictyostelium/enzymology/*growth & development/metabolism ; *Gene Expression Regulation, Developmental ; Membrane Potential, Mitochondrial ; *Oxidative Stress ; Phylogeny ; Poly (ADP-Ribose) Polymerase-1/genetics/*metabolism ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Amino Acid ; }, abstract = {Poly (ADP-ribose) polymerase (PARP)-1 regulates various biological processes like DNA repair, cell death etc. However, the role of PARP-1 in growth and differentiation still remains elusive. The present study has been undertaken to understand the role of PARP-1 in growth and development of a unicellular eukaryote, Dictyostelium discoideum. In silico analysis demonstrates ADPRT1A as the ortholog of human PARP-1 in D. discoideum. The present study shows that ADPRT1A overexpression (A OE) led to slow growth of D. discoideum and significant population of AOE cells were in S and G2/M phase. Also, AOE cells exhibited high endogenous PARP activity, significant NAD(+) depletion and also significantly lower ADPRT1B and ADPRT2 transcript levels. Moreover, AOE cells are intrinsically stressed and also exhibited susceptibility to oxidative stress. AOE also affected development of D. discoideum predominantly streaming, aggregation and formation of early culminant which are concomitant with reports on PARP's role in D. discoideum development. In addition, under developmental stimuli, increased PARP activity was seen along with developmentally regulated transcript levels of ADPRT1A during D. discoideum multicellularity. Thus the present study suggests that PARP-1 regulates growth as well as the developmental morphogenesis of D. discoideum, thereby opening new avenues to understand the same in higher eukaryotes.}, } @article {pmid26999858, year = {2015}, author = {Titov, VN}, title = {[THE INCONSISTENCIES OF REGULATION OF METABOLISM IN PHYLOGENESIS AT THREE LEVELS OF "RELATIVE BIOLOGICAL PERFECTION": ETIOLOGY OF METABOLIC PANDEMICS].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {60}, number = {11}, pages = {4-12}, pmid = {26999858}, issn = {0869-2084}, mesh = {Adipocytes/classification/metabolism/pathology ; Albumins/metabolism ; Diabetes Mellitus/*epidemiology/genetics/metabolism/pathology ; Essential Hypertension ; Fatty Acids, Nonesterified/metabolism ; Humans ; Hypertension/*epidemiology/genetics/metabolism/pathology ; Insulin/metabolism ; Insulin Resistance ; Macrophages/metabolism/pathology ; Metabolic Networks and Pathways/genetics ; Metabolic Syndrome/*epidemiology/genetics/metabolism/pathology ; Microcirculation/genetics ; Obesity/*epidemiology/genetics/metabolism/pathology ; Organogenesis/genetics ; *Pandemics ; Paracrine Communication/genetics ; *Phylogeny ; }, abstract = {The regulation of metabolism in vivo can be comprehended by considering stages of becoming inphylogenesis of humoral, hormonal, vegetative regulators separately: at the level of cells; in paracrin-regulated cenosises of cells; organs and systems under open blood circulation and closed system of blood flow. The levels of regulations formed at different stages of phylogenesis. Their completion occurred at achievement of "relative biological perfection". Only this way need of cells in functional, structural interaction and forming of multicellular developed. The development of organs and systems of organs also completed at the level of "relative biological perfection". From the same level the third stage of becoming of regulation of metabolism at the level of organism started. When three conditions of "relative biological perfection" achieved consequently at level in vivo are considered in species Homo sapiens using system approach it is detected that "relative biological perfection" in vivo is accompanied by different inconsistencies of regulation of metabolism. They are etiologic factors of "metabolic pandemics ". The inconsistencies (etiological factors) are consider as exemplified by local (at the level of paracrin-regulated cenosises of cells) and system (at the level of organism) regulation of biological reaction metabolism-microcirculation that results in dysfunction of target organs and development of pathogenesis of essential metabolic arterial hypertension. The article describes phylogenetic difference between visceral fatty cells and adpocytes, regulation of metabolism by phylogenetically late insulin, reaction of albumin at increasing of content of unesterified fatty acids in blood plasma, difference of function of resident macrophage and monocytes-macrophages in pathogenesis of atherosclerosis, metabolic syndrome, insulin resistance, obesity, under diabetes mellitus and essential metabolic arterial hypertension.}, } @article {pmid26993504, year = {2016}, author = {D'Asti, E and Chennakrishnaiah, S and Lee, TH and Rak, J}, title = {Extracellular Vesicles in Brain Tumor Progression.}, journal = {Cellular and molecular neurobiology}, volume = {36}, number = {3}, pages = {383-407}, pmid = {26993504}, issn = {1573-6830}, mesh = {Animals ; Brain Neoplasms/diagnosis/genetics/*metabolism/*pathology/therapy ; Cell Communication ; Cell Transformation, Neoplastic/pathology ; *Disease Progression ; Extracellular Vesicles/*metabolism ; Humans ; Mutation/genetics ; }, abstract = {Brain tumors can be viewed as multicellular 'ecosystems' with increasingly recognized cellular complexity and systemic impact. While the emerging diversity of malignant disease entities affecting brain tissues is often described in reference to their signature alterations within the cellular genome and epigenome, arguably these cell-intrinsic changes can be regarded as hardwired adaptations to a variety of cell-extrinsic microenvironmental circumstances. Conversely, oncogenic events influence the microenvironment through their impact on the cellular secretome, including emission of membranous structures known as extracellular vesicles (EVs). EVs serve as unique carriers of bioactive lipids, secretable and non-secretable proteins, mRNA, non-coding RNA, and DNA and constitute pathway(s) of extracellular exit of molecules into the intercellular space, biofluids, and blood. EVs are also highly heterogeneous as reflected in their nomenclature (exosomes, microvesicles, microparticles) attempting to capture their diverse origin, as well as structural, molecular, and functional properties. While EVs may act as a mechanism of molecular expulsion, their non-random uptake by heterologous cellular recipients defines their unique roles in the intercellular communication, horizontal molecular transfer, and biological activity. In the central nervous system, EVs have been implicated as mediators of homeostasis and repair, while in cancer they may act as regulators of cell growth, clonogenicity, angiogenesis, thrombosis, and reciprocal tumor-stromal interactions. EVs produced by specific brain tumor cell types may contain the corresponding oncogenic drivers, such as epidermal growth factor receptor variant III (EGFRvIII) in glioblastoma (and hence are often referred to as 'oncosomes'). Through this mechanism, mutant oncoproteins and nucleic acids may be transferred horizontally between cellular populations altering their individual and collective phenotypes. Oncogenic pathways also impact the emission rates, types, cargo, and biogenesis of EVs, as reflected by preliminary analyses pointing to differences in profiles of EV-regulating genes (vesiculome) between molecular subtypes of glioblastoma, and in other brain tumors. Molecular regulators of vesiculation can also act as oncogenes. These intimate connections suggest the context-specific roles of different EV subsets in the progression of specific brain tumors. Advanced efforts are underway to capture these events through the use of EVs circulating in biofluids as biomarker reservoirs and to guide diagnostic and therapeutic decisions.}, } @article {pmid26990199, year = {2016}, author = {Espinosa, A and Paz-Y-Miño-C, G and Hackey, M and Rutherford, S}, title = {Entamoeba Clone-Recognition Experiments: Morphometrics, Aggregative Behavior, and Cell-Signaling Characterization.}, journal = {The Journal of eukaryotic microbiology}, volume = {63}, number = {3}, pages = {384-393}, pmid = {26990199}, issn = {1550-7408}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/metabolism ; Animals ; Ankyrins/metabolism ; Biological Evolution ; Clone Cells/physiology ; Entamoeba/classification/*genetics/*physiology ; HSP70 Heat-Shock Proteins/metabolism ; Phylogeny ; Protein Kinases/metabolism ; *Signal Transduction ; }, abstract = {Studies on clone- and kin-discrimination in protists have proliferated during the past decade. We report clone-recognition experiments in seven Entamoeba lineages (E. invadens IP-1, E. invadens VK-1:NS, E. terrapinae, E. moshkovskii Laredo, E. moshkovskii Snake, E. histolytica HM-1:IMSS and E. dispar). First, we characterized morphometrically each clone (length, width, and cell-surface area) and documented how they differed statistically from one another (as per single-variable or canonical-discriminant analyses). Second, we demonstrated that amebas themselves could discriminate self (clone) from different (themselves vs. other clones). In mix-cell-line cultures between closely-related (E. invadens IP-1 vs. E. invadens VK-1:NS) or distant-phylogenetic clones (E. terrapinae vs. E. moshkovskii Laredo), amebas consistently aggregated with same-clone members. Third, we identified six putative cell-signals secreted by the amebas (RasGap/Ankyrin, coronin-WD40, actin, protein kinases, heat shock 70, and ubiquitin) and which known functions in Entamoeba spp. included: cell proliferation, cell adhesion, cell movement, and stress-induced encystation. To our knowledge, this is the first multi-clone characterization of Entamoeba spp. morphometrics, aggregative behavior, and cell-signaling secretion in the context of clone-recognition. Protists allow us to study cell-cell recognition from ecological and evolutionary perspectives. Modern protistan lineages can be central to studies about the origins and evolution of multicellularity.}, } @article {pmid26988968, year = {2016}, author = {Hugenholtz, P and Skarshewski, A and Parks, DH}, title = {Genome-Based Microbial Taxonomy Coming of Age.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {8}, number = {6}, pages = {}, pmid = {26988968}, issn = {1943-0264}, mesh = {Animals ; Archaea/genetics ; *Biodiversity ; Biological Evolution ; *Classification ; Genome ; *Genomics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Reconstructing the complete evolutionary history of extant life on our planet will be one of the most fundamental accomplishments of scientific endeavor, akin to the completion of the periodic table, which revolutionized chemistry. The road to this goal is via comparative genomics because genomes are our most comprehensive and objective evolutionary documents. The genomes of plant and animal species have been systematically targeted over the past decade to provide coverage of the tree of life. However, multicellular organisms only emerged in the last 550 million years of more than three billion years of biological evolution and thus comprise a small fraction of total biological diversity. The bulk of biodiversity, both past and present, is microbial. We have only scratched the surface in our understanding of the microbial world, as most microorganisms cannot be readily grown in the laboratory and remain unknown to science. Ground-breaking, culture-independent molecular techniques developed over the past 30 years have opened the door to this so-called microbial dark matter with an accelerating momentum driven by exponential increases in sequencing capacity. We are on the verge of obtaining representative genomes across all life for the first time. However, historical use of morphology, biochemical properties, behavioral traits, and single-marker genes to infer organismal relationships mean that the existing highly incomplete tree is riddled with taxonomic errors. Concerted efforts are now needed to synthesize and integrate the burgeoning genomic data resources into a coherent universal tree of life and genome-based taxonomy.}, } @article {pmid26988136, year = {2016}, author = {Dornbos, SQ and Oji, T and Kanayama, A and Gonchigdorj, S}, title = {A new Burgess Shale-type deposit from the Ediacaran of western Mongolia.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {23438}, pmid = {26988136}, issn = {2045-2322}, mesh = {Animals ; Biological Evolution ; Biota ; Fossils ; Geologic Sediments/*analysis ; Mongolia ; }, abstract = {Preservation of soft-bodied organisms is exceedingly rare in the fossil record. One way that such fossils are preserved is as carbonaceous compressions in fined-grained marine sedimentary rocks. These deposits of exceptional preservation are known as Burgess Shale-type (BST) deposits. During the Cambrian Period, BST deposits are more common and provide a crucial view of early animal evolution. The earliest definitive fossil evidence for macroscopic animal-grade organisms is found in the preceding Ediacaran Period. BST deposits from the Ediacaran are rarer and lack conclusive evidence for animals. Here we report the discovery of a new Ediacaran BST deposit with exceptional preservation of non-mineralizing macro-organisms in thinly bedded black shale from Zavkhan Province, western Mongolia. This fossil assemblage, here named the Zuun-Arts biota, currently consists of two new species of probable macroscopic multicellular benthic algae. One species, Chinggiskhaania bifurcata n. gen., n. sp., dominates the biota. The other species, Zuunartsphyton delicatum n. gen., n. sp., is known from three specimens. SEM-EDS analysis shows that the fossils are composed of aluminosilicate clay minerals and some carbon, a composition comparable to fossils from the Cambrian Burgess Shale biota. This discovery opens a new window through which to view late Precambrian life.}, } @article {pmid26987708, year = {2016}, author = {Rensing, SA}, title = {(Why) Does Evolution Favour Embryogenesis?.}, journal = {Trends in plant science}, volume = {21}, number = {7}, pages = {562-573}, doi = {10.1016/j.tplants.2016.02.004}, pmid = {26987708}, issn = {1878-4372}, mesh = {*Biological Evolution ; Embryonic Development/*physiology ; Phaeophyceae/physiology ; Plants/metabolism ; }, abstract = {Complex multicellular organisms typically possess life cycles in which zygotes (formed by gamete fusion) and meiosis occur. Canonical animal embryogenesis describes development from zygote to birth. It involves polarisation of the egg/zygote, asymmetric cell divisions, establishment of axes, symmetry breaking, formation of organs, and parental nutrition (at least in early stages). Similar developmental patterns have independently evolved in other eukaryotic lineages, including land plants and brown algae. The question arises whether embryo-like structures and associated developmental processes recurrently emerge because they are local optima of the evolutionary landscape. To understand which evolutionary principles govern complex multicellularity, we need to analyse why and how similar processes evolve convergently - von Baer's and Haeckel's phylotypic stage revisited in other phyla.}, } @article {pmid26986966, year = {2016}, author = {Jaiteh, M and Taly, A and Hénin, J}, title = {Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors.}, journal = {PloS one}, volume = {11}, number = {3}, pages = {e0151934}, pmid = {26986966}, issn = {1932-6203}, mesh = {Animals ; Archaea/classification/genetics/physiology ; Conserved Sequence/genetics/physiology ; Cysteine Loop Ligand-Gated Ion Channel Receptors/genetics/physiology ; Eukaryota/genetics/physiology ; Evolution, Molecular ; Fungi/genetics/physiology ; Invertebrates/genetics/physiology ; Ligand-Gated Ion Channels/*genetics/physiology ; Phylogeny ; Plants/genetics ; Receptors, Neurotransmitter/*genetics/physiology ; Sequence Alignment ; }, abstract = {Pentameric ligand-gated ion channels (pLGICs) are ubiquitous neurotransmitter receptors in Bilateria, with a small number of known prokaryotic homologues. Here we describe a new inventory and phylogenetic analysis of pLGIC genes across all kingdoms of life. Our main finding is a set of pLGIC genes in unicellular eukaryotes, some of which are metazoan-like Cys-loop receptors, and others devoid of Cys-loop cysteines, like their prokaryotic relatives. A number of such "Cys-less" receptors also appears in invertebrate metazoans. Together, those findings draw a new distribution of pLGICs in eukaryotes. A broader distribution of prokaryotic channels also emerges, including a major new archaeal taxon, Thaumarchaeota. More generally, pLGICs now appear nearly ubiquitous in major taxonomic groups except multicellular plants and fungi. However, pLGICs are sparsely present in unicellular taxa, suggesting a high rate of gene loss and a non-essential character, contrasting with their essential role as synaptic receptors of the bilaterian nervous system. Multiple alignments of these highly divergent sequences reveal a small number of conserved residues clustered at the interface between the extracellular and transmembrane domains. Only the "Cys-loop" proline is absolutely conserved, suggesting the more fitting name "Pro loop" for that motif, and "Pro-loop receptors" for the superfamily. The infered molecular phylogeny shows a Cys-loop and a Cys-less clade in eukaryotes, both containing metazoans and unicellular members. This suggests new hypotheses on the evolutionary history of the superfamily, such as a possible origin of the Cys-loop cysteines in an ancient unicellular eukaryote. Deeper phylogenetic relationships remain uncertain, particularly around the split between bacteria, archaea, and eukaryotes.}, } @article {pmid26986787, year = {2015}, author = {Qiu, H and Price, DC and Yang, EC and Yoon, HS and Bhattacharya, D}, title = {Evidence of ancient genome reduction in red algae (Rhodophyta).}, journal = {Journal of phycology}, volume = {51}, number = {4}, pages = {624-636}, doi = {10.1111/jpy.12294}, pmid = {26986787}, issn = {1529-8817}, abstract = {Red algae (Rhodophyta) comprise a monophyletic eukaryotic lineage of ~6,500 species with a fossil record that extends back 1.2 billion years. A surprising aspect of red algal evolution is that sequenced genomes encode a relatively limited gene inventory (~5-10 thousand genes) when compared with other free-living algae or to other eukaryotes. This suggests that the common ancestor of red algae may have undergone extensive genome reduction, which can result from lineage specialization to a symbiotic or parasitic lifestyle or adaptation to an extreme or oligotrophic environment. We gathered genome and transcriptome data from a total of 14 red algal genera that represent the major branches of this phylum to study genome evolution in Rhodophyta. Analysis of orthologous gene gains and losses identifies two putative major phases of genome reduction: (i) in the stem lineage leading to all red algae resulting in the loss of major functions such as flagellae and basal bodies, the glycosyl-phosphatidylinositol anchor biosynthesis pathway, and the autophagy regulation pathway; and (ii) in the common ancestor of the extremophilic Cyanidiophytina. Red algal genomes are also characterized by the recruitment of hundreds of bacterial genes through horizontal gene transfer that have taken on multiple functions in shared pathways and have replaced eukaryotic gene homologs. Our results suggest that Rhodophyta may trace their origin to a gene depauperate ancestor. Unlike plants, it appears that a limited gene inventory is sufficient to support the diversification of a major eukaryote lineage that possesses sophisticated multicellular reproductive structures and an elaborate triphasic sexual cycle.}, } @article {pmid26973658, year = {2016}, author = {Rahman, H and Yang, J and Xu, YP and Munyampundu, JP and Cai, XZ}, title = {Phylogeny of Plant CAMTAs and Role of AtCAMTAs in Nonhost Resistance to Xanthomonas oryzae pv. oryzae.}, journal = {Frontiers in plant science}, volume = {7}, number = {}, pages = {177}, pmid = {26973658}, issn = {1664-462X}, abstract = {Calmodulin-binding transcription activator (CAMTA) constitutes one of the most important Ca(2+)/CaM-regulated transcription factor families in plants. Nevertheless, the phylogeny, protein interaction network, and role in nonhost resistance of plant CAMTAs are not well understood. In this study, 200 CAMTA genes were identified from 35 species representing four major plant lineages. The CAMTA genes were conserved in multicellular land plants but absent in unicellular eukaryotes, and were likely to emerge from the fusion of two separate genes encoding a CAMTA-like protein and an IQ/CaM binding motif containing protein, respectively, in the embryophyta lineage ancestor. Approximately one fourth of plant CAMTAs did not contain a TIG domain. This non-TIG class of CAMTAs seems to have newly evolved through mutation of some key amino acids in the TIG domain of flowering land plants after divergence from the non-flowering plants. Phylogenetic analysis classified CAMTA proteins into three major groups and nine distinct subgroups, a result supported by protein domain and motif conservation analyses. Most (59.0 and 21.5%) of the identified CAMTA genes contained 12 or 11 introns, respectively. Gene duplication, intron invasion, enlargement and turnover, as well as exon rearrangements and skipping have apparently occurred during evolution of the CAMTA family. Moreover, 38 potential interactors of six Arabidopsis CAMTAs were predicted and 10 predicted target genes of AtCAMTA3 exhibited changes in expression between Atcamta3 mutants and wild-type plants. The majority of predicted interactors are transcription factors and/or Ca(2+)/CaM-regulated proteins, suggesting that transcriptional regulation of the target genes might be the dominant functional mechanism of AtCAMTAs, and AtCAMTAs might act together with other Ca(2+) signaling components to regulate Ca(2+)-related biological processes. Furthermore, functional analyses employing Atcamta mutants revealed that AtCAMTA3 negatively regulated the immunity triggered by flg22 and nonhost resistance to Xanthomonas oryzae pv. oryzae via repressing accumulation of reactive oxygen species probably by targeting CBP60G, EDS1, and NDR1 and involving SA pathway.}, } @article {pmid26970004, year = {2016}, author = {Woodland, HR}, title = {The Birth of Animal Development: Multicellularity and the Germline.}, journal = {Current topics in developmental biology}, volume = {117}, number = {}, pages = {609-630}, doi = {10.1016/bs.ctdb.2015.10.020}, pmid = {26970004}, issn = {1557-8933}, mesh = {Animals ; *Biological Evolution ; Germ Cells/*cytology ; Reproduction/*physiology ; }, abstract = {The evolution of multicellular animals has been attributed to many kinds of selective advantage; here I suggest that the evolution of somatic cells to feed and protect the germline was central to the appearance of animals. This would have been driven by selection for extreme anisogamy--the evolution of sperm and egg. Evidence is adduced from the germline stem cells of simple animals (defining germline as any cell that normally produces the next generation via the sexual process) and from the control circuitry ubiquitous in animal germlines. With the soma and its elaboration came animal development, as we understand it.}, } @article {pmid26967282, year = {2016}, author = {Stoeger, T and Battich, N and Pelkmans, L}, title = {Passive Noise Filtering by Cellular Compartmentalization.}, journal = {Cell}, volume = {164}, number = {6}, pages = {1151-1161}, doi = {10.1016/j.cell.2016.02.005}, pmid = {26967282}, issn = {1097-4172}, mesh = {Animals ; Cell Nucleus/physiology ; *Cell Physiological Phenomena ; Feedback ; Humans ; Intracellular Membranes/*physiology ; Single-Cell Analysis ; *Stochastic Processes ; }, abstract = {Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity.}, } @article {pmid26961431, year = {2016}, author = {Morrill, GA and Kostellow, AB and Liu, L and Gupta, RK and Askari, A}, title = {Evolution of the α-Subunit of Na/K-ATPase from Paramecium to Homo sapiens: Invariance of Transmembrane Helix Topology.}, journal = {Journal of molecular evolution}, volume = {82}, number = {4-5}, pages = {183-198}, pmid = {26961431}, issn = {1432-1432}, support = {P01 HL036573/HL/NHLBI NIH HHS/United States ; R01 GM071324/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Binding Sites ; Biological Evolution ; Cell Membrane/metabolism ; *Evolution, Molecular ; Humans ; Molecular Sequence Data ; Protein Conformation, alpha-Helical/physiology ; Sodium/metabolism ; Sodium-Potassium-Exchanging ATPase/*genetics/metabolism ; }, abstract = {Na/K-ATPase is a key plasma membrane enzyme involved in cell signaling, volume regulation, and maintenance of electrochemical gradients. The α-subunit, central to these functions, belongs to a large family of P-type ATPases. Differences in transmembrane (TM) helix topology, sequence homology, helix-helix contacts, cell signaling, and protein domains of Na/K-ATPase α-subunit were compared in fungi (Beauveria), unicellular organisms (Paramecia), primitive multicellular organisms (Hydra), and vertebrates (Xenopus, Homo sapiens), and correlated with evolution of physiological functions in the α-subunit. All α-subunits are of similar length, with groupings of four and six helices in the N- and C-terminal regions, respectively. Minimal homology was seen for protein domain patterns in Paramecium and Hydra, with high correlation between Hydra and vertebrates. Paramecium α-subunits display extensive disorder, with minimal helix contacts. Increases in helix contacts in Hydra approached vertebrates. Protein motifs known to be associated with membrane lipid rafts and cell signaling reveal significant positional shifts between Paramecium and Hydra vulgaris, indicating that regional membrane fluidity changes occur during evolution. Putative steroid binding sites overlapping TM-3 occurred in all species. Sites associated with G-protein-receptor stimulation occur both in vertebrates and amphibia but not in Hydra or Paramecia. The C-terminus moiety "KETYY," necessary for the Na(+) activation of pump phosphorylation, is not present in unicellular species indicating the absence of classical Na(+)/K(+)-pumps. The basic protein topology evolved earliest, followed by increases in protein domains and ordered helical arrays, correlated with appearance of α-subunit regions known to involve cell signaling, membrane recycling, and ion channel formation.}, } @article {pmid26958911, year = {2015}, author = {Zwart, MP and Elena, SF}, title = {Matters of Size: Genetic Bottlenecks in Virus Infection and Their Potential Impact on Evolution.}, journal = {Annual review of virology}, volume = {2}, number = {1}, pages = {161-179}, doi = {10.1146/annurev-virology-100114-055135}, pmid = {26958911}, issn = {2327-0578}, mesh = {Animals ; *Biological Evolution ; *Genome Size ; Humans ; Virus Diseases/*virology ; Virus Physiological Phenomena ; Viruses/classification/*genetics/isolation & purification ; }, abstract = {For virus infections of multicellular hosts, narrow genetic bottlenecks during transmission and within-host spread appear to be widespread. These bottlenecks will affect the maintenance of genetic variation in a virus population and the prevalence of mixed-strain infections, thereby ultimately determining the strength with which different random forces act during evolution. Here we consider different approaches for estimating bottleneck sizes and weigh their merits. We then review quantitative estimates of bottleneck size during cellular infection, within-host spread, horizontal transmission, and finally vertical transmission. In most cases we find that bottlenecks do regularly occur, although in many cases they appear to be virion-concentration dependent. Finally, we consider the evolutionary implications of genetic bottlenecks during virus infection. Although on average strong bottlenecks will lead to declines in fitness, we consider a number of scenarios in which bottlenecks could also be advantageous for viruses.}, } @article {pmid26941230, year = {2016}, author = {Reyes-Bermudez, A and Villar-Briones, A and Ramirez-Portilla, C and Hidaka, M and Mikheyev, AS}, title = {Developmental Progression in the Coral Acropora digitifera Is Controlled by Differential Expression of Distinct Regulatory Gene Networks.}, journal = {Genome biology and evolution}, volume = {8}, number = {3}, pages = {851-870}, pmid = {26941230}, issn = {1759-6653}, mesh = {Animals ; Anthozoa/*genetics/growth & development ; Cell Differentiation/genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks/*genetics ; Larva/*genetics/growth & development ; Transcriptome/*genetics ; }, abstract = {Corals belong to the most basal class of the Phylum Cnidaria, which is considered the sister group of bilaterian animals, and thus have become an emerging model to study the evolution of developmental mechanisms. Although cell renewal, differentiation, and maintenance of pluripotency are cellular events shared by multicellular animals, the cellular basis of these fundamental biological processes are still poorly understood. To understand how changes in gene expression regulate morphogenetic transitions at the base of the eumetazoa, we performed quantitative RNA-seq analysis duringAcropora digitifera's development. We collected embryonic, larval, and adult samples to characterize stage-specific transcription profiles, as well as broad expression patterns. Transcription profiles reconstructed development revealing two main expression clusters. The first cluster grouped blastula and gastrula and the second grouped subsequent developmental time points. Consistently, we observed clear differences in gene expression between early and late developmental transitions, with higher numbers of differentially expressed genes and fold changes around gastrulation. Furthermore, we identified three coexpression clusters that represented discrete gene expression patterns. During early transitions, transcriptional networks seemed to regulate cellular fate and morphogenesis of the larval body. In late transitions, these networks seemed to play important roles preparing planulae for switch in lifestyle and regulation of adult processes. Although developmental progression inA. digitiferais regulated to some extent by differential coexpression of well-defined gene networks, stage-specific transcription profiles appear to be independent entities. While negative regulation of transcription is predominant in early development, cell differentiation was upregulated in larval and adult stages.}, } @article {pmid26940948, year = {2016}, author = {Tice, AK and Silberman, JD and Walthall, AC and Le, KN and Spiegel, FW and Brown, MW}, title = {Sorodiplophrys stercorea: Another Novel Lineage of Sorocarpic Multicellularity.}, journal = {The Journal of eukaryotic microbiology}, volume = {63}, number = {5}, pages = {623-628}, doi = {10.1111/jeu.12311}, pmid = {26940948}, issn = {1550-7408}, mesh = {Animals ; Base Sequence ; Cattle/parasitology ; DNA, Protozoan/isolation & purification ; DNA, Ribosomal ; Genes, rRNA/genetics ; Horses/parasitology ; Mississippi ; *Phylogeny ; Rhizaria/classification ; Stramenopiles/*classification/cytology/genetics/*isolation & purification ; }, abstract = {Sorodiplophrys stercorea is a sorocarpic organism that utilizes filose pseudopodia for locomotion and absorptive nutrition. It has traditionally been considered to be a member of the Labyrinthulae based on its morphology. Its closest relatives were thought to be species in the taxon Diplophrys. Since the genus Diplophrys has been shown to be paraphyletic and S. stercorea has pseudopodia similar to some members of Rhizaria, we examined its relationship with other eukaryotes. We obtained four isolates from the dung of cow and horse, brought each into monoeukaryotic culture, and sequenced their SSU rRNA gene for phylogenetic analysis. All our isolates were shown to form a monophyletic group in the Labyrinthulae, nested in the Amphifiloidea clade. Our results demonstrate that Sorodiplophrys is more closely related to species of the genus Amphifila than to Diplophrys and represents an additional independent origin of sorocarpic multicellularity among eukaryotes. This study represents the first confirmed sorocarpic lifestyle in the Stramenopiles.}, } @article {pmid26933058, year = {2016}, author = {Singletary, LA and Karlinsey, JE and Libby, SJ and Mooney, JP and Lokken, KL and Tsolis, RM and Byndloss, MX and Hirao, LA and Gaulke, CA and Crawford, RW and Dandekar, S and Kingsley, RA and Msefula, CL and Heyderman, RS and Fang, FC}, title = {Loss of Multicellular Behavior in Epidemic African Nontyphoidal Salmonella enterica Serovar Typhimurium ST313 Strain D23580.}, journal = {mBio}, volume = {7}, number = {2}, pages = {e02265}, pmid = {26933058}, issn = {2150-7511}, support = {U19 AI090882/AI/NIAID NIH HHS/United States ; T32 AI060555/AI/NIAID NIH HHS/United States ; R01 AI112640/AI/NIAID NIH HHS/United States ; AI91966/AI/NIAID NIH HHS/United States ; R56 AI098078/AI/NIAID NIH HHS/United States ; R01 AI098078/AI/NIAID NIH HHS/United States ; AI44486/AI/NIAID NIH HHS/United States ; T32AI60555/AI/NIAID NIH HHS/United States ; AI90882/AI/NIAID NIH HHS/United States ; AI1112640/AI/NIAID NIH HHS/United States ; AI43274/AI/NIAID NIH HHS/United States ; R01 AI044486/AI/NIAID NIH HHS/United States ; R01 AI043274/AI/NIAID NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; AI98078/AI/NIAID NIH HHS/United States ; }, mesh = {*Adaptation, Biological ; Africa South of the Sahara/epidemiology ; Animals ; Catalase/genetics/metabolism ; Disease Models, Animal ; Epidemics ; Glucosyltransferases/genetics/metabolism ; Humans ; Macaca mulatta ; Mice ; Mutant Proteins/genetics/metabolism ; Salmonella Infections/epidemiology/*microbiology ; Salmonella typhimurium/*enzymology/genetics/isolation & purification/*physiology ; *Stress, Physiological ; }, abstract = {UNLABELLED: Nontyphoidal Salmonella enterica serovar Typhimurium is a frequent cause of bloodstream infections in children and HIV-infected adults in sub-Saharan Africa. Most isolates from African patients with bacteremia belong to a single sequence type, ST313, which is genetically distinct from gastroenteritis-associated ST19 strains, such as 14028s and SL1344. Some studies suggest that the rapid spread of ST313 across sub-Saharan Africa has been facilitated by anthroponotic (person-to-person) transmission, eliminating the need for Salmonella survival outside the host. While these studies have not ruled out zoonotic or other means of transmission, the anthroponotic hypothesis is supported by evidence of extensive genomic decay, a hallmark of host adaptation, in the sequenced ST313 strain D23580. We have identified and demonstrated 2 loss-of-function mutations in D23580, not present in the ST19 strain 14028s, that impair multicellular stress resistance associated with survival outside the host. These mutations result in inactivation of the KatE stationary-phase catalase that protects high-density bacterial communities from oxidative stress and the BcsG cellulose biosynthetic enzyme required for the RDAR (red, dry, and rough) colonial phenotype. However, we found that like 14028s, D23580 is able to elicit an acute inflammatory response and cause enteritis in mice and rhesus macaque monkeys. Collectively, these observations suggest that African S. Typhimurium ST313 strain D23580 is becoming adapted to an anthroponotic mode of transmission while retaining the ability to infect and cause enteritis in multiple host species.

IMPORTANCE: The last 3 decades have witnessed an epidemic of invasive nontyphoidal Salmonella infections in sub-Saharan Africa. Genomic analysis and clinical observations suggest that the Salmonella strains responsible for these infections are evolving to become more typhoid-like with regard to patterns of transmission and virulence. This study shows that a prototypical African nontyphoidal Salmonella strain has lost traits required for environmental stress resistance, consistent with an adaptation to a human-to-human mode of transmission. However, in contrast to predictions, the strain remains capable of causing acute inflammation in the mammalian intestine. This suggests that the systemic clinical presentation of invasive nontyphoidal Salmonella infections in Africa reflects the immune status of infected hosts rather than intrinsic differences in the virulence of African Salmonella strains. Our study provides important new insights into the evolution of host adaptation in bacterial pathogens.}, } @article {pmid26932355, year = {2016}, author = {Luo, T and He, X and Xing, K}, title = {Lineage analysis by microsatellite loci deep sequencing in mice.}, journal = {Molecular reproduction and development}, volume = {83}, number = {5}, pages = {387-391}, doi = {10.1002/mrd.22632}, pmid = {26932355}, issn = {1098-2795}, mesh = {Animals ; Female ; *Genetic Loci ; Genome-Wide Association Study ; *High-Throughput Nucleotide Sequencing ; Male ; Mice ; *Microsatellite Repeats ; }, abstract = {Lineage analysis is the identification of all the progeny of a single progenitor cell, and has become particularly useful for studying developmental processes and cancer biology. Here, we propose a novel and effective method for lineage analysis that combines sequence capture and next-generation sequencing technology. Genome-wide mononucleotide and dinucleotide microsatellite loci in eight samples from two mice were identified and used to construct phylogenetic trees based on somatic indel mutations at these loci, which were unique enough to distinguish and parse samples from different mice into different groups along the lineage tree. For example, biopsies from the liver and stomach, which originate from the endoderm, were located in the same clade, while samples in kidney, which originate from the mesoderm, were located in another clade. Yet, tissue with a common developmental origin may still contain cells of a mixed ancestry. This genome-wide approach thus provides a non-invasive lineage analysis method based on mutations that accumulate in the genomes of opaque multicellular organism somatic cells. Mol. Reprod. Dev. 83: 387-391, 2016. © 2016 Wiley Periodicals, Inc.}, } @article {pmid26931797, year = {2016}, author = {Smith, J and Strassmann, JE and Queller, DC}, title = {Fine-scale spatial ecology drives kin selection relatedness among cooperating amoebae.}, journal = {Evolution; international journal of organic evolution}, volume = {70}, number = {4}, pages = {848-859}, doi = {10.1111/evo.12895}, pmid = {26931797}, issn = {1558-5646}, mesh = {Dictyostelium/*genetics/physiology ; Ecology ; Genotype ; *Microbial Interactions ; Population Density ; *Selection, Genetic ; Soil Microbiology ; }, abstract = {Cooperation among microbes is important for traits as diverse as antibiotic resistance, pathogen virulence, and sporulation. The evolutionary stability of cooperation against "cheater" mutants depends critically on the extent to which microbes interact with genetically similar individuals. The causes of this genetic social structure in natural microbial systems, however, are unknown. Here, we show that social structure among cooperative Dictyostelium amoebae is driven by the population ecology of colonization, growth, and dispersal acting at spatial scales as small as fruiting bodies themselves. Despite the fact that amoebae disperse while grazing, all it takes to create substantial genetic clonality within multicellular fruiting bodies is a few millimeters distance between the cells colonizing a feeding site. Even adjacent fruiting bodies can consist of different genotypes. Soil populations of amoebae are sparse and patchily distributed at millimeter scales. The fine-scale spatial structure of cells and genotypes can thus account for the otherwise unexplained high genetic uniformity of spores in fruiting bodies from natural substrates. These results show how a full understanding of microbial cooperation requires understanding ecology and social structure at the small spatial scales microbes themselves experience.}, } @article {pmid26931578, year = {2016}, author = {Zaccard, CR and Rinaldo, CR and Mailliard, RB}, title = {Linked in: immunologic membrane nanotube networks.}, journal = {Journal of leukocyte biology}, volume = {100}, number = {1}, pages = {81-94}, pmid = {26931578}, issn = {1938-3673}, support = {S10 OD010625/OD/NIH HHS/United States ; R37 AI041870/AI/NIAID NIH HHS/United States ; U01 AI035041/AI/NIAID NIH HHS/United States ; UM1 AI035043/AI/NIAID NIH HHS/United States ; T32 AI065380/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigen Presentation/*immunology ; Cell Membrane/*immunology ; Dendritic Cells/*immunology ; Humans ; Immunity, Cellular/*immunology ; *Nanotubes ; }, abstract = {Membrane nanotubes, also termed tunneling nanotubes, are F-actin-based structures that can form direct cytoplasmic connections and support rapid communication between distant cells. These nanoscale conduits have been observed in diverse cell types, including immune, neuronal, stromal, cancer, and stem cells. Until recently, little was known about the mechanisms involved in membrane nanotube development in myeloid origin APCs or how membrane nanotube networks support their ability to bridge innate and adaptive immunity. New research has provided insight into the modes of induction and regulation of the immune process of "reticulation" or the development of multicellular membrane nanotube networks in dendritic cells. Preprogramming by acute type 1 inflammatory mediators at their immature stage licenses mature type 1-polarized dendritic cells to reticulate upon subsequent interaction with CD40 ligand-expressing CD4(+) Th cells. Dendritic cell reticulation can support direct antigen transfer for amplification of specific T cell responses and can be positively or negatively regulated by signals from distinct Th cell subsets. Membrane nanotubes not only enhance the ability of immature dendritic cells to sense pathogens and rapidly mobilize nearby antigen-presenting cells in the peripheral tissues but also likely support communication of pathogen-related information from mature migratory dendritic cells to resident dendritic cells in lymph nodes. Therefore, the reticulation process facilitates a coordinated multicellular response for the efficient initiation of cell-mediated adaptive immune responses. Herein, we discuss studies focused on the molecular mechanisms of membrane nanotube formation, structure, and function in the context of immunity and how pathogens, such as HIV-1, may use dendritic cell reticulation to circumvent host defenses.}, } @article {pmid26927887, year = {2016}, author = {Zhang, X and Zhuchenko, O and Kuspa, A and Soldati, T}, title = {Social amoebae trap and kill bacteria by casting DNA nets.}, journal = {Nature communications}, volume = {7}, number = {}, pages = {10938}, pmid = {26927887}, issn = {2041-1723}, support = {P01 HD039691/HD/NICHD NIH HHS/United States ; HD39691/HD/NICHD NIH HHS/United States ; }, mesh = {Bacteria ; DNA/*physiology ; Dictyostelium/*physiology ; Extracellular Traps/*physiology ; Klebsiella pneumoniae/*physiology ; *Microbial Viability ; Pseudomonas aeruginosa/*physiology ; Reactive Oxygen Species ; }, abstract = {Extracellular traps (ETs) from neutrophils are reticulated nets of DNA decorated with anti-microbial granules, and are capable of trapping and killing extracellular pathogens. Various phagocytes of mammals and invertebrates produce ETs, however, the evolutionary history of this DNA-based host defence strategy is unclear. Here we report that Sentinel (S) cells of the multicellular slug stage of the social amoeba Dictyostelium discoideum produce ETs upon stimulation with bacteria or lipopolysaccharide in a reactive oxygen species-dependent manner. The production of ETs by S cells requires a Toll/Interleukin-1 receptor domain-containing protein TirA and reactive oxygen species-generating NADPH oxidases. Disruption of these genes results in decreased clearance of bacterial infections. Our results demonstrate that D. discoideum is a powerful model organism to study the evolution and conservation of mechanisms of cell-intrinsic immunity, and suggest that the origin of DNA-based ETs as an innate immune defence predates the emergence of metazoans.}, } @article {pmid26923142, year = {2016}, author = {Derst, C and Dircksen, H and Meusemann, K and Zhou, X and Liu, S and Predel, R}, title = {Evolution of neuropeptides in non-pterygote hexapods.}, journal = {BMC evolutionary biology}, volume = {16}, number = {}, pages = {51}, pmid = {26923142}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Arthropods/classification/genetics ; *Evolution, Molecular ; Insect Proteins/chemistry/*genetics ; Insecta/classification/*genetics/metabolism ; Molecular Sequence Data ; Neuropeptides/chemistry/*genetics ; Phylogeny ; Transcriptome ; }, abstract = {BACKGROUND: Neuropeptides are key players in information transfer and act as important regulators of development, growth, metabolism, and reproduction within multi-cellular animal organisms (Metazoa). These short protein-like substances show a high degree of structural variability and are recognized as the most diverse group of messenger molecules. We used transcriptome sequences from the 1KITE (1K Insect Transcriptome Evolution) project to search for neuropeptide coding sequences in 24 species from the non-pterygote hexapod lineages Protura (coneheads), Collembola (springtails), Diplura (two-pronged bristletails), Archaeognatha (jumping bristletails), and Zygentoma (silverfish and firebrats), which are often referred to as "basal" hexapods. Phylogenetically, Protura, Collembola, Diplura, and Archaeognatha are currently placed between Remipedia and Pterygota (winged insects); Zygentoma is the sistergroup of Pterygota. The Remipedia are assumed to be among the closest relatives of all hexapods and belong to the crustaceans.

RESULTS: We identified neuropeptide precursor sequences within whole-body transcriptome data from these five hexapod groups and complemented this dataset with homologous sequences from three crustaceans (including Daphnia pulex), three myriapods, and the fruit fly Drosophila melanogaster. Our results indicate that the reported loss of several neuropeptide genes in a number of winged insects, particularly holometabolous insects, is a trend that has occurred within Pterygota. The neuropeptide precursor sequences of the non-pterygote hexapods show numerous amino acid substitutions, gene duplications, variants following alternative splicing, and numbers of paracopies. Nevertheless, most of these features fall within the range of variation known from pterygote insects. However, the capa/pyrokinin genes of non-pterygote hexapods provide an interesting example of rapid evolution, including duplication of a neuropeptide gene encoding different ligands.

CONCLUSIONS: Our findings delineate a basic pattern of neuropeptide sequences that existed before lineage-specific developments occurred during the evolution of pterygote insects.}, } @article {pmid26921294, year = {2016}, author = {Hamaji, T and Mogi, Y and Ferris, PJ and Mori, T and Miyagishima, S and Kabeya, Y and Nishimura, Y and Toyoda, A and Noguchi, H and Fujiyama, A and Olson, BJ and Marriage, TN and Nishii, I and Umen, JG and Nozaki, H}, title = {Sequence of the Gonium pectorale Mating Locus Reveals a Complex and Dynamic History of Changes in Volvocine Algal Mating Haplotypes.}, journal = {G3 (Bethesda, Md.)}, volume = {6}, number = {5}, pages = {1179-1189}, pmid = {26921294}, issn = {2160-1836}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; }, mesh = {Chromosome Walking ; Computational Biology ; Evolution, Molecular ; Gene Expression ; Genetic Linkage ; Genome, Plant ; Genomics/methods ; *Haplotypes ; High-Throughput Nucleotide Sequencing ; Phylogeny ; *Quantitative Trait Loci ; Reproduction/*genetics ; Sex Determination Processes/genetics ; Volvox/classification/*genetics ; }, abstract = {Sex-determining regions (SDRs) or mating-type (MT) loci in two sequenced volvocine algal species, Chlamydomonas reinhardtii and Volvox carteri, exhibit major differences in size, structure, gene content, and gametolog differentiation. Understanding the origin of these differences requires investigation of MT loci from related species. Here, we determined the sequences of the minus and plus MT haplotypes of the isogamous 16-celled volvocine alga, Gonium pectorale, which is more closely related to the multicellular V. carteri than to C. reinhardtii Compared to C. reinhardtii MT, G. pectorale MT is moderately larger in size, and has a less complex structure, with only two major syntenic blocs of collinear gametologs. However, the gametolog content of G. pectorale MT has more overlap with that of V. carteri MT than with C. reinhardtii MT, while the allelic divergence between gametologs in G. pectorale is even lower than that in C. reinhardtii Three key sex-related genes are conserved in G. pectorale MT: GpMID and GpMTD1 in MT-, and GpFUS1 in MT+. GpFUS1 protein exhibited specific localization at the plus-gametic mating structure, indicating a conserved function in fertilization. Our results suggest that the G. pectorale-V. carteri common ancestral MT experienced at least one major reformation after the split from C. reinhardtii, and that the V. carteri ancestral MT underwent a subsequent expansion and loss of recombination after the divergence from G. pectorale These data begin to polarize important changes that occurred in volvocine MT loci, and highlight the potential for discontinuous and dynamic evolution in SDRs.}, } @article {pmid26917726, year = {2016}, author = {Vilanova, E and Santos, GR and Aquino, RS and Valle-Delgado, JJ and Anselmetti, D and Fernàndez-Busquets, X and Mourão, PA}, title = {Carbohydrate-Carbohydrate Interactions Mediated by Sulfate Esters and Calcium Provide the Cell Adhesion Required for the Emergence of Early Metazoans.}, journal = {The Journal of biological chemistry}, volume = {291}, number = {18}, pages = {9425-9437}, pmid = {26917726}, issn = {1083-351X}, mesh = {Animals ; *Biological Evolution ; Calcium/*chemistry/metabolism ; Microscopy, Atomic Force ; Polysaccharides/*chemistry/metabolism/ultrastructure ; Porifera/*chemistry/metabolism/ultrastructure ; Sulfates/*chemistry/metabolism ; }, abstract = {Early metazoans had to evolve the first cell adhesion mechanism addressed to maintain a distinctive multicellular morphology. As the oldest extant animals, sponges are good candidates for possessing remnants of the molecules responsible for this crucial evolutionary innovation. Cell adhesion in sponges is mediated by the calcium-dependent multivalent self-interactions of sulfated polysaccharides components of extracellular membrane-bound proteoglycans, namely aggregation factors. Here, we used atomic force microscopy to demonstrate that the aggregation factor of the sponge Desmapsamma anchorata has a circular supramolecular structure and that it thus belongs to the spongican family. Its sulfated polysaccharide units, which were characterized via nuclear magnetic resonance analysis, consist preponderantly of a central backbone composed of 3-α-Glc1 units partially sulfated at 2- and 4-positions and branches of Pyr(4,6)α-Gal1→3-α-Fuc2(SO3)1→3-α-Glc4(SO3)1→3-α-Glc→4-linked to the central α-Glc units. Single-molecule force measurements of self-binding forces of this sulfated polysaccharide and their chemically desulfated and carboxyl-reduced derivatives revealed that the sulfate epitopes and extracellular calcium are essential for providing the strength and stability necessary to sustain cell adhesion in sponges. We further discuss these findings within the framework of the role of molecular structures in the early evolution of metazoans.}, } @article {pmid26916163, year = {2016}, author = {Cai, M and Hruby, VJ}, title = {The Melanocortin Receptor System: A Target for Multiple Degenerative Diseases.}, journal = {Current protein & peptide science}, volume = {17}, number = {5}, pages = {488-496}, pmid = {26916163}, issn = {1875-5550}, support = {R01 GM108040/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Drug Design ; Humans ; *Ligands ; Melanocortins/chemistry/genetics/metabolism ; Melanocyte-Stimulating Hormones/chemistry/metabolism ; Models, Molecular ; Molecular Mimicry ; Molecular Structure ; Peptides/chemistry/metabolism ; Protein Conformation ; Receptors, Melanocortin/*chemistry/genetics/*metabolism ; Structure-Activity Relationship ; }, abstract = {The melanocortin receptor system consists of five closely related G-protein coupled receptors (MC1R, MC2R, MC3R, MC4R and MC5R). These receptors are involved in many of the key biological functions for multicellular animals, including human beings. The natural agonist ligands for these receptors are derived by processing of a primordial animal gene product, proopiomelanocortin (POMC). The ligand for the MC2R is ACTH (Adrenal Corticotropic Hormone), a larger processed peptide from POMC. The natural ligands for the other 4 melanocortin receptors are smaller peptides including α-melanocyte stimulating hormone (α-MSH) and related peptides from POMC (β-MSH and γ-MSH). They all contain the sequence His-Phe-Arg-Trp that is conserved throughout evolution. Thus, there has been considerable difficulty in developing highly selective ligands for the MC1R, MC3R, MC4R and MC5R. In this brief review, we discuss the various approaches that have been taken to design agonist and antagonist analogues and derivatives of the POMC peptides that are selective for the MC1R, MC3R, MC4R and MC5R receptors, via peptide, nonpeptide and peptidomimetic derivatives and analogues and their differential interactions with receptors that may help account for these selectivities.}, } @article {pmid26909677, year = {2016}, author = {Strassmann, JE}, title = {Kin Discrimination in Dictyostelium Social Amoebae.}, journal = {The Journal of eukaryotic microbiology}, volume = {63}, number = {3}, pages = {378-383}, doi = {10.1111/jeu.12307}, pmid = {26909677}, issn = {1550-7408}, mesh = {Amoeba/genetics/*physiology ; Animals ; Biological Evolution ; Cell Adhesion/genetics ; Cell Movement ; Dictyostelium/*genetics/*physiology ; Fruiting Bodies, Fungal/genetics ; Protozoan Proteins/genetics ; }, abstract = {Evolved cooperation is stable only when the benefactor is compensated, either directly or through its relatives. Social amoebae cooperate by forming a mobile multicellular body in which, about 20% of participants ultimately die to form a stalk. This benefits the remaining individuals that become hardy spores at the top of the stalk, together making up the fruiting body. In studied species with stalked migration, P. violaceum, D. purpureum, and D. giganteum, sorting based on clone identity occurs in laboratory mixes, maintaining high relatedness within the fruiting bodies. D. discoideum has unstalked migration, where cell fate is not fixed until the slug forms a fruiting body. Laboratory mixes show some degree of both spatial and genotype-based sorting, yet most laboratory fruiting bodies remain chimeric. However, wild fruiting bodies are made up mostly of clonemates. A genetic mechanism for sorting is likely to be cell adhesion genes tgrB1 and tgrC1, which bind to each other. They are highly variable, as expected for a kin discrimination gene. It is a puzzle that these genes do not cause stronger discrimination between mixed wild clones, but laboratory conditions or strong sorting early in the social stage diminished by later slug fusion could be explanations.}, } @article {pmid26904394, year = {2016}, author = {Grahame Hardie, D}, title = {Regulation of AMP-activated protein kinase by natural and synthetic activators.}, journal = {Acta pharmaceutica Sinica. B}, volume = {6}, number = {1}, pages = {1-19}, pmid = {26904394}, issn = {2211-3835}, support = {/WT_/Wellcome Trust/United Kingdom ; 097726/WT_/Wellcome Trust/United Kingdom ; 15101/CRUK_/Cancer Research UK/United Kingdom ; }, abstract = {The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function.}, } @article {pmid26898901, year = {2016}, author = {Yeo, JH and McAllan, BM and Fraser, ST}, title = {Scanning Electron Microscopy Reveals Two Distinct Classes of Erythroblastic Island Isolated from Adult Mammalian Bone Marrow.}, journal = {Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada}, volume = {22}, number = {2}, pages = {368-378}, doi = {10.1017/S1431927616000155}, pmid = {26898901}, issn = {1435-8115}, mesh = {Animals ; Antigens, CD/analysis ; Blood Group Antigens/analysis ; Bone Marrow/*anatomy & histology ; Bone Marrow Cells/*ultrastructure ; Erythroblasts/*ultrastructure ; Guinea Pigs ; Marsupialia ; Membrane Proteins/analysis ; *Microscopy, Electron, Scanning ; Microscopy, Immunoelectron ; Receptors, Transferrin/analysis ; }, abstract = {Erythroblastic islands are multicellular clusters in which a central macrophage supports the development and maturation of red blood cell (erythroid) progenitors. These clusters play crucial roles in the pathogenesis observed in animal models of hematological disorders. The precise structure and function of erythroblastic islands is poorly understood. Here, we have combined scanning electron microscopy and immuno-gold labeling of surface proteins to develop a better understanding of the ultrastructure of these multicellular clusters. The erythroid-specific surface antigen Ter-119 and the transferrin receptor CD71 exhibited distinct patterns of protein sorting during erythroid cell maturation as detected by immuno-gold labeling. During electron microscopy analysis we observed two distinct classes of erythroblastic islands. The islands varied in size and morphology, and the number and type of erythroid cells interacting with the central macrophage. Assessment of femoral marrow isolated from a cavid rodent species (guinea pig, Cavis porcellus) and a marsupial carnivore species (fat-tailed dunnarts, Sminthopsis crassicaudata) showed that while the morphology of the central macrophage varied, two different types of erythroblastic islands were consistently identifiable. Our findings suggest that these two classes of erythroblastic islands are conserved in mammalian evolution and may play distinct roles in red blood cell production.}, } @article {pmid26897340, year = {2016}, author = {Liongue, C and Taznin, T and Ward, AC}, title = {Signaling via the CytoR/JAK/STAT/SOCS pathway: Emergence during evolution.}, journal = {Molecular immunology}, volume = {71}, number = {}, pages = {166-175}, doi = {10.1016/j.molimm.2016.02.002}, pmid = {26897340}, issn = {1872-9142}, mesh = {Animals ; *Biological Evolution ; Cell Communication/*genetics ; Computational Biology ; Humans ; Janus Kinases/genetics ; Phylogeny ; Receptors, Cytokine/*genetics ; STAT Transcription Factors/genetics ; Signal Transduction/*genetics ; Suppressor of Cytokine Signaling Proteins ; }, abstract = {Cell-cell signaling represents an essential hallmark of multicellular organisms, which necessarily require a means of communicating between different cell populations, particularly immune cells. Cytokine receptor signaling through the Janus kinase/Signal Transducer and Activator of Transcription/Suppressor of Cytokine Signaling (CytoR/JAK/STAT/SOCS) pathway embodies one important paradigm by which this is achieved. This pathway has been extensively studied in vertebrates and protostomes and shown to play fundamental roles in development and function of immune and other cells. However, our understanding of the origins of the individual pathway components and their assembly into a functional pathway has remained limited. This study examined the origins of each component of this pathway through bioinformatics analysis of key extant species. This has revealed step-wise accretion of individual components over a large evolutionary time-frame, but only in bilateria did a series of innovations allow their final coalescence to form a complete pathway. Assembly of the CytoR/JAK/STAT pathway has followed the retrograde model of pathway evolution, whereas addition of the SOCS component has adhered to the patchwork model.}, } @article {pmid26892537, year = {2016}, author = {Yang, EC and Boo, SM and Bhattacharya, D and Saunders, GW and Knoll, AH and Fredericq, S and Graf, L and Yoon, HS}, title = {Divergence time estimates and the evolution of major lineages in the florideophyte red algae.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {21361}, pmid = {26892537}, issn = {2045-2322}, mesh = {Biological Evolution ; *Evolution, Molecular ; Fossils ; *Phylogeny ; Rhodophyta/*classification/*genetics ; }, abstract = {The Florideophyceae is the most abundant and taxonomically diverse class of red algae (Rhodophyta). However, many aspects of the systematics and divergence times of the group remain unresolved. Using a seven-gene concatenated dataset (nuclear EF2, LSU and SSU rRNAs, mitochondrial cox1, and plastid rbcL, psaA and psbA genes), we generated a robust phylogeny of red algae to provide an evolutionary timeline for florideophyte diversification. Our relaxed molecular clock analysis suggests that the Florideophyceae diverged approximately 943 (817-1,049) million years ago (Ma). The major divergences in this class involved the emergence of Hildenbrandiophycidae [ca. 781 (681-879) Ma], Nemaliophycidae [ca. 661 (597-736) Ma], Corallinophycidae [ca. 579 (543-617) Ma], and the split of Ahnfeltiophycidae and Rhodymeniophycidae [ca. 508 (442-580) Ma]. Within these clades, extant diversity reflects largely Phanerozoic diversification. Divergences within Florideophyceae were accompanied by evolutionary changes in the carposporophyte stage, leading to a successful strategy for maximizing spore production from each fertilization event. Our research provides robust estimates for the divergence times of major lineages within the Florideophyceae. This timeline was used to interpret the emergence of key morphological innovations that characterize these multicellular red algae.}, } @article {pmid26886723, year = {2016}, author = {Papaevgeniou, N and Sakellari, M and Jha, S and Tavernarakis, N and Holmberg, CI and Gonos, ES and Chondrogianni, N}, title = {18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures.}, journal = {Antioxidants & redox signaling}, volume = {25}, number = {16}, pages = {855-869}, pmid = {26886723}, issn = {1557-7716}, mesh = {Aging/*metabolism ; Alzheimer Disease/*metabolism/*pathology ; Amyloid beta-Peptides/metabolism ; Animals ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/metabolism ; Cell Death ; Cells, Cultured ; Disease Progression ; Glycyrrhetinic Acid/*analogs & derivatives/metabolism/pharmacology ; Longevity ; Neurons/drug effects/*metabolism ; Oxidation-Reduction ; Phenotype ; Proteasome Endopeptidase Complex/*metabolism ; Protein Aggregation, Pathological/metabolism ; }, abstract = {AIMS: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression.

RESULTS: Feeding of wild-type Caenorhabditis elegans with 18α-glycyrrhetinic acid (18α-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Aβ deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18α-GA treatment.

INNOVATION: This is the first report of the use of 18α-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism.

CONCLUSION: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet. Antioxid. Redox Signal. 25, 855-869.}, } @article {pmid26873616, year = {2016}, author = {Paz-Y-Miño-C, G and Espinosa, A}, title = {Kin Discrimination in Protists: From Many Cells to Single Cells and Backwards.}, journal = {The Journal of eukaryotic microbiology}, volume = {63}, number = {3}, pages = {367-377}, pmid = {26873616}, issn = {1550-7408}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Biological Evolution ; Eukaryota/*classification/*genetics/physiology ; Genetic Fitness ; Phenotype ; }, abstract = {During four decades (1960-1990s), the conceptualization and experimental design of studies in kin recognition relied on work with multicellular eukaryotes, particularly Unikonta (including invertebrates and vertebrates) and some Bikonta (including plants). This pioneering research had an animal behavior approach. During the 2000s, work on taxa-, clone- and kin-discrimination and recognition in protists produced genetic and molecular evidence that unicellular organisms (e.g. Saccharomyces, Dictyostelium, Polysphondylium, Tetrahymena, Entamoeba and Plasmodium) could distinguish between same (self or clone) and different (diverse clones), as well as among conspecifics of close or distant genetic relatedness. Here, we discuss some of the research on the genetics of kin discrimination/recognition and highlight the scientific progress made by switching emphasis from investigating multicellular to unicellular systems (and backwards). We document how studies with protists are helping us to understand the microscopic, cellular origins and evolution of the mechanisms of kin discrimination/recognition and their significance for the advent of multicellularity. We emphasize that because protists are among the most ancient organisms on Earth, belong to multiple taxonomic groups and occupy all environments, they can be central to reexamining traditional hypotheses in the field of kin recognition, reformulating concepts, and generating new knowledge.}, } @article {pmid26872675, year = {2016}, author = {Moe, GW and Marín-García, J}, title = {Role of cell death in the progression of heart failure.}, journal = {Heart failure reviews}, volume = {21}, number = {2}, pages = {157-167}, pmid = {26872675}, issn = {1573-7322}, mesh = {*Cell Death ; *Disease Progression ; Heart Failure/*physiopathology ; Humans ; Mitochondria, Heart/*metabolism ; Myocytes, Cardiac/*pathology ; Signal Transduction/physiology ; }, abstract = {All multicellular organisms develop during evolution the highly regulated and interconnected pathways of cell death. This complex network contributes to the pathogenesis of various cardiovascular disorders including ischemia/reperfusion injury, myocardial infarction, heart failure, dysrhythmias and atherosclerosis. Chronic cardiac remodeling response and transition to overt HF have been associated with modestly increased apoptosis, although the actual burden of chronic cell loss attributable to apoptosis is not clear. Central mediators of cardiomyocyte survival and death are the mitochondrial organelles. Based on its morphological characteristics, cell death can be classified into three major types: apoptosis, necrosis and autophagy. Recently, a new pathway of regulated necrosis, necroptosis, has also been reported in the failing heart. The mitochondrial (intrinsic) and the death-receptor-mediated (extrinsic) converge at mitochondria inducing release of mitochondrial apoptogens to initiate the caspase cascade and eventually degradation of the doomed cardiomyocyte. Activation of death receptors can initiate not only extrinsic apoptotic pathway, but also necrosis. On the other hand, autophagy, which is characterized by the massive formation of lysosomal-derived vesicles, containing degenerating cytoplasmic contents, is primarily a survival response to nutrient deprivation, and a selective form of autophagy, mitophagy, is also a protective mechanism that allows to eliminate damaged mitochondria and thereby to attenuate mitochondria-mediated apoptosis and necrosis in the myocardium. Further insight into the molecular mechanisms underlying cell death will increase the efficiency and repertoire of therapeutic interventions available in cardiovascular disease.}, } @article {pmid26871911, year = {2016}, author = {Boucher, B and Lee, AY and Hallett, M and Jenna, S}, title = {Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways.}, journal = {PLoS computational biology}, volume = {12}, number = {2}, pages = {e1004738}, pmid = {26871911}, issn = {1553-7358}, mesh = {Animals ; Caenorhabditis elegans/*genetics ; Caenorhabditis elegans Proteins/*genetics/metabolism ; Computational Biology ; Gene Regulatory Networks/*genetics ; Models, Biological ; Protein Interaction Maps/*genetics ; }, abstract = {A genetic interaction (GI) is defined when the mutation of one gene modifies the phenotypic expression associated with the mutation of a second gene. Genome-wide efforts to map GIs in yeast revealed structural and functional properties of a GI network. This provided insights into the mechanisms underlying the robustness of yeast to genetic and environmental insults, and also into the link existing between genotype and phenotype. While a significant conservation of GIs and GI network structure has been reported between distant yeast species, such a conservation is not clear between unicellular and multicellular organisms. Structural and functional characterization of a GI network in these latter organisms is consequently of high interest. In this study, we present an in-depth characterization of ~1.5K GIs in the nematode Caenorhabditis elegans. We identify and characterize six distinct classes of GIs by examining a wide-range of structural and functional properties of genes and network, including co-expression, phenotypical manifestations, relationship with protein-protein interaction dense subnetworks (PDS) and pathways, molecular and biological functions, gene essentiality and pleiotropy. Our study shows that GI classes link genes within pathways and display distinctive properties, specifically towards PDS. It suggests a model in which pathways are composed of PDS-centric and PDS-independent GIs coordinating molecular machines through two specific classes of GIs involving pleiotropic and non-pleiotropic connectors. Our study provides the first in-depth characterization of a GI network within pathways of a multicellular organism. It also suggests a model to understand better how GIs control system robustness and evolution.}, } @article {pmid26866800, year = {2016}, author = {Koga, H and Fujitani, H and Morino, Y and Miyamoto, N and Tsuchimoto, J and Shibata, TF and Nozawa, M and Shigenobu, S and Ogura, A and Tachibana, K and Kiyomoto, M and Amemiya, S and Wada, H}, title = {Experimental Approach Reveals the Role of alx1 in the Evolution of the Echinoderm Larval Skeleton.}, journal = {PloS one}, volume = {11}, number = {2}, pages = {e0149067}, pmid = {26866800}, issn = {1932-6203}, mesh = {Animals ; Biological Evolution ; Echinodermata/genetics/*physiology ; Gene Expression Profiling ; *Gene Expression Regulation ; Homeodomain Proteins/*genetics/*physiology ; Immunohistochemistry ; In Situ Hybridization ; Larva/genetics/physiology ; Phenotype ; Phylogeny ; Sea Cucumbers/genetics/physiology ; Sequence Analysis, RNA ; Starfish/*genetics/*physiology ; Strongylocentrotus purpuratus/genetics/physiology ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Over the course of evolution, the acquisition of novel structures has ultimately led to wide variation in morphology among extant multicellular organisms. Thus, the origins of genetic systems for new morphological structures are a subject of great interest in evolutionary biology. The larval skeleton is a novel structure acquired in some echinoderm lineages via the activation of the adult skeletogenic machinery. Previously, VEGF signaling was suggested to have played an important role in the acquisition of the larval skeleton. In the present study, we compared expression patterns of Alx genes among echinoderm classes to further explore the factors involved in the acquisition of a larval skeleton. We found that the alx1 gene, originally described as crucial for sea urchin skeletogenesis, may have also played an essential role in the evolution of the larval skeleton. Unlike those echinoderms that have a larval skeleton, we found that alx1 of starfish was barely expressed in early larvae that have no skeleton. When alx1 overexpression was induced via injection of alx1 mRNA into starfish eggs, the expression patterns of certain genes, including those possibly involved in skeletogenesis, were altered. This suggested that a portion of the skeletogenic program was induced solely by alx1. However, we observed no obvious external phenotype or skeleton. We concluded that alx1 was necessary but not sufficient for the acquisition of the larval skeleton, which, in fact, requires several genetic events. Based on these results, we discuss how the larval expression of alx1 contributed to the acquisition of the larval skeleton in the putative ancestral lineage of echinoderms.}, } @article {pmid26864038, year = {2016}, author = {Singer, MA}, title = {The Origins of Aging: Evidence that Aging is an Adaptive Phenotype.}, journal = {Current aging science}, volume = {9}, number = {2}, pages = {95-115}, doi = {10.2174/1874609809666160211124947}, pmid = {26864038}, issn = {1874-6128}, mesh = {*Adaptation, Physiological ; *Aging ; Animals ; Biological Evolution ; Cellular Senescence ; Ecosystem ; Humans ; Models, Biological ; }, abstract = {BACKGROUND: Aging can be defined as the time-related decline in biological functions which ultimately results in organismal death. Beyond the stage of reproductive maturity as fertility declines, cell and tissue functions come under reduced selection pressure since organismal survival is considered no longer an evolutionary priority. Repair mechanisms become less robust and the resulting stochastic accumulation of tissue and genomic damage is believed to underlie the aging process. The objective of this review is to challenge this construct and to present evidence that aging represents a species-specific adaptive developmental program.

METHODS: Through a review of published data, the cellular aging programs of both single cell and multicellular organisms are described. Since all organisms live in communities (ecosystems) of diverse species, the role of multi-level selection is discussed within this context and a proposal is advanced that aging represents an adaptive phenotype.

RESULTS: Single cell organisms evolved an aging phenotype in which the primary feature was replicative arrest prior to cell death. The evolution of multicellularity represented the emergence of a new level of biological organization. Multicellularity required cell-cell cooperation as well as a division of labor. In simple multicellular organisms aging was rooted in an age-related decline in stem cell function (renewal and differentiation). In complex multicellular organisms cellular aging/ death programs (senescence, autophagy, apoptosis) were used as a form of cell "altruistic" suicide carried out for the benefit of the whole organism (morphogenesis, tissue repair and maintenance). Organisms do not live in isolation. Species occupy ecological niches and communities of diverse species comprise an ecosystem. Ecosystems are highly regulated and structured biological organizations. The effective functioning and productivity of an ecosystem is determined by its biological diversity and relative species densities. Multilevel selection acts to balance optimal functioning of both the whole ecosystem and its compositional species/organisms.

CONCLUSIONS: Organismal aging and death programs are adaptive; these programs provide a mechanism for regulating species population densities within the constraints imposed by the ecosystem organization. A unique feature of humans has been the development of a second inheritance system, culture. Through cultural practices, humans have expanded our ecological niche to be global in size. Our technology enriched urban ecosystem is very different from natural ecosystems. Our future evolution, including aging and lifespan, will be determined by our unique urban ecosystem through geneculture co-evolution.}, } @article {pmid26863993, year = {2016}, author = {Lavrov, AI and Kosevich, IA}, title = {Sponge cell reaggregation: Cellular structure and morphogenetic potencies of multicellular aggregates.}, journal = {Journal of experimental zoology. Part A, Ecological genetics and physiology}, volume = {325}, number = {2}, pages = {158-177}, doi = {10.1002/jez.2006}, pmid = {26863993}, issn = {1932-5231}, mesh = {Animals ; Cell Aggregation ; Cell Movement ; Cellular Structures/cytology ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; *Morphogenesis ; Porifera/*cytology/*growth & development/ultrastructure ; Species Specificity ; }, abstract = {Sponges (phylum Porifera) are one of the most ancient extant multicellular animals and can provide valuable insights into origin and early evolution of Metazoa. High plasticity of cell differentiations and anatomical structure is characteristic feature of sponges. Present study deals with sponge cell reaggregation after dissociation as the most outstanding case of sponge plasticity. Dynamic of cell reaggregation and structure of multicellular aggregates of three demosponge species (Halichondria panicea (Pallas, 1766), Haliclona aquaeductus (Sсhmidt, 1862), and Halisarca dujardinii Johnston, 1842) were studied. Sponge tissue dissociation was performed mechanically. Resulting cell suspensions were cultured at 8-10°C for at least 5 days. Structure of multicellular aggregates was studied by light, transmission and scanning electron microscopy. Studied species share common stages of cell reaggregation-primary multicellular aggregates, early-stage primmorphs and primmorphs, but the rate of reaggregation varies considerably among species. Only cells of H. dujardinii are able to reconstruct functional and viable sponge after primmorphs formation. Sponge reconstruction in this species occurs due to active cell locomotion. Development of H. aquaeductus and H. panicea cells ceases at the stages of early primmorphs and primmorphs, respectively. Development of aggregates of these species is most likely arrested due to immobility of the majority of cells inside them. However, the inability of certain sponge species to reconstruct functional and viable individuals during cell reaggregation may be not a permanent species-specific characteristic, but depends on various factors, including the stage of the life cycle and experimental conditions.}, } @article {pmid26836977, year = {2016}, author = {Trapani, MR and Parisi, MG and Parrinello, D and Sanfratello, MA and Benenati, G and Palla, F and Cammarata, M}, title = {Specific inflammatory response of Anemonia sulcata (Cnidaria) after bacterial injection causes tissue reaction and enzymatic activity alteration.}, journal = {Journal of invertebrate pathology}, volume = {135}, number = {}, pages = {15-21}, doi = {10.1016/j.jip.2016.01.010}, pmid = {26836977}, issn = {1096-0805}, mesh = {Alkaline Phosphatase/metabolism ; Animals ; Densitometry ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli/*physiology ; Esterases/metabolism ; Fibrinogen/metabolism ; Fibrinolysis ; Gelatin/metabolism ; Host-Pathogen Interactions ; Inflammation ; Peptide Hydrolases/metabolism ; Phosphoric Monoester Hydrolases/metabolism ; Sea Anemones/enzymology/*microbiology/physiology ; Vibrio alginolyticus/*physiology ; }, abstract = {The evolution of multicellular organisms was marked by adaptations to protect against pathogens. The mechanisms for discriminating the ''self'' from ''non-self" have evolved into a long history of cellular and molecular strategies, from damage repair to the co-evolution of host-pathogen interactions. We investigated the inflammatory response in Anemonia sulcata (Cnidaria: Anthozoa) following injection of substances that varied in type and dimension, and observed clear, strong and specific reactions, especially after injection of Escherichia coli and Vibrio alginolyticus. Moreover, we analyzed enzymatic activity of protease, phosphatase and esterase, showing how the injection of different bacterial strains alters the expression of these enzymes and suggesting a correlation between the appearance of the inflammatory reaction and the modification of enzymatic activities. Our study shows for the first time, a specific reaction and enzymatic responses following injection of bacteria in a cnidarian.}, } @article {pmid26833268, year = {2016}, author = {Ripamonti, U}, title = {Redefining the induction of periodontal tissue regeneration in primates by the osteogenic proteins of the transforming growth factor-β supergene family.}, journal = {Journal of periodontal research}, volume = {51}, number = {6}, pages = {699-715}, doi = {10.1111/jre.12356}, pmid = {26833268}, issn = {1600-0765}, mesh = {Animals ; Cementogenesis/drug effects ; Collagen/pharmacology ; Drug Combinations ; Laminin/pharmacology ; Papio ursinus ; Periodontium/drug effects/*physiology ; Primates ; Proteoglycans/pharmacology ; Regeneration/*drug effects/physiology ; Transforming Growth Factor beta/genetics/*pharmacology ; }, abstract = {The molecular bases of periodontal tissue induction and regeneration are the osteogenic proteins of the transforming growth factor-β (TGF-β) supergene family. These morphogens act as soluble mediators for the induction of tissues morphogenesis sculpting the multicellular mineralized structures of the periodontal tissues with functionally oriented ligament fibers into newly formed cementum. Human TGF-β3 (hTGF-β3) in growth factor-reduced Matrigel[®] matrix induces cementogenesis when implanted in class II mandibular furcation defects surgically prepared in the non-human primate Chacma baboon, Papio ursinus. The newly formed periodontal ligament space is characterized by running fibers tightly attached to the cementoid surface penetrating as mineralized constructs within the newly formed cementum assembling and initiating within the mineralized dentine. Angiogenesis heralds the newly formed periodontal ligament space, and newly sprouting capillaries are lined by cellular elements with condensed chromatin interpreted as angioblasts responsible for the rapid and sustained induction of angiogenesis. The inductive activity of hTGF-β3 in Matrigel[®] matrix is enhanced by the addition of autogenous morcellated fragments of the rectus abdominis muscle potentially providing myoblastic, pericytic/perivascular stem cells for continuous tissue induction and morphogenesis. The striated rectus abdominis muscle is endowed with stem cell niches in para/perivascular location, which can be dominant, thus imposing stem cell features or stemness to the surrounding cells. This capacity to impose stemness is morphologically shown by greater alveolar bone induction and cementogenesis when hTGF-β3 in Matrigel[®] matrix is combined with morcellated fragments of autogenous rectus abdominis muscle. The induction of periodontal tissue morphogenesis develops as a mosaic structure in which the osteogenic proteins of the TGF-β supergene family singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis. In primates, the presence of several homologous yet molecularly different isoforms with osteogenic activity highlights the biological significance of this apparent redundancy and indicates multiple interactions during embryonic development and bone regeneration in postnatal life. Molecular redundancy with associated different biological functionalities in primate tissues may simply represent the fine-tuning of speciation-related molecular evolution in anthropoid apes at the early Pliocene boundary, which resulted in finer tuning of the bone induction cascade.}, } @article {pmid26831906, year = {2016}, author = {Jindrich, K and Degnan, BM}, title = {The diversification of the basic leucine zipper family in eukaryotes correlates with the evolution of multicellularity.}, journal = {BMC evolutionary biology}, volume = {16}, number = {}, pages = {28}, pmid = {26831906}, issn = {1471-2148}, mesh = {Animals ; Chromosome Mapping ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Fungi/genetics ; Leucine Zippers ; Phylogeny ; Plants/genetics ; Protein Structure, Tertiary ; Transcription Factors/chemistry/*genetics ; }, abstract = {BACKGROUND: Multicellularity evolved multiple times in eukaryotes. In all cases, this required an elaboration of the regulatory mechanisms controlling gene expression. Amongst the conserved eukaryotic transcription factor families, the basic leucine zipper (bZIP) superfamily is one of the most ancient and best characterised. This gene family plays a diversity of roles in the specification, differentiation and maintenance of cell types in plants and animals. bZIPs are also involved in stress responses and the regulation of cell proliferation in fungi, amoebozoans and heterokonts.

RESULTS: Using 49 sequenced genomes from across the Eukaryota, we demonstrate that the bZIP superfamily has evolved from a single ancestral eukaryotic gene and undergone multiple independent expansions. bZIP family diversification is largely restricted to multicellular lineages, consistent with bZIPs contributing to the complex regulatory networks underlying differential and cell type-specific gene expression in these lineages. Analyses focused on the Metazoa suggest an elaborate bZIP network was in place in the most recent shared ancestor of all extant animals that was comprised of 11 of the 12 previously recognized families present in modern taxa. In addition this analysis identifies three bZIP families that appear to have been lost in mammals. Thus the ancestral metazoan and eumetazoan bZIP repertoire consists of 12 and 16 bZIPs, respectively. These diversified from 7 founder genes present in the holozoan ancestor.

CONCLUSIONS: Our results reveal the ancestral opisthokont, holozoan and metazoan bZIP repertoire and provide insights into the progressive expansion and divergence of bZIPs in the five main eukaryotic kingdoms, suggesting that the early diversification of bZIPs in multiple eukaryotic lineages was a prerequisite for the evolution of complex multicellular organisms.}, } @article {pmid26822195, year = {2016}, author = {Herron, MD}, title = {Origins of multicellular complexity: Volvox and the volvocine algae.}, journal = {Molecular ecology}, volume = {25}, number = {6}, pages = {1213-1223}, pmid = {26822195}, issn = {1365-294X}, support = {NNA17BB05A//Intramural NASA/United States ; }, mesh = {*Biological Evolution ; Cell Differentiation ; Cell Movement ; Chlamydomonas/genetics/physiology ; Congresses as Topic ; Phylogeny ; Volvox/*genetics/*physiology ; }, abstract = {The collection of evolutionary transformations known as the 'major transitions' or 'transitions in individuality' resulted in changes in the units of evolution and in the hierarchical structure of cellular life. Volvox and related algae have become an important model system for the major transition from unicellular to multicellular life, which touches on several fundamental questions in evolutionary biology. The Third International Volvox Conference was held at the University of Cambridge in August 2015 to discuss recent advances in the biology and evolution of this group of algae. Here, I highlight the benefits of integrating phylogenetic comparative methods and experimental evolution with detailed studies of developmental genetics in a model system with substantial genetic and genomic resources. I summarize recent research on Volvox and its relatives and comment on its implications for the genomic changes underlying major evolutionary transitions, evolution and development of complex traits, evolution of sex and sexes, evolution of cellular differentiation and the biophysics of motility. Finally, I outline challenges and suggest future directions for research into the biology and evolution of the volvocine algae.}, } @article {pmid26787743, year = {2016}, author = {Kumar, D and Blaby-Haas, CE and Merchant, SS and Mains, RE and King, SM and Eipper, BA}, title = {Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity.}, journal = {Journal of cell science}, volume = {129}, number = {5}, pages = {943-956}, pmid = {26787743}, issn = {1477-9137}, support = {GM051293/GM/NIGMS NIH HHS/United States ; R37 GM042143/GM/NIGMS NIH HHS/United States ; R56 DK032949/DK/NIDDK NIH HHS/United States ; DK032949/DK/NIDDK NIH HHS/United States ; GM100753/GM/NIGMS NIH HHS/United States ; R37 DK032949/DK/NIDDK NIH HHS/United States ; R01 DK032949/DK/NIDDK NIH HHS/United States ; R01 GM042143/GM/NIGMS NIH HHS/United States ; GM042143/GM/NIGMS NIH HHS/United States ; R01 GM051293/GM/NIGMS NIH HHS/United States ; F32 GM100753/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chlamydomonas reinhardtii/*enzymology/ultrastructure ; Cilia/*enzymology ; Evolution, Molecular ; HEK293 Cells ; Humans ; Mice ; NIH 3T3 Cells ; Nitrogenous Group Transferases/*genetics/metabolism ; Plant Proteins/*genetics/metabolism ; Protein Processing, Post-Translational ; Protein Transport ; }, abstract = {Ciliary axonemes and basal bodies were present in the last eukaryotic common ancestor and play crucial roles in sensing and responding to environmental cues. Peptidergic signaling, generally considered a metazoan innovation, is essential for organismal development and homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) is crucial for the last step of bioactive peptide biosynthesis. However, identification of a complete PAM-like gene in green algal genomes suggests ancient evolutionary roots for bioactive peptide signaling. We demonstrate that the Chlamydomonas reinhardtii PAM gene encodes an active peptide-amidating enzyme (CrPAM) that shares key structural and functional features with the mammalian enzyme, indicating that components of the peptide biosynthetic pathway predate multicellularity. In addition to its secretory pathway localization, CrPAM localizes to cilia and tightly associates with the axonemal superstructure, revealing a new axonemal enzyme activity. This localization pattern is conserved in mammals, with PAM present in both motile and immotile sensory cilia. The conserved ciliary localization of PAM adds to the known signaling capabilities of the eukaryotic cilium and provides a potential mechanistic link between peptidergic signaling and endocrine abnormalities commonly observed in ciliopathies.}, } @article {pmid26777788, year = {2016}, author = {Gillings, MR and Hilbert, M and Kemp, DJ}, title = {Information in the Biosphere: Biological and Digital Worlds.}, journal = {Trends in ecology & evolution}, volume = {31}, number = {3}, pages = {180-189}, doi = {10.1016/j.tree.2015.12.013}, pmid = {26777788}, issn = {1872-8383}, mesh = {Biological Evolution ; Humans ; *Information Dissemination ; *Online Systems ; Selection, Genetic ; }, abstract = {Evolution has transformed life through key innovations in information storage and replication, including RNA, DNA, multicellularity, and culture and language. We argue that the carbon-based biosphere has generated a cognitive system (humans) capable of creating technology that will result in a comparable evolutionary transition. Digital information has reached a similar magnitude to information in the biosphere. It increases exponentially, exhibits high-fidelity replication, evolves through differential fitness, is expressed through artificial intelligence (AI), and has facility for virtually limitless recombination. Like previous evolutionary transitions, the potential symbiosis between biological and digital information will reach a critical point where these codes could compete via natural selection. Alternatively, this fusion could create a higher-level superorganism employing a low-conflict division of labor in performing informational tasks.}, } @article {pmid26777340, year = {2016}, author = {Neill, D}, title = {Individual Cell Longevity, 'Life's Timekeeper', and Metazoan Evolution.}, journal = {Current aging science}, volume = {9}, number = {2}, pages = {87-98}, doi = {10.2174/1874609809666160114092340}, pmid = {26777340}, issn = {1874-6128}, mesh = {Animals ; *Biological Evolution ; Cell Survival ; *Cellular Senescence ; Humans ; Signal Transduction ; }, abstract = {It is proposed that a primary and fundamental aspect of metazoan evolution is an ability to control and extend the longevity of individual cells. This was achieved through an intracellular oscillator, dubbed 'Life's Timekeeper', which evolved in the hypothetical ancestor of all metazoans. Slower oscillatory frequencies directed metazoan evolution towards extended longevity of individual cells, enabling generation of many specialised types of terminally differentiated cells. As the longevity of these cells was still relatively short in more primitive metazoans, stem cells, capable of differentiating into all specialised cell types, were retained in order to replace senescent cells. With increasing cell longevity, continual replacement of all senescent cells was no longer necessary. Cells such as neurons could be sustained throughout life, enabling the evolution of brains, hence, complex behaviour and intelligence. In multicellular metazoans the oscillator remains synchronised across all cells. It coordinates the timing of all cell-cell signalling systems, hence controls the timing of development and aging/senescence. In advanced metazoans, where senescent cells are not continually replaced, it controls lifespan. With regards to morphological evolution the oscillator, through alterations to developmental timing, controls change in size and shape. With regards to life history theory it functions as the key variable mediating the correlation between life history traits. This theory is compatible with a prominent role for environmental selection but, as it implicates some degree of internal mediation and direction, it is not entirely compatible with the 'modern synthesis' view of natural selection.}, } @article {pmid26775799, year = {2016}, author = {Mukherjee, S and Karmakar, S and Babu, SP}, title = {TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {20}, number = {2}, pages = {193-204}, pmid = {26775799}, issn = {1678-4391}, mesh = {Communicable Diseases/*immunology ; Host-Parasite Interactions/*immunology ; Host-Pathogen Interactions/*immunology ; Humans ; Immunity, Humoral/*immunology ; Toll-Like Receptor 2/*immunology ; Toll-Like Receptor 4/*immunology ; }, abstract = {During the course of evolution, multicellular organisms have been orchestrated with an efficient and versatile immune system to counteract diverse group of pathogenic organisms. Pathogen recognition is considered as the most critical step behind eliciting adequate immune response during an infection. Hitherto Toll-like receptors (TLRs), especially the surface ones viz. TLR2 and TLR4 have gained immense importance due to their extreme ability of identifying distinct molecular patterns from invading pathogens. These pattern recognition receptors (PRRs) not only act as innate sensor but also shape and bridge innate and adaptive immune responses. In addition, they also play a pivotal role in regulating the balance between Th1 and Th2 type of response essential for the survivability of the host. In this work, major achievements rather findings made on the typical signalling and immunopathological attributes of TLR2 and TLR4 mediated host response against the major infectious diseases have been reviewed. Infectious diseases like tuberculosis, trypanosomiasis, malaria, and filariasis are still posing myriad threat to mankind. Furthermore, increasing resistance of the causative organisms against available therapeutics is also an emerging problem. Thus, stimulation of host immune response with TLR2 and TLR4 agonist can be the option of choice to treat such diseases in future.}, } @article {pmid26774793, year = {2016}, author = {Soares, MP and Yilmaz, B}, title = {Microbiota Control of Malaria Transmission.}, journal = {Trends in parasitology}, volume = {32}, number = {2}, pages = {120-130}, doi = {10.1016/j.pt.2015.11.004}, pmid = {26774793}, issn = {1471-5007}, mesh = {Antibodies/immunology ; Biological Evolution ; Host-Pathogen Interactions/*immunology ; Humans ; Intestines/microbiology ; Malaria, Falciparum/immunology/*microbiology/prevention & control/*transmission ; Microbiota/immunology/*physiology ; Plasmodium falciparum/physiology ; Polysaccharides/immunology ; Protozoan Vaccines/immunology ; }, abstract = {Stable mutualistic interactions between multicellular organisms and microbes are an evolutionarily conserved process with a major impact on host physiology and fitness. Humans establish such interactions with a consortium of microorganisms known as the microbiota. Despite the mutualistic nature of these interactions, some bacterial components of the human microbiota express immunogenic glycans that elicit glycan-specific antibody (Ab) responses. The ensuing circulating Abs are protective against infections by pathogens that express those glycans, as demonstrated for Plasmodium, the causative agent of malaria. Presumably, a similar protective Ab response acts against other vector-borne diseases.}, } @article {pmid26761184, year = {2016}, author = {Chhetri, J and Gueven, N}, title = {Targeting mitochondrial function to protect against vision loss.}, journal = {Expert opinion on therapeutic targets}, volume = {20}, number = {6}, pages = {721-736}, doi = {10.1517/14728222.2015.1134489}, pmid = {26761184}, issn = {1744-7631}, mesh = {Animals ; Eye Diseases/etiology/*prevention & control ; Humans ; Mitochondria/metabolism/*pathology ; Mitochondrial Diseases/*complications/physiopathology ; Neurodegenerative Diseases/complications/physiopathology ; Vision Disorders/etiology/prevention & control ; }, abstract = {INTRODUCTION: Mitochondria, essential to multicellular life, convert food into ATP to satisfy cellular energy demands. Since different tissues have different energy requirements, mitochondrial density is high in tissues with high metabolic needs, such as the visual system, which is therefore highly susceptible to limited energy supply as a result of mitochondrial dysfunction.

AREAS COVERED: Vision impairment is a common feature of most mitochondrial diseases. At the same time, there is mounting evidence that mitochondrial impairment contributes to the pathogenesis of major eye diseases such as glaucoma and might also be involved in the reported vision impairment in neurodegenerative disorders such as Alzheimer's disease.

EXPERT OPINION: Rather than relying on symptomatic treatment, acknowledging the mitochondrial origin of visual disorders in mitochondrial, neurodegenerative and ocular diseases could lead to novel therapeutics that aim to modulate mitochondrial function in order to protect against vision loss. This approach has already shown some promising clinical results in inherited retinal disorders, which supports the idea that targeting mitochondria could also be a treatment option for other optic neuropathies.}, } @article {pmid26756664, year = {2016}, author = {Ambrose, BA and Vasco, A}, title = {Bringing the multicellular fern meristem into focus.}, journal = {The New phytologist}, volume = {210}, number = {3}, pages = {790-793}, doi = {10.1111/nph.13825}, pmid = {26756664}, issn = {1469-8137}, mesh = {Ferns/*cytology/genetics/metabolism ; Genes, Plant ; Meristem/*cytology/genetics/metabolism ; Phylogeny ; Plant Proteins/metabolism ; }, } @article {pmid26740169, year = {2016}, author = {Anderson, DP and Whitney, DS and Hanson-Smith, V and Woznica, A and Campodonico-Burnett, W and Volkman, BF and King, N and Thornton, JW and Prehoda, KE}, title = {Evolution of an ancient protein function involved in organized multicellularity in animals.}, journal = {eLife}, volume = {5}, number = {}, pages = {e10147}, pmid = {26740169}, issn = {2050-084X}, support = {UL1 TR000430/TR/NCATS NIH HHS/United States ; R01GM089977/GM/NIGMS NIH HHS/United States ; //Canadian Institutes of Health Research/Canada ; R01 GM087457/GM/NIGMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 GM089977/GM/NIGMS NIH HHS/United States ; R01 GM104397/GM/NIGMS NIH HHS/United States ; R01GM087457/GM/NIGMS NIH HHS/United States ; R01GM104397/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Cell Cycle ; Cell Cycle Proteins/chemistry/*genetics/*metabolism ; *Evolution, Molecular ; Guanylate Kinases/chemistry/*genetics/*metabolism ; Models, Molecular ; Protein Binding ; Protein Multimerization ; Spindle Apparatus/*metabolism ; }, abstract = {To form and maintain organized tissues, multicellular organisms orient their mitotic spindles relative to neighboring cells. A molecular complex scaffolded by the GK protein-interaction domain (GKPID) mediates spindle orientation in diverse animal taxa by linking microtubule motor proteins to a marker protein on the cell cortex localized by external cues. Here we illuminate how this complex evolved and commandeered control of spindle orientation from a more ancient mechanism. The complex was assembled through a series of molecular exploitation events, one of which - the evolution of GKPID's capacity to bind the cortical marker protein - can be recapitulated by reintroducing a single historical substitution into the reconstructed ancestral GKPID. This change revealed and repurposed an ancient molecular surface that previously had a radically different function. We show how the physical simplicity of this binding interface enabled the evolution of a new protein function now essential to the biological complexity of many animals.}, } @article {pmid26725198, year = {2016}, author = {Proust, H and Honkanen, S and Jones, VA and Morieri, G and Prescott, H and Kelly, S and Ishizaki, K and Kohchi, T and Dolan, L}, title = {RSL Class I Genes Controlled the Development of Epidermal Structures in the Common Ancestor of Land Plants.}, journal = {Current biology : CB}, volume = {26}, number = {1}, pages = {93-99}, pmid = {26725198}, issn = {1879-0445}, mesh = {Amino Acid Sequence ; Basic Helix-Loop-Helix Transcription Factors/*genetics/metabolism ; *Biological Evolution ; Bryophyta/genetics/growth & development ; Bryopsida/genetics ; Gene Expression Regulation, Plant ; *Genes, Plant ; Germ Cells, Plant/growth & development ; Indoleacetic Acids/metabolism ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Epidermis/cytology/*genetics/*growth & development ; Plant Proteins/genetics/metabolism ; Plants, Genetically Modified ; Transcription Factors/metabolism ; }, abstract = {The colonization of the land by plants, sometime before 470 million years ago, was accompanied by the evolution tissue systems [1-3]. Specialized structures with diverse functions-from nutrient acquisition to reproduction-derived from single cells in the outermost layer (epidermis) were important sources of morphological innovation at this time [2, 4, 5]. In extant plants, these structures may be unicellular extensions, such as root hairs or rhizoids [6-9], or multicellular structures, such as asexual propagules or secretory hairs (papillae) [10-12]. Here, we show that a ROOTHAIR DEFECTIVE SIX-LIKE (RSL) class I basic helix-loop-helix transcription factor positively regulates the development of the unicellular and multicellular structures that develop from individual cells that expand out of the epidermal plane of the liverwort Marchantia polymorpha; mutants that lack MpRSL1 function do not develop rhizoids, slime papillae, mucilage papillae, or gemmae. Furthermore, we discovered that RSL class I genes are also required for the development of multicellular axillary hairs on the gametophyte of the moss Physcomitrella patens. Because class I RSL proteins also control the development of rhizoids in mosses and root hairs in angiosperms [13, 14], these data demonstrate that the function of RSL class I genes was to control the development of structures derived from single epidermal cells in the common ancestor of the land plants. Class I RSL genes therefore controlled the generation of adaptive morphological diversity as plants colonized the land from the water.}, } @article {pmid29513353, year = {2016}, author = {Cummings, FW}, title = {Early metazoan development: the origin of the Cambrian exuberance.}, journal = {Theoretical biology forum}, volume = {109}, number = {1-2}, pages = {71-92}, doi = {10.19272/201611402005}, pmid = {29513353}, issn = {2282-2593}, mesh = {*Algorithms ; Animals ; *Biological Evolution ; Blastula/growth & development ; *Body Patterning ; Cell Movement ; Mesoderm/cytology/growth & development ; *Models, Biological ; Wnt Signaling Pathway ; }, abstract = {A number of common features can be observed in the earliest developing embryos of all animal phyla. A simple extant model of morphogenesis is outlined here, with the aim of giving a model of the relatively rapid appearance of Cambrian animals, 541-515 mya. Developmental patterning, elucidated by a simple linear model with only short-range diffusion of ligands, is given as the origin of the most primitive animals. The key aspect of the model involves the interaction between the emergence of the Wnt and Hedgehog (Hh) signaling pathways. The non-canonical Wnt pathway is crucial in first establishing a sphere of cells, by way of cell-cell connection fi bers. A mutation in the Wnt pathway at the dawn of multicellular organisms is argued to have given rise to the early Hh pathway, and their interaction gives two spatially separate gene determination regions, the key goal of biological patterning.}, } @article {pmid26715509, year = {2016}, author = {Lambropoulos, N and Garcia, A and Clarke, RJ}, title = {Stimulation of Na(+),K(+)-ATPase Activity as a Possible Driving Force in Cholesterol Evolution.}, journal = {The Journal of membrane biology}, volume = {249}, number = {3}, pages = {251-259}, pmid = {26715509}, issn = {1432-1424}, mesh = {Biological Evolution ; Cell Membrane/*metabolism ; Cholesterol/*metabolism ; Cytochromes c/genetics/metabolism ; Membrane Proteins/metabolism ; Oxidoreductases Acting on CH-CH Group Donors/genetics/metabolism ; Phylogeny ; Sodium-Potassium-Exchanging ATPase/genetics/*metabolism ; Squalene Monooxygenase/metabolism ; }, abstract = {Cholesterol is exclusively produced by animals and is present in the plasma membrane of all animal cells. In contrast, the membranes of fungi and plants contain other sterols. To explain the exclusive preference of animal cells for cholesterol, we propose that cholesterol may have evolved to optimize the activity of a crucial protein found in the plasma membrane of all multicellular animals, namely the Na(+),K(+)-ATPase. To test this hypothesis, mirror tree and phylogenetic distribution analyses have been conducted of the Na(+),K(+)-ATPase and 3β-hydroxysterol Δ(24)-reductase (DHCR24), the last enzyme in the Bloch cholesterol biosynthetic pathway. The results obtained support the hypothesis of a co-evolution of the Na(+),K(+)-ATPase and DHCR24. The evolutionary correlation between DHCR24 and the Na(+),K(+)-ATPase was found to be stronger than between DHCR24 and any other membrane protein investigated. The results obtained, thus, also support the hypothesis that cholesterol evolved together with the Na(+),K(+)-ATPase in multicellular animals to support Na(+),K(+)-ATPase activity.}, } @article {pmid26714637, year = {2015}, author = {Pan, Y and Bo, K and Cheng, Z and Weng, Y}, title = {The loss-of-function GLABROUS 3 mutation in cucumber is due to LTR-retrotransposon insertion in a class IV HD-ZIP transcription factor gene CsGL3 that is epistatic over CsGL1.}, journal = {BMC plant biology}, volume = {15}, number = {}, pages = {302}, pmid = {26714637}, issn = {1471-2229}, mesh = {Cucumis sativus/*genetics/growth & development/metabolism ; Epistasis, Genetic ; *Gene Expression Regulation, Plant ; Molecular Sequence Data ; Organogenesis, Plant ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Retroelements ; Terminal Repeat Sequences ; Transcription Factors/*genetics/metabolism ; Trichomes/growth & development ; }, abstract = {BACKGROUND: Trichomes, developed from the protodermal cells (the outermost cell layer of the embryo), are hair-like structures covering the aerial parts of plants. The genetic network regulating trichome development has been extensively studied and well understood in the model species Arabidopsis thaliana, which bears unicellular, non-glandular and branched trichomes. However, little is known about the genetic and molecular basis of organogenesis of multi-cellular trichomes in plant species like cucumber (Cucumis sativus L.), which are likely different from Arabidopsis.

RESULTS: We identified a new trichome mutant in cucumber which exhibited a completely glabrous phenotype on all aerial organs. Genetic analysis indicated that the glabrous phenotype was inherited as a single recessive gene, csgl3. Fine genetic mapping delimited the csgl3 locus into a 68.4 kb region with 12 predicted genes. Genetic analysis, sequence alignment and allelic variation survey in natural populations identified Csa6G514870 encoding a class IV homeodomain-associated leucine zipper (HD-ZIP) transcription factor as the only candidate for CsGL3, which was 5188 bp in length with 10 predicted exons. Gene expression analysis revealed the loss-of-function of CsGL3 in the mutant due to the insertion of a 5-kb long terminal repeat (LTR) retrotransposon in the 4th exon of CsGL3. Linkage analysis in a segregating population and gene expression analysis of the CsGL1 and CsGL3 genes in csgl1, csgl3, and csgl1 + 3 genetic backgrounds uncovered interactions between the two genes. Phylogenetic analysis among 28 class IV HD-ZIP protein sequences from five species placed cucumber CsGL3 into the same clade with 7 other members that play important roles in trichome initiation.

CONCLUSIONS: The new glabrous mutation in cucumber was controlled by a single recessive locus csgl3, which was phenotypically and genetically distinct from two previously reported glabrous mutants csgl1 and csgl2. The glabrous phenotype in csgl3 was due to insertion of an autonomous, active, class I transposable element in CsGL3, a class IV HD-ZIP transcription factor. CsGL3 was epistatic to CsGL1. CsGL3 seemed to play important roles in cucumber trichome initiation whereas CsGL1 may act downstream in the trichome development pathway(s). Findings from the present study provide new insights into genetic control of trichome development in cucumber.}, } @article {pmid26714105, year = {2015}, author = {Shou, W}, title = {Acknowledging selection at sub-organismal levels resolves controversy on pro-cooperation mechanisms.}, journal = {eLife}, volume = {4}, number = {}, pages = {}, pmid = {26714105}, issn = {2050-084X}, mesh = {*Biological Evolution ; Eukaryota ; *Symbiosis ; }, abstract = {Cooperators who pay a cost to produce publically-available benefits can be exploited by cheaters who do not contribute fairly. How might cooperation persist against cheaters? Two classes of mechanisms are known to promote cooperation: 'partner choice', where a cooperator preferentially interacts with cooperative over cheating partners; and 'partner fidelity feedback', where repeated interactions between individuals ensure that cheaters suffer as their cooperative partners languish (see, for example, Momeni et al., 2013). However when both mechanisms can act, differentiating them has generated controversy. Here, I resolve this controversy by noting that selection can operate on organismal and sub-organismal 'entities' such that partner fidelity feedback at sub-organismal level can appear as partner choice at organismal level. I also show that cooperation between multicellular eukaryotes and mitochondria is promoted by partner fidelity feedback and partner choice between sub-organismal entities, in addition to being promoted by partner fidelity feedback between hosts and symbionts, as was previously known.}, } @article {pmid26709836, year = {2016}, author = {Mallet, J and Besansky, N and Hahn, MW}, title = {How reticulated are species?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {38}, number = {2}, pages = {140-149}, pmid = {26709836}, issn = {1521-1878}, support = {BB/G006903/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; R01 AI076584/AI/NIAID NIH HHS/United States ; R01 AI76584/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Eukaryota/genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; *Genetic Speciation ; Genomics/methods ; Organisms, Genetically Modified/genetics ; *Phylogeny ; Plants/genetics ; }, abstract = {Many groups of closely related species have reticulate phylogenies. Recent genomic analyses are showing this in many insects and vertebrates, as well as in microbes and plants. In microbes, lateral gene transfer is the dominant process that spoils strictly tree-like phylogenies, but in multicellular eukaryotes hybridization and introgression among related species is probably more important. Because many species, including the ancestors of ancient major lineages, seem to evolve rapidly in adaptive radiations, some sexual compatibility may exist among them. Introgression and reticulation can thereby affect all parts of the tree of life, not just the recent species at the tips. Our understanding of adaptive evolution, speciation, phylogenetics, and comparative biology must adapt to these mostly recent findings. Introgression has important practical implications as well, not least for the management of genetically modified organisms in pest and disease control.}, } @article {pmid26704468, year = {2016}, author = {McCoy-Simandle, K and Hanna, SJ and Cox, D}, title = {Exosomes and nanotubes: Control of immune cell communication.}, journal = {The international journal of biochemistry & cell biology}, volume = {71}, number = {}, pages = {44-54}, pmid = {26704468}, issn = {1878-5875}, support = {P01 CA100324/CA/NCI NIH HHS/United States ; K12GM102779/GM/NIGMS NIH HHS/United States ; K12 GM102779/GM/NIGMS NIH HHS/United States ; R01 GM071828/GM/NIGMS NIH HHS/United States ; P30 CA013330/CA/NCI NIH HHS/United States ; }, mesh = {Cell Communication/*immunology ; Exosomes/*metabolism ; Humans ; }, abstract = {Cell-cell communication is critical to coordinate the activity and behavior of a multicellular organism. The cells of the immune system not only must communicate with similar cells, but also with many other cell types in the body. Therefore, the cells of the immune system have evolved multiple ways to communicate. Exosomes and tunneling nanotubes (TNTs) are two means of communication used by immune cells that contribute to immune functions. Exosomes are small membrane vesicles secreted by most cell types that can mediate intercellular communication and in the immune system they are proposed to play a role in antigen presentation and modulation of gene expression. TNTs are membranous structures that mediate direct cell-cell contact over several cell diameters in length (and possibly longer) and facilitate the interaction and/or the transfer of signals, material and other cellular organelles between connected cells. Recent studies have revealed additional, but sometimes conflicting, structural and functional features of both exosomes and TNTs. Despite the new and exciting information in exosome and TNT composition, origin and in vitro function, biologically significant functions are still being investigated and determined. In this review, we discuss the current field regarding exosomes and TNTs in immune cells providing evaluation and perspectives of the current literature.}, } @article {pmid26695632, year = {2015}, author = {Dewachter, L and Verstraeten, N and Monteyne, D and Kint, CI and Versées, W and Pérez-Morga, D and Michiels, J and Fauvart, M}, title = {A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in Escherichia coli.}, journal = {mBio}, volume = {6}, number = {6}, pages = {e01935-15}, pmid = {26695632}, issn = {2150-7511}, mesh = {*Amino Acid Substitution ; *Apoptosis ; DNA Fragmentation ; Escherichia coli/genetics/*physiology ; Escherichia coli Proteins/*genetics/*metabolism ; Membrane Potentials ; Microbial Viability ; Monomeric GTP-Binding Proteins/*genetics/*metabolism ; Mutant Proteins/genetics/metabolism ; Phosphatidylserines/analysis ; }, abstract = {UNLABELLED: Programmed cell death (PCD) is an important hallmark of multicellular organisms. Cells self-destruct through a regulated series of events for the benefit of the organism as a whole. The existence of PCD in bacteria has long been controversial due to the widely held belief that only multicellular organisms would profit from this kind of altruistic behavior at the cellular level. However, over the past decade, compelling experimental evidence has established the existence of such pathways in bacteria. Here, we report that expression of a mutant isoform of the essential GTPase ObgE causes rapid loss of viability in Escherichia coli. The physiological changes that occur upon expression of this mutant protein--including loss of membrane potential, chromosome condensation and fragmentation, exposure of phosphatidylserine on the cell surface, and membrane blebbing--point to a PCD mechanism. Importantly, key regulators and executioners of known bacterial PCD pathways were shown not to influence this cell death program. Collectively, our results suggest that the cell death pathway described in this work constitutes a new mode of bacterial PCD.

IMPORTANCE: Programmed cell death (PCD) is a well-known phenomenon in higher eukaryotes. In these organisms, PCD is essential for embryonic development--for example, the disappearance of the interdigital web--and also functions in tissue homeostasis and elimination of pathogen-invaded cells. The existence of PCD mechanisms in unicellular organisms like bacteria, on the other hand, has only recently begun to be recognized. We here demonstrate the existence of a bacterial PCD pathway that induces characteristics that are strikingly reminiscent of eukaryotic apoptosis, such as fragmentation of DNA, exposure of phosphatidylserine on the cell surface, and membrane blebbing. Our results can provide more insight into the mechanism and evolution of PCD pathways in higher eukaryotes. More importantly, especially in the light of the looming antibiotic crisis, they may point to a bacterial Achilles' heel and can inspire innovative ways of combating bacterial infections, directed at the targeted activation of PCD pathways.}, } @article {pmid26667994, year = {2016}, author = {Hervé, C and Siméon, A and Jam, M and Cassin, A and Johnson, KL and Salmeán, AA and Willats, WG and Doblin, MS and Bacic, A and Kloareg, B}, title = {Arabinogalactan proteins have deep roots in eukaryotes: identification of genes and epitopes in brown algae and their role in Fucus serratus embryo development.}, journal = {The New phytologist}, volume = {209}, number = {4}, pages = {1428-1441}, doi = {10.1111/nph.13786}, pmid = {26667994}, issn = {1469-8137}, mesh = {Amino Acid Sequence ; Cell Division/radiation effects ; Cell Wall/metabolism/radiation effects ; Epitopes/*metabolism ; Fucus/*genetics/*growth & development/radiation effects ; Genes, Plant ; Genome ; Indicators and Reagents ; Light ; Models, Biological ; Mucoproteins/chemistry/*metabolism ; Phylogeny ; Plant Proteins/chemistry/metabolism ; Protein Domains ; Sequence Homology, Nucleic Acid ; Zygote/metabolism ; }, abstract = {Arabinogalactan proteins (AGPs) are highly glycosylated, hydroxyproline-rich proteins found at the cell surface of plants, where they play key roles in developmental processes. Brown algae are marine, multicellular, photosynthetic eukaryotes. They belong to the phylum Stramenopiles, which is unrelated to land plants and green algae (Chloroplastida). Brown algae share common evolutionary features with other multicellular organisms, including a carbohydrate-rich cell wall. They differ markedly from plants in their cell wall composition, and AGPs have not been reported in brown algae. Here we investigated the presence of chimeric AGP-like core proteins in this lineage. We report that the genome sequence of the brown algal model Ectocarpus siliculosus encodes AGP protein backbone motifs, in a gene context that differs considerably from what is known in land plants. We showed the occurrence of AGP glycan epitopes in a range of brown algal cell wall extracts. We demonstrated that these chimeric AGP-like core proteins are developmentally regulated in embryos of the order Fucales and showed that AGP loss of function seriously impairs the course of early embryogenesis. Our findings shine a new light on the role of AGPs in cell wall sensing and raise questions about the origin and evolution of AGPs in eukaryotes.}, } @article {pmid26663204, year = {2016}, author = {Fisher, RM and Bell, T and West, SA}, title = {Multicellular group formation in response to predators in the alga Chlorella vulgaris.}, journal = {Journal of evolutionary biology}, volume = {29}, number = {3}, pages = {551-559}, doi = {10.1111/jeb.12804}, pmid = {26663204}, issn = {1420-9101}, mesh = {Animals ; Biological Evolution ; Chlorella vulgaris/*physiology ; Predatory Behavior ; Tetrahymena thermophila/*physiology ; }, abstract = {A key step in the evolution of multicellular organisms is the formation of cooperative multicellular groups. It has been suggested that predation pressure may promote multicellular group formation in some algae and bacteria, with cells forming groups to lower their chance of being eaten. We use the green alga Chlorella vulgaris and the protist Tetrahymena thermophila to test whether predation pressure can initiate the formation of colonies. We found that: (1) either predators or just predator exoproducts promote colony formation; (2) higher predator densities cause more colonies to form; and (3) colony formation in this system is facultative, with populations returning to being unicellular when the predation pressure is removed. These results provide empirical support for the hypothesis that predation pressure promotes multicellular group formation. The speed of the reversion of populations to unicellularity suggests that this response is due to phenotypic plasticity and not evolutionary change.}, } @article {pmid26655898, year = {2015}, author = {Sugihara, K and Nishiyama, K and Fukuhara, S and Uemura, A and Arima, S and Kobayashi, R and Köhn-Luque, A and Mochizuki, N and Suda, T and Ogawa, H and Kurihara, H}, title = {Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling.}, journal = {Cell reports}, volume = {13}, number = {9}, pages = {1814-1827}, doi = {10.1016/j.celrep.2015.10.051}, pmid = {26655898}, issn = {2211-1247}, mesh = {Animals ; Aorta/cytology/metabolism ; Cell Movement/drug effects ; Embryo, Nonmammalian/metabolism ; Endothelial Cells/drug effects/metabolism ; Mice ; Mice, Inbred C57BL ; *Models, Biological ; Neovascularization, Physiologic/drug effects ; Retina/drug effects/metabolism ; Time-Lapse Imaging ; Vascular Endothelial Growth Factor A/pharmacology ; Zebrafish/growth & development ; }, abstract = {Angiogenesis is a multicellular phenomenon driven by morphogenetic cell movements. We recently reported morphogenetic vascular endothelial cell (EC) behaviors to be dynamic and complex. However, the principal mechanisms orchestrating individual EC movements in angiogenic morphogenesis remain largely unknown. Here we present an experiment-driven mathematical model that enables us to systematically dissect cellular mechanisms in branch elongation. We found that cell-autonomous and coordinated actions governed these multicellular behaviors, and a cell-autonomous process sufficiently illustrated essential features of the morphogenetic EC dynamics at both the single-cell and cell-population levels. Through refining our model and experimental verification, we further identified a coordinated mode of tip EC behaviors regulated via a spatial relationship between tip and follower ECs, which facilitates the forward motility of tip ECs. These findings provide insights that enhance our mechanistic understanding of not only angiogenic morphogenesis, but also other types of multicellular phenomenon.}, } @article {pmid26648040, year = {2015}, author = {Longo, G and Montevil, M and Sonnenschein, C and Soto, AM}, title = {In search of principles for a Theory of Organisms.}, journal = {Journal of biosciences}, volume = {40}, number = {5}, pages = {955-968}, pmid = {26648040}, issn = {0973-7138}, support = {R01 ES008314/ES/NIEHS NIH HHS/United States ; U01 ES020888/ES/NIEHS NIH HHS/United States ; ES08314/ES/NIEHS NIH HHS/United States ; U01-ES020888/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Biophysics/methods ; Cell Division ; Mice, Inbred C57BL ; *Models, Biological ; *Morphogenesis ; Physics/methods ; Thermodynamics ; }, abstract = {Lacking an operational theory to explain the organization and behaviour of matter in unicellular and multicellular organisms hinders progress in biology. Such a theory should address life cycles from ontogenesis to death. This theory would complement the theory of evolution that addresses phylogenesis, and would posit theoretical extensions to accepted physical principles and default states in order to grasp the living state of matter and define proper biological observables. Thus, we favour adopting the default state implicit in Darwin's theory, namely, cell proliferation with variation plus motility, and a framing principle, namely, life phenomena manifest themselves as non-identical iterations of morphogenetic processes. From this perspective, organisms become a consequence of the inherent variability generated by proliferation, motility and self-organization. Morphogenesis would then be the result of the default state plus physical constraints, like gravity, and those present in living organisms, like muscular tension.}, } @article {pmid26644562, year = {2015}, author = {Alié, A and Hayashi, T and Sugimura, I and Manuel, M and Sugano, W and Mano, A and Satoh, N and Agata, K and Funayama, N}, title = {The ancestral gene repertoire of animal stem cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {51}, pages = {E7093-100}, pmid = {26644562}, issn = {1091-6490}, mesh = {Animals ; Evolution, Molecular ; Genomic Instability ; Hydra/cytology/genetics ; Mammals ; Phylogeny ; Porifera/cytology/genetics ; RNA, Small Interfering/genetics ; RNA-Binding Proteins/genetics ; Stem Cells/*metabolism ; Transcription Factors/genetics ; Transcriptome ; }, abstract = {Stem cells are pivotal for development and tissue homeostasis of multicellular animals, and the quest for a gene toolkit associated with the emergence of stem cells in a common ancestor of all metazoans remains a major challenge for evolutionary biology. We reconstructed the conserved gene repertoire of animal stem cells by transcriptomic profiling of totipotent archeocytes in the demosponge Ephydatia fluviatilis and by tracing shared molecular signatures with flatworm and Hydra stem cells. Phylostratigraphy analyses indicated that most of these stem-cell genes predate animal origin, with only few metazoan innovations, notably including several partners of the Piwi machinery known to promote genome stability. The ancestral stem-cell transcriptome is strikingly poor in transcription factors. Instead, it is rich in RNA regulatory actors, including components of the "germ-line multipotency program" and many RNA-binding proteins known as critical regulators of mammalian embryonic stem cells.}, } @article {pmid26644561, year = {2015}, author = {Schaible, R and Scheuerlein, A and Dańko, MJ and Gampe, J and Martínez, DE and Vaupel, JW}, title = {Constant mortality and fertility over age in Hydra.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {51}, pages = {15701-15706}, pmid = {26644561}, issn = {1091-6490}, support = {R01 AG037965/AG/NIA NIH HHS/United States ; AG037965/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Fertility ; Hydra/*physiology ; Life Expectancy ; }, abstract = {Senescence, the increase in mortality and decline in fertility with age after maturity, was thought to be inevitable for all multicellular species capable of repeated breeding. Recent theoretical advances and compilations of data suggest that mortality and fertility trajectories can go up or down, or remain constant with age, but the data are scanty and problematic. Here, we present compelling evidence for constant age-specific death and reproduction rates in Hydra, a basal metazoan, in a set of experiments comprising more than 3.9 million days of observations of individual Hydra. Our data show that 2,256 Hydra from two closely related species in two laboratories in 12 cohorts, with cohort age ranging from 0 to more than 41 y, have extremely low, constant rates of mortality. Fertility rates for Hydra did not systematically decline with advancing age. This falsifies the universality of the theories of the evolution of aging that posit that all species deteriorate with age after maturity. The nonsenescent life history of Hydra implies levels of maintenance and repair that are sufficient to prevent the accumulation of damage for at least decades after maturity, far longer than the short life expectancy of Hydra in the wild. A high proportion of stem cells, constant and rapid cell turnover, few cell types, a simple body plan, and the fact that the germ line is not segregated from the soma are characteristics of Hydra that may make nonsenescence feasible. Nonsenescence may be optimal because lifetime reproduction may be enhanced more by extending adult life spans than by increasing daily fertility.}, } @article {pmid26638678, year = {2015}, author = {Libertini, G}, title = {Phylogeny of Aging and Related Phenoptotic Phenomena.}, journal = {Biochemistry. Biokhimiia}, volume = {80}, number = {12}, pages = {1529-1546}, doi = {10.1134/S0006297915120019}, pmid = {26638678}, issn = {1608-3040}, mesh = {Aging/*genetics ; Animals ; Apoptosis/physiology ; Biological Evolution ; DNA/genetics ; Humans ; Phylogeny ; Telomere/genetics ; }, abstract = {The interpretation of aging as adaptive, i.e. as a phenomenon genetically determined and modulated, and with an evolutionary advantage, implies that aging, as any physiologic mechanism, must have phylogenetic connections with similar phenomena. This review tries to find the phylogenetic connections between vertebrate aging and some related phenomena in other species, especially within those phenomena defined as phenoptotic, i.e. involving the death of one or more individuals for the benefit of other individuals. In particular, the aim of the work is to highlight and analyze similarities and connections, in the mechanisms and in the evolutionary causes, between: (i) proapoptosis in prokaryotes and apoptosis in unicellular eukaryotes; (ii) apoptosis in unicellular and multicellular eukaryotes; (iii) aging in yeast and in vertebrates; and (iv) the critical importance of the DNA subtelomeric segment in unicellular and multicellular eukaryotes. In short, there is strong evidence that vertebrate aging has clear similarities and connections with phenomena present in organisms with simpler organization. These phylogenetic connections are a necessary element for the sustainability of the thesis of aging explained as an adaptive phenomenon, and, on the contrary, are incompatible with the opposite view of aging as being due to the accumulation of random damages of various kinds.}, } @article {pmid26637532, year = {2015}, author = {Igaki, T}, title = {Communicating the molecular basis of cancer cell-by-cell: an interview with Tatsushi Igaki.}, journal = {Disease models & mechanisms}, volume = {8}, number = {12}, pages = {1491-1494}, doi = {10.1242/dmm.024059}, pmid = {26637532}, issn = {1754-8411}, mesh = {Animals ; Apoptosis ; Cell Communication ; Drosophila/cytology ; History, 20th Century ; History, 21st Century ; Humans ; Japan ; Neoplasms/*history ; }, abstract = {Tatsushi Igaki is currently based at the Kyoto University Graduate School of Biostudies, where he leads a research group dedicated to using Drosophila genetics to build a picture of the cell-cell communications underlying the establishment and maintenance of multicellular systems. His work has provided insight into the molecular bases of cell competition in the context of development and tumorigenesis, including the landmark discovery that oncogenic cells communicate with normal cells in the tumor microenvironment to induce tumor progression in a non-autonomous fashion. In this interview, he describes his career path, highlighting the shift in his research focus from the basic principles of apoptosis to clonal evolution in cancer, and also explains why Drosophila provides a powerful model system for studying cancer biology.}, } @article {pmid26636317, year = {2016}, author = {Li, XQ}, title = {Natural Attributes and Agricultural Implications of Somatic Genome Variation.}, journal = {Current issues in molecular biology}, volume = {20}, number = {}, pages = {29-46}, pmid = {26636317}, issn = {1467-3045}, mesh = {Agriculture ; Animals ; Evolution, Molecular ; *Genetic Variation ; Genome ; Humans ; Livestock/*genetics ; Models, Genetic ; Mutation ; Ploidies ; }, abstract = {This article proposes the concept of genome network, describes different variations of the somatic genome network, and reviews the agricultural implications of such variations. All genetic materials in a cell constitute the genome network of the cell and can jointly influence the cell's function and fate. The somatic genome of a plant is the genome network of cells in somatic tissues and of nonreproductive cells in pollen and ovules. Somatic genome variation (SGV, approximately equivalent to somagenetic variation) occurs at multiple levels, including stoichiometric, ploidy, and sequence variations. For a multicellular organism, the term "somatic genome variation" covers both the variation in part of the organism and the generation of new genotype individuals through somatic means from a sexually produced original genotype. For unicellular organisms, genome variation in somatic nuclei occurs at the whole organism level because there is only a single cell per individual. Growth, development and evolution of living organisms require both stability and instability of their genomes. Somatic genome variation displays many more attributes than genetic mutation and has strong implications for agriculture.}, } @article {pmid26634291, year = {2016}, author = {Boehm, CR and Ueda, M and Nishimura, Y and Shikanai, T and Haseloff, J}, title = {A Cyan Fluorescent Reporter Expressed from the Chloroplast Genome of Marchantia polymorpha.}, journal = {Plant & cell physiology}, volume = {57}, number = {2}, pages = {291-299}, pmid = {26634291}, issn = {1471-9053}, support = {BB/F011458/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L014130/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Base Sequence ; Fluorescence ; *Genome, Chloroplast ; Green Fluorescent Proteins/chemistry/genetics/*metabolism ; Marchantia/*genetics ; Molecular Sequence Data ; Plants, Genetically Modified ; Transformation, Genetic ; }, abstract = {Recently, the liverwort Marchantia polymorpha has received increasing attention as a basal plant model for multicellular studies. Its ease of handling, well-characterized plastome and proven protocols for biolistic plastid transformation qualify M. polymorpha as an attractive platform to study the evolution of chloroplasts during the transition from water to land. In addition, chloroplasts of M. polymorpha provide a convenient test-bed for the characterization of genetic elements involved in plastid gene expression due to the absence of mechanisms for RNA editing. While reporter genes have proven valuable to the qualitative and quantitative study of gene expression in chloroplasts, expression of green fluorescent protein (GFP) in chloroplasts of M. polymorpha has proven problematic. We report the design of a codon-optimized gfp varian, mturq2cp, which allowed successful expression of a cyan fluorescent protein under control of the tobacco psbA promoter from the chloroplast genome of M. polymorpha. We demonstrate the utility of mturq2cp in (i) early screening for transplastomic events following biolistic transformation of M. polymorpha spores; (ii) visualization of stromules as elements of plastid structure in Marchantia; and (iii) quantitative microscopy for the analysis of promoter activity.}, } @article {pmid26627241, year = {2015}, author = {Chang, ES and Neuhof, M and Rubinstein, ND and Diamant, A and Philippe, H and Huchon, D and Cartwright, P}, title = {Genomic insights into the evolutionary origin of Myxozoa within Cnidaria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {48}, pages = {14912-14917}, pmid = {26627241}, issn = {1091-6490}, mesh = {Animals ; *Evolution, Molecular ; *Genome ; Genomics ; Myxobolus/*genetics ; *Phylogeny ; Polypodium/parasitology ; }, abstract = {The Myxozoa comprise over 2,000 species of microscopic obligate parasites that use both invertebrate and vertebrate hosts as part of their life cycle. Although the evolutionary origin of myxozoans has been elusive, a close relationship with cnidarians, a group that includes corals, sea anemones, jellyfish, and hydroids, is supported by some phylogenetic studies and the observation that the distinctive myxozoan structure, the polar capsule, is remarkably similar to the stinging structures (nematocysts) in cnidarians. To gain insight into the extreme evolutionary transition from a free-living cnidarian to a microscopic endoparasite, we analyzed genomic and transcriptomic assemblies from two distantly related myxozoan species, Kudoa iwatai and Myxobolus cerebralis, and compared these to the transcriptome and genome of the less reduced cnidarian parasite, Polypodium hydriforme. A phylogenomic analysis, using for the first time to our knowledge, a taxonomic sampling that represents the breadth of myxozoan diversity, including four newly generated myxozoan assemblies, confirms that myxozoans are cnidarians and are a sister taxon to P. hydriforme. Estimations of genome size reveal that myxozoans have one of the smallest reported animal genomes. Gene enrichment analyses show depletion of expressed genes in categories related to development, cell differentiation, and cell-cell communication. In addition, a search for candidate genes indicates that myxozoans lack key elements of signaling pathways and transcriptional factors important for multicellular development. Our results suggest that the degeneration of the myxozoan body plan from a free-living cnidarian to a microscopic parasitic cnidarian was accompanied by extreme reduction in genome size and gene content.}, } @article {pmid26610912, year = {2015}, author = {Mao, M and Alavi, MV and Labelle-Dumais, C and Gould, DB}, title = {Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms.}, journal = {Current topics in membranes}, volume = {76}, number = {}, pages = {61-116}, doi = {10.1016/bs.ctm.2015.09.002}, pmid = {26610912}, issn = {1063-5823}, mesh = {Animals ; Basement Membrane/metabolism/*pathology ; *Cell Biology ; *Collagen Type IV/chemistry/genetics/metabolism ; *Disease ; Genomics ; Humans ; }, abstract = {Basement membranes are highly specialized extracellular matrices. Once considered inert scaffolds, basement membranes are now viewed as dynamic and versatile environments that modulate cellular behaviors to regulate tissue development, function, and repair. Increasing evidence suggests that, in addition to providing structural support to neighboring cells, basement membranes serve as reservoirs of growth factors that direct and fine-tune cellular functions. Type IV collagens are a major component of all basement membranes. They evolved along with the earliest multicellular organisms and have been integrated into diverse fundamental biological processes as time and evolution shaped the animal kingdom. The roles of basement membranes in humans are as complex and diverse as their distributions and molecular composition. As a result, basement membrane defects result in multisystem disorders with ambiguous and overlapping boundaries that likely reflect the simultaneous interplay and integration of multiple cellular pathways and processes. Consequently, there will be no single treatment for basement membrane disorders, and therapies are likely to be as varied as the phenotypes. Understanding tissue-specific pathology and the underlying molecular mechanism is the present challenge; personalized medicine will rely upon understanding how a given mutation impacts diverse cellular functions.}, } @article {pmid26609133, year = {2016}, author = {Cournac, A and Koszul, R and Mozziconacci, J}, title = {The 3D folding of metazoan genomes correlates with the association of similar repetitive elements.}, journal = {Nucleic acids research}, volume = {44}, number = {1}, pages = {245-255}, pmid = {26609133}, issn = {1362-4962}, support = {260822/ERC_/European Research Council/International ; }, mesh = {Animals ; Binding Sites ; Cell Nucleus ; Chromosome Mapping ; Chromosomes ; Computational Biology/methods ; Drosophila ; Embryonic Stem Cells/metabolism ; Evolution, Molecular ; *Genome ; Humans ; Mice ; Molecular Sequence Annotation ; *Nucleic Acid Conformation ; Organ Specificity/genetics ; Protein Binding ; *Repetitive Sequences, Nucleic Acid ; Transcription Factors/metabolism ; }, abstract = {The potential roles of the numerous repetitive elements found in the genomes of multi-cellular organisms remain speculative. Several studies have suggested a role in stabilizing specific 3D genomic contacts. To test this hypothesis, we exploited inter-chromosomal contacts frequencies obtained from Hi-C experiments and show that the folding of the human, mouse and Drosophila genomes is associated with a significant co-localization of several specific repetitive elements, notably many elements of the SINE family. These repeats tend to be the oldest ones and are enriched in transcription factor binding sites. We propose that the co-localization of these repetitive elements may explain the global conservation of genome folding observed between homologous regions of the human and mouse genome. Taken together, these results support a contribution of specific repetitive elements in maintaining and/or reshaping genome architecture over evolutionary times.}, } @article {pmid26596625, year = {2015}, author = {Borowiec, ML and Lee, EK and Chiu, JC and Plachetzki, DC}, title = {Extracting phylogenetic signal and accounting for bias in whole-genome data sets supports the Ctenophora as sister to remaining Metazoa.}, journal = {BMC genomics}, volume = {16}, number = {}, pages = {987}, pmid = {26596625}, issn = {1471-2164}, mesh = {Animals ; Bias ; Ctenophora/*genetics ; *Data Mining ; Evolution, Molecular ; Genetic Loci/genetics ; *Genomics ; Humans ; *Phylogeny ; }, abstract = {BACKGROUND: Understanding the phylogenetic relationships among major lineages of multicellular animals (the Metazoa) is a prerequisite for studying the evolution of complex traits such as nervous systems, muscle tissue, or sensory organs. Transcriptome-based phylogenies have dramatically improved our understanding of metazoan relationships in recent years, although several important questions remain. The branching order near the base of the tree, in particular the placement of the poriferan (sponges, phylum Porifera) and ctenophore (comb jellies, phylum Ctenophora) lineages is one outstanding issue. Recent analyses have suggested that the comb jellies are sister to all remaining metazoan phyla including sponges. This finding is surprising because it suggests that neurons and other complex traits, present in ctenophores and eumetazoans but absent in sponges or placozoans, either evolved twice in Metazoa or were independently, secondarily lost in the lineages leading to sponges and placozoans.

RESULTS: To address the question of basal metazoan relationships we assembled a novel dataset comprised of 1080 orthologous loci derived from 36 publicly available genomes representing major lineages of animals. From this large dataset we procured an optimized set of partitions with high phylogenetic signal for resolving metazoan relationships. This optimized data set is amenable to the most appropriate and computationally intensive analyses using site-heterogeneous models of sequence evolution. We also employed several strategies to examine the potential for long-branch attraction to bias our inferences. Our analyses strongly support the Ctenophora as the sister lineage to other Metazoa. We find no support for the traditional view uniting the ctenophores and Cnidaria. Our findings are supported by Bayesian comparisons of topological hypotheses and we find no evidence that they are biased by long-branch attraction.

CONCLUSIONS: Our study further clarifies relationships among early branching metazoan lineages. Our phylogeny supports the still-controversial position of ctenophores as sister group to all other metazoans. This study also provides a workflow and computational tools for minimizing systematic bias in genome-based phylogenetic analyses. Future studies of metazoan phylogeny will benefit from ongoing efforts to sequence the genomes of additional invertebrate taxa that will continue to inform our view of the relationships among the major lineages of animals.}, } @article {pmid26575626, year = {2015}, author = {Lynch, M and Marinov, GK}, title = {The bioenergetic costs of a gene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {51}, pages = {15690-15695}, pmid = {26575626}, issn = {1091-6490}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; R01-GM036827/GM/NIGMS NIH HHS/United States ; }, mesh = {*Energy Metabolism ; *Evolution, Molecular ; Genetic Drift ; Selection, Genetic ; }, abstract = {An enduring mystery of evolutionary genomics concerns the mechanisms responsible for lineage-specific expansions of genome size in eukaryotes, especially in multicellular species. One idea is that all excess DNA is mutationally hazardous, but weakly enough so that genome-size expansion passively emerges in species experiencing relatively low efficiency of selection owing to small effective population sizes. Another idea is that substantial gene additions were impossible without the energetic boost provided by the colonizing mitochondrion in the eukaryotic lineage. Contrary to this latter view, analysis of cellular energetics and genomics data from a wide variety of species indicates that, relative to the lifetime ATP requirements of a cell, the costs of a gene at the DNA, RNA, and protein levels decline with cell volume in both bacteria and eukaryotes. Moreover, these costs are usually sufficiently large to be perceived by natural selection in bacterial populations, but not in eukaryotes experiencing high levels of random genetic drift. Thus, for scaling reasons that are not yet understood, by virtue of their large size alone, eukaryotic cells are subject to a broader set of opportunities for the colonization of novel genes manifesting weakly advantageous or even transiently disadvantageous phenotypic effects. These results indicate that the origin of the mitochondrion was not a prerequisite for genome-size expansion.}, } @article {pmid26573836, year = {2015}, author = {Yuan, S and Zheng, T and Li, P and Yang, R and Ruan, J and Huang, S and Wu, Z and Xu, A}, title = {Characterization of Amphioxus IFN Regulatory Factor Family Reveals an Archaic Signaling Framework for Innate Immune Response.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {195}, number = {12}, pages = {5657-5666}, doi = {10.4049/jimmunol.1501927}, pmid = {26573836}, issn = {1550-6606}, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Humans ; Immunity, Innate ; Interferon Regulatory Factor-1/genetics/*metabolism ; Interferon Regulatory Factors/genetics/*metabolism ; *Lancelets ; Molecular Sequence Data ; Protein Structure, Tertiary/genetics ; Sequence Homology, Amino Acid ; Species Specificity ; }, abstract = {The IFN regulatory factor (IRF) family encodes transcription factors that play important roles in immune defense, stress response, reproduction, development, and carcinogenesis. Although the origin of the IRF family has been dated back to multicellular organisms, invertebrate IRFs differ from vertebrate IRFs in genomic structure and gene synteny, and little is known about their functions. Through comparison of multiple amphioxus genomes, in this study we suggested that amphioxus contains nine IRF members, whose orthologs are supposed to be shared among three amphioxus species. As the orthologs to the vertebrate IRF1 and IRF4 subgroups, Branchiostoma belcheri tsingtauense (bbt)IRF1 and bbtIRF8 bind the IFN-stimulated response element (ISRE) and were upregulated when amphioxus intestinal cells were stimulated with poly(I:C). As amphioxus-specific IRFs, both bbtIRF3 and bbtIRF7 bind ISRE. When activated, they can be phosphorylated by bbtTBK1 and then translocate into nucleus for target gene transcription. As transcriptional repressors, bbtIRF2 and bbtIRF4 can inhibit the transcriptional activities of bbtIRF1, 3, 7, and 8 by competing for the binding of ISRE. Interestingly, amphioxus IRF2, IRF8, and Rel were identified as target genes of bbtIRF1, bbtIRF7, and bbtIRF3, respectively, suggesting a dynamic feedback regulation among amphioxus IRF and NF-κB. Collectively, to our knowledge we present for the first time an archaic IRF signaling framework in a basal chordate, shedding new insights into the origin and evolution of vertebrate IFN-based antiviral networks.}, } @article {pmid26569502, year = {2015}, author = {Amano, R and Nakayama, H and Morohoshi, Y and Kawakatsu, Y and Ferjani, A and Kimura, S}, title = {A Decrease in Ambient Temperature Induces Post-Mitotic Enlargement of Palisade Cells in North American Lake Cress.}, journal = {PloS one}, volume = {10}, number = {11}, pages = {e0141247}, pmid = {26569502}, issn = {1932-6203}, mesh = {Arabidopsis/cytology/genetics/*growth & development ; Cell Communication ; Cell Cycle ; Cell Proliferation ; *Cell Size ; Environment ; Gene Expression Regulation, Plant ; *Mitosis ; Phenotype ; Phylogeny ; Plant Leaves/cytology ; Plant Physiological Phenomena ; Rorippa/cytology/genetics/*growth & development ; Species Specificity ; *Temperature ; }, abstract = {In order to maintain organs and structures at their appropriate sizes, multicellular organisms orchestrate cell proliferation and post-mitotic cell expansion during morphogenesis. Recent studies using Arabidopsis leaves have shown that compensation, which is defined as post-mitotic cell expansion induced by a decrease in the number of cells during lateral organ development, is one example of such orchestration. Some of the basic molecular mechanisms underlying compensation have been revealed by genetic and chimeric analyses. However, to date, compensation had been observed only in mutants, transgenics, and γ-ray-treated plants, and it was unclear whether it occurs in plants under natural conditions. Here, we illustrate that a shift in ambient temperature could induce compensation in Rorippa aquatica (Brassicaceae), a semi-aquatic plant found in North America. The results suggest that compensation is a universal phenomenon among angiosperms and that the mechanism underlying compensation is shared, in part, between Arabidopsis and R. aquatica.}, } @article {pmid26560631, year = {2015}, author = {Cayrou, C and Ballester, B and Peiffer, I and Fenouil, R and Coulombe, P and Andrau, JC and van Helden, J and Méchali, M}, title = {The chromatin environment shapes DNA replication origin organization and defines origin classes.}, journal = {Genome research}, volume = {25}, number = {12}, pages = {1873-1885}, pmid = {26560631}, issn = {1549-5469}, mesh = {Animals ; Base Composition ; Chromatin/*genetics/*metabolism ; Chromatin Assembly and Disassembly ; Chromosome Mapping ; Cluster Analysis ; Computational Biology/methods ; *DNA Replication ; Embryonic Stem Cells ; Genome ; Genomics ; Heterochromatin/genetics/metabolism ; High-Throughput Nucleotide Sequencing ; Histones ; Humans ; Mice ; Nucleosomes/genetics/metabolism ; Nucleotide Motifs ; Origin Recognition Complex ; *Replication Origin ; Transcriptional Activation ; }, abstract = {To unveil the still-elusive nature of metazoan replication origins, we identified them genome-wide and at unprecedented high-resolution in mouse ES cells. This allowed initiation sites (IS) and initiation zones (IZ) to be differentiated. We then characterized their genetic signatures and organization and integrated these data with 43 chromatin marks and factors. Our results reveal that replication origins can be grouped into three main classes with distinct organization, chromatin environment, and sequence motifs. Class 1 contains relatively isolated, low-efficiency origins that are poor in epigenetic marks and are enriched in an asymmetric AC repeat at the initiation site. Late origins are mainly found in this class. Class 2 origins are particularly rich in enhancer elements. Class 3 origins are the most efficient and are associated with open chromatin and polycomb protein-enriched regions. The presence of Origin G-rich Repeated elements (OGRE) potentially forming G-quadruplexes (G4) was confirmed at most origins. These coincide with nucleosome-depleted regions located upstream of the initiation sites, which are associated with a labile nucleosome containing H3K64ac. These data demonstrate that specific chromatin landscapes and combinations of specific signatures regulate origin localization. They explain the frequently observed links between DNA replication and transcription. They also emphasize the plasticity of metazoan replication origins and suggest that in multicellular eukaryotes, the combination of distinct genetic features and chromatin configurations act in synergy to define and adapt the origin profile.}, } @article {pmid26554049, year = {2015}, author = {Jékely, G and Keijzer, F and Godfrey-Smith, P}, title = {An option space for early neural evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {370}, number = {1684}, pages = {}, pmid = {26554049}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Motor Activity ; Nervous System/*anatomy & histology ; *Nervous System Physiological Phenomena ; }, abstract = {The origin of nervous systems has traditionally been discussed within two conceptual frameworks. Input-output models stress the sensory-motor aspects of nervous systems, while internal coordination models emphasize the role of nervous systems in coordinating multicellular activity, especially muscle-based motility. Here we consider both frameworks and apply them to describe aspects of each of three main groups of phenomena that nervous systems control: behaviour, physiology and development. We argue that both frameworks and all three aspects of nervous system function need to be considered for a comprehensive discussion of nervous system origins. This broad mapping of the option space enables an overview of the many influences and constraints that may have played a role in the evolution of the first nervous systems.}, } @article {pmid26537913, year = {2015}, author = {Eyres, I and Boschetti, C and Crisp, A and Smith, TP and Fontaneto, D and Tunnacliffe, A and Barraclough, TG}, title = {Horizontal gene transfer in bdelloid rotifers is ancient, ongoing and more frequent in species from desiccating habitats.}, journal = {BMC biology}, volume = {13}, number = {}, pages = {90}, pmid = {26537913}, issn = {1741-7007}, support = {233232/ERC_/European Research Council/International ; BB/F020562/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F020856/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Desiccation ; *Ecosystem ; *Gene Transfer, Horizontal ; Molecular Sequence Data ; Phylogeny ; Rotifera/*genetics ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {BACKGROUND: Although prevalent in prokaryotes, horizontal gene transfer (HGT) is rarer in multicellular eukaryotes. Bdelloid rotifers are microscopic animals that contain a higher proportion of horizontally transferred, non-metazoan genes in their genomes than typical of animals. It has been hypothesized that bdelloids incorporate foreign DNA when they repair their chromosomes following double-strand breaks caused by desiccation. HGT might thereby contribute to species divergence and adaptation, as in prokaryotes. If so, we expect that species should differ in their complement of foreign genes, rather than sharing the same set of foreign genes inherited from a common ancestor. Furthermore, there should be more foreign genes in species that desiccate more frequently. We tested these hypotheses by surveying HGT in four congeneric species of bdelloids from different habitats: two from permanent aquatic habitats and two from temporary aquatic habitats that desiccate regularly.

RESULTS: Transcriptomes of all four species contain many genes with a closer match to non-metazoan genes than to metazoan genes. Whole genome sequencing of one species confirmed the presence of these foreign genes in the genome. Nearly half of foreign genes are shared between all four species and an outgroup from another family, but many hundreds are unique to particular species, which indicates that HGT is ongoing. Using a dated phylogeny, we estimate an average of 12.8 gains versus 2.0 losses of foreign genes per million years. Consistent with the desiccation hypothesis, the level of HGT is higher in the species that experience regular desiccation events than those that do not. However, HGT still contributed hundreds of foreign genes to the species from permanently aquatic habitats. Foreign genes were mainly enzymes with various annotated functions that include catabolism of complex polysaccharides and stress responses. We found evidence of differential loss of ancestral foreign genes previously associated with desiccation protection in the two non-desiccating species.

CONCLUSIONS: Nearly half of foreign genes were acquired before the divergence of bdelloid families over 60 Mya. Nonetheless, HGT is ongoing in bdelloids and has contributed to putative functional differences among species. Variation among our study species is consistent with the hypothesis that desiccating habitats promote HGT.}, } @article {pmid26536128, year = {2015}, author = {Germer, J and Mann, K and Wörheide, G and Jackson, DJ}, title = {The Skeleton Forming Proteome of an Early Branching Metazoan: A Molecular Survey of the Biomineralization Components Employed by the Coralline Sponge Vaceletia Sp.}, journal = {PloS one}, volume = {10}, number = {11}, pages = {e0140100}, pmid = {26536128}, issn = {1932-6203}, mesh = {Animals ; Biological Evolution ; Calcification, Physiologic/physiology ; Calcium Carbonate/metabolism ; Carbonic Anhydrases/metabolism ; Chromatography, High Pressure Liquid ; Coccidioidin/classification/metabolism ; Extracellular Matrix Proteins/metabolism ; Mass Spectrometry ; Phylogeny ; Porifera/genetics/*metabolism ; Proteome/analysis/*metabolism ; Skeleton/metabolism ; Transcriptome ; }, abstract = {The ability to construct a mineralized skeleton was a major innovation for the Metazoa during their evolution in the late Precambrian/early Cambrian. Porifera (sponges) hold an informative position for efforts aimed at unraveling the origins of this ability because they are widely regarded to be the earliest branching metazoans, and are among the first multi-cellular animals to display the ability to biomineralize in the fossil record. Very few biomineralization associated proteins have been identified in sponges so far, with no transcriptome or proteome scale surveys yet available. In order to understand what genetic repertoire may have been present in the last common ancestor of the Metazoa (LCAM), and that may have contributed to the evolution of the ability to biocalcify, we have studied the skeletal proteome of the coralline demosponge Vaceletia sp. and compare this to other metazoan biomineralizing proteomes. We bring some spatial resolution to this analysis by dividing Vaceletia's aragonitic calcium carbonate skeleton into "head" and "stalk" regions. With our approach we were able to identify 40 proteins from both the head and stalk regions, with many of these sharing some similarity to previously identified gene products from other organisms. Among these proteins are known biomineralization compounds, such as carbonic anhydrase, spherulin, extracellular matrix proteins and very acidic proteins. This report provides the first proteome scale analysis of a calcified poriferan skeletal proteome, and its composition clearly demonstrates that the LCAM contributed several key enzymes and matrix proteins to its descendants that supported the metazoan ability to biocalcify. However, lineage specific evolution is also likely to have contributed significantly to the ability of disparate metazoan lineages to biocalcify.}, } @article {pmid26518574, year = {2016}, author = {Wang, YL and Nie, JT and Chen, HM and Guo, CL and Pan, J and He, HL and Pan, JS and Cai, R}, title = {Identification and mapping of Tril, a homeodomain-leucine zipper gene involved in multicellular trichome initiation in Cucumis sativus.}, journal = {TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik}, volume = {129}, number = {2}, pages = {305-316}, pmid = {26518574}, issn = {1432-2242}, mesh = {Chromosome Mapping ; Cucumis sativus/*genetics/growth & development ; DNA, Plant/genetics ; Epistasis, Genetic ; Fruit/growth & development ; Gene Expression Regulation, Plant ; Genetic Markers ; Homeodomain Proteins/*genetics ; *Leucine Zippers ; Mutation ; Phenotype ; Plant Proteins/*genetics ; Transcriptome ; Trichomes/*growth & development ; }, abstract = {KEY MESSAGE: Using map-based cloning of Tril gene, we identified a homeodomain-leucine zipper gene involved in the initiation of multicellular trichomes (including the spines of fruit) in cucumber.

ABSTRACT: Fruit spines are a special type of trichome that impacts the quality and appearance of cucumber (Cucumis sativus L.) fruit. Scanning electron microscopy revealed that the trichome-less (tril) mutant originating from European greenhouse cucumber has a completely glabrous phenotype on cotyledons, hypocotyls, young leaves, fruits, and fruit stalks. Genetic analysis revealed that tril was inherited as a recessive allele at a single locus. Using 1058 F2 individuals derived from a cross between cucumber tril mutant CGN19839 and the micro-trichome (mict) mutant 06-2, tril was mapped to chromosome 6, and narrowed down to a 37.4 kb genomic region which carries seven predicted genes. Genetic and molecular analyses revealed that gene Cucsa.045360 is a possible candidate gene for the differentiation of epidermal cells to trichomes. It is a member of the class IV homeodomain-leucine zipper (HD-Zip IV) family and encodes homeodomain and START domain, sharing 66.7% predicted amino acid sequence identity to PROTODERMAL FACTOR2 (PDF2) and 35.0% to GLABRA2 (GL2) of Arabidopsis. The homeobox domain had changed amino acid sequence because of an insertion in tril mutant. The results of genetic analysis and transcriptome profiling indicated that the Tril gene had an epistatic effect on the Mict gene in trichome development. Phenotypes of the tril mutant such as glabrous fruits and female flowers at every node could be used in developing new cultivars.}, } @article {pmid26518483, year = {2016}, author = {Ninova, M and Ronshaugen, M and Griffiths-Jones, S}, title = {MicroRNA evolution, expression, and function during short germband development in Tribolium castaneum.}, journal = {Genome research}, volume = {26}, number = {1}, pages = {85-96}, pmid = {26518483}, issn = {1549-5469}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/M008908/1/MRC_/Medical Research Council/United Kingdom ; 093161/Z/10/Z/WT_/Wellcome Trust/United Kingdom ; BB/M011275/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Down-Regulation ; Drosophila/genetics ; Embryonic Development/genetics ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Gene Library ; MicroRNAs/*genetics/metabolism ; Molecular Sequence Annotation ; Sequence Analysis, RNA ; Tribolium/*embryology/*genetics ; }, abstract = {MicroRNAs are well-established players in the development of multicellular animals. Most of our understanding of microRNA function in arthropod development comes from studies in Drosophila. Despite their advantages as model systems, the long germband embryogenesis of fruit flies is an evolutionary derived state restricted to several holometabolous insect lineages. MicroRNA evolution and expression across development in animals exhibiting the ancestral and more widespread short germband mode of embryogenesis has not been characterized. We sequenced small RNA libraries of oocytes and successive intervals covering the embryonic development of the short germband model organism, Tribolium castaneum. We analyzed the evolution and temporal expression of the microRNA complement and sequenced libraries of total RNA to investigate the relationships with microRNA target expression. We show microRNA maternal loading and sequence-specific 3' end nontemplate oligoadenylation of maternally deposited microRNAs that is conserved between Tribolium and Drosophila. We further uncover large clusters encoding multiple paralogs from several Tribolium-specific microRNA families expressed during a narrow interval of time immediately after the activation of zygotic transcription. These novel microRNAs, together with several early expressed conserved microRNAs, target a significant number of maternally deposited transcripts. Comparison with Drosophila shows that microRNA-mediated maternal transcript targeting is a conserved process in insects, but the number and sequences of microRNAs involved have diverged. The expression of fast-evolving and species-specific microRNAs in the early blastoderm of T. castaneum is consistent with previous findings in Drosophila and shows that the unique permissiveness for microRNA innovation at this stage is a conserved phenomenon.}, } @article {pmid26518480, year = {2016}, author = {Keith, N and Tucker, AE and Jackson, CE and Sung, W and Lucas Lledó, JI and Schrider, DR and Schaack, S and Dudycha, JL and Ackerman, M and Younge, AJ and Shaw, JR and Lynch, M}, title = {High mutational rates of large-scale duplication and deletion in Daphnia pulex.}, journal = {Genome research}, volume = {26}, number = {1}, pages = {60-69}, pmid = {26518480}, issn = {1549-5469}, support = {R01GM036827/GM/NIGMS NIH HHS/United States ; R01 GM101672/GM/NIGMS NIH HHS/United States ; R01ES019324/ES/NIEHS NIH HHS/United States ; R01 GM036827/GM/NIGMS NIH HHS/United States ; R01GM101672-01A1/GM/NIGMS NIH HHS/United States ; R01 ES019324/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; DNA Copy Number Variations ; Daphnia/*genetics ; Evolution, Molecular ; Female ; *Gene Deletion ; *Gene Duplication ; Genetic Association Studies ; Genetic Variation ; Heterozygote ; Male ; *Mutation Rate ; Sequence Analysis, DNA ; }, abstract = {Knowledge of the genome-wide rate and spectrum of mutations is necessary to understand the origin of disease and the genetic variation driving all evolutionary processes. Here, we provide a genome-wide analysis of the rate and spectrum of mutations obtained in two Daphnia pulex genotypes via separate mutation-accumulation (MA) experiments. Unlike most MA studies that utilize haploid, homozygous, or self-fertilizing lines, D. pulex can be propagated ameiotically while maintaining a naturally heterozygous, diploid genome, allowing the capture of the full spectrum of genomic changes that arise in a heterozygous state. While base-substitution mutation rates are similar to those in other multicellular eukaryotes (about 4 × 10(-9) per site per generation), we find that the rates of large-scale (>100 kb) de novo copy-number variants (CNVs) are significantly elevated relative to those seen in previous MA studies. The heterozygosity maintained in this experiment allowed for estimates of gene-conversion processes. While most of the conversion tract lengths we report are similar to those generated by meiotic processes, we also find larger tract lengths that are indicative of mitotic processes. Comparison of MA lines to natural isolates reveals that a majority of large-scale CNVs in natural populations are removed by purifying selection. The mutations observed here share similarities with disease-causing, complex, large-scale CNVs, thereby demonstrating that MA studies in D. pulex serve as a system for studying the processes leading to such alterations.}, } @article {pmid26501252, year = {2015}, author = {Tan, DX and Manchester, LC and Esteban-Zubero, E and Zhou, Z and Reiter, RJ}, title = {Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism.}, journal = {Molecules (Basel, Switzerland)}, volume = {20}, number = {10}, pages = {18886-18906}, pmid = {26501252}, issn = {1420-3049}, mesh = {Animals ; Antioxidants/*metabolism ; Biosynthetic Pathways ; Humans ; Melatonin/*biosynthesis ; Oxidative Stress ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin's synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress.}, } @article {pmid26497146, year = {2015}, author = {Gutzwiller, F and Carmo, CR and Miller, DE and Rice, DW and Newton, IL and Hawley, RS and Teixeira, L and Bergman, CM}, title = {Dynamics of Wolbachia pipientis Gene Expression Across the Drosophila melanogaster Life Cycle.}, journal = {G3 (Bethesda, Md.)}, volume = {5}, number = {12}, pages = {2843-2856}, pmid = {26497146}, issn = {2160-1836}, support = {BB/L002817/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Cluster Analysis ; Computational Biology ; Drosophila melanogaster/*growth & development/microbiology ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; Genome, Bacterial ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions/genetics ; Life Cycle Stages ; Phylogeny ; Stress, Physiological/genetics ; Symbiosis ; Transcriptome ; Wolbachia/*genetics ; }, abstract = {Symbiotic interactions between microbes and their multicellular hosts have manifold biological consequences. To better understand how bacteria maintain symbiotic associations with animal hosts, we analyzed genome-wide gene expression for the endosymbiotic α-proteobacteria Wolbachia pipientis across the entire life cycle of Drosophila melanogaster. We found that the majority of Wolbachia genes are expressed stably across the D. melanogaster life cycle, but that 7.8% of Wolbachia genes exhibit robust stage- or sex-specific expression differences when studied in the whole-organism context. Differentially-expressed Wolbachia genes are typically up-regulated after Drosophila embryogenesis and include many bacterial membrane, secretion system, and ankyrin repeat-containing proteins. Sex-biased genes are often organized as small operons of uncharacterized genes and are mainly up-regulated in adult Drosophila males in an age-dependent manner. We also systematically investigated expression levels of previously-reported candidate genes thought to be involved in host-microbe interaction, including those in the WO-A and WO-B prophages and in the Octomom region, which has been implicated in regulating bacterial titer and pathogenicity. Our work provides comprehensive insight into the developmental dynamics of gene expression for a widespread endosymbiont in its natural host context, and shows that public gene expression data harbor rich resources to probe the functional basis of the Wolbachia-Drosophila symbiosis and annotate the transcriptional outputs of the Wolbachia genome.}, } @article {pmid26486321, year = {2016}, author = {Wagner, GP}, title = {What is "homology thinking" and what is it for?.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {326}, number = {1}, pages = {3-8}, doi = {10.1002/jez.b.22656}, pmid = {26486321}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Developmental Biology ; Genetics, Population ; Models, Biological ; Phenotype ; Phylogeny ; }, abstract = {In this paper I examine the thesis by Marc Ereshefsky that, in evolutionary biology, there is a third style of thinking, besides the well-known "population thinking" and "tree thinking." Ereshefsky proposes "homology thinking" as a third approach, focused on the transformation of organismal phenotypes. In this short commentary, I aim at identifying the underlying biological assumptions for homology thinking and how they can be put to work in a research program within evolutionary biology. I propose that homology thinking is based on three insights: 1) multicellular organisms consist of developmentally individualized parts (sub-systems); 2) that developmental individuation entails evolutionary individuation, that is, variational quasi-independence; and 3) these individuated body parts are inherited, though indirectly, and form lineages that are recognized as homologies. These facts support a research program focused on the modification and origination of individuated body parts that supplements and puts into perspective the population genetic and phylogenetic approaches to the study of evolution.}, } @article {pmid26465111, year = {2015}, author = {de Mendoza, A and Suga, H and Permanyer, J and Irimia, M and Ruiz-Trillo, I}, title = {Complex transcriptional regulation and independent evolution of fungal-like traits in a relative of animals.}, journal = {eLife}, volume = {4}, number = {}, pages = {e08904}, pmid = {26465111}, issn = {2050-084X}, support = {206883/ERC_/European Research Council/International ; 616960/ERC_/European Research Council/International ; }, mesh = {Animals ; *Cell Differentiation ; *Gene Expression Regulation ; Mesomycetozoea/*genetics/growth & development/*physiology ; Proteome/analysis ; }, abstract = {Cell-type specification through differential genome regulation is a hallmark of complex multicellularity. However, it remains unclear how this process evolved during the transition from unicellular to multicellular organisms. To address this question, we investigated transcriptional dynamics in the ichthyosporean Creolimax fragrantissima, a relative of animals that undergoes coenocytic development. We find that Creolimax utilizes dynamic regulation of alternative splicing, long inter-genic non-coding RNAs and co-regulated gene modules associated with animal multicellularity in a cell-type specific manner. Moreover, our study suggests that the different cell types of the three closest animal relatives (ichthyosporeans, filastereans and choanoflagellates) are the product of lineage-specific innovations. Additionally, a proteomic survey of the secretome reveals adaptations to a fungal-like lifestyle. In summary, the diversity of cell types among protistan relatives of animals and their complex genome regulation demonstrates that the last unicellular ancestor of animals was already capable of elaborate specification of cell types.}, } @article {pmid26462996, year = {2015}, author = {Kin, K}, title = {Inferring cell type innovations by phylogenetic methods-concepts, methods, and limitations.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {324}, number = {8}, pages = {653-661}, doi = {10.1002/jez.b.22657}, pmid = {26462996}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation/genetics ; Cell Lineage/genetics ; *Cells/classification/cytology ; Embryonic Development ; Gene Regulatory Networks ; *Phylogeny ; }, abstract = {Multicellular organisms are composed of distinct cell types that have specific roles in the body. Each cell type is a product of two kinds of historical processes-development and evolution. Although the concept of a cell type is difficult to define, the cell type concept based on the idea of the core regulatory network (CRN), a gene regulatory network that determines the identity of a cell type, illustrates the essential aspects of the cell type concept. The first step toward elucidating cell type evolution is to reconstruct the evolutionary relationships of cell types, or the cell type tree. The sister cell type model assumes that a new cell type evolves through divergence from a multifunctional ancestral cell type, creating tree-like evolutionary relationships between cell types. The process of generating a cell type tree can also be understood as the sequential addition of a new branching point on an ancestral cell differentiation hierarchy in evolution. A cell type tree thus represents an intertwined history of cell type evolution and development. Cell type trees can be reconstructed from high-throughput sequencing data, and the reconstruction of a cell type tree leads to the discovery of genes that are functionally important for a cell type. Although many issues including the lack of cross-species comparisons and the lack of a proper model for cell type evolution remain, the study of the origin of a new cell type using phylogenetic methods offers a promising new research avenue in developmental evolution. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 653-661, 2015. © 2015 Wiley Periodicals, Inc.}, } @article {pmid26451642, year = {2015}, author = {Stolzer, M and Siewert, K and Lai, H and Xu, M and Durand, D}, title = {Event inference in multidomain families with phylogenetic reconciliation.}, journal = {BMC bioinformatics}, volume = {16 Suppl 14}, number = {Suppl 14}, pages = {S8}, pmid = {26451642}, issn = {1471-2105}, mesh = {*Algorithms ; Animals ; *Evolution, Molecular ; Gene Duplication ; Guanylate Kinases/*genetics ; *Multigene Family ; *Phylogeny ; Protein Structure, Tertiary ; *Software ; Vertebrates/genetics ; }, abstract = {BACKGROUND: Reconstructing evolution provides valuable insights into the processes of gene evolution and function. However, while there have been great advances in algorithms and software to reconstruct the history of gene families, these tools do not model the domain shuffling events (domain duplication, insertion, transfer, and deletion) that drive the evolution of multidomain protein families. Protein evolution through domain shuffling events allows for rapid exploration of functions by introducing new combinations of existing folds. This powerful mechanism was key to some significant evolutionary innovations, such as multicellularity and the vertebrate immune system. A method for reconstructing this important evolutionary process is urgently needed.

RESULTS: Here, we introduce a novel, event-based framework for studying multidomain evolution by reconciling a domain tree with a gene tree, with additional information provided by the species tree. In the context of this framework, we present the first reconciliation algorithms to infer domain shuffling events, while addressing the challenges inherent in the inference of evolution across three levels of organization.

CONCLUSIONS: We apply these methods to the evolution of domains in the Membrane associated Guanylate Kinase family. These case studies reveal a more vivid and detailed evolutionary history than previously provided. Our algorithms have been implemented in software, freely available at http://www.cs.cmu.edu/˜durand/Notung.}, } @article {pmid26439347, year = {2015}, author = {Butterfield, NJ}, title = {The Neoproterozoic.}, journal = {Current biology : CB}, volume = {25}, number = {19}, pages = {R859-63}, doi = {10.1016/j.cub.2015.07.021}, pmid = {26439347}, issn = {1879-0445}, mesh = {Archaea/physiology ; Bacterial Physiological Phenomena ; *Biological Evolution ; Earth, Planet ; Eukaryota/physiology ; *Evolution, Planetary ; Fossils/anatomy & histology ; }, abstract = {The Neoproterozoic era was arguably the most revolutionary in Earth history. Extending from 1000 to 541 million years ago, it stands at the intersection of the two great tracts of evolutionary time: on the one side, some three billion years of pervasively microbial 'Precambrian' life, and on the other the modern 'Phanerozoic' biosphere with its extraordinary diversity of large multicellular organisms. The disturbance doesn't stop here, however: over this same stretch of time the planet itself was in the throes of change. Tectonically, it saw major super-continental reconfigurations, climatically its deepest ever glacial freeze, and geochemically some of the most anomalous perturbations on record. What lies behind this dramatic convergence of biological and geological phenomena, and how exactly did it give rise to the curiously complex world that we now inhabit?}, } @article {pmid26431572, year = {2015}, author = {Shklover, J and Levy-Adam, F and Kurant, E}, title = {Apoptotic Cell Clearance in Development.}, journal = {Current topics in developmental biology}, volume = {114}, number = {}, pages = {297-334}, doi = {10.1016/bs.ctdb.2015.07.024}, pmid = {26431572}, issn = {1557-8933}, mesh = {Animals ; Apoptosis/*physiology ; Caenorhabditis elegans/cytology/growth & development ; Caspases/metabolism ; Central Nervous System/cytology/*growth & development ; Drosophila melanogaster/cytology/growth & development ; Mice ; Neuroglia/cytology ; Phagocytes/*cytology/physiology ; Phagocytosis ; Signal Transduction ; Zebrafish/growth & development ; }, abstract = {Programmed cell death and its specific form apoptosis play an important role during development of multicellular organisms. They are crucial for morphogenesis and organ sculpting as well as for adjusting cell number in different systems. Removal of apoptotic cells is the last critical step of apoptosis. Apoptotic cells are properly and efficiently recognized and eliminated through phagocytosis, which is performed by professional and nonprofessional phagocytes. Phagocytosis of apoptotic cells or apoptotic cell clearance is a dynamic multistep process, involving interactions between phagocytic receptors and ligands on apoptotic cells, which are highly conserved in evolution. However, this process is extremely redundant in mammals, containing multiple factors playing similar roles in the process. Using model organisms such as Caenorhabditis elegans, Drosophila melanogaster, zebrafish, and mouse permits addressing fundamental questions in developmental cell clearance by a comprehensive approach including powerful genetics and cell biological tools enriched by live imaging. Recent studies in model organisms have enhanced significantly our understanding of the molecular and cellular basis of apoptotic cell clearance during development. Here, we review the current knowledge and illuminate the great potential of the research performed in genetic models, which opens new directions in developmental biology.}, } @article {pmid26423844, year = {2015}, author = {Drobnitch, ST and Jensen, KH and Prentice, P and Pittermann, J}, title = {Convergent evolution of vascular optimization in kelp (Laminariales).}, journal = {Proceedings. Biological sciences}, volume = {282}, number = {1816}, pages = {20151667}, pmid = {26423844}, issn = {1471-2954}, mesh = {*Biological Evolution ; Macrocystis/growth & development/*physiology ; Models, Biological ; }, abstract = {Terrestrial plants and mammals, although separated by a great evolutionary distance, have each arrived at a highly conserved body plan in which universal allometric scaling relationships govern the anatomy of vascular networks and key functional metabolic traits. The universality of allometric scaling suggests that these phyla have each evolved an 'optimal' transport strategy that has been overwhelmingly adopted by extant species. To truly evaluate the dominance and universality of vascular optimization, however, it is critical to examine other, lesser-known, vascularized phyla. The brown algae (Phaeophyceae) are one such group--as distantly related to plants as mammals, they have convergently evolved a plant-like body plan and a specialized phloem-like transport network. To evaluate possible scaling and optimization in the kelp vascular system, we developed a model of optimized transport anatomy and tested it with measurements of the giant kelp, Macrocystis pyrifera, which is among the largest and most successful of macroalgae. We also evaluated three classical allometric relationships pertaining to plant vascular tissues with a diverse sampling of kelp species. Macrocystis pyrifera displays strong scaling relationships between all tested vascular parameters and agrees with our model; other species within the Laminariales display weak or inconsistent vascular allometries. The lack of universal scaling in the kelps and the presence of optimized transport anatomy in M. pyrifera raises important questions about the evolution of optimization and the possible competitive advantage conferred by optimized vascular systems to multicellular phyla.}, } @article {pmid26416251, year = {2015}, author = {Haug, JT and Labandeira, CC and Santiago-Blay, JA and Haug, C and Brown, S}, title = {Life habits, hox genes, and affinities of a 311 million-year-old holometabolan larva.}, journal = {BMC evolutionary biology}, volume = {15}, number = {}, pages = {208}, pmid = {26416251}, issn = {1471-2148}, mesh = {Animals ; Biological Evolution ; Eye/anatomy & histology ; *Fossils ; Genes, Homeobox ; Head/anatomy & histology ; Insecta/*anatomy & histology/*genetics/growth & development/physiology ; Larva/anatomy & histology/genetics/physiology ; Phylogeny ; }, abstract = {BACKGROUND: Holometabolous insects are the most diverse, speciose and ubiquitous group of multicellular organisms in terrestrial and freshwater ecosystems. The enormous evolutionary and ecological success of Holometabola has been attributed to their unique postembryonic life phases in which nonreproductive and wingless larvae differ significantly in morphology and life habits from their reproductive and mostly winged adults, separated by a resting stage, the pupa. Little is known of the evolutionary developmental mechanisms that produced the holometabolous larval condition and their Paleozoic origin based on fossils and phylogeny.

RESULTS: We provide a detailed anatomic description of a 311 million-year-old specimen, the oldest known holometabolous larva, from the Mazon Creek deposits of Illinois, U.S.A. The head is ovoidal, downwardly oriented, broadly attached to the anterior thorax, and bears possible simple eyes and antennae with insertions encircled by molting sutures; other sutures are present but often indistinct. Mouthparts are generalized, consisting of five recognizable segments: a clypeo-labral complex, mandibles, possible hypopharynx, a maxilla bearing indistinct palp-like appendages, and labium. Distinctive mandibles are robust, triangular, and dicondylic. The thorax is delineated into three, nonoverlapping regions of distinctive surface texture, each with legs of seven elements, the terminal-most bearing paired claws. The abdomen has ten segments deployed in register with overlapping tergites; the penultimate segment bears a paired, cercus-like structure. The anterior eight segments bear clawless leglets more diminutive than the thoracic legs in length and cross-sectional diameter, and inserted more ventrolaterally than ventrally on the abdominal sidewall.

CONCLUSIONS: Srokalarva berthei occurred in an evolutionary developmental context likely responsible for the early macroevolutionary success of holometabolous insects. Srokalarva berthei bore head and prothoracic structures, leglet series on successive abdominal segments - in addition to comparable features on a second taxon eight million-years-younger - that indicates Hox-gene regulation of segmental and appendage patterning among earliest Holometabola. Srokalarva berthei body features suggest a caterpillar-like body plan and head structures indicating herbivory consistent with known, contemporaneous insect feeding damage on seed plants. Taxonomic resolution places Srokalarva berthei as an extinct lineage, apparently possessing features closer to neuropteroid than other holometabolous lineages.}, } @article {pmid26411889, year = {2015}, author = {Yu, X and Huo, L and Liu, H and Chen, L and Wang, Y and Zhu, X}, title = {Melanin is required for the formation of the multi-cellular conidia in the endophytic fungus Pestalotiopsis microspora.}, journal = {Microbiological research}, volume = {179}, number = {}, pages = {1-11}, doi = {10.1016/j.micres.2015.06.004}, pmid = {26411889}, issn = {1618-0623}, mesh = {Agrobacterium/genetics ; Fungal Proteins/genetics ; Genes, Fungal ; Germination ; Melanins/*biosynthesis/metabolism ; Microbial Viability ; Morphogenesis ; Phylogeny ; Polyketide Synthases/genetics/metabolism ; Spores, Fungal/growth & development/*physiology ; Xylariales/physiology ; }, abstract = {Melanin plays an important role in regulating various biological processes in many fungi. However, its biological role in conidiation remains largely elusive. We report here that conidia production, morphogenesis, integrity, germination and their viability in Pestalotiopsis microspora require the polyketide-derived melanin. A polyketide synthase gene, pks1, was identified and demonstrated responsible for melanin biosynthesis in this fungus. A targeted deletion mutant strain Δpks1 displayed a defect in pigmentation of conidia and had an albino colonial phenotype. Interestingly, Δpks1 produced approximately 6-fold as many conidia as the wild type did, suggesting a negative modulation of melanin on conidia production in this fungus. Moreover, the conidia failed to develop into the normal five-cell morphology, rather the three main-body cells separated via constriction at the original septum position to generate three independent mutant conidia. This result suggests a novel role of melanin in the formation of the multi-cellular conidia. Germ tubes could develop from the three different types of mutant conidia and kept elongating, despite a significantly lower germination rate was observed for them. Still more, the unpigmented conidia became permeable to Calcofluor White and DAPI, suggesting the integrity of the conidia was impaired. Deliberate inhibition of melanin biosynthesis by a specific inhibitor, tricyclazole, led to a similar phenotypes. This work demonstrates a new function of fungal melanin in conidial development.}, } @article {pmid26385555, year = {2016}, author = {Górz, A and Boroń, P}, title = {The Yeast Fungus Trichosporon lactis Found as an Epizoic Colonizer of Dung Beetle Exoskeletons.}, journal = {Microbial ecology}, volume = {71}, number = {2}, pages = {422-427}, pmid = {26385555}, issn = {1432-184X}, mesh = {Animal Shells/*microbiology ; Animals ; Coleoptera/*microbiology ; Phylogeny ; Trichosporon/classification/genetics/growth & development/*isolation & purification ; }, abstract = {The study on the biology and biodiversity of coprophagous Scarabaeoidea carried out in the Polish Carpathians revealed the occurrence of unusual epizoic excrescences on various dung beetles species of the genus Onthophagus. The excrescences occur on the elytra, prothorax, and head of the studied beetles. Detailed research on this phenomenon determined that the fungus grew in the form of multicellular thalli. The ITS-based identification of fungal material collected from beetles' exoskeletons resulted in a 100 % match with Trichosporon lactis. Until now, only a yeast lifestyle/stage was known for this basidiomycete species. Therefore, in this paper, we describe a new substrate for growth of T. lactis and its unknown and intriguing relationship with dung beetles. The results obtained in this study open up numerous research possibilities on the new role of dung beetles in terrestrial ecosystems, as well as on using the physiological properties of T. lactis to restore soils.}, } @article {pmid26381745, year = {2015}, author = {Salali, GD and Whitehouse, H and Hochberg, ME}, title = {A Life-Cycle Model of Human Social Groups Produces a U-Shaped Distribution in Group Size.}, journal = {PloS one}, volume = {10}, number = {9}, pages = {e0138496}, pmid = {26381745}, issn = {1932-6203}, mesh = {*Cultural Evolution ; *Group Processes ; Humans ; *Models, Theoretical ; *Social Behavior ; *Social Environment ; }, abstract = {One of the central puzzles in the study of sociocultural evolution is how and why transitions from small-scale human groups to large-scale, hierarchically more complex ones occurred. Here we develop a spatially explicit agent-based model as a first step towards understanding the ecological dynamics of small and large-scale human groups. By analogy with the interactions between single-celled and multicellular organisms, we build a theory of group lifecycles as an emergent property of single cell demographic and expansion behaviours. We find that once the transition from small-scale to large-scale groups occurs, a few large-scale groups continue expanding while small-scale groups gradually become scarcer, and large-scale groups become larger in size and fewer in number over time. Demographic and expansion behaviours of groups are largely influenced by the distribution and availability of resources. Our results conform to a pattern of human political change in which religions and nation states come to be represented by a few large units and many smaller ones. Future enhancements of the model should include decision-making rules and probabilities of fragmentation for large-scale societies. We suggest that the synthesis of population ecology and social evolution will generate increasingly plausible models of human group dynamics.}, } @article {pmid26379197, year = {2015}, author = {Roberts, SE and Gladfelter, AS}, title = {Nuclear autonomy in multinucleate fungi.}, journal = {Current opinion in microbiology}, volume = {28}, number = {}, pages = {60-65}, pmid = {26379197}, issn = {1879-0364}, support = {R01 GM081506/GM/NIGMS NIH HHS/United States ; R01-GM081506/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Nucleus/genetics/*physiology ; *Cell Nucleus Division ; Cytoplasm/physiology ; Fungi/*genetics/growth & development/*physiology/ultrastructure ; }, abstract = {Within many fungal syncytia, nuclei behave independently despite sharing a common cytoplasm. Creation of independent nuclear zones of control in one cell is paradoxical considering random protein synthesis sites, predicted rapid diffusion rates, and well-mixed cytosol. In studying the surprising fungal nuclear autonomy, new principles of cellular organization are emerging. We discuss the current understanding of nuclear autonomy, focusing on asynchronous cell cycle progression where most work has been directed. Mechanisms underlying nuclear autonomy are diverse including mRNA localization, ploidy variability, and nuclear spacing control. With the challenges fungal syncytia face due to cytoplasmic size and shape, they serve as powerful models for uncovering new subcellular organization modes, variability sources among isogenic uninucleate cells, and the evolution of multicellularity.}, } @article {pmid26373338, year = {2015}, author = {Pascoe, B and Méric, G and Murray, S and Yahara, K and Mageiros, L and Bowen, R and Jones, NH and Jeeves, RE and Lappin-Scott, HM and Asakura, H and Sheppard, SK}, title = {Enhanced biofilm formation and multi-host transmission evolve from divergent genetic backgrounds in Campylobacter jejuni.}, journal = {Environmental microbiology}, volume = {17}, number = {11}, pages = {4779-4789}, pmid = {26373338}, issn = {1462-2920}, support = {//Wellcome Trust/United Kingdom ; 088786/C09/Z//Wellcome Trust/United Kingdom ; BB/I02464X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/L015080/1//Medical Research Council/United Kingdom ; }, mesh = {Biofilms/*growth & development ; Biological Evolution ; Campylobacter jejuni/classification/*genetics/isolation & purification ; *Genetic Background ; Genetic Variation/*genetics ; Genome-Wide Association Study ; Humans ; Oxygen/metabolism ; }, abstract = {Multicellular biofilms are an ancient bacterial adaptation that offers a protective environment for survival in hostile habitats. In microaerophilic organisms such as Campylobacter, biofilms play a key role in transmission to humans as the bacteria are exposed to atmospheric oxygen concentrations when leaving the reservoir host gut. Genetic determinants of biofilm formation differ between species, but little is known about how strains of the same species achieve the biofilm phenotype with different genetic backgrounds. Our approach combines genome-wide association studies with traditional microbiology techniques to investigate the genetic basis of biofilm formation in 102 Campylobacter jejuni isolates. We quantified biofilm formation among the isolates and identified hotspots of genetic variation in homologous sequences that correspond to variation in biofilm phenotypes. Thirteen genes demonstrated a statistically robust association including those involved in adhesion, motility, glycosylation, capsule production and oxidative stress. The genes associated with biofilm formation were different in the host generalist ST-21 and ST-45 clonal complexes, which are frequently isolated from multiple host species and clinical samples. This suggests the evolution of enhanced biofilm from different genetic backgrounds and a possible role in colonization of multiple hosts and transmission to humans.}, } @article {pmid26370559, year = {2015}, author = {Baskaran, P and Rödelsperger, C and Prabh, N and Serobyan, V and Markov, GV and Hirsekorn, A and Dieterich, C}, title = {Ancient gene duplications have shaped developmental stage-specific expression in Pristionchus pacificus.}, journal = {BMC evolutionary biology}, volume = {15}, number = {}, pages = {185}, pmid = {26370559}, issn = {1471-2148}, mesh = {Animals ; Biological Evolution ; Caenorhabditis elegans/genetics ; *Gene Duplication ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Library ; Larva/growth & development ; Multigene Family ; Nematoda/*genetics/growth & development ; Phylogeny ; }, abstract = {BACKGROUND: The development of multicellular organisms is accompanied by gene expression changes in differentiating cells. Profiling stage-specific expression during development may reveal important insights into gene sets that contributed to the morphological diversity across the animal kingdom.

RESULTS: We sequenced RNA-seq libraries throughout a developmental timecourse of the nematode Pristionchus pacificus. The transcriptomes reflect early larval stages, adult worms including late larvae, and growth-arrested dauer larvae and allowed the identification of developmentally regulated gene clusters. Our data reveals similar trends as previous transcriptome profiling of dauer worms and represents the first expression data for early larvae in P. pacificus. Gene expression clusters characterizing early larval stages show most significant enrichments of chaperones, while collagens are most significantly enriched in transcriptomes of late larvae and adult worms. By combining expression data with phylogenetic analysis, we found that developmentally regulated genes are found in paralogous clusters that have arisen through lineage-specific duplications after the split from the Caenorhabditis elegans branch.

CONCLUSIONS: We propose that gene duplications of developmentally regulated genes represent a plausible evolutionary mechanism to increase the dosage of stage-specific expression. Consequently, this may contribute to the substantial divergence in expression profiles that has been observed across larger evolutionary time scales.}, } @article {pmid26360326, year = {2015}, author = {Hale, R and Strutt, D}, title = {Conservation of Planar Polarity Pathway Function Across the Animal Kingdom.}, journal = {Annual review of genetics}, volume = {49}, number = {}, pages = {529-551}, doi = {10.1146/annurev-genet-112414-055224}, pmid = {26360326}, issn = {1545-2948}, support = {100986//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Body Patterning/physiology ; Cadherins/genetics/metabolism ; Cell Adhesion Molecules/genetics/metabolism ; Cell Polarity/*physiology ; Drosophila Proteins/genetics/*metabolism ; Signal Transduction ; Vertebrates/metabolism ; }, abstract = {Planar polarity is a well-studied phenomenon resulting in the directional coordination of cells in the plane of a tissue. In invertebrates and vertebrates, planar polarity is established and maintained by the largely independent core and Fat/Dachsous/Four-jointed (Ft-Ds-Fj) pathways. Loss of function of these pathways can result in a wide range of developmental or cellular defects, including failure of gastrulation and problems with placement and function of cilia. This review discusses the conservation of these pathways across the animal kingdom. The lack of vital core pathway components in basal metazoans suggests that the core planar polarity pathway evolved shortly after, but not necessarily alongside, the emergence of multicellularity.}, } @article {pmid26347030, year = {2015}, author = {Long, A and Liti, G and Luptak, A and Tenaillon, O}, title = {Elucidating the molecular architecture of adaptation via evolve and resequence experiments.}, journal = {Nature reviews. Genetics}, volume = {16}, number = {10}, pages = {567-582}, pmid = {26347030}, issn = {1471-0064}, support = {310944/ERC_/European Research Council/International ; R01 GM094929/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; Animals ; Bacteria/genetics ; Biological Evolution ; Drosophila melanogaster/genetics ; Epistasis, Genetic ; Evolution, Molecular ; Genetics, Microbial/methods ; Genetics, Population/*methods ; High-Throughput Nucleotide Sequencing ; Mutation ; RNA Folding ; *Selection, Genetic ; }, abstract = {Evolve and resequence (E&R) experiments use experimental evolution to adapt populations to a novel environment, then next-generation sequencing to analyse genetic changes. They enable molecular evolution to be monitored in real time on a genome-wide scale. Here, we review the field of E&R experiments across diverse systems, ranging from simple non-living RNA to bacteria, yeast and the complex multicellular organism Drosophila melanogaster. We explore how different evolutionary outcomes in these systems are largely consistent with common population genetics principles. Differences in outcomes across systems are largely explained by different starting population sizes, levels of pre-existing genetic variation, recombination rates and adaptive landscapes. We highlight emerging themes and inconsistencies that future experiments must address.}, } @article {pmid26344197, year = {2015}, author = {Wan, C and Borgeson, B and Phanse, S and Tu, F and Drew, K and Clark, G and Xiong, X and Kagan, O and Kwan, J and Bezginov, A and Chessman, K and Pal, S and Cromar, G and Papoulas, O and Ni, Z and Boutz, DR and Stoilova, S and Havugimana, PC and Guo, X and Malty, RH and Sarov, M and Greenblatt, J and Babu, M and Derry, WB and Tillier, ER and Wallingford, JB and Parkinson, J and Marcotte, EM and Emili, A}, title = {Panorama of ancient metazoan macromolecular complexes.}, journal = {Nature}, volume = {525}, number = {7569}, pages = {339-344}, pmid = {26344197}, issn = {1476-4687}, support = {F32GM112495/GM/NIGMS NIH HHS/United States ; R01 GM076536/GM/NIGMS NIH HHS/United States ; DP1 GM106408/GM/NIGMS NIH HHS/United States ; R01 GM067779/GM/NIGMS NIH HHS/United States ; //Canadian Institutes of Health Research/Canada ; F32 GM112495/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Datasets as Topic ; *Evolution, Molecular ; Humans ; Multiprotein Complexes/*chemistry/*metabolism ; Protein Interaction Mapping ; *Protein Interaction Maps ; Reproducibility of Results ; Systems Biology ; Tandem Mass Spectrometry ; }, abstract = {Macromolecular complexes are essential to conserved biological processes, but their prevalence across animals is unclear. By combining extensive biochemical fractionation with quantitative mass spectrometry, here we directly examined the composition of soluble multiprotein complexes among diverse metazoan models. Using an integrative approach, we generated a draft conservation map consisting of more than one million putative high-confidence co-complex interactions for species with fully sequenced genomes that encompasses functional modules present broadly across all extant animals. Clustering reveals a spectrum of conservation, ranging from ancient eukaryotic assemblies that have probably served cellular housekeeping roles for at least one billion years, ancestral complexes that have accrued contemporary components, and rarer metazoan innovations linked to multicellularity. We validated these projections by independent co-fractionation experiments in evolutionarily distant species, affinity purification and functional analyses. The comprehensiveness, centrality and modularity of these reconstructed interactomes reflect their fundamental mechanistic importance and adaptive value to animal cell systems.}, } @article {pmid26333839, year = {2015}, author = {Lorin, T and Salzburger, W and Böhne, A}, title = {Evolutionary Fate of the Androgen Receptor-Signaling Pathway in Ray-Finned Fishes with a Special Focus on Cichlids.}, journal = {G3 (Bethesda, Md.)}, volume = {5}, number = {11}, pages = {2275-2283}, pmid = {26333839}, issn = {2160-1836}, mesh = {Animals ; Cichlids/*genetics ; *Evolution, Molecular ; Fish Proteins/*genetics/metabolism ; Gene Duplication ; Receptors, Androgen/*genetics/metabolism ; Selection, Genetic ; Signal Transduction ; }, abstract = {The emergence of the steroid system is coupled to the evolution of multicellular animals. In vertebrates in particular, the steroid receptor repertoire has been shaped by genome duplications characteristic to this lineage. Here, we investigate for the first time the composition of the androgen receptor-signaling pathway in ray-finned fish genomes by focusing in particular on duplicates that emerged from the teleost-specific whole-genome duplication. We trace lineage- and species-specific duplications and gene losses for the genomic and nongenomic pathway of androgen signaling and subsequently investigate the sequence evolution of these genes. In one particular fish lineage, the cichlids, we find evidence for differing selection pressures acting on teleost-specific whole-genome duplication paralogs at a derived evolutionary stage. We then look into the expression of these duplicated genes in four cichlid species from Lake Tanganyika indicating, once more, rapid changes in expression patterns in closely related fish species. We focus on a particular case, the cichlid specific duplication of the rac1 GTPase, which shows possible signs of a neofunctionalization event.}, } @article {pmid26315993, year = {2015}, author = {Zhang, J and Debets, AJ and Verweij, PE and Melchers, WJ and Zwaan, BJ and Schoustra, SE}, title = {Asexual sporulation facilitates adaptation: The emergence of azole resistance in Aspergillus fumigatus.}, journal = {Evolution; international journal of organic evolution}, volume = {69}, number = {10}, pages = {2573-2586}, doi = {10.1111/evo.12763}, pmid = {26315993}, issn = {1558-5646}, mesh = {Adaptation, Biological/genetics ; Aspergillus fumigatus/*drug effects/*genetics ; Biological Evolution ; Drug Resistance, Multiple, Fungal/*genetics ; Fungicides, Industrial/*pharmacology ; Genes, Fungal ; *Mutation ; Reproduction, Asexual/*drug effects/*genetics ; *Selection, Genetic ; Triazoles/*pharmacology ; }, abstract = {Understanding the occurrence and spread of azole resistance in Aspergillus fumigatus is crucial for public health. It has been hypothesized that asexual sporulation, which is abundant in nature, is essential for phenotypic expression of azole resistance mutations in A. fumigatus facilitating subsequent spread through natural selection. Furthermore, the disease aspergilloma is associated with asexual sporulation within the lungs of patients and the emergence of azole resistance. This study assessed the evolutionary advantage of asexual sporulation by growing the fungus under pressure of one of five different azole fungicides over seven weeks and by comparing the rate of adaptation between scenarios of culturing with and without asexual sporulation. Results unequivocally show that asexual sporulation facilitates adaptation. This can be explained by the combination of more effective selection because of the transition from a multicellular to a unicellular stage, and by increased mutation supply due to the production of spores, which involves numerous mitotic divisions. Insights from this study are essential to unravel the resistance mechanisms of sporulating pathogens to chemical compounds and disease agents in general, and for designing strategies that prevent or overcome the emerging threat of azole resistance in particular.}, } @article {pmid26311623, year = {2015}, author = {Wegener Parfrey, L}, title = {Mock communities highlight the diversity of host-associated eukaryotes.}, journal = {Molecular ecology}, volume = {24}, number = {17}, pages = {4337-4339}, doi = {10.1111/mec.13311}, pmid = {26311623}, issn = {1365-294X}, mesh = {Animals ; Apicomplexa ; *Biodiversity ; Eukaryota ; *High-Throughput Nucleotide Sequencing ; Oligochaeta/microbiology ; *Soil Microbiology ; Symbiosis ; }, abstract = {Host-associated microbes are ubiquitous. Every multicellular eukaryote, and even many unicellular eukaryotes (protists), hosts a diverse community of microbes. High-throughput sequencing (HTS) tools have illuminated the vast diversity of host-associated microbes and shown that they have widespread influence on host biology, ecology and evolution (McFall-Ngai et al.). Bacteria receive most of the attention, but protists are also important components of microbial communities associated with humans (Parfrey et al.) and other hosts. As HTS tools are increasingly used to study eukaryotes, the presence of numerous and diverse host-associated eukaryotes is emerging as a common theme across ecosystems. Indeed, HTS studies demonstrate that host-associated lineages account for between 2 and 12% of overall eukaryotic sequences detected in soil, marine and freshwater data sets, with much higher relative abundances observed in some samples (Ramirez et al. ; Simon et al. ; de Vargas et al.). Previous studies in soil detected large numbers of predominantly parasitic lineages such as Apicomplexa, but did not delve into their origin [e.g. (Ramirez et al.)]. In this issue of Molecular Ecology, Geisen et al. () use mock communities to show that many of the eukaryotic organisms detected by environmental sequencing in soils are potentially associated with animal hosts rather than free-living. By isolating the host-associated fraction of soil microbial communities, Geisen and colleagues help explain the surprisingly high diversity of parasitic eukaryotic lineages often detected in soil/terrestrial studies using high-throughput sequencing (HTS) and reinforce the ubiquity of these host-associated microbes. It is clear that we can no longer assume that organisms detected in bulk environmental sequencing are free-living, but instead need to design studies that specifically enumerate the diversity and function of host-associated eukaryotes. Doing so will allow the field to determine the role host-associated eukaryotes play in soils and other environments and to evaluate hypotheses on assembly of host-associated communities, disease ecology and more.}, } @article {pmid26307549, year = {2015}, author = {McCormack, R and Podack, ER}, title = {Perforin-2/Mpeg1 and other pore-forming proteins throughout evolution.}, journal = {Journal of leukocyte biology}, volume = {98}, number = {5}, pages = {761-768}, pmid = {26307549}, issn = {1938-3673}, support = {F31AI106290/AI/NIAID NIH HHS/United States ; R56AI107062/AI/NIAID NIH HHS/United States ; R01 NR015649/NR/NINR NIH HHS/United States ; R01AI110810/AI/NIAID NIH HHS/United States ; R56 AI107062/AI/NIAID NIH HHS/United States ; F31 AI106290/AI/NIAID NIH HHS/United States ; R01 AI110810/AI/NIAID NIH HHS/United States ; R01NR015649/NR/NINR NIH HHS/United States ; }, mesh = {Animals ; Complement Membrane Attack Complex/*immunology ; *Evolution, Molecular ; Humans ; Membrane Proteins/*immunology ; Pore Forming Cytotoxic Proteins/*immunology ; Protein Structure, Tertiary ; }, abstract = {Development of the ancient innate immune system required not only a mechanism to recognize foreign organisms from self but also to destroy them. Pore-forming proteins containing the membrane attack complex Perforin domain were one of the first triumphs of an innate immune system needing to eliminate microbes and virally infected cells. Membrane attack complex of complement and Perforin domain proteins is unique from other immune effector molecules in that the mechanism of attack is strictly physical and unspecific. The large water-filled holes created by membrane attack complex of complement and Perforin domain pore formation allow access for additional effectors to complete the destruction of the foreign organism via chemical or enzymatic attack. Perforin-2/macrophage-expressed protein 1 is one of the oldest membrane attack complexes of complement and Perforin domain protein involved in immune defense, and it is still functional today in vertebrates. Here, we trace the impact of Perforin-2/macrophage-expressed protein 1 from the earliest multicellular organisms to modern vertebrates, as well as review the development of other membrane attack complexes of complement and Perforin domain member proteins.}, } @article {pmid26293347, year = {2015}, author = {Vázquez, E and Antequera, F}, title = {Replication dynamics in fission and budding yeasts through DNA polymerase tracking.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {37}, number = {10}, pages = {1067-1073}, pmid = {26293347}, issn = {1521-1878}, mesh = {DNA ; *DNA Replication ; DNA, Fungal/metabolism ; DNA-Directed DNA Polymerase/analysis/*metabolism ; Genome, Fungal ; Genomic Instability ; Replication Origin ; Saccharomyces cerevisiae/genetics ; Saccharomycetales/*genetics ; Schizosaccharomyces/*genetics ; }, abstract = {The dynamics of eukaryotic DNA polymerases has been difficult to establish because of the difficulty of tracking them along the chromosomes during DNA replication. Recent work has addressed this problem in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae through the engineering of replicative polymerases to render them prone to incorporating ribonucleotides at high rates. Their use as tracers of the passage of each polymerase has provided a picture of unprecedented resolution of the organization of replicons and replication origins in the two yeasts and has uncovered important differences between them. Additional studies have found an overlapping distribution of DNA polymorphisms and the junctions of Okazaki fragments along mononucleosomal DNA. This sequence instability is caused by the premature release of polymerase δ and the retention of non proof-read DNA tracts replicated by polymerase α. The possible implementation of these new experimental approaches in multicellular organisms opens the door to the analysis of replication dynamics under a broad range of genetic backgrounds and physiological or pathological conditions.}, } @article {pmid26286983, year = {2015}, author = {Godfrey-Smith, P}, title = {Reproduction, symbiosis, and the eukaryotic cell.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {33}, pages = {10120-10125}, pmid = {26286983}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Eukaryotic Cells/*physiology ; Humans ; Mitochondria/physiology ; Models, Biological ; *Reproduction ; Selection, Genetic ; Social Behavior ; *Symbiosis ; }, abstract = {This paper develops a conceptual framework for addressing questions about reproduction, individuality, and the units of selection in symbiotic associations, with special attention to the origin of the eukaryotic cell. Three kinds of reproduction are distinguished, and a possible evolutionary sequence giving rise to a mitochondrion-containing eukaryotic cell from an endosymbiotic partnership is analyzed as a series of transitions between each of the three forms of reproduction. The sequence of changes seen in this "egalitarian" evolutionary transition is compared with those that apply in "fraternal" transitions, such as the evolution of multicellularity in animals.}, } @article {pmid26284972, year = {2015}, author = {Du, Q and Kawabe, Y and Schilde, C and Chen, ZH and Schaap, P}, title = {The Evolution of Aggregative Multicellularity and Cell-Cell Communication in the Dictyostelia.}, journal = {Journal of molecular biology}, volume = {427}, number = {23}, pages = {3722-3733}, pmid = {26284972}, issn = {1089-8638}, support = {100293//Wellcome Trust/United Kingdom ; 100293/Z/12/Z//Wellcome Trust/United Kingdom ; BB/K000799/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Cyclic AMP/genetics/*metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cyclic GMP/analogs & derivatives/metabolism ; Dictyostelium/metabolism/*physiology ; Genome, Protozoan ; Genomics/methods ; Hexanones/metabolism ; Histidine Kinase ; Protein Kinases/metabolism ; Protozoan Proteins/genetics/*metabolism ; Quorum Sensing ; Signal Transduction ; }, abstract = {Aggregative multicellularity, resulting in formation of a spore-bearing fruiting body, evolved at least six times independently amongst both eukaryotes and prokaryotes. Amongst eukaryotes, this form of multicellularity is mainly studied in the social amoeba Dictyostelium discoideum. In this review, we summarise trends in the evolution of cell-type specialisation and behavioural complexity in the four major groups of Dictyostelia. We describe the cell-cell communication systems that control the developmental programme of D. discoideum, highlighting the central role of cAMP in the regulation of cell movement and cell differentiation. Comparative genomic studies showed that the proteins involved in cAMP signalling are deeply conserved across Dictyostelia and their unicellular amoebozoan ancestors. Comparative functional analysis revealed that cAMP signalling in D. discoideum originated from a second messenger role in amoebozoan encystation. We highlight some molecular changes in cAMP signalling genes that were responsible for the novel roles of cAMP in multicellular development.}, } @article {pmid26268215, year = {2015}, author = {Burgess, AL and David, R and Searle, IR}, title = {Conservation of tRNA and rRNA 5-methylcytosine in the kingdom Plantae.}, journal = {BMC plant biology}, volume = {15}, number = {}, pages = {199}, pmid = {26268215}, issn = {1471-2229}, mesh = {5-Methylcytosine/*metabolism ; Cell Nucleus/genetics ; Chloroplasts/genetics ; *Evolution, Molecular ; Methylation ; Methyltransferases/genetics ; Mitochondria/genetics ; Phylogeny ; Plants/*genetics/metabolism ; RNA, Transfer/*genetics/metabolism ; RNA, Untranslated/genetics ; Transcriptome ; }, abstract = {BACKGROUND: Post-transcriptional methylation of RNA cytosine residues to 5-methylcytosine (m(5)C) is an important modification that regulates RNA metabolism and occurs in both eukaryotes and prokaryotes. Yet, to date, no transcriptome-wide identification of m(5)C sites has been undertaken in plants. Plants provide a unique comparative system for investigating the origin and evolution of m(5)C as they contain three different genomes, the nucleus, mitochondria and chloroplast. Here we use bisulfite conversion of RNA combined with high-throughput IIlumina sequencing (RBS-seq) to identify single-nucleotide resolution of m(5)C sites in non-coding ribosomal RNAs and transfer RNAs of all three sub-cellular transcriptomes across six diverse species that included, the single-celled algae Nannochloropsis oculata, the macro algae Caulerpa taxifolia and multi-cellular higher plants Arabidopsis thaliana, Brassica rapa, Triticum durum and Ginkgo biloba.

RESULTS: Using the plant model Arabidopsis thaliana, we identified a total of 39 highly methylated m(5)C sites in predicted structural positions of nuclear tRNAs and 7 m(5)C sites in rRNAs from nuclear, chloroplast and mitochondrial transcriptomes. Both the nucleotide position and percent methylation of tRNAs and rRNAs m(5)C sites were conserved across all species analysed, from single celled algae N. oculata to multicellular plants. Interestingly the mitochondrial and chloroplast encoded tRNAs were devoid of m(5)C in A. thaliana and this is generally conserved across Plantae. This suggests independent evolution of organelle methylation in animals and plants, as animal mitochondrial tRNAs have m(5)C sites. Here we characterize 5 members of the RNA 5-methylcytosine family in Arabidopsis and extend the functional characterization of TRDMT1 and NOP2A/OLI2. We demonstrate that nuclear tRNA methylation requires two evolutionarily conserved methyltransferases, TRDMT1 and TRM4B. trdmt1 trm4b double mutants are hypersensitive to the antibiotic hygromycin B, demonstrating the function of tRNA methylation in regulating translation. Additionally we demonstrate that nuclear large subunit 25S rRNA methylation requires the conserved RNA methyltransferase NSUN5. Our results also suggest functional redundancy of at least two of the NOP2 paralogs in Arabidopsis.

CONCLUSIONS: Our data demonstrates widespread occurrence and conservation of non-coding RNA methylation in the kingdom Plantae, suggesting important and highly conserved roles of this post-transcriptional modification.}, } @article {pmid26248158, year = {2015}, author = {Palfree, RG and Bennett, HP and Bateman, A}, title = {The Evolution of the Secreted Regulatory Protein Progranulin.}, journal = {PloS one}, volume = {10}, number = {8}, pages = {e0133749}, pmid = {26248158}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Databases, Genetic ; *Evolution, Molecular ; Fungi/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism ; Likelihood Functions ; Molecular Sequence Data ; Plants/metabolism ; Progranulins ; Protein Structure, Tertiary ; Sequence Alignment ; }, abstract = {Progranulin is a secreted growth factor that is active in tumorigenesis, wound repair, and inflammation. Haploinsufficiency of the human progranulin gene, GRN, causes frontotemporal dementia. Progranulins are composed of chains of cysteine-rich granulin modules. Modules may be released from progranulin by proteolysis as 6kDa granulin polypeptides. Both intact progranulin and some of the granulin polypeptides are biologically active. The granulin module occurs in certain plant proteases and progranulins are present in early diverging metazoan clades such as the sponges, indicating their ancient evolutionary origin. There is only one Grn gene in mammalian genomes. More gene-rich Grn families occur in teleost fish with between 3 and 6 members per species including short-form Grns that have no tetrapod counterparts. Our goals are to elucidate progranulin and granulin module evolution by investigating (i): the origins of metazoan progranulins (ii): the evolutionary relationships between the single Grn of tetrapods and the multiple Grn genes of fish (iii): the evolution of granulin module architectures of vertebrate progranulins (iv): the conservation of mammalian granulin polypeptide sequences and how the conserved granulin amino acid sequences map to the known three dimensional structures of granulin modules. We report that progranulin-like proteins are present in unicellular eukaryotes that are closely related to metazoa suggesting that progranulin is among the earliest extracellular regulatory proteins still employed by multicellular animals. From the genomes of the elephant shark and coelacanth we identified contemporary representatives of a precursor for short-from Grn genes of ray-finned fish that is lost in tetrapods. In vertebrate Grns pathways of exon duplication resulted in a conserved module architecture at the amino-terminus that is frequently accompanied by an unusual pattern of tandem nearly identical module repeats near the carboxyl-terminus. Polypeptide sequence conservation of mammalian granulin modules identified potential structure-activity relationships that may be informative in designing progranulin based therapeutics.}, } @article {pmid26247819, year = {2015}, author = {Ferrante, E and Turgut, AE and Duéñez-Guzmán, E and Dorigo, M and Wenseleers, T}, title = {Evolution of Self-Organized Task Specialization in Robot Swarms.}, journal = {PLoS computational biology}, volume = {11}, number = {8}, pages = {e1004273}, pmid = {26247819}, issn = {1553-7358}, mesh = {Animals ; Ants/physiology ; *Artificial Intelligence ; *Biological Evolution ; Computational Biology ; *Models, Biological ; *Robotics/instrumentation/methods ; *Social Behavior ; Task Performance and Analysis ; Work ; }, abstract = {Division of labor is ubiquitous in biological systems, as evidenced by various forms of complex task specialization observed in both animal societies and multicellular organisms. Although clearly adaptive, the way in which division of labor first evolved remains enigmatic, as it requires the simultaneous co-occurrence of several complex traits to achieve the required degree of coordination. Recently, evolutionary swarm robotics has emerged as an excellent test bed to study the evolution of coordinated group-level behavior. Here we use this framework for the first time to study the evolutionary origin of behavioral task specialization among groups of identical robots. The scenario we study involves an advanced form of division of labor, common in insect societies and known as "task partitioning", whereby two sets of tasks have to be carried out in sequence by different individuals. Our results show that task partitioning is favored whenever the environment has features that, when exploited, reduce switching costs and increase the net efficiency of the group, and that an optimal mix of task specialists is achieved most readily when the behavioral repertoires aimed at carrying out the different subtasks are available as pre-adapted building blocks. Nevertheless, we also show for the first time that self-organized task specialization could be evolved entirely from scratch, starting only from basic, low-level behavioral primitives, using a nature-inspired evolutionary method known as Grammatical Evolution. Remarkably, division of labor was achieved merely by selecting on overall group performance, and without providing any prior information on how the global object retrieval task was best divided into smaller subtasks. We discuss the potential of our method for engineering adaptively behaving robot swarms and interpret our results in relation to the likely path that nature took to evolve complex sociality and task specialization.}, } @article {pmid26247630, year = {2015}, author = {Le, LT and Couvet, M and Favier, B and Coll, JL and Nguyen, CH and Molla, A}, title = {Discovery of benzo[e]pyridoindolones as kinase inhibitors that disrupt mitosis exit while erasing AMPK-Thr172 phosphorylation on the spindle.}, journal = {Oncotarget}, volume = {6}, number = {26}, pages = {22152-22166}, pmid = {26247630}, issn = {1949-2553}, mesh = {AMP-Activated Protein Kinases/*antagonists & inhibitors ; Animals ; Aurora Kinase B/*antagonists & inhibitors ; Drug Screening Assays, Antitumor ; Female ; HeLa Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; Indoles/chemistry/*pharmacology ; Mice ; Mitosis/*drug effects ; Phosphorylation/drug effects ; Protein Kinase Inhibitors/*pharmacology ; Pyridines/chemistry/*pharmacology ; Random Allocation ; Spheroids, Cellular ; Xenograft Model Antitumor Assays ; }, abstract = {Aurora kinases play an essential role in mitotic progression and are attractive targets in cancer therapy. The first generation of benzo[e]pyridoindole exhibited powerful aurora kinase inhibition but their low solubility limited further development. Grafting a pyperidine-ethoxy group gives rise to a hydrosoluble inhibitor: compound C5M.C5M could efficiently inhibit the proliferation of cells from different origins. C5M prevented cell cycling, induced a strong mitotic arrest then, cells became polyploid and finally died. C5M did not impair the spindle checkpoint, the separation of the sister chromatids and the transfer of aurora B on the mid-zone. C5M prevented histone H3 phosphorylation at mitotic entry and erased AMPK-Thr172 phosphorylation in late mitosis. With this unique profile of inhibition, C5M could be useful for understanding the role of phospho-Thr172-AMPK in abscission and the relationship between the chromosomal complex and the energy sensing machinery.C5M is a multikinase inhibitor with interesting preclinical characteristics: high hydro-solubility and a good stability in plasma. A single dose prevents the expansion of multicellular spheroids. C5M can safely be injected to mice and reduces significantly the development of xenograft. The next step will be to define the protocol of treatment and the cancer therapeutic field of this new anti-proliferative drug.}, } @article {pmid26245677, year = {2015}, author = {Yang, EC and Kim, KM and Kim, SY and Lee, J and Boo, GH and Lee, JH and Nelson, WA and Yi, G and Schmidt, WE and Fredericq, S and Boo, SM and Bhattacharya, D and Yoon, HS}, title = {Highly Conserved Mitochondrial Genomes among Multicellular Red Algae of the Florideophyceae.}, journal = {Genome biology and evolution}, volume = {7}, number = {8}, pages = {2394-2406}, pmid = {26245677}, issn = {1759-6653}, mesh = {Conserved Sequence ; *Evolution, Molecular ; *Genome, Mitochondrial ; Molecular Sequence Data ; Phylogeny ; Plant Proteins/genetics ; Rhodophyta/classification/*genetics ; Synteny ; }, abstract = {Two red algal classes, the Florideophyceae (approximately 7,100 spp.) and Bangiophyceae (approximately 193 spp.), comprise 98% of red algal diversity in marine and freshwater habitats. These two classes form well-supported monophyletic groups in most phylogenetic analyses. Nonetheless, the interordinal relationships remain largely unresolved, in particular in the largest subclass Rhodymeniophycidae that includes 70% of all species. To elucidate red algal phylogenetic relationships and study organelle evolution, we determined the sequence of 11 mitochondrial genomes (mtDNA) from 5 florideophycean subclasses. These mtDNAs were combined with existing data, resulting in a database of 25 florideophytes and 12 bangiophytes (including cyanidiophycean species). A concatenated alignment of mt proteins was used to resolve ordinal relationships in the Rhodymeniophycidae. Red algal mtDNA genome comparisons showed 47 instances of gene rearrangement including 12 that distinguish Bangiophyceae from Hildenbrandiophycidae, and 5 that distinguish Hildenbrandiophycidae from Nemaliophycidae. These organelle data support a rapid radiation and surprisingly high conservation of mtDNA gene syntheny among the morphologically divergent multicellular lineages of Rhodymeniophycidae. In contrast, we find extensive mitochondrial gene rearrangements when comparing Bangiophyceae and Florideophyceae and multiple examples of gene loss among the different red algal lineages.}, } @article {pmid26239915, year = {2015}, author = {Sinkovics, JG}, title = {The cnidarian origin of the proto-oncogenes NF-κB/STAT and WNT-like oncogenic pathway drives the ctenophores (Review).}, journal = {International journal of oncology}, volume = {47}, number = {4}, pages = {1211-1229}, pmid = {26239915}, issn = {1791-2423}, mesh = {Animals ; Cnidaria/*physiology ; Ctenophora/*physiology ; Humans ; Lymphoma/*metabolism ; NF-kappa B/*metabolism ; Proto-Oncogenes/physiology ; Wnt Proteins/*metabolism ; Wnt Signaling Pathway/*physiology ; }, abstract = {The cell survival pathways of the diploblastic early multicellular eukaryotic hosts contain and operate the molecular machinery resembling those of malignantly transformed individual cells of highly advanced multicellular hosts (including Homo). In the present review, the STAT/NF-κB pathway of the cnidarian Nematostella vectensis is compared with that of human tumors (malignant lymphomas, including Reed-Sternberg cells) pointing out similarities, including possible viral initiation in both cases. In the ctenophore genome and proteome, β-catenin gains intranuclear advantages due to a physiologically weak destructive complex in the cytoplasm, and lack of natural inhibitors (the dickkopfs). Thus, a scenario similar to what tumor cells initiate and achieve is presented through several constitutive loss-of-function type mutations in the destructive complex and in the elimination of inhibitors. Vice versa, malignantly transformed individual cells of advanced multicellular hosts assume pheno-genotypic resemblance to cells of unicellular or early multicellular hosts, and presumably to their ancient predecessors, by returning to the semblance of immortality and to the resumption of the state of high degree of resistance to physicochemical insults. Human leukemogenic and oncogenic pathways are presented for comparisons. The supreme bioengineers RNA/DNA complex encoded both the malignantly transformed immortal cell and the human cerebral cortex. The former generates molecules for the immortality of cellular life in the Universe. The latter invents the inhibitors of the process in order to gain control over it.}, } @article {pmid26237574, year = {2015}, author = {Singh, RK and Pandey, SP}, title = {Evolution of structural and functional diversification among plant Argonautes.}, journal = {Plant signaling & behavior}, volume = {10}, number = {10}, pages = {e1069455}, pmid = {26237574}, issn = {1559-2324}, mesh = {Argonaute Proteins/*genetics/metabolism ; Biological Evolution ; Bryophyta/genetics/metabolism ; Chlamydomonas/genetics/metabolism ; *Evolution, Molecular ; *Gene Expression Regulation, Plant ; *Gene Silencing ; *Genes, Plant ; Oryza/genetics/metabolism ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Plants/*genetics/metabolism ; }, abstract = {Argonautes (AGOs) are the effector proteins of the RNA-induced silencing (RISC) complex, formed during the phenomena of small-RNA mediated post-transcriptional gene silencing. AGOs are a large family of proteins; their number varies from a few (4 in Chlamydomonas reinhardtii) to many (18 in Oryza sativa) in plants. Genetics-guided analysis have demonstrated the roles of some of the AGOs during growth and development of plants. Biochemical studies have further revealed differences in functional specificities among AGOs. How the AGO family expanded in different plant species during the course of evolution is starting to emerge. We hypothesized that 4 classes of AGOs evolved after divergence of unicellular green algae when an ancestral AGO underwent duplication events. Evolution of multicellularity may have coincided with the diversification of AGOs. A comparative sequence and structure analysis of the plant AGOs, including those from the mosses and the unicellular algae, show not only conformational differences between those from lower and higher plants, but also functional divergence of important sites.}, } @article {pmid26227665, year = {2015}, author = {Park, S and Lehner, B}, title = {Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types.}, journal = {Molecular systems biology}, volume = {11}, number = {7}, pages = {824}, pmid = {26227665}, issn = {1744-4292}, mesh = {Cell Plasticity ; *Epistasis, Genetic ; Gene Expression Regulation, Neoplastic ; *Genes, Neoplasm ; Genetic Predisposition to Disease ; Humans ; Neoplasms/*genetics ; Polymorphism, Single Nucleotide ; }, abstract = {Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expected from their individual effects. In a stringent statistical analysis of data from > 3,000 tumors, we find that the co-occurrence and mutual exclusivity relationships between cancer driver alterations change quite extensively in different types of cancer. This cannot be accounted for by variation in tumor heterogeneity or unrecognized cancer subtypes. Rather, it suggests that how genomic alterations interact cooperatively or partially redundantly to driver cancer changes in different types of cancers. This re-wiring of epistasis across cell types is likely to be a basic feature of genetic architecture, with important implications for understanding the evolution of multicellularity and human genetic diseases. In addition, if this plasticity of epistasis across cell types is also true for synthetic lethal interactions, a synthetic lethal strategy to kill cancer cells may frequently work in one type of cancer but prove ineffective in another.}, } @article {pmid26216949, year = {2015}, author = {Chen, L and Rashid, F and Shah, A and Awan, HM and Wu, M and Liu, A and Wang, J and Zhu, T and Luo, Z and Shan, G}, title = {The isolation of an RNA aptamer targeting to p53 protein with single amino acid mutation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {32}, pages = {10002-10007}, pmid = {26216949}, issn = {1091-6490}, mesh = {Administration, Intravenous ; Amino Acid Substitution ; Amino Acids/*genetics ; Animals ; Aptamers, Nucleotide/*isolation & purification ; Base Sequence ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; HEK293 Cells ; HeLa Cells ; Humans ; Mice ; Molecular Sequence Data ; Mutant Proteins/metabolism ; Mutation/*genetics ; Nanoparticles/chemistry ; Neoplasms/pathology ; SELEX Aptamer Technique ; Tumor Suppressor Protein p53/*genetics/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {p53, known as a tumor suppressor, is a DNA binding protein that regulates cell cycle, activates DNA repair proteins, and triggers apoptosis in multicellular animals. More than 50% of human cancers contain a mutation or deletion of the p53 gene, and p53R175 is one of the hot spots of p53 mutation. Nucleic acid aptamers are short single-stranded oligonucleotides that are able to bind various targets, and they are typically isolated from an experimental procedure called systematic evolution of ligand exponential enrichment (SELEX). Using a previously unidentified strategy of contrast screening with SELEX, we have isolated an RNA aptamer targeting p53R175H. This RNA aptamer (p53R175H-APT) has a significantly stronger affinity to p53R175H than to the wild-type p53 in both in vitro and in vivo assays. p53R175H-APT decreased the growth rate, weakened the migration capability, and triggered apoptosis in human lung cancer cells harboring p53R175H. Further analysis actually indicated that p53R175H-APT might partially rescue or correct the p53R175H to function more like the wild-type p53. In situ injections of p53R175H-APT to the tumor xenografts confirmed the effects of this RNA aptamer on p53R175H mutation in mice.}, } @article {pmid26206087, year = {2016}, author = {Causeret, F and Sumia, I and Pierani, A}, title = {Kremen1 and Dickkopf1 control cell survival in a Wnt-independent manner.}, journal = {Cell death and differentiation}, volume = {23}, number = {2}, pages = {323-332}, pmid = {26206087}, issn = {1476-5403}, mesh = {Animals ; Apoptosis ; Cell Survival ; Embryo Culture Techniques ; Evolution, Molecular ; HEK293 Cells ; Humans ; Intercellular Signaling Peptides and Proteins/*physiology ; Membrane Proteins/*physiology ; Mice ; Mutation ; Neoplasms/genetics ; Wnt Proteins/metabolism ; *Wnt Signaling Pathway ; }, abstract = {In multicellular organisms, a tight control of cell death is required to ensure normal development and tissue homeostasis. Improper function of apoptotic or survival pathways can not only affect developmental programs but also favor cancer progression. Here we describe a novel apoptotic signaling pathway involving the transmembrane receptor Kremen1 and its ligand, the Wnt-antagonist Dickkopf1. Using a whole embryo culture system, we first show that Dickkopf1 treatment promotes cell survival in a mouse model exhibiting increased apoptosis in the developing neural plate. Remarkably, this effect was not recapitulated by chemical Wnt inhibition. We then show that Dickkopf1 receptor Kremen1 is a bona fide dependence receptor, triggering cell death unless bound to its ligand. We performed Wnt-activity assays to demonstrate that the pro-apoptotic and anti-Wnt functions mediated by Kremen1 are strictly independent. Furthermore, we combined phylogenetic and mutagenesis approaches to identify a specific motif in the cytoplasmic tail of Kremen1, which is (i) specifically conserved in the lineage of placental mammals and (ii) strictly required for apoptosis induction. Finally, we show that somatic mutations of kremen1 found in human cancers can affect its pro-apoptotic activity, supporting a tumor suppressor function. Our findings thus reveal a new Wnt-independent function for Kremen1 and Dickkopf1 in the regulation of cell survival with potential implications in cancer therapies.}, } @article {pmid26199361, year = {2015}, author = {Nores, MJ and López, HA and Anton, AM and Rudall, PJ}, title = {Contrasting models of the female reproductive tract in four o'clocks (Nyctaginaceae).}, journal = {American journal of botany}, volume = {102}, number = {7}, pages = {1026-1039}, doi = {10.3732/ajb.1400521}, pmid = {26199361}, issn = {1537-2197}, mesh = {Biological Evolution ; Cluster Analysis ; Fertilization ; Flowers/genetics/*ultrastructure ; *Models, Structural ; Nyctaginaceae/genetics/*ultrastructure ; Pollen Tube/genetics/ultrastructure ; Pollination ; Reproduction ; Species Specificity ; }, abstract = {UNLABELLED: •

PREMISE OF THE STUDY: In angiosperms, several carpel tissues are specialized to facilitate pollen-tube elongation to achieve fertilization. We evaluated the possible evolutionary pathways of the diverse female reproductive tracts in Nyctaginaceae.•

METHODS: We studied the anatomy of a range of species representing different tribes, using light, fluorescence, scanning electron, and transmission electron microscopy.•

KEY RESULTS: Stigmas have multicellular, multiseriate papillae, except for Boerhavia diffusa with unicellular papillae. The styles are solid, with a strand of transmitting tissue linking the stigma with the ventral ovary wall. In Allionia, Boerhavia, and Mirabilis, the transmitting tissue branches into two independent tracts at the base of the ovary and continues across the lateral margins of the funicle to the micropyle; it is composed of cells with thick walls surrounded by abundant extracellular matrix. Bougainvillea, Pisonia, and Pisoniella have a diffuse transmitting tissue and an obturator, a proliferation of cells covered by a layer of secretory papillae that encloses the funicle, placenta, and ventral wall of the gynoecium and contacts with the micropyle.•

CONCLUSIONS: We propose two models of female reproductive tract, (A) one in which an obturator is absent and the transmitting tissue is compact and branched and (B) one in which an obturator is present and the transmitting tissue is diffuse. On the basis of character optimization, we hypothesize that model B represents the ancestral (plesiomorphic) condition in the family and model A originated once during evolution, within the tribe Nyctagineae.}, } @article {pmid26198319, year = {2015}, author = {Ramilowski, JA and Goldberg, T and Harshbarger, J and Kloppmann, E and Lizio, M and Satagopam, VP and Itoh, M and Kawaji, H and Carninci, P and Rost, B and Forrest, AR}, title = {A draft network of ligand-receptor-mediated multicellular signalling in human.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {7866}, pmid = {26198319}, issn = {2041-1723}, support = {U54 GM095315/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Cell Communication ; Evolution, Molecular ; Humans ; Ligands ; Receptors, Cell Surface/*metabolism ; Software ; }, abstract = {Cell-to-cell communication across multiple cell types and tissues strictly governs proper functioning of metazoans and extensively relies on interactions between secreted ligands and cell-surface receptors. Herein, we present the first large-scale map of cell-to-cell communication between 144 human primary cell types. We reveal that most cells express tens to hundreds of ligands and receptors to create a highly connected signalling network through multiple ligand-receptor paths. We also observe extensive autocrine signalling with approximately two-thirds of partners possibly interacting on the same cell type. We find that plasma membrane and secreted proteins have the highest cell-type specificity, they are evolutionarily younger than intracellular proteins, and that most receptors had evolved before their ligands. We provide an online tool to interactively query and visualize our networks and demonstrate how this tool can reveal novel cell-to-cell interactions with the prediction that mast cells signal to monoblastic lineages via the CSF1-CSF1R interacting pair.}, } @article {pmid26195746, year = {2015}, author = {Speijer, D and Lukeš, J and Eliáš, M}, title = {Sex is a ubiquitous, ancient, and inherent attribute of eukaryotic life.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {29}, pages = {8827-8834}, pmid = {26195746}, issn = {1091-6490}, mesh = {Cell Fusion ; Eukaryotic Cells/*physiology ; Genome ; Meiosis ; Mitochondria/metabolism ; Molecular Sequence Data ; Reactive Oxygen Species/metabolism ; *Reproduction ; Sequence Analysis, DNA ; }, abstract = {Sexual reproduction and clonality in eukaryotes are mostly seen as exclusive, the latter being rather exceptional. This view might be biased by focusing almost exclusively on metazoans. We analyze and discuss reproduction in the context of extant eukaryotic diversity, paying special attention to protists. We present results of phylogenetically extended searches for homologs of two proteins functioning in cell and nuclear fusion, respectively (HAP2 and GEX1), providing indirect evidence for these processes in several eukaryotic lineages where sex has not been observed yet. We argue that (i) the debate on the relative significance of sex and clonality in eukaryotes is confounded by not appropriately distinguishing multicellular and unicellular organisms; (ii) eukaryotic sex is extremely widespread and already present in the last eukaryotic common ancestor; and (iii) the general mode of existence of eukaryotes is best described by clonally propagating cell lines with episodic sex triggered by external or internal clues. However, important questions concern the relative longevity of true clonal species (i.e., species not able to return to sexual procreation anymore). Long-lived clonal species seem strikingly rare. We analyze their properties in the light of meiotic sex development from existing prokaryotic repair mechanisms. Based on these considerations, we speculate that eukaryotic sex likely developed as a cellular survival strategy, possibly in the context of internal reactive oxygen species stress generated by a (proto) mitochondrion. Thus, in the context of the symbiogenic model of eukaryotic origin, sex might directly result from the very evolutionary mode by which eukaryotic cells arose.}, } @article {pmid26194954, year = {2015}, author = {Wynns, AA}, title = {Convergent evolution of highly reduced fruiting bodies in Pezizomycotina suggests key adaptations to the bee habitat.}, journal = {BMC evolutionary biology}, volume = {15}, number = {}, pages = {145}, pmid = {26194954}, issn = {1471-2148}, mesh = {Animals ; Ascomycota/*classification/genetics/*isolation & purification/physiology ; Bees/microbiology/*physiology ; *Biological Evolution ; DNA, Fungal/genetics ; DNA, Ribosomal/genetics ; Ecosystem ; Phylogeny ; }, abstract = {BACKGROUND: Among the understudied fungi found in nature are those living in close association with social and solitary bees. The bee-specialist genera Bettsia, Ascosphaera and Eremascus are remarkable not only for their specialized niche but also for their simple fruiting bodies or ascocarps, which are morphologically anomalous in Pezizomycotina. Bettsia and Ascosphaera are characterized by a unicellular cyst-like cleistothecium known as a spore cyst, while Eremascus is characterized by completely naked asci, or asci not formed within a protective ascocarp. Before molecular phylogenetics the placement of these genera within Pezizomycotina remained tentative; morphological characters were misleading because they do not produce multicellular ascocarps, a defining character of Pezizomycotina. Because of their unique fruiting bodies, the close relationship of these bee-specialist fungi and their monophyly appeared certain. However, recent molecular studies have shown that Bettsia is not closely related to Ascosphaera. In this study, I isolated the very rare fungus Eremascus fertilis (Ascomycota, Pezizomycotina) from the bee bread of honey bees. These isolates represent the second report of E. fertilis both in nature and in the honey bee hive. To establish the systematic position of E. fertilis and Bettsia alvei, I performed phylogenetic analyses of nuclear ribosomal LSU + SSU DNA sequences from these species and 63 additional ascomycetes.

RESULTS: The phylogenetic analyses revealed that Eremascus is not monophyletic. Eremascus albus is closely related to Ascosphaera in Eurotiomycetes while E. fertilis belongs in Myxotrichaceae, a putative member of Leotiomycetes. Bettsia is not closely related to Ascosphaera and like E. fertilis apparently belongs in Leotiomycetes. These results indicate that both the naked ascus and spore cyst evolved twice in the Pezizomycotina and in distantly related lineages. The new genus Skoua is described to accommodate E. fertilis.

CONCLUSIONS: The naked ascus and spore cyst are both shown to have evolved convergently within the bee habitat. The convergent evolution of these unusual ascocarps is hypothesized to be adaptive for bee-mediated dispersal. Elucidating the dispersal strategies of these fungal symbionts contributes to our understanding of their interaction with bees and provides insight into the factors which potentially drive the evolution of reduced ascocarps in Pezizomycotina.}, } @article {pmid26193902, year = {2015}, author = {Greaves, M}, title = {Evolutionary determinants of cancer.}, journal = {Cancer discovery}, volume = {5}, number = {8}, pages = {806-820}, pmid = {26193902}, issn = {2159-8290}, support = {/WT_/Wellcome Trust/United Kingdom ; 105104/WT_/Wellcome Trust/United Kingdom ; 11021/LLR_/Blood Cancer UK/United Kingdom ; 105104/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Clonal Evolution ; Evolution, Molecular ; Humans ; Neoplasms/epidemiology/*etiology ; Neoplastic Stem Cells/metabolism ; Risk ; }, abstract = {UNLABELLED: Our understanding of cancer is being transformed by exploring clonal diversity, drug resistance, and causation within an evolutionary framework. The therapeutic resilience of advanced cancer is a consequence of its character as a complex, dynamic, and adaptive ecosystem engendering robustness, underpinned by genetic diversity and epigenetic plasticity. The risk of mutation-driven escape by self-renewing cells is intrinsic to multicellularity but is countered by multiple restraints, facilitating increasing complexity and longevity of species. But our own species has disrupted this historical narrative by rapidly escalating intrinsic risk. Evolutionary principles illuminate these challenges and provide new avenues to explore for more effective control.

SIGNIFICANCE: Lifetime risk of cancer now approximates to 50% in Western societies. And, despite many advances, the outcome for patients with disseminated disease remains poor, with drug resistance the norm. An evolutionary perspective may provide a clearer understanding of how cancer clones develop robustness and why, for us as a species, risk is now off the scale. And, perhaps, of what we might best do to achieve more effective control.}, } @article {pmid26184597, year = {2015}, author = {Soucy, SM and Huang, J and Gogarten, JP}, title = {Horizontal gene transfer: building the web of life.}, journal = {Nature reviews. Genetics}, volume = {16}, number = {8}, pages = {472-482}, pmid = {26184597}, issn = {1471-0064}, mesh = {Eukaryota/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics/*physiology ; *Models, Genetic ; *Phylogeny ; *Selection, Genetic ; Symbiosis/*genetics ; }, abstract = {Horizontal gene transfer (HGT) is the sharing of genetic material between organisms that are not in a parent-offspring relationship. HGT is a widely recognized mechanism for adaptation in bacteria and archaea. Microbial antibiotic resistance and pathogenicity are often associated with HGT, but the scope of HGT extends far beyond disease-causing organisms. In this Review, we describe how HGT has shaped the web of life using examples of HGT among prokaryotes, between prokaryotes and eukaryotes, and even between multicellular eukaryotes. We discuss replacement and additive HGT, the proposed mechanisms of HGT, selective forces that influence HGT, and the evolutionary impact of HGT on ancestral populations and existing populations such as the human microbiome.}, } @article {pmid26178988, year = {2015}, author = {Gutiérrez, S and Pirolles, E and Yvon, M and Baecker, V and Michalakis, Y and Blanc, S}, title = {The Multiplicity of Cellular Infection Changes Depending on the Route of Cell Infection in a Plant Virus.}, journal = {Journal of virology}, volume = {89}, number = {18}, pages = {9665-9675}, pmid = {26178988}, issn = {1098-5514}, mesh = {Animals ; Aphids/virology ; Brassica rapa/metabolism/*virology ; Genome, Viral/*physiology ; Plant Leaves/metabolism/*virology ; Tymovirus/*physiology ; *Viral Tropism ; }, abstract = {UNLABELLED: The multiplicity of cellular infection (MOI) is the number of virus genomes of a given virus species that infect individual cells. This parameter chiefly impacts the severity of within-host population bottlenecks as well as the intensity of genetic exchange, competition, and complementation among viral genotypes. Only a few formal estimations of the MOI currently are available, and most theoretical reports have considered this parameter as constant within the infected host. Nevertheless, the colonization of a multicellular host is a complex process during which the MOI may dramatically change in different organs and at different stages of the infection. We have used both qualitative and quantitative approaches to analyze the MOI during the colonization of turnip plants by Turnip mosaic virus. Remarkably, different MOIs were observed at two phases of the systemic infection of a leaf. The MOI was very low in primary infections from virus circulating within the vasculature, generally leading to primary foci founded by a single genome. Each lineage then moved from cell to cell at a very high MOI. Despite this elevated MOI during cell-to-cell progression, coinfection of cells by lineages originating in different primary foci is severely limited by the rapid onset of a mechanism inhibiting secondary infection. Thus, our results unveil an intriguing colonization pattern where individual viral genomes initiate distinct lineages within a leaf. Kin genomes then massively coinfect cells, but coinfection by two distinct lineages is strictly limited.

IMPORTANCE: The MOI is the size of the viral population colonizing cells and defines major phenomena in virus evolution, like the intensity of genetic exchange and the size of within-host population bottlenecks. However, few studies have quantified the MOI, and most consider this parameter as constant during infection. Our results reveal that the MOI can depend largely on the route of cell infection in a systemically infected leaf. The MOI is usually one genome per cell when cells are infected from virus particles moving long distances in the vasculature, whereas it is much higher during subsequent cell-to-cell movement in mesophyll. However, a fast-acting superinfection exclusion prevents cell coinfection by merging populations originating from different primary foci within a leaf. This complex colonization pattern results in a situation where within-cell interactions are occurring almost exclusively among kin and explains the common but uncharacterized phenomenon of genotype spatial segregation in infected plants.}, } @article {pmid26173445, year = {2015}, author = {Arenas-Mena, C and Coffman, JA}, title = {Developmental control of transcriptional and proliferative potency during the evolutionary emergence of animals.}, journal = {Developmental dynamics : an official publication of the American Association of Anatomists}, volume = {244}, number = {10}, pages = {1193-1201}, pmid = {26173445}, issn = {1097-0177}, support = {P20 GM103423/GM/NIGMS NIH HHS/United States ; P20 GM104318/GM/NIGMS NIH HHS/United States ; P20-GM103423/GM/NIGMS NIH HHS/United States ; P20-GM104318/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Cell Proliferation ; Chromatin/metabolism ; *Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; *Regulatory Elements, Transcriptional ; }, abstract = {It is proposed that the evolution of complex animals required repressive genetic mechanisms for controlling the transcriptional and proliferative potency of cells. Unicellular organisms are transcriptionally potent, able to express their full genetic complement as the need arises through their life cycle, whereas differentiated cells of multicellular organisms can only express a fraction of their genomic potential. Likewise, whereas cell proliferation in unicellular organisms is primarily limited by nutrient availability, cell proliferation in multicellular organisms is developmentally regulated. Repressive genetic controls limiting the potency of cells at the end of ontogeny would have stabilized the gene expression states of differentiated cells and prevented disruptive proliferation, allowing the emergence of diverse cell types and functional shapes. We propose that distal cis-regulatory elements represent the primary innovations that set the stage for the evolution of developmental gene regulatory networks and the repressive control of key multipotency and cell-cycle control genes. The testable prediction of this model is that the genomes of extant animals, unlike those of our unicellular relatives, encode gene regulatory circuits dedicated to the developmental control of transcriptional and proliferative potency.}, } @article {pmid26159581, year = {2016}, author = {Rosa, TM and Giovanna, PM and Maria, M and Angela, M and Matteo, C}, title = {Old Weapons for New Wars: Bioactive Molecules From Cnidarian Internal Defense Systems.}, journal = {Central nervous system agents in medicinal chemistry}, volume = {16}, number = {3}, pages = {183-196}, doi = {10.2174/1871524915666150710120650}, pmid = {26159581}, issn = {1875-6166}, mesh = {Animals ; Anti-Infective Agents/immunology/isolation & purification/toxicity ; *Cnidaria ; Cnidarian Venoms/immunology/isolation & purification/*toxicity ; Humans ; Neurotoxins/immunology/isolation & purification/*toxicity ; Peptides/immunology/isolation & purification/*toxicity ; Sodium Channel Blockers/immunology/isolation & purification/toxicity ; }, abstract = {The renewed interest in the study of genes of immunity in Cnidaria has led to additional information to the scenario of the first stages of immunity evolution revealing the cellular processes involved in symbiosis, in the regulation of homeostasis and in the fight against infections. The recent study with new molecular and functional approach on these organisms have therefore contributed with unexpected information on the knowledge of the stages of capturing activities and defense mechanisms strongly associated with toxin production. Cnidarians are diblastic aquatic animals with radial symmetry; they represent the ancestral state of Metazoa, they are the simplest multicellular organisms that have reached the level of tissue organization.The Cnidaria phylum has evolved using biotoxins as defense or predation mechanisms for ensure survival in hostile and competitive environments such as the seas and oceans. From benthic and pelagic species a large number of toxic compounds that have been determined can have an active role in the development of various antiviral, anticancer and antibacterial functions. Although the immune defense response of these animals is scarcely known, the tissues and the mucus produced by cnidarians are involved in immune defense and contain a large variety of peptides such as sodium and potassium channel neurotoxins, cytolysins, phospholipase A2 (PLA2), acid-sensing ion channel peptide toxins (ASICs) and other toxins, classified following biochemical and pharmacological studies on the basis of functional, molecular and structural parameters. These basal metazoan in fact, are far from "simple" in the range of methods at their disposal to deal with potential prey but also invading microbes and pathogens. They could also take advantage of the multi-functionality of some of their toxins, for example, some bioactive molecules have characteristics of toxicity associated with a potential antimicrobial activity. The interest in cnidarians was not only directed to the study of toxins and venom, but also to the fact these animals have been suggested as source of new molecules potentially relevant for biotechnology and pharmaceutical applications. Here, we review the cnidarian type of toxins regarding their multifunctional role and the future possibility of drawing important applications in fields ranging from biology to pharmacology.}, } @article {pmid26156204, year = {2015}, author = {Niklas, KJ and Kutschera, U}, title = {Kleiber's Law: How the Fire of Life ignited debate, fueled theory, and neglected plants as model organisms.}, journal = {Plant signaling & behavior}, volume = {10}, number = {7}, pages = {e1036216}, pmid = {26156204}, issn = {1559-2324}, mesh = {Animals ; Autotrophic Processes ; Cell Respiration ; Metabolism ; *Models, Biological ; Phototrophic Processes ; Plants/*metabolism ; }, abstract = {Size is a key feature of any organism since it influences the rate at which resources are consumed and thus affects metabolic rates. In the 1930s, size-dependent relationships were codified as "allometry" and it was shown that most of these could be quantified using the slopes of log-log plots of any 2 variables of interest. During the decades that followed, physiologists explored how animal respiration rates varied as a function of body size across taxa. The expectation was that rates would scale as the 2/3 power of body size as a reflection of the Euclidean relationship between surface area and volume. However, the work of Max Kleiber (1893-1976) and others revealed that animal respiration rates apparently scale more closely as the 3/4 power of body size. This phenomenology, which is called "Kleiber's Law," has been described for a broad range of organisms, including some algae and plants. It has also been severely criticized on theoretical and empirical grounds. Here, we review the history of the analysis of metabolism, which originated with the works of Antoine L. Lavoisier (1743-1794) and Julius Sachs (1832-1897), and culminated in Kleiber's book The Fire of Life (1961; 2. ed. 1975). We then evaluate some of the criticisms that have been leveled against Kleiber's Law and some examples of the theories that have tried to explain it. We revive the speculation that intracellular exo- and endocytotic processes are resource delivery-systems, analogous to the supercellular systems in multicellular organisms. Finally, we present data that cast doubt on the existence of a single scaling relationship between growth and body size in plants.}, } @article {pmid26156140, year = {2015}, author = {Wallace-Salinas, V and Brink, DP and Ahrén, D and Gorwa-Grauslund, MF}, title = {Cell periphery-related proteins as major genomic targets behind the adaptive evolution of an industrial Saccharomyces cerevisiae strain to combined heat and hydrolysate stress.}, journal = {BMC genomics}, volume = {16}, number = {1}, pages = {514}, pmid = {26156140}, issn = {1471-2164}, mesh = {Biological Evolution ; Ethanol/metabolism ; Genomics/*methods ; Hot Temperature ; Industrial Microbiology ; *Mutation ; Saccharomyces cerevisiae/genetics/*growth & development/metabolism ; Saccharomyces cerevisiae Proteins/*genetics/metabolism ; Selection, Genetic ; Sequence Analysis, DNA ; Stress, Physiological ; }, abstract = {BACKGROUND: Laboratory evolution is an important tool for developing robust yeast strains for bioethanol production since the biological basis behind combined tolerance requires complex alterations whose proper regulation is difficult to achieve by rational metabolic engineering. Previously, we reported on the evolved industrial Saccharomyces cerevisiae strain ISO12 that had acquired improved tolerance to grow and ferment in the presence of lignocellulose-derived inhibitors at high temperature (39 °C). In the current study, we used comparative genomics to uncover the extent of the genomic alterations that occurred during the evolution process and investigated possible associations between the mutations and the phenotypic traits in ISO12.

RESULTS: Through whole-genome sequencing and variant calling we identified a high number of strain-unique SNPs and INDELs in both ISO12 and the parental strain Ethanol Red. The variants were predicted to have 760 non-synonymous effects in both strains combined and were significantly enriched in Gene Ontology terms related to cell periphery, membranes and cell wall. Eleven genes, including MTL1, FLO9/FLO11, and CYC3 were found to be under positive selection in ISO12. Additionally, the FLO genes exhibited changes in copy number, and the alterations to this gene family were correlated with experimental results of multicellularity and invasive growth in the adapted strain. An independent lipidomic analysis revealed further differences between the strains in the content of nine lipid species. Finally, ISO12 displayed improved viability in undiluted spruce hydrolysate that was unrelated to reduction of inhibitors and changes in cell wall integrity, as shown by HPLC and lyticase assays.

CONCLUSIONS: Together, the results of the sequence comparison and the physiological characterisations indicate that cell-periphery proteins (e.g. extracellular sensors such as MTL1) and peripheral lipids/membranes are important evolutionary targets in the process of adaptation to the combined stresses. The capacity of ISO12 to develop complex colony formation also revealed multicellularity as a possible evolutionary strategy to improve competitiveness and tolerance to environmental stresses (also reflected by the FLO genes). Although a panel of altered genes with high relevance to the novel phenotype was detected, this study also demonstrates that the observed long-term molecular effects of thermal and inhibitor stress have polygenetic basis.}, } @article {pmid26150498, year = {2015}, author = {Rendueles, O and Zee, PC and Dinkelacker, I and Amherd, M and Wielgoss, S and Velicer, GJ}, title = {Rapid and widespread de novo evolution of kin discrimination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {29}, pages = {9076-9081}, pmid = {26150498}, issn = {1091-6490}, support = {R01 GM079690/GM/NIGMS NIH HHS/United States ; GM079690/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; *Biological Evolution ; Chimera ; Myxococcus xanthus/genetics/isolation & purification/*physiology ; Phenotype ; Time Factors ; }, abstract = {Diverse forms of kin discrimination, broadly defined as alteration of social behavior as a function of genetic relatedness among interactants, are common among social organisms from microbes to humans. However, the evolutionary origins and causes of kin-discriminatory behavior remain largely obscure. One form of kin discrimination observed in microbes is the failure of genetically distinct colonies to merge freely upon encounter. Here, we first use natural isolates of the highly social bacterium Myxococcus xanthus to show that colony-merger incompatibilities can be strong barriers to social interaction, particularly by reducing chimerism in multicellular fruiting bodies that develop near colony-territory borders. We then use experimental laboratory populations to test hypotheses regarding the evolutionary origins of kin discrimination. We show that the generic process of adaptation, irrespective of selective environment, is sufficient to repeatedly generate kin-discriminatory behaviors between evolved populations and their common ancestor. Further, we find that kin discrimination pervasively evolves indirectly between allopatric replicate populations that adapt to the same ecological habitat and that this occurs generically in many distinct habitats. Patterns of interpopulation discrimination imply that kin discrimination phenotypes evolved via many diverse genetic mechanisms and mutation-accumulation patterns support this inference. Strong incompatibility phenotypes emerged abruptly in some populations but strengthened gradually in others. The indirect evolution of kin discrimination in an asexual microbe is analogous to the indirect evolution of reproductive incompatibility in sexual eukaryotes and linguistic incompatibility among human cultures, the commonality being indirect, noncoordinated divergence of complex systems evolving in isolation.}, } @article {pmid26141828, year = {2016}, author = {Gu, X}, title = {Understanding tissue expression evolution: from expression phylogeny to phylogenetic network.}, journal = {Briefings in bioinformatics}, volume = {17}, number = {2}, pages = {249-254}, doi = {10.1093/bib/bbv041}, pmid = {26141828}, issn = {1477-4054}, mesh = {Animals ; *Evolution, Molecular ; Gene Expression Profiling/*methods ; Gene Expression Regulation/*genetics ; Gene Regulatory Networks/*genetics ; Humans ; Phylogeny ; Transcriptome/*genetics ; Viscera/*physiology ; }, abstract = {Our understanding of tissue expression evolution in multi-cellular model organisms has been considerably advanced with the help of high-throughput technologies from EST, microarray to RNA-seq. Yet, many controversies remained unsolved, ranging from the evolutionary patterns of tissue expressions to expression phylogenetic analysis. Moreover, despite numerous reports published, it is desirable to have a general framework for study of tissue expression evolution. In this article, we first provide an up-to-date and concise review for the study of tissue expression evolution in multi-cellular organisms. While the expression phylogeny of the same tissues sampled from closely or intermediately related species largely reflects the species phylogeny, we demonstrate that phylogenetic network approach may shed some lights for our understanding of the developmental similarity and evolutionary relatedness during the multi-tissue evolution.}, } @article {pmid26131935, year = {2015}, author = {Gavelis, GS and Hayakawa, S and White, RA and Gojobori, T and Suttle, CA and Keeling, PJ and Leander, BS}, title = {Eye-like ocelloids are built from different endosymbiotically acquired components.}, journal = {Nature}, volume = {523}, number = {7559}, pages = {204-207}, pmid = {26131935}, issn = {1476-4687}, mesh = {Dinoflagellida/*genetics/physiology/*ultrastructure ; Genome, Protozoan/genetics ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Mitochondria/metabolism/ultrastructure ; Molecular Sequence Data ; Plastids/metabolism/ultrastructure ; Protozoan Proteins/genetics ; Rhodophyta/genetics ; *Symbiosis ; }, abstract = {Multicellularity is often considered a prerequisite for morphological complexity, as seen in the camera-type eyes found in several groups of animals. A notable exception exists in single-celled eukaryotes called dinoflagellates, some of which have an eye-like 'ocelloid' consisting of subcellular analogues to a cornea, lens, iris, and retina. These planktonic cells are uncultivated and rarely encountered in environmental samples, obscuring the function and evolutionary origin of the ocelloid. Here we show, using a combination of electron microscopy, tomography, isolated-organelle genomics, and single-cell genomics, that ocelloids are built from pre-existing organelles, including a cornea-like layer made of mitochondria and a retinal body made of anastomosing plastids. We find that the retinal body forms the central core of a network of peridinin-type plastids, which in dinoflagellates and their relatives originated through an ancient endosymbiosis with a red alga. As such, the ocelloid is a chimaeric structure, incorporating organelles with different endosymbiotic histories. The anatomical complexity of single-celled organisms may be limited by the components available for differentiation, but the ocelloid shows that pre-existing organelles can be assembled into a structure so complex that it was initially mistaken for a multicellular eye. Although mitochondria and plastids are acknowledged chiefly for their metabolic roles, they can also be building blocks for greater structural complexity.}, } @article {pmid26124052, year = {2015}, author = {Tomic, B and Kusic-Tisma, J}, title = {HsOrc4-Dependent Dna Remodeling of the ori-β Dhfr Replicator.}, journal = {Cellular & molecular biology letters}, volume = {20}, number = {4}, pages = {549-561}, doi = {10.1515/cmble-2015-0032}, pmid = {26124052}, issn = {1689-1392}, mesh = {AT Rich Sequence ; Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Binding Sites ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; Cricetulus ; DNA Replication ; DNA-Binding Proteins ; *Nucleic Acid Conformation ; Origin Recognition Complex/chemistry/genetics/*metabolism ; Plant Proteins/chemistry/metabolism ; Plasmids/chemistry/genetics ; RNA-Binding Proteins ; *Replication Origin ; Single-Strand Specific DNA and RNA Endonucleases/chemistry/metabolism ; Tetrahydrofolate Dehydrogenase/*genetics ; }, abstract = {Replication of DNA in multicellular organisms initiates from origin of replication (ori) sequences, which significantly differ in length and complexity. One of the best characterized is hamster dihydrofolate reductase (DHFR), which contains the ori-β sequence with several functionally relevant domains, such as an AT-rich region, dinucleotide repeat element (DNR), sequence-induced bend DNA (BEND) and a RIP60 protein-binding site (RIP60). Prior to initiation, ori sequences are recognized by origin recognition complex (ORC), which is a hetero hexamer complex that serves as the landing pad for proteins of the pre-replication complex. The function of each ORC subunit is still unclear. In this study, we analyze the function of subunit 4 of the human ORC complex (HsOrc4) in interaction with a plasmid bearing the ori-β DHFR sequence. We show that the topologically closed DHFR ori-β replicator contains a bubble-like structure within its AT-rich region and that it is reversibly modified in the interaction with HsOrc4. The non-canonical structure of the AT-rich region in the topologically closed ori sequence is recognized and changed by HsOrc4 using the energy of supercoiled DNA. These findings could help to further elucidate DNA replication and its possible association with human genetic diseases.}, } @article {pmid26124000, year = {2015}, author = {Schwessinger, B and Rathjen, JP}, title = {Changing SERKs and priorities during plant life.}, journal = {Trends in plant science}, volume = {20}, number = {9}, pages = {531-533}, doi = {10.1016/j.tplants.2015.06.006}, pmid = {26124000}, issn = {1878-4372}, mesh = {Biological Evolution ; *Gene Expression Regulation, Plant ; Magnoliopsida/*genetics/metabolism ; Plant Proteins/*genetics/metabolism ; Protein Kinases/*genetics/metabolism ; *Signal Transduction ; }, abstract = {SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASES (SERKs) are coreceptors for diverse extracellular signals. SERKs are involved in a wide array of developmental and immune related processes first discovered in Arabidopsis. Recent work demonstrates the evolutionary conservation of SERKs in all multicellular plants, and highlights their functional conservation in monocots and dicots.}, } @article {pmid26121931, year = {2016}, author = {Mishra, RC and Grover, A}, title = {ClpB/Hsp100 proteins and heat stress tolerance in plants.}, journal = {Critical reviews in biotechnology}, volume = {36}, number = {5}, pages = {862-874}, doi = {10.3109/07388551.2015.1051942}, pmid = {26121931}, issn = {1549-7801}, mesh = {Endopeptidase Clp/*genetics ; Global Warming ; Heat-Shock Proteins/*genetics ; Molecular Chaperones ; Mutation ; Phylogeny ; Plants, Genetically Modified/*genetics ; Stress, Physiological/genetics ; Thermotolerance/*genetics ; }, abstract = {High-temperature stress can disrupt cellular proteostasis, resulting in the accumulation of insoluble protein aggregates. For survival under stressful conditions, it is important for cells to maintain a pool of native soluble proteins by preventing and/or dissociating these aggregates. Chaperones such as GroEL/GroES (Hsp60/Hsp10) and DnaK/DnaJ/GrpE (Hsp70/Hsp40/nucleotide exchange factor) help cells minimize protein aggregation. Protein disaggregation is accomplished by chaperones belonging to the Caseinolytic Protease (Clp) family of proteins. ClpB/Hsp100 proteins are strikingly ubiquitous and are found in bacteria, yeast and multi-cellular plants. The expression of these proteins is regulated by heat stress (HS) and developmental cues. Bacteria and yeast contain one and two forms of ClpB proteins, respectively. Plants possess multiple forms of these proteins that are localized to different cellular compartments (i.e. cytoplasm/nucleus, chloroplast or mitochondria). Overwhelming evidence suggests that ClpB/Hsp100 proteins play decisive roles in cell adaptation to HS. Mutant bacteria and yeast cells lacking active ClpB/Hsp100 proteins are critically sensitive to high-temperature stress. Likewise, Arabidopsis, maize and rice mutants lacking cytoplasmic ClpB proteins are very sensitive to heat. In this study, we present the structural and functional attributes of plant ClpB forms.}, } @article {pmid26116421, year = {2016}, author = {Ishizaki, K and Nishihama, R and Yamato, KT and Kohchi, T}, title = {Molecular Genetic Tools and Techniques for Marchantia polymorpha Research.}, journal = {Plant & cell physiology}, volume = {57}, number = {2}, pages = {262-270}, doi = {10.1093/pcp/pcv097}, pmid = {26116421}, issn = {1471-9053}, mesh = {Crosses, Genetic ; Marchantia/*genetics ; Molecular Biology/*methods ; Plastids/genetics ; *Research ; Transformation, Genetic ; }, abstract = {Liverworts occupy a basal position in the evolution of land plants, and are a key group to address a wide variety of questions in plant biology. Marchantia polymorpha is a common, easily cultivated, dioecious liverwort species, and is emerging as an experimental model organism. The haploid gametophytic generation dominates the diploid sporophytic generation in its life cycle. Genetically homogeneous lines in the gametophyte generation can be established easily and propagated through asexual reproduction, which aids genetic and biochemical experiments. Owing to its dioecy, male and female sexual organs are formed in separate individuals, which enables crossing in a fully controlled manner. Reproductive growth can be induced at the desired times under laboratory conditions, which helps genetic analysis. The developmental process from a single-celled spore to a multicellular body can be observed directly in detail. As a model organism, molecular techniques for M. polymorpha are well developed; for example, simple and efficient protocols of Agrobacterium-mediated transformation have been established. Based on them, various strategies for molecular genetics, such as introduction of reporter constructs, overexpression, gene silencing and targeted gene modification, are available. Herein, we describe the technologies and resources for reverse and forward genetics in M. polymorpha, which offer an excellent experimental platform to study the evolution and diversity of regulatory systems in land plants.}, } @article {pmid26106978, year = {2015}, author = {Zielezinski, A and Karlowski, WM}, title = {Early origin and adaptive evolution of the GW182 protein family, the key component of RNA silencing in animals.}, journal = {RNA biology}, volume = {12}, number = {7}, pages = {761-770}, pmid = {26106978}, issn = {1555-8584}, mesh = {Animals ; Autoantigens/genetics/*metabolism ; *Evolution, Molecular ; Humans ; Invertebrates/genetics/metabolism ; *RNA Interference ; RNA-Binding Proteins/genetics/*metabolism ; Vertebrates/genetics/metabolism ; }, abstract = {The GW182 proteins are a key component of the miRNA-dependent post-transcriptional silencing pathway in animals. They function as scaffold proteins to mediate the interaction of Argonaute (AGO)-containing complexes with cytoplasmic poly(A)-binding proteins (PABP) and PAN2-PAN3 and CCR4-NOT deadenylases. The AGO-GW182 complexes mediate silencing of the target mRNA through induction of translational repression and/or mRNA degradation. Although the GW182 proteins are a subject of extensive experimental research in the recent years, very little is known about their origin and evolution. Here, based on complex functional annotation and phylogenetic analyses, we reveal 448 members of the GW182 protein family from the earliest animals to humans. Our results indicate that a single-copy GW182/TNRC6C progenitor gene arose with the emergence of multicellularity and it multiplied in the last common ancestor of vertebrates in 2 rounds of whole genome duplication (WGD) resulting in 3 genes. Before the divergence of vertebrates, both the AGO- and CCR4-NOT-binding regions of GW182s showed significant acceleration in the accumulation of amino acid changes, suggesting functional adaptation toward higher specificity to the molecules of the silencing complex. We conclude that the silencing ability of the GW182 proteins improves with higher position in the taxonomic classification and increasing complexity of the organism. The first reconstruction of the molecular journey of GW182 proteins from the ancestral metazoan protein to the current mammalian configuration provides new insight into development of the miRNA-dependent post-transcriptional silencing pathway in animals.}, } @article {pmid26105654, year = {2015}, author = {Koeduka, T and Ishizaki, K and Mwenda, CM and Hori, K and Sasaki-Sekimoto, Y and Ohta, H and Kohchi, T and Matsui, K}, title = {Biochemical characterization of allene oxide synthases from the liverwort Marchantia polymorpha and green microalgae Klebsormidium flaccidum provides insight into the evolutionary divergence of the plant CYP74 family.}, journal = {Planta}, volume = {242}, number = {5}, pages = {1175-1186}, pmid = {26105654}, issn = {1432-2048}, mesh = {Cytochrome P-450 Enzyme System/genetics/*metabolism ; *Evolution, Molecular ; Intramolecular Oxidoreductases/genetics/*metabolism ; Marchantia/*enzymology ; Microalgae/*enzymology ; Plant Proteins/genetics/*metabolism ; }, abstract = {Allene oxide synthases (AOSs) were isolated from liverworts and charophytes. These AOSs exhibited enzymatic properties similar to those of angiosperms but formed a distinct phylogenetic clade. Allene oxide synthase (AOS) and hydroperoxide lyase (HPL) mediate the formation of precursors of jasmonates and carbon-six volatiles, respectively. AOS and HPL utilize fatty acid hydroperoxides and belong to the plant cytochrome P450 74 (CYP74) family that mediates plant defense against herbivores, pathogens, or abiotic stresses. Although members of the CYP74 family have been reported in mosses and other species, the evolution and function of multiple CYP74 genes in plants remain elusive. Here, we show that the liverwort Marchantia polymorpha belongs to a basal group in the evolution of land plants; has two closely related proteins (59% identity), MpAOS1 and MpAOS2, that are similar to moss PpAOS1 (49 and 47% identity, respectively); and exhibits AOS activity but not HPL activity. We also found that the green microalgae Klebsormidium flaccidum, consist of multicellular and non-branching filaments, contains an enzyme, KfAOS, that is similar to PpAOS1 (37% identity), and converts 13-hydroperoxide of linolenic acid to 12-oxo-phytodienoic acid in a coupled reaction with allene oxide cyclase. Phylogenetic analysis showed two evolutionarily distinct clusters. One cluster comprised AOS and HPL from charophytic algae, liverworts, and mosses, including MpAOSs and KfAOS. The other cluster was formed by angiosperm CYP74. Our results suggest that plant CYP74 enzymes with AOS, HPL, and divinyl ether synthase activities have arisen multiple times and in the two different clades, which occurred prior to the divergence of the flowering plant lineage.}, } @article {pmid26101255, year = {2015}, author = {Tarver, JE and Cormier, A and Pinzón, N and Taylor, RS and Carré, W and Strittmatter, M and Seitz, H and Coelho, SM and Cock, JM}, title = {microRNAs and the evolution of complex multicellularity: identification of a large, diverse complement of microRNAs in the brown alga Ectocarpus.}, journal = {Nucleic acids research}, volume = {43}, number = {13}, pages = {6384-6398}, pmid = {26101255}, issn = {1362-4962}, mesh = {*Evolution, Molecular ; Genetic Loci ; Genetic Variation ; Genome ; MicroRNAs/chemistry/classification/*genetics/metabolism ; Phaeophyceae/*genetics/metabolism ; Polymerase Chain Reaction ; Sequence Analysis, RNA ; }, abstract = {There is currently convincing evidence that microRNAs have evolved independently in at least six different eukaryotic lineages: animals, land plants, chlorophyte green algae, demosponges, slime molds and brown algae. MicroRNAs from different lineages are not homologous but some structural features are strongly conserved across the eukaryotic tree allowing the application of stringent criteria to identify novel microRNA loci. A large set of 63 microRNA families was identified in the brown alga Ectocarpus based on mapping of RNA-seq data and nine microRNAs were confirmed by northern blotting. The Ectocarpus microRNAs are highly diverse at the sequence level with few multi-gene families, and do not tend to occur in clusters but exhibit some highly conserved structural features such as the presence of a uracil at the first residue. No homologues of Ectocarpus microRNAs were found in other stramenopile genomes indicating that they emerged late in stramenopile evolution and are perhaps specific to the brown algae. The large number of microRNA loci in Ectocarpus is consistent with the developmental complexity of many brown algal species and supports a proposed link between the emergence and expansion of microRNA regulatory systems and the evolution of complex multicellularity.}, } @article {pmid26100885, year = {2015}, author = {Skippington, E and Barkman, TJ and Rice, DW and Palmer, JD}, title = {Miniaturized mitogenome of the parasitic plant Viscum scurruloideum is extremely divergent and dynamic and has lost all nad genes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {27}, pages = {E3515-24}, pmid = {26100885}, issn = {1091-6490}, mesh = {Base Sequence ; DNA, Mitochondrial/classification/*genetics ; Electron Transport Complex I/*genetics ; Genes, Mitochondrial/genetics ; Genetic Variation ; Genome, Mitochondrial/*genetics ; Mitochondrial Proteins/genetics ; Molecular Sequence Data ; Phylogeny ; Plant Proteins/*genetics ; RNA, Plant/genetics ; RNA, Ribosomal/genetics ; Sequence Homology, Nucleic Acid ; Viscum/*genetics ; }, abstract = {Despite the enormous diversity among parasitic angiosperms in form and structure, life-history strategies, and plastid genomes, little is known about the diversity of their mitogenomes. We report the sequence of the wonderfully bizarre mitogenome of the hemiparasitic aerial mistletoe Viscum scurruloideum. This genome is only 66 kb in size, making it the smallest known angiosperm mitogenome by a factor of more than three and the smallest land plant mitogenome. Accompanying this size reduction is exceptional reduction of gene content. Much of this reduction arises from the unexpected loss of respiratory complex I (NADH dehydrogenase), universally present in all 300+ other angiosperms examined, where it is encoded by nine mitochondrial and many nuclear nad genes. Loss of complex I in a multicellular organism is unprecedented. We explore the potential relationship between this loss in Viscum and its parasitic lifestyle. Despite its small size, the Viscum mitogenome is unusually rich in recombinationally active repeats, possessing unparalleled levels of predicted sublimons resulting from recombination across short repeats. Many mitochondrial gene products exhibit extraordinary levels of divergence in Viscum, indicative of highly relaxed if not positive selection. In addition, all Viscum mitochondrial protein genes have experienced a dramatic acceleration in synonymous substitution rates, consistent with the hypothesis of genomic streamlining in response to a high mutation rate but completely opposite to the pattern seen for the high-rate but enormous mitogenomes of Silene. In sum, the Viscum mitogenome possesses a unique constellation of extremely unusual features, a subset of which may be related to its parasitic lifestyle.}, } @article {pmid26089366, year = {2015}, author = {Kamo, T and Akazawa, H and Komuro, I}, title = {Cardiac nonmyocytes in the hub of cardiac hypertrophy.}, journal = {Circulation research}, volume = {117}, number = {1}, pages = {89-98}, doi = {10.1161/CIRCRESAHA.117.305349}, pmid = {26089366}, issn = {1524-4571}, mesh = {Animals ; Autocrine Communication ; Blood Cells/pathology ; Cardiomegaly/*pathology ; Cell Lineage ; Endothelial Cells/metabolism/pathology ; Endothelin-1/physiology ; Fibroblasts/metabolism/pathology ; Humans ; Intercellular Signaling Peptides and Proteins/physiology ; Macrophages/physiology ; Mast Cells/physiology ; Mice ; MicroRNAs/physiology ; Myocardium/*pathology ; Myocytes, Cardiac/pathology ; Natriuretic Peptides/physiology ; Paracrine Communication ; }, abstract = {Cardiac hypertrophy is characterized by complex multicellular alterations, such as cardiomyocyte growth, angiogenesis, fibrosis, and inflammation. The heart consists of myocytes and nonmyocytes, such as fibroblasts, vascular cells, and blood cells, and these cells communicate with each other directly or indirectly via a variety of autocrine or paracrine mediators. Accumulating evidence has suggested that nonmyocytes actively participate in the development of cardiac hypertrophy. In this review, recent progress in our understanding of the importance of nonmyocytes as a hub for induction of cardiac hypertrophy is summarized with an emphasis of the contribution of noncontact communication mediated by diffusible factors between cardiomyocytes and nonmyocytes in the heart.}, } @article {pmid26079199, year = {2015}, author = {Scianna, M and Bassino, E and Munaron, L}, title = {A cellular Potts model analyzing differentiated cell behavior during in vivo vascularization of a hypoxic tissue.}, journal = {Computers in biology and medicine}, volume = {63}, number = {}, pages = {143-156}, doi = {10.1016/j.compbiomed.2015.05.020}, pmid = {26079199}, issn = {1879-0534}, mesh = {Animals ; *Cell Differentiation ; Endothelial Cells/*metabolism ; Humans ; *Hypoxia/metabolism/physiopathology ; *Models, Cardiovascular ; *Neovascularization, Physiologic ; Protein Isoforms/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {Angiogenesis, the formation of new blood vessel networks from existing capillary or post-capillary venules, is an intrinsically multiscale process occurring in several physio-pathological conditions. In particular, hypoxic tissue cells activate downstream cascades culminating in the secretion of a wide range of angiogenic factors, including VEGF isoforms. Such diffusive chemicals activate the endothelial cells (ECs) forming the external walls of the nearby vessels that chemotactically migrate toward the hypoxic areas of the tissue as multicellular sprouts. A functional network eventually emerges by further branching and anastomosis processes. We here propose a CPM-based approach reproducing selected features of the angiogenic progression necessary for the reoxygenation of a hypoxic tissue. Our model is able to span the different scale involved in the angiogenic progression as it incorporates reaction-diffusion equations for the description of the evolution of microenvironmental variables in a discrete mesoscopic cellular Potts model (CPM) that reproduces the dynamics of the vascular cells. A key feature of this work is the explicit phenotypic differentiation of the ECs themselves, distinguished in quiescent, stalk and tip. The simulation results allow identifying a set of key mechanisms underlying tissue vascularization. Further, we provide evidence that the nascent pattern is characterized by precise topological properties. Finally, we link abnormal sprouting angiogenesis with alteration in selected cell behavior.}, } @article {pmid26066639, year = {2015}, author = {Peng, M and Aye, TT and Snel, B and van Breukelen, B and Scholten, A and Heck, AJ}, title = {Spatial Organization in Protein Kinase A Signaling Emerged at the Base of Animal Evolution.}, journal = {Journal of proteome research}, volume = {14}, number = {7}, pages = {2976-2987}, doi = {10.1021/acs.jproteome.5b00370}, pmid = {26066639}, issn = {1535-3907}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Catalytic Domain ; Conserved Sequence ; Cyclic AMP-Dependent Protein Kinases/*metabolism ; Molecular Sequence Data ; Phylogeny ; Proteomics ; Sequence Homology, Amino Acid ; *Signal Transduction ; Subcellular Fractions/enzymology ; }, abstract = {In phosphorylation-directed signaling, spatial and temporal control is organized by complex interaction networks that diligently direct kinases toward distinct substrates to fine-tune specificity. How these protein networks originate and evolve into complex regulatory machineries are among the most fascinating research questions in biology. Here, spatiotemporal signaling is investigated by tracing the evolutionary dynamics of each functional domain of cAMP-dependent protein kinase (PKA) and its diverse set of A-kinase anchoring proteins (AKAPs). Homologues of the catalytic (PKA-C) and regulatory (PKA-R) domains of the (PKA-R)2-(PKA-C)2 holoenzyme were found throughout evolution. Most variation was observed in the RIIa of PKA-R, crucial for dimerization and docking to AKAPs. The RIIa domain was not observed in all PKA-R homologues. In the fungi and distinct protist lineages, the RIIa domain emerges within PKA-R, but it displays large sequence variation. These organisms do not harbor homologues of AKAPs, suggesting that efficient docking to direct spatiotemporal PKA activity evolved in multicellular eukaryotes. To test this in silico hypothesis, we experimentally screened organisms with increasing complexity by cAMP-based chemical proteomics to reveal that the occurrence of PKA-AKAP interactions indeed coincided and expanded within vertebrates, suggesting a crucial role for AKAPs in the advent of metazoan multicellularity.}, } @article {pmid26063749, year = {2015}, author = {Maliet, O and Shelton, DE and Michod, RE}, title = {A model for the origin of group reproduction during the evolutionary transition to multicellularity.}, journal = {Biology letters}, volume = {11}, number = {6}, pages = {20150157}, pmid = {26063749}, issn = {1744-957X}, mesh = {*Biological Evolution ; *Models, Biological ; Reproduction ; *Selection, Genetic ; Volvocida/*physiology ; }, abstract = {During the evolution of multicellular organisms, the unit of selection and adaptation, the individual, changes from the single cell to the multicellular group. To become individuals, groups must evolve a group life cycle in which groups reproduce other groups. Investigations into the origin of group reproduction have faced a chicken-and-egg problem: traits related to reproduction at the group level often appear both to be a result of and a prerequisite for natural selection at the group level. With a focus on volvocine algae, we model the basic elements of the cell cycle and show how group reproduction can emerge through the coevolution of a life-history trait with a trait underpinning cell cycle change. Our model explains how events in the cell cycle become reordered to create a group life cycle through continuous change in the cell cycle trait, but only if the cell cycle trait can coevolve with the life-history trait. Explaining the origin of group reproduction helps us understand one of life's most familiar, yet fundamental, aspects-its hierarchical structure.}, } @article {pmid26063660, year = {2015}, author = {Gent, JI and Wang, K and Jiang, J and Dawe, RK}, title = {Stable Patterns of CENH3 Occupancy Through Maize Lineages Containing Genetically Similar Centromeres.}, journal = {Genetics}, volume = {200}, number = {4}, pages = {1105-1116}, pmid = {26063660}, issn = {1943-2631}, mesh = {Centromere/*genetics ; Chromatin Immunoprecipitation ; *Chromosomal Instability ; DNA, Plant/genetics ; Genome, Plant/genetics ; Inbreeding ; Repetitive Sequences, Nucleic Acid/genetics ; Zea mays/*genetics ; }, abstract = {While the approximate chromosomal position of centromeres has been identified in many species, little is known about the dynamics and diversity of centromere positions within species. Multiple lines of evidence indicate that DNA sequence has little or no impact in specifying centromeres in maize and in most multicellular organisms. Given that epigenetically defined boundaries are expected to be dynamic, we hypothesized that centromere positions would change rapidly over time, which would result in a diversity of centromere positions in isolated populations. To test this hypothesis, we used CENP-A/cenH3 (CENH3 in maize) chromatin immunoprecipitation to define centromeres in breeding pedigrees that included the B73 inbred as a common parent. While we found a diversity of CENH3 profiles for centromeres with divergent sequences that were not inherited from B73, the CENH3 profiles from centromeres that were inherited from B73 were indistinguishable from each other. We propose that specific genetic elements in centromeric regions favor or inhibit CENH3 accumulation, leading to reproducible patterns of CENH3 occupancy. These data also indicate that dramatic shifts in centromere position normally originate from accumulated or large-scale genetic changes rather than from epigenetic positional drift.}, } @article {pmid26056368, year = {2015}, author = {Ewald, PW and Swain Ewald, HA}, title = {Infection and cancer in multicellular organisms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {370}, number = {1673}, pages = {}, pmid = {26056368}, issn = {1471-2970}, mesh = {Animals ; Biological Evolution ; Environmental Pollutants/toxicity ; Humans ; Infections/*complications ; Models, Biological ; Neoplasms/*etiology ; Oncogenic Viruses/pathogenicity ; Tumor Virus Infections/etiology ; }, abstract = {Evolutionary considerations suggest that oncogenic infections should be pervasive among animal species. Infection-associated cancers are well documented in humans and domestic animals, less commonly reported in undomesticated captive animals, and rarely documented in nature. In this paper, we review the literature associating infectious agents with cancer to evaluate the reasons for this pattern. Non-malignant infectious neoplasms occur pervasively in multicellular life, but oncogenic progression to malignancy is often uncertain. Evidence from humans and domestic animals shows that non-malignant infectious neoplasms can develop into cancer, although generally with low frequency. Malignant neoplasms could be difficult to find in nature because of a low frequency of oncogenic transformation, short survival after malignancy and reduced survival prior to malignancy. Moreover, the evaluation of malignancy can be ambiguous in nature, because criteria for malignancy may be difficult to apply consistently across species. The information available in the literature therefore does not allow for a definitive assessment of the pervasiveness of infectious cancers in nature, but the presence of infectious neoplasias and knowledge about the progression of benign neoplasias to cancer is consistent with a widespread but largely undetected occurrence.}, } @article {pmid26056363, year = {2015}, author = {Aktipis, CA and Boddy, AM and Jansen, G and Hibner, U and Hochberg, ME and Maley, CC and Wilkinson, GS}, title = {Cancer across the tree of life: cooperation and cheating in multicellularity.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {370}, number = {1673}, pages = {}, pmid = {26056363}, issn = {1471-2970}, support = {R01 CA185138/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA170595/CA/NCI NIH HHS/United States ; P01 CA91955/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; BC132057/BC/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Cell Communication ; Cell Differentiation ; Cell Proliferation ; Humans ; Models, Biological ; Neoplasms/etiology/*pathology/physiopathology ; Phylogeny ; Tumor Microenvironment ; }, abstract = {Multicellularity is characterized by cooperation among cells for the development, maintenance and reproduction of the multicellular organism. Cancer can be viewed as cheating within this cooperative multicellular system. Complex multicellularity, and the cooperation underlying it, has evolved independently multiple times. We review the existing literature on cancer and cancer-like phenomena across life, not only focusing on complex multicellularity but also reviewing cancer-like phenomena across the tree of life more broadly. We find that cancer is characterized by a breakdown of the central features of cooperation that characterize multicellularity, including cheating in proliferation inhibition, cell death, division of labour, resource allocation and extracellular environment maintenance (which we term the five foundations of multicellularity). Cheating on division of labour, exhibited by a lack of differentiation and disorganized cell masses, has been observed in all forms of multicellularity. This suggests that deregulation of differentiation is a fundamental and universal aspect of carcinogenesis that may be underappreciated in cancer biology. Understanding cancer as a breakdown of multicellular cooperation provides novel insights into cancer hallmarks and suggests a set of assays and biomarkers that can be applied across species and characterize the fundamental requirements for generating a cancer.}, } @article {pmid26054350, year = {2015}, author = {Olovnikov, AM}, title = {Chronographic theory of development, aging, and origin of cancer: role of chronomeres and printomeres.}, journal = {Current aging science}, volume = {8}, number = {1}, pages = {76-88}, pmid = {26054350}, issn = {1874-6128}, mesh = {*Aging ; Animals ; Humans ; *Neoplasms/genetics ; Polymers/*pharmacology ; Sex Characteristics ; Telomere ; Telomere Shortening ; }, abstract = {It is supposed that the development and aging of multicellular animals and humans are controlled by a special form of the clock mechanism - a chronograph. The development of animals and their aging are interconnected by the program of the species lifespan that has been selected in the evolution of each species to fit the resources of its ecological niche. The theory is based on the idea about a controlled loss by the neurons in the brain of hypothetical organelles - chronomeres that represent themselves small DNA molecules, which are amplificates of the segments of chromosomal DNA. A regular mode of the process of chronomere losses by neurons is provided by a pacemaker localized in the pineal gland and activated at least once per lunar month. Neurons, consecutively losing their chronomeres, are organized in the brain in the temporal relay race. Analogues of chronomeres, namely printomeres, are supposed to exist in dividing non-neuronal cells. Printomeres are not involved in a performance of temporal function, instead they are responsible for the maintenance in dividing cells of their memory about the state of differentiation. A critical shortening or loss of a printomere in a dividing cell leads to a cellular senescence, whereas telomere shortening is a bystander of this process. Thus, aging of a multicellular organism is associated with the loss of chronomeres, whereas senescence of dividing cells is associated with the loss of regulatory RNAs encoded by printomeres. If the cells that have lost their printomeres are environmentally forced to divide, they can transform into cancer cells.}, } @article {pmid26048704, year = {2015}, author = {Sheikh, S and Gloeckner, G and Kuwayama, H and Schaap, P and Urushihara, H and Baldauf, SL}, title = {Root of Dictyostelia based on 213 universal proteins.}, journal = {Molecular phylogenetics and evolution}, volume = {92}, number = {}, pages = {53-62}, doi = {10.1016/j.ympev.2015.05.017}, pmid = {26048704}, issn = {1095-9513}, support = {BB/E016308//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Amoeba/chemistry/metabolism ; Bayes Theorem ; Dictyostelium/*classification/genetics/*metabolism ; Genome/genetics ; *Phylogeny ; Proteins/*analysis/chemistry ; RNA, Ribosomal/genetics ; }, abstract = {Dictyostelia are common soil microbes that can aggregate when starved to form multicellular fruiting bodies, a characteristic that has also led to their long history of study and widespread use as model systems. Ribosomal RNA phylogeny of Dictyostelia identified four major divisions (Groups 1-4), none of which correspond to traditional genera. Group 1 was also tentatively identified as sister lineage to the other three Groups, although not consistently or with strong support. We tested the dictyostelid root using universal protein-coding genes identified by exhaustive comparison of six completely sequenced dictyostelid genomes, which include representatives of all four major molecular Groups. A set of 213 genes are low-copy number in all genomes, present in at least one amoebozoan outgroup taxon (Acanthamoeba castellanii or Physarum polycephalum), and phylogenetically congruent. Phylogenetic analysis of a concatenation of the deduced protein sequences produces a single topology dividing Dictyostelia into two major divisions: Groups 1+2 and Groups 3+4. All clades in the tree are fully supported by maximum likelihood and Bayesian inference, and all alternative roots are unambiguously rejected by the approximately unbiased (AU) test. The 1+2, 3+4 root is also fully supported even after deleting clusters with strong individual support for this root, or concatenating all clusters with low support for alternative roots. The 213 putatively ancestral amoebozoan proteins encode a wide variety of functions including 21 KOG categories out of a total of 25. These comprehensive analyses and consistent results indicate that it is time for full taxonomic revision of Dictyostelia, which will also enable more effective exploitation of its unique potential as an evolutionary model system.}, } @article {pmid26047467, year = {2015}, author = {Wideman, JG and Moore, BP}, title = {The Evolutionary History of MAPL (Mitochondria-Associated Protein Ligase) and Other Eukaryotic BAM/GIDE Domain Proteins.}, journal = {PloS one}, volume = {10}, number = {6}, pages = {e0128795}, pmid = {26047467}, issn = {1932-6203}, mesh = {Animals ; Biological Evolution ; Fungal Proteins/chemistry/genetics ; Fungi/chemistry/genetics ; Humans ; *Phylogeny ; Plant Proteins/chemistry/genetics ; Plants/chemistry/genetics ; Protein Structure, Tertiary ; Ubiquitin-Protein Ligases/chemistry/*genetics ; }, abstract = {MAPL (mitochondria-associated protein ligase, also called MULAN/GIDE/MUL1) is a multifunctional mitochondrial outer membrane protein found in human cells that contains a unique BAM (beside a membrane) domain and a C-terminal RING-finger domain. MAPL has been implicated in several processes that occur in animal cells such as NF-kB activation, innate immunity and antiviral signaling, suppression of PINK1/parkin defects, mitophagy in skeletal muscle, and caspase-dependent apoptosis. Previous studies demonstrated that the BAM domain is present in diverse organisms in which most of these processes do not occur, including plants, archaea, and bacteria. Thus the conserved function of MAPL and its BAM domain remains an open question. In order to gain insight into its conserved function, we investigated the evolutionary origins of MAPL by searching for homologues in predicted proteomes of diverse eukaryotes. We show that MAPL proteins with a conserved BAM-RING architecture are present in most animals, protists closely related to animals, a single species of fungus, and several multicellular plants and related green algae. Phylogenetic analysis demonstrated that eukaryotic MAPL proteins originate from a common ancestor and not from independent horizontal gene transfers from bacteria. We also determined that two independent duplications of MAPL occurred, one at the base of multicellular plants and another at the base of vertebrates. Although no other eukaryote genome examined contained a verifiable MAPL orthologue, BAM domain-containing proteins were identified in the protists Bigelowiella natans and Ectocarpus siliculosis. Phylogenetic analyses demonstrated that these proteins are more closely related to prokaryotic BAM proteins and therefore likely arose from independent horizontal gene transfers from bacteria. We conclude that MAPL proteins with BAM-RING architectures have been present in the holozoan and viridiplantae lineages since their very beginnings. Our work paves the way for future studies into MAPL function in alternative model organisms like Capsaspora owczarzaki and Chlamydomonas reinhardtii that will help to answer the question of MAPL's ancestral function in ways that cannot be answered by studying animal cells alone.}, } @article {pmid26041885, year = {2015}, author = {Kurakin, A and Bredesen, DE}, title = {Dynamic self-guiding analysis of Alzheimer's disease.}, journal = {Oncotarget}, volume = {6}, number = {16}, pages = {14092-14122}, pmid = {26041885}, issn = {1949-2553}, support = {R21 AG036975/AG/NIA NIH HHS/United States ; AG16570/AG/NIA NIH HHS/United States ; AG034427/AG/NIA NIH HHS/United States ; AG036975/AG/NIA NIH HHS/United States ; P50 AG016570/AG/NIA NIH HHS/United States ; R01 AG034427/AG/NIA NIH HHS/United States ; }, mesh = {Algorithms ; Alzheimer Disease/*metabolism/*pathology ; Amyloid beta-Protein Precursor/metabolism ; Cell Adhesion/physiology ; Humans ; }, abstract = {We applied a self-guiding evolutionary algorithm to initiate the synthesis of the Alzheimer's disease-related data and literature. A protein interaction network associated with amyloid-beta precursor protein (APP) and a seed model that treats Alzheimer's disease as progressive dysregulation of APP-associated signaling were used as dynamic "guides" and structural "filters" in the recursive search, analysis, and assimilation of data to drive the evolution of the seed model in size, detail, and complexity. Analysis of data and literature across sub-disciplines and system-scale discovery platforms suggests a key role of dynamic cytoskeletal connectivity in the stability, plasticity, and performance of multicellular networks and architectures. Chronic impairment and/or dysregulation of cell adhesions/synapses, cytoskeletal networks, and/or reversible epithelial-to-mesenchymal-like transitions, which enable and mediate the stable and coherent yet dynamic and reconfigurable multicellular architectures, may lead to the emergence and persistence of the disordered, wound-like pockets/microenvironments of chronically disconnected cells. Such wound-like microenvironments support and are supported by pro-inflammatory, pro-secretion, de-differentiated cellular phenotypes with altered metabolism and signaling. The co-evolution of wound-like microenvironments and their inhabitants may lead to the selection and stabilization of degenerated cellular phenotypes, via acquisition of epigenetic modifications and mutations, which eventually result in degenerative disorders such as cancer and Alzheimer's disease.}, } @article {pmid26040592, year = {2015}, author = {Brumley, DR and Polin, M and Pedley, TJ and Goldstein, RE}, title = {Metachronal waves in the flagellar beating of Volvox and their hydrodynamic origin.}, journal = {Journal of the Royal Society, Interface}, volume = {12}, number = {108}, pages = {20141358}, pmid = {26040592}, issn = {1742-5662}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Flagella/*physiology ; Hydrodynamics ; *Models, Biological ; Volvox/*physiology ; }, abstract = {Groups of eukaryotic cilia and flagella are capable of coordinating their beating over large scales, routinely exhibiting collective dynamics in the form of metachronal waves. The origin of this behavior--possibly influenced by both mechanical interactions and direct biological regulation--is poorly understood, in large part due to a lack of quantitative experimental studies. Here we characterize in detail flagellar coordination on the surface of the multicellular alga Volvox carteri, an emerging model organism for flagellar dynamics. Our studies reveal for the first time that the average metachronal coordination observed is punctuated by periodic phase defects during which synchrony is partial and limited to specific groups of cells. A minimal model of hydrodynamically coupled oscillators can reproduce semi-quantitatively the characteristics of the average metachronal dynamics, and the emergence of defects. We systematically study the model's behaviour by assessing the effect of changing intrinsic rotor characteristics, including oscillator stiffness and the nature of their internal driving force, as well as their geometric properties and spatial arrangement. Our results suggest that metachronal coordination follows from deformations in the oscillators' limit cycles induced by hydrodynamic stresses, and that defects result from sufficiently steep local biases in the oscillators' intrinsic frequencies. Additionally, we find that random variations in the intrinsic rotor frequencies increase the robustness of the average properties of the emergent metachronal waves.}, } @article {pmid26021328, year = {2015}, author = {Santos, J and Monteagudo, Á}, title = {Analysis of behaviour transitions in tumour growth using a cellular automaton simulation.}, journal = {IET systems biology}, volume = {9}, number = {3}, pages = {75-87}, pmid = {26021328}, issn = {1751-8849}, mesh = {Animals ; Carcinogenesis/*pathology ; Cell Proliferation ; Computer Simulation ; Humans ; *Models, Biological ; Neoplasms/*pathology/*physiopathology ; Spheroids, Cellular/*pathology/*physiology ; }, abstract = {The authors used computational biology as an approach for analysing the emergent dynamics of tumour growth at cellular level. They applied cellular automata for modelling the behaviour of cells when the main cancer cell hallmarks are present. Their model is oriented to mimic the development of multicellular spheroids of tumour cells. In their modelling, cells have a genome associated with the different cancer hallmarks, indicating if those are acquired as a consequence of mutations. The presence of the cancer hallmarks defines cell states and cell mitotic behaviours. These hallmarks are associated with a series of parameters, and depending on their values and the activation of the hallmarks in each of the cells, the system can evolve to different dynamics. With the simulation tool the authors performed an analysis of the first phases of cancer growth, using different and alternative strategies: firstly, studying the evolution of cancer cells and hallmarks in different representative situations regarding initial conditions and parameters, analysing the relative importance of the hallmarks for tumour progression; secondly, being the focus of this work, inspecting the behaviour transitions when the cancer cells are killed with a given probability during the cellular system progression.}, } @article {pmid26018043, year = {2015}, author = {Ho, HI and Shaulsky, G}, title = {Temporal regulation of kin recognition maintains recognition-cue diversity and suppresses cheating.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {7144}, pmid = {26018043}, issn = {2041-1723}, support = {CA125123/CA/NCI NIH HHS/United States ; HD007495/HD/NICHD NIH HHS/United States ; T32 HD007495/HD/NICHD NIH HHS/United States ; U54 HD007495/HD/NICHD NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; DK56338/DK/NIDDK NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R01 GM098276/GM/NIGMS NIH HHS/United States ; P30 HD007495/HD/NICHD NIH HHS/United States ; }, mesh = {Biological Evolution ; Cues ; Dictyostelium/*genetics/metabolism ; Fruiting Bodies, Fungal/*genetics/metabolism ; *Genetic Variation ; Membrane Proteins/*genetics/metabolism ; *Microbial Interactions ; Polymorphism, Genetic ; Protozoan Proteins/*genetics/metabolism ; Spores, Protozoan ; }, abstract = {Kin recognition, the ability to distinguish kin from non-kin, can facilitate cooperation between relatives. Evolutionary theory predicts that polymorphism in recognition cues, which is essential for effective recognition, would be unstable. Individuals carrying rare recognition cues would benefit less from social interactions than individuals with common cues, leading to loss of the genetic-cue diversity. We test this evolutionary hypothesis in Dictyostelium discoideum, which forms multicellular fruiting bodies by aggregation and utilizes two polymorphic membrane proteins to facilitate preferential cooperation. Surprisingly, we find that rare recognition variants are tolerated and maintain their frequencies among incompatible majority during development. Although the rare variants are initially excluded from the aggregates, they subsequently rejoin the aggregate and produce spores. Social cheating is also refrained in late development, thus limiting the cost of chimerism. Our results suggest a potential mechanism to sustain the evolutionary stability of kin-recognition genes and to suppress cheating.}, } @article {pmid26014922, year = {2015}, author = {Torday, JS}, title = {The cell as the mechanistic basis for evolution.}, journal = {Wiley interdisciplinary reviews. Systems biology and medicine}, volume = {7}, number = {5}, pages = {275-284}, doi = {10.1002/wsbm.1305}, pmid = {26014922}, issn = {1939-005X}, mesh = {Animals ; *Biological Evolution ; Genotype ; Humans ; Lung/cytology/metabolism ; Phenotype ; *Phylogeny ; }, abstract = {The First Principles for Physiology originated in and emanate from the unicellular state of life. Viewing physiology as a continuum from unicellular to multicellular organisms provides fundamental insight to ontogeny and phylogeny as a functionally integral whole. Such mechanisms are most evident under conditions of physiologic stress; all of the molecular pathways that evolved in service to the vertebrate water-land transition aided and abetted the evolution of the vertebrate lung, for example. Reduction of evolution to cell biology has an important scientific feature—it is predictive. One implication of this perspective on evolution is the likelihood that it is the unicellular state that is actually the object of selection. By looking at the process of evolution from its unicellular origins, the causal relationships between genotype and phenotype are revealed, as are many other aspects of physiology and medicine that have remained anecdotal and counter-intuitive. Evolutionary development can best be considered as a cyclical, epigenetic, reiterative environmental assessment process, originating from the unicellular state, both forward and backward, to sustain and perpetuate unicellular homeostasis.}, } @article {pmid25994183, year = {2015}, author = {Labeeuw, L and Martone, PT and Boucher, Y and Case, RJ}, title = {Ancient origin of the biosynthesis of lignin precursors.}, journal = {Biology direct}, volume = {10}, number = {}, pages = {23}, pmid = {25994183}, issn = {1745-6150}, mesh = {Alcohols/chemistry ; Aldehyde Oxidoreductases/metabolism ; Arabidopsis/genetics ; Biological Evolution ; Chlamydomonas/*genetics ; Chlorella/*genetics ; Computational Biology ; Dinoflagellida/genetics ; Evolution, Molecular ; Gene Transfer, Horizontal ; Haptophyta/genetics ; Lignin/*biosynthesis ; Likelihood Functions ; Photosynthesis ; Phylogeny ; Selaginellaceae/genetics ; }, abstract = {BACKGROUND: Lignin plays an important role in plant structural support and water transport, and is considered one of the hallmarks of land plants. The recent discovery of lignin or its precursors in various algae has raised questions on the evolution of its biosynthetic pathway, which could be much more ancient than previously thought. To determine the taxonomic distribution of the lignin biosynthesis genes, we screened all publicly available genomes of algae and their closest non-photosynthetic relatives, as well as representative land plants. We also performed phylogenetic analysis of these genes to decipher the evolution and origin(s) of lignin biosynthesis.

RESULTS: Enzymes involved in making p-coumaryl alcohol, the simplest lignin monomer, are found in a variety of photosynthetic eukaryotes, including diatoms, dinoflagellates, haptophytes, cryptophytes as well as green and red algae. Phylogenetic analysis of these enzymes suggests that they are ancient and spread to some secondarily photosynthetic lineages when they acquired red and/or green algal endosymbionts. In some cases, one or more of these enzymes was likely acquired through lateral gene transfer (LGT) from bacteria.

CONCLUSIONS: Genes associated with p-coumaryl alcohol biosynthesis are likely to have evolved long before the transition of photosynthetic eukaryotes to land. The original function of this lignin precursor is therefore unlikely to have been related to water transport. We suggest that it participates in the biological defense of some unicellular and multicellular algae.}, } @article {pmid25993239, year = {2015}, author = {Shlush, LI and Hershkovitz, D}, title = {Clonal evolution models of tumor heterogeneity.}, journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting}, volume = {}, number = {}, pages = {e662-5}, doi = {10.14694/EdBook_AM.2015.35.e662}, pmid = {25993239}, issn = {1548-8756}, mesh = {*Clonal Evolution ; Genetic Heterogeneity ; Humans ; Neoplasms/diagnosis/genetics/*pathology ; Neoplastic Stem Cells/*pathology ; Precancerous Conditions/diagnosis/genetics/pathology ; }, abstract = {Somatic/clonal evolution is the process of sequential acquisition of vertically transmittable genetic/epigenetic elements in multicellular organisms. Cancer is the result of somatic evolution. Understanding the processes that shape the evolution of individual tumors might help us to treat cancer more efficiently. The initiating genetic/epigenetic events occur in functional cells and provide the cell of origin a selective advantage under a changing environment. The initiating genetic events tend to be enriched in specific tissues (and are sometimes specific for those tissues), as different tissues undergo different changes in the environment that will activate selective forces on different cells of origin. For the initial clonal expansion to occur premalignant clones need to have a relative fitness advantage over their competitors. It is estimated that the premalignant phase can take several years. Once the premalignant clonal expansion is established, the premalignant cells will contribute to the changing environment and will start competing among themselves. In late stages of cancer evolution the environmental changes might be similar across different tissues, including a lack of physical space, a shortage of energy, and activation of the immune system, and more and more of the hallmarks of cancer will evolve. In this review we will explore the possible clinical relevance of the heterogeneity that evolves during this long somatic evolution. Above all, it should be stressed that the earlier the clonal expansion is recognized, the less diverse and less fit for survival the cells in the population are.}, } @article {pmid25984697, year = {2015}, author = {Sarioglu, AF and Aceto, N and Kojic, N and Donaldson, MC and Zeinali, M and Hamza, B and Engstrom, A and Zhu, H and Sundaresan, TK and Miyamoto, DT and Luo, X and Bardia, A and Wittner, BS and Ramaswamy, S and Shioda, T and Ting, DT and Stott, SL and Kapur, R and Maheswaran, S and Haber, DA and Toner, M}, title = {A microfluidic device for label-free, physical capture of circulating tumor cell clusters.}, journal = {Nature methods}, volume = {12}, number = {7}, pages = {685-691}, pmid = {25984697}, issn = {1548-7105}, support = {U01 EB012493/EB/NIBIB NIH HHS/United States ; R01 EB008047/EB/NIBIB NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; K12 CA087723/CA/NCI NIH HHS/United States ; P41 EB002503/EB/NIBIB NIH HHS/United States ; }, mesh = {Breast Neoplasms/pathology ; Cell Line, Tumor ; Female ; Humans ; Immunohistochemistry ; Male ; *Microfluidic Analytical Techniques ; *Neoplastic Cells, Circulating ; Prostatic Neoplasms/pathology ; Sequence Analysis, RNA ; }, abstract = {Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC clusters). Existing technologies for CTC enrichment are designed to isolate single CTCs, and although CTC clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here we developed a microchip technology (the Cluster-Chip) to capture CTC clusters independently of tumor-specific markers from unprocessed blood. CTC clusters are isolated through specialized bifurcating traps under low-shear stress conditions that preserve their integrity, and even two-cell clusters are captured efficiently. Using the Cluster-Chip, we identified CTC clusters in 30-40% of patients with metastatic breast or prostate cancer or with melanoma. RNA sequencing of CTC clusters confirmed their tumor origin and identified tissue-derived macrophages within the clusters. Efficient capture of CTC clusters will enable the detailed characterization of their biological properties and role in metastasis.}, } @article {pmid25983206, year = {2015}, author = {Kawashima, T and Lorković, ZJ and Nishihama, R and Ishizaki, K and Axelsson, E and Yelagandula, R and Kohchi, T and Berger, F}, title = {Diversification of histone H2A variants during plant evolution.}, journal = {Trends in plant science}, volume = {20}, number = {7}, pages = {419-425}, doi = {10.1016/j.tplants.2015.04.005}, pmid = {25983206}, issn = {1878-4372}, mesh = {Amino Acid Sequence ; *Biological Evolution ; Histones/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Plants/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {Among eukaryotes, the four core histones show an extremely high conservation of their structure and form nucleosomes that compact, protect, and regulate access to genetic information. Nevertheless, in multicellular eukaryotes the two families, histone H2A and histone H3, have diversified significantly in key residues. We present a phylogenetic analysis across the green plant lineage that reveals an early diversification of the H2A family in unicellular green algae and remarkable expansions of H2A variants in flowering plants. We define motifs and domains that differentiate plant H2A proteins into distinct variant classes. In non-flowering land plants, we identify a new class of H2A variants and propose their possible role in the emergence of the H2A.W variant class in flowering plants.}, } @article {pmid25976758, year = {2015}, author = {Otten, AB and Smeets, HJ}, title = {Evolutionary defined role of the mitochondrial DNA in fertility, disease and ageing.}, journal = {Human reproduction update}, volume = {21}, number = {5}, pages = {671-689}, doi = {10.1093/humupd/dmv024}, pmid = {25976758}, issn = {1460-2369}, mesh = {Aging/*genetics ; Animals ; *Biological Evolution ; DNA, Mitochondrial/*genetics/*physiology ; Fertility/*genetics ; Fungi/genetics ; Genome/genetics ; Humans ; Mutation/genetics ; Phylogeny ; Plants/genetics ; Reproduction/genetics ; }, abstract = {BACKGROUND: The endosymbiosis of an alpha-proteobacterium and a eubacterium a billion years ago paved the way for multicellularity and enabled eukaryotes to flourish. The selective advantage for the host was the acquired ability to generate large amounts of intracellular hydrogen-dependent adenosine triphosphate. The price was increased reactive oxygen species (ROS) inside the eukaryotic cell, causing high mutation rates of the mitochondrial DNA (mtDNA). According to the Muller's ratchet theory, this accumulation of mutations in asexually transmitted mtDNA would ultimately lead to reduced reproductive fitness and eventually extinction. However, mitochondria have persisted over the course of evolution, initially due to a rapid, extreme evolutionary reduction of the mtDNA content. After the phylogenetic divergence of eukaryotes into animals, fungi and plants, differences in evolution of the mtDNA occurred with different adaptations for coping with the mutation burden within these clades. As a result, mitochondrial evolutionary mechanisms have had a profound effect on human adaptation, fertility, healthy reproduction, mtDNA disease manifestation and transmission and ageing. An understanding of these mechanisms might elucidate novel approaches for treatment and prevention of mtDNA disease.

METHODS: The scientific literature was investigated to determine how mtDNA evolved in animals, plants and fungi. Furthermore, the different mechanisms of mtDNA inheritance and of balancing Muller's ratchet in these species were summarized together with the consequences of these mechanisms for human health and reproduction.

RESULTS: Animal, plant and fungal mtDNA have evolved differently. Animals have compact genomes, little recombination, a stable number of genes and a high mtDNA copy number, whereas plants have larger genomes with variable gene counts, a low mtDNA copy number and many recombination events. Fungal mtDNA is somewhere in between. In plants, the mtDNA mutation rate is kept low by effective ROS defence and efficient recombination-mediated mtDNA repair. In animal mtDNA, these mechanisms are not or less well-developed and the detrimental mutagenesis events are controlled by a high mtDNA copy number in combination with a genetic bottleneck and purifying selection during transmission. The mtDNA mutation rates in animals are higher than in plants, which allow mobile animals to adapt more rapidly to various environmental conditions in terms of energy production, whereas static plants do not have this need. Although at the level of the species, these mechanisms have been extremely successful, they can have adverse effects for the individual, resulting, in humans, in severe or unpredictably segregating mtDNA diseases, as well as fertility problems and unhealthy ageing.

CONCLUSIONS: Understanding the forces and processes that underlie mtDNA evolution among different species increases our knowledge on the detrimental consequences that individuals can have from these evolutionary end-points. Alternative outcomes in animals, fungi and plants will lead to a better understanding of the inheritance of mtDNA disorders and mtDNA-related fertility problems. These will allow the development of options to ameliorate, cure and/or prevent mtDNA diseases and mtDNA-related fertility problems.}, } @article {pmid25976756, year = {2015}, author = {Breugelmans, B and Ansell, BR and Young, ND and Amani, P and Stroehlein, AJ and Sternberg, PW and Jex, AR and Boag, PR and Hofmann, A and Gasser, RB}, title = {Flatworms have lost the right open reading frame kinase 3 gene during evolution.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {9417}, pmid = {25976756}, issn = {2045-2322}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Biological Evolution ; Evolution, Molecular ; Open Reading Frames/*genetics ; Platyhelminths/*genetics ; Protein Serine-Threonine Kinases/*genetics ; }, abstract = {All multicellular organisms studied to date have three right open reading frame kinase genes (designated riok-1, riok-2 and riok-3). Current evidence indicates that riok-1 and riok-2 have essential roles in ribosome biosynthesis, and that the riok-3 gene assists this process. In the present study, we conducted a detailed bioinformatic analysis of the riok gene family in 25 parasitic flatworms (platyhelminths) for which extensive genomic and transcriptomic data sets are available. We found that none of the flatworms studied have a riok-3 gene, which is unprecedented for multicellular organisms. We propose that, unlike in other eukaryotes, the loss of RIOK-3 from flatworms does not result in an evolutionary disadvantage due to the unique biology and physiology of this phylum. We show that the loss of RIOK-3 coincides with a loss of particular proteins associated with essential cellular pathways linked to cell growth and apoptosis. These findings indicate multiple, key regulatory functions of RIOK-3 in other metazoan species. Taking advantage of a known partial crystal structure of human RIOK-1, molecular modelling revealed variability in nucleotide binding sites between flatworm and human RIOK proteins.}, } @article {pmid25964342, year = {2015}, author = {West, SA and Fisher, RM and Gardner, A and Kiers, ET}, title = {Major evolutionary transitions in individuality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {33}, pages = {10112-10119}, pmid = {25964342}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; Communication ; Cooperative Behavior ; Diploidy ; Ecology ; Female ; Genetic Drift ; Haploidy ; Humans ; Individuality ; Male ; Social Behavior ; Symbiosis/*physiology ; }, abstract = {The evolution of life on earth has been driven by a small number of major evolutionary transitions. These transitions have been characterized by individuals that could previously replicate independently, cooperating to form a new, more complex life form. For example, archaea and eubacteria formed eukaryotic cells, and cells formed multicellular organisms. However, not all cooperative groups are en route to major transitions. How can we explain why major evolutionary transitions have or haven't taken place on different branches of the tree of life? We break down major transitions into two steps: the formation of a cooperative group and the transformation of that group into an integrated entity. We show how these steps require cooperation, division of labor, communication, mutual dependence, and negligible within-group conflict. We find that certain ecological conditions and the ways in which groups form have played recurrent roles in driving multiple transitions. In contrast, we find that other factors have played relatively minor roles at many key points, such as within-group kin discrimination and mechanisms to actively repress competition. More generally, by identifying the small number of factors that have driven major transitions, we provide a simpler and more unified description of how life on earth has evolved.}, } @article {pmid25963254, year = {2015}, author = {Mishra, H and Saran, S}, title = {Classification and expression analyses of homeobox genes from Dictyostelium discoideum.}, journal = {Journal of biosciences}, volume = {40}, number = {2}, pages = {241-255}, pmid = {25963254}, issn = {0973-7138}, mesh = {Amino Acid Sequence ; Animals ; Dictyostelium/*genetics ; Genes, Homeobox/*genetics ; Genome/genetics ; Homeodomain Proteins/*classification/*genetics ; Molecular Sequence Data ; Phylogeny ; Promoter Regions, Genetic/*genetics ; Sequence Alignment ; }, abstract = {Homeobox genes are compared between genomes in an attempt to understand the evolution of animal development. The ability of the protist, Dictyostelium discoideum, to shift between uni- and multicellularity makes this group ideal for studying the genetic changes that may have occurred during this transition. We present here the first genome-wide classification and comparative genomic analysis of the 14 homeobox genes present in D. discoideum. Based on the structural alignment of the homeodomains, they can be broadly divided into TALE and non-TALE classes. When individual homeobox genes were compared with members of known class or family, we could further classify them into 3 groups, namely, TALE, OTHER and NOVEL classes, but no HOX family was found. The 5 members of TALE class could be further divided into PBX, PKNOX, IRX and CUP families; 4 homeobox genes classified as NOVEL did not show any similarity to any known homeobox genes; while the remaining 5 were classified as OTHERS as they did show certain degree of similarity to few known homeobox genes. No unique RNA expression pattern during development of D. discoideum emerged for members of an individual group. Putative promoter analysis revealed binding sites for few homeobox transcription factors among many probable factors.}, } @article {pmid25960408, year = {2015}, author = {Kraushaar, T and Brückner, S and Veelders, M and Rhinow, D and Schreiner, F and Birke, R and Pagenstecher, A and Mösch, HU and Essen, LO}, title = {Interactions by the Fungal Flo11 Adhesin Depend on a Fibronectin Type III-like Adhesin Domain Girdled by Aromatic Bands.}, journal = {Structure (London, England : 1993)}, volume = {23}, number = {6}, pages = {1005-1017}, doi = {10.1016/j.str.2015.03.021}, pmid = {25960408}, issn = {1878-4186}, mesh = {Amino Acid Sequence ; Amino Acids, Aromatic/chemistry ; Cell Adhesion/*physiology ; Fibronectins/*metabolism ; Membrane Glycoproteins/*chemistry/genetics/*metabolism ; *Models, Molecular ; Molecular Sequence Data ; Multigene Family/*genetics ; Phylogeny ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/*chemistry ; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*metabolism ; }, abstract = {Saccharomyces cerevisiae harbors a family of GPI-anchored cell wall proteins for interaction with its environment. The flocculin Flo11, a major representative of these fungal adhesins, confers formation of different types of multicellular structures such as biofilms, flors, or filaments. To understand these environment-dependent growth phenotypes on a molecular level, we solved the crystal structure of the N-terminal Flo11A domain at 0.89-Å resolution. Besides a hydrophobic apical region, the Flo11A domain consists of a β sandwich of the fibronectin type III domain (FN3). We further show that homophilic Flo11-Flo11 interactions and heterophilic Flo11-plastic interactions solely depend on the Flo11A domain and are strongly pH dependent. These functions of Flo11A involve an apical region with its surface-exposed aromatic band, which is accompanied by acidic stretches. Together with electron microscopic reconstructions of yeast cell-cell contact sites, our data suggest that Flo11 acts as a spacer-like, pH-sensitive adhesin that resembles a membrane-tethered hydrophobin.}, } @article {pmid25944666, year = {2015}, author = {Dall, SR and McNamara, JM and Leimar, O}, title = {Genes as cues: phenotypic integration of genetic and epigenetic information from a Darwinian perspective.}, journal = {Trends in ecology & evolution}, volume = {30}, number = {6}, pages = {327-333}, doi = {10.1016/j.tree.2015.04.002}, pmid = {25944666}, issn = {1872-8383}, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; *Epigenesis, Genetic ; Gene-Environment Interaction ; *Genes ; Growth and Development/genetics ; Phenotype ; Plant Development/genetics ; Selection, Genetic ; }, abstract = {The development of multicellular organisms involves a delicate interplay between genetic and environmental influences. It is often useful to think of developmental systems as integrating available sources of information about current conditions to produce organisms. Genes and inherited physiology provide cues, as does the state of the environment during development. The integration systems themselves are under genetic control and subject to Darwinian selection, so we expect them to evolve to produce organisms that fit well with current ecological (including social) conditions. We argue for the scientific value of this explicitly informational perspective by providing detailed examples of how it can elucidate taxonomically diverse phenomena. We also present a general framework for linking genetic and phenotypic variation from an informational perspective. This application of Darwinian logic at the organismal level can elucidate genetic influences on phenotypic variation in novel and counterintuitive ways.}, } @article {pmid25942385, year = {2015}, author = {McKenney, EA and Williamson, L and Yoder, AD and Rawls, JF and Bilbo, SD and Parker, W}, title = {Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta.}, journal = {Gut microbes}, volume = {6}, number = {3}, pages = {182-193}, pmid = {25942385}, issn = {1949-0984}, mesh = {Animals ; Bacteria/*classification/*isolation & purification ; Cecum/*microbiology/*parasitology ; Female ; *Gastrointestinal Microbiome ; Hymenolepis diminuta/*growth & development ; Male ; Rats, Sprague-Dawley ; }, abstract = {The microbiome is now widely recognized as being important in health and disease, and makes up a substantial subset of the biome within the ecosystem of the vertebrate body. At the same time, multicellular, eukaryotic organisms such as helminths are being recognized as an important component of the biome that shaped the evolution of our genes. The absence of these macroscopic organisms during the early development and life of humans in Western culture probably leads to a wide range of human immunological diseases. However, the interaction between the microbiome and macroscopic components of the biome remains poorly characterized. In this study, the microbiome of the cecum in rats colonized for 2 generations with the small intestinal helminth Hymenolepis diminuta was evaluated. The introduction of this benign helminth, which is of considerable therapeutic interest, led to several changes in the cecal microbiome. Most of the changes were within the Firmicutes phylum, involved about 20% of the total bacteria, and generally entailed a shift from Bacilli to Clostridia species in the presence of the helminth. The results point toward ecological relationships between various components of the biome, with the observed shifts in the microbiome suggesting potential mechanisms by which this helminth might exert therapeutic effects.}, } @article {pmid25934012, year = {2015}, author = {Niklas, KJ}, title = {A phyletic perspective on cell growth.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {7}, number = {5}, pages = {}, pmid = {25934012}, issn = {1943-0264}, mesh = {Animals ; *Cell Division ; Cell Size ; Humans ; *Phylogeny ; }, abstract = {Commonalities, as well as lineage-specific differences among bacteria, fungi, plants, and animals, are reviewed in the context of (1) the coordination of cell growth, (2) the flow of mass and energy affecting the physiological status of cells, (3) cytoskeletal dynamics during cell division, and (4) the coordination of cell size in multicellular organs and organisms. A comparative approach reveals that similar mechanisms are used to gauge and regulate cell size and proliferation, and shows that these mechanisms share similar modules to measure cell size, cycle status, competence, and number, as well as ploidy levels, nutrient availability, and other variables affecting cell growth. However, this approach also reveals that these modules often use nonhomologous subsystems when viewed at modular or genomic levels; that is, different lineages have evolved functionally analogous, but not genomically homologous, ways of either sensing or regulating cell size and growth, in much the same way that multicellularity has evolved in different lineages using analogous developmental modules.}, } @article {pmid25926981, year = {2015}, author = {Urban, JM and Foulk, MS and Casella, C and Gerbi, SA}, title = {The hunt for origins of DNA replication in multicellular eukaryotes.}, journal = {F1000prime reports}, volume = {7}, number = {}, pages = {30}, pmid = {25926981}, issn = {2051-7599}, support = {T32 GM007601/GM/NIGMS NIH HHS/United States ; }, abstract = {Origins of DNA replication (ORIs) occur at defined regions in the genome. Although DNA sequence defines the position of ORIs in budding yeast, the factors for ORI specification remain elusive in metazoa. Several methods have been used recently to map ORIs in metazoan genomes with the hope that features for ORI specification might emerge. These methods are reviewed here with analysis of their advantages and shortcomings. The various factors that may influence ORI selection for initiation of DNA replication are discussed.}, } @article {pmid25923201, year = {2015}, author = {Nam, HJ and Kim, I and Bowie, JU and Kim, S}, title = {Metazoans evolved by taking domains from soluble proteins to expand intercellular communication network.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {9576}, pmid = {25923201}, issn = {2045-2322}, support = {R01 GM063919/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Cell Adhesion/genetics ; Cell Communication/*genetics ; Membrane Proteins/*genetics ; Protein Interaction Domains and Motifs/*genetics ; Protein Structure, Tertiary/*genetics ; Signal Transduction/*genetics ; }, abstract = {A central question in animal evolution is how multicellular animals evolved from unicellular ancestors. We hypothesize that membrane proteins must be key players in the development of multicellularity because they are well positioned to form the cell-cell contacts and to provide the intercellular communication required for the creation of complex organisms. Here we find that a major mechanism for the necessary increase in membrane protein complexity in the transition from non-metazoan to metazoan life was the new incorporation of domains from soluble proteins. The membrane proteins that have incorporated soluble domains in metazoans are enriched in many of the functions unique to multicellular organisms such as cell-cell adhesion, signaling, immune defense and developmental processes. They also show enhanced protein-protein interaction (PPI) network complexity and centrality, suggesting an important role in the cellular diversification found in complex organisms. Our results expose an evolutionary mechanism that contributed to the development of higher life forms.}, } @article {pmid25918398, year = {2015}, author = {Takeuchi, T and Suzuki, M and Fujikake, N and Popiel, HA and Kikuchi, H and Futaki, S and Wada, K and Nagai, Y}, title = {Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {19}, pages = {E2497-506}, pmid = {25918398}, issn = {1091-6490}, mesh = {Animals ; Animals, Genetically Modified ; Cell Line ; Drosophila ; Drosophila melanogaster ; Exosomes/*metabolism ; HSP40 Heat-Shock Proteins/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; Heat-Shock Proteins/metabolism ; Homeostasis ; Mice ; Microscopy, Electron ; Molecular Chaperones/*metabolism ; Neurodegenerative Diseases/pathology ; Peptides/chemistry ; Protein Folding ; Protein Structure, Tertiary ; Signal Transduction ; Transcription, Genetic ; Transfection ; }, abstract = {The heat shock response (HSR), a transcriptional response that up-regulates molecular chaperones upon heat shock, is necessary for cell survival in a stressful environment to maintain protein homeostasis (proteostasis). However, there is accumulating evidence that the HSR does not ubiquitously occur under stress conditions, but largely depends on the cell types. Despite such imbalanced HSR among different cells and tissues, molecular mechanisms by which multicellular organisms maintain their global proteostasis have remained poorly understood. Here, we report that proteostasis can be maintained by molecular chaperones not only in a cell-autonomous manner but also in a non-cell-autonomous manner. We found that elevated expression of molecular chaperones, such as Hsp40 and Hsp70, in a group of cells improves proteostasis in other groups of cells, both in cultured cells and in Drosophila expressing aggregation-prone polyglutamine proteins. We also found that Hsp40, as well as Hsp70 and Hsp90, is physiologically secreted from cells via exosomes, and that the J domain at the N terminus is responsible for its exosome-mediated secretion. Addition of Hsp40/Hsp70-containing exosomes to the culture medium of the polyglutamine-expressing cells results in efficient suppression of inclusion body formation, indicating that molecular chaperones non-cell autonomously improve the protein-folding environment via exosome-mediated transmission. Our study reveals that intercellular chaperone transmission mediated by exosomes is a novel molecular mechanism for non-cell-autonomous maintenance of organismal proteostasis that could functionally compensate for the imbalanced state of the HSR among different cells, and also provides a novel physiological role of exosomes that contributes to maintenance of organismal proteostasis.}, } @article {pmid25917826, year = {2015}, author = {Liu, C and Peng, J and Matzuk, MM and Yao, HH}, title = {Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {6934}, pmid = {25917826}, issn = {2041-1723}, support = {ZIA ES102965-03//Intramural NIH HHS/United States ; R01 HD033438/HD/NICHD NIH HHS/United States ; ZIA ES102965-02//Intramural NIH HHS/United States ; ZIA ES102965-04//Intramural NIH HHS/United States ; Z99 ES999999//Intramural NIH HHS/United States ; ZIA ES102965-01//Intramural NIH HHS/United States ; ES102965/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Cell Lineage ; Female ; Granulosa Cells/metabolism ; Growth Differentiation Factor 9/*metabolism ; Hedgehog Proteins/*metabolism ; Kruppel-Like Transcription Factors/metabolism ; Male ; Mesonephros/cytology ; Mice ; Oocytes/*metabolism ; Organ Culture Techniques ; Ovary/*embryology ; Repressor Proteins/metabolism ; *Theca Cells ; Transcriptome ; WT1 Proteins ; Zinc Finger Protein GLI1 ; }, abstract = {Organogenesis of the ovary is a highly orchestrated process involving multiple lineage determination of ovarian surface epithelium, granulosa cells and theca cells. Although the sources of ovarian surface epithelium and granulosa cells are known, the origin(s) of theca progenitor cells have not been definitively identified. Here we show that theca cells derive from two sources: Wt1(+) cells indigenous to the ovary and Gli1(+) mesenchymal cells that migrate from the mesonephros. These progenitors acquire theca lineage marker Gli1 in response to paracrine signals Desert hedgehog (Dhh) and Indian hedgehog (Ihh) from granulosa cells. Ovaries lacking Dhh/Ihh exhibit theca layer loss, blunted steroid production, arrested folliculogenesis and failure to form corpora lutea. Production of Dhh/Ihh in granulosa cells requires growth differentiation factor 9 (GDF9) from the oocyte. Our studies provide the first genetic evidence for the origins of theca cells and reveal a multicellular interaction critical for the formation of a functional theca.}, } @article {pmid25912359, year = {2015}, author = {Elvitigala, DA and Premachandra, HK and Whang, I and Yeo, SY and Choi, CY and Noh, JK and Lee, J}, title = {Molecular cloning, expression and functional characterization of a teleostan cytokine-induced apoptosis inhibitor from rock bream (Oplegnathus fasciatus).}, journal = {Developmental and comparative immunology}, volume = {52}, number = {1}, pages = {48-57}, doi = {10.1016/j.dci.2015.03.016}, pmid = {25912359}, issn = {1879-0089}, mesh = {Animals ; Apoptosis/genetics ; Base Sequence ; Blood Proteins/metabolism ; Caspase 3/metabolism ; Chemokine CXCL10/genetics/*metabolism ; Cloning, Molecular ; Cypriniformes/genetics/*immunology ; Fish Proteins/genetics/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Liver/*physiology ; Molecular Sequence Data ; Phylogeny ; Transcriptome ; }, abstract = {Apoptosis plays a key role in the physiology of multicellular organisms and is regulated by different promoting and inhibitory mechanisms. Cytokine-induced apoptotic inhibitor (CIAPI) was recently identified as a key factor involved in apoptosis inhibition in higher vertebrate lineages. However, most of the CIAPIs of lower vertebrate species are yet to be characterized. Herein, we molecularly characterized a teleostan counterpart of CIAPI from rock bream (Oplegnathus fasciatus), designating as RbCIAPI. The complete coding region of RbCIAPI was consisted of 942 nucleotides encoding a protein of 313 amino acids with a predicted molecular mass of ~33 kDa. RbCIAPI gene exhibited a multi-exonic architecture, consisting 9 exons interrupted by 8 introns. Protein sequence analysis revealed that RbCIAPI shares significant homology with known CIAPI counterparts, and phylogenetic reconstruction confirmed its closer evolutionary relationship with its fish counterparts. Ubiquitous spatial distribution of RbCIAPI was detected in our quantitative real time polymerase chain reaction (qPCR) analysis, where more prominent expression levels were observed in the blood and liver tissues. Moreover, the RbCIAPI basal transcription level was found to be modulated by different bacterial and viral stimuli, which could be plausibly supported by our previous observations on the transcriptional modulation of the caspase 3 counterpart of rock bream (Rbcasp3) in response to the same stimuli. In addition, our in vitro functional assay demonstrated that recombinant RbCIAPI could detectably inhibit the proteolysis activity of recombinant Rbcasp3. Collectively, our preliminary results suggest that RbCIAPI may play an anti-apoptotic role in rock bream physiology, likely by inhibiting the caspase-dependent apoptosis pathway. Therefore, RbCIAPI potentially plays an important role in host immunity by regulating the apoptosis process under pathogenic stress.}, } @article {pmid25904926, year = {2015}, author = {Gao, D and Jiang, N and Wing, RA and Jiang, J and Jackson, SA}, title = {Transposons play an important role in the evolution and diversification of centromeres among closely related species.}, journal = {Frontiers in plant science}, volume = {6}, number = {}, pages = {216}, pmid = {25904926}, issn = {1664-462X}, abstract = {Centromeres are important chromosomal regions necessary for eukaryotic cell segregation and replication. Due to high amounts of tandem repeats and transposons, centromeres have been difficult to sequence in most multicellular organisms, thus their sequence structure and evolution are poorly understood. In this study, we analyzed transposons in the centromere 8 (Cen8) from the African cultivated rice (O. glaberrima) and two subspecies of the Asian cultivated rice (O. sativa), indica and japonica. We detected much higher transposon contents (>69%) in centromere regions than in the whole genomes of O. sativa ssp. japonica and O. glaberrima (~35%). We compared the three Cen8s and identified numerous recent insertions of transposons that were frequently organized into multiple-layer nested blocks, similar to nested transposons in maize. Except for the Hopi retrotransposon, all LTR retrotransposons were shared but exhibit different abundances amongst the three Cen8s. Even though a majority of the transposons were located in intergenic regions, some gene-related transposons were found and may be involved in gene diversification. Chromatin immunoprecipitated (ChIP) data analysis revealed that 165 families from both Class I and Class II transposons were found in CENH3-associated chromatin sequences. These results indicate essential roles for transposons in centromeres and that the rapid divergence of the Cen8 sequences between the two cultivated rice species was primarily caused by recent transposon insertions.}, } @article {pmid25903626, year = {2015}, author = {Holland, ND and Holland, LZ and Holland, PW}, title = {Scenarios for the making of vertebrates.}, journal = {Nature}, volume = {520}, number = {7548}, pages = {450-455}, pmid = {25903626}, issn = {1476-4687}, mesh = {Animals ; Annelida/anatomy & histology/classification ; Invertebrates/anatomy & histology/classification ; Models, Biological ; *Phylogeny ; Research ; *Vertebrates/anatomy & histology/classification ; }, abstract = {Over the past 200 years, almost every invertebrate phylum has been proposed as a starting point for evolving vertebrates. Most of these scenarios are outdated, but several are still seriously considered. The short-range transition from ancestral invertebrate chordates (similar to amphioxus and tunicates) to vertebrates is well accepted. However, longer-range transitions leading up to the invertebrate chordates themselves are more controversial. Opinion is divided between the annelid and the enteropneust scenarios, predicting, respectively, a complex or a simple ancestor for bilaterian animals. Deciding between these ideas will be facilitated by further comparative studies of multicellular animals, including enigmatic taxa such as xenacoelomorphs.}, } @article {pmid25901306, year = {2015}, author = {Droser, ML and Gehling, JG}, title = {The advent of animals: The view from the Ediacaran.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {16}, pages = {4865-4870}, pmid = {25901306}, issn = {1091-6490}, mesh = {Animals ; *Biota ; *Fossils ; Movement ; Population Dynamics ; Reproduction ; South Australia ; Time Factors ; }, abstract = {Patterns of origination and evolution of early complex life on this planet are largely interpreted from the fossils of the Precambrian soft-bodied Ediacara Biota. These fossils occur globally and represent a diverse suite of organisms living in marine environments. Although these exceptionally preserved fossil assemblages are typically difficult to reconcile with modern phyla, examination of the morphology, ecology, and taphonomy of these taxa provides keys to their relationships with modern taxa. Within the more than 30 million y range of the Ediacara Biota, fossils of these multicellular organisms demonstrate the advent of mobility, heterotrophy by multicellular animals, skeletonization, sexual reproduction, and the assembly of complex ecosystems, all of which are attributes of modern animals. This approach to these fossils, without the constraint of attempting phylogenetic reconstructions, provides a mechanism for comparing these taxa with both living and extinct animals.}, } @article {pmid25898350, year = {2015}, author = {Ovchinnikov, VY and Afonnikov, DA and Vasiliev, GV and Kashina, EV and Sripa, B and Mordvinov, VA and Katokhin, AV}, title = {Identification of microRNA genes in three opisthorchiids.}, journal = {PLoS neglected tropical diseases}, volume = {9}, number = {4}, pages = {e0003680}, pmid = {25898350}, issn = {1935-2735}, mesh = {Animals ; MicroRNAs/genetics ; Multigene Family ; Opisthorchiasis/parasitology ; Opisthorchis/*genetics ; Polymerase Chain Reaction/methods ; RNA, Helminth/*genetics ; }, abstract = {BACKGROUND: Opisthorchis felineus, O. viverrini, and Clonorchis sinensis (family Opisthorchiidae) are parasitic flatworms that pose a serious threat to humans in some countries and cause opisthorchiasis/clonorchiasis. Chronic disease may lead to a risk of carcinogenesis in the biliary ducts. MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression at post-transcriptional level and are implicated in the regulation of various cellular processes during the parasite- host interplay. However, to date, the miRNAs of opisthorchiid flukes, in particular those essential for maintaining their complex biology and parasitic mode of existence, have not been satisfactorily described.

Using a SOLiD deep sequencing-bioinformatic approach, we identified 43 novel and 18 conserved miRNAs for O. felineus (miracidia, metacercariae and adult worms), 20 novel and 16 conserved miRNAs for O. viverrini (adult worms), and 33 novel and 18 conserved miRNAs for C. sinensis (adult worms). The analysis of the data revealed differences in the expression level of conserved miRNAs among the three species and among three the developmental stages of O. felineus. Analysis of miRNA genes revealed two gene clusters, one cluster-like region and one intronic miRNA in the genome. The presence and structure of the two gene clusters were validated using a PCR-based approach in the three flukes.

CONCLUSIONS: This study represents a comprehensive description of miRNAs in three members of the family Opistorchiidae, significantly expands our knowledge of miRNAs in multicellular parasites and provides a basis for understanding the structural and functional evolution of miRNAs in these metazoan parasites. Results of this study also provides novel resources for deeper understanding the complex parasite biology, for further research on the pathogenesis and molecular events of disease induced by the liver flukes. The present data may also facilitate the development of novel approaches for the prevention and treatment of opisthorchiasis/clonorchiasis.}, } @article {pmid25881075, year = {2015}, author = {Kawabe, Y and Schilde, C and Du, Q and Schaap, P}, title = {A conserved signalling pathway for amoebozoan encystation that was co-opted for multicellular development.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {9644}, pmid = {25881075}, issn = {2045-2322}, support = {090276/WT_/Wellcome Trust/United Kingdom ; 100293/WT_/Wellcome Trust/United Kingdom ; 100293Z/12/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; BB/K000799/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adenylyl Cyclases/chemistry/genetics/metabolism ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/chemistry/metabolism ; Dictyostelium/growth & development/*metabolism ; Parasite Encystment ; Phenotype ; Protozoan Proteins/chemistry/genetics/metabolism ; *Signal Transduction ; Stress, Physiological ; }, abstract = {The evolution of multicellularity required novel mechanisms for intercellular communication, but their origin is unclear. Dictyostelium cells exchange signals to position specialized cell types in multicellular spore-bearing structures. These signals activate complex pathways that converge on activation of cAMP-dependent protein kinase (PKA). Genes controlling PKA were detected in the Dictyostelid unicellular ancestors, which like most protists form dormant cysts when experiencing environmental stress. We deleted PKA and the adenylate cyclases AcrA and AcgA, which synthesize cAMP for PKA activation, in the intermediate species Polysphondylium, which can develop into either cysts or into multicellular structures. Loss of PKA prevented multicellular development, but also completely blocked encystation. Loss of AcrA and AcgA, both essential for sporulation in Dictyostelium, did not affect Polysphondylium sporulation, but prevented encystation. We conclude that multicellular cAMP signalling was co-opted from PKA regulation of protist encystation with progressive refunctionalization of pathway components.}, } @article {pmid25876075, year = {2015}, author = {Warren, CR and Kassir, E and Spurlin, J and Martinez, J and Putnam, NH and Farach-Carson, MC}, title = {Evolution of the perlecan/HSPG2 gene and its activation in regenerating Nematostella vectensis.}, journal = {PloS one}, volume = {10}, number = {4}, pages = {e0124578}, pmid = {25876075}, issn = {1932-6203}, support = {P01 CA098912/CA/NCI NIH HHS/United States ; P01CA098912/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Basement Membrane/metabolism/ultrastructure ; Cnidaria/classification/*genetics/metabolism/ultrastructure ; Ctenophora/classification/*genetics/metabolism/ultrastructure ; Evolution, Molecular ; Gene Expression ; Heparan Sulfate Proteoglycans/chemistry/*genetics/metabolism ; Humans ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Placozoa/classification/*genetics/metabolism/ultrastructure ; Polymerase Chain Reaction ; Porifera/classification/*genetics/metabolism/ultrastructure ; Regeneration/*genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {The heparan sulfate proteoglycan 2 (HSPG2)/perlecan gene is ancient and conserved in all triploblastic species. Its presence maintains critical cell boundaries in tissue and its large (up to ~900 kDa) modular structure has prompted speculation about the evolutionary origin of the gene. The gene's conservation amongst basal metazoans is unclear. After the recent sequencing of their genomes, the cnidarian Nematostella vectensis and the placozoan Trichoplax adhaerens have become favorite models for studying tissue regeneration and the evolution of multicellularity. More ancient basal metazoan phyla include the poriferan and ctenophore, whose evolutionary relationship has been clarified recently. Our in silico and PCR-based methods indicate that the HSPG2 gene is conserved in both the placozoan and cnidarian genomes, but not in those of the ctenophores and only partly in poriferan genomes. HSPG2 also is absent from published ctenophore and Capsaspora owczarzaki genomes. The gene in T. adhaerens is encoded as two separate but genetically juxtaposed genes that house all of the constituent pieces of the mammalian HSPG2 gene in tandem. These genetic constituents are found in isolated genes of various poriferan species, indicating a possible intronic recombinatory mechanism for assembly of the HSPG2 gene. Perlecan's expression during wound healing and boundary formation is conserved, as expression of the gene was activated during tissue regeneration and reformation of the basement membrane of N. vectensis. These data indicate that the complex HSPG2 gene evolved concurrently in a common ancestor of placozoans, cnidarians and bilaterians, likely along with the development of differentiated cell types separated by acellular matrices, and is activated to reestablish these tissue borders during wound healing.}, } @article {pmid25874475, year = {2015}, author = {Kianianmomeni, A}, title = {Cell-type specific photoreceptors and light signaling pathways in the multicellular green alga Volvox carteri and their potential role in cellular differentiation.}, journal = {Plant signaling & behavior}, volume = {10}, number = {4}, pages = {e1010935}, pmid = {25874475}, issn = {1559-2324}, mesh = {*Cell Differentiation ; *Light Signal Transduction ; Models, Biological ; Organ Specificity ; Photoreceptors, Plant/*metabolism ; Volvox/*cytology/*metabolism ; }, abstract = {The formation of multicellular organisms requires genetically predefined signaling pathways in various cell types. Besides differences in size, energy balance and life time, cell types should be enable to modulate appropriate developmental and adaptive responses in ever-changing surrounding environment. One of the most important environmental cues is light which regulates a variety of physiological and cellular processes. During evolution, diverse light-sensitive proteins, so-called photoreceptors, and corresponding signaling pathways have evolved, in almost all kingdoms of life, to monitor light continuously and adjust their growth and development accordingly. However, considering the fact that different cell types should be enable to trigger distinct light signaling pathways according to their needs, cell-type specific light signaling pathways are required to guarantee cell type-matched modulation of cellular and developmental processes in response to different light signals. The multicellular green alga Volvox carteri, which has only 2 cell types with clear division of labor, possesses cell-type specific photoreceptors and light signaling pathways which allow differential regulation of genes involved in various cellular and metabolic pathways in response to environmental light. The existence of cell-type specific light signaling pathways in multicellular organism like Volvox reflects an early development of cell-type specific signaling mechanisms during evolution to ensure maintenance of differentiation.}, } @article {pmid25873590, year = {2015}, author = {Chen, H and Xing, K and He, X}, title = {The dJ/dS Ratio Test Reveals Hundreds of Novel Putative Cancer Drivers.}, journal = {Molecular biology and evolution}, volume = {32}, number = {8}, pages = {2181-2185}, pmid = {25873590}, issn = {1537-1719}, mesh = {Animals ; *Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; *Genes, Neoplasm ; Humans ; *Models, Genetic ; Neoplasms/*genetics/metabolism ; RNA Splice Sites ; RNA Splicing/genetics ; }, abstract = {Computational tools with a balanced sensitivity and specificity in identification of candidate cancer drivers are highly desired. In this study, we propose a new statistical test, namely the dJ/dS ratio test, to compute the relative mutation rate of exon/intron junction sites (dJ) to synonymous sites (dS); observation of dJ/dS ratio larger than 1 in cancer indicates positive selection for splicing deregulation, a signature of cancer driver genes. Using this method, we analyzed the data from The Cancer Genome Atlas and identified hundreds of novel putative cancer drivers. Interestingly, these genes are highly enriched in biological processes related to the development and maintenance of multicellularity, paralleling a previous finding that cancer evolves back to be unicellular by knocking down the multicellularity-associated genetic network.}, } @article {pmid25867922, year = {2015}, author = {Achim, K and Pettit, JB and Saraiva, LR and Gavriouchkina, D and Larsson, T and Arendt, D and Marioni, JC}, title = {High-throughput spatial mapping of single-cell RNA-seq data to tissue of origin.}, journal = {Nature biotechnology}, volume = {33}, number = {5}, pages = {503-509}, pmid = {25867922}, issn = {1546-1696}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Gene Expression Regulation, Developmental ; High-Throughput Nucleotide Sequencing/*methods ; Organ Specificity/genetics ; Polychaeta/*genetics/growth & development ; Single-Cell Analysis/*methods ; Transcriptome/genetics ; }, abstract = {Understanding cell type identity in a multicellular organism requires the integration of gene expression profiles from individual cells with their spatial location in a particular tissue. Current technologies allow whole-transcriptome sequencing of spatially identified cells but lack the throughput needed to characterize complex tissues. Here we present a high-throughput method to identify the spatial origin of cells assayed by single-cell RNA-sequencing within a tissue of interest. Our approach is based on comparing complete, specificity-weighted mRNA profiles of a cell with positional gene expression profiles derived from a gene expression atlas. We show that this method allocates cells to precise locations in the brain of the marine annelid Platynereis dumerilii with a success rate of 81%. Our method is applicable to any system that has a reference gene expression database of sufficiently high resolution.}, } @article {pmid25855805, year = {2015}, author = {Školáková, P and Foldynová-Trantírková, S and Bednářová, K and Fiala, R and Vorlíčková, M and Trantírek, L}, title = {Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA.}, journal = {Nucleic acids research}, volume = {43}, number = {9}, pages = {4733-4745}, pmid = {25855805}, issn = {1362-4962}, mesh = {Animals ; Caenorhabditis elegans/genetics ; DNA/*chemistry ; *Evolution, Molecular ; Humans ; Nucleic Acid Conformation ; Telomere/*chemistry ; }, abstract = {There are two basic mechanisms that are associated with the maintenance of the telomere length, which endows cancer cells with unlimited proliferative potential. One mechanism, referred to as alternative lengthening of telomeres (ALT), accounts for approximately 10-15% of all human cancers. Tumours engaged in the ALT pathway are characterised by the presence of the single stranded 5'-C-rich telomeric overhang (C-overhang). This recently identified hallmark of ALT cancers distinguishes them from healthy tissues and renders the C-overhang as a clear target for anticancer therapy. We analysed structures of the 5'-C-rich and 3'-G-rich telomeric overhangs from human and Caenorhabditis elegans, the recently established multicellular in vivo model of ALT tumours. We show that the telomeric DNA from C. elegans and humans forms fundamentally different secondary structures. The unique structural characteristics of C. elegans telomeric DNA that are distinct not only from those of humans but also from those of other multicellular eukaryotes allowed us to identify evolutionarily conserved properties of telomeric DNA. Differences in structural organisation of the telomeric DNA between the C. elegans and human impose limitations on the use of the C. elegans as an ALT tumour model.}, } @article {pmid25850291, year = {2014}, author = {Kogan, GL and Gvozdev, VA}, title = {[Multifunctional protein complex NAC (nascent polypeptide associated complex].}, journal = {Molekuliarnaia biologiia}, volume = {48}, number = {2}, pages = {223-231}, pmid = {25850291}, issn = {0026-8984}, mesh = {Caspase 3/genetics/metabolism ; Eukaryotic Cells/cytology/*metabolism ; Evolution, Molecular ; *Gene Expression Regulation ; Humans ; Molecular Chaperones/chemistry/*genetics/metabolism ; Protein Binding ; *Protein Biosynthesis ; Protein Folding ; Protein Multimerization ; Protein Stability ; Protein Subunits/chemistry/*genetics/metabolism ; Ribosomes/genetics/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Signal Transduction ; }, abstract = {The functions of the evolutionary conservative complex NAC (Nascent polypepetide Associated Complex) and its subunits are discussed. The heterodimeric NAC protein contains alpha- and beta-subunits and is found to be reversibly bounded to the ribosome in all eukaryotes, from yeast to humans. NAC contacts the nascent polypeptide and protects it from proteolysis. NAC participates in polypeptide chain folding and modulates protein secretion and transmembrane protein formation. Mutations and deletions of genes, encoding NAC subunits are lethal in early development of multicellular eukaryotes. NAC is involved in the ribosome biogenesis. The beta-subunit interacts with caspase-3 and may be involved in the regulation of the apoptotic pathway. The variants of NAC proteins can be considered as chaperone complexes, involved in the response of the cell and the organism to stress factors, as well as regulators of apoptosis. The genes encoding beta-subunits are rapidly evolved, their duplications cause the formation of tissue specific beta-subunit variants with a different number of putative caspase cleavage sites. The homodimer of alpha-subunits is shown to be the RNA/DNA binding protein and acts as a transcriptional cofactor. The diversity in the functioning of NAC is a prime example of a protein that performs a variety of biological functions (moonlighting protein).}, } @article {pmid25847029, year = {2015}, author = {Yue, JX and Li, KL and Yu, JK}, title = {Discovery of germline-related genes in Cephalochordate amphioxus: A genome wide survey using genome annotation and transcriptome data.}, journal = {Marine genomics}, volume = {24 Pt 2}, number = {}, pages = {147-157}, doi = {10.1016/j.margen.2015.03.010}, pmid = {25847029}, issn = {1876-7478}, mesh = {Animals ; DNA, Complementary ; Evolution, Molecular ; Expressed Sequence Tags ; Gene Expression Regulation, Developmental/physiology ; *Genome ; *Genome-Wide Association Study ; Lancelets/*genetics ; Species Specificity ; *Transcriptome ; }, abstract = {The generation of germline cells is a critical process in the reproduction of multicellular organisms. Studies in animal models have identified a common repertoire of genes that play essential roles in primordial germ cell (PGC) formation. However, comparative studies also indicate that the timing and regulation of this core genetic program vary considerably in different animals, raising the intriguing questions regarding the evolution of PGC developmental mechanisms in metazoans. Cephalochordates (commonly called amphioxus or lancelets) represent one of the invertebrate chordate groups and can provide important information about the evolution of developmental mechanisms in the chordate lineage. In this study, we used genome and transcriptome data to identify germline-related genes in two distantly related cephalochordate species, Branchiostoma floridae and Asymmetron lucayanum. Branchiostoma and Asymmetron diverged more than 120 MYA, and the most conspicuous difference between them is their gonadal morphology. We used important germline developmental genes in several model animals to search the amphioxus genome and transcriptome dataset for conserved homologs. We also annotated the assembled transcriptome data using Gene Ontology (GO) terms to facilitate the discovery of putative genes associated with germ cell development and reproductive functions in amphioxus. We further confirmed the expression of 14 genes in developing oocytes or mature eggs using whole mount in situ hybridization, suggesting their potential functions in amphioxus germ cell development. The results of this global survey provide a useful resource for testing potential functions of candidate germline-related genes in cephalochordates and for investigating differences in gonad developmental mechanisms between Branchiostoma and Asymmetron species.}, } @article {pmid25845915, year = {2015}, author = {Rehorek, SJ and Cunningham, J and Bruening, AE and Johnson, JL and Bhatnagar, KP and Smith, TD and Hillenius, WJ}, title = {Development of the nasolacrimal apparatus in the Mongolian gerbil (Meriones unguiculatus), with notes on network topology and function.}, journal = {Journal of morphology}, volume = {276}, number = {9}, pages = {1005-1024}, doi = {10.1002/jmor.20393}, pmid = {25845915}, issn = {1097-4687}, mesh = {Animals ; Gerbillinae/*embryology/growth & development ; Head/embryology/growth & development ; Vomeronasal Organ/*growth & development/physiology ; }, abstract = {The nasolacrimal apparatus (NLA) is a multicomponent functional system comprised of multiple orbital glands (up to four larger multicellular exocrine structures), a nasal chemosensory structure (vomeronasal organ: VNO), and a connecting duct (nasolacrimal duct: NLD). Although this system has been described in all tetrapod vertebrate lineages, albeit not always with all three main components present, considerably less is known about its ontogeny. The Mongolian gerbil (Meriones unguiculatus) is a common lab rodent in which the individual components of the adult NLA have been well studied, but as yet nothing is known about the ontogeny of the NLA. In this study, serial sections of 15 fetal and three adult Mongolian gerbil heads show that the development of the NLA falls into three fetal stages: inception (origin of all features), elongation (lengthening of all features), and expansion (widening of all features). No postnatal or juvenile specimens were observed in this study, but considerable growth evidently occurs before the final adult condition is reached. The development of the orbital glands and the VNO in the Mongolian gerbil is largely consistent with those in other mammals, despite a slight nomenclatural conundrum for the anterior orbital glands. However, the Mongolian gerbil NLD follows a more circuitous route than in other tetrapods, due mainly to the convoluted arrangement of the narial cartilages, the development of a pair of enlarged incisors as well as an enlarged infraorbital foramen. The impact of these associated features on the ontogeny and phylogeny of the NLA could be examined through the approach of network science. This approach allows for the incorporation of adaptations to specific lifestyles as potential explanations for the variation observed in the NLA across different tetrapod clades.}, } @article {pmid25838283, year = {2015}, author = {Szathmáry, E}, title = {Toward major evolutionary transitions theory 2.0.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {33}, pages = {10104-10111}, pmid = {25838283}, issn = {1091-6490}, support = {294332/ERC_/European Research Council/International ; }, mesh = {Animals ; Bacteria/genetics ; *Biological Evolution ; Cultural Characteristics ; Ecosystem ; Eukaryotic Cells/cytology ; Female ; Gene Transfer, Horizontal ; Genetic Code ; Humans ; Language ; Male ; Mitochondria/genetics ; Organelle Biogenesis ; Phagocytosis ; Phylogeny ; Plastids/genetics ; Reproducibility of Results ; Stochastic Processes ; }, abstract = {The impressive body of work on the major evolutionary transitions in the last 20 y calls for a reconstruction of the theory although a 2D account (evolution of informational systems and transitions in individuality) remains. Significant advances include the concept of fraternal and egalitarian transitions (lower-level units like and unlike, respectively). Multilevel selection, first without, then with, the collectives in focus is an important explanatory mechanism. Transitions are decomposed into phases of origin, maintenance, and transformation (i.e., further evolution) of the higher level units, which helps reduce the number of transitions in the revised list by two so that it is less top-heavy. After the transition, units show strong cooperation and very limited realized conflict. The origins of cells, the emergence of the genetic code and translation, the evolution of the eukaryotic cell, multicellularity, and the origin of human groups with language are reconsidered in some detail in the light of new data and considerations. Arguments are given why sex is not in the revised list as a separate transition. Some of the transitions can be recursive (e.g., plastids, multicellularity) or limited (transitions that share the usual features of major transitions without a massive phylogenetic impact, such as the micro- and macronuclei in ciliates). During transitions, new units of reproduction emerge, and establishment of such units requires high fidelity of reproduction (as opposed to mere replication).}, } @article {pmid25825767, year = {2015}, author = {Karkar, S and Facchinelli, F and Price, DC and Weber, AP and Bhattacharya, D}, title = {Metabolic connectivity as a driver of host and endosymbiont integration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {33}, pages = {10208-10215}, pmid = {25825767}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/metabolism ; *Biological Evolution ; Biological Transport ; Computational Biology ; Evolution, Molecular ; Oxidation-Reduction ; Photosynthesis ; Phylogeny ; Plastids/*genetics/metabolism ; Rhodophyta/metabolism ; Symbiosis/*genetics ; }, abstract = {The origin of oxygenic photosynthesis in the Archaeplastida common ancestor was foundational for the evolution of multicellular life. It is very likely that the primary endosymbiosis that explains plastid origin relied initially on the establishment of a metabolic connection between the host cell and captured cyanobacterium. We posit that these connections were derived primarily from existing host-derived components. To test this idea, we used phylogenomic and network analysis to infer the phylogenetic origin and evolutionary history of 37 validated plastid innermost membrane (permeome) metabolite transporters from the model plant Arabidopsis thaliana. Our results show that 57% of these transporter genes are of eukaryotic origin and that the captured cyanobacterium made a relatively minor (albeit important) contribution to the process. We also tested the hypothesis that the bacterium-derived hexose-phosphate transporter UhpC might have been the primordial sugar transporter in the Archaeplastida ancestor. Bioinformatic and protein localization studies demonstrate that this protein in the extremophilic red algae Galdieria sulphuraria and Cyanidioschyzon merolae are plastid targeted. Given this protein is also localized in plastids in the glaucophyte alga Cyanophora paradoxa, we suggest it played a crucial role in early plastid endosymbiosis by connecting the endosymbiont and host carbon storage networks. In summary, our work significantly advances understanding of plastid integration and favors a host-centric view of endosymbiosis. Under this view, nuclear genes of either eukaryotic or bacterial (noncyanobacterial) origin provided key elements of the toolkit needed for establishing metabolic connections in the primordial Archaeplastida lineage.}, } @article {pmid25815986, year = {2015}, author = {Chantranupong, L and Wolfson, RL and Sabatini, DM}, title = {Nutrient-sensing mechanisms across evolution.}, journal = {Cell}, volume = {161}, number = {1}, pages = {67-83}, pmid = {25815986}, issn = {1097-4172}, support = {R01 AI047389/AI/NIAID NIH HHS/United States ; R01 CA103866/CA/NCI NIH HHS/United States ; T32 GM007287/GM/NIGMS NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; F31 CA180271/CA/NCI NIH HHS/United States ; R37 AI047389/AI/NIAID NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; AI47389/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/genetics/*metabolism ; Biological Evolution ; Eukaryota/genetics/metabolism ; Food ; *Signal Transduction ; }, abstract = {For organisms to coordinate their growth and development with nutrient availability, they must be able to sense nutrient levels in their environment. Here, we review select nutrient-sensing mechanisms in a few diverse organisms. We discuss how these mechanisms reflect the nutrient requirements of specific species and how they have adapted to the emergence of multicellularity in eukaryotes.}, } @article {pmid25814207, year = {2015}, author = {Rashidi, A and Shelton, DE and Michod, RE}, title = {A Darwinian approach to the origin of life cycles with group properties.}, journal = {Theoretical population biology}, volume = {102}, number = {}, pages = {76-84}, doi = {10.1016/j.tpb.2015.03.003}, pmid = {25814207}, issn = {1096-0325}, mesh = {Animals ; *Biological Evolution ; Body Size ; Cell Growth Processes ; Genotype ; Life Cycle Stages/*physiology ; Models, Theoretical ; Mutation/physiology ; *Origin of Life ; Selection, Genetic ; }, abstract = {A selective explanation for the evolution of multicellular organisms from unicellular ones requires knowledge of both selective pressures and factors affecting the response to selection. Understanding the response to selection is particularly challenging in the case of evolutionary transitions in individuality, because these transitions involve a shift in the very units of selection. We develop a conceptual framework in which three fundamental processes (growth, division, and splitting) are the scaffold for unicellular and multicellular life cycles alike. We (i) enumerate the possible ways in which these processes can be linked to create more complex life cycles, (ii) introduce three genes based on growth, division and splitting that, acting in concert, determine the architecture of the life cycles, and finally, (iii) study the evolution of the simplest five life cycles using a heuristic model of coupled ordinary differential equations in which mutations are allowed in the three genes. We demonstrate how changes in the regulation of three fundamental aspects of colonial form (cell size, colony size, and colony cell number) could lead unicellular life cycles to evolve into primitive multicellular life cycles with group properties. One interesting prediction of the model is that selection generally favors cycles with group level properties when intermediate body size is associated with lowest mortality. That is, a universal requirement for the evolution of group cycles in the model is that the size-mortality curve be U-shaped. Furthermore, growth must decelerate with size.}, } @article {pmid25786324, year = {2014}, author = {Maryanovich, AT}, title = {[Phylogeny of peptide regulation: the beginning].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {50}, number = {5}, pages = {402-410}, pmid = {25786324}, issn = {0044-4529}, mesh = {Animals ; *Autocrine Communication ; *Evolution, Molecular ; Peptide Hormones/biosynthesis/*genetics/metabolism ; *Phylogeny ; Proteolysis ; }, abstract = {Analyzing existing literature sources and his own experimental data, the author has concluded that (i) regulatory peptides arise solely as a result of cleavage of protein precursors, but not by non-ribosomal synthesis; (ii) the peptide regulation of physiological functions emerged as a part of autocrine regulation system almost simultaneously with life itself; peptide paracrine regulation appeared in the colonial prokaryotes, and peptide endocrine regulation in the multicellular eukaryotes; (iii) the regulatory peptides and their receptors could occur either sequentially (in any order) or simultaneously; (iv) conservatism of the primary structure of regulatory peptides is not significantly different from that of proteins; (v) the regulatory peptides are presented in the most evolutionarily ancient species wider than specialists think.}, } @article {pmid25784475, year = {2015}, author = {Haig, D}, title = {Coleochaete and the origin of sporophytes.}, journal = {American journal of botany}, volume = {102}, number = {3}, pages = {417-422}, doi = {10.3732/ajb.1400526}, pmid = {25784475}, issn = {1537-2197}, mesh = {*Biological Evolution ; *Cell Division ; Charophyceae/*growth & development ; Models, Biological ; Ploidies ; Reproduction ; }, abstract = {UNLABELLED: •

PREMISE OF THE STUDY: Zygotes of Coleochaete are provisioned by the maternal thallus before undergoing 3-5 rounds of division to produce 8-32 zoospores. An understanding of the selective forces favoring postzygotic divisions would be relevant not only to the interpretation of Coleochaete life history but also to the origin of a multicellular diploid phase in embryophytes.•

METHODS: Simple optimization models are developed of the number of zygotes per maternal thallus and number of zoospores per zygote.•

KEY RESULTS: Zygotic mitosis is favored once zygotic size exceeds a threshold, but natural selection usually promotes investment in additional zygotes before zygotes reach this threshold. Factors that favor production of fewer, larger zygotes include multiple paternity, low fecundity, and accessory costs of zygote production. Such factors can result in zygotes exceeding the size at which zygotic mitosis becomes profitable.•

CONCLUSIONS: Coleochaete may possess large zygotes that undergo multiple fission because of accessory costs associated with matrotrophy, including costs of cortical cells and unfertilized oogonia. The unpredictability of fertilization on land is proposed to have increased accessory costs from unfertilized ova and, as a consequence, to have favored the production of larger zygotes that underwent postzygotic division to produce diploid sporophytes.}, } @article {pmid25782278, year = {2014}, author = {Zhuravleva, AIu}, title = {[Early history of the Metazoa--a palaeontologist's viewpoint].}, journal = {Zhurnal obshchei biologii}, volume = {75}, number = {6}, pages = {411-465}, pmid = {25782278}, issn = {0044-4596}, mesh = {Animals ; *Biological Evolution ; Paleontology ; }, abstract = {The molecular biology success, which became influential for a revision of principal views on the relationships and evolutionary pathways of major groups ("phyla") of multicellular animals, were much more appreciated by palaeontologists rather than by neontologists. This is not surprising because this is the fossil record that serves as a firm test for molecular biological hypotheses. The fossil record indicates that the different "phyla" united nowadays into the Ecdysozoa, namely, arthropods, onychophorans, tardigrades, priapulids, nematomorphs, comprise a number of transitional forms having become extinct already in the early Palaeozoic. The very appearance of those organisms fits entirely to hypothetical ancestral forms which have to exist in accordance with some data on ontogeny. There are no even tentative intermediates between arthropods and annelids in the fossil record. The oldest Deuterostomia, which is the only branch of the Bilateria being agreed upon by all the biological disciplines, allow us, although in less details, to present their early history and point to agile bilaterally-symmetrical forms at the dawn of chordates, hemichordates, and echinoderms. The interpretation of the early history of the Lophotrochozoa is even more difficult because in comparison to other bilaterians, their oldest fossils are preserved as mineralized skeletons only. However, a unity of microstructures of molluscs, brachiopods, and bryozoans, absent in other metazoans, is indicative of the presence of close relatives among different earliest lophotrochozoans some of which are sedentary filterers while others are motile epibenthic detritophages. In the aggregate, modern data of molecular biology, palaeontology, and comparative embryology/morphology, having got a second wind with an introduction of new microscopy techniques, imply that the suggestion of a planktotrophic gastraea-like common ancestor is the least possible among diverse suggestions on the Metazoa origins. The common ancestor of the Bilateria had to be a motile epibenthic animal and the explosive metazoan diversification embracing the late Ediacaran--early Cambrian interval (c. 40 Ma) was probably a real event, which was predated by a long (c. a billion years) assembly of the metazoan genome within unicellular and colonial common ancestors of the Opisthokonta and even the Unikonta as a whole.}, } @article {pmid25778404, year = {2015}, author = {Selvan, N and Mariappa, D and van den Toorn, HW and Heck, AJ and Ferenbach, AT and van Aalten, DM}, title = {The Early Metazoan Trichoplax adhaerens Possesses a Functional O-GlcNAc System.}, journal = {The Journal of biological chemistry}, volume = {290}, number = {19}, pages = {11969-11982}, pmid = {25778404}, issn = {1083-351X}, support = {WT087590MA/WT_/Wellcome Trust/United Kingdom ; 087590/WT_/Wellcome Trust/United Kingdom ; G0900138/MRC_/Medical Research Council/United Kingdom ; MR/M004139/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Acetylglucosamine/chemistry ; Animals ; Animals, Genetically Modified ; Cell Nucleus/enzymology ; Crosses, Genetic ; Cytoplasm/enzymology ; Drosophila melanogaster ; HEK293 Cells ; Humans ; Inhibitory Concentration 50 ; Molecular Sequence Data ; N-Acetylglucosaminyltransferases/*metabolism ; Placozoa/*enzymology ; Protein Processing, Post-Translational ; Protein Structure, Tertiary ; RNA Interference ; Signal Transduction ; }, abstract = {Protein O-GlcNAcylation is a reversible post-translational signaling modification of nucleocytoplasmic proteins that is essential for embryonic development in bilateria. In a search for a reductionist model to study O-GlcNAc signaling, we discovered the presence of functional O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), and nucleocytoplasmic protein O-GlcNAcylation in the most basal extant animal, the placozoan Trichoplax adhaerens. We show via enzymatic characterization of Trichoplax OGT/OGA and genetic rescue experiments in Drosophila melanogaster that these proteins possess activities/functions similar to their bilaterian counterparts. The acquisition of O-GlcNAc signaling by metazoa may have facilitated the rapid and complex signaling mechanisms required for the evolution of multicellular organisms.}, } @article {pmid25775948, year = {2015}, author = {Wu, H and Shang, LQ and Chen, RL and Yang, SM and Wang, SL and Wang, J and Sun, G}, title = {Significance of Trask protein interactions in brain metastatic cohorts of lung cancers.}, journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine}, volume = {36}, number = {6}, pages = {4181-4187}, pmid = {25775948}, issn = {1423-0380}, mesh = {Adenocarcinoma/*genetics/pathology ; Antigens, CD/*genetics/metabolism ; Antigens, Neoplasm ; Brain Neoplasms/*genetics/pathology/secondary ; Calcium/metabolism ; Calcium Channels/genetics/metabolism ; Cell Adhesion/genetics ; Cell Adhesion Molecules/*genetics/metabolism ; Cell Line, Tumor ; Humans ; Membrane Proteins/genetics/metabolism ; Neoplasm Proteins/*genetics/metabolism ; ORAI1 Protein ; Phosphorylation ; Protein Interaction Maps ; Small Cell Lung Carcinoma/*genetics/pathology ; Stromal Interaction Molecule 1 ; src-Family Kinases/genetics/metabolism ; }, abstract = {A class of adhesion protein that occurs in the membrane with both extracellular and intracellular domain and play vital role in maintaining multicellularity is TRASK, also called CUB-domain containing protein1, CD318 (CDCP1). Specifically, in the current study, documented aggressive grades of lung cancers and distant metastatic tissues were examined for protein interactions of Trask and compared with lung cancer variants in situ. The intracellular domain of Trask has the ability to undergo tyrosine phosphorylation and thereafter undergo increased genomic expression, as well as interact with cytoskeletal proteins in the cell periphery and other local signal transduction machinery to induce invadopodia formation and distant metastasis. We incorporated proximity ligation assay to examine protein interactions of Trask in metastatic lung cancer tissues and compare with advanced and low-grade lung cancers restricted to the primary site of origins. Here, we provide direct evidence that activated Trask, which is a phosphorylated form, binds with cytoskeletal proteins actin and spectrin. These interactions were not seen in locally growing lung cancer and cancer in situ. These interactions may be responsible for invadopodia formation and breaking free from a multicellular environment. Functional studies demonstrated interaction between Trask and the STOCs Orai1 and Stim1. Calcium release from internal stores was highest in metastatic lung cancers, suggesting this mechanism as an initial stimulus for the cells to respond chaotically to external growth factor stimulation, especially in aggressive metastatic variants of lung cancers. Recently, inhibitors of STOCs have been identified, and preclinical evidence may be obtained whether these drugs may be of benefit in preventing the deadly consequences of lung cancer.}, } @article {pmid25775860, year = {2014}, author = {Ivanova, VP and Krivchenko, AI}, title = {[A current viewpoint on structure and evolution of collagens. II. The fibril-associated collagens with interrupted triple helices].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {50}, number = {4}, pages = {245-254}, pmid = {25775860}, issn = {0044-4529}, mesh = {Animals ; *Evolution, Molecular ; Fibril-Associated Collagens/*chemistry/genetics/metabolism ; Humans ; Protein Structure, Tertiary ; }, abstract = {Fibril-associated collagens with interrupted triple helices (FACITs) form one of the subfamilies of collagen family. Being minor components of connective tissues in multicellular animals, FACITs play an important role in structurization of extracellular matrix whose peculiarities determine differences among tissues. FACITs take part in regulation of the sizes of banded collagen fibrils and are also a link between diverse components of extracellular matrix and cells in different tissues. The functional characteristics of FACIT molecules are determined by peculiarities of α-chain structure (interruptions in collagenous domains and module structure of N-terminal noncollagenous regions), trimeric molecules (trimerization domains), and supramolecular assemblies (mainly, association with banded fibrils and inability to form homopolymeric suprastructural aggregates). The evolution of FACITs is also discussed. A hypothetical model of structural changes leading to formation of FACIT subfamily is propounded.}, } @article {pmid25772340, year = {2015}, author = {Levin, SR and Brock, DA and Queller, DC and Strassmann, JE}, title = {Concurrent coevolution of intra-organismal cheaters and resisters.}, journal = {Journal of evolutionary biology}, volume = {28}, number = {4}, pages = {756-765}, doi = {10.1111/jeb.12618}, pmid = {25772340}, issn = {1420-9101}, mesh = {*Biological Evolution ; Dictyostelium/*physiology ; }, abstract = {The evolution of multicellularity is a major transition that is not yet fully understood. Specifically, we do not know whether there are any mechanisms by which multicellularity can be maintained without a single-cell bottleneck or other relatedness-enhancing mechanisms. Under low relatedness, cheaters can evolve that benefit from the altruistic behaviour of others without themselves sacrificing. If these are obligate cheaters, incapable of cooperating, their spread can lead to the demise of multicellularity. One possibility, however, is that cooperators can evolve resistance to cheaters. We tested this idea in a facultatively multicellular social amoeba, Dictyostelium discoideum. This amoeba usually exists as a single cell but, when stressed, thousands of cells aggregate to form a multicellular organism in which some of the cells sacrifice for the good of others. We used lineages that had undergone experimental evolution at very low relatedness, during which time obligate cheaters evolved. Unlike earlier experiments, which found resistance to cheaters that were prevented from evolving, we competed cheaters and noncheaters that evolved together, and cheaters with their ancestors. We found that noncheaters can evolve resistance to cheating before cheating sweeps through the population and multicellularity is lost. Our results provide insight into cheater-resister coevolutionary dynamics, in turn providing experimental evidence for the maintenance of at least a simple form of multicellularity by means other than high relatedness.}, } @article {pmid25765996, year = {2015}, author = {Ross, CR and DeFelice, DS and Hunt, GJ and Ihle, KE and Amdam, GV and Rueppell, O}, title = {Genomic correlates of recombination rate and its variability across eight recombination maps in the western honey bee (Apis mellifera L.).}, journal = {BMC genomics}, volume = {16}, number = {1}, pages = {107}, pmid = {25765996}, issn = {1471-2164}, support = {R15 GM102753/GM/NIGMS NIH HHS/United States ; R15GM102753/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Composition/genetics ; Bees/*genetics ; Chromosome Mapping ; Chromosome Segregation/genetics ; Chromosomes/genetics ; *Evolution, Molecular ; Genome, Insect/genetics ; Meiosis/*genetics ; *Recombination, Genetic ; }, abstract = {BACKGROUND: Meiotic recombination has traditionally been explained based on the structural requirement to stabilize homologous chromosome pairs to ensure their proper meiotic segregation. Competing hypotheses seek to explain the emerging findings of significant heterogeneity in recombination rates within and between genomes, but intraspecific comparisons of genome-wide recombination patterns are rare. The honey bee (Apis mellifera) exhibits the highest rate of genomic recombination among multicellular animals with about five cross-over events per chromatid.

RESULTS: Here, we present a comparative analysis of recombination rates across eight genetic linkage maps of the honey bee genome to investigate which genomic sequence features are correlated with recombination rate and with its variation across the eight data sets, ranging in average marker spacing ranging from 1 Mbp to 120 kbp. Overall, we found that GC content explained best the variation in local recombination rate along chromosomes at the analyzed 100 kbp scale. In contrast, variation among the different maps was correlated to the abundance of microsatellites and several specific tri- and tetra-nucleotides.

CONCLUSIONS: The combined evidence from eight medium-scale recombination maps of the honey bee genome suggests that recombination rate variation in this highly recombining genome might be due to the DNA configuration instead of distinct sequence motifs. However, more fine-scale analyses are needed. The empirical basis of eight differing genetic maps allowed for robust conclusions about the correlates of the local recombination rates and enabled the study of the relation between DNA features and variability in local recombination rates, which is particularly relevant in the honey bee genome with its exceptionally high recombination rate.}, } @article {pmid25758444, year = {2015}, author = {Urushihara, H and Kuwayama, H and Fukuhara, K and Itoh, T and Kagoshima, H and Shin-I, T and Toyoda, A and Ohishi, K and Taniguchi, T and Noguchi, H and Kuroki, Y and Hata, T and Uchi, K and Mohri, K and King, JS and Insall, RH and Kohara, Y and Fujiyama, A}, title = {Comparative genome and transcriptome analyses of the social amoeba Acytostelium subglobosum that accomplishes multicellular development without germ-soma differentiation.}, journal = {BMC genomics}, volume = {16}, number = {1}, pages = {80}, pmid = {25758444}, issn = {1471-2164}, support = {15672/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Amoeba/*genetics/growth & development ; Cell Differentiation/genetics ; Gene Expression ; Gene Expression Profiling ; *Genome, Protozoan ; Phylogeny ; Transcriptome/*genetics ; }, abstract = {BACKGROUND: Social amoebae are lower eukaryotes that inhabit the soil. They are characterized by the construction of a starvation-induced multicellular fruiting body with a spore ball and supportive stalk. In most species, the stalk is filled with motile stalk cells, as represented by the model organism Dictyostelium discoideum, whose developmental mechanisms have been well characterized. However, in the genus Acytostelium, the stalk is acellular and all aggregated cells become spores. Phylogenetic analyses have shown that it is not an ancestral genus but has lost the ability to undergo cell differentiation.

RESULTS: We performed genome and transcriptome analyses of Acytostelium subglobosum and compared our findings to other available dictyostelid genome data. Although A. subglobosum adopts a qualitatively different developmental program from other dictyostelids, its gene repertoire was largely conserved. Yet, families of polyketide synthase and extracellular matrix proteins have not expanded and a serine protease and ABC transporter B family gene, tagA, and a few other developmental genes are missing in the A. subglobosum lineage. Temporal gene expression patterns are astonishingly dissimilar from those of D. discoideum, and only a limited fraction of the ortholog pairs shared the same expression patterns, so that some signaling cascades for development seem to be disabled in A. subglobosum.

CONCLUSIONS: The absence of the ability to undergo cell differentiation in Acytostelium is accompanied by a small change in coding potential and extensive alterations in gene expression patterns.}, } @article {pmid25751731, year = {2015}, author = {Chen, H and Lin, F and Xing, K and He, X}, title = {The reverse evolution from multicellularity to unicellularity during carcinogenesis.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {6367}, doi = {10.1038/ncomms7367}, pmid = {25751731}, issn = {2041-1723}, mesh = {Animals ; Base Sequence ; *Biological Evolution ; Carcinogenesis/*pathology ; Comparative Genomic Hybridization ; Exome/genetics ; Heterografts/*physiopathology ; *Models, Biological ; Neoplasm Metastasis/*genetics/*physiopathology ; Neoplasms/genetics/*physiopathology ; Sequence Analysis, DNA ; }, abstract = {Theoretical reasoning suggests that cancer may result from a knockdown of the genetic constraints that evolved for the maintenance of metazoan multicellularity. By characterizing the whole-life history of a xenograft tumour, here we show that metastasis is driven by positive selection for general loss-of-function mutations on multicellularity-related genes. Expression analyses reveal mainly downregulation of multicellularity-related genes and an evolving expression profile towards that of embryonic stem cells, the cell type resembling unicellular life in its capacity of unlimited clonal proliferation. Also, the emergence of metazoan multicellularity ~600 Myr ago is accompanied by an elevated birth rate of cancer genes, and there are more loss-of-function tumour suppressors than activated oncogenes in a typical tumour. These data collectively suggest that cancer represents a loss-of-function-driven reverse evolution back to the unicellular 'ground state'. This cancer evolution model may account for inter-/intratumoural genetic heterogeneity, could explain distant-organ metastases and hold implications for cancer therapy.}, } @article {pmid25750178, year = {2015}, author = {Jin, J and He, K and Tang, X and Li, Z and Lv, L and Zhao, Y and Luo, J and Gao, G}, title = {An Arabidopsis Transcriptional Regulatory Map Reveals Distinct Functional and Evolutionary Features of Novel Transcription Factors.}, journal = {Molecular biology and evolution}, volume = {32}, number = {7}, pages = {1767-1773}, pmid = {25750178}, issn = {1537-1719}, mesh = {Arabidopsis/*genetics/physiology ; *Evolution, Molecular ; Gene Expression Regulation, Plant ; Gene Regulatory Networks/*genetics ; Protein Binding ; Stress, Physiological/genetics ; Transcription Factors/*metabolism ; }, abstract = {Transcription factors (TFs) play key roles in both development and stress responses. By integrating into and rewiring original systems, novel TFs contribute significantly to the evolution of transcriptional regulatory networks. Here, we report a high-confidence transcriptional regulatory map covering 388 TFs from 47 families in Arabidopsis. Systematic analysis of this map revealed the architectural heterogeneity of developmental and stress response subnetworks and identified three types of novel network motifs that are absent from unicellular organisms and essential for multicellular development. Moreover, TFs of novel families that emerged during plant landing present higher binding specificities and are preferentially wired into developmental processes and these novel network motifs. Further unveiled connection between the binding specificity and wiring preference of TFs explains the wiring preferences of novel-family TFs. These results reveal distinct functional and evolutionary features of novel TFs, suggesting a plausible mechanism for their contribution to the evolution of multicellular organisms.}, } @article {pmid25737280, year = {2015}, author = {Murn, J and Zarnack, K and Yang, YJ and Durak, O and Murphy, EA and Cheloufi, S and Gonzalez, DM and Teplova, M and Curk, T and Zuber, J and Patel, DJ and Ule, J and Luscombe, NM and Tsai, LH and Walsh, CA and Shi, Y}, title = {Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt.}, journal = {Genes & development}, volume = {29}, number = {5}, pages = {501-512}, pmid = {25737280}, issn = {1549-5477}, support = {T32 GM007753/GM/NIGMS NIH HHS/United States ; R01 CA118487/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 HD018655/HD/NICHD NIH HHS/United States ; MH096066/MH/NIMH NIH HHS/United States ; T32GM007753/GM/NIGMS NIH HHS/United States ; 16358/CRUK_/Cancer Research UK/United Kingdom ; R01 NS032457/NS/NINDS NIH HHS/United States ; R01 NS35129/NS/NINDS NIH HHS/United States ; R01 NS035129/NS/NINDS NIH HHS/United States ; R01 MH096066/MH/NIMH NIH HHS/United States ; CA118487/CA/NCI NIH HHS/United States ; R01 GM058012/GM/NIGMS NIH HHS/United States ; GM058012/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Brain/metabolism ; Cell Line ; Cell Shape/*genetics ; Embryo, Mammalian ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; HeLa Cells ; Humans ; Mice ; Neurons/*cytology ; Protein Binding ; RNA, Messenger ; }, abstract = {Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mouse embryos disrupts the shape of migrating neurons, while ectopic expression confers neuronal-like morphology to cells of different nonneuronal lineages. We found that Unkempt is a sequence-specific RNA-binding protein and identified its precise binding sites within coding regions of mRNAs linked to protein metabolism and trafficking. RNA binding is required for Unkempt-induced remodeling of cellular shape and is directly coupled to a reduced production of the encoded proteins. These findings link post-transcriptional regulation of gene expression with cellular shape and have general implications for the development and disease of multicellular organisms.}, } @article {pmid25736565, year = {2015}, author = {Neumann, S and El Maadidi, S and Faletti, L and Haun, F and Labib, S and Schejtman, A and Maurer, U and Borner, C}, title = {How do viruses control mitochondria-mediated apoptosis?.}, journal = {Virus research}, volume = {209}, number = {}, pages = {45-55}, pmid = {25736565}, issn = {1872-7492}, mesh = {*Apoptosis ; *Host-Pathogen Interactions ; Humans ; *Immunity, Innate ; Mitochondria/*metabolism ; *Virus Replication ; Viruses/*growth & development/*immunology ; }, abstract = {There is no doubt that viruses require cells to successfully reproduce and effectively infect the next host. The question is what is the fate of the infected cells? All eukaryotic cells can "sense" viral infections and exhibit defence strategies to oppose viral replication and spread. This often leads to the elimination of the infected cells by programmed cell death or apoptosis. This "sacrifice" of infected cells represents the most primordial response of multicellular organisms to viruses. Subverting host cell apoptosis, at least for some time, is therefore a crucial strategy of viruses to ensure their replication, the production of essential viral proteins, virus assembly and the spreading to new hosts. For that reason many viruses harbor apoptosis inhibitory genes, which once inside infected cells are expressed to circumvent apoptosis induction during the virus reproduction phase. On the other hand, viruses can take advantage of stimulating apoptosis to (i) facilitate shedding and hence dissemination, (ii) to prevent infected cells from presenting viral antigens to the immune system or (iii) to kill non-infected bystander and immune cells which would limit viral propagation. Hence the decision whether an infected host cell undergoes apoptosis or not depends on virus type and pathogenicity, its capacity to oppose antiviral responses of the infected cells and/or to evade any attack from immune cells. Viral genomes have therefore been adapted throughout evolution to satisfy the need of a particular virus to induce or inhibit apoptosis during its life cycle. Here we review the different strategies used by viruses to interfere with the two major apoptosis as well as with the innate immune signaling pathways in mammalian cells. We will focus on the intrinsic mitochondrial pathway and discuss new ideas about how particular viruses could activately engage mitochondria to induce apoptosis of their host.}, } @article {pmid25735194, year = {2015}, author = {Zhao, JL and Pan, JS and Guan, Y and Zhang, WW and Bie, BB and Wang, YL and He, HL and Lian, HL and Cai, R}, title = {Micro-trichome as a class I homeodomain-leucine zipper gene regulates multicellular trichome development in Cucumis sativus.}, journal = {Journal of integrative plant biology}, volume = {57}, number = {11}, pages = {925-935}, doi = {10.1111/jipb.12345}, pmid = {25735194}, issn = {1744-7909}, mesh = {Amino Acid Sequence ; Cucumis sativus/*genetics/growth & development/ultrastructure ; Homeodomain Proteins/*physiology ; Leucine Zippers ; Molecular Sequence Data ; Phenotype ; Phylogeny ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Transcriptome ; Trichomes/*growth & development/ultrastructure ; }, abstract = {Plant trichomes serve as a highly suitable model for investigating cell differentiation at the single-cell level. The regulatory genes involved in unicellular trichome development in Arabidopsis thaliana have been intensively studied, but genes regulating multicellular trichome development in plants remain unclear. Here, we characterized Cucumis sativus (cucumber) trichomes as representative multicellular and unbranched structures, and identified Micro-trichome (Mict), using map-based cloning in an F2 segregating population of 7,936 individuals generated from a spontaneous mict mutant. In mict plants, trichomes in both leaves and fruits, are small, poorly developed, and denser than in the wild type. Sequence analysis revealed that a 2,649-bp genomic deletion, spanning the first and second exons, occurred in a plant-specific class I homeodomain-leucine zipper gene. Tissue-specific expression analysis indicated that Mict is strongly expressed in the trichome cells. Transcriptome profiling identified potential targets of Mict including putative homologs of genes known in other systems to regulate trichome development, meristem determinacy, and hormone responsiveness. Phylogenic analysis charted the relationships among putative homologs in angiosperms. Our paper represents initial steps toward understanding the development of multicellular trichomes.}, } @article {pmid25734540, year = {2015}, author = {Hayakawa, S and Takaku, Y and Hwang, JS and Horiguchi, T and Suga, H and Gehring, W and Ikeo, K and Gojobori, T}, title = {Function and evolutionary origin of unicellular camera-type eye structure.}, journal = {PloS one}, volume = {10}, number = {3}, pages = {e0118415}, pmid = {25734540}, issn = {1932-6203}, mesh = {Animal Structures/*physiology/radiation effects/ultrastructure ; Animals ; Biological Evolution ; Dinoflagellida/classification/*physiology/radiation effects/ultrastructure ; Gene Expression ; In Situ Hybridization ; Lens, Crystalline/*physiology/radiation effects/ultrastructure ; Light ; Photic Stimulation ; Photoreceptor Cells/*physiology/radiation effects/ultrastructure ; Phylogeny ; Protozoan Proteins/genetics/*metabolism ; Rhodopsin/genetics/*metabolism ; Rhodopsins, Microbial/genetics/metabolism ; Sequence Homology, Amino Acid ; Symbiosis/physiology ; }, abstract = {The ocelloid is an extraordinary eyespot organelle found only in the dinoflagellate family Warnowiaceae. It contains retina- and lens-like structures called the retinal body and the hyalosome. The ocelloid has been an evolutionary enigma because of its remarkable resemblance to the multicellular camera-type eye. To determine if the ocelloid is functionally photoreceptive, we investigated the warnowiid dinoflagellate Erythropsidinium. Here, we show that the morphology of the retinal body changed depending on different illumination conditions and the hyalosome manifests the refractile nature. Identifying a rhodopsin gene fragment in Erythropsidinium ESTs that is expressed in the retinal body by in situ hybridization, we also show that ocelloids are actually light sensitive photoreceptors. The rhodopsin gene identified is most closely related to bacterial rhodopsins. Taken together, we suggest that the ocelloid is an intracellular camera-type eye, which might be originated from endosymbiotic origin.}, } @article {pmid25734073, year = {2015}, author = {Cullen, PJ}, title = {Investigating filamentous growth and biofilm/mat formation in budding yeast.}, journal = {Cold Spring Harbor protocols}, volume = {2015}, number = {3}, pages = {235-238}, pmid = {25734073}, issn = {1559-6095}, support = {R01 GM098629/GM/NIGMS NIH HHS/United States ; GM098629/GM/NIGMS NIH HHS/United States ; }, mesh = {Biofilms/*growth & development ; Hyphae/*growth & development ; Saccharomycetales/*cytology/growth & development/*physiology ; }, abstract = {In response to nutrient limitation, budding yeast can undergo filamentous growth by differentiating into elongated chains of interconnected cells. Filamentous growth is regulated by signal transduction pathways that oversee the reorganization of cell polarity, changes to the cell cycle, and an increase in cell adhesion that occur in response to nutrient limitation. Each of these changes can be easily measured. Yeast can also grow colonially atop surfaces in a biofilm or mat of connected cells. Filamentous growth and biofilm/mat formation require cooperation among individuals; therefore, studying these responses can shed light on the origin and genetic basis of multicellular behaviors. The assays introduced here can be used to study analogous behaviors in other fungal species, including pathogens, which require filamentous growth and biofilm/mat formation for virulence.}, } @article {pmid25733140, year = {2015}, author = {McCrea, PD and Maher, MT and Gottardi, CJ}, title = {Nuclear signaling from cadherin adhesion complexes.}, journal = {Current topics in developmental biology}, volume = {112}, number = {}, pages = {129-196}, pmid = {25733140}, issn = {1557-8933}, support = {R01 GM076561/GM/NIGMS NIH HHS/United States ; R01 GM107079/GM/NIGMS NIH HHS/United States ; GM076561/GM/NIGMS NIH HHS/United States ; GM107079/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cadherins/*metabolism ; Cell Adhesion/*physiology ; Cell Nucleus/*metabolism ; Humans ; Signal Transduction ; beta Catenin/*metabolism ; }, abstract = {The arrival of multicellularity in evolution facilitated cell-cell signaling in conjunction with adhesion. As the ectodomains of cadherins interact with each other directly in trans (as well as in cis), spanning the plasma membrane and associating with multiple other entities, cadherins enable the transduction of "outside-in" or "inside-out" signals. We focus this review on signals that originate from the larger family of cadherins that are inwardly directed to the nucleus, and thus have roles in gene control or nuclear structure-function. The nature of cadherin complexes varies considerably depending on the type of cadherin and its context, and we will address some of these variables for classical cadherins versus other family members. Substantial but still fragmentary progress has been made in understanding the signaling mediators used by varied cadherin complexes to coordinate the state of cell-cell adhesion with gene expression. Evidence that cadherin intracellular binding partners also localize to the nucleus is a major point of interest. In some models, catenins show reduced binding to cadherin cytoplasmic tails favoring their engagement in gene control. When bound, cadherins may serve as stoichiometric competitors of nuclear signals. Cadherins also directly or indirectly affect numerous signaling pathways (e.g., Wnt, receptor tyrosine kinase, Hippo, NFκB, and JAK/STAT), enabling cell-cell contacts to touch upon multiple biological outcomes in embryonic development and tissue homeostasis.}, } @article {pmid25710177, year = {2015}, author = {Erives, AJ and Fassler, JS}, title = {Metabolic and chaperone gene loss marks the origin of animals: evidence for Hsp104 and Hsp78 chaperones sharing mitochondrial enzymes as clients.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0117192}, pmid = {25710177}, issn = {1932-6203}, mesh = {Aconitate Hydratase/classification/genetics ; Animals ; Bayes Theorem ; Choanoflagellata/genetics ; Endopeptidase Clp/classification/genetics ; Heat-Shock Proteins/*genetics/metabolism ; Likelihood Functions ; Mitochondria/*enzymology/metabolism ; Mutation ; Phylogeny ; Promoter Regions, Genetic ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; }, abstract = {The evolution of animals involved acquisition of an emergent gene repertoire for gastrulation. Whether loss of genes also co-evolved with this developmental reprogramming has not yet been addressed. Here, we identify twenty-four genetic functions that are retained in fungi and choanoflagellates but undetectable in animals. These lost genes encode: (i) sixteen distinct biosynthetic functions; (ii) the two ancestral eukaryotic ClpB disaggregases, Hsp78 and Hsp104, which function in the mitochondria and cytosol, respectively; and (iii) six other assorted functions. We present computational and experimental data that are consistent with a joint function for the differentially localized ClpB disaggregases, and with the possibility of a shared client/chaperone relationship between the mitochondrial Fe/S homoaconitase encoded by the lost LYS4 gene and the two ClpBs. Our analyses lead to the hypothesis that the evolution of gastrulation-based multicellularity in animals led to efficient extraction of nutrients from dietary sources, loss of natural selection for maintenance of energetically expensive biosynthetic pathways, and subsequent loss of their attendant ClpB chaperones.}, } @article {pmid25696824, year = {2015}, author = {Satterlie, RA}, title = {The search for ancestral nervous systems: an integrative and comparative approach.}, journal = {The Journal of experimental biology}, volume = {218}, number = {Pt 4}, pages = {612-617}, doi = {10.1242/jeb.110387}, pmid = {25696824}, issn = {1477-9145}, mesh = {Animals ; Behavior, Animal ; Biological Evolution ; Cnidaria/anatomy & histology/*physiology ; Ctenophora/anatomy & histology/*physiology ; *Nervous System Physiological Phenomena ; Phylogeny ; }, abstract = {Even the most basal multicellular nervous systems are capable of producing complex behavioral acts that involve the integration and combination of simple responses, and decision-making when presented with conflicting stimuli. This requires an understanding beyond that available from genomic investigations, and calls for a integrative and comparative approach, where the power of genomic/transcriptomic techniques is coupled with morphological, physiological and developmental experimentation to identify common and species-specific nervous system properties for the development and elaboration of phylogenomic reconstructions. With careful selection of genes and gene products, we can continue to make significant progress in our search for ancestral nervous system organizations.}, } @article {pmid25688864, year = {2015}, author = {Mendes, TK and Novakovic, S and Raymant, G and Bertram, SE and Esmaillie, R and Nadarajan, S and Breugelmans, B and Hofmann, A and Gasser, RB and Colaiácovo, MP and Boag, PR}, title = {Investigating the role of RIO protein kinases in Caenorhabditis elegans.}, journal = {PloS one}, volume = {10}, number = {2}, pages = {e0117444}, pmid = {25688864}, issn = {1932-6203}, support = {R01 GM072551/GM/NIGMS NIH HHS/United States ; R01 GM105853/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Animals, Genetically Modified/metabolism ; Caenorhabditis elegans/*enzymology/genetics ; Caenorhabditis elegans Proteins/antagonists & inhibitors/classification/*metabolism ; Cell Proliferation ; Female ; Genome ; Germ Cells/cytology/metabolism ; Gonads/metabolism ; Male ; Phylogeny ; Promoter Regions, Genetic ; Protein Kinases/classification/genetics/*metabolism ; RNA Interference ; RNA, Double-Stranded/metabolism ; Sequence Alignment ; }, abstract = {RIO protein kinases (RIOKs) are a relatively conserved family of enzymes implicated in cell cycle control and ribosomal RNA processing. Despite their functional importance, they remain a poorly understood group of kinases in multicellular organisms. Here, we show that the C. elegans genome contains one member of each of the three RIOK sub-families and that each of the genes coding for them has a unique tissue expression pattern. Our analysis showed that the gene encoding RIOK-1 (riok-1) was broadly and strongly expressed. Interestingly, the intestinal expression of riok-1 was dependent upon two putative binding sites for the oxidative and xenobiotic stress response transcription factor SKN-1. RNA interference (RNAi)-mediated knock down of riok-1 resulted in germline defects, including defects in germ line stem cell proliferation, oocyte maturation and the production of endomitotic oocytes. Taken together, our findings indicate new functions for RIOK-1 in post mitotic tissues and in reproduction.}, } @article {pmid25688421, year = {2015}, author = {Bastiaans, E and Debets, AJ and Aanen, DK}, title = {Experimental demonstration of the benefits of somatic fusion and the consequences for allorecognition.}, journal = {Evolution; international journal of organic evolution}, volume = {69}, number = {4}, pages = {1091-1099}, doi = {10.1111/evo.12626}, pmid = {25688421}, issn = {1558-5646}, mesh = {Alleles ; *Biological Evolution ; Genetic Fitness ; *Genetic Variation ; Neurospora crassa/cytology/*genetics ; Spores, Fungal/cytology ; }, abstract = {Allorecognition, the ability to distinguish "self" from "nonself" based on allelic differences at allorecognition loci, is common in all domains of life. Allorecognition restricts the opportunities for social parasitism, and is therefore crucial for the evolution of cooperation. However, the maintenance of allorecognition diversity provides a paradox. If allorecognition is costly relative to cooperation, common alleles will be favored. Thus, the cost of allorecognition may reduce the genetic variation upon which allorecognition crucially relies, a prediction now known as "Crozier's paradox." We establish the relative costs of allorecognition, and their consequences for the short-term evolution of recognition labels theoretically predicted by Crozier. We use fusion among colonies of the fungus Neurospora crassa, regulated by highly variable allorecognition genes, as an experimental model system. We demonstrate that fusion among colonies is mutually beneficial, relative to absence of fusion upon allorecognition. This benefit is due not only to absence of mutual antagonism, which occurs upon allorecognition, but also to an increase in colony size per se. We then experimentally demonstrate that the benefit of fusion selects against allorecognition diversity, as predicted by Crozier. We discuss what maintains allorecognition diversity.}, } @article {pmid25678667, year = {2015}, author = {Worden, AZ and Follows, MJ and Giovannoni, SJ and Wilken, S and Zimmerman, AE and Keeling, PJ}, title = {Environmental science. Rethinking the marine carbon cycle: factoring in the multifarious lifestyles of microbes.}, journal = {Science (New York, N.Y.)}, volume = {347}, number = {6223}, pages = {1257594}, doi = {10.1126/science.1257594}, pmid = {25678667}, issn = {1095-9203}, mesh = {Animals ; Biological Evolution ; *Carbon Cycle ; Eukaryota/*metabolism ; Phytoplankton/*metabolism ; Seawater/*microbiology ; Symbiosis ; Zooplankton/*metabolism ; }, abstract = {The profound influence of marine plankton on the global carbon cycle has been recognized for decades, particularly for photosynthetic microbes that form the base of ocean food chains. However, a comprehensive model of the carbon cycle is challenged by unicellular eukaryotes (protists) having evolved complex behavioral strategies and organismal interactions that extend far beyond photosynthetic lifestyles. As is also true for multicellular eukaryotes, these strategies and their associated physiological changes are difficult to deduce from genome sequences or gene repertoires—a problem compounded by numerous unknown function proteins. Here, we explore protistan trophic modes in marine food webs and broader biogeochemical influences. We also evaluate approaches that could resolve their activities, link them to biotic and abiotic factors, and integrate them into an ecosystems biology framework.}, } @article {pmid25675537, year = {2015}, author = {Liebeskind, BJ and Hillis, DM and Zakon, HH}, title = {Convergence of ion channel genome content in early animal evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {8}, pages = {E846-51}, pmid = {25675537}, issn = {1091-6490}, support = {R01 DK051131/DK/NIDDK NIH HHS/United States ; R01 DK069463/DK/NIDDK NIH HHS/United States ; R01 GM095538/GM/NIGMS NIH HHS/United States ; //Intramural NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Extinction, Biological ; Genome/*genetics ; Ion Channels/*genetics ; Multigene Family ; Nervous System/metabolism ; Phylogeny ; }, abstract = {Multicellularity has evolved multiple times, but animals are the only multicellular lineage with nervous systems. This fact implies that the origin of nervous systems was an unlikely event, yet recent comparisons among extant taxa suggest that animal nervous systems may have evolved multiple times independently. Here, we use ancestral gene content reconstruction to track the timing of gene family expansions for the major families of ion-channel proteins that drive nervous system function. We find that animals with nervous systems have broadly similar complements of ion-channel types but that these complements likely evolved independently. We also find that ion-channel gene family evolution has included large loss events, two of which were immediately followed by rounds of duplication. Ctenophores, cnidarians, and bilaterians underwent independent bouts of gene expansion in channel families involved in synaptic transmission and action potential shaping. We suggest that expansions of these family types may represent a genomic signature of expanding nervous system complexity. Ancestral nodes in which nervous systems are currently hypothesized to have originated did not experience large expansions, making it difficult to distinguish among competing hypotheses of nervous system origins and suggesting that the origin of nerves was not attended by an immediate burst of complexity. Rather, the evolution of nervous system complexity appears to resemble a slow fuse in stem animals followed by many independent bouts of gene gain and loss.}, } @article {pmid25674102, year = {2015}, author = {Palazzo, AF and Lee, ES}, title = {Non-coding RNA: what is functional and what is junk?.}, journal = {Frontiers in genetics}, volume = {6}, number = {}, pages = {2}, pmid = {25674102}, issn = {1664-8021}, abstract = {The genomes of large multicellular eukaryotes are mostly comprised of non-protein coding DNA. Although there has been much agreement that a small fraction of these genomes has important biological functions, there has been much debate as to whether the rest contributes to development and/or homeostasis. Much of the speculation has centered on the genomic regions that are transcribed into RNA at some low level. Unfortunately these RNAs have been arbitrarily assigned various names, such as "intergenic RNA," "long non-coding RNAs" etc., which have led to some confusion in the field. Many researchers believe that these transcripts represent a vast, unchartered world of functional non-coding RNAs (ncRNAs), simply because they exist. However, there are reasons to question this Panglossian view because it ignores our current understanding of how evolution shapes eukaryotic genomes and how the gene expression machinery works in eukaryotic cells. Although there are undoubtedly many more functional ncRNAs yet to be discovered and characterized, it is also likely that many of these transcripts are simply junk. Here, we discuss how to determine whether any given ncRNA has a function. Importantly, we advocate that in the absence of any such data, the appropriate null hypothesis is that the RNA in question is junk.}, } @article {pmid25667072, year = {2015}, author = {Takahashi, N and Kami, C and Ota, I and Morita, N and Imaichi, R}, title = {Developmental morphology of the typical cordate gametophyte of a homosporous leptosporangiate fern, Lygodium japonicum (Lygodiaceae), focusing on the initial cell behavior of two distinct meristems.}, journal = {American journal of botany}, volume = {102}, number = {2}, pages = {197-207}, doi = {10.3732/ajb.1400333}, pmid = {25667072}, issn = {1537-2197}, mesh = {Biological Evolution ; Cell Division ; Ferns/anatomy & histology/*growth & development ; Germ Cells, Plant/*growth & development ; Meristem/*growth & development ; *Plant Cells ; Polypodiaceae ; Spores ; }, abstract = {PREMISE OF THE STUDY: Understanding the origin and early evolution of vascular plants requires thorough consideration of the gametophyte generation of ferns and lycophytes. Unfortunately, information about this generation is quite limited. To reveal the origin and evolution of varied gametophyte shapes, we used comparative morphological studies of meristem behavior of gametophytes of Lygodium japonicum, which exhibit the typical cordate shape.

METHODS: Microscopic images of epi-illuminated growing gametophytes cultured from spores were captured periodically using a metallurgical microscope equipped with a digital camera to analyze the cell lineage in the meristem.

KEY RESULTS: Gametophytes form from two meristems: the apical-cell-based meristem and the multicellular meristem. The triangular apical cell produces six to eight derivatives from two lateral facets, then disappears. Subsequently, the multicellular meristem, with a row of several rectangular cells, forms in the notch. These rectangular cells divide asynchronously in the periclinal and anticlinal walls to produce cells to both lateral sides and downward. Usually two, and sometimes three, cells located at the center of the meristem divide at a slower pace in the periclinal and anticlinal planes than others at the periphery. The cells at the periphery are pushed away and become involved in the wing base.

CONCLUSIONS: The triangular apical cell behaves as a permanent initial cell. In the multicellular meristem, however, two or three central cells behave as initial cells that are transient and regulated in a position-dependent manner. The organization and behavior of both meristems are shared with the ribbon-shaped gametophytes of Colysis.}, } @article {pmid25662101, year = {2015}, author = {He, Y and Cao, X and Li, K and Hu, Y and Chen, YR and Blissard, G and Kanost, MR and Jiang, H}, title = {A genome-wide analysis of antimicrobial effector genes and their transcription patterns in Manduca sexta.}, journal = {Insect biochemistry and molecular biology}, volume = {62}, number = {}, pages = {23-37}, pmid = {25662101}, issn = {1879-0240}, support = {R37 GM041247/GM/NIGMS NIH HHS/United States ; GM58634/GM/NIGMS NIH HHS/United States ; GM041247/GM/NIGMS NIH HHS/United States ; R01 GM058634/GM/NIGMS NIH HHS/United States ; R01 GM041247/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antimicrobial Cationic Peptides/chemistry/*genetics/immunology ; Gene Expression Profiling ; *Genome, Insect ; Immunity, Innate/genetics ; Insect Proteins/chemistry/*genetics/immunology ; Larva/genetics/immunology ; Manduca/*genetics/immunology/metabolism ; Molecular Sequence Data ; Phylogeny ; Protein Conformation ; *Transcriptome ; }, abstract = {Antimicrobial proteins/peptides (AMPs) are effectors of innate immune systems against pathogen infection in multicellular organisms. Over half of the AMPs reported so far come from insects, and these effectors act in concert to suppress or kill bacteria, fungi, viruses, and parasites. In this work, we have identified 86 AMP genes in the Manduca sexta genome, most of which seem likely to be functional. They encode 15 cecropins, 6 moricins, 6 defensins, 3 gallerimycins, 4 X-tox splicing variants, 14 diapausins, 15 whey acidic protein homologs, 11 attacins, 1 gloverin, 4 lebocins, 6 lysozyme-related proteins, and 4 transferrins. Some of these genes (e.g. attacins, cecropins) constitute large clusters, likely arising after rounds of gene duplication. We compared the amino acid sequences of M. sexta AMPs with their homologs in other insects to reveal conserved structural features and phylogenetic relationships. Expression data showed that many of them are synthesized in fat body and midgut during the larval-pupal molt. Certain genes contain one or more predicted κB binding sites and other regulatory elements in their promoter regions, which may account for the dramatic mRNA level increases in fat body and hemocytes after an immune challenge. Consistent with these strong mRNA increases, many AMPs become highly abundant in the larval plasma at 24 h after the challenge, as demonstrated in our previous peptidomic study. Taken together, these data suggest the existence of a large repertoire of AMPs in M. sexta, whose expression is up-regulated via immune signaling pathways to fight off invading pathogens in a coordinated manner.}, } @article {pmid25659377, year = {2015}, author = {Godin, SK and Meslin, C and Kabbinavar, F and Bratton-Palmer, DS and Hornack, C and Mihalevic, MJ and Yoshida, K and Sullivan, M and Clark, NL and Bernstein, KA}, title = {Evolutionary and functional analysis of the invariant SWIM domain in the conserved Shu2/SWS1 protein family from Saccharomyces cerevisiae to Homo sapiens.}, journal = {Genetics}, volume = {199}, number = {4}, pages = {1023-1033}, pmid = {25659377}, issn = {1943-2631}, support = {R01 ES024872/ES/NIEHS NIH HHS/United States ; ES-0244872/ES/NIEHS NIH HHS/United States ; K99 GM088413/GM/NIGMS NIH HHS/United States ; GM-088413/GM/NIGMS NIH HHS/United States ; R00 GM088413/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cell Cycle Proteins/*genetics/metabolism ; *Conserved Sequence ; *Evolution, Molecular ; Humans ; Molecular Sequence Data ; Multigene Family ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/*genetics ; Schizosaccharomyces pombe Proteins/*genetics/metabolism ; }, abstract = {The Saccharomyces cerevisiae Shu2 protein is an important regulator of Rad51, which promotes homologous recombination (HR). Shu2 functions in the Shu complex with Shu1 and the Rad51 paralogs Csm2 and Psy3. Shu2 belongs to the SWS1 protein family, which is characterized by its SWIM domain (CXC...Xn...CXH), a zinc-binding motif. In humans, SWS1 interacts with the Rad51 paralog SWSAP1. Using genetic and evolutionary analyses, we examined the role of the Shu complex in mitotic and meiotic processes across eukaryotic lineages. We provide evidence that the SWS1 protein family contains orthologous genes in early-branching eukaryote lineages (e.g., Giardia lamblia), as well as in multicellular eukaryotes including Caenorhabditis elegans and Drosophila melanogaster. Using sequence analysis, we expanded the SWIM domain to include an invariant alanine three residues after the terminal CXH motif (CXC…Xn…CXHXXA). We found that the SWIM domain is conserved in all eukaryotic orthologs, and accordingly, in vivo disruption of the invariant residues within the canonical SWIM domain inhibits DNA damage tolerance in yeast and protein-protein interactions in yeast and humans. Furthermore, using evolutionary analyses, we found that yeast and Drosophila Shu2 exhibit strong coevolutionary signatures with meiotic proteins, and in yeast, its disruption leads to decreased meiotic progeny. Together our data indicate that the SWS1 family is an ancient and highly conserved eukaryotic regulator of meiotic and mitotic HR.}, } @article {pmid25653025, year = {2015}, author = {Kuijper, B and Lane, N and Pomiankowski, A}, title = {Can paternal leakage maintain sexually antagonistic polymorphism in the cytoplasm?.}, journal = {Journal of evolutionary biology}, volume = {28}, number = {2}, pages = {468-480}, pmid = {25653025}, issn = {1420-9101}, mesh = {Alleles ; Animals ; Cytoplasm ; DNA, Mitochondrial/genetics ; Epistasis, Genetic ; Female ; Haploidy ; Male ; *Models, Genetic ; Polymorphism, Genetic/*genetics/physiology ; }, abstract = {A growing number of studies in multicellular organisms highlight low or moderate frequencies of paternal transmission of cytoplasmic organelles, including both mitochondria and chloroplasts. It is well established that strict maternal inheritance is selectively blind to cytoplasmic elements that are deleterious to males - 'mother's curse'. But it is not known how sensitive this conclusion is to slight levels of paternal cytoplasmic leakage. We assess the scope for polymorphism when individuals bear multiple cytoplasmic alleles in the presence of paternal leakage, bottlenecks and recurrent mutation. When fitness interactions among cytoplasmic elements within an individual are additive, we find that sexually antagonistic polymorphism is restricted to cases of strong selection on males. However, when fitness interactions among cytoplasmic elements are nonlinear, much more extensive polymorphism can be supported in the cytoplasm. In particular, mitochondrial mutants that have strong beneficial fitness effects in males and weak deleterious fitness effects in females when rare (i.e. 'reverse dominance') are strongly favoured under paternal leakage. We discuss how such epistasis could arise through preferential segregation of mitochondria in sex-specific somatic tissues. Our analysis shows how paternal leakage can dampen the evolution of deleterious male effects associated with predominant maternal inheritance of cytoplasm, potentially explaining why 'mother's curse' is less pervasive than predicted by earlier work.}, } @article {pmid25634491, year = {2015}, author = {Imamura, Y and Mukohara, T and Shimono, Y and Funakoshi, Y and Chayahara, N and Toyoda, M and Kiyota, N and Takao, S and Kono, S and Nakatsura, T and Minami, H}, title = {Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer.}, journal = {Oncology reports}, volume = {33}, number = {4}, pages = {1837-1843}, doi = {10.3892/or.2015.3767}, pmid = {25634491}, issn = {1791-2431}, mesh = {Antineoplastic Agents/pharmacology ; Breast Neoplasms/*drug therapy/metabolism ; Caspases/metabolism ; Cell Culture Techniques/*methods ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Female ; Humans ; Ki-67 Antigen/metabolism ; Spheroids, Cellular ; }, abstract = {It is becoming recognized that screening of oncology drugs on a platform using two-dimensionally (2D)-cultured cell lines is unable to precisely select clinically active drugs; therefore three-dimensional (3D)-culture systems are emerging and show potential for better simulating the in vivo tumor microenvironment. The purpose of this study was to reveal the differential effects of chemotherapeutic drugs between 2D- and 3D-cultures and to explore their underlying mechanisms. We evaluated differences between 2D- and 3D-cultured breast cancer cell lines by assessing drug sensitivity, oxygen status and expression of Ki-67 and caspases. Three cell lines (BT-549, BT-474 and T-47D) developed dense multicellular spheroids (MCSs) in 3D-culture, and showed greater resistance to paclitaxel and doxorubicin compared to the 2D-cultured cells. An additional three cell lines (MCF-7, HCC-1954, and MDA-MB‑231) developed only loose MCSs in 3D, and showed drug sensitivities similar to those found in the 2D-culture. Treatment with paclitaxel resulted in greater increases in cleaved-PARP expression in the 2D-culture compared with the 3D-culture, but only in cell lines forming dense 3D-MCSs, suggesting that MCS formation protected the cells from paclitaxel-induced apoptosis. Hypoxia was observed only in the dense 3D-MCSs. BT-549 had fewer cells positive for Ki-67 in 3D- than in 2D-culture, suggesting that the greater G0-dormant subpopulation was responsible for its drug resistance in the 3D-culture. BT-474 had a lower level of caspase-3 in the 3D- than in the 2D-culture, suggesting that the 3D-environment was anti-apoptotic. Finally, we compared staining for Ki-67 and caspases in the 2D- and 3D-primary‑cultured cells originating from a patient-derived xenograft (PDX), fresh PDX tumor, and the patient's original tumor; 2D-cultured cells showed greater proportions of Ki-67-positive and caspase-3-positive cells, in agreement with the view that 3D-primary culture better represents characteristics of tumors in vivo. In conclusion, 3D-cultured cells forming dense MCSs may be better than 2D-cultured cells in simulating important tumor characteristics in vivo, namely hypoxia, dormancy, anti-apoptotic features and their resulting drug resistance.}, } @article {pmid25634368, year = {2015}, author = {Cowie, P and Hay, EA and MacKenzie, A}, title = {The noncoding human genome and the future of personalised medicine.}, journal = {Expert reviews in molecular medicine}, volume = {17}, number = {}, pages = {e4}, doi = {10.1017/erm.2014.23}, pmid = {25634368}, issn = {1462-3994}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Genetic Predisposition to Disease ; Genome, Human/*genetics ; Humans ; *Precision Medicine ; Regulatory Sequences, Nucleic Acid/*genetics ; }, abstract = {Non-coding cis-regulatory sequences act as the 'eyes' of the genome and their role is to perceive, organise and relay cellular communication information to RNA polymerase II at gene promoters. The evolution of these sequences, that include enhancers, silencers, insulators and promoters, has progressed in multicellular organisms to the extent that cis-regulatory sequences make up as much as 10% of the human genome. Parallel evidence suggests that 75% of polymorphisms associated with heritable disease occur within predicted cis-regulatory sequences that effectively alter the 'perception' of cis-regulatory sequences or render them blind to cell communication cues. Cis-regulatory sequences also act as major functional targets of epigenetic modification thus representing an important conduit through which changes in DNA-methylation affects disease susceptibility. The objectives of the current review are (1) to describe what has been learned about identifying and characterising cis-regulatory sequences since the sequencing of the human genome; (2) to discuss their role in interpreting cell signalling pathways pathways; and (3) outline how this role may be altered by polymorphisms and epigenetic changes. We argue that the importance of the cis-regulatory genome for the interpretation of cellular communication pathways cannot be overstated and understanding its role in health and disease will be critical for the future development of personalised medicine.}, } @article {pmid25621522, year = {2015}, author = {Foox, J and Siddall, ME}, title = {The Road To Cnidaria: History of Phylogeny of the Myxozoa.}, journal = {The Journal of parasitology}, volume = {101}, number = {3}, pages = {269-274}, doi = {10.1645/14-671.1}, pmid = {25621522}, issn = {1937-2345}, mesh = {Animals ; Cnidaria/*classification/genetics ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Myxozoa/classification/genetics ; Parasitic Diseases/*history/*parasitology ; *Phylogeny ; }, abstract = {Myxozoans are a clade of highly derived cnidarians. The phylogenetic identity of these extremely simplified parasites of aquatic vertebrates and invertebrates had long been uncertain, with all early classifications designating Myxozoa as protists. Though suggestions were frequently made that the infective spores of these parasites are multicellular and possibly of cnidarian origin, it would take a phylogenetic analysis of ultrastructural developmental characters in combination with rRNA gene sequences to verify the Myxozoa as secondarily reduced cnidarians, sister to the polypoidozoan parasite Polypodium hydriforme . While a series of subsequent molecular studies suggested hypotheses of Myxozoa as basal bilaterians, triploblasts, or even nematodes, phylogenomic analyses with improved taxon sampling corroborated the landmark paper that verified the cnidarian nature of this group. This review of the body of phylogenetic work on Myxozoa aims to clarify historical progress and current knowledge, as well as to emphasize the opportune position that myxozoan biologists now are in, to address fundamental questions of cell biology of these parasites as well as the evolution of animal life.}, } @article {pmid25616141, year = {2015}, author = {Gilbert, OM}, title = {Histocompatibility as adaptive response to discriminatory within-organism conflict: a historical model.}, journal = {The American naturalist}, volume = {185}, number = {2}, pages = {228-242}, doi = {10.1086/679442}, pmid = {25616141}, issn = {1537-5323}, mesh = {Animals ; *Biological Evolution ; *Game Theory ; Histocompatibility/*genetics ; Invertebrates/genetics/*immunology ; *Models, Genetic ; }, abstract = {Multicellular tissue compatibility, or histocompatibility, restricts fusion to close kin. Histocompatibility depends on hypervariable cue genes, which often have more than 100 alleles in a population. To explain the evolution of histocompatibility, I here take a historical approach. I focus on the specific example of marine invertebrate histocompatibility. I use simple game-theoretical models to show that histocompatibility can evolve through five steps. These steps include the evolution of indiscriminate fusion, the evolution of discriminatory within-organism conflict, the evolution of minor histocompatibility, the evolution of major histocompatibility, and the evolution of major histocompatibility cue polymorphism. Allowing for gradual evolution reveals discriminatory within-organism conflict as a selective pressure for histocompatibility and associated cue polymorphism. Existing data from marine invertebrates and other organisms are consistent with this hypothesis.}, } @article {pmid25603395, year = {2015}, author = {Annenkova, NV and Hansen, G and Moestrup, Ø and Rengefors, K}, title = {Recent radiation in a marine and freshwater dinoflagellate species flock.}, journal = {The ISME journal}, volume = {9}, number = {8}, pages = {1821-1834}, pmid = {25603395}, issn = {1751-7370}, mesh = {DNA, Protozoan/analysis ; DNA, Ribosomal/genetics ; Dinoflagellida/genetics/*isolation & purification ; Lakes/*parasitology ; Phylogeny ; Russia ; Seawater/*parasitology ; Species Specificity ; }, abstract = {Processes of rapid radiation among unicellular eukaryotes are much less studied than among multicellular organisms. We have investigated a lineage of cold-water microeukaryotes (protists) that appear to have diverged recently. This lineage stands in stark contrast to known examples of phylogenetically closely related protists, in which genetic difference is typically larger than morphological differences. We found that the group not only consists of the marine-brackish dinoflagellate species Scrippsiella hangoei and the freshwater species Peridinium aciculiferum as discovered previously but also of a whole species flock. The additional species include Peridinium euryceps and Peridinium baicalense, which are restricted to a few lakes, in particular to the ancient Lake Baikal, Russia, and freshwater S. hangoei from Lake Baikal. These species are characterized by relatively large conspicuous morphological differences, which have given rise to the different species descriptions. However, our scanning electron microscopic studies indicate that they belong to a single genus according to traditional morphological characterization of dinoflagellates (thecal plate patterns). Moreover, we found that they have identical SSU (small subunit) rDNA fragments and distinct but very small differences in the DNA markers LSU (large subunit) rDNA, ITS2 (internal transcribed spacer 2) and COB (cytochrome b) gene, which are used to delineate dinoflagellates species. As some of the species co-occur, and all four have small but species-specific sequence differences, we suggest that these taxa are not a case of phenotypic plasticity but originated via recent adaptive radiation. We propose that this is the first clear example among free-living microeukaryotes of recent rapid diversification into several species followed by dispersion to environments with different ecological conditions.}, } @article {pmid25600558, year = {2015}, author = {Ratcliff, WC and Fankhauser, JD and Rogers, DW and Greig, D and Travisano, M}, title = {Origins of multicellular evolvability in snowflake yeast.}, journal = {Nature communications}, volume = {6}, number = {}, pages = {6102}, pmid = {25600558}, issn = {2041-1723}, mesh = {Angiotensin-Converting Enzyme 2 ; Mutation ; Peptidyl-Dipeptidase A/genetics ; Saccharomyces cerevisiae/*cytology/*genetics/physiology ; }, abstract = {Complex life has arisen through a series of 'major transitions' in which collectives of formerly autonomous individuals evolve into a single, integrated organism. A key step in this process is the origin of higher-level evolvability, but little is known about how higher-level entities originate and gain the capacity to evolve as an individual. Here we report a single mutation that not only creates a new level of biological organization, but also potentiates higher-level evolvability. Disrupting the transcription factor ACE2 in Saccharomyces cerevisiae prevents mother-daughter cell separation, generating multicellular 'snowflake' yeast. Snowflake yeast develop through deterministic rules that produce geometrically defined clusters that preclude genetic conflict and display a high broad-sense heritability for multicellular traits; as a result they are preadapted to multicellular adaptation. This work demonstrates that simple microevolutionary changes can have profound macroevolutionary consequences, and suggests that the formation of clonally developing clusters may often be the first step to multicellularity.}, } @article {pmid25573960, year = {2015}, author = {Boon, E and Halary, S and Bapteste, E and Hijri, M}, title = {Studying genome heterogeneity within the arbuscular mycorrhizal fungal cytoplasm.}, journal = {Genome biology and evolution}, volume = {7}, number = {2}, pages = {505-521}, pmid = {25573960}, issn = {1759-6653}, mesh = {Alleles ; Base Sequence ; Cluster Analysis ; Computer Simulation ; Cytoplasm/*genetics ; Evolution, Molecular ; Gene Dosage ; Genetic Markers ; *Genetic Variation ; Genome Size ; Genome, Fungal ; Glomeromycota/*genetics/isolation & purification ; Molecular Sequence Annotation ; Mutation/genetics ; Mycorrhizae/*genetics/isolation & purification ; Polymorphism, Genetic ; Real-Time Polymerase Chain Reaction ; Repetitive Sequences, Nucleic Acid/genetics ; Reproducibility of Results ; }, abstract = {Although heterokaryons have been reported in nature, multicellular organisms are generally assumed genetically homogeneous. Here, we investigate the case of arbuscular mycorrhizal fungi (AMF) that form symbiosis with plant roots. The growth advantages they confer to their hosts are of great potential benefit to sustainable agricultural practices. However, measuring genetic diversity for these coenocytes is a major challenge: Within the same cytoplasm, AMF contain thousands of nuclei and show extremely high levels of genetic variation for some loci. The extent and physical location of polymorphism within and between AMF genomes is unclear. We used two complementary strategies to estimate genetic diversity in AMF, investigating polymorphism both on a genome scale and in putative single copy loci. First, we used data from whole-genome pyrosequencing of four AMF isolates to describe genetic diversity, based on a conservative network-based clustering approach. AMF isolates showed marked differences in genome-wide diversity patterns in comparison to a panel of control fungal genomes. This clustering approach further allowed us to provide conservative estimates of Rhizophagus spp. genomes sizes. Second, we designed new putative single copy genomic markers, which we investigated by massive parallel amplicon sequencing for two Rhizophagus irregularis and one Rhizophagus sp. isolates. Most loci showed high polymorphism, with up to 103 alleles per marker. This polymorphism could be distributed within or between nuclei. However, we argue that the Rhizophagus isolates under study might be heterokaryotic, at least for the putative single copy markers we studied. Considering that genetic information is the main resource for identification of AMF, we suggest that special attention is warranted for the study of these ecologically important organisms.}, } @article {pmid25562138, year = {2015}, author = {Gomes, AP and Blenis, J}, title = {A nexus for cellular homeostasis: the interplay between metabolic and signal transduction pathways.}, journal = {Current opinion in biotechnology}, volume = {34}, number = {}, pages = {110-117}, pmid = {25562138}, issn = {1879-0429}, support = {HL121266/HL/NHLBI NIH HHS/United States ; R01 HL121266/HL/NHLBI NIH HHS/United States ; R01 CA046595/CA/NCI NIH HHS/United States ; R37 CA046595/CA/NCI NIH HHS/United States ; CA46595/CA/NCI NIH HHS/United States ; R01 GM051405/GM/NIGMS NIH HHS/United States ; GM51405/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Homeostasis ; Metabolic Networks and Pathways ; Protein Kinases/metabolism ; *Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {In multicellular organisms, individual cells have evolved to sense external and internal cues in order to maintain cellular homeostasis and survive under different environmental conditions. Cells efficiently adjust their metabolism to reflect the abundance of nutrients, energy and growth factors. The ability to rewire cellular metabolism between anabolic and catabolic processes is crucial for cells to thrive. Thus, cells have developed, through evolution, metabolic networks that are highly plastic and tightly regulated to meet the requirements necessary to maintain cellular homeostasis. The plasticity of these cellular systems is tightly regulated by complex signaling networks that integrate the intracellular and extracellular information. The coordination of signal transduction and metabolic pathways is essential in maintaining a healthy and rapidly responsive cellular state.}, } @article {pmid25558847, year = {2015}, author = {Boileau, E and George, CH and Parthimos, D and Mitchell, AN and Aziz, S and Nithiarasu, P}, title = {Synergy Between Intercellular Communication and Intracellular Ca(2+) Handling in Arrhythmogenesis.}, journal = {Annals of biomedical engineering}, volume = {43}, number = {7}, pages = {1614-1625}, doi = {10.1007/s10439-014-1243-x}, pmid = {25558847}, issn = {1573-9686}, support = {094219/Z/10/Z//Wellcome Trust/United Kingdom ; FS/06/082/21723//British Heart Foundation/United Kingdom ; FS/09/028/27602//British Heart Foundation/United Kingdom ; }, mesh = {Animals ; Arrhythmias, Cardiac/*physiopathology ; Calcium/*physiology ; Cell Communication/*physiology ; Cell Line ; Mice ; }, abstract = {Calcium is the primary signalling component of excitation-contraction coupling, the process linking electrical excitability of cardiac muscle cells to coordinated contraction of the heart. Understanding [Formula: see text] handling processes at the cellular level and the role of intercellular communication in the emergence of multicellular synchronization are key aspects in the study of arrhythmias. To probe these mechanisms, we have simulated cellular interactions on large scale arrays that mimic cardiac tissue, and where individual cells are represented by a mathematical model of intracellular [Formula: see text] dynamics. Theoretical predictions successfully reproduced experimental findings and provide novel insights on the action of two pharmacological agents (ionomycin and verapamil) that modulate [Formula: see text] signalling pathways via distinct mechanisms. Computational results have demonstrated how transitions between local synchronisation events and large scale wave formation are affected by these agents. Entrainment phenomena are shown to be linked to both intracellular [Formula: see text] and coupling-specific dynamics in a synergistic manner. The intrinsic variability of the cellular matrix is also shown to affect emergent patterns of rhythmicity, providing insights into the origins of arrhythmogenic [Formula: see text] perturbations in cardiac tissue in situ.}, } @article {pmid25552080, year = {2014}, author = {Akhmadeev, AV and Kalimullina, LB}, title = {[Structural and functional organization of cart peptide-expressing neurons in brain amygdala].}, journal = {Morfologiia (Saint Petersburg, Russia)}, volume = {146}, number = {4}, pages = {11-14}, pmid = {25552080}, issn = {1026-3543}, mesh = {Amygdala/*cytology/*metabolism ; Animals ; Dendrites/*metabolism ; Gene Expression Regulation/*physiology ; Nerve Tissue Proteins/*biosynthesis ; Rats ; Rats, Wistar ; Cocaine- and Amphetamine-Regulated Transcript Protein ; }, abstract = {The aim of the study was to identify the specific features of structural and functional organization of the neurons in dorsomedial nucleus of amygdala containing immunoreactive CART peptide. The study was carried out on 15 Wistar rats using an immunocytochemical demonstration of CART peptide and Golgi method. CART peptide-expressing neurons in subependymal zone of the nucleus were shown to be neuroblastoformal, while those located in its central zones were short-dendritic. These data demonstrate that CART peptide-expressing neurons are belong to a sparcely branched neuronal system. The results obtained in this work together with the analysis of the literature and the provisions of A.L. Polenov (1993) concept on the origin and evolution of the neuroendocrine cells and neurohormonal regulation in Metazoa, suggest that CART peptide appeared during the early stages of the formation of the regulatory chemical communication in the multicellular organisms.}, } @article {pmid27008743, year = {2015}, author = {Isakov, DV and Isakov, VA}, title = {[CYCLOFERON: MECHANISM OF ACTION, AND NEW PROSPECTS FOR APPLICATION IN CLINICAL PRACTICE].}, journal = {Klinicheskaia meditsina}, volume = {93}, number = {9}, pages = {46-51}, pmid = {27008743}, issn = {0023-2149}, mesh = {Acridines/*pharmacology ; Adaptive Immunity/*drug effects ; Animals ; Humans ; Infections/*drug therapy/immunology ; Interferon Inducers/pharmacology ; }, abstract = {Multicellular organisms exist in constant interaction with various species of microflora both at the body surface and in internal media. The mechanism of recognition of conservative molecular structures of infectious origin formed at the earliest stages of evolution before the appearance of the genes of the immunoglobulin superfamily in jawed vertebrates (Gnathostomata) that made up a basis for the development of clonal specificity of B- and T-lymphocytes as adaptive immunity factors. This paper considers the mechanism of action of cycloferon as an inductor of endogenous interferon synthesis and the new prospects for its application in clinical medicine.}, } @article {pmid25551152, year = {2015}, author = {Duran-Nebreda, S and Solé, R}, title = {Emergence of multicellularity in a model of cell growth, death and aggregation under size-dependent selection.}, journal = {Journal of the Royal Society, Interface}, volume = {12}, number = {102}, pages = {20140982}, pmid = {25551152}, issn = {1742-5662}, mesh = {Algorithms ; Apoptosis ; *Biological Evolution ; Cluster Analysis ; Computer Simulation ; Models, Biological ; Mutation ; Phylogeny ; Saccharomyces cerevisiae/*genetics/*physiology ; Selection, Genetic ; }, abstract = {How multicellular life forms evolved from unicellular ones constitutes a major problem in our understanding of the evolution of our biosphere. A recent set of experiments involving yeast cell populations have shown that selection for faster sedimenting cells leads to the appearance of stable aggregates of cells that are able to split into smaller clusters. It was suggested that the observed evolutionary patterns could be the result of evolved programmes affecting cell death. Here, we show, using a simple model of cell-cell interactions and evolving adhesion rates, that the observed patterns in cluster size and localized mortality can be easily interpreted in terms of waste accumulation and toxicity-driven apoptosis. This simple mechanism would have played a key role in the early evolution of multicellular life forms based on both aggregative and clonal development. The potential extensions of this work and its implications for natural and synthetic multicellularity are discussed.}, } @article {pmid25547403, year = {2015}, author = {Messina, G and Celauro, E and Atterrato, MT and Giordano, E and Iwashita, S and Dimitri, P}, title = {The Bucentaur (BCNT) protein family: a long-neglected class of essential proteins required for chromatin/chromosome organization and function.}, journal = {Chromosoma}, volume = {124}, number = {2}, pages = {153-162}, pmid = {25547403}, issn = {1432-0886}, mesh = {Amino Acid Sequence ; Animals ; Carrier Proteins/genetics/metabolism ; Chickens/genetics ; Chromatin/*genetics ; Drosophila/genetics ; Drosophila Proteins/genetics/metabolism ; Evolution, Molecular ; Extracellular Matrix Proteins/*genetics/metabolism ; Gene Expression Regulation, Developmental ; Humans ; Mice ; Molecular Sequence Data ; *Multigene Family ; Nuclear Proteins ; Phosphoproteins/*genetics/metabolism ; Saccharomyces cerevisiae/genetics ; Sequence Alignment ; Zebrafish/genetics ; }, abstract = {The evolutionarily conserved Bucentaur (BCNT) protein superfamily was identified about two decades ago in bovines, but its biological role has long remained largely unknown. Sparse studies in the literature suggest that BCNT proteins perform important functions during development. Only recently, a functional analysis of the Drosophila BCNT ortholog, called YETI, has provided evidence that it is essential for proper fly development and plays roles in chromatin organization. Here, we introduce the BCNT proteins and comprehensively review data that contribute to clarify their function and mechanistic clues on how they may control development in multicellular organisms.}, } @article {pmid25540429, year = {2015}, author = {Meller, J and Rogozin, IB and Poliakov, E and Meller, N and Bedanov-Pack, M and Plow, EF and Qin, J and Podrez, EA and Byzova, TV}, title = {Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness.}, journal = {Molecular biology of the cell}, volume = {26}, number = {4}, pages = {786-796}, pmid = {25540429}, issn = {1939-4586}, support = {R01 HL071625/HL/NHLBI NIH HHS/United States ; //Intramural NIH HHS/United States ; R01 HL058758/HL/NHLBI NIH HHS/United States ; P01 HL073311/HL/NHLBI NIH HHS/United States ; R01 HL096062/HL/NHLBI NIH HHS/United States ; HL073311/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Cell Adhesion ; Conserved Sequence ; Evolution, Molecular ; Genome ; Humans ; Integrins/genetics/metabolism/*physiology ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment ; Sequence Analysis, Protein ; Species Specificity ; Talin/genetics/metabolism/*physiology ; }, abstract = {Kindlins are integrin-interacting proteins essential for integrin-mediated cell adhesiveness. In this study, we focused on the evolutionary origin and functional specialization of kindlins as a part of the evolutionary adaptation of cell adhesive machinery. Database searches revealed that many members of the integrin machinery (including talin and integrins) existed before kindlin emergence in evolution. Among the analyzed species, all metazoan lineages—but none of the premetazoans—had at least one kindlin-encoding gene, whereas talin was present in several premetazoan lineages. Kindlin appears to originate from a duplication of the sequence encoding the N-terminal fragment of talin (the talin head domain) with a subsequent insertion of the PH domain of separate origin. Sequence analysis identified a member of the actin filament-associated protein 1 (AFAP1) superfamily as the most likely origin of the kindlin PH domain. The functional divergence between kindlin paralogues was assessed using the sequence swap (chimera) approach. Comparison of kindlin 2 (K2)/kindlin 3 (K3) chimeras revealed that the F2 subdomain, in particular its C-terminal part, is crucial for the differential functional properties of K2 and K3. The presence of this segment enables K2 but not K3 to localize to focal adhesions. Sequence analysis of the C-terminal part of the F2 subdomain of K3 suggests that insertion of a variable glycine-rich sequence in vertebrates contributed to the loss of constitutive K3 targeting to focal adhesions. Thus emergence and subsequent functional specialization of kindlins allowed multicellular organisms to develop additional tissue-specific adaptations of cell adhesiveness.}, } @article {pmid25540145, year = {2015}, author = {Rossier, BC and Baker, ME and Studer, RA}, title = {Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited.}, journal = {Physiological reviews}, volume = {95}, number = {1}, pages = {297-340}, doi = {10.1152/physrev.00011.2014}, pmid = {25540145}, issn = {1522-1210}, mesh = {Aldosterone/*metabolism ; Animals ; *Biological Evolution ; Epithelial Sodium Channels/chemistry/genetics/*metabolism ; Genome, Human ; Humans ; Nephrons/physiology ; Signal Transduction/physiology ; Sodium/*metabolism ; Sodium-Potassium-Exchanging ATPase/chemistry/genetics/*metabolism ; }, abstract = {Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.}, } @article {pmid25538686, year = {2014}, author = {Soto, W and Nishiguchi, MK}, title = {Microbial experimental evolution as a novel research approach in the Vibrionaceae and squid-Vibrio symbiosis.}, journal = {Frontiers in microbiology}, volume = {5}, number = {}, pages = {593}, pmid = {25538686}, issn = {1664-302X}, support = {SC1 AI081659/AI/NIAID NIH HHS/United States ; }, abstract = {The Vibrionaceae are a genetically and metabolically diverse family living in aquatic habitats with a great propensity toward developing interactions with eukaryotic microbial and multicellular hosts (as either commensals, pathogens, and mutualists). The Vibrionaceae frequently possess a life history cycle where bacteria are attached to a host in one phase and then another where they are free from their host as either part of the bacterioplankton or adhered to solid substrates such as marine sediment, riverbeds, lakebeds, or floating particulate debris. These two stages in their life history exert quite distinct and separate selection pressures. When bound to solid substrates or to host cells, the Vibrionaceae can also exist as complex biofilms. The association between bioluminescent Vibrio spp. and sepiolid squids (Cephalopoda: Sepiolidae) is an experimentally tractable model to study bacteria and animal host interactions, since the symbionts and squid hosts can be maintained in the laboratory independently of one another. The bacteria can be grown in pure culture and the squid hosts raised gnotobiotically with sterile light organs. The partnership between free-living Vibrio symbionts and axenic squid hatchlings emerging from eggs must be renewed every generation of the cephalopod host. Thus, symbiotic bacteria and animal host can each be studied alone and together in union. Despite virtues provided by the Vibrionaceae and sepiolid squid-Vibrio symbiosis, these assets to evolutionary biology have yet to be fully utilized for microbial experimental evolution. Experimental evolution studies already completed are reviewed, along with exploratory topics for future study.}, } @article {pmid25525215, year = {2015}, author = {Grau-Bové, X and Sebé-Pedrós, A and Ruiz-Trillo, I}, title = {The eukaryotic ancestor had a complex ubiquitin signaling system of archaeal origin.}, journal = {Molecular biology and evolution}, volume = {32}, number = {3}, pages = {726-739}, pmid = {25525215}, issn = {1537-1719}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Cluster Analysis ; Eukaryota/*genetics ; *Evolution, Molecular ; Genes/genetics ; Genes, Archaeal/*genetics ; Phylogeny ; Small Ubiquitin-Related Modifier Proteins/*genetics ; Ubiquitin/*genetics ; }, abstract = {The origin of the eukaryotic cell is one of the most important transitions in the history of life. However, the emergence and early evolution of eukaryotes remains poorly understood. Recent data have shown that the last eukaryotic common ancestor (LECA) was much more complex than previously thought. The LECA already had the genetic machinery encoding the endomembrane apparatus, spliceosome, nuclear pore, and myosin and kinesin cytoskeletal motors. It is unclear, however, when the functional regulation of these cellular components evolved. Here, we address this question by analyzing the origin and evolution of the ubiquitin (Ub) signaling system, one of the most important regulatory layers in eukaryotes. We delineated the evolution of the whole Ub, Small-Ub-related MOdifier (SUMO), and Ub-fold modifier 1 (Ufm1) signaling networks by analyzing representatives from all major eukaryotic, bacterial, and archaeal lineages. We found that the Ub toolkit had a pre-eukaryotic origin and is present in three extant archaeal groups. The pre-eukaryotic Ub toolkit greatly expanded during eukaryogenesis, through massive gene innovation and diversification of protein domain architectures. This resulted in a LECA with essentially all of the Ub-related genes, including the SUMO and Ufm1 Ub-like systems. Ub and SUMO signaling further expanded during eukaryotic evolution, especially labeling and delabeling enzymes responsible for substrate selection. Additionally, we analyzed protein domain architecture evolution and found that multicellular lineages have the most complex Ub systems in terms of domain architectures. Together, we demonstrate that the Ub system predates the origin of eukaryotes and that a burst of innovation during eukaryogenesis led to a LECA with complex posttranslational regulation.}, } @article {pmid25498309, year = {2015}, author = {Cai, X and Wang, X and Patel, S and Clapham, DE}, title = {Insights into the early evolution of animal calcium signaling machinery: a unicellular point of view.}, journal = {Cell calcium}, volume = {57}, number = {3}, pages = {166-173}, pmid = {25498309}, issn = {1532-1991}, support = {/HHMI/Howard Hughes Medical Institute/United States ; BB/G013721/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Calcium Signaling/*physiology ; Eukaryota/*metabolism ; Fungi/*metabolism ; Phylogeny ; Plants/*metabolism ; }, abstract = {The basic principles of Ca(2+) regulation emerged early in prokaryotes. Ca(2+) signaling acquired more extensive and varied functions when life evolved into multicellular eukaryotes with intracellular organelles. Animals, fungi and plants display differences in the mechanisms that control cytosolic Ca(2+) concentrations. The aim of this review is to examine recent findings from comparative genomics of Ca(2+) signaling molecules in close unicellular relatives of animals and in common unicellular ancestors of animals and fungi. Also discussed are the evolution and origins of the sperm-specific CatSper channel complex, cation/Ca(2+) exchangers and four-domain voltage-gated Ca(2+) channels. Newly identified evolutionary evidence suggests that the distinct Ca(2+) signaling machineries in animals, plants and fungi likely originated from an ancient Ca(2+) signaling machinery prior to early eukaryotic radiation.}, } @article {pmid25487147, year = {2015}, author = {Hashimshony, T and Feder, M and Levin, M and Hall, BK and Yanai, I}, title = {Spatiotemporal transcriptomics reveals the evolutionary history of the endoderm germ layer.}, journal = {Nature}, volume = {519}, number = {7542}, pages = {219-222}, pmid = {25487147}, issn = {1476-4687}, support = {310927/ERC_/European Research Council/International ; }, mesh = {Animals ; Caenorhabditis elegans/cytology/*embryology/*genetics ; Cell Lineage ; Eating ; Ectoderm/cytology/embryology/metabolism ; Endoderm/cytology/embryology/*metabolism ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/*genetics ; Mesoderm/cytology/embryology/metabolism ; Models, Biological ; Porifera/cytology/embryology/genetics ; Sea Anemones/cytology/embryology/genetics ; *Spatio-Temporal Analysis ; Time Factors ; Transcriptome/*genetics ; Xenopus/embryology/genetics ; }, abstract = {The concept of germ layers has been one of the foremost organizing principles in developmental biology, classification, systematics and evolution for 150 years (refs 1 - 3). Of the three germ layers, the mesoderm is found in bilaterian animals but is absent in species in the phyla Cnidaria and Ctenophora, which has been taken as evidence that the mesoderm was the final germ layer to evolve. The origin of the ectoderm and endoderm germ layers, however, remains unclear, with models supporting the antecedence of each as well as a simultaneous origin. Here we determine the temporal and spatial components of gene expression spanning embryonic development for all Caenorhabditis elegans genes and use it to determine the evolutionary ages of the germ layers. The gene expression program of the mesoderm is induced after those of the ectoderm and endoderm, thus making it the last germ layer both to evolve and to develop. Strikingly, the C. elegans endoderm and ectoderm expression programs do not co-induce; rather the endoderm activates earlier, and this is also observed in the expression of endoderm orthologues during the embryology of the frog Xenopus tropicalis, the sea anemone Nematostella vectensis and the sponge Amphimedon queenslandica. Querying the phylogenetic ages of specifically expressed genes reveals that the endoderm comprises older genes. Taken together, we propose that the endoderm program dates back to the origin of multicellularity, whereas the ectoderm originated as a secondary germ layer freed from ancestral feeding functions.}, } @article {pmid25486567, year = {2014}, author = {Iranzo, J and Lobkovsky, AE and Wolf, YI and Koonin, EV}, title = {Virus-host arms race at the joint origin of multicellularity and programmed cell death.}, journal = {Cell cycle (Georgetown, Tex.)}, volume = {13}, number = {19}, pages = {3083-3088}, pmid = {25486567}, issn = {1551-4005}, support = {//Intramural NIH HHS/United States ; }, mesh = {*Apoptosis ; Biological Evolution ; Eukaryota/*physiology ; *Models, Biological ; Viruses/metabolism/*pathogenicity ; }, abstract = {Unicellular eukaryotes and most prokaryotes possess distinct mechanisms of programmed cell death (PCD). How an "altruistic" trait, such as PCD, could evolve in unicellular organisms? To address this question, we developed a mathematical model of the virus-host co-evolution that involves interaction between immunity, PCD and cellular aggregation. Analysis of the parameter space of this model shows that under high virus load and imperfect immunity, joint evolution of cell aggregation and PCD is the optimal evolutionary strategy. Given the abundance of viruses in diverse habitats and the wide spread of PCD in most organisms, these findings imply that multiple instances of the emergence of multicellularity and its essential attribute, PCD, could have been driven, at least in part, by the virus-host arms race.}, } @article {pmid25483255, year = {2014}, author = {Bocksberger, M and Karch, F and Gibert, JM}, title = {In vivo analysis of a fluorescent SUMO fusion in transgenic Drosophila.}, journal = {Fly}, volume = {8}, number = {2}, pages = {108-112}, pmid = {25483255}, issn = {1933-6942}, mesh = {Animals ; Animals, Genetically Modified ; Drosophila ; *Luminescent Proteins ; Polytene Chromosomes/chemistry ; Recombinant Fusion Proteins/analysis ; SUMO-1 Protein/*analysis ; Red Fluorescent Protein ; }, abstract = {Sumoylation, the covalent attachment of SUMO, a 90 amino acid peptide related to ubiquitin, is a major modulator of protein functions. Fluorescent SUMO protein fusions have been used in cell cultures to visualize SUMO in vivo but not in multicellular organisms. We generated a transgenic line of Drosophila expressing an mCherry-SUMO fusion. We analyzed its pattern in vivo in salivary gland nuclei expressing Venus-HP1 to recognize the different chromatin components (Chromocenter, chromosome IV). We compared it to SUMO immunostaining on squashed polytene chromosomes and observed similar patterns. In addition to the previously reported SUMO localizations (chromosome arms and chromocenter), we identify 2 intense binding sites: the fourth chromosome telomere and the DAPI-bright band in the region 81F.}, } @article {pmid25477034, year = {2014}, author = {Yuan, W and Liu, Y and Lok, JB and Stoltzfus, JD and Gasser, RB and Lei, W and Fang, R and Zhao, J and Hu, M}, title = {Exploring features and function of Ss-riok-3, an enigmatic kinase gene from Strongyloides stercoralis.}, journal = {Parasites & vectors}, volume = {7}, number = {}, pages = {561}, pmid = {25477034}, issn = {1756-3305}, support = {AI-105856/AI/NIAID NIH HHS/United States ; R21 AI105856/AI/NIAID NIH HHS/United States ; R01 AI050668/AI/NIAID NIH HHS/United States ; AI-050688/AI/NIAID NIH HHS/United States ; R01 AI082548/AI/NIAID NIH HHS/United States ; AI-082548/AI/NIAID NIH HHS/United States ; R33 AI105856/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animal Structures/enzymology ; Animals ; Cluster Analysis ; DNA, Complementary/genetics/isolation & purification ; Gene Expression Profiling ; Microscopy, Fluorescence ; Molecular Sequence Data ; Open Reading Frames ; Phylogeny ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Protein Serine-Threonine Kinases/*genetics ; Sequence Alignment ; Sequence Homology ; Strongyloides stercoralis/*enzymology/genetics/growth & development ; }, abstract = {BACKGROUND: Right open reading frame protein kinase 3 (RIOK-3) belongs to the atypical kinase family. Unlike the other two members, RIOK-1 and RIOK-2, which are conserved from Archaea to humans, RIOK-3 occurs only in multicellular organisms. Studies on HeLa cells indicate that human RIOK-3 is a component of the 40S small ribosome subunit and supports cancer cell growth and survival. However, almost nothing is known about the function of RIOK-3. We explored the functional role of RIOK-3 encoding gene from Strongyloides stercoralis, a parasitic nematode of humans and dogs.

METHODS: To analyze the gene and promoter structure of Ss-riok-3, RACE-PCR and Genome-walker PCR were performed to isolate the full length cDNA, gDNA and promoter region of Ss-riok-3. RNA-seq was conducted to assess the transcript abundance of Ss-riok-3 in different stages of S. stercoralis. Transgenesis was employed to determine the anatomic expression patterns of Ss-riok-3.

RESULTS: The RIOK-3 protein-encoding gene (designated Ss-riok-3) of S. stercoralis was characterized. The full-length complementary and genomic DNAs of the RIOK-3 encoding gene (riok-3) were isolated from this nematode. The cDNA of Ss-riok-3 is 1,757 bp in length, including a 23 bp 5'-UTR, a 36 bp 3'-UTR and a 1,698 bp coding region encoding a protein of 565 amino acids (aa) containing a RIO kinase domain. RNA sequencing (RNA-seq) analysis revealed that Ss-riok-3 is transcribed in all developmental stages of S. stercoralis assessed, with transcripts being particularly abundant in parasitic females. Gene structure analysis revealed that Ss-riok-3 contains no intron. The putative promoter contains conserved promoter elements, including four TATA, two GATA, one inverse GATA and one inverse CAAT boxes. The promoter of Ss-riok-3 drives GFP expression in the head neuron, intestine and body wall muscle of transgenic S. stercoralis larvae, and the TATA boxes present in the 3'-UTR of the gene immediately upstream of Ss-riok-3 initiate transcription.

CONCLUSIONS: The characterization of the RIOK-3 encoding gene from S. stercoralis provides a sound foundation for investigating in detail its function in the development and reproduction of this important pathogen.}, } @article {pmid25474005, year = {2014}, author = {Arnoult, LA}, title = {[The genetic walk of evolution].}, journal = {Biologie aujourd'hui}, volume = {208}, number = {3}, pages = {237-249}, doi = {10.1051/jbio/2014027}, pmid = {25474005}, issn = {2105-0686}, mesh = {Adaptation, Biological/genetics ; Animals ; Animals, Laboratory ; Directed Molecular Evolution ; Drosophila/genetics ; *Evolution, Molecular ; Humans ; Selection, Genetic ; }, abstract = {Genetic mutations are the main fuel of evolution. In each generation, they produce new variations, which may be sorted out by natural or sexual selection. Mutations are generated by chance; yet which are the mutations actually sorted out by evolution, and why? This review presents some recent advances regarding this question. First, we gather results obtained at molecular and cellular levels, through synthetic experiments and under artificial selection paradigms. Next, we highlight studies at the multi-cellular level, especially studies of repeated evolution, whereby independent lineages acquire similar traits. Recent meta-analysis and quantifications are being presented; together they suggest that evolutionary relevant mutations accumulate around hotspots, spanning different levels of genetic organization. Pioneering work suggests that many causes, corresponding to many biological contexts, may explain the existence of these genetic hotspots. We finally discuss methodological limits, empirical challenges and a few future potential directions for this domain of research dedicated to the genetic path of evolution.}, } @article {pmid25457940, year = {2014}, author = {Reece, SE and Mideo, N}, title = {Malaria parasites prepare for flight.}, journal = {Trends in parasitology}, volume = {30}, number = {12}, pages = {551-553}, doi = {10.1016/j.pt.2014.10.004}, pmid = {25457940}, issn = {1471-5007}, mesh = {*Adaptation, Physiological ; Animals ; Culicidae/parasitology ; Female ; Host-Parasite Interactions/*physiology ; Humans ; Life Cycle Stages/physiology ; Malaria/*parasitology/*transmission ; Male ; Plasmodium/*physiology ; Seasons ; Sex Ratio ; }, abstract = {Life in seasonal environments often means facing extreme environmental fluctuations. Many multicellular organisms have evolved strategies to cope with this lifestyle. Single-celled malaria parasites are no different. An elegant experiment reveals that they respond to the availability of mosquitoes to make the most of seasonal transmission opportunities.}, } @article {pmid25457111, year = {2015}, author = {Van Hautegem, T and Waters, AJ and Goodrich, J and Nowack, MK}, title = {Only in dying, life: programmed cell death during plant development.}, journal = {Trends in plant science}, volume = {20}, number = {2}, pages = {102-113}, doi = {10.1016/j.tplants.2014.10.003}, pmid = {25457111}, issn = {1878-4372}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Apoptosis ; Arabidopsis/growth & development/physiology ; Gene Expression Regulation, Developmental/genetics ; Gene Expression Regulation, Plant/*genetics ; Oryza/growth & development/physiology ; Plant Development/genetics/*physiology ; Zea mays/growth & development/physiology ; }, abstract = {Programmed cell death (PCD) is a fundamental process of life. During the evolution of multicellular organisms, the actively controlled demise of cells has been recruited to fulfil a multitude of functions in development, differentiation, tissue homeostasis, and immune systems. In this review we discuss some of the multiple cases of PCD that occur as integral parts of plant development in a remarkable variety of cell types, tissues, and organs. Although research in the last decade has discovered a number of PCD regulators, mediators, and executers, we are still only beginning to understand the mechanistic complexity that tightly controls preparation, initiation, and execution of PCD as a process that is indispensable for successful vegetative and reproductive development of plants.}, } @article {pmid25445586, year = {2014}, author = {Zhao, BF and Zhao, ZJ}, title = {Molecular cloning and characterization of a tyrosine phosphatase from Monosiga brevicollis.}, journal = {Biochemical and biophysical research communications}, volume = {453}, number = {4}, pages = {761-766}, doi = {10.1016/j.bbrc.2014.10.019}, pmid = {25445586}, issn = {1090-2104}, support = {HL079441/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Choanoflagellata/classification/*enzymology ; Cloning, Molecular/methods ; Enzyme Activation ; Molecular Sequence Data ; Protein Tyrosine Phosphatases/*chemistry/genetics/*metabolism ; Recombinant Proteins/chemistry/metabolism ; Species Specificity ; Substrate Specificity ; }, abstract = {Protein tyrosine phosphorylation is thought to be a unique feature of multicellular animals. Interestingly, the genome of the unicellular protist Monosiga brevicollis reveals a surprisingly high number and diversity of protein tyrosine kinases, protein tyrosine phosphatases (PTPs), and phosphotyrosine-binding domains. Our study focuses on a hypothetical SH2 domain-containing PTP (SHP), which interestingly has a predicted structure that is distinct from SHPs found in animals. In this study, we isolated cDNA of the enzyme and discovered that its actual sequence was different from the predicted sequence as a result of non-consensus RNA splicing. Contrary to the predicted structure with one SH2 domain and a disrupted phosphatase domain, Monosiga brevicollis SHP (MbSHP) contains two SH2 domains and an intact PTP domain, closely resembling SHP enzymes found in animals. We further expressed the full-length and SH2 domain-truncated forms of the enzyme in Escherichiacoli cells and characterized their enzymatic activities. The double-SH2 domain-truncated form of the enzyme effectively dephosphorylated a common PTP substrate with a specific activity among the highest in characterized PTPs, while the full-length and the N-terminal SH2 domain-truncated forms of the enzyme showed much lower activity with altered pH dependency and responses to ionic strength and common PTP inhibitors. This indicates that SH2 domains suppress the catalytic activity. SHP represents a highly conserved ancient PTP, and studying MbSHP should provide a better understanding about the evolution of tyrosine phosphorylation.}, } @article {pmid25438594, year = {2013}, author = {Khokhlov, AN}, title = {[Impairment of regeneration in aging: appropriateness or stochastics?].}, journal = {Ontogenez}, volume = {44}, number = {6}, pages = {434-440}, pmid = {25438594}, issn = {0475-1450}, mesh = {Aging/*metabolism/pathology ; Cell Differentiation ; Cell Transformation, Neoplastic/metabolism/pathology ; Cellular Senescence ; Humans ; *Models, Biological ; *Regeneration ; }, abstract = {There is a viewpoint that suppression of the proliferative capacity of cells and impairment of the regeneration of tissues and organs in aging are a consequence of specially arisen during evolution mechanisms that reduce the risk of malignant transformation and, thus, protect against cancer. At the same time, senescent cells of the body begin to accumulate a variety of macromolecular defects, which, conversely, increase the likelihood of their transformation into cancer cells. Thus, according to the point, the restriction of cell proliferation is a double-edged sword, which, on the one hand, reduces the likelihood of developing cancer at an early age, but on the other hand--limits life span due to the accumulation of "damaged" cells in old age. However, it remains unclear why normal human cells in vitro, with none of the mentioned "anticancer" barriers functioning at the organismal level only, NEVER undergo spontaneous malignant transformation. In addition, it is also unclear how the freshwater hydra which, under certain conditions, has really no postmitotic and senescent cells, escapes both aging and cancer and, at such conditions (excluding the need for sexual reproduction), can live almost indefinitely, having a great regenerative potential (new organism can arise even from a 1/100 of the old one). I believe that the restriction of cell proliferation in an aging multicellular organism is not a consequence of implementing a special program. Apparently, there is no special program of aging. It is only a "byproduct" of the program of development, implementation of which in higher organisms suggests the need for the emergence of cell populations with very low or even zero proliferative activity, which determines the limited capacity of relevant organs and tissues to regenerate. At the same time, it is the presence of highly differentiated cell populations, barely able or completely unable to reproduce (neurons, cardiomyocytes, hepatocytes), that ensures the normal functioning of the higher animals and humans. Even the regeneration of these organs with the help of stem cells could lead to a breach of the necessary interactions in complex systems. Reductionism in experimental-gerontological research ("everything is determined by deleterious changes in single cells") that has become widespread in recent decades, stimulated the emergence of a number of model systems for studying mechanisms of aging in isolated cells (Hayflick phenomenon, the model of "stationary phase aging", the cell-kinetic model for testing geroprotectors and geropromoters, etc.). However, at present it seems that the data obtained in such models cannot be automatically applied to the situation in the whole organism. Apparently, the impairment of regulatory processes, realized at the neurohumoral level, still plays the main role in the mechanisms of aging of multicellular organisms, not just the accumulation of macromolecular defects in individual cells. It is possible that it is the deterioration of such regulation that may be the cause of the observed abnormal INCREASE of the intensity of proliferation of some cell populations in old age, resulting in senile acromegaly and age-related rise of numerous benign tumors. It seems that the quality of the cells themselves does not worsen with age as much as reliability of the organism CONTROL over cells, organs and tissues, which leads to an increase in the probability of death.}, } @article {pmid25435097, year = {2015}, author = {Horn, T and Adel, S and Schumann, R and Sur, S and Kakularam, KR and Polamarasetty, A and Redanna, P and Kuhn, H and Heydeck, D}, title = {Evolutionary aspects of lipoxygenases and genetic diversity of human leukotriene signaling.}, journal = {Progress in lipid research}, volume = {57}, number = {}, pages = {13-39}, pmid = {25435097}, issn = {1873-2194}, mesh = {Animals ; Evolution, Molecular ; *Genetic Variation ; Humans ; Leukotrienes/*metabolism ; Lipoxygenases/*genetics/*metabolism ; Phylogeny ; Receptors, Leukotriene/genetics/metabolism ; *Signal Transduction ; Vertebrates/metabolism ; }, abstract = {Leukotrienes are pro-inflammatory lipid mediators, which are biosynthesized via the lipoxygenase pathway of the arachidonic acid cascade. Lipoxygenases form a family of lipid peroxidizing enzymes and human lipoxygenase isoforms have been implicated in the pathogenesis of inflammatory, hyperproliferative (cancer) and neurodegenerative diseases. Lipoxygenases are not restricted to humans but also occur in a large number of pro- and eucaryotic organisms. Lipoxygenase-like sequences have been identified in the three domains of life (bacteria, archaea, eucarya) but because of lacking functional data the occurrence of catalytically active lipoxygenases in archaea still remains an open question. Although the physiological and/or pathophysiological functions of various lipoxygenase isoforms have been studied throughout the last three decades there is no unifying concept for the biological importance of these enzymes. In this review we are summarizing the current knowledge on the distribution of lipoxygenases in living single and multicellular organisms with particular emphasis to higher vertebrates and will also focus on the genetic diversity of enzymes and receptors involved in human leukotriene signaling.}, } @article {pmid25427284, year = {2014}, author = {Sciumè, G and Santagiuliana, R and Ferrari, M and Decuzzi, P and Schrefler, BA}, title = {A tumor growth model with deformable ECM.}, journal = {Physical biology}, volume = {11}, number = {6}, pages = {065004}, pmid = {25427284}, issn = {1478-3975}, support = {U54 CA143837/CA/NCI NIH HHS/United States ; U54 CA151668/CA/NCI NIH HHS/United States ; U54CA143837/CA/NCI NIH HHS/United States ; U54CA151668/CA/NCI NIH HHS/United States ; }, mesh = {Biomechanical Phenomena ; Computational Biology/*methods ; Extracellular Matrix/metabolism/*pathology ; Humans ; Melanoma/metabolism/*pathology ; *Models, Biological ; Oxygen/metabolism ; Porosity ; Skin Neoplasms/*pathology ; Spheroids, Cellular/metabolism/pathology ; Tumor Cells, Cultured ; }, abstract = {Existing tumor growth models based on fluid analogy for the cells do not generally include the extracellular matrix (ECM), or if present, take it as rigid. The three-fluid model originally proposed by the authors and comprising tumor cells (TC), host cells (HC), interstitial fluid (IF) and an ECM, considered up to now only a rigid ECM in the applications. This limitation is here relaxed and the deformability of the ECM is investigated in detail. The ECM is modeled as a porous solid matrix with Green-elastic and elasto-visco-plastic material behavior within a large strain approach. Jauman and Truesdell objective stress measures are adopted together with the deformation rate tensor. Numerical results are first compared with those of a reference experiment of a multicellular tumor spheroid (MTS) growing in vitro, then three different tumor cases are studied: growth of an MTS in a decellularized ECM, growth of a spheroid in the presence of host cells and growth of a melanoma. The influence of the stiffness of the ECM is evidenced and comparison with the case of a rigid ECM is made. The processes in a deformable ECM are more rapid than in a rigid ECM and the obtained growth pattern differs. The reasons for this are due to the changes in porosity induced by the tumor growth. These changes are inhibited in a rigid ECM. This enhanced computational model emphasizes the importance of properly characterizing the biomechanical behavior of the malignant mass in all its components to correctly predict its temporal and spatial pattern evolution.}, } @article {pmid25400313, year = {2014}, author = {Espinosa, A and Paz-Y-Miño-C, G}, title = {Evidence of Taxa-, Clone-, and Kin-discrimination in Protists: Ecological and Evolutionary Implications.}, journal = {Evolutionary ecology}, volume = {28}, number = {6}, pages = {1019-1029}, pmid = {25400313}, issn = {0269-7653}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, abstract = {Unicellular eukaryotes, or protists, are among the most ancient organisms on Earth. Protists belong to multiple taxonomic groups; they are widely distributed geographically and in all environments. Their ability to discriminate among con- and heterospecifics has been documented during the past decade. Here we discuss exemplar cases of taxa-, clone-, and possible kin-discrimination in five major lineages: Mycetozoa (Dictyostelium, Polysphondylium), Dikarya (Saccharomyces), Ciliophora (Tetrahymena), Apicomplexa (Plasmodium) and Archamoebae (Entamoeba). We summarize the proposed genetic mechanisms involved in discrimination-mediated aggregation (self versus different), including the csA, FLO and trg (formerly lag) genes, and the Proliferation Activation Factors (PAFs), which facilitate clustering in some protistan taxa. We caution about the experimental challenges intrinsic to studying recognition in protists, and highlight the opportunities for exploring the ecology and evolution of complex forms of cell-cell communication, including social behavior, in a polyphyletic, still superficially understood group of organisms. Because unicellular eukaryotes are the evolutionary precursors of multicellular life, we infer that their mechanisms of taxa-, clone-, and possible kin-discrimination gave origin to the complex diversification and sophistication of traits associated with species and kin recognition in plants, fungi, invertebrates and vertebrates.}, } @article {pmid25395297, year = {2014}, author = {Kagan, JC and Barton, GM}, title = {Emerging principles governing signal transduction by pattern-recognition receptors.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {7}, number = {3}, pages = {a016253}, pmid = {25395297}, issn = {1943-0264}, support = {R01 AI093589/AI/NIAID NIH HHS/United States ; P30DK34854/DK/NIDDK NIH HHS/United States ; R56 AI095587/AI/NIAID NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; AI072429/AI/NIAID NIH HHS/United States ; K99 AI072955/AI/NIAID NIH HHS/United States ; AI104914/AI/NIAID NIH HHS/United States ; AI063302/AI/NIAID NIH HHS/United States ; P01 AI063302/AI/NIAID NIH HHS/United States ; AI072955/AI/NIAID NIH HHS/United States ; R56 AI093589/AI/NIAID NIH HHS/United States ; R01 AI095587/AI/NIAID NIH HHS/United States ; AI095587/AI/NIAID NIH HHS/United States ; R01 AI104914/AI/NIAID NIH HHS/United States ; R01 AI072429/AI/NIAID NIH HHS/United States ; AI093589/AI/NIAID NIH HHS/United States ; R00 AI072955/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; Immunity, Innate/*physiology ; *Models, Immunological ; Nucleic Acids/metabolism ; Plakins/*metabolism ; Receptors, Cytoplasmic and Nuclear/*metabolism ; Signal Transduction/*immunology ; Toll-Like Receptors/*metabolism ; }, abstract = {The problem of recognizing and disposing of non-self-organisms, whether for nutrients or defense, predates the evolution of multicellularity. Accordingly, the function of the innate immune system is often intimately associated with fundamental aspects of cell biology. Here, we review our current understanding of the links between cell biology and pattern-recognition receptors of the innate immune system. We highlight the importance of receptor localization for the detection of microbes and for the initiation of antimicrobial signaling pathways. We discuss examples that illustrate how pattern-recognition receptors influence, and are influenced by, the general membrane trafficking machinery of mammalian cells. In the future, cell biological analysis likely will rival pure genetic analysis as a tool to uncover fundamental principles that govern host-microbe interactions.}, } @article {pmid25375671, year = {2014}, author = {Buitrago-Flórez, FJ and Restrepo, S and Riaño-Pachón, DM}, title = {Identification of transcription factor genes and their correlation with the high diversity of stramenopiles.}, journal = {PloS one}, volume = {9}, number = {11}, pages = {e111841}, pmid = {25375671}, issn = {1932-6203}, mesh = {Animals ; Biodiversity ; Evolution, Molecular ; Gene Expression Regulation ; Genome ; Multigene Family ; Phylogeny ; Stramenopiles/*classification/*genetics ; Transcription Factors/*genetics ; }, abstract = {The biological diversity among Stramenopiles is striking; they range from large multicellular seaweeds to tiny unicellular species, they embrace many ecologically important autothrophic (e.g., diatoms, brown algae), and heterotrophic (e.g., oomycetes) groups. Transcription factors (TFs) and other transcription regulators (TRs) regulate spatial and temporal gene expression. A plethora of transcriptional regulatory proteins have been identified and classified into families on the basis of sequence similarity. The purpose of this work is to identify the TF and TR complement in diverse species belonging to Stramenopiles in order to understand how these regulators may contribute to their observed diversity. We identified and classified 63 TF and TR families in 11 species of Stramenopiles. In some species we found gene families with high relative importance. Taking into account the 63 TF and TR families identified, 28 TF and TR families were established to be positively correlated with specific traits like number of predicted proteins, number of flagella and number of cell types during the life cycle. Additionally, we found gains and losses in TF and TR families specific to some species and clades, as well as, two families with high abundance specific to the autotrophic species and three families with high abundance specific to the heterotropic species. For the first time, there is a systematic search of TF and TR families in Stramenopiles. The attempts to uncover relationships between these families and the complexity of this group may be of great impact, considering that there are several important pathogens of plants and animals, as well as, important species involved in carbon cycling. Specific TF and TR families identified in this work appear to be correlated with particular traits in the Stramenopiles group and may be correlated with the high complexity and diversity in Stramenopiles.}, } @article {pmid25371433, year = {2015}, author = {Frank, MH and Scanlon, MJ}, title = {Transcriptomic evidence for the evolution of shoot meristem function in sporophyte-dominant land plants through concerted selection of ancestral gametophytic and sporophytic genetic programs.}, journal = {Molecular biology and evolution}, volume = {32}, number = {2}, pages = {355-367}, doi = {10.1093/molbev/msu303}, pmid = {25371433}, issn = {1537-1719}, mesh = {Biological Evolution ; Bryopsida/classification/metabolism ; Evolution, Molecular ; Gene Expression Regulation, Plant ; Germ Cells, Plant/classification/*metabolism ; Meristem/genetics/*metabolism ; Plant Proteins/genetics ; }, abstract = {Alternation of generations, in which the haploid and diploid stages of the life cycle are each represented by multicellular forms that differ in their morphology, is a defining feature of the land plants (embryophytes). Anciently derived lineages of embryophytes grow predominately in the haploid gametophytic generation from apical cells that give rise to the photosynthetic body of the plant. More recently evolved plant lineages have multicellular shoot apical meristems (SAMs), and photosynthetic shoot development is restricted to the sporophyte generation. The molecular genetic basis for this evolutionary shift from gametophyte-dominant to sporophyte-dominant life cycles remains a major question in the study of land plant evolution. We used laser microdissection and next generation RNA sequencing to address whether angiosperm meristem patterning genes expressed in the sporophytic SAM of Zea mays are expressed in the gametophytic apical cells, or in the determinate sporophytes, of the model bryophytes Marchantia polymorpha and Physcomitrella patens. A wealth of upregulated genes involved in stem cell maintenance and organogenesis are identified in the maize SAM and in both the gametophytic apical cell and sporophyte of moss, but not in Marchantia. Significantly, meiosis-specific genetic programs are expressed in bryophyte sporophytes, long before the onset of sporogenesis. Our data suggest that this upregulated accumulation of meiotic gene transcripts suppresses indeterminate cell fate in the Physcomitrella sporophyte, and overrides the observed accumulation of meristem patterning genes. A model for the evolution of indeterminate growth in the sporophytic generation through the concerted selection of ancestral meristem gene programs from gametophyte-dominant lineages is proposed.}, } @article {pmid25369637, year = {2014}, author = {de Mendoza, A and Ruiz-Trillo, I}, title = {Forward genetics for back-in-time questions.}, journal = {eLife}, volume = {3}, number = {}, pages = {}, pmid = {25369637}, issn = {2050-084X}, mesh = {Animals ; Choanoflagellata/*genetics/growth & development ; *Genetics ; Lectins, C-Type/metabolism ; Life Cycle Stages ; Mutation/genetics ; }, abstract = {A genetic screen has revealed one of the molecules that allow choanoflagellates, the closest unicellular relative of animals, to form colonies, which could help researchers to answer questions about the earliest days of animal evolution.}, } @article {pmid25354656, year = {2015}, author = {Beech, RN and Neveu, C}, title = {The evolution of pentameric ligand-gated ion-channels and the changing family of anthelmintic drug targets.}, journal = {Parasitology}, volume = {142}, number = {2}, pages = {303-317}, doi = {10.1017/S003118201400170X}, pmid = {25354656}, issn = {1469-8161}, mesh = {Animals ; Anthelmintics/*pharmacology ; Helminths/*drug effects/genetics/*metabolism ; Ion Channel Gating/*physiology ; Ion Channels/genetics/*metabolism ; Phylogeny ; }, abstract = {SUMMARY Pentameric ligand-gated ion-channels rapidly transduce synaptic neurotransmitter signals to an electrical response in post-synaptic neuronal or muscle cells and control the neuromusculature of a majority of multicellular animals. A wide range of pharmaceuticals target these receptors including ethanol, nicotine, anti-depressants and other mood regulating drugs, compounds that control pain and mobility and are targeted by a majority of anthelmintic drugs used to control parasitic infection of humans and livestock. Major advances have been made in recent years to our understanding of the structure, function, activity and the profile of compounds that can activate specific receptors. It is becoming clear that these anthelmintic drug targets are not fixed, but differ in significant details from one nematode species to another. Here we review what is known about the evolution of the pentameric ligand-gated ion-channels, paying particular attention to the nematodes, how we can infer the origins of such receptors and understand the factors that determine how they change both over time and from one species to another. Using this knowledge provides a biological framework in which to understand these important drug targets and avenues to identify new receptors and aid the search for new anthelmintic drugs.}, } @article {pmid25342789, year = {2014}, author = {Libby, E and Ratcliff, WC}, title = {Evolution. Ratcheting the evolution of multicellularity.}, journal = {Science (New York, N.Y.)}, volume = {346}, number = {6208}, pages = {426-427}, doi = {10.1126/science.1262053}, pmid = {25342789}, issn = {1095-9203}, mesh = {Animals ; Apoptosis ; *Biological Evolution ; Cells/*cytology ; Life Cycle Stages ; }, } @article {pmid25329823, year = {2014}, author = {Lehr, NA and Wang, Z and Li, N and Hewitt, DA and López-Giráldez, F and Trail, F and Townsend, JP}, title = {Gene expression differences among three Neurospora species reveal genes required for sexual reproduction in Neurospora crassa.}, journal = {PloS one}, volume = {9}, number = {10}, pages = {e110398}, pmid = {25329823}, issn = {1932-6203}, support = {UL1 TR000142/TR/NCATS NIH HHS/United States ; }, mesh = {Cinnamates/pharmacology ; Drug Resistance, Fungal/genetics ; Fruiting Bodies, Fungal/genetics ; Fungal Proteins/biosynthesis/genetics/metabolism ; *Gene Expression Regulation, Fungal/drug effects ; Gene Knockout Techniques ; Hygromycin B/analogs & derivatives/pharmacology ; Mutation ; Neurospora crassa/drug effects/*genetics/metabolism/*physiology ; Phenotype ; Protein Transport ; Reproduction/drug effects/genetics ; Species Specificity ; Time Factors ; Transcription, Genetic/drug effects ; }, abstract = {Many fungi form complex three-dimensional fruiting bodies, within which the meiotic machinery for sexual spore production has been considered to be largely conserved over evolutionary time. Indeed, much of what we know about meiosis in plant and animal taxa has been deeply informed by studies of meiosis in Saccharomyces and Neurospora. Nevertheless, the genetic basis of fruiting body development and its regulation in relation to meiosis in fungi is barely known, even within the best studied multicellular fungal model Neurospora crassa. We characterized morphological development and genome-wide transcriptomics in the closely related species Neurospora crassa, Neurospora tetrasperma, and Neurospora discreta, across eight stages of sexual development. Despite diverse life histories within the genus, all three species produce vase-shaped perithecia. Transcriptome sequencing provided gene expression levels of orthologous genes among all three species. Expression of key meiosis genes and sporulation genes corresponded to known phenotypic and developmental differences among these Neurospora species during sexual development. We assembled a list of genes putatively relevant to the recent evolution of fruiting body development by sorting genes whose relative expression across developmental stages increased more in N. crassa relative to the other species. Then, in N. crassa, we characterized the phenotypes of fruiting bodies arising from crosses of homozygous knockout strains of the top genes. Eight N. crassa genes were found to be critical for the successful formation of perithecia. The absence of these genes in these crosses resulted in either no perithecium formation or in arrested development at an early stage. Our results provide insight into the genetic basis of Neurospora sexual reproduction, which is also of great importance with regard to other multicellular ascomycetes, including perithecium-forming pathogens, such as Claviceps purpurea, Ophiostoma ulmi, and Glomerella graminicola.}, } @article {pmid25328099, year = {2015}, author = {Dzutsev, A and Goldszmid, RS and Viaud, S and Zitvogel, L and Trinchieri, G}, title = {The role of the microbiota in inflammation, carcinogenesis, and cancer therapy.}, journal = {European journal of immunology}, volume = {45}, number = {1}, pages = {17-31}, doi = {10.1002/eji.201444972}, pmid = {25328099}, issn = {1521-4141}, support = {HHSN26120080001E//PHS HHS/United States ; //Intramural NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Animals ; Antineoplastic Agents/therapeutic use ; Autoimmune Diseases/drug therapy/*microbiology/pathology ; Biological Evolution ; Carcinogenesis/*immunology/pathology ; Humans ; Immunity, Innate ; Immunomodulation ; Inflammation/drug therapy/immunology/microbiology/pathology ; Metagenome/immunology ; Mice ; Microbiota/*immunology ; Neoplasms/drug therapy/immunology/*microbiology/pathology ; Symbiosis/immunology ; Tumor Escape ; }, abstract = {Commensal microorganisms colonize barrier surfaces of all multicellular organisms, including those of humans. For more than 500 million years, commensal microorganisms and their hosts have coevolved and adapted to each other. As a result, the commensal microbiota affects many immune and nonimmune functions of their hosts, and de facto the two together comprise one metaorganism. The commensal microbiota communicates with the host via biologically active molecules. Recently, it has been reported that microbial imbalance may play a critical role in the development of multiple diseases, such as cancer, autoimmune conditions, and increased susceptibility to infection. In this review, we focus on the role of the commensal microbiota in the development, progression, and immune evasion of cancer, as well as some modulatory effects on the treatment of cancer. In particular, we discuss the mechanisms of microbiota-mediated regulation of innate and adaptive immune responses to tumors, and the consequences on cancer progression and whether tumors subsequently become resistant or susceptible to different anticancer therapeutic regiments.}, } @article {pmid25324214, year = {2014}, author = {Umen, JG}, title = {Green algae and the origins of multicellularity in the plant kingdom.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {6}, number = {11}, pages = {a016170}, pmid = {25324214}, issn = {1943-0264}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; R01 GM092744/GM/NIGMS NIH HHS/United States ; R01GM092744/GM/NIGMS NIH HHS/United States ; R01GM078376/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cell Differentiation ; Chlorophyta/*cytology/genetics/growth & development ; Phylogeny ; Plant Cells/physiology ; Plants/anatomy & histology/genetics ; Reproduction ; }, abstract = {The green lineage of chlorophyte algae and streptophytes form a large and diverse clade with multiple independent transitions to produce multicellular and/or macroscopically complex organization. In this review, I focus on two of the best-studied multicellular groups of green algae: charophytes and volvocines. Charophyte algae are the closest relatives of land plants and encompass the transition from unicellularity to simple multicellularity. Many of the innovations present in land plants have their roots in the cell and developmental biology of charophyte algae. Volvocine algae evolved an independent route to multicellularity that is captured by a graded series of increasing cell-type specialization and developmental complexity. The study of volvocine algae has provided unprecedented insights into the innovations required to achieve multicellularity.}, } @article {pmid25315413, year = {2014}, author = {Laporte, D and Huot, JL and Bader, G and Enkler, L and Senger, B and Becker, HD}, title = {Exploring the evolutionary diversity and assembly modes of multi-aminoacyl-tRNA synthetase complexes: lessons from unicellular organisms.}, journal = {FEBS letters}, volume = {588}, number = {23}, pages = {4268-4278}, doi = {10.1016/j.febslet.2014.10.007}, pmid = {25315413}, issn = {1873-3468}, mesh = {Amino Acyl-tRNA Synthetases/*chemistry/*metabolism ; Animals ; *Evolution, Molecular ; Humans ; *Protein Structure, Quaternary ; Protein Structure, Tertiary ; Species Specificity ; }, abstract = {Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous and ancient enzymes, mostly known for their essential role in generating aminoacylated tRNAs. During the last two decades, many aaRSs have been found to perform additional and equally crucial tasks outside translation. In metazoans, aaRSs have been shown to assemble, together with non-enzymatic assembly proteins called aaRSs-interacting multifunctional proteins (AIMPs), into so-called multi-synthetase complexes (MSCs). Metazoan MSCs are dynamic particles able to specifically release some of their constituents in response to a given stimulus. Upon their release from MSCs, aaRSs can reach other subcellular compartments, where they often participate to cellular processes that do not exploit their primary function of synthesizing aminoacyl-tRNAs. The dynamics of MSCs and the expansion of the aaRSs functional repertoire are features that are so far thought to be restricted to higher and multicellular eukaryotes. However, much can be learnt about how MSCs are assembled and function from apparently 'simple' organisms. Here we provide an overview on the diversity of these MSCs, their composition, mode of assembly and the functions that their constituents, namely aaRSs and AIMPs, exert in unicellular organisms.}, } @article {pmid25309530, year = {2014}, author = {Garcia, JR and Gerardo, NM}, title = {The symbiont side of symbiosis: do microbes really benefit?.}, journal = {Frontiers in microbiology}, volume = {5}, number = {}, pages = {510}, pmid = {25309530}, issn = {1664-302X}, abstract = {Microbial associations are integral to all eukaryotes. Mutualism, the interaction of two species for the benefit of both, is an important aspect of microbial associations, with evidence that multicellular organisms in particular benefit from microbes. However, the microbe's perspective has largely been ignored, and it is unknown whether most microbial symbionts benefit from their associations with hosts. It has been presumed that microbial symbionts receive host-derived nutrients or a competition-free environment with reduced predation, but there have been few empirical tests, or even critical assessments, of these assumptions. We evaluate these hypotheses based on available evidence, which indicate reduced competition and predation are not universal benefits for symbionts. Some symbionts do receive nutrients from their host, but this has not always been linked to a corresponding increase in symbiont fitness. We recommend experiments to test symbiont fitness using current experimental systems of symbiosis and detail considerations for other systems. Incorporating symbiont fitness into symbiosis research will provide insight into the evolution of mutualistic interactions and cooperation in general.}, } @article {pmid25307499, year = {2015}, author = {Dunker, AK and Bondos, SE and Huang, F and Oldfield, CJ}, title = {Intrinsically disordered proteins and multicellular organisms.}, journal = {Seminars in cell & developmental biology}, volume = {37}, number = {}, pages = {44-55}, doi = {10.1016/j.semcdb.2014.09.025}, pmid = {25307499}, issn = {1096-3634}, mesh = {*Biological Evolution ; Eukaryotic Cells/chemistry/cytology/*metabolism ; Intrinsically Disordered Proteins/*chemistry/genetics/*metabolism ; Prokaryotic Cells/chemistry/cytology/*metabolism ; Protein Folding ; Protein Processing, Post-Translational ; }, abstract = {Intrinsically disordered proteins (IDPs) and IDP regions lack stable tertiary structure yet carry out numerous biological functions, especially those associated with signaling, transcription regulation, DNA condensation, cell division, and cellular differentiation. Both post-translational modifications (PTMs) and alternative splicing (AS) expand the functional repertoire of IDPs. Here we propose that an "IDP-based developmental toolkit," which is comprised of IDP regions, PTMs, especially multiple PTMs, within these IDP regions, and AS events within segments of pre-mRNA that code for these same IDP regions, allows functional diversification and environmental responsiveness for molecules that direct the development of complex metazoans.}, } @article {pmid25305337, year = {2014}, author = {Czárán, T and Hoekstra, RF and Aanen, DK}, title = {Selection against somatic parasitism can maintain allorecognition in fungi.}, journal = {Fungal genetics and biology : FG & B}, volume = {73}, number = {}, pages = {128-137}, doi = {10.1016/j.fgb.2014.09.010}, pmid = {25305337}, issn = {1096-0937}, mesh = {Animals ; Ascomycota ; *Biological Evolution ; Models, Biological ; Parasites/*genetics/metabolism ; Symbiosis/*genetics ; }, abstract = {Fusion between multicellular individuals is possible in many organisms with modular, indeterminate growth, such as marine invertebrates and fungi. Although fusion may provide various benefits, fusion usually is restricted to close relatives by allorecognition, also called heterokaryon or somatic incompatibility in fungi. A possible selective explanation for allorecognition is protection against somatic parasites. Such mutants contribute less to colony functions but more to reproduction. However, previous models testing this idea have failed to explain the high diversity of allorecognition alleles in nature. These models did not, however, consider the possible role of spatial structure. We model the joint evolution of allorecognition and somatic parasitism in a multicellular organism resembling an asexual ascomycete fungus in a spatially explicit simulation. In a 1000-by-1000 grid, neighbouring individuals can fuse, but only if they have the same allotype. Fusion with a parasitic individual decreases the total reproductive output of the fused individuals, but the parasite compensates for this individual-level fitness reduction by a disproportional share of the offspring. Allorecognition prevents the invasion of somatic parasites, and vice versa, mutation towards somatic parasitism provides the selective conditions for extensive allorecognition diversity. On the one hand, if allorecognition diversity did not build up fast enough, somatic parasites went to fixation; conversely, once parasites had gone to fixation no allorecognition diversity built up. On the other hand, the mere threat of parasitism could select for high allorecognition diversity, preventing invasion of somatic parasites. Moderate population viscosity combined with weak global dispersal was optimal for the joint evolution of allorecognition and protection against parasitism. Our results are consistent with the widespread occurrence of allorecognition in fungi and the low degree of somatic parasitism. We discuss the implications of our results for allorecognition in other organism groups.}, } @article {pmid25299705, year = {2014}, author = {Rodríguez-Rojas, A and Makarova, O and Rolff, J}, title = {Antimicrobials, stress and mutagenesis.}, journal = {PLoS pathogens}, volume = {10}, number = {10}, pages = {e1004445}, pmid = {25299705}, issn = {1553-7374}, mesh = {Animals ; Anti-Infective Agents/immunology/*pharmacology ; Antimicrobial Cationic Peptides/immunology/*pharmacology ; Bacteria/immunology ; Immunity, Innate/immunology ; Mutagenesis/*immunology ; Vertebrates/*immunology ; }, abstract = {Cationic antimicrobial peptides are ancient and ubiquitous immune effectors that multicellular organisms use to kill and police microbes whereas antibiotics are mostly employed by microorganisms. As antimicrobial peptides (AMPs) mostly target the cell wall, a microbial 'Achilles heel', it has been proposed that bacterial resistance evolution is very unlikely and hence AMPs are ancient 'weapons' of multicellular organisms. Here we provide a new hypothesis to explain the widespread distribution of AMPs amongst multicellular organism. Studying five antimicrobial peptides from vertebrates and insects, we show, using a classic Luria-Delbrück fluctuation assay, that cationic antimicrobial peptides (AMPs) do not increase bacterial mutation rates. Moreover, using rtPCR and disc diffusion assays we find that AMPs do not elicit SOS or rpoS bacterial stress pathways. This is in contrast to the main classes of antibiotics that elevate mutagenesis via eliciting the SOS and rpoS pathways. The notion of the 'Achilles heel' has been challenged by experimental selection for AMP-resistance, but our findings offer a new perspective on the evolutionary success of AMPs. Employing AMPs seems advantageous for multicellular organisms, as it does not fuel the adaptation of bacteria to their immune defenses. This has important consequences for our understanding of host-microbe interactions, the evolution of innate immune defenses, and also sheds new light on antimicrobial resistance evolution and the use of AMPs as drugs.}, } @article {pmid25299189, year = {2014}, author = {Levin, TC and Greaney, AJ and Wetzel, L and King, N}, title = {The Rosetteless gene controls development in the choanoflagellate S. rosetta.}, journal = {eLife}, volume = {3}, number = {}, pages = {}, pmid = {25299189}, issn = {2050-084X}, support = {R01 GM089977/GM/NIGMS NIH HHS/United States ; T32 GM007232/GM/NIGMS NIH HHS/United States ; GM089977/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Choanoflagellata/*genetics/*growth & development ; Gene Expression Regulation ; *Genes, Protozoan ; Lectins, C-Type/metabolism ; Models, Biological ; Molecular Sequence Data ; Mutation/genetics ; Phenotype ; Protozoan Proteins/chemistry/genetics/metabolism ; }, abstract = {The origin of animal multicellularity may be reconstructed by comparing animals with one of their closest living relatives, the choanoflagellate Salpingoeca rosetta. Just as animals develop from a single cell-the zygote-multicellular rosettes of S. rosetta develop from a founding cell. To investigate rosette development, we established forward genetics in S. rosetta. We find that the rosette defect of one mutant, named Rosetteless, maps to a predicted C-type lectin, a class of signaling and adhesion genes required for the development and innate immunity in animals. Rosetteless protein is essential for rosette development and forms an extracellular layer that coats and connects the basal poles of each cell in rosettes. This study provides the first link between genotype and phenotype in choanoflagellates and raises the possibility that a protein with C-type lectin-like domains regulated development in the last common ancestor of choanoflagellates and animals.}, } @article {pmid25295041, year = {2014}, author = {Buchmann, K}, title = {Evolution of Innate Immunity: Clues from Invertebrates via Fish to Mammals.}, journal = {Frontiers in immunology}, volume = {5}, number = {}, pages = {459}, pmid = {25295041}, issn = {1664-3224}, abstract = {Host responses against invading pathogens are basic physiological reactions of all living organisms. Since the appearance of the first eukaryotic cells, a series of defense mechanisms have evolved in order to secure cellular integrity, homeostasis, and survival of the host. Invertebrates, ranging from protozoans to metazoans, possess cellular receptors, which bind to foreign elements and differentiate self from non-self. This ability is in multicellular animals associated with presence of phagocytes, bearing different names (amebocytes, hemocytes, coelomocytes) in various groups including animal sponges, worms, cnidarians, mollusks, crustaceans, chelicerates, insects, and echinoderms (sea stars and urchins). Basically, these cells have a macrophage-like appearance and function and the repair and/or fight functions associated with these cells are prominent even at the earliest evolutionary stage. The cells possess pathogen recognition receptors recognizing pathogen-associated molecular patterns, which are well-conserved molecular structures expressed by various pathogens (virus, bacteria, fungi, protozoans, helminths). Scavenger receptors, Toll-like receptors, and Nod-like receptors (NLRs) are prominent representatives within this group of host receptors. Following receptor-ligand binding, signal transduction initiates a complex cascade of cellular reactions, which lead to production of one or more of a wide array of effector molecules. Cytokines take part in this orchestration of responses even in lower invertebrates, which eventually may result in elimination or inactivation of the intruder. Important innate effector molecules are oxygen and nitrogen species, antimicrobial peptides, lectins, fibrinogen-related peptides, leucine rich repeats (LRRs), pentraxins, and complement-related proteins. Echinoderms represent the most developed invertebrates and the bridge leading to the primitive chordates, cephalochordates, and urochordates, in which many autologous genes and functions from their ancestors can be found. They exhibit numerous variants of innate recognition and effector molecules, which allow fast and innate responses toward diverse pathogens despite lack of adaptive responses. The primitive vertebrates (agnathans also termed jawless fish) were the first to supplement innate responses with adaptive elements. Thus hagfish and lampreys use LRRs as variable lymphocyte receptors, whereas higher vertebrates [cartilaginous and bony fishes (jawed fish), amphibians, reptiles, birds, and mammals] developed the major histocompatibility complex, T-cell receptors, and B-cell receptors (immunoglobulins) as additional adaptive weaponry to assist innate responses. Extensive cytokine networks are recognized in fish, but related signal molecules can be traced among invertebrates. The high specificity, antibody maturation, immunological memory, and secondary responses of adaptive immunity were so successful that it allowed higher vertebrates to reduce the number of variants of the innate molecules originating from both invertebrates and lower vertebrates. Nonetheless, vertebrates combine the two arms in an intricate inter-dependent network. Organisms at all developmental stages have, in order to survive, applied available genes and functions of which some may have been lost or may have changed function through evolution. The molecular mechanisms involved in evolution of immune molecules, might apart from simple base substitutions be as diverse as gene duplication, deletions, alternative splicing, gene recombination, domain shuffling, retrotransposition, and gene conversion. Further, variable regulation of gene expression may have played a role.}, } @article {pmid25283544, year = {2015}, author = {Jiang, J and Wu, S and Wang, J and Feng, Y}, title = {AHL-type quorum sensing and its regulation on symplasmata formation in Pantoea agglomerans YS19.}, journal = {Journal of basic microbiology}, volume = {55}, number = {5}, pages = {607-616}, doi = {10.1002/jobm.201400472}, pmid = {25283544}, issn = {1521-4028}, mesh = {Acyl-Butyrolactones/chemistry/*metabolism ; Bacterial Adhesion/*drug effects ; Cloning, Molecular ; Cluster Analysis ; Conserved Sequence ; Endophytes/genetics/growth & development/metabolism/*physiology ; *Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Molecular Sequence Data ; Oryza/microbiology ; Pantoea/genetics/growth & development/metabolism/*physiology ; Phylogeny ; *Quorum Sensing ; Sequence Analysis, DNA ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Pantoea agglomerans YS19, an endophytic diazotrophic bacterium isolated from rice, is characterized by the formation of multicellular aggregate structure called symplasmata, which not only bestow the strong stress-resistance of the bacterium, but also contribute to the specific adaptation in the endophyte-host association. Acyl-homoserine lactones (AHLs), as the important signal molecule in the quorum sensing (QS) system of gram-negative bacteria, were demonstrated to regulate motility, cell-aggregation, and other bacterial behaviors. Here, the production of AHL by P. agglomerans YS19 and its regulation on the symplasmata formation were studied. It was revealed that the production of AHL by YS19 was initiated at the exponential growth stage and from then on, reached the peak values at the stationary growth stage in LB medium. The AHL was identified as N-3-oxooctanoyl-L-homoserine lactone (OOHL) by MALDI-TOF-MS analysis. The AHL synthesis gene pagI and receptor gene pagR in YS19 were cloned and phylogenetic analysis showed that they were high conservative among strains in species of P. agglomerans. It was revealed that AHL promoted the bacterial growth and symplasmata formation of YS19. Meanwhile, the colonization ability and growth-promoting effect of YS19 on the host plant were also enhanced by AHL. These results strongly suggest the pleiotropic effects of the AHL-type QS system in endophytic life of the strain.}, } @article {pmid25280764, year = {2014}, author = {Alegado, RA and King, N}, title = {Bacterial influences on animal origins.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {6}, number = {11}, pages = {a016162}, pmid = {25280764}, issn = {1943-0264}, support = {F32 GM086054/GM/NIGMS NIH HHS/United States ; R01 GM099533/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; 5F32GM086054/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*genetics/metabolism ; *Biological Evolution ; Cell Adhesion ; Choanoflagellata/genetics/*physiology ; Eukaryota/genetics/physiology ; Phagocytosis ; Phylogeny ; Signal Transduction ; }, abstract = {Animals evolved in seas teeming with bacteria, yet the influences of bacteria on animal origins are poorly understood. Comparisons among modern animals and their closest living relatives, the choanoflagellates, suggest that the first animals used flagellated collar cells to capture bacterial prey. The cell biology of prey capture, such as cell adhesion between predator and prey, involves mechanisms that may have been co-opted to mediate intercellular interactions during the evolution of animal multicellularity. Moreover, a history of bacterivory may have influenced the evolution of animal genomes by driving the evolution of genetic pathways for immunity and facilitating lateral gene transfer. Understanding the interactions between bacteria and the progenitors of animals may help to explain the myriad ways in which bacteria shape the biology of modern animals, including ourselves.}, } @article {pmid25252979, year = {2014}, author = {Chen, L and Xiao, S and Pang, K and Zhou, C and Yuan, X}, title = {Cell differentiation and germ-soma separation in Ediacaran animal embryo-like fossils.}, journal = {Nature}, volume = {516}, number = {7530}, pages = {238-241}, pmid = {25252979}, issn = {1476-4687}, mesh = {Animals ; Apoptosis ; Blastula/cytology ; *Cell Differentiation ; China ; Chlorophyta/cytology ; Embryo, Nonmammalian/*cytology ; Eukaryotic Cells/classification/cytology ; *Fossils ; *Phylogeny ; }, abstract = {Phosphorites of the Ediacaran Doushantuo Formation (∼600 million years old) yield spheroidal microfossils with a palintomic cell cleavage pattern. These fossils have been variously interpreted as sulphur-oxidizing bacteria, unicellular protists, mesomycetozoean-like holozoans, green algae akin to Volvox, and blastula embryos of early metazoans or bilaterian animals. However, their complete life cycle is unknown and it is uncertain whether they had a cellularly differentiated ontogenetic stage, making it difficult to test their various phylogenetic interpretations. Here we describe new spheroidal fossils from black phosphorites of the Doushantuo Formation that have been overlooked in previous studies. These fossils represent later developmental stages of previously published blastula-like fossils, and they show evidence for cell differentiation, germ-soma separation, and programmed cell death. Their complex multicellularity is inconsistent with a phylogenetic affinity with bacteria, unicellular protists, or mesomycetozoean-like holozoans. Available evidence also indicates that the Doushantuo fossils are unlikely crown-group animals or volvocine green algae. We conclude that an affinity with cellularly differentiated multicellular eukaryotes, including stem-group animals or algae, is likely but more data are needed to constrain further the exact phylogenetic affinity of the Doushantuo fossils.}, } @article {pmid25249249, year = {2015}, author = {Kang, L and Michalak, P}, title = {The evolution of cancer-related genes in hominoids.}, journal = {Journal of molecular evolution}, volume = {80}, number = {1}, pages = {37-41}, pmid = {25249249}, issn = {1432-1432}, mesh = {Animals ; Base Sequence ; *Evolution, Molecular ; *Genes, Tumor Suppressor ; Hominidae/*genetics ; Humans ; *Oncogenes ; Sequence Homology, Nucleic Acid ; }, abstract = {The evolution of cancer suppression is essential for the maintenance of multicellularity. The lack of correlation between body size and cancer risk across species, known as Peto's paradox, suggests that genetic variation in cancer resistance is sufficient to compensate for increases of cell numbers in bigger animals. To assess evolutionary dynamics of cancer-related genes, we analyzed Ka, Ks,and Ka/Ks values in 120 oncogenes and tumor suppressor genes (TSG) among seven hominoid species, including two extinct species, Neanderthal and Denisovan. Ka/Ks of tumor suppressor genes tended to be higher relative to that of oncogenes, consistent with relaxed purifying selection acting on the former. Ka/Ks values were positively correlated with TSG scores, but negatively correlated with oncogene scores, suggesting opposing selection pressures operating on the two groups of cancer-related genes. Additionally, we found 108 species-divergent substitutions that were prevalent germline genotypes in some species but in humans appeared only as somatic cancerous mutations. Better understanding the resistance to cancer may lead to new methods of cancer prevention in humans.}, } @article {pmid25248478, year = {2014}, author = {Delidakis, C and Monastirioti, M and Magadi, SS}, title = {E(spl): genetic, developmental, and evolutionary aspects of a group of invertebrate Hes proteins with close ties to Notch signaling.}, journal = {Current topics in developmental biology}, volume = {110}, number = {}, pages = {217-262}, doi = {10.1016/B978-0-12-405943-6.00006-3}, pmid = {25248478}, issn = {1557-8933}, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Central Nervous System/embryology ; Drosophila/embryology/genetics/metabolism ; Drosophila Proteins/genetics/*metabolism ; Embryo, Nonmammalian ; Evolution, Molecular ; *Gene Expression Regulation ; Invertebrates/genetics/*metabolism ; Neurons/cytology/physiology ; Receptors, Notch/*metabolism ; Repressor Proteins/genetics/*metabolism ; }, abstract = {Enhancer-of-split (E(spl)) was genetically characterized in Drosophila as a dominant mutation that interacts with an allele of Notch, the receptor in a multipurpose signaling pathway throughout development. Although dominant mutations are often not informative of the normal gene function, E(spl) turned out to encode a family of seven paralogous basic helix-loop-helix proteins of utmost importance in the implementation of the Notch signal in the receiving cell. They are transcriptionally induced by Notch in almost every instance where the signal is deployed, and they participate in numerous feedback circuits, where they interface with a panoply of additional more tissue-specific Notch targets to ensure the proper signaling outcome. Besides the bHLH domain, E(spl) contain a characteristic Orange domain and are classified in the Hes (hairy and enhancer-of-split) branch of the bHLH-Orange proteins. They act as DNA-binding repressors in close collaboration with the corepressor Groucho. In this review, we will focus on the regulation of E(spl) expression and on the function of E(spl) proteins. In the latter section, we will present some of the best-studied developmental events where E(spl) function has been analysed as well as the molecular mechanism of E(spl) activity that has transpired. Finally, we will review the evolution of this protein family, which, albeit of relatively recent origin, present only in insects and crustaceans, has undergone extensive diversification, including gene loss and duplication. Importantly, many of the characteristics of E(spl) proteins are more deeply rooted in the very ancient larger bHLH-O family, which seems to have forged a connection with the Notch pathway from the very beginning of multicellular animal life.}, } @article {pmid25246576, year = {2014}, author = {Daum, G and Medzihradszky, A and Suzaki, T and Lohmann, JU}, title = {A mechanistic framework for noncell autonomous stem cell induction in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {40}, pages = {14619-14624}, pmid = {25246576}, issn = {1091-6490}, mesh = {Arabidopsis/cytology/*genetics/metabolism ; Arabidopsis Proteins/chemistry/*genetics/metabolism ; Cell Communication/genetics ; Fluorescence Resonance Energy Transfer ; Gene Expression Regulation, Plant ; Homeodomain Proteins/chemistry/*genetics/metabolism ; In Situ Hybridization ; Luminescent Proteins/genetics/metabolism ; Meristem/cytology/*metabolism ; Microscopy, Confocal ; Plant Stems/cytology/genetics/metabolism ; Plants, Genetically Modified ; Plasmodesmata/metabolism ; Protein Multimerization ; Protein Transport/genetics ; Signal Transduction/genetics ; Stem Cells/*metabolism ; }, abstract = {Cell-cell communication is essential for multicellular development and, consequently, evolution has brought about an array of distinct mechanisms serving this purpose. Consistently, induction and maintenance of stem cell fate by noncell autonomous signals is a feature shared by many organisms and may depend on secreted factors, direct cell-cell contact, matrix interactions, or a combination of these mechanisms. Although many basic cellular processes are well conserved between animals and plants, cell-to-cell signaling is one function where substantial diversity has arisen between the two kingdoms of life. One of the most striking differences is the presence of cytoplasmic bridges, called plasmodesmata, which facilitate the exchange of molecules between neighboring plant cells and provide a unique route for cell-cell communication in the plant lineage. Here, we provide evidence that the stem cell inducing transcription factor WUSCHEL (WUS), expressed in the niche, moves to the stem cells via plasmodesmata in a highly regulated fashion and that this movement is required for WUS function and, thus, stem cell activity in Arabidopsis thaliana. We show that cell context-independent mobility is encoded in the WUS protein sequence and mediated by multiple domains. Finally, we demonstrate that parts of the protein that restrict movement are required for WUS homodimerization, suggesting that formation of WUS dimers might contribute to the regulation of apical stem cell activity.}, } @article {pmid25239794, year = {2014}, author = {Iriarte, A and Jara, E and Leytón, L and Diana, L and Musto, H}, title = {General trends in selectively driven codon usage biases in the domain archaea.}, journal = {Journal of molecular evolution}, volume = {79}, number = {3-4}, pages = {105-110}, pmid = {25239794}, issn = {1432-1432}, mesh = {Archaea/*genetics ; *Codon ; *Evolution, Molecular ; *Phylogeny ; }, abstract = {Since the advent of rapid techniques for sequencing DNA in the mid 70's, it became clear that all codons coding for the same amino acid are not used according to neutral expectations. In the last 30 years, several theories were proposed for explaining this fact. However, the most important concepts were the result of analyses carried out in Bacteria, and unicellular and multicellular eukaryotes like mammals (in other words, in two of the three Domains of life). In this communication, we study the main forces that shape codon usage in Archaeae under an evolutionary perspective. This is important because, as known, the orthologous genes related with the informational system in this Domain (replication, transcription and translation) are more similar to eukaryotes than to Bacteria. Our results show that the effect of selection acting at the level of translation is present in the Domain but mainly restricted to only a phylum (Euryarchaeota) and therefore is not as extended as in Bacteria. Besides, we describe the phylogenetic distribution of translational optimal codons and estimate the effect of selection acting at the level of accuracy. Finally, we discuss these results under some peculiarities that characterize this Domain.}, } @article {pmid25238093, year = {2014}, author = {Diefenbach, A and Colonna, M and Koyasu, S}, title = {Development, differentiation, and diversity of innate lymphoid cells.}, journal = {Immunity}, volume = {41}, number = {3}, pages = {354-365}, pmid = {25238093}, issn = {1097-4180}, support = {R01 DE021255/DE/NIDCR NIH HHS/United States ; 1U01AI095542/AI/NIAID NIH HHS/United States ; R01DE021255/DE/NIDCR NIH HHS/United States ; R21CA16719/CA/NCI NIH HHS/United States ; R21 CA167192/CA/NCI NIH HHS/United States ; U01 AI095542/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/immunology ; Cell Lineage/immunology ; Cytokines/*immunology ; Gene Expression Regulation/immunology ; Humans ; Immunity, Innate ; Killer Cells, Natural/*immunology ; Mice ; Signal Transduction/immunology ; Stem Cells/*immunology ; T-Lymphocytes, Helper-Inducer/*immunology ; Tight Junctions/immunology ; Transcription, Genetic ; }, abstract = {Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILCs). ILCs are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILCs has been linked to the pathogenesis of inflammatory and autoimmune disorders. Recent evidence suggests that ILCs can be grouped into two separate lineages, cytotoxic ILCs represented by conventional natural killer (cNK) cells and cytokine-producing helper-like ILCs (i.e., ILC1s, ILC2s, ILC3s). We will focus here on current work in humans and mice that has identified core transcriptional circuitry required for the commitment of lymphoid progenitors to the ILC lineage. The striking similarities in transcriptional control of ILC and T cell lineages reveal important insights into the evolution of transcriptional programs required to protect multicellular organisms against infections and to fortify barrier surfaces.}, } @article {pmid25233196, year = {2014}, author = {Libby, E and Ratcliff, W and Travisano, M and Kerr, B}, title = {Geometry shapes evolution of early multicellularity.}, journal = {PLoS computational biology}, volume = {10}, number = {9}, pages = {e1003803}, pmid = {25233196}, issn = {1553-7358}, mesh = {Apoptosis ; *Biological Evolution ; Cell Physiological Phenomena/*physiology ; Computational Biology ; *Models, Biological ; Yeasts/cytology/physiology ; }, abstract = {Organisms have increased in complexity through a series of major evolutionary transitions, in which formerly autonomous entities become parts of a novel higher-level entity. One intriguing feature of the higher-level entity after some major transitions is a division of reproductive labor among its lower-level units in which reproduction is the sole responsibility of a subset of units. Although it can have clear benefits once established, it is unknown how such reproductive division of labor originates. We consider a recent evolution experiment on the yeast Saccharomyces cerevisiae as a unique platform to address the issue of reproductive differentiation during an evolutionary transition in individuality. In the experiment, independent yeast lineages evolved a multicellular "snowflake-like" cluster formed in response to gravity selection. Shortly after the evolution of clusters, the yeast evolved higher rates of cell death. While cell death enables clusters to split apart and form new groups, it also reduces their performance in the face of gravity selection. To understand the selective value of increased cell death, we create a mathematical model of the cellular arrangement within snowflake yeast clusters. The model reveals that the mechanism of cell death and the geometry of the snowflake interact in complex, evolutionarily important ways. We find that the organization of snowflake yeast imposes powerful limitations on the available space for new cell growth. By dying more frequently, cells in clusters avoid encountering space limitations, and, paradoxically, reach higher numbers. In addition, selection for particular group sizes can explain the increased rate of apoptosis both in terms of total cell number and total numbers of collectives. Thus, by considering the geometry of a primitive multicellular organism we can gain insight into the initial emergence of reproductive division of labor during an evolutionary transition in individuality.}, } @article {pmid25230797, year = {2014}, author = {Armenta-Medina, D and Segovia, L and Perez-Rueda, E}, title = {Comparative genomics of nucleotide metabolism: a tour to the past of the three cellular domains of life.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {800}, pmid = {25230797}, issn = {1471-2164}, mesh = {Archaea/*genetics/metabolism ; Bacteria/*genetics/metabolism ; Eukaryota/*genetics/metabolism ; *Evolution, Molecular ; *Genomics ; Nucleotides/*metabolism ; }, abstract = {BACKGROUND: Nucleotide metabolism is central to all biological systems, due to their essential role in genetic information and energy transfer, which in turn suggests its possible presence in the last common ancestor (LCA) of Bacteria, Archaea and Eukarya. In this context, elucidation of the contribution of the origin and diversification of de novo and salvage pathways of nucleotide metabolism will allow us to understand the links between the enzymatic steps associated with the LCA and the emergence of the first metabolic pathways.

RESULTS: In this work, the taxonomical distribution of the enzymes associated with nucleotide metabolism was evaluated in 1,606 complete genomes. 151 sequence profiles associated with 120 enzymatic reactions were used. The evaluation was based on profile comparisons, using RPS-Blast. Organisms were clustered based on their taxonomical classifications, in order to obtain a normalized measure of the taxonomical distribution of enzymes according to the average of presence/absence of enzymes per genus, which in turn was used for the second step, to calculate the average presence/absence of enzymes per Clade.

CONCLUSION: From these analyses, it was suggested that divergence at the enzymatic level correlates with environmental changes and related modifications of the cell wall and membranes that took place during cell evolution. Specifically, the divergence of the 5-(carboxyamino) imidazole ribonucleotide mutase to phosphoribosylaminoimidazole carboxylase could be related to the emergence of multicellularity in eukaryotic cells. In addition, segments of salvage and de novo pathways were probably complementary in the LCA to the synthesis of purines and pyrimidines. We also suggest that a large portion of the pathway to inosine 5'-monophosphate (IMP) in purines could have been involved in thiamine synthesis or its derivatives in early stages of cellular evolution, correlating with the fact that these molecules may have played an active role in the protein-RNA world. The analysis presented here provides general observations concerning the adaptation of the enzymatic steps in the early stages of the emergence of life and the LCA.}, } @article {pmid25227255, year = {2015}, author = {Auld, SK and Tinsley, MC}, title = {The evolutionary ecology of complex lifecycle parasites: linking phenomena with mechanisms.}, journal = {Heredity}, volume = {114}, number = {2}, pages = {125-132}, pmid = {25227255}, issn = {1365-2540}, mesh = {Animals ; *Biological Evolution ; Host-Parasite Interactions/*genetics ; *Life Cycle Stages ; Models, Biological ; Parasites/genetics/*growth & development ; Parasitic Diseases/genetics/immunology/parasitology ; }, abstract = {Many parasitic infections, including those of humans, are caused by complex lifecycle parasites (CLPs): parasites that sequentially infect different hosts over the course of their lifecycle. CLPs come from a wide range of taxonomic groups-from single-celled bacteria to multicellular flatworms-yet share many common features in their life histories. Theory tells us when CLPs should be favoured by selection, but more empirical studies are required in order to quantify the costs and benefits of having a complex lifecycle, especially in parasites that facultatively vary their lifecycle complexity. In this article, we identify ecological conditions that favour CLPs over their simple lifecycle counterparts and highlight how a complex lifecycle can alter transmission rate and trade-offs between growth and reproduction. We show that CLPs participate in dynamic host-parasite coevolution, as more mobile hosts can fuel CLP adaptation to less mobile hosts. Then, we argue that a more general understanding of the evolutionary ecology of CLPs is essential for the development of effective frameworks to manage the many diseases they cause. More research is needed identifying the genetics of infection mechanisms used by CLPs, particularly into the role of gene duplication and neofunctionalisation in lifecycle evolution. We propose that testing for signatures of selection in infection genes will reveal much about how and when complex lifecycles evolved, and will help quantify complex patterns of coevolution between CLPs and their various hosts. Finally, we emphasise four key areas where new research approaches will provide fertile opportunities to advance this field.}, } @article {pmid27008999, year = {2012}, author = {Stiller, JW and Perry, J and Rymarquis, LA and Accerbi, M and Green, PJ and Prochnik, S and Lindquist, E and Chan, CX and Yarish, C and Lin, S and Zhuang, Y and Blouin, NA and Brawley, SH}, title = {MAJOR DEVELOPMENTAL REGULATORS AND THEIR EXPRESSION IN TWO CLOSELY RELATED SPECIES OF PORPHYRA (RHODOPHYTA)(1).}, journal = {Journal of phycology}, volume = {48}, number = {4}, pages = {883-896}, doi = {10.1111/j.1529-8817.2012.01138.x}, pmid = {27008999}, issn = {0022-3646}, abstract = {Little is known about the genetic and biochemical mechanisms that underlie red algal development, for example, why the group failed to evolve complex parenchyma and tissue differentiation. Here we examined expressed sequence tag (EST) data from two closely related species, Porphyra umbilicalis (L.) J. Agardh and P. purpurea (Roth) C. Agardh, for conserved developmental regulators known from model eukaryotes, and their expression levels in several developmental stages. Genes for most major developmental families were present, including MADS-box and homeodomain (HD) proteins, SNF2 chromatin-remodelers, and proteins involved in sRNA biogenesis. Some of these genes displayed altered expression correlating with different life history stages or cell types. Notably, two ESTs encoding HD proteins showed eightfold higher expression in the P. purpurea sporophyte (conchocelis) than in the gametophyte (blade), whereas two MADS domain-containing paralogs showed significantly different patterns of expression in the conchocelis and blade respectively. These developmental gene families do not appear to have undergone the kinds of dramatic expansions in copy number found in multicellular land plants and animals, which are important for regulating developmental processes in those groups. Analyses of small RNAs did not validate the presence of miRNAs, but homologs of Argonaute were present. In general, it appears that red algae began with a similar molecular toolkit for directing development as did other multicellular eukaryotes, but probably evolved altered roles for many key proteins, as well as novel mechanisms yet to be discovered.}, } @article {pmid25883411, year = {2012}, author = {Umen, JG and Olson, BJ}, title = {Genomics of Volvocine Algae.}, journal = {Advances in botanical research}, volume = {64}, number = {}, pages = {185-243}, pmid = {25883411}, issn = {0065-2296}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; R01 GM092744/GM/NIGMS NIH HHS/United States ; }, abstract = {Volvocine algae are a group of chlorophytes that together comprise a unique model for evolutionary and developmental biology. The species Chlamydomonas reinhardtii and Volvox carteri represent extremes in morphological diversity within the Volvocine clade. Chlamydomonas is unicellular and reflects the ancestral state of the group, while Volvox is multicellular and has evolved numerous innovations including germ-soma differentiation, sexual dimorphism, and complex morphogenetic patterning. The Chlamydomonas genome sequence has shed light on several areas of eukaryotic cell biology, metabolism and evolution, while the Volvox genome sequence has enabled a comparison with Chlamydomonas that reveals some of the underlying changes that enabled its transition to multicellularity, but also underscores the subtlety of this transition. Many of the tools and resources are in place to further develop Volvocine algae as a model for evolutionary genomics.}, } @article {pmid28564863, year = {1995}, author = {Blackstone, NW}, title = {PERSPECTIVE A UNITS-OF-EVOLUTION PERSPECTIVE ON THE ENDOSYMBIONT THEORY OF THE ORIGIN OF THE MITOCHONDRION.}, journal = {Evolution; international journal of organic evolution}, volume = {49}, number = {5}, pages = {785-796}, doi = {10.1111/j.1558-5646.1995.tb02315.x}, pmid = {28564863}, issn = {1558-5646}, abstract = {Discussions of mitochondria and their hosts often conceptualize this relationship in a more or less modern form, focusing on the metabolic benefits of mitochondria to the host cell or on the possibility of intragenomic conflict. A more inclusive units-of-evolution perspective recognizes that both costs and benefits must be viewed from the level of the cells that initiated this interaction, the protomitochondrion and the primitive host cell. From this perspective, ecological and physiological considerations become central to the characterization of initial and subsequent host-mitochondria associations. Foremost among these considerations is the generation of superoxide radicals by modern mitochondria and the deleterious effects of these endogenous oxidants on modern eukaryotic cells. Because of their photosynthetic and aerobic ecologies, protomitochondria likely were relatively tolerant of such oxidants; anaerobic, heterotrophic, primitive host cells, on the other hand, likely were not. In the initial association of host and symbiont, the latter may have manipulated the former's life history by means of both endogenous oxidants and a superabundance of ATP. A resolution of this units-of-evolution conflict was necessary to continue this association, and this resolution, in a ritualized form, may have shaped the evolution of many features of modern eukaryotic cells and mitochondria, for example, the messenger functions of calcium ions, the regulatory role of phosphorylation cascades in cell-division cycles, the absence from the mitochondrial genome of replication factors, transcription factors, and adenine nucleotide carrier genes. The initial host-mitochondria interaction may have further channeled the evolution of multicellular eukaryotes, particularly animals, resulting in the association of mitochondria and the germinal plasm and in the use of extracellular ATP and endogenous oxidants as developmental signals. Evolutionary explanations for "free-radical" theories of development and aging are thus suggested.}, } @article {pmid25223736, year = {2015}, author = {Gruber, R}, title = {Molecular and cellular basis of bone resorption.}, journal = {Wiener medizinische Wochenschrift (1946)}, volume = {165}, number = {3-4}, pages = {48-53}, pmid = {25223736}, issn = {1563-258X}, mesh = {Animals ; Biphenyl Compounds/therapeutic use ; Bone Remodeling/drug effects/genetics/physiology ; Bone Resorption/drug therapy/*genetics/*physiopathology ; Cathepsin K/antagonists & inhibitors/genetics/physiology ; Humans ; Osteoblasts/drug effects/*physiology ; Osteoclasts/drug effects/*physiology ; Osteoporosis/drug therapy/genetics/physiopathology ; RANK Ligand/genetics/physiology ; }, abstract = {Osteoclast research has an exciting history and a challenging future. More than 3 decades ago, it became evident that bone-resorbing osteoclasts are of hematopoietic origin and are ultimately linked to the "basic multicellular unit," where they team up with the other cell types, including bone-forming osteoblasts. Since 2 decades, we have learned about the signaling pathways controlling genes relevant for osteoclastogenesis and bone resorption. It took another decade until the hypothesized "osteoclast differentiation" factor was discovered and was translated into an approved pharmacologic strategy. Here, the focus is on another molecular target, cathepsin K, a cysteine protease being released by the osteoclast into the resorption compartment. Genetic deletion and pharmacological blocking of cathepsin K reduces bone resorption but with ongoing bone formation. This observation not only holds great promise to become a new pharmacologic strategy, but it also provides new insights into the coordinated work of cells in the "basic multicellular unit" and thus, bridges the history and future of osteoclast research. This article is a short primer on osteoclast biology for readers of the special issue on odanacatib, a cathepsin K inhibitor.}, } @article {pmid25185827, year = {2014}, author = {Joerger, AC and Wilcken, R and Andreeva, A}, title = {Tracing the evolution of the p53 tetramerization domain.}, journal = {Structure (London, England : 1993)}, volume = {22}, number = {9}, pages = {1301-1310}, pmid = {25185827}, issn = {1878-4186}, support = {MC_EX_G0901534/MRC_/Medical Research Council/United Kingdom ; MC_U105192716/MRC_/Medical Research Council/United Kingdom ; G0901534/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence ; Crystallography, X-Ray ; Evolution, Molecular ; Humans ; Molecular Sequence Data ; Phylogeny ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Sequence Analysis, Protein ; Tumor Suppressor Protein p53/*chemistry/genetics ; Zebrafish ; Zebrafish Proteins/*chemistry/genetics ; }, abstract = {The tetrameric transcription factors p53, p63, and p73 evolved from a common ancestor and play key roles in tumor suppression and development. Surprisingly, p63 and p73 require a second helix in their tetramerization domain for the formation of stable tetramers that is absent in human p53, raising questions about the evolutionary processes leading to diversification. Here we determined the crystal structure of the zebrafish p53 tetramerization domain, which contains a second helix, reminiscent of p63 and p73, combined with p53-like features. Through comprehensive phylogenetic analyses, we systematically traced the evolution of vertebrate p53 family oligomerization domains back to the beginning of multicellular life. We provide evidence that their last common ancestor also had an extended p63/p73-like domain and pinpoint evolutionary events that shaped this domain during vertebrate radiation. Domain compaction and transformation of a structured into a flexible, intrinsically disordered region may have contributed to the expansion of the human p53 interactome.}, } @article {pmid25184567, year = {2014}, author = {Furuse, Y and Finethy, R and Saka, HA and Xet-Mull, AM and Sisk, DM and Smith, KL and Lee, S and Coers, J and Valdivia, RH and Tobin, DM and Cullen, BR}, title = {Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells.}, journal = {PloS one}, volume = {9}, number = {9}, pages = {e106434}, pmid = {25184567}, issn = {1932-6203}, support = {R01-AI100759/AI/NIAID NIH HHS/United States ; T32 GM007184/GM/NIGMS NIH HHS/United States ; R01 AI100759/AI/NIAID NIH HHS/United States ; P30-AI064518/AI/NIAID NIH HHS/United States ; 1DP2-OD008614-01/OD/NIH HHS/United States ; P30 AI064518/AI/NIAID NIH HHS/United States ; DP2 OD008614/OD/NIH HHS/United States ; }, mesh = {Carboxypeptidases/*genetics ; Chlamydia/genetics/isolation & purification ; Gene Expression Regulation ; *High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/*genetics ; Legionella/genetics/isolation & purification ; MicroRNAs/genetics/*isolation & purification ; Mycobacterium tuberculosis/genetics/isolation & purification ; RNA, Bacterial/genetics/isolation & purification ; }, abstract = {MicroRNAs are expressed by all multicellular organisms and play a critical role as post-transcriptional regulators of gene expression. Moreover, different microRNA species are known to influence the progression of a range of different diseases, including cancer and microbial infections. A number of different human viruses also encode microRNAs that can attenuate cellular innate immune responses and promote viral replication, and a fungal pathogen that infects plants has recently been shown to express microRNAs in infected cells that repress host cell immune responses and promote fungal pathogenesis. Here, we have used deep sequencing of total expressed small RNAs, as well as small RNAs associated with the cellular RNA-induced silencing complex RISC, to search for microRNAs that are potentially expressed by intracellular bacterial pathogens and translocated into infected animal cells. In the case of Legionella and Chlamydia and the two mycobacterial species M. smegmatis and M. tuberculosis, we failed to detect any bacterial small RNAs that had the characteristics expected for authentic microRNAs, although large numbers of small RNAs of bacterial origin could be recovered. However, a third mycobacterial species, M. marinum, did express an ∼ 23-nt small RNA that was bound by RISC and derived from an RNA stem-loop with the characteristics expected for a pre-microRNA. While intracellular expression of this candidate bacterial microRNA was too low to effectively repress target mRNA species in infected cultured cells in vitro, artificial overexpression of this potential bacterial pre-microRNA did result in the efficient repression of a target mRNA. This bacterial small RNA therefore represents the first candidate microRNA of bacterial origin.}, } @article {pmid25174994, year = {2014}, author = {Bosch, TC}, title = {Rethinking the role of immunity: lessons from Hydra.}, journal = {Trends in immunology}, volume = {35}, number = {10}, pages = {495-502}, doi = {10.1016/j.it.2014.07.008}, pmid = {25174994}, issn = {1471-4981}, mesh = {Animals ; Biological Evolution ; Humans ; Hydra/*immunology ; Immunity, Innate/*immunology ; Receptors, Pattern Recognition/immunology ; }, abstract = {The ability of multicellular organisms to detect and respond to microorganisms is fundamental and has ancient evolutionary origins. In this review, I evaluate our current understanding of the evolution of epithelial-based innate immunity in Hydra, an apparently simple animal that shares deep evolutionary connections with all animals, including humans. I highlight growing evidence that the innate immune system with its host-specific antimicrobial peptides and rich repertoire of pattern recognition receptors has evolved in response to the need for controlling resident beneficial microbes rather than to defend against invasive pathogens. These findings provide new insight into how developmental pathways beyond those associated with the immune system, such as stem cell transcriptional programs, interact with environmental cues such as microbes.}, } @article {pmid25164483, year = {2014}, author = {Hubka, V and Réblová, M and Rehulka, J and Selbmann, L and Isola, D and de Hoog, SG and Kolařík, M}, title = {Bradymyces gen. nov. (Chaetothyriales, Trichomeriaceae), a new ascomycete genus accommodating poorly differentiated melanized fungi.}, journal = {Antonie van Leeuwenhoek}, volume = {106}, number = {5}, pages = {979-992}, doi = {10.1007/s10482-014-0267-4}, pmid = {25164483}, issn = {1572-9699}, mesh = {Animals ; Ascomycota/*classification/cytology/genetics/*isolation & purification ; Cluster Analysis ; DNA, Fungal/chemistry/genetics ; DNA, Intergenic/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Environmental Microbiology ; Microscopy ; Molecular Sequence Data ; Oncorhynchus mykiss/microbiology ; Phylogeny ; RNA, Ribosomal, 18S/genetics ; RNA, Ribosomal, 28S/genetics ; Sequence Analysis, DNA ; Temperature ; Tubulin/genetics ; }, abstract = {Three slow growing, melanized and morphologically poorly differentiated fungal strains were isolated from a hyperaemic focus near the enlarged spleen of a farmed rainbow trout (Oncorhynchus mykiss) and from a rock collected at 3,200 m a. s. l. (Alps, Italy). Two phylogenetic analyses of the combined nuc18S and nuc28S rDNA and ITS rDNA and β-tubulin sequences showed that these isolates belong to the Trichomeriaceae, a family of the ascomycete order Chaetothyriales containing black yeasts that cause infections in humans and animals. The strains form a well-supported monophyletic clade. The new genus Bradymyces, with two new species, Bradymyces oncorhynchi and Bradymyces alpinus, is proposed based on phylogenetic, ecophysiological and morphological data. It is characterized by the presence of moniliform hyphae, blastic proliferation, endoconidia, multicellular and muriform bodies, and bodies with dark fragmented incrustations on the surface. Bradymyces most closely resembles members of Knufia. The ex-type isolate of B. oncorhynchi CCF 4369(T) (= CBS 133066(T) = CCFEE 6134(T)) represents the first case of a Trichomeriaceae member isolated from cold-blooded water vertebrates. B. alpinus [ex-type strain CCFEE 5493(T) (= CBS 138368(T) = CCF 4803(T))] is represented by two isolates from a single locality in the Alps and in contrast to B. oncorhynchi shows overall slower growth parameters and does not grow at 25 °C.}, } @article {pmid25158977, year = {2014}, author = {Yin, K and Ueda, M and Takagi, H and Kajihara, T and Sugamata Aki, S and Nobusawa, T and Umeda-Hara, C and Umeda, M}, title = {A dual-color marker system for in vivo visualization of cell cycle progression in Arabidopsis.}, journal = {The Plant journal : for cell and molecular biology}, volume = {80}, number = {3}, pages = {541-552}, doi = {10.1111/tpj.12652}, pmid = {25158977}, issn = {1365-313X}, mesh = {Arabidopsis/cytology/genetics/*metabolism ; Cell Cycle/genetics ; *DNA Replication ; G2 Phase/genetics ; *Gene Expression Regulation, Plant ; Genes, Reporter ; Histones/*metabolism ; Mitosis ; Plant Roots/genetics ; Time-Lapse Imaging/*methods ; }, abstract = {Visualization of the spatiotemporal pattern of cell division is crucial to understand how multicellular organisms develop and how they modify their growth in response to varying environmental conditions. The mitotic cell cycle consists of four phases: S (DNA replication), M (mitosis and cytokinesis), and the intervening G1 and G2 phases; however, only G2/M-specific markers are currently available in plants, making it difficult to measure cell cycle duration and to analyze changes in cell cycle progression in living tissues. Here, we developed another cell cycle marker that labels S-phase cells by manipulating Arabidopsis CDT1a, which functions in DNA replication origin licensing. Truncations of the CDT1a coding sequence revealed that its carboxy-terminal region is responsible for proteasome-mediated degradation at late G2 or in early mitosis. We therefore expressed this region as a red fluorescent protein fusion protein under the S-specific promoter of a histone 3.1-type gene, HISTONE THREE RELATED2 (HTR2), to generate an S/G2 marker. Combining this marker with the G2/M-specific CYCB1-GFP marker enabled us to visualize both S to G2 and G2 to M cell cycle stages, and thus yielded an essential tool for time-lapse imaging of cell cycle progression. The resultant dual-color marker system, Cell Cycle Tracking in Plant Cells (Cytrap), also allowed us to identify root cells in the last mitotic cell cycle before they entered the endocycle. Our results demonstrate that Cytrap is a powerful tool for in vivo monitoring of the plant cell cycle, and thus for deepening our understanding of cell cycle regulation in particular cell types during organ development.}, } @article {pmid25150025, year = {2014}, author = {Ali, RH and Khan, AA}, title = {Tracing the evolution of FERM domain of Kindlins.}, journal = {Molecular phylogenetics and evolution}, volume = {80}, number = {}, pages = {193-204}, doi = {10.1016/j.ympev.2014.08.008}, pmid = {25150025}, issn = {1095-9513}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Membrane Proteins/*genetics ; Molecular Sequence Data ; *Phylogeny ; *Protein Structure, Tertiary ; Sequence Analysis, DNA ; }, abstract = {Kindlin proteins represent a novel family of evolutionarily conserved FERM domain containing proteins (FDCPs) and are members of B4.1 superfamily. Kindlins consist of three conserved protein homologs in vertebrates: Kindlin-1, Kindlin-2 and Kindlin-3. All three homologs are associated with focal adhesions and are involved in Integrin activation. FERM domain of each Kindlin is bipartite and plays a key role in Integrin activation. A single ancestral Kindlin protein can be traced back to earliest metazoans, e.g., to Parazoa. This protein underwent multiple rounds of duplication in vertebrates, leading to the present Kindlin family. In this study, we trace phylogenetic and evolutionary history of Kindlin FERM domain with respect to FERM domain of other FDCPs. We show that FERM domain in Kindlin homologs is conserved among Kindlins but amount of conservation is less in comparison with FERM domain of other members in B4.1 superfamily. Furthermore, insertion of Pleckstrin Homology like domain in Kindlin FERM domain has important evolutionary and functional consequences. Important residues in Kindlins are traced and ranked according to their evolutionary significance. The structural and functional significance of high ranked residues is highlighted and validated by their known involvement in Kindlin associated diseases. In light of these findings, we hypothesize that FERM domain originated from a proto-Talin protein in unicellular or proto-multicellular organism and advent of multi-cellularity was accompanied by burst of FDCPs, which supported multi-cellularity functions required for complex organisms. This study helps in developing a better understanding of evolutionary history of FERM domain of FDCPs and the role of FERM domain in metazoan evolution.}, } @article {pmid25146840, year = {2015}, author = {Ortiz, MF and Wallau, GL and Graichen, DÂ and Loreto, EL}, title = {An evaluation of the ecological relationship between Drosophila species and their parasitoid wasps as an opportunity for horizontal transposon transfer.}, journal = {Molecular genetics and genomics : MGG}, volume = {290}, number = {1}, pages = {67-78}, pmid = {25146840}, issn = {1617-4623}, mesh = {Animals ; Base Sequence ; DNA Transposable Elements/*genetics ; Drosophila/microbiology/*parasitology ; Gene Transfer, Horizontal/*genetics ; Genes, Mitochondrial ; Genome, Insect/genetics ; *Host-Parasite Interactions ; Phylogeny ; Reproducibility of Results ; Species Specificity ; Wasps/*physiology/virology ; Wolbachia/physiology ; }, abstract = {Evidences of horizontal transfer, the exchange of genetic material between reproductively isolated species, have accumulated over the last decades, including for multicellular eukaryotic organisms. However, the mechanisms and ecological relationships that promote such phenomenon is still poorly known. Host-parasite interaction is one type of relationship usually pointed in the literature that could potentially increase the probability of the horizontal transfer between species, because the species involved in such relationships are generally in close contact. Transposable elements, which are well-known genomic parasites, are DNA entities that tend to be involved in horizontal transfer due to their ability to mobilize between different genomic locations. Using Drosophila species and their parasitoid wasps as a host-parasite model, we evaluated the hypothesis that horizontal transposon transfers (HTTs) are more frequent in this set of species than in species that do not exhibit a close ecological and phylogenetic relationship. For this purpose, we sequenced two sets of species using a metagenomic and single-species genomic sampling approach through next-generation DNA sequencing. The first set was composed of five generalist Drosophila (D. maculifrons, D. bandeirantorum, D. polymorpha, D. mercatorum and D. willistoni) species and their associated parasitoid wasps, whereas the second set was composed of D. incompta, which is a flower specialist species, and its parasitoid wasp. We did not find strong evidence of HTT in the two sets of Drosophila and wasp parasites. However, at least five cases of HTT were observed between the generalist and specialist Drosophila species. Moreover, we detected an HT event involving a Wolbachia lineage between generalist and specialist species, indicating that these endosymbiotic bacteria could play a role as HTT vectors. In summary, our results do not support the hypothesis of prevalent HTT between species with a host-parasite relationship, at least for the studied wasp-Drosophila pairs. Moreover, it suggests that other mechanisms or parasites are involved in promoting HTT between Drosophila species as the Wolbachia endosymbiotic bacteria.}, } @article {pmid25143284, year = {2014}, author = {Niklas, KJ and Cobb, ED and Kutschera, U}, title = {Did meiosis evolve before sex and the evolution of eukaryotic life cycles?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {36}, number = {11}, pages = {1091-1101}, doi = {10.1002/bies.201400045}, pmid = {25143284}, issn = {1521-1878}, mesh = {Animals ; Biological Evolution ; Chlorophyta ; Fertilization/*physiology ; Life Cycle Stages ; Meiosis/*genetics ; Polyploidy ; Reproduction, Asexual/*physiology ; *Sex ; }, abstract = {Biologists have long theorized about the evolution of life cycles, meiosis, and sexual reproduction. We revisit these topics and propose that the fundamental difference between life cycles is where and when multicellularity is expressed. We develop a scenario to explain the evolutionary transition from the life cycle of a unicellular organism to one in which multicellularity is expressed in either the haploid or diploid phase, or both. We propose further that meiosis might have evolved as a mechanism to correct for spontaneous whole-genome duplication (auto-polyploidy) and thus before the evolution of sexual reproduction sensu stricto (i.e. the formation of a diploid zygote via the fusion of haploid gametes) in the major eukaryotic clades. In addition, we propose, as others have, that sexual reproduction, which predominates in all eukaryotic clades, has many different advantages among which is that it produces variability among offspring and thus reduces sibling competition.}, } @article {pmid25133612, year = {2014}, author = {Peña, EJ and Ferriol, I and Sambade, A and Buschmann, H and Niehl, A and Elena, SF and Rubio, L and Heinlein, M}, title = {Experimental virus evolution reveals a role of plant microtubule dynamics and TORTIFOLIA1/SPIRAL2 in RNA trafficking.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e105364}, pmid = {25133612}, issn = {1932-6203}, mesh = {Arabidopsis/genetics/metabolism/*virology ; Arabidopsis Proteins/genetics/*metabolism ; Biological Evolution ; Host-Pathogen Interactions ; Microtubule-Associated Proteins/genetics/*metabolism ; Microtubules/genetics/*metabolism ; Mutation ; Plant Diseases/genetics/*virology ; RNA/genetics/metabolism ; *RNA Transport ; Tobacco Mosaic Virus/genetics/*physiology ; }, abstract = {The cytoskeleton is a dynamic network composed of filamentous polymers and regulatory proteins that provide a flexible structural scaffold to the cell and plays a fundamental role in developmental processes. Mutations that alter the spatial orientation of the cortical microtubule (MT) array of plants are known to cause important changes in the pattern of cell wall synthesis and developmental phenotypes; however, the consequences of such alterations on other MT-network-associated functions in the cytoplasm are not known. In vivo observations suggested a role of cortical MTs in the formation and movement of Tobacco mosaic virus (TMV) RNA complexes along the endoplasmic reticulum (ER). Thus, to probe the significance of dynamic MT behavior in the coordination of MT-network-associated functions related to TMV infection and, thus, in the formation and transport of RNA complexes in the cytoplasm, we performed an evolution experiment with TMV in Arabidopsis thaliana tor1/spr2 and tor2 mutants with specific defects in MT dynamics and asked whether TMV is sensitive to these changes. We show that the altered cytoskeleton induced genetic changes in TMV that were correlated with efficient spread of infection in the mutant hosts. These observations demonstrate a role of dynamic MT rearrangements and of the MT-associated protein TORTIFOLIA1/SPIRAL2 in cellular functions related to virus spread and indicate that MT dynamics and MT-associated proteins represent constraints for virus evolution and adaptation. The results highlight the importance of the dynamic plasticity of the MT network in directing cytoplasmic functions in macromolecular assembly and trafficking and illustrate the value of experimental virus evolution for addressing the cellular functions of dynamic, long-range order systems in multicellular organisms.}, } @article {pmid25119834, year = {2014}, author = {Hill, J and Rom, S and Ramirez, SH and Persidsky, Y}, title = {Emerging roles of pericytes in the regulation of the neurovascular unit in health and disease.}, journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology}, volume = {9}, number = {5}, pages = {591-605}, pmid = {25119834}, issn = {1557-1904}, support = {AA015913/AA/NIAAA NIH HHS/United States ; R01 MH065151/MH/NIMH NIH HHS/United States ; P30 DA013429/DA/NIDA NIH HHS/United States ; NS086570/NS/NINDS NIH HHS/United States ; R37 AA015913/AA/NIAAA NIH HHS/United States ; R01 AA015913/AA/NIAAA NIH HHS/United States ; MH65151/MH/NIMH NIH HHS/United States ; DA013429/DA/NIDA NIH HHS/United States ; R01 NS086570/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Blood-Brain Barrier/cytology/*metabolism/pathology ; Central Nervous System Diseases/*metabolism/pathology ; Endothelium, Vascular/cytology/*metabolism ; *Health Status ; Humans ; Pericytes/*physiology ; Signal Transduction/physiology ; }, abstract = {Pericytes of the central nervous system (CNS) are uniquely positioned within a multicellular structure termed the neurovascular unit (NVU) to provide crucial support to blood brain barrier (BBB) formation, maintenance, and stability. Numerous CNS diseases are associated with some aspect of BBB dysfunction. A dysfunction can manifest as one or multiple disruptions to any of the following barriers: physical, metabolic, immunological and transport barrier. A breach in the BBB can notably result in BBB hyper-permeability, endothelial activation and enhanced immune-endothelial interaction. How the BBB is regulated within this integrated unit remains largely unknown, especially as it relates to pericyte-endothelial interaction. We summarize the latest findings on pericyte origin, possible marker expression, and availability within different organ systems. We highlight pericyte-endothelial cell interactions, concentrating on extra- and intra- cellular signaling mechanisms linked to platelet derived growth factor-B, transforming growth factor -β, angiopoietins, Notch, and gap junctions. We discuss the role of pericytes in the NVU under inflammatory insult, focusing on how pericytes may indirectly affect leukocyte CNS infiltration, the direct role of pericyte-mediated basement membrane modifications, and immune responses. We review new findings of pericyte actions in CNS pathologies including Alzheimer's disease, stroke, multiple sclerosis, diabetic retinopathy, and HIV-1 infection. The uncovering of the regulatory role of pericytes on the BBB will provide key insight into how barrier integrity can be re-established during neuroinflammation.}, } @article {pmid25087460, year = {2015}, author = {An, G and Kulkarni, S}, title = {An agent-based modeling framework linking inflammation and cancer using evolutionary principles: description of a generative hierarchy for the hallmarks of cancer and developing a bridge between mechanism and epidemiological data.}, journal = {Mathematical biosciences}, volume = {260}, number = {}, pages = {16-24}, pmid = {25087460}, issn = {1879-3134}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; P50GM53789/GM/NIGMS NIH HHS/United States ; P50 GM053789/GM/NIGMS NIH HHS/United States ; UL1 TR000430/TR/NCATS NIH HHS/United States ; P30DK42086/DK/NIDDK NIH HHS/United States ; }, mesh = {Black or African American/ethnology ; *Biological Evolution ; Breast Neoplasms/immunology ; Carcinogenesis/*immunology ; Female ; Humans ; Inflammation/*complications ; Neoplasms/*etiology ; Premenopause/immunology ; *Systems Biology ; }, abstract = {Inflammation plays a critical role in the development and progression of cancer, evident in multiple patient populations manifesting increased, non-resolving inflammation, such as inflammatory bowel disease, viral hepatitis and obesity. Given the complexity of both the inflammatory response and the process of oncogenesis, we utilize principles from the field of Translational Systems Biology to bridge the gap between basic mechanistic knowledge and clinical/epidemiologic data by integrating inflammation and oncogenesis within an agent-based model, the Inflammation and Cancer Agent-based Model (ICABM). The ICABM utilizes two previously published and clinically/epidemiologically validated mechanistic models to demonstrate the role of an increased inflammatory milieu on oncogenesis. Development of the ICABM required the creation of a generative hierarchy of the basic hallmarks of cancer to provide a foundation to ground the plethora of molecular and pathway components currently being studied. The ordering schema emphasizes the essential role of a fitness/selection frame shift to sub-organismal evolution as a basic property of cancer, where the generation of genetic instability as a negative effect for multicellular eukaryotic organisms represents the restoration of genetic plasticity used as an adaptive strategy by colonies of prokaryotic unicellular organisms. Simulations with the ICABM demonstrate that inflammation provides a functional environmental context that drives the shift to sub-organismal evolution, where increasingly inflammatory environments led to increasingly damaged genomes in microtumors (tumors below clinical detection size) and cancers. The flexibility of this platform readily facilitates tailoring the ICABM to specific cancers, their associated mechanisms and available epidemiological data. One clinical example of an epidemiological finding that could be investigated with this platform is the increased incidence of triple negative breast cancers in the premenopausal African-American population, which has been identified as having up-regulated of markers of inflammation. The fundamental nature of the ICABM suggests its usefulness as a base platform upon which additional molecular detail could be added as needed.}, } @article {pmid25078701, year = {2014}, author = {Jiang, H and Franz, CJ and Wang, D}, title = {Engineering recombinant Orsay virus directly in the metazoan host Caenorhabditis elegans.}, journal = {Journal of virology}, volume = {88}, number = {20}, pages = {11774-11781}, pmid = {25078701}, issn = {1098-5514}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Blotting, Western ; Caenorhabditis elegans/*virology ; DNA Primers ; DNA, Complementary ; Nodaviridae/*genetics/physiology ; Real-Time Polymerase Chain Reaction ; Virus Replication ; }, abstract = {The recent identification of Orsay virus, the first virus that is capable of naturally infecting Caenorhabditis elegans, provides a unique opportunity to explore host-virus interaction studies in this invaluable model organism. A key feature of this system is the robust genetic tractability of the host, C. elegans, which would ideally be complemented by the ability to genetically manipulate Orsay virus in parallel. To this end, we developed a plasmid-based reverse genetics system for Orsay virus by creating transgenic C. elegans strains harboring Orsay virus cDNAs. Both wild-type and mutant Orsay viruses, including a FLAG epitope-tagged recombinant Orsay virus, were generated by use of the reverse genetics system. This is the first plasmid-based virus reverse genetics system in the metazoan C. elegans. The Orsay virus reverse genetics we established will serve as a fundamental tool in host-virus interaction studies in the model organism C. elegans. Importance: To date, Orsay virus is the first and the only identified virus capable of naturally infecting Caenorhabditis elegans. C. elegans is a simple multicellular model organism that mimics many fundamental features of human biology and has been used to define many biological properties conserved through evolution. Thus, the Orsay virus-C. elegans infection system provides a unique opportunity to study host-virus interactions. In order to take maximal advantage of this system, the ability to genetically engineer mutant forms of Orsay virus would be highly desirable. Most efforts to engineer viruses have been done with cultured cells. Here we describe the creation of mutant viruses directly in the multicellular organism C. elegans without the use of cell culture. We engineered a virus expressing a genetically tagged protein that could be detected in C. elegans. This provides proof of concept for modifying Orsay virus, which will greatly facilitate studies in this experimental system.}, } @article {pmid25048306, year = {2014}, author = {Li, SI and Buttery, NJ and Thompson, CR and Purugganan, MD}, title = {Sociogenomics of self vs. non-self cooperation during development of Dictyostelium discoideum.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {616}, pmid = {25048306}, issn = {1471-2164}, support = {095643//Wellcome Trust/United Kingdom ; }, mesh = {Cell Adhesion Molecules/genetics/metabolism ; Chimera/genetics ; Cluster Analysis ; Dictyostelium/*genetics/growth & development ; Gene Expression Regulation ; Gene Regulatory Networks ; *Genes, Protozoan ; Principal Component Analysis ; Protozoan Proteins/genetics/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Dictyostelium discoideum, a microbial model for social evolution, is known to distinguish self from non-self and show genotype-dependent behavior during chimeric development. Aside from a small number of cell-cell recognition genes, however, little is known about the genetic basis of self/non-self recognition in this species. Based on the key hypothesis that there should be differential expression of genes if D. discoideum cells were interacting with non-clone mates, we performed transcriptomic profiling study in this species during clonal vs. chimeric development. The transcriptomic profiles of D. discoideum cells in clones vs. different chimeras were compared at five different developmental stages using a customized microarray. Effects of chimerism on global transcriptional patterns associated with social interactions were observed.

RESULTS: We find 1,759 genes significantly different between chimera and clone, 1,144 genes associated significant strain differences, and 6,586 genes developmentally regulated over time. Principal component analysis showed a small amount of the transcriptional variance to chimerism-related factors (Chimerism: 0.18%, Chimerism × Timepoint: 0.03%). There are 162 genes specifically regulated under chimeric development, with continuous small differences between chimera vs. clone over development. Almost 60% of chimera-associated differential genes were differentially expressed at the 4 h aggregate stage, which corresponds to the initial transition of D. discoideum from solitary life to a multicellular phase.

CONCLUSIONS: A relatively small proportion of over-all variation in gene expression is explained by differences between chimeric and clonal development. The relatively small modifications in gene expression associated with chimerism is compatible with the high level of cooperation observed among different strains of D. discoideum; cells of distinct genetic backgrounds will co-aggregate indiscriminately and co-develop into fruiting bodies. Chimeric development may involve re-programming of the transcriptome through small modifications of the developmental genetic network, which may also indicate that response to social interaction involves many genes with individually small transcriptional effect.}, } @article {pmid25045925, year = {2014}, author = {Yang, Y and Yang, Y and Xie, X and Cai, X and Mei, X}, title = {Preparation and characterization of photo-responsive cell-penetrating peptide-mediated nanostructured lipid carrier.}, journal = {Journal of drug targeting}, volume = {22}, number = {10}, pages = {891-900}, doi = {10.3109/1061186X.2014.940589}, pmid = {25045925}, issn = {1029-2330}, mesh = {Antineoplastic Agents, Phytogenic/*administration & dosage/pharmacology ; Cell Line, Tumor ; Cell-Penetrating Peptides/*chemistry ; Drug Carriers/chemistry ; *Drug Delivery Systems ; Drug Stability ; Fibrosarcoma/drug therapy/pathology ; Humans ; Lipids/chemistry ; Nanostructures ; Paclitaxel/*administration & dosage/pharmacology ; Particle Size ; Tumor Microenvironment ; Ultraviolet Rays ; }, abstract = {Tumor-oriented nanocarrier drug delivery approaches with photo-sensitivity have been drawing considerable attention over the years. Here we described a nanostructured lipid carrier (NLC) modified with photo-responsive cell-penetrating peptides (pCPP-NLC). The conventional cell penetrating peptide (CPP)-mediated intracellular drug delivery system sometimes seemed limited due to the lack of target selectivity of the cell penetrating activity. In this study, pCPP (CKRRMK(Nvoc)WK(Nvo0c)K(Nvoc)), a photo-responsive CPP originated from the CPP (CKRRMKWKK), was endowed photo-responsiveness after masking of lysines in the sequence of CPP with photolabile-protective groups, and was introduced onto the surface of NLC. Accordingly, upon reaching the tumor tissues, pCPP-NLC enhance specific cancer cellular uptake after rapidly cleaving the photolabile-protective group, in this case, illumination in the presence of UV-light. In contrast, in circulation, the penetration was shielded. The pCPP-NLC carrying paclitaxel (PTX) prepared in this work possessed suitable physiochemical properties such as small particle size, high drug encapsulation efficiency, and good stability. The strong cellular uptake and cytotoxic activity of pCPP-NLC in HT-1080 cells verified the correlation with illumination. The remarkable penetration into HT-1080 multicellular tumor spheroids confirmed that the temporary mask of the photolabile-protective group in pCPP does not disturb the penetration ability of CPP in the tumor microenvironment with illumination. Furthermore, the triggered activation exhibited higher antitumor efficacy with the tumor spheroids compared with the non-modified NLC (N-NLC) and Taxol(®). In conclusion, the application of pCPP modifications may be an approach for the selectively targeted delivery of anti-tumor agents.}, } @article {pmid25043755, year = {2014}, author = {Lineweaver, CH and Davies, PC and Vincent, MD}, title = {Targeting cancer's weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {36}, number = {9}, pages = {827-835}, pmid = {25043755}, issn = {1521-1878}, support = {U54 CA143862/CA/NCI NIH HHS/United States ; U54 CA143682/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Proliferation ; Energy Metabolism ; Humans ; Immunotherapy ; Neoplasms/immunology/pathology/*therapy ; Phenotype ; Tumor Escape ; }, abstract = {In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target-the-weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target-the-weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation.}, } @article {pmid25043003, year = {2014}, author = {Behjati, S and Huch, M and van Boxtel, R and Karthaus, W and Wedge, DC and Tamuri, AU and Martincorena, I and Petljak, M and Alexandrov, LB and Gundem, G and Tarpey, PS and Roerink, S and Blokker, J and Maddison, M and Mudie, L and Robinson, B and Nik-Zainal, S and Campbell, P and Goldman, N and van de Wetering, M and Cuppen, E and Clevers, H and Stratton, MR}, title = {Genome sequencing of normal cells reveals developmental lineages and mutational processes.}, journal = {Nature}, volume = {513}, number = {7518}, pages = {422-425}, pmid = {25043003}, issn = {1476-4687}, support = {092096/WT_/Wellcome Trust/United Kingdom ; WT100183MA/WT_/Wellcome Trust/United Kingdom ; 088340/WT_/Wellcome Trust/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; 077012/Z/05/Z/WT_/Wellcome Trust/United Kingdom ; 104151/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biological Clocks/genetics ; Cell Division ; Cell Lineage/*genetics ; Cells, Cultured ; Clone Cells/*cytology/*metabolism ; Embryo, Mammalian/cytology ; Genome/*genetics ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mutagenesis/*genetics ; Mutation/*genetics ; Mutation Rate ; Organoids/cytology/metabolism ; Phylogeny ; Sequence Analysis, DNA ; Tail/cytology ; }, abstract = {The somatic mutations present in the genome of a cell accumulate over the lifetime of a multicellular organism. These mutations can provide insights into the developmental lineage tree, the number of divisions that each cell has undergone and the mutational processes that have been operative. Here we describe whole genomes of clonal lines derived from multiple tissues of healthy mice. Using somatic base substitutions, we reconstructed the early cell divisions of each animal, demonstrating the contributions of embryonic cells to adult tissues. Differences were observed between tissues in the numbers and types of mutations accumulated by each cell, which likely reflect differences in the number of cell divisions they have undergone and varying contributions of different mutational processes. If somatic mutation rates are similar to those in mice, the results indicate that precise insights into development and mutagenesis of normal human cells will be possible.}, } @article {pmid25042404, year = {2015}, author = {Ćetković, H and Perina, D and Harcet, M and Mikoč, A and Herak Bosnar, M}, title = {Nme family of proteins--clues from simple animals.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {388}, number = {2}, pages = {133-142}, pmid = {25042404}, issn = {1432-1912}, mesh = {Animals ; Humans ; *Nucleoside-Diphosphate Kinase/genetics/metabolism ; Phylogeny ; }, abstract = {Nucleoside-diphosphate kinases (Nme/Nm23/NDPK) are evolutionarily conserved enzymes involved in many biological processes in vertebrates. The biochemical mechanisms of these processes are still largely unknown. The Nme family consists of ten members in humans of which Nme1/2 have been extensively studied in the context of carcinogenesis, especially metastasis formation. Lately, it has been proven that the majority of genes linked to human diseases were already present in species distantly related to humans. Most of cancer-related protein domains appeared during the two main evolutionary transitions-the emergence of unicellular eukaryotes and the transition to multicellular metazoans. In spite of these recent insights, current knowledge about cancer and status of cancer-related genes in simple animals is limited. One possible way of studying human diseases relies on analyzing genes/proteins that cause a certain disease by using model organism that represent the evolutionary level at which these genes have emerged. Therefore, basal metazoans are ideal model organisms for gaining a clearer picture how characteristics and functions of Nme genes changed in the transition to multicellularity and increasing complexity in animals, giving us exciting new evidence of their possible functions in potential pathological conditions in humans.}, } @article {pmid25041157, year = {2014}, author = {Thomas, F and Cosse, A and Le Panse, S and Kloareg, B and Potin, P and Leblanc, C}, title = {Kelps feature systemic defense responses: insights into the evolution of innate immunity in multicellular eukaryotes.}, journal = {The New phytologist}, volume = {204}, number = {3}, pages = {567-576}, doi = {10.1111/nph.12925}, pmid = {25041157}, issn = {1469-8137}, mesh = {Animals ; *Biological Evolution ; Feeding Behavior ; Gene Expression Regulation, Plant/*physiology ; Hydrogen Peroxide ; Immunity, Innate/*physiology ; Laminaria/enzymology/genetics/*immunology/*metabolism ; Mollusca/physiology ; Plant Leaves ; }, abstract = {Brown algae are one of the few eukaryotic lineages that have evolved complex multicellularity, together with Opisthokonts (animals, fungi) and Plantae (land plants, green and red algae). In these three lineages, biotic stresses induce similar local defense reactions. Animals and land plants also feature a systemic immune response, protecting the whole organism after an attack on one of its parts. However, the occurrence of systemic defenses has never been investigated in brown algae. We elicited selected parts of the kelp Laminaria digitata and monitored distant, nonchallenged areas of the same individual for subsequent defense reactions. A systemic reaction was detected following elicitation on a distant area, including an oxidative response, an increase in haloperoxidase activities and a stronger resistance against herbivory. Based on experiments with pharmacological inhibitors, the liberation of free fatty acids is proposed to play a key role in systemic signaling, reminiscent of what is known in land plants. This study is the first report, outside the phyla of Opisthokonts and Plantae, of an intraorganism communication leading to defense reactions. These findings indicate that systemic immunity emerged independently at least three times, as a consequence of convergent evolution in multicellular eukaryotic lineages.}, } @article {pmid25031031, year = {2014}, author = {Lerche, K and Hallmann, A}, title = {Stable nuclear transformation of Pandorina morum.}, journal = {BMC biotechnology}, volume = {14}, number = {}, pages = {65}, pmid = {25031031}, issn = {1472-6750}, mesh = {Base Sequence ; Cell Nucleus/*metabolism ; Chlorophyta/drug effects/*metabolism ; Fungal Proteins/genetics ; Genes, Reporter ; Gold/chemistry ; HSP70 Heat-Shock Proteins/genetics ; Kanamycin Kinase/genetics ; Luciferases/genetics ; Molecular Sequence Data ; Paromomycin/pharmacology ; Plasmids/metabolism ; Promoter Regions, Genetic ; Ribulose-Bisphosphate Carboxylase/genetics ; Streptomyces/enzymology ; Transformation, Genetic ; Volvox/enzymology ; }, abstract = {BACKGROUND: Volvocine green algae like Pandorina morum represent one of the most recent inventions of multicellularity diverged from their unicellular relatives. The 8-16 celled P. morum alga and its close multicellular relatives constitute a model lineage for research into cellular differentiation, morphogenesis and epithelial folding, sexual reproduction and evolution of multicellularity. Pandorina is the largest and most complex organism in the volvocine lineage that still exhibits isogamous sexual reproduction. So far, molecular-biological investigations in P. morum were constricted due to the absence of methods for transformation of this species, which is a prerequisite for introduction of reporter genes and (modified) genes of interest.

RESULTS: Stable nuclear transformation of P. morum was achieved using chimeric constructs with a selectable marker, a reporter gene, promoters and upstream and downstream flanking sequences from heterologous sources. DNA was introduced into the cells by particle bombardment with plasmid-coated gold particles. The aminoglycoside 3'-phosphotransferase VIII (aphVIII) gene of Streptomyces rimosus under control of an artificial, heterologous promoter was used as the selectable marker. The artificial promoter contained a tandem arrangement of the promoter of both the heat shock protein 70A (hsp70A) and the ribulose-1,5-bisphosphat-carboxylase/-oxygenase S3 (rbcS3) gene of Volvox carteri. Due to the expression of aphVIII, transformants gained up to 333-fold higher resistance to paromomycin in comparison to the parent wild-type strain.The heterologous luciferase (gluc) gene of Gaussia princeps, which was previously genetically engineered to match the nuclear codon usage of Chlamydomonas reinhardtii, was used as a co-transformed, unselectable reporter gene. The expression of the co-bombarded gluc gene in transformants and the induction of gluc by heat shock were demonstrated through bioluminescence assays.

CONCLUSION: Stable nuclear transformation of P. morum using the particle bombardment technique is now feasible. Functional expression of heterologous genes is achieved using heterologous flanking sequences from Volvox carteri and Chlamydomonas reinhardtii. The aphVIII gene of the actinobacterium S. rimosus can be used as a selectable marker for transformation experiments in the green alga P. morum. The gluc gene of the marine copepod G. princeps, expressed under control of heterologous promoter elements, represents a suitable reporter gene for monitoring gene expression or for other applications in P. morum.}, } @article {pmid25028340, year = {2014}, author = {Allen, JE and Sutherland, TE}, title = {Host protective roles of type 2 immunity: parasite killing and tissue repair, flip sides of the same coin.}, journal = {Seminars in immunology}, volume = {26}, number = {4}, pages = {329-340}, pmid = {25028340}, issn = {1096-3618}, support = {//Wellcome Trust/United Kingdom ; 095831//Wellcome Trust/United Kingdom ; MR/K01207X/1/MRC_/Medical Research Council/United Kingdom ; MR/J001929/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Cytokines/immunology ; Mice ; Nippostrongylus/*physiology ; Respiratory System/injuries/parasitology ; Strongylida Infections/*immunology/*parasitology ; Wound Healing ; }, abstract = {Metazoan parasites typically induce a type 2 immune response, characterized by T helper 2 (Th2) cells that produce the cytokines IL-4, IL-5 and IL-13 among others. The type 2 response is host protective, reducing the number of parasites either through direct killing in the tissues, or expulsion from the intestine. Type 2 immunity also protects the host against damage mediated by these large extracellular parasites as they migrate through the body. At the center of both the innate and adaptive type 2 immune response, is the IL-4Rα that mediates many of the key effector functions. Here we highlight the striking overlap between the molecules, cells and pathways that mediate both parasite control and tissue repair. We have proposed that adaptive Th2 immunity evolved out of our innate repair pathways to mediate both accelerated repair and parasite control in the face of continual assault from multicellular pathogens. Type 2 cytokines are involved in many aspects of mammalian physiology independent of helminth infection. Therefore understanding the evolutionary relationship between helminth killing and tissue repair should provide new insight into immune mechanisms of tissue protection in the face of physical injury.}, } @article {pmid25026440, year = {2014}, author = {Gawryluk, RM and Chisholm, KA and Pinto, DM and Gray, MW}, title = {Compositional complexity of the mitochondrial proteome of a unicellular eukaryote (Acanthamoeba castellanii, supergroup Amoebozoa) rivals that of animals, fungi, and plants.}, journal = {Journal of proteomics}, volume = {109}, number = {}, pages = {400-416}, doi = {10.1016/j.jprot.2014.07.005}, pmid = {25026440}, issn = {1876-7737}, support = {MOP-4124//Canadian Institutes of Health Research/Canada ; }, mesh = {Acanthamoeba castellanii/genetics/*metabolism ; Animals ; Computational Biology ; Fungi ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/*metabolism ; Plants ; Proteome/*metabolism ; Proteomics ; Protozoan Proteins/*metabolism ; }, abstract = {UNLABELLED: We present a combined proteomic and bioinformatic investigation of mitochondrial proteins from the amoeboid protist Acanthamoeba castellanii, the first such comprehensive investigation in a free-living member of the supergroup Amoebozoa. This protist was chosen both for its phylogenetic position (as a sister to animals and fungi) and its ecological ubiquity and physiological flexibility. We report 1033 A. castellanii mitochondrial protein sequences, 709 supported by mass spectrometry data (676 nucleus-encoded and 33 mitochondrion-encoded), including two previously unannotated mtDNA-encoded proteins, which we identify as highly divergent mitochondrial ribosomal proteins. Other notable findings include duplicate proteins for all of the enzymes of the tricarboxylic acid (TCA) cycle-which, along with the identification of a mitochondrial malate synthase-isocitrate lyase fusion protein, suggests the interesting possibility that the glyoxylate cycle operates in A. castellanii mitochondria. Additionally, the A. castellanii genome encodes an unusually high number (at least 29) of mitochondrion-targeted pentatricopeptide repeat (PPR) proteins, organellar RNA metabolism factors in other organisms. We discuss several key mitochondrial pathways, including DNA replication, transcription and translation, protein degradation, protein import and Fe-S cluster biosynthesis, highlighting similarities and differences in these pathways in other eukaryotes. In compositional and functional complexity, the mitochondrial proteome of A. castellanii rivals that of multicellular eukaryotes.

BIOLOGICAL SIGNIFICANCE: Comprehensive proteomic surveys of mitochondria have been undertaken in a limited number of predominantly multicellular eukaryotes. This phylogenetically narrow perspective constrains and biases our insights into mitochondrial function and evolution, as it neglects protists, which account for most of the evolutionary and functional diversity within eukaryotes. We report here the first comprehensive investigation of the mitochondrial proteome in a member (A. castellanii) of the eukaryotic supergroup Amoebozoa. Through a combination of tandem mass spectrometry (MS/MS) and in silico data mining, we have retrieved 1033 candidate mitochondrial protein sequences, 709 having MS support. These data were used to reconstruct the metabolic pathways and protein complexes of A. castellanii mitochondria, and were integrated with data from other characterized mitochondrial proteomes to augment our understanding of mitochondrial proteome evolution. Our results demonstrate the power of combining direct proteomic and bioinformatic approaches in the discovery of novel mitochondrial proteins, both nucleus-encoded and mitochondrion-encoded, and highlight the compositional complexity of the A. castellanii mitochondrial proteome, which rivals that of animals, fungi and plants.}, } @article {pmid25016582, year = {2014}, author = {Cheatle Jarvela, AM and Brubaker, L and Vedenko, A and Gupta, A and Armitage, BA and Bulyk, ML and Hinman, VF}, title = {Modular evolution of DNA-binding preference of a Tbrain transcription factor provides a mechanism for modifying gene regulatory networks.}, journal = {Molecular biology and evolution}, volume = {31}, number = {10}, pages = {2672-2688}, pmid = {25016582}, issn = {1537-1719}, support = {R01 HG003985/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; DNA/*metabolism ; Evolution, Molecular ; Gene Regulatory Networks ; Molecular Sequence Data ; Phylogeny ; Protein Array Analysis ; Sea Urchins/genetics/*metabolism ; Sequence Analysis, DNA ; Starfish/genetics/*metabolism ; T-Box Domain Proteins/*genetics/*metabolism ; }, abstract = {Gene regulatory networks (GRNs) describe the progression of transcriptional states that take a single-celled zygote to a multicellular organism. It is well documented that GRNs can evolve extensively through mutations to cis-regulatory modules (CRMs). Transcription factor proteins that bind these CRMs may also evolve to produce novelty. Coding changes are considered to be rarer, however, because transcription factors are multifunctional and hence are more constrained to evolve in ways that will not produce widespread detrimental effects. Recent technological advances have unearthed a surprising variation in DNA-binding abilities, such that individual transcription factors may recognize both a preferred primary motif and an additional secondary motif. This provides a source of modularity in function. Here, we demonstrate that orthologous transcription factors can also evolve a changed preference for a secondary binding motif, thereby offering an unexplored mechanism for GRN evolution. Using protein-binding microarray, surface plasmon resonance, and in vivo reporter assays, we demonstrate an important difference in DNA-binding preference between Tbrain protein orthologs in two species of echinoderms, the sea star, Patiria miniata, and the sea urchin, Strongylocentrotus purpuratus. Although both orthologs recognize the same primary motif, only the sea star Tbr also has a secondary binding motif. Our in vivo assays demonstrate that this difference may allow for greater evolutionary change in timing of regulatory control. This uncovers a layer of transcription factor binding divergence that could exist for many pairs of orthologs. We hypothesize that this divergence provides modularity that allows orthologous transcription factors to evolve novel roles in GRNs through modification of binding to secondary sites.}, } @article {pmid25016215, year = {2014}, author = {Zheng, Y and Hsu, FN and Xu, W and Xie, XJ and Ren, X and Gao, X and Ni, JQ and Ji, JY}, title = {A developmental genetic analysis of the lysine demethylase KDM2 mutations in Drosophila melanogaster.}, journal = {Mechanisms of development}, volume = {133}, number = {}, pages = {36-53}, pmid = {25016215}, issn = {1872-6356}, support = {R01 DK095013/DK/NIDDK NIH HHS/United States ; 1R01DK095013/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Chromosome Deletion ; Conserved Sequence ; DNA Transposable Elements ; Drosophila Proteins/chemistry/deficiency/*genetics ; Drosophila melanogaster/*enzymology/*genetics/growth & development ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Gene Knockout Techniques ; Genes, Insect ; Genetic Complementation Test ; Humans ; Jumonji Domain-Containing Histone Demethylases/chemistry/deficiency/*genetics ; Mutation ; Phylogeny ; Protein Structure, Tertiary ; }, abstract = {Post-translational modification of histones plays essential roles in the transcriptional regulation of genes in eukaryotes. Methylation on basic residues of histones is regulated by histone methyltransferases and histone demethylases, and misregulation of these enzymes has been linked to a range of diseases such as cancer. Histone lysine demethylase 2 (KDM2) family proteins have been shown to either promote or suppress tumorigenesis in different human malignancies. However, the roles and regulation of KDM2 in development are poorly understood, and the exact roles of KDM2 in regulating demethylation remain controversial. Since KDM2 proteins are highly conserved in multicellular animals, we analyzed the KDM2 ortholog in Drosophila. We have observed that dKDM2 is a nuclear protein and its level fluctuates during fly development. We generated three deficiency lines that disrupt the dKdm2 locus, and together with 10 transposon insertion lines within the dKdm2 locus, we characterized the developmental defects of these alleles. The alleles of dKdm2 define three phenotypic classes, and the intragenic complementation observed among these alleles and our subsequent analyses suggest that dKDM2 is not required for viability. In addition, loss of dKDM2 appears to have rather weak effects on histone H3 lysine 36 and 4 methylation (H3K36me and H3K4me) in the third instar wandering larvae, and we observed no effect on methylation of H3K9me2, H3K27me2 and H3K27me3 in dKdm2 mutants. Taken together, these genetic, molecular and biochemical analyses suggest that dKDM2 is not required for viability of flies, indicating that dKdm2 is likely redundant with other histone lysine demethylases in regulating normal development in Drosophila.}, } @article {pmid25013378, year = {2014}, author = {Dröge, J and Buczek, D and Suzuki, Y and Makałowski, W}, title = {Amoebozoa possess lineage-specific globin gene repertoires gained by individual horizontal gene transfers.}, journal = {International journal of biological sciences}, volume = {10}, number = {7}, pages = {689-701}, pmid = {25013378}, issn = {1449-2288}, mesh = {Amino Acid Sequence ; Amoebozoa/*genetics ; Evolution, Molecular ; *Gene Transfer, Horizontal ; Genes, Bacterial ; Genes, Protozoan ; Genome, Protozoan ; Globins/chemistry/*genetics ; Molecular Sequence Data ; *Phylogeny ; Sequence Alignment ; Sequence Analysis, Protein ; }, abstract = {The Amoebozoa represent a clade of unicellular amoeboid organisms that display a wide variety of lifestyles, including free-living and parasitic species. For example, the social amoeba Dictyostelium discoideum has the ability to aggregate into a multicellular fruiting body upon starvation, while the pathogenic amoeba Entamoeba histolytica is a parasite of humans. Globins are small heme proteins that are present in almost all extant organisms. Although several genomes of amoebozoan species have been sequenced, little is known about the phyletic distribution of globin genes within this phylum. Only two flavohemoglobins (FHbs) of D. discoideum have been reported and characterized previously while the genomes of Entamoeba species are apparently devoid of globin genes. We investigated eleven amoebozoan species for the presence of globin genes by genomic and phylogenetic in silico analyses. Additional FHb genes were identified in the genomes of four social amoebas and the true slime mold Physarum polycephalum. Moreover, a single-domain globin (SDFgb) of Hartmannella vermiformis, as well as two truncated hemoglobins (trHbs) of Acanthamoeba castellanii were identified. Phylogenetic evidence suggests that these globin genes were independently acquired via horizontal gene transfer from some ancestral bacteria. Furthermore, the phylogenetic tree of amoebozoan FHbs indicates that they do not share a common ancestry and that a transfer of FHbs from bacteria to amoeba occurred multiple times.}, } @article {pmid25009239, year = {2014}, author = {Price, S and Toal, S and Anandan, S}, title = {The TrpA protein of Trichodesmium erythraeum IMS101 is a non-fibril-forming collagen and a component of the outer sheath.}, journal = {Microbiology (Reading, England)}, volume = {160}, number = {Pt 10}, pages = {2148-2156}, doi = {10.1099/mic.0.079475-0}, pmid = {25009239}, issn = {1465-2080}, mesh = {Bacterial Proteins/chemistry/genetics/*metabolism ; Circular Dichroism ; Cluster Analysis ; Collagen/chemistry/genetics/*metabolism ; Cyanobacteria/genetics/*metabolism/*ultrastructure ; Membrane Proteins/chemistry/genetics/*metabolism ; Microscopy, Electron, Scanning ; Models, Molecular ; Phylogeny ; Protein Stability ; Sequence Homology, Amino Acid ; }, abstract = {Collagen molecules are structural in nature and primarily found in eukaryotic, multicellular organisms. Recently, a collagen-like protein, TrpA, was identified and characterized in the marine cyanobacterium Trichodesmium erythraeum IMS 101, and it was shown to be involved in maintaining the structural integrity of the trichomes. The TrpA protein contains one glycine interruption in the otherwise perfectly uninterrupted collagenous domain. In this study, we used phylogenetic analysis to determine that the TrpA protein sequence is most closely associated with non-fibril-forming collagen proteins. Structural modelling and circular dichroism data suggest that the glycine insertion decreases the stability of TrpA compared to uninterrupted collagen sequences. Additionally, scanning electron microscopy revealed that TrpA is expressed entirely on the surface of the trichomes, with no specific pattern of localization. These data indicate that the TrpA protein is part of the outer sheath of this organism. As such, this protein may function to promote adhesion between individual T. erythraeum trichomes, and between this organism and heterotrophic bacteria found in the same environment.}, } @article {pmid25003332, year = {2014}, author = {Geng, S and De Hoff, P and Umen, JG}, title = {Evolution of sexes from an ancestral mating-type specification pathway.}, journal = {PLoS biology}, volume = {12}, number = {7}, pages = {e1001904}, pmid = {25003332}, issn = {1545-7885}, support = {R01 GM078376/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Nucleus/metabolism ; Evolution, Molecular ; Gene Expression Regulation ; Phylogeny ; Reproduction/*genetics ; Sex ; *Sex Chromosomes ; Sex Determination Processes ; Spermatogenesis/genetics ; Volvox/*genetics ; }, abstract = {Male and female sexes have evolved repeatedly in eukaryotes but the origins of dimorphic sexes and their relationship to mating types in unicellular species are not understood. Volvocine algae include isogamous species such as Chlamydomonas reinhardtii, with two equal-sized mating types, and oogamous multicellular species such as Volvox carteri with sperm-producing males and egg-producing females. Theoretical work predicts genetic linkage of a gamete cell-size regulatory gene(s) to an ancestral mating-type locus as a possible step in the evolution of dimorphic gametes, but this idea has not been tested. Here we show that, contrary to predictions, a single conserved mating locus (MT) gene in volvocine algae-MID, which encodes a RWP-RK domain transcription factor-evolved from its ancestral role in C. reinhardtii as a mating-type specifier, to become a determinant of sperm and egg development in V. carteri. Transgenic female V. carteri expressing male MID produced functional sperm packets during sexual development. Transgenic male V. carteri with RNA interference (RNAi)-mediated knockdowns of VcMID produced functional eggs, or self-fertile hermaphrodites. Post-transcriptional controls were found to regulate cell-type-limited expression and nuclear localization of VcMid protein that restricted its activity to nuclei of developing male germ cells and sperm. Crosses with sex-reversed strains uncoupled sex determination from sex chromosome identity and revealed gender-specific roles for male and female mating locus genes in sexual development, gamete fitness and reproductive success. Our data show genetic continuity between the mating-type specification and sex determination pathways of volvocine algae, and reveal evidence for gender-specific adaptations in the male and female mating locus haplotypes of Volvox. These findings will enable a deeper understanding of how a master regulator of mating-type determination in an ancestral unicellular species was reprogrammed to control sexually dimorphic gamete development in a multicellular descendant.}, } @article {pmid24999371, year = {2014}, author = {Desjardins, M and Xie, J and Gurler, H and Muralidhar, GG and Sacks, JD and Burdette, JE and Barbolina, MV}, title = {Versican regulates metastasis of epithelial ovarian carcinoma cells and spheroids.}, journal = {Journal of ovarian research}, volume = {7}, number = {}, pages = {70}, pmid = {24999371}, issn = {1757-2215}, mesh = {Animals ; Carcinoma, Ovarian Epithelial ; Cell Adhesion/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Disease Models, Animal ; Extracellular Matrix ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunophenotyping ; Mice ; Neoplasm Metastasis ; Neoplasms, Glandular and Epithelial/genetics/*metabolism/*pathology ; Ovarian Neoplasms/genetics/*metabolism/*pathology ; Peritoneal Neoplasms/genetics/pathology/secondary ; Peritoneum/metabolism/pathology ; RNA Interference ; Spheroids, Cellular ; Tumor Cells, Cultured ; Up-Regulation ; Versicans/genetics/*metabolism ; }, abstract = {BACKGROUND: Epithelial ovarian carcinoma is a deadly disease characterized by overt peritoneal metastasis. Individual cells and multicellular aggregates, or spheroids, seed these metastases, both commonly found in ascites. Mechanisms that foster spheroid attachment to the peritoneal tissues preceding formation of secondary lesions are largely unknown.

METHODS: Cell culture models of SKOV-3, OVCAR3, OVCAR4, Caov-3, IGROV-1, and A2780 were used. In this report the role of versican was examined in adhesion of EOC spheroids and cells to peritoneal mesothelial cell monolayers in vitro as well as in formation of peritoneal tumors using an in vivo xenograft mouse model.

RESULTS: The data demonstrate that versican is instrumental in facilitating cell and spheroid adhesion to the mesothelial cell monolayers, as its reduction with specific shRNAs led to decreased adhesion. Furthermore, spheroids with reduced expression of versican failed to disaggregate to complete monolayers when seeded atop monolayers of peritoneal mesothelial cells. Failure of spheroids lacking versican to disaggregate as efficiently as controls could be attributed to a reduced cell migration that was observed in the absence of versican expression. Importantly, both spheroids and cells with reduced expression of versican demonstrated significantly impaired ability to generate peritoneal tumors when injected intraperitoneally into athymic nude mice.

CONCLUSIONS: Taken together these data suggest that versican regulates the development of peritoneal metastasis originating from cells and spheroids.}, } @article {pmid24997592, year = {2014}, author = {Biryukova, I and Ye, T and Levashina, E}, title = {Transcriptome-wide analysis of microRNA expression in the malaria mosquito Anopheles gambiae.}, journal = {BMC genomics}, volume = {15}, number = {1}, pages = {557}, pmid = {24997592}, issn = {1471-2164}, mesh = {Animals ; Anopheles/*genetics/metabolism ; Base Sequence ; Chromosomes, Insect/genetics ; Cluster Analysis ; Conserved Sequence ; Female ; Gene Duplication ; Gene Expression Profiling ; Genes, Insect ; Insect Vectors/*genetics/metabolism ; MicroRNAs/*genetics/metabolism ; Multigene Family ; Postprandial Period ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {BACKGROUND: microRNAs (miRNAs) are a highly abundant class of small noncoding regulatory RNAs that post-transcriptionally regulate gene expression in multicellular organisms. miRNAs are involved in a wide range of biological and physiological processes, including the regulation of host immune responses to microbial infections. Small-scale studies of miRNA expression in the malaria mosquito Anopheles gambiae have been reported, however no comprehensive analysis of miRNAs has been performed so far.

RESULTS: Using small RNA sequencing, we characterized de novo A. gambiae miRNA repertoire expressed in adult sugar- and blood-fed females. We provided transcriptional evidences for 123 miRNAs, including 58 newly identified miRNAs. Out of the newly described miRNAs, 19 miRNAs are homologs to known miRNAs in other insect species and 17 miRNAs share sequence similarity restricted to the seed sequence. The remaining 21 novel miRNAs displayed no obvious sequence homology with known miRNAs. Detailed bioinformatics analysis of the mature miRNAs revealed a sequence variation occurring at their 5'-end and leading to functional seed shifting in more than 5% of miRNAs. We also detected significant sequence heterogeneity at the 3'-ends of the mature miRNAs, mostly due to imprecise processing and post-transcriptional modifications. Comparative analysis of arm-switching events revealed the existence of species-specific production of dominant mature miRNAs induced by blood feeding in mosquitoes. We also identified new conserved and fragmented miRNA clusters and A. gambiae-specific miRNA gene duplication. Using miRNA expression profiling, we identified the differentially expressed miRNAs at an early time point after regular blood feeding and after infection with the rodent malaria parasite Plasmodium berghei. Significant changes were detected in the expression levels of 4 miRNAs in blood-fed mosquitoes, whereas 6 miRNAs were significantly upregulated after P. berghei infection.

CONCLUSIONS: In the current study, we performed the first systematic analysis of miRNAs in A. gambiae. We provided new insights on mature miRNA sequence diversity and functional shifts in the mosquito miRNA evolution. We identified a set of the differentially expressed miRNAs that respond to normal and infectious blood meals. The extended set of Anopheles miRNAs and their isoforms provides a basis for further experimental studies of miRNA expression patterns and biological functions in A. gambiae.}, } @article {pmid24984201, year = {2015}, author = {Kostrouchova, M and Kostrouch, Z}, title = {Nuclear receptors in nematode development: Natural experiments made by a phylum.}, journal = {Biochimica et biophysica acta}, volume = {1849}, number = {2}, pages = {224-237}, doi = {10.1016/j.bbagrm.2014.06.016}, pmid = {24984201}, issn = {0006-3002}, mesh = {Animals ; Caenorhabditis elegans/embryology/genetics ; Conserved Sequence ; *Evolution, Molecular ; Nematoda/*embryology/genetics/growth & development ; Receptors, Cytoplasmic and Nuclear/classification/*physiology ; }, abstract = {The development of complex multicellular organisms is dependent on regulatory decisions that are necessary for the establishment of specific differentiation and metabolic cellular states. Nuclear receptors (NRs) form a large family of transcription factors that play critical roles in the regulation of development and metabolism of Metazoa. Based on their DNA binding and ligand binding domains, NRs are divided into eight NR subfamilies from which representatives of six subfamilies are present in both deuterostomes and protostomes indicating their early evolutionary origin. In some nematode species, especially in Caenorhabditis, the family of NRs expanded to a large number of genes strikingly exceeding the number of NR genes in vertebrates or insects. Nematode NRs, including the multiplied Caenorhabditis genes, show clear relation to vertebrate and insect homologues belonging to six of the eight main NR subfamilies. This review summarizes advances in research of nematode NRs and their developmental functions. Nematode NRs can reveal evolutionarily conserved mechanisms that regulate specific developmental and metabolic processes as well as new regulatory adaptations. They represent the results of a large number of natural experiments with structural and functional potential of NRs for the evolution of the phylum. The conserved and divergent character of nematode NRs adds a new dimension to our understanding of the general biology of regulation by NRs. This article is part of a Special Issue entitled: Nuclear receptors in animal development.}, } @article {pmid24983513, year = {2014}, author = {Beemelmanns, C and Woznica, A and Alegado, RA and Cantley, AM and King, N and Clardy, J}, title = {Synthesis of the rosette-inducing factor RIF-1 and analogs.}, journal = {Journal of the American Chemical Society}, volume = {136}, number = {29}, pages = {10210-10213}, pmid = {24983513}, issn = {1520-5126}, support = {/HHMI/Howard Hughes Medical Institute/United States ; GM086258/GM/NIGMS NIH HHS/United States ; R01 GM099533/GM/NIGMS NIH HHS/United States ; T32 GM007127/GM/NIGMS NIH HHS/United States ; R01 GM086258/GM/NIGMS NIH HHS/United States ; GM099533/GM/NIGMS NIH HHS/United States ; }, mesh = {Alkanesulfonic Acids/*chemical synthesis/chemistry/pharmacology ; Bacteroidetes/*metabolism ; Choanoflagellata/*drug effects/growth & development/ultrastructure ; Lipids/*chemical synthesis/chemistry/pharmacology ; Molecular Structure ; *Morphogenesis ; Stereoisomerism ; }, abstract = {Studies on the origin of animal multicellularity have increasingly focused on one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. Single cells of S. rosetta can develop into multicellular rosette-shaped colonies through a process of incomplete cytokinesis. Unexpectedly, the initiation of rosette development requires bacterially produced small molecules. Previously, our laboratories reported the planar structure and femtomolar rosette-inducing activity of one rosette-inducing small molecule, dubbed rosette-inducing factor 1 (RIF-1), produced by the Gram-negative Bacteroidetes bacterium Algoriphagus machipongonensis. RIF-1 belongs to the small and poorly explored class of sulfonolipids. Here, we report a modular total synthesis of RIF-1 stereoisomers and structural analogs. Rosette-induction assays using synthetic RIF-1 stereoisomers and naturally occurring analogs defined the absolute stereochemistry of RIF-1 and revealed a remarkably restrictive set of structural requirements for inducing rosette development.}, } @article {pmid24981559, year = {2015}, author = {Peng, G and Shi, X and Kadowaki, T}, title = {Evolution of TRP channels inferred by their classification in diverse animal species.}, journal = {Molecular phylogenetics and evolution}, volume = {84}, number = {}, pages = {145-157}, doi = {10.1016/j.ympev.2014.06.016}, pmid = {24981559}, issn = {1095-9513}, mesh = {Animals ; *Biological Evolution ; Invertebrates/genetics ; *Phylogeny ; Sequence Analysis, DNA ; Transient Receptor Potential Channels/*classification ; }, abstract = {The functions of TRP channels have primarily been characterized in model organisms within a limited evolutionary context. We thus characterize the TRP channels in choanoflagellate, sponge, Cnidaria, Lophotrochozoa, and arthropods to understand how they emerged during early evolution of animals and have changed during diversification of various species. As previously reported, five metazoan TRP subfamily members (TRPA, TRPC, TRPM, TRPML, and TRPV) were identified in choanoflagellates, demonstrating that they evolved before the emergence of multicellular animals. TRPN was identified in Hydra magnipapillata, and therefore emerged in the last common ancestor of Cnidaria-Bilateria. A novel subfamily member (TRPVL) was identified in Cnidaria and Capitella teleta, indicating that it was present in the last common ancestor of Cnidaria-Bilateria but has since been lost in most bilaterians. The characterization of arthropod TRP channels revealed that Daphnia pulex and insects have specifically expanded the TRPA subfamily, which diverged from the ancient TRPA1 channel gene. The diversity of TRPA channels except TRPA1 was detectable even within a single insect family, namely the ant lineage. The present study demonstrates the evolutionary history of TRP channel genes, which may have diverged in conjunction with the specific habitats and life histories of individual species.}, } @article {pmid24976004, year = {2014}, author = {Kennedy, P and Uller, T and Helanterä, H}, title = {Are ant supercolonies crucibles of a new major transition in evolution?.}, journal = {Journal of evolutionary biology}, volume = {27}, number = {9}, pages = {1784-1796}, doi = {10.1111/jeb.12434}, pmid = {24976004}, issn = {1420-9101}, mesh = {Animals ; *Ants ; *Behavior, Animal ; *Biological Evolution ; Genetic Fitness ; Models, Biological ; Selection, Genetic ; }, abstract = {The biological hierarchy of genes, cells, organisms and societies is a fundamental reality in the living world. This hierarchy of entities did not arise ex nihilo at the origin of life, but rather has been serially generated by a succession of critical events known as 'evolutionary transitions in individuality' (ETIs). Given the sequential nature of ETIs, it is natural to look for candidates to form the next hierarchical tier. We analyse claims that these candidates are found among 'supercolonies', ant populations in which discrete nests cooperate as part of a wider collective, in ways redolent of cells in a multicellular organism. Examining earlier empirical work and new data within the recently proposed 'Darwinian space' framework, we offer a novel analysis of the evolutionary status of supercolonies and show how certain key conditions might be satisfied in any future process transforming these collaborative networks into true Darwinian individuals.}, } @article {pmid24974231, year = {2014}, author = {Wakimoto, T and Egami, Y and Nakashima, Y and Wakimoto, Y and Mori, T and Awakawa, T and Ito, T and Kenmoku, H and Asakawa, Y and Piel, J and Abe, I}, title = {Calyculin biogenesis from a pyrophosphate protoxin produced by a sponge symbiont.}, journal = {Nature chemical biology}, volume = {10}, number = {8}, pages = {648-655}, pmid = {24974231}, issn = {1552-4469}, mesh = {Animals ; Antineoplastic Agents/pharmacology ; Diphosphates/*metabolism ; Drug Screening Assays, Antitumor ; HeLa Cells ; Humans ; Leukemia/drug therapy/pathology ; Marine Toxins ; Metagenome ; Mice ; Molecular Sequence Data ; Multigene Family ; Organophosphates/chemistry/metabolism/pharmacology ; Oxazoles/chemistry/*metabolism/pharmacology ; Phosphorylation ; Phosphotransferases/genetics/metabolism ; Phylogeny ; Polyketide Synthases/genetics ; Porifera/*microbiology/physiology ; RNA, Ribosomal, 16S ; Symbiosis ; }, abstract = {The Japanese marine sponge Discodermia calyx contains a major cytotoxic compound, calyculin A, which exhibits selective inhibition of protein phosphatases 1 and 2A. It has long been used as a chemical tool to evaluate intracellular signal transduction regulated by reversible protein phosphorylation. We describe the identification of the biosynthetic gene cluster of calyculin A by a metagenome mining approach. Single-cell analysis revealed that the gene cluster originates in the symbiont bacterium 'Candidatus Entotheonella' sp. A phosphotransferase encoded in the gene cluster deactivated calyculin A to produce a newly discovered diphosphate, which was actually the biosynthetic end product. The diphosphate had been previously overlooked because of the enzymatic dephosphorylation that occurred in response to sponge tissue disruption. Our work presents what is to our knowledge the first evidence for the biosynthetic process of calyculin A along with a notable phosphorylation-dephosphorylation mechanism to regulate toxicity, suggesting activated chemical defense in the most primitive of all multicellular animals.}, } @article {pmid24973266, year = {2015}, author = {Smith, JA and Leonardi, T and Huang, B and Iraci, N and Vega, B and Pluchino, S}, title = {Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases.}, journal = {Biogerontology}, volume = {16}, number = {2}, pages = {147-185}, pmid = {24973266}, issn = {1573-6768}, support = {260511/ERC_/European Research Council/International ; }, mesh = {Aging/*physiology ; Animals ; Brain/*metabolism ; Brain Diseases/*metabolism ; Cell Communication/*physiology ; Extracellular Vesicles/*metabolism ; Humans ; *Models, Biological ; }, abstract = {Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs-or specific EV cargoes-are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases.}, } @article {pmid24966537, year = {2014}, author = {Saad, II and Saha, SB and Thomas, G}, title = {The RAS subfamily Evolution - tracing evolution for its utmost exploitation.}, journal = {Bioinformation}, volume = {10}, number = {5}, pages = {293-298}, pmid = {24966537}, issn = {0973-2063}, abstract = {In the development of multicellularity, signaling proteins has played a very important role. Among them, RAS family is one of the most widely studied protein family. However, evolutionary analysis has been carried out mainly on super family level leaving sub family information in scanty. Thus, a subfamily evolutionary study on RAS evolutionary expansion is imperative as it will aid in better drug designing against dreadful diseases like Cancer and other developmental diseases. The present study was aimed to understand RAS evolution on both holistic as well as reductive level. All human RAS family genes and protein were subjected to BLAST tools to find orthologs and paralogs with different parameters followed by phylogenetic tree generation. Our results clearly showed that H-RAS is the most primitive RAS in higher eukaryotes and then diverged into other RAS family members due to different gene modification events. Furthermore, a site specific selection pressure analysis was carried out using SELECTON server which showed that H-RAS, M-RAS and N-RAS are evolving faster than K-RAS and R-RAS. Thus, the results ascertain a new ground to cancer biologists to exploit negatively selected K-RAS and R-RAS as potent drug targets in cancer therapeutics.}, } @article {pmid24960463, year = {2014}, author = {Cuadrat, RR and da Serra Cruz, SM and Tschoeke, DA and Silva, E and Tosta, F and Jucá, H and Jardim, R and Campos, ML and Mattoso, M and Dávila, AM}, title = {An orthology-based analysis of pathogenic protozoa impacting global health: an improved comparative genomics approach with prokaryotes and model eukaryote orthologs.}, journal = {Omics : a journal of integrative biology}, volume = {18}, number = {8}, pages = {524-538}, pmid = {24960463}, issn = {1557-8100}, mesh = {Archaea/genetics ; Bacteria/genetics ; Databases, Protein ; Entamoeba histolytica/genetics ; *Genes, Protozoan ; Genomics ; Global Health ; Humans ; Leishmania major/genetics ; Molecular Sequence Annotation ; Phylogeny ; Plasmodium falciparum/genetics ; Protozoan Proteins/*genetics ; Sequence Homology, Nucleic Acid ; Trypanosoma brucei brucei/genetics ; Trypanosoma cruzi/genetics ; }, abstract = {A key focus in 21(st) century integrative biology and drug discovery for neglected tropical and other diseases has been the use of BLAST-based computational methods for identification of orthologous groups in pathogenic organisms to discern orthologs, with a view to evaluate similarities and differences among species, and thus allow the transfer of annotation from known/curated proteins to new/non-annotated ones. We used here a profile-based sensitive methodology to identify distant homologs, coupled to the NCBI's COG (Unicellular orthologs) and KOG (Eukaryote orthologs), permitting us to perform comparative genomics analyses on five protozoan genomes. OrthoSearch was used in five protozoan proteomes showing that 3901 and 7473 orthologs can be identified by comparison with COG and KOG proteomes, respectively. The core protozoa proteome inferred was 418 Protozoa-COG orthologous groups and 704 Protozoa-KOG orthologous groups: (i) 31.58% (132/418) belongs to the category J (translation, ribosomal structure, and biogenesis), and 9.81% (41/418) to the category O (post-translational modification, protein turnover, chaperones) using COG; (ii) 21.45% (151/704) belongs to the categories J, and 13.92% (98/704) to the O using KOG. The phylogenomic analysis showed four well-supported clades for Eukarya, discriminating Multicellular [(i) human, fly, plant and worm] and Unicellular [(ii) yeast, (iii) fungi, and (iv) protozoa] species. These encouraging results attest to the usefulness of the profile-based methodology for comparative genomics to accelerate semi-automatic re-annotation, especially of the protozoan proteomes. This approach may also lend itself for applications in global health, for example, in the case of novel drug target discovery against pathogenic organisms previously considered difficult to research with traditional drug discovery tools.}, } @article {pmid24954141, year = {2014}, author = {Vostarek, F and Sankova, B and Sedmera, D}, title = {Studying dynamic events in the developing myocardium.}, journal = {Progress in biophysics and molecular biology}, volume = {115}, number = {2-3}, pages = {261-269}, doi = {10.1016/j.pbiomolbio.2014.06.002}, pmid = {24954141}, issn = {1873-1732}, mesh = {Action Potentials/physiology ; Animals ; Body Surface Potential Mapping/*methods ; Calcium Signaling/*physiology ; Heart Conduction System/*embryology/*physiology ; Humans ; Myocytes, Cardiac/*physiology ; Neural Conduction/physiology ; Voltage-Sensitive Dye Imaging/*methods ; }, abstract = {Differentiation and conduction properties of the cardiomyocytes are critically dependent on physical conditioning both in vitro and in vivo. Historically, various techniques were introduced to study dynamic events such as electrical currents and changes in ionic concentrations in live cells, multicellular preparations, or entire hearts. Here we review this technological progress demonstrating how each improvement in spatial or temporal resolution provided answers to old and provoked new questions. We further demonstrate how high-speed optical mapping of voltage and calcium can uncover pacemaking potential within the outflow tract myocardium, providing a developmental explanation of ectopic beats originating from this region in the clinical settings.}, } @article {pmid24935989, year = {2014}, author = {Zamer, WE and Scheiner, SM}, title = {A conceptual framework for organismal biology: linking theories, models, and data.}, journal = {Integrative and comparative biology}, volume = {54}, number = {5}, pages = {736-756}, doi = {10.1093/icb/icu075}, pmid = {24935989}, issn = {1557-7023}, mesh = {Archaea/*physiology ; *Bacterial Physiological Phenomena ; Biological Evolution ; *Biology ; Cell Physiological Phenomena ; Ecology ; Eukaryota/*physiology ; Genetic Phenomena ; *Models, Biological ; *Virus Physiological Phenomena ; }, abstract = {Implicit or subconscious theory is especially common in the biological sciences. Yet, theory plays a variety of roles in scientific inquiry. First and foremost, it determines what does and does not count as a valid or interesting question or line of inquiry. Second, theory determines the background assumptions within which inquiries are pursued. Third, theory provides linkages among disciplines. For these reasons, it is important and useful to develop explicit theories for biology. A general theory of organisms is developed, which includes 10 fundamental principles that apply to all organisms, and 6 that apply to multicellular organisms only. The value of a general theory comes from its utility to help guide the development of more specific theories and models. That process is demonstrated by examining two domains: ecoimmunology and development. For the former, a constitutive theory of ecoimmunology is presented, and used to develop a specific model that explains energetic trade-offs that may result from an immunological response of a host to a pathogen. For the latter, some of the issues involved in trying to devise a constitutive theory that covers all of development are explored, and a more narrow theory of phenotypic novelty is presented. By its very nature, little of a theory of organisms will be new. Rather, the theory presented here is a formal expression of nearly two centuries of conceptual advances and practice in research. Any theory is dynamic and subject to debate and change. Such debate will occur as part of the present, initial formulation, as the ideas presented here are refined. The very process of debating the form of the theory acts to clarify thinking. The overarching goal is to stimulate debate about the role of theory in the study of organisms, and thereby advance our understanding of them.}, } @article {pmid24934091, year = {2014}, author = {Eguale, T and Marshall, J and Molla, B and Bhatiya, A and Gebreyes, WA and Engidawork, E and Asrat, D and Gunn, JS}, title = {Association of multicellular behaviour and drug resistance in Salmonella enterica serovars isolated from animals and humans in Ethiopia.}, journal = {Journal of applied microbiology}, volume = {117}, number = {4}, pages = {961-971}, pmid = {24934091}, issn = {1365-2672}, support = {R01 AI066208/AI/NIAID NIH HHS/United States ; D43 TW008650/TW/FIC NIH HHS/United States ; 043TW008650/TW/FIC NIH HHS/United States ; R56 AI109002/AI/NIAID NIH HHS/United States ; AI066208/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Biofilms/growth & development ; Cellulose/metabolism ; Drug Resistance, Multiple, Bacterial/genetics ; Ethiopia ; Genomic Islands ; Humans ; Integrons/genetics ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Salmonella Infections/*microbiology ; Salmonella Infections, Animal/*microbiology ; Salmonella enterica/*classification/genetics/*isolation & purification/physiology ; }, abstract = {AIMS: To determine the association between multicellular behaviour, integron status and antibiotic resistance among 87 Ethiopian Salmonella enterica isolates of animal and human origin.

METHODS AND RESULTS: Isolates were characterized for their biofilm forming ability, antimicrobial susceptibility and the presence and characteristics of a class 1 integron and Salmonella genomic island 1 (SGI1). The majority of isolates grown at environmental temperatures (20°C) exhibited robust biofilm formation (72·4%) and displayed RDAR colony morphology on Congo red agar plates. The presence of a class 1 integron correlated with the extent of drug resistance and ability to exhibit multicellular behaviour.

CONCLUSIONS: Although cellulose production and RDAR morphology correlated with increased multicellular behaviour, neither was required for biofilm formation. Contrary to previous reports, colony morphology was generally consistent within a serovar. No integrons were detected in isolates deficient for multicellular behaviour, indicating a potential role of bacterial community formation in transfer of genetic elements among environmental isolates.

Infection by Salm. enterica is a major public health problem worldwide. The dominance of multidrug resistance and multicellular behaviour in Salmonella isolates of Ethiopian origin highlights a need for integrated surveillance and further detailed phenotypic and molecular studies of isolates from this region.}, } @article {pmid24927538, year = {2014}, author = {McKay, CP}, title = {Requirements and limits for life in the context of exoplanets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {35}, pages = {12628-12633}, pmid = {24927538}, issn = {1091-6490}, mesh = {Animals ; Atmosphere/chemistry ; Brachyura ; Carbon/chemistry ; *Exobiology ; Extraterrestrial Environment/*chemistry ; *Hydrothermal Vents ; Light ; *Origin of Life ; *Photosynthesis ; Solar System ; Temperature ; *Water ; }, abstract = {The requirements for life on Earth, its elemental composition, and its environmental limits provide a way to assess the habitability of exoplanets. Temperature is key both because of its influence on liquid water and because it can be directly estimated from orbital and climate models of exoplanetary systems. Life can grow and reproduce at temperatures as low as -15 °C, and as high as 122 °C. Studies of life in extreme deserts show that on a dry world, even a small amount of rain, fog, snow, and even atmospheric humidity can be adequate for photosynthetic production producing a small but detectable microbial community. Life is able to use light at levels less than 10(-5) of the solar flux at Earth. UV or ionizing radiation can be tolerated by many microorganisms at very high levels and is unlikely to be life limiting on an exoplanet. Biologically available nitrogen may limit habitability. Levels of O2 over a few percent on an exoplanet would be consistent with the presence of multicellular organisms and high levels of O2 on Earth-like worlds indicate oxygenic photosynthesis. Other factors such as pH and salinity are likely to vary and not limit life over an entire planet or moon.}, } @article {pmid24910306, year = {2014}, author = {Petralia, RS and Mattson, MP and Yao, PJ}, title = {Aging and longevity in the simplest animals and the quest for immortality.}, journal = {Ageing research reviews}, volume = {16}, number = {}, pages = {66-82}, pmid = {24910306}, issn = {1872-9649}, support = {ZIC DC000081-01//Intramural NIH HHS/United States ; }, mesh = {Age Factors ; Aging/*physiology ; Animals ; Biological Evolution ; Ciliophora/physiology ; Cnidaria/physiology ; Humans ; Hydra/physiology ; Invertebrates/*physiology ; *Longevity ; Platyhelminths/physiology ; Porifera/physiology ; Species Specificity ; Yeasts/physiology ; }, abstract = {Here we review the examples of great longevity and potential immortality in the earliest animal types and contrast and compare these to humans and other higher animals. We start by discussing aging in single-celled organisms such as yeast and ciliates, and the idea of the immortal cell clone. Then we describe how these cell clones could become organized into colonies of different cell types that lead to multicellular animal life. We survey aging and longevity in all of the basal metazoan groups including ctenophores (comb jellies), sponges, placozoans, cnidarians (hydras, jellyfish, corals and sea anemones) and myxozoans. Then we move to the simplest bilaterian animals (with a head, three body cell layers, and bilateral symmetry), the two phyla of flatworms. A key determinant of longevity and immortality in most of these simple animals is the large numbers of pluripotent stem cells that underlie the remarkable abilities of these animals to regenerate and rejuvenate themselves. Finally, we discuss briefly the evolution of the higher bilaterians and how longevity was reduced and immortality lost due to attainment of greater body complexity and cell cycle strategies that protect these complex organisms from developing tumors. We also briefly consider how the evolution of multiple aging-related mechanisms/pathways hinders our ability to understand and modify the aging process in higher organisms.}, } @article {pmid24907565, year = {2014}, author = {Blackstone, NW}, title = {sAC as a model for understanding the impact of endosymbiosis on cell signaling.}, journal = {Biochimica et biophysica acta}, volume = {1842}, number = {12 Pt B}, pages = {2548-2554}, doi = {10.1016/j.bbadis.2014.05.037}, pmid = {24907565}, issn = {0006-3002}, mesh = {Adenylyl Cyclases/*metabolism ; Biological Evolution ; Humans ; *Signal Transduction ; *Symbiosis ; }, abstract = {As signaling pathways evolve, selection for new functions guides the co-option of existing material. Major transitions in the history of life, including the evolution of eukaryotes and multicellularity, exemplify this process. These transitions provided both strong selection and a plenitude of available material for the evolution of signaling pathways. Mechanisms that evolved to mediate conflict during the evolution of eukaryotes may subsequently have been co-opted during the many independent derivations of multicellularity. The soluble adenylyl cyclase (sAC) signaling pathway illustrates this hypothesis. Class III adenylyl cyclases, which include sAC, are found in bacteria, including the α-proteobacteria. These adenylyl cyclases are the only ones present in eukaryotes but appear to be absent in archaeans. This pattern suggests that the mitochondrial endosymbiosis brought sAC signaling to eukaryotes as part of an intact module. After transfer to the proto-nuclear genome, this module was then co-opted into numerous new functions. In the evolution of eukaryotes, sAC signaling may have mediated conflicts by maintaining metabolic homeostasis. In the evolution of multicellularity, in different lineages sAC may have been co-opted into parallel tasks originally related to conflict mediation. Elucidating the history of the sAC pathway may be relatively straightforward because it is ubiquitous and linked to near universal metabolic by-products (CO2/HCO(3)(-)). Other signaling pathways (e.g., those involving STAT and VEGF) present a greater challenge but may suggest a complementary pattern. The impact of the mitochondrial endosymbiosis on cell signaling may thus have been profound. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease.}, } @article {pmid24904645, year = {2014}, author = {Lauc, G and Krištić, J and Zoldoš, V}, title = {Glycans - the third revolution in evolution.}, journal = {Frontiers in genetics}, volume = {5}, number = {}, pages = {145}, pmid = {24904645}, issn = {1664-8021}, abstract = {The development and maintenance of a complex organism composed of trillions of cells is an extremely complex task. At the molecular level every process requires a specific molecular structures to perform it, thus it is difficult to imagine how less than tenfold increase in the number of genes between simple bacteria and higher eukaryotes enabled this quantum leap in complexity. In this perspective article we present the hypothesis that the invention of glycans was the third revolution in evolution (the appearance of nucleic acids and proteins being the first two), which enabled the creation of novel molecular entities that do not require a direct genetic template. Contrary to proteins and nucleic acids, which are made from a direct DNA template, glycans are product of a complex biosynthetic pathway affected by hundreds of genetic and environmental factors. Therefore glycans enable adaptive response to environmental changes and, unlike other epiproteomic modifications, which act as off/on switches, glycosylation significantly contributes to protein structure and enables novel functions. The importance of glycosylation is evident from the fact that nearly all proteins invented after the appearance of multicellular life are composed of both polypeptide and glycan parts.}, } @article {pmid24901223, year = {2014}, author = {Kuhn, M and Hyman, AA and Beyer, A}, title = {Coiled-coil proteins facilitated the functional expansion of the centrosome.}, journal = {PLoS computational biology}, volume = {10}, number = {6}, pages = {e1003657}, pmid = {24901223}, issn = {1553-7358}, mesh = {Algorithms ; Animals ; Centrosome/chemistry/*physiology ; Computational Biology ; Fungi ; Humans ; Phylogeny ; Protein Interaction Maps/*physiology ; Proteins/*chemistry/*classification ; }, abstract = {Repurposing existing proteins for new cellular functions is recognized as a main mechanism of evolutionary innovation, but its role in organelle evolution is unclear. Here, we explore the mechanisms that led to the evolution of the centrosome, an ancestral eukaryotic organelle that expanded its functional repertoire through the course of evolution. We developed a refined sequence alignment technique that is more sensitive to coiled coil proteins, which are abundant in the centrosome. For proteins with high coiled-coil content, our algorithm identified 17% more reciprocal best hits than BLAST. Analyzing 108 eukaryotic genomes, we traced the evolutionary history of centrosome proteins. In order to assess how these proteins formed the centrosome and adopted new functions, we computationally emulated evolution by iteratively removing the most recently evolved proteins from the centrosomal protein interaction network. Coiled-coil proteins that first appeared in the animal-fungi ancestor act as scaffolds and recruit ancestral eukaryotic proteins such as kinases and phosphatases to the centrosome. This process created a signaling hub that is crucial for multicellular development. Our results demonstrate how ancient proteins can be co-opted to different cellular localizations, thereby becoming involved in novel functions.}, } @article {pmid24895293, year = {2014}, author = {Ollivaux, C and Soyez, D and Toullec, JY}, title = {Biogenesis of D-amino acid containing peptides/proteins: where, when and how?.}, journal = {Journal of peptide science : an official publication of the European Peptide Society}, volume = {20}, number = {8}, pages = {595-612}, doi = {10.1002/psc.2637}, pmid = {24895293}, issn = {1099-1387}, mesh = {Alanine Racemase/metabolism ; Amino Acids/*chemistry ; Animals ; Anura ; Peptides/*chemistry ; Protein Processing, Post-Translational ; Ranidae ; Spiders ; Stereoisomerism ; Substrate Specificity ; }, abstract = {Peptides and proteins are chiral molecules with their structure determined by the composition and configuration of the amino acids constituting them. Natural amino acids (except glycine) display two chiral types (l- and d-enantiomers). For example, the presence of octopine, a derivative of l-arginine and d-alanine in octopus, or peptidyl poly-d-glutamic acid in a bacterial cell wall was demonstrated in the 1920s and 1930s, respectively. Nevertheless, an old dogma in biology was that proteins (in a strict sense) are composed of amino acids in the l-configuration exclusively, until a d-alanyl residue was reported in a frog skin opioid peptide in the early 1980s, and since, numerous d-amino acid containing peptides (DAACPs) have been discovered in multicellular organisms. Several hypotheses may be formulated to explain the origin of a d-residue in the peptide/protein chain. It may result from different mechanisms such as incorporation of a d-amino acid, non-enzymatic racemisation associated with ageing or diseases and enzymatic posttranslational modification. In the last case, the DAACPs are synthesised via a ribosome-dependent manner, and a normal codon for l-amino acid is present in the mRNA at the position where the d-residue is processed in the mature peptide by peptidyl aminoacyl l-d isomerisation, a peculiar and subtle posttranslational modification. In this review, the different pathways of biogenesis of DAACPs not only in bacteria but also in multicellular organisms are discussed, along with the description of the cellular specificity, the enzyme specificity and the substrate specificity of peptidyl aminoacyl l-d isomerisation.}, } @article {pmid24890266, year = {2014}, author = {Storch, D and Menzel, L and Frickenhaus, S and Pörtner, HO}, title = {Climate sensitivity across marine domains of life: limits to evolutionary adaptation shape species interactions.}, journal = {Global change biology}, volume = {20}, number = {10}, pages = {3059-3067}, doi = {10.1111/gcb.12645}, pmid = {24890266}, issn = {1365-2486}, mesh = {Acclimatization/physiology ; *Adaptation, Physiological ; *Aquatic Organisms ; Archaea ; Bacteria ; *Biological Evolution ; *Climate Change ; *Ecosystem ; Eukaryota ; Hot Temperature ; Oceans and Seas ; Oxygen/metabolism ; }, abstract = {Organisms in all domains, Archaea, Bacteria, and Eukarya will respond to climate change with differential vulnerabilities resulting in shifts in species distribution, coexistence, and interactions. The identification of unifying principles of organism functioning across all domains would facilitate a cause and effect understanding of such changes and their implications for ecosystem shifts. For example, the functional specialization of all organisms in limited temperature ranges leads us to ask for unifying functional reasons. Organisms also specialize in either anoxic or various oxygen ranges, with animals and plants depending on high oxygen levels. Here, we identify thermal ranges, heat limits of growth, and critically low (hypoxic) oxygen concentrations as proxies of tolerance in a meta-analysis of data available for marine organisms, with special reference to domain-specific limits. For an explanation of the patterns and differences observed, we define and quantify a proxy for organismic complexity across species from all domains. Rising complexity causes heat (and hypoxia) tolerances to decrease from Archaea to Bacteria to uni- and then multicellular Eukarya. Within and across domains, taxon-specific tolerance limits likely reflect ultimate evolutionary limits of its species to acclimatization and adaptation. We hypothesize that rising taxon-specific complexities in structure and function constrain organisms to narrower environmental ranges. Low complexity as in Archaea and some Bacteria provide life options in extreme environments. In the warmest oceans, temperature maxima reach and will surpass the permanent limits to the existence of multicellular animals, plants and unicellular phytoplankter. Smaller, less complex unicellular Eukarya, Bacteria, and Archaea will thus benefit and predominate even more in a future, warmer, and hypoxic ocean.}, } @article {pmid24887200, year = {2014}, author = {Stewart, JE}, title = {The direction of evolution: the rise of cooperative organization.}, journal = {Bio Systems}, volume = {123}, number = {}, pages = {27-36}, doi = {10.1016/j.biosystems.2014.05.006}, pmid = {24887200}, issn = {1872-8324}, mesh = {Animals ; *Biodiversity ; *Biological Evolution ; Conservation of Energy Resources/trends ; Ecosystem ; *Environment ; Eukaryotic Cells/metabolism/physiology ; *Genetic Variation ; Humans ; Prokaryotic Cells/metabolism/physiology ; }, abstract = {Two great trends are evident in the evolution of life on Earth: towards increasing diversification and towards increasing integration. Diversification has spread living processes across the planet, progressively increasing the range of environments and free energy sources exploited by life. Integration has proceeded through a stepwise process in which living entities at one level are integrated into cooperative groups that become larger-scale entities at the next level, and so on, producing cooperative organizations of increasing scale (for example, cooperative groups of simple cells gave rise to the more complex eukaryote cells, groups of these gave rise to multi-cellular organisms, and cooperative groups of these organisms produced animal societies). The trend towards increasing integration has continued during human evolution with the progressive increase in the scale of human groups and societies. The trends towards increasing diversification and integration are both driven by selection. An understanding of the trajectory and causal drivers of the trends suggests that they are likely to culminate in the emergence of a global entity. This entity would emerge from the integration of the living processes, matter, energy and technology of the planet into a global cooperative organization. Such an integration of the results of previous diversifications would enable the global entity to exploit the widest possible range of resources across the varied circumstances of the planet. This paper demonstrates that it's case for directionality meets the tests and criticisms that have proven fatal to previous claims for directionality in evolution.}, } @article {pmid24885189, year = {2014}, author = {Ritter, A and Dittami, SM and Goulitquer, S and Correa, JA and Boyen, C and Potin, P and Tonon, T}, title = {Transcriptomic and metabolomic analysis of copper stress acclimation in Ectocarpus siliculosus highlights signaling and tolerance mechanisms in brown algae.}, journal = {BMC plant biology}, volume = {14}, number = {}, pages = {116}, pmid = {24885189}, issn = {1471-2229}, mesh = {Acclimatization/drug effects/*genetics ; Algal Proteins/metabolism ; Amino Acids/metabolism ; Chromatography, High Pressure Liquid ; Cluster Analysis ; Copper/*toxicity ; Discriminant Analysis ; Down-Regulation/drug effects/genetics ; Fatty Acids/metabolism ; Gas Chromatography-Mass Spectrometry ; Gene Expression Profiling ; Humans ; Least-Squares Analysis ; Metabolic Networks and Pathways/drug effects/genetics ; Metabolome/*drug effects/genetics ; Metabolomics ; Oxidative Stress/drug effects/genetics ; Oxylipins/metabolism ; Phaeophyceae/drug effects/*genetics/*physiology ; Photosynthesis/drug effects/genetics ; Phylogeny ; Signal Transduction/drug effects/*genetics ; Stress, Physiological/drug effects/*genetics ; Transcriptome/*drug effects ; Up-Regulation/drug effects/genetics ; }, abstract = {BACKGROUND: Brown algae are sessile macro-organisms of great ecological relevance in coastal ecosystems. They evolved independently from land plants and other multicellular lineages, and therefore hold several original ontogenic and metabolic features. Most brown algae grow along the coastal zone where they face frequent environmental changes, including exposure to toxic levels of heavy metals such as copper (Cu).

RESULTS: We carried out large-scale transcriptomic and metabolomic analyses to decipher the short-term acclimation of the brown algal model E. siliculosus to Cu stress, and compared these data to results known for other abiotic stressors. This comparison demonstrates that Cu induces oxidative stress in E. siliculosus as illustrated by the transcriptomic overlap between Cu and H2O2 treatments. The common response to Cu and H2O2 consisted in the activation of the oxylipin and the repression of inositol signaling pathways, together with the regulation of genes coding for several transcription-associated proteins. Concomitantly, Cu stress specifically activated a set of genes coding for orthologs of ABC transporters, a P1B-type ATPase, ROS detoxification systems such as a vanadium-dependent bromoperoxidase, and induced an increase of free fatty acid contents. Finally we observed, as a common abiotic stress mechanism, the activation of autophagic processes on one hand and the repression of genes involved in nitrogen assimilation on the other hand.

CONCLUSIONS: Comparisons with data from green plants indicate that some processes involved in Cu and oxidative stress response are conserved across these two distant lineages. At the same time the high number of yet uncharacterized brown alga-specific genes induced in response to copper stress underlines the potential to discover new components and molecular interactions unique to these organisms. Of particular interest for future research is the potential cross-talk between reactive oxygen species (ROS)-, myo-inositol-, and oxylipin signaling.}, } @article {pmid24875633, year = {2014}, author = {Deniaud-Bouët, E and Kervarec, N and Michel, G and Tonon, T and Kloareg, B and Hervé, C}, title = {Chemical and enzymatic fractionation of cell walls from Fucales: insights into the structure of the extracellular matrix of brown algae.}, journal = {Annals of botany}, volume = {114}, number = {6}, pages = {1203-1216}, pmid = {24875633}, issn = {1095-8290}, mesh = {Biological Evolution ; Cell Wall/*chemistry/metabolism ; Cellulose/metabolism ; Extracellular Matrix/*metabolism ; Fucose/metabolism ; Models, Structural ; Phaeophyceae/*chemistry/metabolism/ultrastructure ; Polysaccharides/*metabolism ; }, abstract = {BACKGROUND AND AIMS: Brown algae are photosynthetic multicellular marine organisms evolutionarily distant from land plants, with a distinctive cell wall. They feature carbohydrates shared with plants (cellulose), animals (fucose-containing sulfated polysaccharides, FCSPs) or bacteria (alginates). How these components are organized into a three-dimensional extracellular matrix (ECM) still remains unclear. Recent molecular analysis of the corresponding biosynthetic routes points toward a complex evolutionary history that shaped the ECM structure in brown algae.

METHODS: Exhaustive sequential extractions and composition analyses of cell wall material from various brown algae of the order Fucales were performed. Dedicated enzymatic degradations were used to release and identify cell wall partners. This approach was complemented by systematic chromatographic analysis to study polymer interlinks further. An additional structural assessment of the sulfated fucan extracted from Himanthalia elongata was made.

KEY RESULTS: The data indicate that FCSPs are tightly associated with proteins and cellulose within the walls. Alginates are associated with most phenolic compounds. The sulfated fucans from H. elongata were shown to have a regular α-(1→3) backbone structure, while an alternating α-(1→3), (1→4) structure has been described in some brown algae from the order Fucales.

CONCLUSIONS: The data provide a global snapshot of the cell wall architecture in brown algae, and contribute to the understanding of the structure-function relationships of the main cell wall components. Enzymatic cross-linking of alginates by phenols may regulate the strengthening of the wall, and sulfated polysaccharides may play a key role in the adaptation to osmotic stress. The emergence and evolution of ECM components is further discussed in relation to the evolution of multicellularity in brown algae.}, } @article {pmid24870021, year = {2014}, author = {Alam, T and Alazmi, M and Gao, X and Arold, ST}, title = {How to find a leucine in a haystack? Structure, ligand recognition and regulation of leucine-aspartic acid (LD) motifs.}, journal = {The Biochemical journal}, volume = {460}, number = {3}, pages = {317-329}, doi = {10.1042/BJ20140298}, pmid = {24870021}, issn = {1470-8728}, mesh = {Adaptor Proteins, Signal Transducing/physiology ; Amino Acid Motifs/*physiology ; Apoptosis Regulatory Proteins/physiology ; Aspartic Acid/*metabolism ; Cell Cycle Proteins/physiology ; Focal Adhesion Kinase 2/chemistry ; Humans ; Leucine/*metabolism ; Ligands ; Membrane Proteins/physiology ; Microfilament Proteins/metabolism ; Paxillin/chemistry ; Poly(A)-Binding Protein I/metabolism ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/physiology ; Proto-Oncogene Proteins c-bcl-2/physiology ; Vinculin/physiology ; }, abstract = {LD motifs (leucine-aspartic acid motifs) are short helical protein-protein interaction motifs that have emerged as key players in connecting cell adhesion with cell motility and survival. LD motifs are required for embryogenesis, wound healing and the evolution of multicellularity. LD motifs also play roles in disease, such as in cancer metastasis or viral infection. First described in the paxillin family of scaffolding proteins, LD motifs and similar acidic LXXLL interaction motifs have been discovered in several other proteins, whereas 16 proteins have been reported to contain LDBDs (LD motif-binding domains). Collectively, structural and functional analyses have revealed a surprising multivalency in LD motif interactions and a wide diversity in LDBD architectures. In the present review, we summarize the molecular basis for function, regulation and selectivity of LD motif interactions that has emerged from more than a decade of research. This overview highlights the intricate multi-level regulation and the inherently noisy and heterogeneous nature of signalling through short protein-protein interaction motifs.}, } @article {pmid24862531, year = {2014}, author = {Yan, A and Wu, M and Zhao, Y and Zhang, A and Liu, B and Schiefelbein, J and Gan, Y}, title = {Involvement of C2H2 zinc finger proteins in the regulation of epidermal cell fate determination in Arabidopsis.}, journal = {Journal of integrative plant biology}, volume = {56}, number = {12}, pages = {1112-1117}, doi = {10.1111/jipb.12221}, pmid = {24862531}, issn = {1744-7909}, mesh = {Arabidopsis/*cytology/*metabolism ; Arabidopsis Proteins/*metabolism/physiology ; Cell Differentiation/*genetics ; Gene Expression Regulation, Plant ; Plant Roots/metabolism ; Trichomes/metabolism ; Zinc Fingers/physiology ; }, abstract = {Cell fate determination is a basic developmental process during the growth of multicellular organisms. Trichomes and root hairs of Arabidopsis are both readily accessible structures originating from the epidermal cells of the aerial tissues and roots respectively, and they serve as excellent models for understanding the molecular mechanisms controlling cell fate determination and cell morphogenesis. The regulation of trichome and root hair formation is a complex program that consists of the integration of hormonal signals with a large number of transcriptional factors, including MYB and bHLH transcriptional factors. Studies during recent years have uncovered an important role of C2H2 type zinc finger proteins in the regulation of epidermal cell fate determination. Here in this minireview we briefly summarize the involvement of C2H2 zinc finger proteins in the control of trichome and root hair formation in Arabidopsis.}, } @article {pmid24857678, year = {2014}, author = {Spurrier, RG and Speer, AL and Grant, CN and Levin, DE and Grikscheit, TC}, title = {Vitrification preserves murine and human donor cells for generation of tissue-engineered intestine.}, journal = {The Journal of surgical research}, volume = {190}, number = {2}, pages = {399-406}, doi = {10.1016/j.jss.2014.04.041}, pmid = {24857678}, issn = {1095-8673}, mesh = {Adult Stem Cells/pathology ; Animals ; Humans ; *Intestine, Small/pathology ; Mesoderm/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; *Tissue Engineering ; *Vitrification ; }, abstract = {BACKGROUND: Short bowel syndrome causes significant morbidity and mortality. Tissue-engineered intestine may serve as a viable replacement. Tissue-engineered small intestine (TESI) has previously been generated in the mouse model from donor cells that were harvested and immediately reimplanted; however, this technique may prove impossible in children who are critically ill, hemodynamically unstable, or septic. We hypothesized that organoid units (OU), multicellular clusters containing epithelium and mesenchyme, could be cryopreserved for delayed production of TESI.

METHODS: OU were isolated from <3 wk-old mouse or human ileum. OU were then cryopreserved by either standard snap freezing or vitrification. In the snap freezing protocol, OU were suspended in cryoprotectant and transferred directly to -80°C for storage. The vitrification protocol began with a stepwise increase in cryoprotectant concentration followed by liquid supercooling of the OU solution to -13°C and nucleation with a metal rod to induce vitrification. Samples were then cooled to -80°C at a controlled rate of -1°C/min and subsequently plunged into liquid nitrogen for long-term storage. OU from both groups were maintained in cryostorage for at least 72 h and thawed in a 37°C water bath. Cryoprotectant was removed with serial sucrose dilutions and OU were assessed by Trypan blue assay for post-cryopreservation viability. Via techniques previously described by our laboratory, the thawed murine or human OU were either cultured in vitro or implanted on a scaffold into the omentum of a syngeneic or irradiated Nonobese Diabetic/Severe Combined Immunodeficiency, gamma chain deficient adult mouse. The resultant TESI was analyzed by histology and immunofluorescence.

RESULTS: After cryopreservation, the viability of murine OU was significantly higher in the vitrification group (93 ± 2%, mean ± standard error of the mean) compared with standard freezing (56 ± 6%) (P < 0.001, unpaired t-test, n = 25). Human OU demonstrated similar viability after vitrification (89 ± 2%). In vitro culture of thawed OU produced expanding epithelial spheres supported by a layer of mesenchyme. TESI was successfully generated from the preserved OU. Hematoxylin and eosin staining demonstrated a mucosa composed of a simple columnar epithelium whereas immunofluorescence staining confirmed the presence of both progenitor and differentiated epithelial cells. Furthermore, beta-2-microglobulin confirmed that the human TESI epithelium originated from human cells.

CONCLUSIONS: We demonstrated improved multicellular viability after vitrification over conventional cryopreservation techniques and the first successful vitrification of murine and human OU with subsequent TESI generation. Clinical application of this method may allow for delayed autologous implantation of TESI for children in extremis.}, } @article {pmid24856210, year = {2014}, author = {Petkova, MD and Little, SC and Liu, F and Gregor, T}, title = {Maternal origins of developmental reproducibility.}, journal = {Current biology : CB}, volume = {24}, number = {11}, pages = {1283-1288}, pmid = {24856210}, issn = {1879-0445}, support = {P50 GM071508/GM/NIGMS NIH HHS/United States ; R01 GM097275/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Drosophila Proteins ; Drosophila melanogaster/*embryology/*genetics/metabolism ; Embryo, Nonmammalian/embryology/metabolism ; Embryonic Development ; Female ; Gene Dosage ; Homeodomain Proteins/*genetics/metabolism ; Oogenesis ; RNA, Messenger/genetics/metabolism ; Trans-Activators/*genetics/metabolism ; }, abstract = {Cell fate decisions during multicellular development are precisely coordinated, leading to highly reproducible macroscopic structural outcomes [1-3]. The origins of this reproducibility are found at the molecular level during the earliest stages of development when patterns of morphogen molecules emerge reproducibly [4, 5]. However, although the initial conditions for these early stages are determined by the female during oogenesis, it is unknown whether reproducibility is perpetuated from oogenesis or reacquired by the zygote. To address this issue in the early Drosophila embryo, we sought to count individual maternally deposited bicoid mRNA molecules and compare variability between embryos with previously observed fluctuations in the Bicoid protein gradient [6, 7]. Here, we develop independent methods to quantify total amounts of mRNA in individual embryos and show that mRNA counts are highly reproducible between embryos to within ~9%, matching the reproducibility of the protein gradient. Reproducibility emerges from perfectly linear feedforward processes: changing the genetic dosage in the female leads to proportional changes in both mRNA and protein numbers in the embryo. Our results indicate that the reproducibility of the morphological structures of embryos originates during oogenesis, which is when the expression of maternally provided patterning factors is precisely controlled.}, } @article {pmid24853750, year = {2014}, author = {Vulin, C and Di Meglio, JM and Lindner, AB and Daerr, A and Murray, A and Hersen, P}, title = {Growing yeast into cylindrical colonies.}, journal = {Biophysical journal}, volume = {106}, number = {10}, pages = {2214-2221}, pmid = {24853750}, issn = {1542-0086}, mesh = {Biological Transport ; Cell Proliferation/drug effects ; Culture Techniques/*methods ; Dose-Response Relationship, Drug ; Glucose/metabolism/pharmacology ; Membranes, Artificial ; Microtechnology ; Porosity ; Saccharomyces cerevisiae/cytology/drug effects/*growth & development/metabolism ; }, abstract = {Microorganisms often form complex multicellular assemblies such as biofilms and colonies. Understanding the interplay between assembly expansion, metabolic yield, and nutrient diffusion within a freely growing colony remains a challenge. Most available data on microorganisms are from planktonic cultures, due to the lack of experimental tools to control the growth of multicellular assemblies. Here, we propose a method to constrain the growth of yeast colonies into simple geometric shapes such as cylinders. To this end, we designed a simple, versatile culture system to control the location of nutrient delivery below a growing colony. Under such culture conditions, yeast colonies grow vertically and only at the locations where nutrients are delivered. Colonies increase in height at a steady growth rate that is inversely proportional to the cylinder radius. We show that the vertical growth rate of cylindrical colonies is not defined by the single-cell division rate, but rather by the colony metabolic yield. This contrasts with cells in liquid culture, in which the single-cell division rate is the only parameter that defines the population growth rate. This method also provides a direct, simple method to estimate the metabolic yield of a colony. Our study further demonstrates the importance of the shape of colonies on setting their expansion. We anticipate that our approach will be a starting point for elaborate studies of the population dynamics, evolution, and ecology of microbial colonies in complex landscapes.}, } @article {pmid24848562, year = {2014}, author = {Whittle, CA and Sun, Y and Johannesson, H}, title = {Dynamics of transcriptome evolution in the model eukaryote Neurospora.}, journal = {Journal of evolutionary biology}, volume = {27}, number = {6}, pages = {1125-1135}, doi = {10.1111/jeb.12386}, pmid = {24848562}, issn = {1420-9101}, mesh = {*Evolution, Molecular ; Gene Expression Profiling ; Genome, Fungal ; Molecular Sequence Data ; Neurospora/cytology/*genetics ; Phenotype ; Reproduction ; *Transcriptome ; }, abstract = {Mounting evidence indicates that changes in the transcriptome contribute significantly to the phenotypic differentiation of closely related species. Nonetheless, further genome-wide studies, spanning a broad range of organisms, are needed to decipher the factors driving transcriptome evolution. The model Neurospora (Ascomycota) comprises a simple system for empirically studying the evolutionary dynamics of the transcriptome. Here, we studied the evolution of gene expression in Neurospora crassa and Neurospora tetrasperma and show that patterns of transcriptome evolution are connected to genome evolution, tissue type and sexual identity (mating types, mat A and mat a) in these eukaryotes. Based on the comparisons of inter- and intraspecies expression divergence, our data reveal that rapid expression divergence is more apt to occur in sexual/female (SF) than vegetative/male (VM) tissues. In addition, interspecies gene expression and protein sequence divergence were strongly correlated for SF, but not VM, tissue. A correlation between transcriptome and protein evolution parallels findings from certain animals, but not yeast, and add support for the theory that expression evolution differs fundamentally among multicellular and unicellular eukaryotes. Finally, we found that sexual identity in these hermaphroditic Neurospora species is connected to interspecies expression divergence in a tissue-dependent manner: rapid divergence occurred for mat A- and mat a-biased genes from SF and VM tissues, respectively. Based on these findings, it is hypothesized that rapid interspecies transcriptome evolution is shifting the mating types of Neurospora towards distinct female and male phenotypes, that is, sexual dimorphism.}, } @article {pmid24840820, year = {2014}, author = {El-Guizani, T and Guibert, C and Triki, S and St-Pierre, B and Ducos, E}, title = {Identification of a human ABCC10 orthologue in Catharanthus roseus reveals a U12-type intron determinant for the N-terminal domain feature.}, journal = {Journal of genetics}, volume = {93}, number = {1}, pages = {21-33}, pmid = {24840820}, issn = {0973-7731}, mesh = {ATP-Binding Cassette Transporters/chemistry/genetics ; Amino Acid Sequence ; Base Sequence ; Catharanthus/*genetics ; DNA, Complementary/chemistry/genetics ; Expressed Sequence Tags ; Gene Expression ; Gene Order ; Genetic Loci ; Humans ; Intracellular Space/metabolism ; *Introns ; Molecular Sequence Data ; Multidrug Resistance-Associated Proteins/chemistry/*genetics ; Multigene Family ; Open Reading Frames ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; *Protein Interaction Domains and Motifs ; Protein Transport ; RNA Splice Sites ; RNA Splicing ; RNA, Small Nuclear/*genetics ; Sequence Alignment ; }, abstract = {ABC (ATP-binding cassette) transporters are members of a large superfamily of proteins that utilize ATP hydrolysis to translocate a wide range of substrates across biological membranes. In general, members of C subfamily (ABCC) are structurally characterized by an additional (N-terminal) transmembrane domain (TMD0). Phylogenetic analysis of plant ABCCs separates their protein sequences into three distinct clusters: I and II are plant specific whereas cluster III contains both human and plant ABCCs. Screening of the Plant Medicinal Genomics Resource database allowed us to identify 16 ABCCs partial sequences in Catharanthus roseus; two of which belong to the unique CrABCC1 transcript that we identified in cluster III. Genomic organization of CrABCC1 TMD0 coding sequence displays an AT-AC U12-type intron that is conserved in higher plant orthologues. We showed that CrABCC1, like its human orthologue ABCC10, produces alternative transcripts that encode protein sequences with a truncated form of TMD0 without the first transmembrane span (TM1). Subcellular localization of CrABCC1 TMD0 variants using yellow fluorescent protein fusions reveals that the TM1 is required for a correct routing of the TMD0 to the tonoplast. Finally, the specific repartition of CrABCC1 orthologues in some species suggests that this gene was lost several times during evolution and that its physiological function may, rely on a common feature of multicellular eukaryotes.}, } @article {pmid24838875, year = {2014}, author = {Yaung, SJ and Church, GM and Wang, HH}, title = {Recent progress in engineering human-associated microbiomes.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1151}, number = {}, pages = {3-25}, doi = {10.1007/978-1-4939-0554-6_1}, pmid = {24838875}, issn = {1940-6029}, support = {1DP5OD009172-01/OD/NIH HHS/United States ; }, mesh = {Animals ; Genetic Engineering/*methods ; Host-Pathogen Interactions ; Humans ; Metagenomics/methods ; *Microbiota ; Models, Animal ; Synthetic Biology/methods ; }, abstract = {Recent progress in molecular biology and genetics opens up the possibility of engineering a variety of biological systems, from single-cellular to multicellular organisms. The consortia of microbes that reside on the human body, the human-associated microbiota, are particularly interesting as targets for forward engineering and manipulation due to their relevance in health and disease. New technologies in analysis and perturbation of the human microbiota will lead to better diagnostic and therapeutic strategies against diseases of microbial origin or pathogenesis. Here, we discuss recent advances that are bringing us closer to realizing the true potential of an engineered human-associated microbial community.}, } @article {pmid24826801, year = {2014}, author = {Morgan, AD and Ness, RW and Keightley, PD and Colegrave, N}, title = {Spontaneous mutation accumulation in multiple strains of the green alga, Chlamydomonas reinhardtii.}, journal = {Evolution; international journal of organic evolution}, volume = {68}, number = {9}, pages = {2589-2602}, pmid = {24826801}, issn = {1558-5646}, support = {BB/H006109/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Chlamydomonas reinhardtii/*genetics ; *Genetic Fitness ; *Genetic Variation ; Genome, Plant ; *Mutation ; }, abstract = {Estimates of mutational parameters, such as the average fitness effect of a new mutation and the rate at which new genetic variation for fitness is created by mutation, are important for the understanding of many biological processes. However, the causes of interspecific variation in mutational parameters and the extent to which they vary within species remain largely unknown. We maintained multiple strains of the unicellular eukaryote Chlamydomonas reinhardtii, for approximately 1000 generations under relaxed selection by transferring a single cell every ~10 generations. Mean fitness of the lines tended to decline with generations of mutation accumulation whereas mutational variance increased. We did not find any evidence for differences among strains in any of the mutational parameters estimated. The overall change in mean fitness per cell division and rate of input of mutational variance per cell division were more similar to values observed in multicellular organisms than to those in other single-celled microbes. However, after taking into account differences in genome size among species, estimates from multicellular organisms and microbes, including our new estimates from C. reinhardtii, become substantially more similar. Thus, we suggest that variation in genome size is an important determinant of interspecific variation in mutational parameters.}, } @article {pmid24823688, year = {2014}, author = {Slabodnick, MM and Ruby, JG and Dunn, JG and Feldman, JL and DeRisi, JL and Marshall, WF}, title = {The kinase regulator mob1 acts as a patterning protein for stentor morphogenesis.}, journal = {PLoS biology}, volume = {12}, number = {5}, pages = {e1001861}, pmid = {24823688}, issn = {1545-7885}, support = {R01 GM090305/GM/NIGMS NIH HHS/United States ; T32 GM007810/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cell Division ; Ciliophora/classification/*genetics/metabolism/ultrastructure ; *Gene Expression Regulation ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors/*genetics/metabolism ; Molecular Sequence Data ; Morphogenesis/*genetics ; Phylogeny ; Plants ; Protozoan Proteins/antagonists & inhibitors/*genetics/metabolism ; RNA Interference ; RNA, Small Interfering/genetics/metabolism ; Regeneration/*genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {Morphogenesis and pattern formation are vital processes in any organism, whether unicellular or multicellular. But in contrast to the developmental biology of plants and animals, the principles of morphogenesis and pattern formation in single cells remain largely unknown. Although all cells develop patterns, they are most obvious in ciliates; hence, we have turned to a classical unicellular model system, the giant ciliate Stentor coeruleus. Here we show that the RNA interference (RNAi) machinery is conserved in Stentor. Using RNAi, we identify the kinase coactivator Mob1--with conserved functions in cell division and morphogenesis from plants to humans-as an asymmetrically localized patterning protein required for global patterning during development and regeneration in Stentor. Our studies reopen the door for Stentor as a model regeneration system.}, } @article {pmid24821426, year = {2014}, author = {Chávez-Mardones, J and Gallardo-Escárate, C}, title = {Immune response of apoptosis-related cysteine peptidases from the red abalone Haliotis rufescens (HrCas8 and HrCas3): molecular characterization and transcription expression.}, journal = {Fish & shellfish immunology}, volume = {39}, number = {1}, pages = {90-98}, doi = {10.1016/j.fsi.2014.04.027}, pmid = {24821426}, issn = {1095-9947}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Caspase 3/chemistry/*genetics/metabolism ; Caspase 8/chemistry/*genetics/metabolism ; Expressed Sequence Tags ; *Gene Expression Regulation, Enzymologic ; Gills/metabolism ; Hemolymph/metabolism ; *Immunity, Innate ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; *Snails/enzymology/genetics/immunology ; Transcriptome ; Vibrio/physiology ; }, abstract = {Caspases play an important role in the different stages of programmed cell death, or apoptosis, which has been related to the immune response in multicellular organisms. The present study characterized an initiator caspase (HrCas8) and an effector caspase (HrCas3) from the red abalone Haliotis rufescens using the RACE method and qPCR analysis. HrCas8 showed a complete sequence of 2529 base pairs (bp) with an open-reading frame (ORF) of 1911 bp, a 5'UTR of 201 bp, and a 3'UTR of 417 bp. The estimated molecular mass for the 636 amino acids from HrCas8 was 71.5 kDa with an isoelectric point of 6.2. The HrCas8 sequence had two death-effector domains (DEDs) and the subunits p20 and p10, in addition to an active site characteristic of cysteine proteins. Meanwhile, the effector caspase HrCas3 showed a complete sequence of 1404 bp, a 5'UTR of 82 bp, and a 3'UTR of 574 bp. The ORF of this caspase had 747 bp that coded for 248 residues. Moreover, the predicted molecular mass of HrCas3 was 29.4 kDa; the theoretical isoelectric point was 5.70, and the sequence evidenced a conserved caspase recruitment domain (CARD). The distribution of the caspases in distinct tissues revealed that HrCas8 was principally expressed in the hemolymph, while HrCas3 had a higher expression in the gills. A basal level of expression was found for both caspases in muscle tissue. The immune response of caspases in H. rufescens was evaluated through an injection of Vibrio anguillarum. The results showed an increase in the transcription of HrCas8 post-challenge, as well as an activation of HrCas3, which together suggest the initiation of apoptosis as a response to bacterial infection in H. rufescens.}, } @article {pmid24812307, year = {2014}, author = {Kelly, AC and Busby, B and Wickner, RB}, title = {Effect of domestication on the spread of the [PIN+] prion in Saccharomyces cerevisiae.}, journal = {Genetics}, volume = {197}, number = {3}, pages = {1007-1024}, pmid = {24812307}, issn = {1943-2631}, support = {//Intramural NIH HHS/United States ; }, mesh = {Base Sequence ; Genetic Variation ; Haplotypes/genetics ; Humans ; Hyphae/growth & development ; Likelihood Functions ; Phenotype ; Phylogeny ; Prions/*genetics ; Risk Factors ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Spores, Fungal/physiology ; }, abstract = {Prions (infectious proteins) cause fatal neurodegenerative diseases in mammals. In the yeast Saccharomyces cerevisiae, many toxic and lethal variants of the [PSI+] and [URE3] prions have been identified in laboratory strains, although some commonly studied variants do not seem to impair cell growth. Phylogenetic analysis has revealed four major clades of S. cerevisiae that share histories of two prion proteins and largely correspond to different ecological niches of yeast. The [PIN+] prion was most prevalent in commercialized niches, infrequent among wine/vineyard strains, and not observed in ancestral isolates. As previously reported, the [PSI+] and [URE3] prions are not found in any of these strains. Patterns of heterozygosity revealed genetic mosaicism and indicated extensive outcrossing among divergent strains in commercialized environments. In contrast, ancestral isolates were all homozygous and wine/vineyard strains were closely related to each other and largely homozygous. Cellular growth patterns were highly variable within and among clades, although ancestral isolates were the most efficient sporulators and domesticated strains showed greater tendencies for flocculation. [PIN+]-infected strains had a significantly higher likelihood of polyploidy, showed a higher propensity for flocculation compared to uninfected strains, and had higher sporulation efficiencies compared to domesticated, uninfected strains. Extensive phenotypic variability among strains from different environments suggests that S. cerevisiae is a niche generalist and that most wild strains are able to switch from asexual to sexual and from unicellular to multicellular growth in response to environmental conditions. Our data suggest that outbreeding and multicellular growth patterns adapted for domesticated environments are ecological risk factors for the [PIN+] prion in wild yeast.}, } @article {pmid24789824, year = {2014}, author = {Hunter, T}, title = {The genesis of tyrosine phosphorylation.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {6}, number = {5}, pages = {a020644}, pmid = {24789824}, issn = {1943-0264}, mesh = {Animals ; Computational Biology ; Humans ; Phosphorylation ; Protein Engineering ; Protein Tyrosine Phosphatases/physiology ; Protein-Tyrosine Kinases/*physiology ; Tyrosine/*metabolism ; }, abstract = {Tyrosine phosphorylation of proteins was discovered in 1979, but this posttranslational modification had been "invented" by evolution more than a billion years ago in single-celled eukaryotic organisms that were the antecedents of the first multicellular animals. Because sophisticated cell-cell communication is a sine qua non for the existence of multicellular organisms, the development of cell-surface receptor systems that use tyrosine phosphorylation for transmembrane signal transduction and intracellular signaling seems likely to have been a crucial event in the evolution of metazoans. Like all types of protein phosphorylation, tyrosine phosphorylation serves to regulate proteins in multiple ways, including causing electrostatic repulsion and inducing allosteric transitions, but the most important function of phosphotyrosine (P.Tyr) is to serve as a docking site that promotes a specific interaction between a tyrosine phosphorylated protein and another protein that contains a P.Tyr-binding domain, such as an SH2 or PTB domain. Such docking interactions are essential for signal transduction downstream from receptor tyrosine kinases (RTKs) on the cell surface, which are activated on binding a cognate extracellular ligand, and, as a consequence, elicit specific cellular outcomes.}, } @article {pmid24786278, year = {2014}, author = {Heger, P and Wiehe, T}, title = {New tools in the box: an evolutionary synopsis of chromatin insulators.}, journal = {Trends in genetics : TIG}, volume = {30}, number = {5}, pages = {161-171}, doi = {10.1016/j.tig.2014.03.004}, pmid = {24786278}, issn = {0168-9525}, mesh = {Animals ; Binding Sites/genetics ; Chromatin/*genetics ; DNA-Binding Proteins/metabolism ; Enhancer Elements, Genetic ; *Evolution, Molecular ; Humans ; Insulator Elements/*genetics ; }, abstract = {Despite progress in understanding genome organization and gene expression during the last decade, the evolutionary pathways that led to the intricate patterns of gene expression in different cells of an organism are still poorly understood. Important steps in this regulation take place at the level of chromatin, where the (epi)genomic environment of a gene determines its expression in time and space. Although the basic mechanisms of gene expression apply to all eukaryotes, multicellular organisms face the additional challenge of coordinating gene expression during development. In this review we summarize and put into evolutionary context current knowledge about chromatin insulators, an important class of regulatory factors mediating these tasks. Our interpretation of historical and recent findings points to a dynamic and ongoing evolution of insulator proteins characterized by multiple instances of convergent evolution, gene loss, and binding site changes in different organisms. The idea of two autonomously evolving insulator functions (as a barrier element and an enhancer blocker) further suggests that the evolution of metazoans and their enhancer-rich gene regulatory repertoire might be connected to the radiation of enhancer blocking insulators. Although speculative at the moment, such coevolution might create tools for complex gene regulation and therefore influence the evolutionary roadmaps of metazoans.}, } @article {pmid24781500, year = {2014}, author = {Birarda, G and Bedolla, DE and Mitri, E and Pacor, S and Grenci, G and Vaccari, L}, title = {Apoptotic pathways of U937 leukemic monocytes investigated by infrared microspectroscopy and flow cytometry.}, journal = {The Analyst}, volume = {139}, number = {12}, pages = {3097-3106}, doi = {10.1039/c4an00317a}, pmid = {24781500}, issn = {1364-5528}, mesh = {*Apoptosis ; Flow Cytometry/*methods ; Humans ; Leukemia/*pathology ; Monocytes/*pathology ; Spectrophotometry, Infrared/*methods ; U937 Cells ; }, abstract = {Apoptosis is a strictly regulated cell death mechanism that plays a pivotal role in the normal evolution of multicellular organisms. Its misregulation has been associated with many diseases, making its early and reliable detection a key point for modern cellular biology. In this paper, we propose the use of infrared microspectroscopy (IRMS) as a label-free methodology for the detection of apoptotic-related biochemical processes induced on U937 leukemic monocytes by serum starvation and CCCP-exposure. The spectroscopic results are in agreement with parallel Flow Cytometry (FC) experiments, where plasma membrane integrity and mitochondrial activity were assessed. Spectroscopic outcomes complement FC data and allow drawing a more complete picture of the apoptotic pathways. In particular, we established that the two apoptosis-inducing treatments, cell starvation and CCCP exposure, affect the cell cycle in a different way. With the former, cell death is preceded by a cell cycle arrest, whereas the latter causes an increased cell cycle progression. Spectral data demonstrate that for both conditions apoptosis proceeds through the accumulation of lipid droplets within cells. Moreover, we were able to establish a spectral marker for DNA condensation/fragmentation: the enhancement of the PhI band component centred at ~1206 cm(-1), which is more sensitive than the relative intensity of the PhII band to which phospholipids and carbohydrates also contribute significantly. In conclusion, we demonstrate that the intrinsic multi-parametric nature of IRMS and its application on cells under physiological conditions can be well exploited for the investigation of apoptotic pathways.}, } @article {pmid24766896, year = {2014}, author = {Reddick, LE and Alto, NM}, title = {Bacteria fighting back: how pathogens target and subvert the host innate immune system.}, journal = {Molecular cell}, volume = {54}, number = {2}, pages = {321-328}, pmid = {24766896}, issn = {1097-4164}, support = {R01GM100486/GM/NIGMS NIH HHS/United States ; 1F32AI098384/AI/NIAID NIH HHS/United States ; R01 GM100486/GM/NIGMS NIH HHS/United States ; R01AI083359/AI/NIAID NIH HHS/United States ; R01 AI083359/AI/NIAID NIH HHS/United States ; F32 AI098384/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*immunology ; Host-Pathogen Interactions ; *Immune Evasion ; *Immunity, Innate ; *Models, Immunological ; Receptors, Pattern Recognition/physiology ; Signal Transduction/immunology ; Toll-Like Receptor 4/metabolism/physiology ; }, abstract = {The innate immune system has evolved under selective pressure since the radiation of multicellular life approximately 600 million years ago. Because of this long history, innate immune mechanisms found in modern eukaryotic organisms today are highly complex but yet built from common molecular strategies. It is now clear that evolution has selected a conserved set of antimicrobial peptides as well as pattern-recognition receptors (PRRs) that initiate cellular-based signals as a first line of defense against invading pathogens. Conversely, microbial pathogens employ their own strategies in order to evade, inhibit, or otherwise manipulate the innate immune response. Here, we discuss recent discoveries that have changed our view of immune modulatory mechanisms employed by bacterial pathogens, focusing specifically on the initial sites of microbial recognition and extending to host cellular signal transduction, proinflammatory cytokine production, and alteration of protein trafficking and secretion.}, } @article {pmid24766052, year = {2016}, author = {Qin, X}, title = {Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution.}, journal = {Critical reviews in microbiology}, volume = {42}, number = {1}, pages = {144-157}, doi = {10.3109/1040841X.2014.907235}, pmid = {24766052}, issn = {1549-7828}, mesh = {Adaptation, Physiological ; Amino Acids/biosynthesis ; Animals ; Chronic Disease ; Coinfection ; Cystic Fibrosis/*complications ; Disease Susceptibility ; Host-Pathogen Interactions ; Humans ; Pneumonia, Bacterial/drug therapy/*etiology/*metabolism/microbiology ; Pseudomonas Infections/drug therapy/*etiology/*metabolism/microbiology ; Pseudomonas aeruginosa/physiology ; Quorum Sensing ; Symbiosis ; Virulence ; }, abstract = {Gain of "antimicrobial resistance" and "adaptive virulence" has been the dominant view of Pseudomonas aeruginosa (Pa) in cystic fibrosis (CF) in the progressively damaged host airway over the course of this chronic infection. However, the pathogenic effects of CF airway-adapted Pa strains are notably reduced. We propose that CF Pa and other bacterial cohabitants undergo host adaptation which resembles the changes found in bacterial symbionts in animal hosts. Development of clonally selected and intraspecific isogenic Pa strains which display divergent colony morphology, growth rate, auxotrophy, and antibiotic susceptibility in vitro suggests an adaptive sequence of infective exploitation-parasitism-symbiotic evolution driven by host defenses. Most importantly, the emergence of CF pseudomonal auxotrophy is frequently associated with a few specific amino acids. The selective retention or loss of specific amino acid biosynthesis in CF-adapted Pa reflects bacterium-host symbiosis and coevolution during chronic infection, not nutrient availability. This principle also argues against the long-standing concept of dietary availability leading to evolution of essential amino acid requirements in humans. A novel model of pseudomonal adaptation through multicellular bacterial syntrophy is proposed to explain early events in bacterial gene decay and decreased (not increased) virulence due to symbiotic response to host defense.}, } @article {pmid24736157, year = {2014}, author = {De Monte, S and Rainey, PB}, title = {Nascent multicellular life and the emergence of individuality.}, journal = {Journal of biosciences}, volume = {39}, number = {2}, pages = {237-248}, pmid = {24736157}, issn = {0973-7138}, mesh = {*Biological Evolution ; Humans ; Microbial Interactions ; Models, Biological ; Population Dynamics ; Selection, Genetic ; }, abstract = {The evolution of multicellular organisms from unicellular ancestors involves a shift in the level at which selection operates. It is usual to think about this shift in terms of the emergence of traits that cause heritable differences in reproductive output at the level of nascent collectives. Defining these traits and the causes of their origin lies at the heart of understanding the evolution of multicellular life. In working toward a mechanistic, take-nothing-for-granted account, we begin by recognizing that the standard Lewontin formulation of properties necessary and sufficient for evolution by natural selection does not necessarily encompass Darwinian evolution in primitive collectives where parent-offspring relationships may have been poorly defined. This, we suggest, limits the ability to conceptualize and capture the earliest manifestations of Darwinian properties. By way of solution we propose a relaxed interpretation of Lewontin's conditions and present these in the form of a set of necessary requirements for evolution by natural selection based upon the establishment of genealogical connections between recurrences of collectives. With emphasis on genealogy - as opposed to reproduction - it is possible to conceive selection acting on collectives prior to any manifestation of heritable variance in fitness. Such possibility draws attention to the evolutionary emergence of traits that strengthen causal relationships between recurrences - traits likely to underpin the emergence of forms of multiplication that establish parent-offspring relationships. Application of this framework to collectives of marginal status, particularly those whose recurrence is not defined by genealogy, makes clear that change at the level of collectives need not arise from selection acting at the higher level. We conclude by outlining applicability of our framework to loosely defined collectives of cells, such as those comprising the slugs of social amoeba and microbes that constitute the human microbiome.}, } @article {pmid24728646, year = {2014}, author = {Zhang, H and Koblížková, A and Wang, K and Gong, Z and Oliveira, L and Torres, GA and Wu, Y and Zhang, W and Novák, P and Buell, CR and Macas, J and Jiang, J}, title = {Boom-Bust Turnovers of Megabase-Sized Centromeric DNA in Solanum Species: Rapid Evolution of DNA Sequences Associated with Centromeres.}, journal = {The Plant cell}, volume = {26}, number = {4}, pages = {1436-1447}, pmid = {24728646}, issn = {1532-298X}, abstract = {Centromeres are composed of long arrays of satellite repeats in most multicellular eukaryotes investigated to date. The satellite repeat-based centromeres are believed to have evolved from "neocentromeres" that originally contained only single- or low-copy sequences. However, the emergence and evolution of the satellite repeats in centromeres has been elusive. Potato (Solanum tuberosum) provides a model system for studying centromere evolution because each of its 12 centromeres contains distinct DNA sequences, allowing comparative analysis of homoeologous centromeres from related species. We conducted genome-wide analysis of the centromeric sequences in Solanum verrucosum, a wild species closely related to potato. Unambiguous homoeologous centromeric sequences were detected in only a single centromere (Cen9) between the two species. Four centromeres (Cen2, Cen4, Cen7, and Cen10) in S. verrucosum contained distinct satellite repeats that were amplified from retrotransposon-related sequences. Strikingly, the same four centromeres in potato contain either different satellite repeats (Cen2 and Cen7) or exclusively single- and low-copy sequences (Cen4 and Cen10). Our sequence comparison of five homoeologous centromeres in two Solanum species reveals rapid divergence of centromeric sequences among closely related species. We propose that centromeric satellite repeats undergo boom-bust cycles before a favorable repeat is fixed in the population.}, } @article {pmid24727478, year = {2014}, author = {Bezsonova, I}, title = {Solution NMR structure of the DNA-binding domain from Scml2 (sex comb on midleg-like 2).}, journal = {The Journal of biological chemistry}, volume = {289}, number = {22}, pages = {15739-15749}, pmid = {24727478}, issn = {1083-351X}, mesh = {Amino Acid Sequence ; Cell Cycle Proteins/chemistry/genetics/metabolism ; DNA-Binding Proteins/*chemistry/*genetics/metabolism ; *Epigenesis, Genetic ; Evolution, Molecular ; Gene Silencing ; Humans ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Phylogeny ; Polycomb-Group Proteins/*chemistry/*genetics/metabolism ; Protein Folding ; Protein Structure, Tertiary ; }, abstract = {Scml2 is a member of the Polycomb group of proteins involved in epigenetic gene silencing. Human Scml2 is a part of a multisubunit protein complex, PRC1 (Polycomb repressive complex 1), which is responsible for maintenance of gene repression, prevention of chromatin remodeling, preservation of the "stemness" of the cell, and cell differentiation. Although the majority of PRC1 subunits have been recently characterized, the structure of Scml2 and its role in PRC1-mediated gene silencing remain unknown. In this work a conserved protein domain within human Scml2 has been identified, and its structure was determined by solution NMR spectroscopy. This module was named Scm-like embedded domain, or SLED. Evolutionarily, the SLED domain emerges in the first multicellular organisms, consistent with the role of Scml2 in cell differentiation. Furthermore, it is exclusively found within the Scm-like family of proteins, often accompanied by malignant brain tumor domain (MBT) and sterile α motif (SAM) domains. The domain adopts a novel α/β fold with no structural analogues found in the Protein Data Bank (PDB). The ability of the SLED to bind double-stranded DNA was also examined, and the isolated domain was shown to interact with DNA in a sequence-specific manner. Because PRC1 complexes localize to the promoters of a specific subset of developmental genes in vivo, the SLED domain of Scml2 may provide an important link connecting the PRC1 complexes to their target genes.}, } @article {pmid24717428, year = {2014}, author = {Ralston, KS and Solga, MD and Mackey-Lawrence, NM and Somlata, and Bhattacharya, A and Petri, WA}, title = {Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion.}, journal = {Nature}, volume = {508}, number = {7497}, pages = {526-530}, pmid = {24717428}, issn = {1476-4687}, support = {5R01 AI-26649/AI/NIAID NIH HHS/United States ; AI07046-32/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32 DK007769/DK/NIDDK NIH HHS/United States ; R37 AI026649/AI/NIAID NIH HHS/United States ; T32 AI055432/AI/NIAID NIH HHS/United States ; T32 AI007046/AI/NIAID NIH HHS/United States ; R01 AI026649/AI/NIAID NIH HHS/United States ; }, mesh = {Biological Evolution ; Caco-2 Cells ; Calcium/metabolism ; *Cell Death ; Cell Survival ; Entamoeba histolytica/cytology/*pathogenicity/*physiology ; Entamoebiasis/*parasitology/*pathology ; Erythrocytes/parasitology ; Humans ; Intestines/*parasitology/*pathology ; Jurkat Cells ; Neglected Diseases/parasitology/pathology ; }, abstract = {Entamoeba histolytica is the causative agent of amoebiasis, a potentially fatal diarrhoeal disease in the developing world. The parasite was named "histolytica" for its ability to destroy host tissues, which is probably driven by direct killing of human cells. The mechanism of human cell killing has been unclear, although the accepted model was that the parasites use secreted toxic effectors to kill cells before ingestion. Here we report the discovery that amoebae kill by ingesting distinct pieces of living human cells, resulting in intracellular calcium elevation and eventual cell death. After cell killing, amoebae detach and cease ingestion. Ingestion of human cell fragments is required for cell killing, and also contributes to invasion of intestinal tissue. The internalization of fragments of living human cells is reminiscent of trogocytosis (from Greek trogo, nibble) observed between immune cells, but amoebic trogocytosis differs because it results in death. The ingestion of live cell material and the rejection of corpses illuminate a stark contrast to the established model of dead cell clearance in multicellular organisms. These findings change the model for tissue destruction in amoebiasis and suggest an ancient origin of trogocytosis as a form of intercellular exchange.}, } @article {pmid24711645, year = {2014}, author = {Lovejoy, DA and Chang, BS and Lovejoy, NR and del Castillo, J}, title = {Molecular evolution of GPCRs: CRH/CRH receptors.}, journal = {Journal of molecular endocrinology}, volume = {52}, number = {3}, pages = {T43-60}, doi = {10.1530/JME-13-0238}, pmid = {24711645}, issn = {1479-6813}, mesh = {Adrenal Glands/physiology ; Animals ; Corticotropin-Releasing Hormone/*genetics ; Diuresis ; Energy Metabolism ; *Evolution, Molecular ; Hypothalamus/physiology ; Pituitary Gland/physiology ; Receptors, Corticotropin-Releasing Hormone/*genetics ; Signal Transduction ; Urocortins/genetics ; Urotensins/genetics ; }, abstract = {Corticotrophin-releasing hormone (CRH) is the pivotal neuroendocrine peptide hormone associated with the regulation of the stress response in vertebrates. However, CRH-like peptides are also found in a number of invertebrate species. The origin of this peptide can be traced to a common ancestor of lineages leading to chordates and to arthropods, postulated to occur some 500 million years ago. Evidence indicates the presence of a single CRH-like receptor and a soluble binding protein system that acted to transduce and regulate the actions of the early CRH peptide. In vertebrates, genome duplications led to the divergence of CRH receptors into CRH1 and CRH2 forms in tandem with the development of four paralogous ligand lineages that included CRH; urotensin I/urocortin (Ucn), Ucn2 and Ucn3. In addition, taxon-specific genome duplications led to further local divergences in CRH ligands and receptors. Functionally, the CRH ligand-receptor system evolved initially as a molecular system to integrate early diuresis and nutrient acquisition. As multicellular organisms evolved into more complex forms, this ligand-receptor system became integrated with the organismal stress response to coordinate homoeostatic challenges with internal energy usage. In vertebrates, CRH and the CRH1 receptor became associated with the hypothalamo-pituitary-adrenal/interrenal axis and the initial stress response, whereas the CRH2 receptor was selected to play a greater role in diuresis, nutrient acquisition and the latter aspects of the stress response.}, } @article {pmid24711388, year = {2014}, author = {Yang, C and Stiller, JW}, title = {Evolutionary diversity and taxon-specific modifications of the RNA polymerase II C-terminal domain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {16}, pages = {5920-5925}, pmid = {24711388}, issn = {1091-6490}, mesh = {Animals ; *Evolution, Molecular ; Fungi/metabolism ; *Genetic Variation ; *Phylogeny ; Plants/metabolism ; Protein Structure, Tertiary ; RNA Polymerase II/*chemistry/*genetics/metabolism ; Repetitive Sequences, Amino Acid ; Rhodophyta/metabolism ; }, abstract = {In model eukaryotes, the C-terminal domain (CTD) of the largest subunit of DNA-dependent RNA polymerase II (RNAP II) is composed of tandemly repeated heptads with the consensus sequence YSPTSPS. The core motif and tandem structure generally are conserved across model taxa, including animals, yeasts and higher plants. Broader investigations revealed that CTDs of many organisms deviate substantially from this canonical structure; however, limited sampling made it difficult to determine whether disordered sequences reflect the CTD's ancestral state or degeneration from ancestral repetitive structures. Therefore, we undertook, to our knowledge, the broadest investigation to date of the evolution of the RNAP II CTD across eukaryotic diversity. Our results indicate that a tandemly repeated CTD existed in the ancestors of each major taxon, and that degeneration and reinvention of this ordered structure are common features of CTD evolution. Lineage-specific CTD modifications appear to be associated with greater developmental complexity in multicellular organisms, a pattern taken to an extreme in fungi and red algae, in which the CTD has undergone dramatic to complete alteration during the transition from unicellular to developmentally complex forms. Overall, loss and reinvention of repeats have punctuated CTD evolution, occurring independently and sometimes repeatedly in various groups.}, } @article {pmid24704442, year = {2014}, author = {Newman, SA}, title = {Why are there eggs?.}, journal = {Biochemical and biophysical research communications}, volume = {450}, number = {3}, pages = {1225-1230}, doi = {10.1016/j.bbrc.2014.03.132}, pmid = {24704442}, issn = {1090-2104}, mesh = {Animals ; *Biological Evolution ; Body Patterning/physiology ; Chimera/growth & development ; Embryonic Development/physiology ; Female ; Fertilization/physiology ; Growth and Development/physiology ; Male ; *Models, Biological ; Ovum/*cytology/*physiology ; Species Specificity ; }, abstract = {A description and update of the "egg-as-novelty" hypothesis is presented. It is proposed that the major animal phylum-characteristic suites of morphological motifs first emerged more than a half-billion years ago in multicellular aggregates and clusters that did not exhibit an egg-soma divergence. These pre-metazoan bodies were organized by "dynamical patterning modules" (DPMs), physical processes and effects mobilized on the new multicellular scale by ancient conserved genes that came to mediate cell-cell interactions in these clusters. "Proto-eggs" were enlarged cells that through cleavage, or physical confinement by a secreted matrix, served to enforce genomic and genetic homogeneity in the cell clusters arising from them. Enlargement of the founder cell was the occasion for spontaneous intra-egg spatiotemporal organization based on single-cell physiological functions - calcium transients and oscillations, cytoplasmic flows - operating on the larger scale. Ooplasmic segregation by egg-patterning processes, while therefore not due to adaptive responses to external challenges, served as evolutionarily fertile "pre-adaptations" by making the implementation of the later-acting (at the multicellular "morphogenetic stage" of embryogenesis) DPMs more reliable, robust, and defining of sub-phylum morphotypes. This perspective is seen to account for a number of otherwise difficult to understand features of the evolution of development, such as the rapid diversification of biological forms with a conserved genetic toolkit at the dawn of animal evolution, the capability of even obligatory sexual reproducers to propagate vegetatively, and the "embryonic hourglass" of comparative developmental biology.}, } @article {pmid24696401, year = {2014}, author = {Carr, M and Suga, H}, title = {The holozoan Capsaspora owczarzaki possesses a diverse complement of active transposable element families.}, journal = {Genome biology and evolution}, volume = {6}, number = {4}, pages = {949-963}, pmid = {24696401}, issn = {1759-6653}, mesh = {DNA Transposable Elements/*physiology ; Eukaryota/*genetics ; *Evolution, Molecular ; Genome/*physiology ; }, abstract = {Capsaspora owczarzaki, a protistan symbiont of the pulmonate snail Biomphalaria glabrata, is the centre of much interest in evolutionary biology due to its close relationship to Metazoa. The whole genome sequence of this protist has revealed new insights into the ancestral genome composition of Metazoa, in particular with regard to gene families involved in the evolution of multicellularity. The draft genome revealed the presence of 23 families of transposable element, made up from DNA transposon as well as long terminal repeat (LTR) and non-LTR retrotransposon families. The phylogenetic analyses presented here show that all of the transposable elements identified in the C. owczarzaki genome have orthologous families in Metazoa, indicating that the ancestral metazoan also had a rich diversity of elements. Molecular evolutionary analyses also show that the majority of families has recently been active within the Capsaspora genome. One family now appears to be inactive and a further five families show no evidence of current transposition. Most individual element copies are evolutionarily young; however, a small proportion of inserts appear to have persisted for longer in the genome. The families present in the genome show contrasting population histories and appear to be in different stages of their life cycles. Transcriptome data have been analyzed from multiple stages in the C. owczarzaki life cycle. Expression levels vary greatly both between families and between different stages of the life cycle, suggesting an unexpectedly complex level of transposable element regulation in a single celled organism.}, } @article {pmid24691450, year = {2014}, author = {Brakel, J and Werner, FJ and Tams, V and Reusch, TB and Bockelmann, AC}, title = {Current European Labyrinthula zosterae are not virulent and modulate seagrass (Zostera marina) defense gene expression.}, journal = {PloS one}, volume = {9}, number = {4}, pages = {e92448}, pmid = {24691450}, issn = {1932-6203}, mesh = {Biomass ; Endophytes ; *Gene Expression Regulation, Plant ; Host-Pathogen Interactions/genetics/immunology ; Plant Leaves/growth & development ; Stramenopiles/*pathogenicity ; Zosteraceae/*genetics/growth & development/immunology/*parasitology ; }, abstract = {Pro- and eukaryotic microbes associated with multi-cellular organisms are receiving increasing attention as a driving factor in ecosystems. Endophytes in plants can change host performance by altering nutrient uptake, secondary metabolite production or defense mechanisms. Recent studies detected widespread prevalence of Labyrinthula zosterae in European Zostera marina meadows, a protist that allegedly caused a massive amphi-Atlantic seagrass die-off event in the 1930's, while showing only limited virulence today. As a limiting factor for pathogenicity, we investigated genotype × genotype interactions of host and pathogen from different regions (10-100 km-scale) through reciprocal infection. Although the endophyte rapidly infected Z. marina, we found little evidence that Z. marina was negatively impacted by L. zosterae. Instead Z. marina showed enhanced leaf growth and kept endophyte abundance low. Moreover, we found almost no interaction of protist × eelgrass-origin on different parameters of L. zosterae virulence/Z. marina performance, and also no increase in mortality after experimental infection. In a target gene approach, we identified a significant down-regulation in the expression of 6/11 genes from the defense cascade of Z. marina after real-time quantitative PCR, revealing strong immune modulation of the host's defense by a potential parasite for the first time in a marine plant. Nevertheless, one gene involved in phenol synthesis was strongly up-regulated, indicating that Z. marina plants were probably able to control the level of infection. There was no change in expression in a general stress indicator gene (HSP70). Mean L. zosterae abundances decreased below 10% after 16 days of experimental runtime. We conclude that under non-stress conditions L. zosterae infection in the study region is not associated with substantial virulence.}, } @article {pmid24689915, year = {2014}, author = {Hanschen, ER and Ferris, PJ and Michod, RE}, title = {Early evolution of the genetic basis for soma in the volvocaceae.}, journal = {Evolution; international journal of organic evolution}, volume = {68}, number = {7}, pages = {2014-2025}, doi = {10.1111/evo.12416}, pmid = {24689915}, issn = {1558-5646}, mesh = {Cell Differentiation ; *Evolution, Molecular ; *Gene Duplication ; *Genes, Plant ; Phylogeny ; Volvox/cytology/*genetics ; }, abstract = {To understand the hierarchy of life in evolutionary terms, we must explain why groups of one kind of individual, say cells, evolve into a new higher level individual, a multicellular organism. A fundamental step in this process is the division of labor into nonreproductive altruistic soma. The regA gene is critical for somatic differentiation in Volvox carteri, a multicellular species of volvocine algae. We report the sequence of regA-like genes and several syntenic markers from divergent species of Volvox. We show that regA evolved early in the volvocines and predict that lineages with and without soma descended from a regA-containing ancestor. We hypothesize an alternate evolutionary history of regA than the prevailing "proto-regA" hypothesis. The variation in presence of soma may be explained by multiple lineages independently evolving soma utilizing regA or alternate genetic pathways. Our prediction that the genetic basis for soma exists in species without somatic cells raises a number of questions, most fundamentally, under what conditions would species with the genetic potential for soma, and hence greater individuality, not evolve these traits. We conclude that the evolution of individuality in the volvocine algae is more complicated and labile than previously appreciated on theoretical grounds.}, } @article {pmid24679530, year = {2014}, author = {Sánchez Alvarado, A and Yamanaka, S}, title = {Rethinking differentiation: stem cells, regeneration, and plasticity.}, journal = {Cell}, volume = {157}, number = {1}, pages = {110-119}, pmid = {24679530}, issn = {1097-4172}, support = {R37 GM057260/GM/NIGMS NIH HHS/United States ; R37GM057260/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *Cell Differentiation ; Humans ; Plant Cells/physiology ; Plants/embryology ; Pluripotent Stem Cells/cytology ; Regeneration ; Stem Cells/*cytology/physiology ; }, abstract = {Cell differentiation is an essential process for the development, growth, reproduction, and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past four decades. The study of natural and induced stem cells has ushered an age of re-examination of what it means to be a stem or a differentiated cell. Past and recent discoveries in plants and animals, as well as novel experimental manipulations, are beginning to erode many of these established concepts and are forcing a re-evaluation of the experimental systems and paradigms presently being used to explore these and other biological process.}, } @article {pmid24678663, year = {2014}, author = {Nakanishi, N and Sogabe, S and Degnan, BM}, title = {Evolutionary origin of gastrulation: insights from sponge development.}, journal = {BMC biology}, volume = {12}, number = {}, pages = {26}, pmid = {24678663}, issn = {1741-7007}, mesh = {Animals ; Apoptosis/genetics ; *Biological Evolution ; Cell Lineage ; Epithelium/embryology ; GATA Transcription Factors/genetics/metabolism ; *Gastrulation ; Gene Expression Regulation, Developmental ; Germ Layers/embryology ; Larva/genetics/ultrastructure ; Metamorphosis, Biological/genetics ; Phagocytosis ; Phylogeny ; Porifera/cytology/*embryology/genetics ; RNA, Messenger/genetics/metabolism ; }, abstract = {BACKGROUND: The evolutionary origin of gastrulation--defined as a morphogenetic event that leads to the establishment of germ layers--remains a vexing question. Central to this debate is the evolutionary relationship between the cell layers of sponges (poriferans) and eumetazoan germ layers. Despite considerable attention, it remains unclear whether sponge cell layers undergo progressive fate determination akin to eumetazoan primary germ layer formation during gastrulation.

RESULTS: Here we show by cell-labelling experiments in the demosponge Amphimedon queenslandica that the cell layers established during embryogenesis have no relationship to the cell layers of the juvenile. In addition, juvenile epithelial cells can transdifferentiate into a range of cell types and move between cell layers. Despite the apparent lack of cell layer and fate determination and stability in this sponge, the transcription factor GATA, a highly conserved eumetazoan endomesodermal marker, is expressed consistently in the inner layer of A. queenslandica larvae and juveniles.

CONCLUSIONS: Our results are compatible with sponge cell layers not undergoing progressive fate determination and thus not being homologous to eumetazoan germ layers. Nonetheless, the expression of GATA in the sponge inner cell layer suggests a shared ancestry with the eumetazoan endomesoderm, and that the ancestral role of GATA in specifying internalised cells may antedate the origin of germ layers. Together, these results support germ layers and gastrulation evolving early in eumetazoan evolution from pre-existing developmental programs used for the simple patterning of cells in the first multicellular animals.}, } @article {pmid24656331, year = {2014}, author = {Lee, JY}, title = {New and old roles of plasmodesmata in immunity and parallels to tunneling nanotubes.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {221-222}, number = {}, pages = {13-20}, pmid = {24656331}, issn = {1873-2259}, support = {P30 GM103519/GM/NIGMS NIH HHS/United States ; 8P30 GM103519-03/GM/NIGMS NIH HHS/United States ; 5P30 RR031160-03/RR/NCRR NIH HHS/United States ; }, mesh = {Biological Evolution ; Cell Communication ; Nanotubes/*chemistry ; Plants/*immunology ; Plasmodesmata/*immunology ; Signal Transduction ; }, abstract = {Effective cell-to-cell communication is critical for the survival of both unicellular and multicellular organisms. In multicellular plants, direct cell coupling across the cell wall boundaries is mediated by long membrane-lined cytoplasmic bridges, the plasmodesmata. Exciting recent discoveries suggest that the occurrence of such membrane-lined intercellular channels is not unique to plant lineages but more prevalent across biological kingdoms than previously assumed. Striking functional analogies exist among those channels, in that not only do they all facilitate the exchange of various forms of macromolecules, but also they are exploited by some opportunistic pathogens to spread infection from one host cell to another. However, host cells may have also evolved strategies to offset such exploitation of the critical cellular infrastructure by the pathogen. Indeed, recent studies support an emerging paradigm that cellular connectivity via plasmodesmata plays an important role in innate immune responses. Preliminary hypotheses are proposed as to how various regulatory mechanisms integrating plasmodesmata into immune signaling pathways may have evolved.}, } @article {pmid24652835, year = {2014}, author = {Messina, G and Damia, E and Fanti, L and Atterrato, MT and Celauro, E and Mariotti, FR and Accardo, MC and Walther, M and Vernì, F and Picchioni, D and Moschetti, R and Caizzi, R and Piacentini, L and Cenci, G and Giordano, E and Dimitri, P}, title = {Yeti, an essential Drosophila melanogaster gene, encodes a protein required for chromatin organization.}, journal = {Journal of cell science}, volume = {127}, number = {Pt 11}, pages = {2577-2588}, doi = {10.1242/jcs.150243}, pmid = {24652835}, issn = {1477-9137}, mesh = {Animals ; Animals, Genetically Modified ; Carrier Proteins/genetics/metabolism ; Cells, Cultured ; Chromatin Assembly and Disassembly/genetics ; Conserved Sequence/genetics ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*physiology ; Evolution, Molecular ; Histones/metabolism ; Mutation/genetics ; Nuclear Proteins ; Phosphoproteins/genetics/*metabolism ; Polytene Chromosomes/*metabolism ; Protein Binding ; Signal Transduction ; Transcription Factors/*metabolism ; }, abstract = {The evolutionarily conserved family of Bucentaur (BCNT) proteins exhibits a widespread distribution in animal and plants, yet its biological role remains largely unknown. Using Drosophila melanogaster as a model organism, we investigated the in vivo role of the Drosophila BCNT member called YETI. We report that loss of YETI causes lethality before pupation and defects in higher-order chromatin organization, as evidenced by severe impairment in the association of histone H2A.V, nucleosomal histones and epigenetic marks with polytene chromosomes. We also find that YETI binds to polytene chromosomes through its conserved BCNT domain and interacts with the histone variant H2A.V, HP1a and Domino-A (DOM-A), the ATPase subunit of the DOM/Tip60 chromatin remodeling complex. Furthermore, we identify YETI as a downstream target of the Drosophila DOM-A. On the basis of these results, we propose that YETI interacts with H2A.V-exchanging machinery, as a chaperone or as a new subunit of the DOM/Tip60 remodeling complex, and acts to regulate the accumulation of H2A.V at chromatin sites. Overall, our findings suggest an unanticipated role of YETI protein in chromatin organization and provide, for the first time, mechanistic clues on how BCNT proteins control development in multicellular organisms.}, } @article {pmid24642410, year = {2014}, author = {Hudry, B and Thomas-Chollier, M and Volovik, Y and Duffraisse, M and Dard, A and Frank, D and Technau, U and Merabet, S}, title = {Molecular insights into the origin of the Hox-TALE patterning system.}, journal = {eLife}, volume = {3}, number = {}, pages = {e01939}, pmid = {24642410}, issn = {2050-084X}, support = {P 24858/FWF_/Austrian Science Fund FWF/Austria ; P 27353/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; Animals, Genetically Modified ; Binding Sites ; *Body Patterning ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/embryology/genetics/*metabolism ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/genetics/*metabolism ; Phylogeny ; Promoter Regions, Genetic ; Protein Binding ; Sea Anemones/embryology/genetics/metabolism ; Species Specificity ; Transcription Factors/genetics/*metabolism ; Xenopus/embryology/genetics/*metabolism ; Xenopus Proteins/genetics/*metabolism ; }, abstract = {Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior-posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox-TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001.}, } @article {pmid24633620, year = {2014}, author = {Niklas, KJ and Kutschera, U}, title = {Amphimixis and the individual in evolving populations: does Weismann's Doctrine apply to all, most or a few organisms?.}, journal = {Die Naturwissenschaften}, volume = {101}, number = {5}, pages = {357-372}, pmid = {24633620}, issn = {1432-1904}, mesh = {Animals ; Bacterial Physiological Phenomena ; *Biological Evolution ; Life Cycle Stages ; Plant Physiological Phenomena ; Reproduction/*physiology ; }, abstract = {The German biologist August Weismann (1834-1914) proposed that amphimixis (sexual reproduction) creates variability for natural selection to act upon, and hence he became one of the founders of the Neo-Darwinian theory of biological evolution. He is perhaps best known for what is called "Weismann's Doctrine" or "Weismann's Barrier" (i.e. the irreversible separation of somatic and germ cell functionalities early during ontogeny in multicellular organisms). This concept provided an unassailable argument against "soft inheritance" sensu Lamarck and informed subsequent theorists that the only "individual" in the context of evolution is the mature, reproductive organism. Herein, we review representative model organisms whose embryology conforms to Weismann's Doctrine (e.g. flies and mammals) and those that do not (e.g. freshwater hydroids and plants) based on this survey and the Five Kingdoms of Life scheme; we point out that most species (notably bacteria, fungi, protists and plants) are "non-Weismannian" in ways that make a canonical definition of the "individual" problematic if not impossible. We also review critical life history functional traits that allow us to create a matrix of all theoretically conceivable life cycles (for eukaryotic algae, embryophytes, fungi and animals), which permits us to establish where this scheme Weismann's Doctrine holds true and where it does not. In addition, we argue that bacteria, the dominant organisms of the biosphere, exist in super-cellular biofilms but rarely as single (planktonic) microbes. Our analysis attempts to show that competition among genomic variants in cell lineages played a critical part in the evolution of multicellularity and life cycle diversity. This feature was largely ignored during the formulation of the synthetic theory of biological evolution and its subsequent elaborations.}, } @article {pmid24614804, year = {2014}, author = {McCracken, A and Locke, J}, title = {Mutations in CG8878, a novel putative protein kinase, enhance P element dependent silencing (PDS) and position effect variegation (PEV) in Drosophila melanogaster.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e71695}, pmid = {24614804}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Chromobox Protein Homolog 5 ; Chromosomal Position Effects/*genetics ; DNA Transposable Elements/*genetics ; Drosophila Proteins/*genetics ; Drosophila melanogaster/*enzymology/*genetics ; Enhancer Elements, Genetic/genetics ; Evolution, Molecular ; Female ; *Gene Silencing ; Humans ; Magnetic Resonance Spectroscopy ; Male ; Models, Molecular ; Molecular Sequence Data ; Mutation/*genetics ; Phenotype ; Phylogeny ; Protein Kinases/*genetics ; Protein Serine-Threonine Kinases/*genetics ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {Genes in multicellular organisms are expressed as part of a developmental program that is largely dependent on self-perpetuating higher-order chromatin states. The mechanism of establishing and maintaining these epigenetic events is well studied in Drosophila. The first known example of an epigenetic effect was that of (PEV) in Drosophila, which has been shown to be due to gene silencing via heterochromatin formation. We are investigating a process similar to Position Effect Variegation (PEV) using a mini-w transgene, called Pci, inserted in the upstream regulatory region of ci. The mini-white+ transgene in Pci is expressed throughout the adult eye; however, when other P or KP elements are present, a variegated eye phenotype results indicating random w+ silencing during development. This P element dependent silencing (PDS) can be modified by the haplo-suppressors/triplo-enhancers, Su(var)205 and Su(var)3-7, indicating that these heterochromatic modifiers also act dose dependently in PDS. Here we use a spontaneous derivative mutation of Pci called PciE1 (E1) that variegates like PDS in the absence of P elements, presumably due to an adjacent gypsy element insertion, to screen for second-site modifier mutations that enhance variable silencing of white+ in E1. We isolated 7 mutations in CG8878, an essential gene, that enhance the E1 variegated phenotype. CG8878, a previously uncharacterized gene, potentially encodes a serine/threonine kinase whose closest Drosophila paralogue, ballchen (nhk-1), phosphorylates histones. These mutant alleles enhance both PDS at E1 and Position Effect Variegation (PEV) at w(m4), indicating a previously unknown common silencing mechanism between the two.}, } @article {pmid24604070, year = {2014}, author = {Gombar, S and MacCarthy, T and Bergman, A}, title = {Epigenetics decouples mutational from environmental robustness. Did it also facilitate multicellularity?.}, journal = {PLoS computational biology}, volume = {10}, number = {3}, pages = {e1003450}, pmid = {24604070}, issn = {1553-7358}, support = {R01 AG028872/AG/NIA NIH HHS/United States ; R01-AG028872/AG/NIA NIH HHS/United States ; P01 AG027734/AG/NIA NIH HHS/United States ; T32 GM007288/GM/NIGMS NIH HHS/United States ; P01-AG027734/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; DNA Mutational Analysis ; Drosophila melanogaster ; Environment ; *Epigenesis, Genetic ; Evolution, Molecular ; *Gene Regulatory Networks ; Gene-Environment Interaction ; Genetic Association Studies ; Histones/chemistry ; *Mutation ; Polycomb-Group Proteins/metabolism ; }, abstract = {The evolution of ever increasing complex life forms has required innovations at the molecular level in order to overcome existing barriers. For example, evolving processes for cell differentiation, such as epigenetic mechanisms, facilitated the transition to multicellularity. At the same time, studies using gene regulatory network models, and corroborated in single-celled model organisms, have shown that mutational robustness and environmental robustness are correlated. Such correlation may constitute a barrier to the evolution of multicellularity since cell differentiation requires sensitivity to cues in the internal environment during development. To investigate how this barrier might be overcome, we used a gene regulatory network model which includes epigenetic control based on the mechanism of histone modification via Polycomb Group Proteins, which evolved in tandem with the transition to multicellularity. Incorporating the Polycomb mechanism allowed decoupling of mutational and environmental robustness, thus allowing the system to be simultaneously robust to mutations while increasing sensitivity to the environment. In turn, this decoupling facilitated cell differentiation which we tested by evaluating the capacity of the system for producing novel output states in response to altered initial conditions. In the absence of the Polycomb mechanism, the system was frequently incapable of adding new states, whereas with the Polycomb mechanism successful addition of new states was nearly certain. The Polycomb mechanism, which dynamically reshapes the network structure during development as a function of expression dynamics, decouples mutational and environmental robustness, thus providing a necessary step in the evolution of multicellularity.}, } @article {pmid24583766, year = {2014}, author = {Hardie, DG and Ashford, ML}, title = {AMPK: regulating energy balance at the cellular and whole body levels.}, journal = {Physiology (Bethesda, Md.)}, volume = {29}, number = {2}, pages = {99-107}, pmid = {24583766}, issn = {1548-9221}, support = {/WT_/Wellcome Trust/United Kingdom ; 097726/WT_/Wellcome Trust/United Kingdom ; MR/K003291/1/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {AMP-Activated Protein Kinases/*metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Calcium/metabolism ; Energy Metabolism/*physiology ; Homeostasis/*physiology ; Hormones/metabolism ; Humans ; }, abstract = {AMP-activated protein kinase appears to have evolved in single-celled eukaryotes as an adenine nucleotide sensor that maintains energy homeostasis at the cellular level. However, during evolution of more complex multicellular organisms, the system has adapted to interact with hormones so that it also plays a key role in balancing energy intake and expenditure at the whole body level.}, } @article {pmid24567306, year = {2014}, author = {de Mendoza, A and Sebé-Pedrós, A and Ruiz-Trillo, I}, title = {The evolution of the GPCR signaling system in eukaryotes: modularity, conservation, and the transition to metazoan multicellularity.}, journal = {Genome biology and evolution}, volume = {6}, number = {3}, pages = {606-619}, pmid = {24567306}, issn = {1759-6653}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Animals ; Arrestin/genetics ; Eukaryota/*classification/*genetics ; Evolution, Molecular ; Eye Proteins/genetics ; G-Protein-Coupled Receptor Kinases/genetics ; GTP-Binding Protein Regulators/genetics ; Genome ; Multigene Family ; Phosphoproteins/genetics ; Phylogeny ; Principal Component Analysis ; Receptors, G-Protein-Coupled/*genetics ; Signal Transduction/*genetics ; }, abstract = {The G-protein-coupled receptor (GPCR) signaling system is one of the main signaling pathways in eukaryotes. Here, we analyze the evolutionary history of all its components, from receptors to regulators, to gain a broad picture of its system-level evolution. Using eukaryotic genomes covering most lineages sampled to date, we find that the various components of the GPCR signaling pathway evolved independently, highlighting the modular nature of this system. Our data show that some GPCR families, G proteins, and regulators of G proteins diversified through lineage-specific diversifications and recurrent domain shuffling. Moreover, most of the gene families involved in the GPCR signaling system were already present in the last common ancestor of eukaryotes. Furthermore, we show that the unicellular ancestor of Metazoa already had most of the cytoplasmic components of the GPCR signaling system, including, remarkably, all the G protein alpha subunits, which are typical of metazoans. Thus, we show how the transition to multicellularity involved conservation of the signaling transduction machinery, as well as a burst of receptor diversification to cope with the new multicellular necessities.}, } @article {pmid24563351, year = {2014}, author = {Lyakhovetsky, R and Gruenbaum, Y}, title = {Studying lamins in invertebrate models.}, journal = {Advances in experimental medicine and biology}, volume = {773}, number = {}, pages = {245-262}, doi = {10.1007/978-1-4899-8032-8_11}, pmid = {24563351}, issn = {0065-2598}, mesh = {Animals ; Lamins/chemistry/genetics/*physiology ; *Models, Biological ; Molecular Structure ; Phylogeny ; }, abstract = {Lamins are nuclear intermediate filament proteins that are conserved in all multicellular animals. Proteins that resemble lamins are also found in unicellular organisms and in plants. Lamins form a proteinaceous meshwork that outlines the nucleoplasmic side of the inner nuclear membrane, while a small fraction of lamin molecules is also present in the nucleoplasm. They provide structural support for the nucleus and help regulate many other nuclear activities. Much of our knowledge on the function of nuclear lamins and their associated proteins comes from studies in invertebrate organisms and specifically in the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. The simpler lamin system and the powerful genetic tools offered by these model organisms greatly promote such studies. Here we provide an overview of recent advances in the biology of invertebrate nuclear lamins, with special emphasis on their assembly, cellular functions and as models for studying the molecular basis underlying the pathology of human heritable diseases caused by mutations in lamins A/C.}, } @article {pmid24561726, year = {2014}, author = {Williams, F and Tew, HA and Paul, CE and Adams, JC}, title = {The predicted secretomes of Monosiga brevicollis and Capsaspora owczarzaki, close unicellular relatives of metazoans, reveal new insights into the evolution of the metazoan extracellular matrix.}, journal = {Matrix biology : journal of the International Society for Matrix Biology}, volume = {37}, number = {}, pages = {60-68}, doi = {10.1016/j.matbio.2014.02.002}, pmid = {24561726}, issn = {1569-1802}, mesh = {Amino Acid Sequence ; *Biological Evolution ; Choanoflagellata/*metabolism ; Extracellular Matrix/*metabolism ; Extracellular Matrix Proteins/genetics/*metabolism ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment ; Signal Transduction/*physiology ; Species Specificity ; }, abstract = {The extracellular matrix (ECM) is a major mediator of multi-cellularity in the metazoa. Multiple ECM proteins are conserved from sponges to human, raising questions about the evolutionary origin of ECM. Choanoflagellates are the closest unicellular relatives of the metazoa and proteins with domains characteristic of metazoan ECM proteins have been identified from the genome-predicted proteome of the choanoflagellate Monosiga brevicollis. However, a systematic analysis of M. brevicollis secretory signal peptide-containing proteins with ECM domains has been lacking. We analysed all predicted secretory signal-peptide-containing proteins of M. brevicollis for ECM domains. Nine domains that are widespread in metazoan ECM proteins are represented, with EGF, fibronectin III, laminin G, and von Willebrand Factor_A domains being the most numerous. Three proteins contain more than one category of ECM domain, however, no proteins correspond to the domain architecture of metazoan ECM proteins. The fibronectin III domains are all present within glycoside hydrolases and none contain an integrin-binding motif. Glycosaminoglycan-binding motifs identified in animal thrombospondin type 1 domains are conserved in some M. brevicollis representatives of this domain, whereas there is little evidence of conservation of glycosaminoglycan-binding motifs in the laminin G domains. The identified proteins were compared with the predicted secretory ECM domain-containing proteins of the integrin-expressing filasterean, Capsaspora owczarzaki. C. owczarzaki encodes a smaller number of secretory, ECM domain-containing proteins and only EGF, fibronectin type III and laminin G domains are represented. The M. brevicollis and C. owczarzaki proteins have distinct domain architectures and all proteins differ in their domain architecture to metazoan ECM proteins. These identifications provide a basis for future experiments to validate the extracellular location of these proteins and uncover their functions in choanoflagellates and C. owczarzaki. The data strengthen the model that ECM proteins are metazoan-specific and evolved as innovations in the last common metazoan ancestor.}, } @article {pmid24552098, year = {2013}, author = {Frederickson, ME}, title = {Rethinking mutualism stability: cheaters and the evolution of sanctions.}, journal = {The Quarterly review of biology}, volume = {88}, number = {4}, pages = {269-295}, doi = {10.1086/673757}, pmid = {24552098}, issn = {0033-5770}, mesh = {Animals ; *Biological Evolution ; Insecta/physiology ; Magnoliopsida/physiology ; Rhizobium/physiology ; *Symbiosis ; }, abstract = {How cooperation originates and persists in diverse species, from bacteria to multicellular organisms to human societies, is a major question in evolutionary biology. A large literature asks: what prevents selection for cheating within cooperative lineages? In mutualisms, or cooperative interactions between species, feedback between partners often aligns their fitness interests, such that cooperative symbionts receive more benefits from their hosts than uncooperative symbionts. But how do these feedbacks evolve? Cheaters might invade symbiont populations and select for hosts that preferentially reward or associate with cooperators (often termed sanctions or partner choice); hosts might adapt to variation in symbiont quality that does not amount to cheating (e.g., environmental variation); or conditional host responses might exist before cheaters do, making mutualisms stable from the outset. I review evidence from yucca-yucca moth, fig-fig wasp, and legume-rhizobium mutualisms, which are commonly cited as mutualisms stabilized by sanctions. Based on the empirical evidence, it is doubtful that cheaters select for host sanctions in these systems; cheaters are too uncommon. Recognizing that sanctions likely evolved for functions other than retaliation against cheaters offers many insights about mutualism coevolution, and about why mutualism evolves in only some lineages of potential hosts.}, } @article {pmid24520931, year = {2014}, author = {Schultheiss, KP and Craddock, BP and Suga, H and Miller, WT}, title = {Regulation of Src and Csk nonreceptor tyrosine kinases in the filasterean Ministeria vibrans.}, journal = {Biochemistry}, volume = {53}, number = {8}, pages = {1320-1329}, pmid = {24520931}, issn = {1520-4995}, support = {R01 CA058530/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; CSK Tyrosine-Protein Kinase ; Cloning, Molecular ; Eukaryota/*enzymology ; HEK293 Cells ; Humans ; Models, Molecular ; Protein Structure, Tertiary ; Sequence Homology ; src-Family Kinases/chemistry/genetics/*metabolism ; }, abstract = {The development of the phosphotyrosine-based signaling system predated the evolution of multicellular animals. Single-celled choanoflagellates, the closest living relatives to metazoans, possess numerous tyrosine kinases, including Src family nonreceptor tyrosine kinases. Choanoflagellates also have Csk (C-terminal Src kinase), the enzyme that regulates Src in metazoans; however, choanoflagellate Csk kinases fail to repress the cognate Src. Here, we have cloned and characterized Src and Csk kinases from Ministeria vibrans, a filasterean (the sister group to metazoans and choanoflagellates). The two Src kinases (MvSrc1 and MvSrc2) are enzymatically active Src kinases, although they have low activity toward mammalian cellular proteins. Unexpectedly, MvSrc2 has significant Ser/Thr kinase activity. The Csk homologue (MvCsk) is enzymatically inactive and fails to repress MvSrc activity. We suggest that the low activity of MvCsk is due to sequences in the SH2-kinase interface, and we show that a point mutation in this region partially restores MvCsk activity. The inactivity of filasterean Csk kinases is consistent with a model in which the stringent regulation of Src family kinases arose more recently in evolution, after the split between choanoflagellates and multicellular animals.}, } @article {pmid24507487, year = {2014}, author = {Cock, JM and Godfroy, O and Macaisne, N and Peters, AF and Coelho, SM}, title = {Evolution and regulation of complex life cycles: a brown algal perspective.}, journal = {Current opinion in plant biology}, volume = {17}, number = {}, pages = {1-6}, doi = {10.1016/j.pbi.2013.09.004}, pmid = {24507487}, issn = {1879-0356}, mesh = {Algal Proteins/genetics ; Diploidy ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Haploidy ; Life Cycle Stages/*genetics ; *Mutation ; Phaeophyceae/classification/*genetics/*growth & development ; Phylogeny ; }, abstract = {The life cycle of an organism is one of its fundamental features, influencing many aspects of its biology. The brown algae exhibit a diverse range of life cycles indicating that transitions between life cycle types may have been key adaptive events in the evolution of this group. Life cycle mutants, identified in the model organism Ectocarpus, are providing information about how life cycle progression is regulated at the molecular level in brown algae. We explore some of the implications of the phenotypes of the life cycle mutants described to date and draw comparisons with recent insights into life cycle regulation in the green lineage. Given the importance of coordinating growth and development with life cycle progression, we suggest that the co-option of ancient life cycle regulators to control key developmental events may be a common feature in diverse groups of multicellular eukaryotes.}, } @article {pmid24499792, year = {2014}, author = {Swer, PB and Bhadoriya, P and Saran, S}, title = {Analysis of Rheb in the cellular slime mold Dictyostelium discoideum: cellular localization, spatial expression and overexpression.}, journal = {Journal of biosciences}, volume = {39}, number = {1}, pages = {75-84}, pmid = {24499792}, issn = {0973-7138}, mesh = {Bacterial Proteins/metabolism ; Base Sequence ; Cluster Analysis ; DNA Primers/genetics ; Dictyostelium/*genetics/metabolism ; Gene Expression Profiling ; Immunoblotting ; In Situ Hybridization ; Luminescent Proteins/metabolism ; Molecular Sequence Data ; Monomeric GTP-Binding Proteins/*genetics/metabolism ; Neuropeptides/*genetics/metabolism ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Signal Transduction/genetics ; TOR Serine-Threonine Kinases/genetics/metabolism ; }, abstract = {Dictyostelium discoideum encodes a single Rheb protein showing sequence similarity to human homologues of Rheb. The DdRheb protein shares 52 percent identity and 100 percent similarity with the human Rheb1 protein. Fluorescence of Rheb yellow fluorescent protein fusion was detected in the D. discoideum cytoplasm. Reverse transcription-polymerase chain reaction and whole-mount in situ hybridization analyses showed that rheb is expressed at all stages of development and in prestalk cells in the multicellular structures developed. When the expression of rheb as a fusion with lacZ was driven under its own promoter, the beta-galactosidase activity was seen in the prestalk cells. D. discoideum overexpressing Rheb shows an increase in the size of the cell. Treatment of the overexpressing Rheb cells with rapamycin confirms its involvement in the TOR signalling pathway.}, } @article {pmid24498429, year = {2014}, author = {Kollmar, M and Hatje, K}, title = {Shared gene structures and clusters of mutually exclusive spliced exons within the metazoan muscle myosin heavy chain genes.}, journal = {PloS one}, volume = {9}, number = {2}, pages = {e88111}, pmid = {24498429}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Arthropods/*genetics ; Drosophila melanogaster/*genetics ; Exons/*genetics ; Molecular Sequence Data ; *Multigene Family ; Muscles/*metabolism ; Myosin Heavy Chains/*genetics ; Phylogeny ; RNA Splicing/*genetics ; Sequence Homology ; Sequence Homology, Amino Acid ; }, abstract = {Multicellular animals possess two to three different types of muscle tissues. Striated muscles have considerable ultrastructural similarity and contain a core set of proteins including the muscle myosin heavy chain (Mhc) protein. The ATPase activity of this myosin motor protein largely dictates muscle performance at the molecular level. Two different solutions to adjusting myosin properties to different muscle subtypes have been identified so far: Vertebrates and nematodes contain many independent differentially expressed Mhc genes while arthropods have single Mhc genes with clusters of mutually exclusive spliced exons (MXEs). The availability of hundreds of metazoan genomes now allowed us to study whether the ancient bilateria already contained MXEs, how MXE complexity subsequently evolved, and whether additional scenarios to control contractile properties in different muscles could be proposed, By reconstructing the Mhc genes from 116 metazoans we showed that all intron positions within the motor domain coding regions are conserved in all bilateria analysed. The last common ancestor of the bilateria already contained a cluster of MXEs coding for part of the loop-2 actin-binding sequence. Subsequently the protostomes and later the arthropods gained many further clusters while MXEs got completely lost independently in several branches (vertebrates and nematodes) and species (for example the annelid Helobdella robusta and the salmon louse Lepeophtheirus salmonis). Several bilateria have been found to encode multiple Mhc genes that might all or in part contain clusters of MXEs. Notable examples are a cluster of six tandemly arrayed Mhc genes, of which two contain MXEs, in the owl limpet Lottia gigantea and four Mhc genes with three encoding MXEs in the predatory mite Metaseiulus occidentalis. Our analysis showed that similar solutions to provide different myosin isoforms (multiple genes or clusters of MXEs or both) have independently been developed several times within bilaterian evolution.}, } @article {pmid24464418, year = {2014}, author = {Vijg, J}, title = {Aging genomes: a necessary evil in the logic of life.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {36}, number = {3}, pages = {282-292}, pmid = {24464418}, issn = {1521-1878}, support = {P01 AG017242/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*genetics ; Animals ; DNA Damage/genetics ; Genome/*genetics ; Humans ; *Life ; Mutation/genetics ; }, abstract = {Genomes are inherently unstable because of the need for DNA sequence variation as a substrate for evolution through natural selection. However, most multicellular organisms have postmitotic tissues, with limited opportunity for selective removal of cells harboring persistent damage and deleterious mutations, which can therefore contribute to functional decline, disease, and death. Key in this process is the role of genome maintenance, the network of protein products that repair DNA damage and signal DNA damage response pathways. Genome maintenance is beneficial early in life by swiftly eliminating DNA damage or damaged cells, facilitating rapid cell proliferation. However, at later ages accumulation of unrepaired damage and mutations, as well as ongoing cell depletion, promotes cancer, atrophy, and other deleterious effects associated with aging. As such, genome maintenance and its phenotypic sequelae provide yet another example of antagonistic pleiotropy in aging and longevity.}, } @article {pmid24463524, year = {2014}, author = {Jiang, C and Brown, PJ and Ducret, A and Brun, YV}, title = {Sequential evolution of bacterial morphology by co-option of a developmental regulator.}, journal = {Nature}, volume = {506}, number = {7489}, pages = {489-493}, pmid = {24463524}, issn = {1476-4687}, support = {F32 AI072992/AI/NIAID NIH HHS/United States ; S10 RR028697/RR/NCRR NIH HHS/United States ; GM051986/GM/NIGMS NIH HHS/United States ; S10RR028697-01/RR/NCRR NIH HHS/United States ; AI072992/AI/NIAID NIH HHS/United States ; R01 GM051986/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*cytology/*metabolism ; Bacterial Proteins/*metabolism ; *Biological Evolution ; Caulobacter crescentus/cytology/metabolism ; Caulobacteraceae/cytology/metabolism ; Cell Membrane/metabolism ; *Cell Polarity ; Evolution, Molecular ; Models, Biological ; Molecular Sequence Data ; Phylogeny ; Protein Transport ; }, abstract = {What mechanisms underlie the transitions responsible for the diverse shapes observed in the living world? Although bacteria exhibit a myriad of morphologies, the mechanisms responsible for the evolution of bacterial cell shape are not understood. We investigated morphological diversity in a group of bacteria that synthesize an appendage-like extension of the cell envelope called the stalk. The location and number of stalks varies among species, as exemplified by three distinct subcellular positions of stalks within a rod-shaped cell body: polar in the genus Caulobacter and subpolar or bilateral in the genus Asticcacaulis. Here we show that a developmental regulator of Caulobacter crescentus, SpmX, is co-opted in the genus Asticcacaulis to specify stalk synthesis either at the subpolar or bilateral positions. We also show that stepwise evolution of a specific region of SpmX led to the gain of a new function and localization of this protein, which drove the sequential transition in stalk positioning. Our results indicate that changes in protein function, co-option and modularity are key elements in the evolution of bacterial morphology. Therefore, similar evolutionary principles of morphological transitions apply to both single-celled prokaryotes and multicellular eukaryotes.}, } @article {pmid24462754, year = {2014}, author = {Wang, N and Yue, Z and Liang, D and Ma, F}, title = {Genome-wide identification of members in the YTH domain-containing RNA-binding protein family in apple and expression analysis of their responsiveness to senescence and abiotic stresses.}, journal = {Gene}, volume = {538}, number = {2}, pages = {292-305}, doi = {10.1016/j.gene.2014.01.039}, pmid = {24462754}, issn = {1879-0038}, mesh = {Chromosome Mapping ; Expressed Sequence Tags ; Gene Duplication ; Gene Expression ; *Genes, Plant ; Genome, Plant ; Malus/*genetics/*metabolism ; Models, Genetic ; Models, Molecular ; Multigene Family ; Phylogeny ; Plant Proteins/chemistry/*genetics/*metabolism ; Protein Structure, Tertiary ; RNA-Binding Proteins/chemistry/*genetics/*metabolism ; Stress, Physiological ; Synteny ; }, abstract = {YT521-homology (YTH) domain-containing RNA-binding proteins (YTPs) are a small gene family involved in post-transcriptional regulation. We identified 26 putative YTP gene models in the apple genome. Although plant YTPs have been classified into three groups, those in multi-cellular organisms belong only to Groups A and B. The apple genome contains 22 YTP gene models in Group A and four in Group B. Duplication analysis showed that tandem and segmental duplications contributed only partially to an expansion in apple YTP numbers. YTH was the only recognizable domain in apple YTPs; its three-dimensional structure implied possible motifs for RNA-binding. After the assembly of expressed sequence tags (ESTs) and gene-cloning, we were able to identify 14 apple YTPs that were expressed in various tissues, especially senescing leaves. Expression analysis showed that these YTPs also responded to several abiotic stresses. Taken together, our genome-wide evaluation provides new insight for further research on the effects of those stresses.}, } @article {pmid24462003, year = {2014}, author = {Ghisalberti, M and Gold, DA and Laflamme, M and Clapham, ME and Narbonne, GM and Summons, RE and Johnston, DT and Jacobs, DK}, title = {Canopy flow analysis reveals the advantage of size in the oldest communities of multicellular eukaryotes.}, journal = {Current biology : CB}, volume = {24}, number = {3}, pages = {305-309}, pmid = {24462003}, issn = {1879-0445}, support = {T32 HG002536/HG/NHGRI NIH HHS/United States ; T32HG002536/HG/NHGRI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Eukaryota/*physiology ; }, abstract = {At Mistaken Point, Newfoundland, Canada, rangeomorph "fronds" dominate the earliest (579-565 million years ago) fossil communities of large (0.1 to 2 m height) multicellular benthic eukaryotes. They lived in low-flow environments, fueled by uptake [1-3] of dissolved reactants (osmotrophy). However, prokaryotes are effective osmotrophs, and the advantage of taller eukaryotic osmotrophs in this deep-water community context has not been addressed. We reconstructed flow-velocity profiles and vertical mixing using canopy flow models appropriate to the densities of the observed communities. Further modeling of processes at organismal surfaces documents increasing uptake with height in the community as a function of thinning of the diffusive boundary layer with increased velocity. The velocity profile, produced by canopy flow in the community, generates this advantage of upward growth. Alternative models of upward growth advantage based on redox/resource gradients fail, given the efficiency of vertical mixing. In benthic communities of osmotrophs of sufficient density, access to flow in low-flow settings provides an advantage to taller architecture, providing a selectional driver for communities of tall eukaryotes in contexts where phototropism cannot contribute to upward growth. These Ediacaran deep-sea fossils were preserved during the increasing oxygenation prior to the Cambrian radiation of animals and likely represent an important phase in the ecological and evolutionary transition to more complex eukaryotic forms.}, } @article {pmid24454845, year = {2014}, author = {Tamura, A and Yamada, N and Yaguchi, Y and Machida, Y and Mori, I and Osanai, M}, title = {Both neurons and astrocytes exhibited tetrodotoxin-resistant metabotropic glutamate receptor-dependent spontaneous slow Ca2+ oscillations in striatum.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e85351}, pmid = {24454845}, issn = {1932-6203}, mesh = {Animals ; Astrocytes/drug effects/metabolism/*physiology ; Calcium/*metabolism ; Corpus Striatum/drug effects/metabolism/*physiology ; Green Fluorescent Proteins/genetics ; Mice ; Mice, Transgenic ; Neurons/drug effects/metabolism/*physiology ; Receptors, Metabotropic Glutamate/*drug effects/*metabolism ; Tetrodotoxin/*pharmacology ; }, abstract = {The striatum plays an important role in linking cortical activity to basal ganglia outputs. Group I metabotropic glutamate receptors (mGluRs) are densely expressed in the medium spiny projection neurons and may be a therapeutic target for Parkinson's disease. The group I mGluRs are known to modulate the intracellular Ca(2+) signaling. To characterize Ca(2+) signaling in striatal cells, spontaneous cytoplasmic Ca(2+) transients were examined in acute slice preparations from transgenic mice expressing green fluorescent protein (GFP) in the astrocytes. In both the GFP-negative cells (putative-neurons) and astrocytes of the striatum, spontaneous slow and long-lasting intracellular Ca(2+) transients (referred to as slow Ca(2+) oscillations), which lasted up to approximately 200 s, were found. Neither the inhibition of action potentials nor ionotropic glutamate receptors blocked the slow Ca(2+) oscillation. Depletion of the intracellular Ca(2+) store and the blockade of inositol 1,4,5-trisphosphate receptors greatly reduced the transient rate of the slow Ca(2+) oscillation, and the application of an antagonist against mGluR5 also blocked the slow Ca(2+) oscillation in both putative-neurons and astrocytes. Thus, the mGluR5-inositol 1,4,5-trisphosphate signal cascade is the primary contributor to the slow Ca(2+) oscillation in both putative-neurons and astrocytes. The slow Ca(2+) oscillation features multicellular synchrony, and both putative-neurons and astrocytes participate in the synchronous activity. Therefore, the mGluR5-dependent slow Ca(2+) oscillation may involve in the neuron-glia interaction in the striatum.}, } @article {pmid24451992, year = {2014}, author = {Benton, MA and Pavlopoulos, A}, title = {Tribolium embryo morphogenesis: may the force be with you.}, journal = {Bioarchitecture}, volume = {4}, number = {1}, pages = {16-21}, pmid = {24451992}, issn = {1949-100X}, mesh = {Animals ; Tribolium/*embryology ; }, abstract = {Development of multicellular organisms depends on patterning and growth mechanisms encoded in the genome, but also on the physical properties and mechanical interactions of the constituent cells that interpret these genetic cues. This fundamental biological problem requires integrated studies at multiple levels of biological organization: from genes, to cell behaviors, to tissue morphogenesis. We have recently combined functional genetics with live imaging approaches in embryos of the insect Tribolium castaneum, in order to understand their remarkable transformation from a uniform single-layered blastoderm into a condensed multi-layered embryo covered by extensive extra-embryonic tissues. We first developed a quick and reliable methodology to fluorescently label various cell components in entire Tribolium embryos. Live imaging of labeled embryos at single cell resolution provided detailed descriptions of cell behaviors and tissue movements during normal embryogenesis. We then compared cell and tissue dynamics between wild-type and genetically perturbed embryos that exhibited altered relative proportions of constituent tissues. This systematic comparison led to a qualitative model of the molecular, cellular and tissue interactions that orchestrate the observed epithelial rearrangements. We expect this work to establish the Tribolium embryo as a powerful and attractive model system for biologists and biophysicists interested in the molecular, cellular and mechanical control of tissue morphogenesis.}, } @article {pmid24448446, year = {2014}, author = {Ninova, M and Ronshaugen, M and Griffiths-Jones, S}, title = {Fast-evolving microRNAs are highly expressed in the early embryo of Drosophila virilis.}, journal = {RNA (New York, N.Y.)}, volume = {20}, number = {3}, pages = {360-372}, pmid = {24448446}, issn = {1469-9001}, support = {/WT_/Wellcome Trust/United Kingdom ; BB/H017801/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Base Sequence ; Conserved Sequence ; Drosophila/classification/*genetics/growth & development ; Embryo, Nonmammalian/cytology/metabolism ; *Evolution, Molecular ; Female ; *Gene Expression Regulation, Developmental ; In Situ Hybridization ; MicroRNAs/*genetics ; Molecular Sequence Data ; Phylogeny ; Sequence Homology, Nucleic Acid ; }, abstract = {MicroRNAs are short non-protein-coding RNAs that regulate gene expression at the post-transcriptional level and are essential for the embryonic development of multicellular animals. Comparative genome-scale analyses have revealed that metazoan evolution is accompanied by the continuous acquisition of novel microRNA genes. This suggests that novel microRNAs may promote innovation and diversity in development. We determined the evolutionary origins of extant Drosophila microRNAs and estimated the sequence divergence between the 130 orthologous microRNAs in Drosophila melanogaster and Drosophila virilis, separated by 63 million years of evolution. We then generated small RNA sequencing data sets covering D. virilis development and explored the relationship between microRNA conservation and expression in a developmental context. We find that late embryonic, larval, and adult stages are dominated by conserved microRNAs. This pattern, however, does not hold for the early embryo, where rapidly evolving microRNAs are uniquely present at high levels in both species. The group of fast-evolving microRNAs that are highly expressed in the early embryo belong to two Drosophilid lineage-specific clusters: mir-310 ∼ 313 and mir-309 ∼ 6. These clusters have particularly complex evolutionary histories of duplication, gain, and loss. Our analyses suggest that the early embryo is a more permissive environment for microRNA changes and innovations. Fast-evolving microRNAs, therefore, have the opportunity to become preferentially integrated in early developmental processes, and may impact the evolution of development. The relationship between microRNA conservation and expression throughout the development of Drosophila differs from that previously observed for protein-coding genes.}, } @article {pmid24443438, year = {2014}, author = {Sebé-Pedrós, A and Grau-Bové, X and Richards, TA and Ruiz-Trillo, I}, title = {Evolution and classification of myosins, a paneukaryotic whole-genome approach.}, journal = {Genome biology and evolution}, volume = {6}, number = {2}, pages = {290-305}, pmid = {24443438}, issn = {1759-6653}, support = {206883/ERC_/European Research Council/International ; BB/G00885X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/G00885X/2/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Eukaryota/chemistry/*classification/*genetics ; *Evolution, Molecular ; *Genome ; Myosins/chemistry/*genetics ; Phylogeny ; Protein Structure, Tertiary ; }, abstract = {Myosins are key components of the eukaryotic cytoskeleton, providing motility for a broad diversity of cargoes. Therefore, understanding the origin and evolutionary history of myosin classes is crucial to address the evolution of eukaryote cell biology. Here, we revise the classification of myosins using an updated taxon sampling that includes newly or recently sequenced genomes and transcriptomes from key taxa. We performed a survey of eukaryotic genomes and phylogenetic analyses of the myosin gene family, reconstructing the myosin toolkit at different key nodes in the eukaryotic tree of life. We also identified the phylogenetic distribution of myosin diversity in terms of number of genes, associated protein domains and number of classes in each taxa. Our analyses show that new classes (i.e., paralogs) and domain architectures were continuously generated throughout eukaryote evolution, with a significant expansion of myosin abundance and domain architectural diversity at the stem of Holozoa, predating the origin of animal multicellularity. Indeed, single-celled holozoans have the most complex myosin complement among eukaryotes, with paralogs of most myosins previously considered animal specific. We recover a dynamic evolutionary history, with several lineage-specific expansions (e.g., the myosin III-like gene family diversification in choanoflagellates), convergence in protein domain architectures (e.g., fungal and animal chitin synthase myosins), and important secondary losses. Overall, our evolutionary scheme demonstrates that the ancestral eukaryote likely had a complex myosin repertoire that included six genes with different protein domain architectures. Finally, we provide an integrative and robust classification, useful for future genomic and functional studies on this crucial eukaryotic gene family.}, } @article {pmid24440719, year = {2014}, author = {Heyn, P and Kircher, M and Dahl, A and Kelso, J and Tomancak, P and Kalinka, AT and Neugebauer, KM}, title = {The earliest transcribed zygotic genes are short, newly evolved, and different across species.}, journal = {Cell reports}, volume = {6}, number = {2}, pages = {285-292}, doi = {10.1016/j.celrep.2013.12.030}, pmid = {24440719}, issn = {2211-1247}, mesh = {Animals ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Genes, Mitochondrial ; RNA, Messenger/genetics/metabolism ; Species Specificity ; *Transcription, Genetic ; Zebrafish ; Zygote/*metabolism ; }, abstract = {The transition from maternal to zygotic control is fundamental to the life cycle of all multicellular organisms. It is widely believed that genomes are transcriptionally inactive from fertilization until zygotic genome activation (ZGA). Thus, the earliest genes expressed probably support the rapid cell divisions that precede morphogenesis and, if so, might be evolutionarily conserved. Here, we identify the earliest zygotic transcripts in the zebrafish, Danio rerio, through metabolic labeling and purification of RNA from staged embryos. Surprisingly, the mitochondrial genome was highly active from the one-cell stage onwards, showing that significant transcriptional activity exists at fertilization. We show that 592 nuclear genes become active when cell cycles are still only 15 min long, confining expression to relatively short genes. Furthermore, these zygotic genes are evolutionarily younger than those expressed at other developmental stages. Comparison of fish, fly, and mouse data revealed different sets of genes expressed at ZGA. This species specificity uncovers an evolutionary plasticity in early embryogenesis that probably confers substantial adaptive potential.}, } @article {pmid24440400, year = {2014}, author = {Mikhail, AS and Eetezadi, S and Ekdawi, SN and Stewart, J and Allen, C}, title = {Image-based analysis of the size- and time-dependent penetration of polymeric micelles in multicellular tumor spheroids and tumor xenografts.}, journal = {International journal of pharmaceutics}, volume = {464}, number = {1-2}, pages = {168-177}, doi = {10.1016/j.ijpharm.2014.01.010}, pmid = {24440400}, issn = {1873-3476}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Female ; HT29 Cells ; HeLa Cells ; Humans ; Mice ; Mice, Nude ; *Micelles ; Microscopy, Electron, Transmission/*methods ; Particle Size ; Polymers/chemistry/*metabolism ; Spheroids, Cellular/*metabolism/pathology/ultrastructure ; Time Factors ; Xenograft Model Antitumor Assays/*methods ; }, abstract = {While the heightened tumor accumulation of systemically administered nanomedicines relative to conventional chemotherapeutic agents has been well established, corresponding improvements in therapeutic efficacy have often been incommensurate. This observation may be attributed to the limited exposure of cancer cells to therapy due to the heterogeneous intratumoral distribution and poor interstitial penetration of nanoparticle-based drug delivery systems. In the present work, the spatio-temporal distribution of block copolymer micelles (BCMs) of different sizes was evaluated in multicellular tumor spheroids (MCTS) and tumor xenografts originating from human cervical (HeLa) and colon (HT29) cancer cells using image-based, computational techniques. Micelle penetration was found to depend on nanoparticle size, time as well as tumor and spheroid cell line. Moreover, spheroids demonstrated the capacity to predict relative trends in nanoparticle interstitial transport in tumor xenografts. Overall, techniques are presented for the assessment of nanoparticle distribution in spheroids and xenografts and used to evaluate the influence of micelle size and cell-line specific tissue properties on micelle interstitial penetration.}, } @article {pmid24417348, year = {2014}, author = {Maciak, S and Bonda-Ostaszewska, E and Czarnołęski, M and Konarzewski, M and Kozłowski, J}, title = {Mice divergently selected for high and low basal metabolic rates evolved different cell size and organ mass.}, journal = {Journal of evolutionary biology}, volume = {27}, number = {3}, pages = {478-487}, doi = {10.1111/jeb.12306}, pmid = {24417348}, issn = {1420-9101}, mesh = {Animals ; *Basal Metabolism ; *Cell Size ; Male ; Mice ; *Organ Size ; }, abstract = {Evolution of metabolic rates of multicellular organisms is hypothesized to reflect the evolution of their cell architecture. This is likely to stem from a tight link between the sizes of cells and nuclei, which are expected to be inversely related to cell metabolism. Here, we analysed basal metabolic rate (BMR), internal organ masses and the cell/nucleus size in different tissues of laboratory mice divergently selected for high/low mass-corrected BMR and four random-bred mouse lines. Random-bred lines had intermediate levels of BMR as compared to low- and high-BMR lines. Yet, this pattern was only partly consistent with the between-line differences in cell/nucleus sizes. Erythrocytes and skin epithelium cells were smaller in the high-BMR line than in other lines, but the cells of low-BMR and random-bred mice were similar in size. On the other hand, the size of hepatocytes, kidney proximal tubule cells and duodenum enterocytes were larger in high-BMR mice than other lines. All cell and nucleus sizes were positively correlated, which supports the role of the nucleus in cell size regulation. Our results suggest that the evolution of high BMR involves a reduction in cell size in specialized tissues, whose functions are primarily dictated by surface-to-volume ratios, such as erythrocytes. High BMR may, however, also incur an increase in cell size in tissues with an intense transcription and translation, such as hepatocytes.}, } @article {pmid24410880, year = {2014}, author = {Ludeman, DA and Farrar, N and Riesgo, A and Paps, J and Leys, SP}, title = {Evolutionary origins of sensation in metazoans: functional evidence for a new sensory organ in sponges.}, journal = {BMC evolutionary biology}, volume = {14}, number = {}, pages = {3}, pmid = {24410880}, issn = {1471-2148}, mesh = {Animals ; *Biological Evolution ; Cilia/genetics/*physiology ; Phylogeny ; Porifera/classification/genetics/*physiology ; Sensation ; }, abstract = {BACKGROUND: One of the hallmarks of multicellular organisms is the ability of their cells to trigger responses to the environment in a coordinated manner. In recent years primary cilia have been shown to be present as 'antennae' on almost all animal cells, and are involved in cell-to-cell signaling in development and tissue homeostasis; how this sophisticated sensory system arose has been little-studied and its evolution is key to understanding how sensation arose in the Animal Kingdom. Sponges (Porifera), one of the earliest evolving phyla, lack conventional muscles and nerves and yet sense and respond to changes in their fluid environment. Here we demonstrate the presence of non-motile cilia in sponges and studied their role as flow sensors.

RESULTS: Demosponges excrete wastes from their body with a stereotypic series of whole-body contractions using a structure called the osculum to regulate the water-flow through the body. In this study we show that short cilia line the inner epithelium of the sponge osculum. Ultrastructure of the cilia shows an absence of a central pair of microtubules and high speed imaging shows they are non-motile, suggesting they are not involved in generating flow. In other animals non-motile, 'primary', cilia are involved in sensation. Here we show that molecules known to block cationic ion channels in primary cilia and which inhibit sensory function in other organisms reduce or eliminate sponge contractions. Removal of the cilia using chloral hydrate, or removal of the whole osculum, also stops the contractions; in all instances the effect is reversible, suggesting that the cilia are involved in sensation. An analysis of sponge transcriptomes shows the presence of several transient receptor potential (TRP) channels including PKD channels known to be involved in sensing changes in flow in other animals. Together these data suggest that cilia in sponge oscula are involved in flow sensation and coordination of simple behaviour.

CONCLUSIONS: This is the first evidence of arrays of non-motile cilia in sponge oscula. Our findings provide support for the hypothesis that the cilia are sensory, and if true, the osculum may be considered a sensory organ that is used to coordinate whole animal responses in sponges. Arrays of primary cilia like these could represent the first step in the evolution of sensory and coordination systems in metazoans.}, } @article {pmid24398598, year = {2014}, author = {Sharma, M and Singh, A and Shankar, A and Pandey, A and Baranwal, V and Kapoor, S and Tyagi, AK and Pandey, GK}, title = {Comprehensive expression analysis of rice Armadillo gene family during abiotic stress and development.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {21}, number = {3}, pages = {267-283}, pmid = {24398598}, issn = {1756-1663}, mesh = {Armadillo Domain Proteins/*genetics/metabolism ; Chromosomes, Plant ; Computational Biology ; Evolution, Molecular ; Gene Duplication ; Gene Expression Profiling ; Genome, Plant ; Microarray Analysis ; Multigene Family ; Oryza/*genetics/growth & development/metabolism ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Promoter Regions, Genetic ; Stress, Physiological ; }, abstract = {Genes in the Armadillo (ARM)-repeat superfamily encode proteins with a range of developmental and physiological processes in unicellular and multicellular eukaryotes. These 42 amino acid, long tandem repeat-containing proteins have been abundantly recognized in many plant species. Previous studies have confirmed that Armadillo proteins constitute a multigene family in Arabidopsis. In this study, we performed a computational analysis in the rice genome (Oryza sativa L. subsp. japonica), and identified 158 genes of Armadillo superfamily. Phylogenetic study classified them into several arbitrary groups based on a varying number of non-conserved ARM repeats and accessory domain(s) associated with them. An in-depth analysis of gene expression through microarray and Q-PCR revealed a number of ARM proteins expressing differentially in abiotic stresses and developmental conditions, suggesting a potential roles of this superfamily in development and stress signalling. Comparative phylogenetic analysis between Arabidopsis and rice Armadillo genes revealed a high degree of evolutionary conservation between the orthologues in two plant species. The non-synonymous and synonymous substitutions per site ratios (Ka/Ks) of duplicated gene pairs indicate a purifying selection. This genome-wide identification and expression analysis provides a basis for further functional analysis of Armadillo genes under abiotic stress and reproductive developmental condition in the plant lineage.}, } @article {pmid24384569, year = {2014}, author = {Knoll, AH}, title = {Paleobiological perspectives on early eukaryotic evolution.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {6}, number = {1}, pages = {}, pmid = {24384569}, issn = {1943-0264}, mesh = {Animals ; *Biological Evolution ; *Fossils ; *Paleontology ; }, abstract = {Eukaryotic organisms radiated in Proterozoic oceans with oxygenated surface waters, but, commonly, anoxia at depth. Exceptionally preserved fossils of red algae favor crown group emergence more than 1200 million years ago, but older (up to 1600-1800 million years) microfossils could record stem group eukaryotes. Major eukaryotic diversification ~800 million years ago is documented by the increase in the taxonomic richness of complex, organic-walled microfossils, including simple coenocytic and multicellular forms, as well as widespread tests comparable to those of extant testate amoebae and simple foraminiferans and diverse scales comparable to organic and siliceous scales formed today by protists in several clades. Mid-Neoproterozoic establishment or expansion of eukaryophagy provides a possible mechanism for accelerating eukaryotic diversification long after the origin of the domain. Protists continued to diversify along with animals in the more pervasively oxygenated oceans of the Phanerozoic Eon.}, } @article {pmid24378600, year = {2014}, author = {Gamazon, ER and Stranger, BE}, title = {Genomics of alternative splicing: evolution, development and pathophysiology.}, journal = {Human genetics}, volume = {133}, number = {6}, pages = {679-687}, pmid = {24378600}, issn = {1432-1203}, mesh = {*Alternative Splicing ; Biological Evolution ; Databases, Genetic ; Genetic Therapy ; Genetic Variation ; *Genome, Human ; Genomics ; Humans ; Muscular Dystrophy, Duchenne/*genetics/physiopathology/therapy ; Myelodysplastic Syndromes/*genetics/physiopathology/therapy ; Oligonucleotides, Antisense/therapeutic use ; *Software ; Transcriptome ; beta-Thalassemia/*genetics/physiopathology/therapy ; }, abstract = {Alternative splicing is a major cellular mechanism in metazoans for generating proteomic diversity. A large proportion of protein-coding genes in multicellular organisms undergo alternative splicing, and in humans, it has been estimated that nearly 90 % of protein-coding genes-much larger than expected-are subject to alternative splicing. Genomic analyses of alternative splicing have illuminated its universal role in shaping the evolution of genomes, in the control of developmental processes, and in the dynamic regulation of the transcriptome to influence phenotype. Disruption of the splicing machinery has been found to drive pathophysiology, and indeed reprogramming of aberrant splicing can provide novel approaches to the development of molecular therapy. This review focuses on the recent progress in our understanding of alternative splicing brought about by the unprecedented explosive growth of genomic data and highlights the relevance of human splicing variation on disease and therapy.}, } @article {pmid24369344, year = {2014}, author = {Li, J and Wu, Y and Qi, Y}, title = {MicroRNAs in a multicellular green alga Volvox carteri.}, journal = {Science China. Life sciences}, volume = {57}, number = {1}, pages = {36-45}, doi = {10.1007/s11427-013-4580-3}, pmid = {24369344}, issn = {1869-1889}, mesh = {Base Sequence ; Blotting, Northern ; MicroRNAs/*genetics ; Molecular Sequence Data ; Reverse Transcriptase Polymerase Chain Reaction ; Volvox/*genetics ; }, abstract = {microRNAs (miRNAs) have emerged as key components in the eukaryotic gene regulatory network. We and others have previously identified many miRNAs in a unicellular green alga, Chlamydomonas reinhardtii. To investigate whether miRNA-mediated gene regulation is a general mechanism in green algae and how miRNAs have been evolved in the green algal lineage, we examined small RNAs in Volvox carteri, a multicellular species in the same family with Chlamydomonas reinhardtii. We identified 174 miRNAs in Volvox, with many of them being highly enriched in gonidia or somatic cells. The targets of the miRNAs were predicted and many of them were subjected to miRNA-mediated cleavage in vivo, suggesting that miRNAs play regulatory roles in the biology of green algae. Our catalog of miRNAs and their targets provides a resource for further studies on the evolution, biological functions, and genomic properties of miRNAs in green algae.}, } @article {pmid24368736, year = {2013}, author = {Olson, BJ}, title = {Multicellularity: From brief encounters to lifelong unions.}, journal = {eLife}, volume = {2}, number = {}, pages = {e01893}, pmid = {24368736}, issn = {2050-084X}, mesh = {Amoeba/*physiology ; *Cell Division ; *Evolution, Molecular ; }, abstract = {Could the transient aggregation of unicellular organisms have paved the way for the evolution of the multicellular animals?}, } @article {pmid24368732, year = {2013}, author = {Sebé-Pedrós, A and Irimia, M and Del Campo, J and Parra-Acero, H and Russ, C and Nusbaum, C and Blencowe, BJ and Ruiz-Trillo, I}, title = {Regulated aggregative multicellularity in a close unicellular relative of metazoa.}, journal = {eLife}, volume = {2}, number = {}, pages = {e01287}, pmid = {24368732}, issn = {2050-084X}, support = {206883/ERC_/European Research Council/International ; MOP-67011/CAPMC/CIHR/Canada ; }, mesh = {Adaptation, Psychological ; Alternative Splicing ; Amoeba/classification/genetics/growth & development/*physiology ; Cell Cycle ; *Cell Division/genetics ; *Evolution, Molecular ; Gene Expression Regulation ; Phylogeny ; Time Factors ; }, abstract = {The evolution of metazoans from their unicellular ancestors was one of the most important events in the history of life. However, the cellular and genetic changes that ultimately led to the evolution of multicellularity are not known. In this study, we describe an aggregative multicellular stage in the protist Capsaspora owczarzaki, a close unicellular relative of metazoans. Remarkably, transition to the aggregative stage is associated with significant upregulation of orthologs of genes known to establish multicellularity and tissue architecture in metazoans. We further observe transitions in regulated alternative splicing during the C. owczarzaki life cycle, including the deployment of an exon network associated with signaling, a feature of splicing regulation so far only observed in metazoans. Our results reveal the existence of a highly regulated aggregative stage in C. owczarzaki and further suggest that features of aggregative behavior in an ancestral protist may had been co-opted to develop some multicellular properties currently seen in metazoans. DOI: http://dx.doi.org/10.7554/eLife.01287.001.}, } @article {pmid24367511, year = {2013}, author = {Libby, E and Rainey, PB}, title = {Eco-evolutionary feedback and the tuning of proto-developmental life cycles.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e82274}, pmid = {24367511}, issn = {1932-6203}, mesh = {Animals ; *Life Cycle Stages ; *Models, Theoretical ; }, abstract = {Multicellular organisms depend on developmental programs to coordinate growth and differentiation from single cells, but the origins of development are unclear. A possible starting point is stochastic phenotypic variation generated by molecular noise. Given appropriate environmental conditions, noise-driven differentiation could conceivably evolve so as to come under regulatory control; however, abiotic conditions are likely to be restrictive. Drawing from an experimental system, we present a model in which environmental fluctuations are coupled to population growth. We show that this coupling generates stable selection for a single optimal strategy that is largely insensitive to environmental conditions, including the number of competitors, carrying capacity of the environment, difference in growth rates among phenotypic variants, and population density. We argue that this optimal strategy establishes stabilizing conditions likely to improve the quality and reliability of information experienced by evolving organisms, thus increasing opportunity for the evolutionary emergence of developmental programs.}, } @article {pmid24363320, year = {2014}, author = {Niklas, KJ}, title = {The evolutionary-developmental origins of multicellularity.}, journal = {American journal of botany}, volume = {101}, number = {1}, pages = {6-25}, doi = {10.3732/ajb.1300314}, pmid = {24363320}, issn = {1537-2197}, mesh = {*Biological Evolution ; Cell Adhesion ; Eukaryotic Cells/*cytology ; *Growth and Development ; Phylogeny ; }, abstract = {Multicellularity has evolved at least once in every major eukaryotic clade (in all ploidy levels) and numerous times among the prokaryotes. According to a standard multilevel selection (MLS) model, in each case, the evolution of multicellularity required the acquisition of cell-cell adhesion, communication, cooperation, and specialization attended by a compulsory alignment-of-fitness phase and an export-of-fitness phase to eliminate cell-cell conflict and to establish a reproductively integrated phenotype. These achievements are reviewed in terms of generalized evolutionary developmental motifs (or "modules") whose overall logic constructs were mobilized and executed differently in bacteria, plants, fungi, and animals. When mapped onto a matrix of theoretically possible body plan morphologies (i.e., a morphospace), these motifs and the MLS model identify a "unicellular ⇒ colonial ⇒ multicellular" transformation series of body plans that mirrors trends observed in the majority of algae (i.e., a polyphyletic collection of photoautotrophic eukaryotes) and in the land plants, fungi, and animals. However, an alternative, more direct route to multicellularity theoretically exists, which may account for some aspects of fungal and algal evolution, i.e., a "siphonous ⇒ multicellular" transformation series. This review of multicellularity attempts to show that natural selection typically acts on functional traits rather than on the mechanisms that generate them ("Many roads lead to Rome.") and that genome sequence homologies do not invariably translate into morphological homologies ("Rome isn't what it used to be.").}, } @article {pmid24361965, year = {2014}, author = {Meersseman, C and Léjard, V and Rebours, E and Boussaha, M and Maftah, A and Petit, D and Rocha, D}, title = {Bovine TWINKLE and mitochondrial ribosomal protein L43 genes are regulated by an evolutionary conserved bidirectional promoter.}, journal = {Gene}, volume = {537}, number = {1}, pages = {154-163}, doi = {10.1016/j.gene.2013.11.088}, pmid = {24361965}, issn = {1879-0038}, mesh = {5' Flanking Region ; Animals ; Base Sequence ; Binding Sites ; Cattle ; Cell Line ; DNA Helicases/*genetics ; DNA, Intergenic ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Mitochondrial Proteins/*genetics ; Molecular Sequence Data ; *Promoter Regions, Genetic ; Ribosomal Proteins/*genetics ; Transcription Factors/genetics/metabolism ; Vertebrates/genetics ; }, abstract = {TWINKLE is a mitochondrial DNA helicase playing an important role in mitochondrial DNA replication. In human, mutations in this gene cause progressive external ophtalmoplegia and mitochondrial DNA depletion syndrome-7. TWINKLE is well conserved among multicellular eukaryotes and is believed to be a key regulator of mitochondrial DNA copy number in mammals. Despite its involvement in several diseases and its important function in mitochondrial DNA metabolism, nothing is known about the regulation of the expression of TWINKLE. We have analysed the 5'-flanking genomic region of the bovine TWINKLE gene and found it was localised adjacent to the MRPL43 gene in a head-to-head orientation, suggesting that both genes are regulated by a shared bidirectional promoter. The bovine 75-bp long intergenic region shows substantial homology across different species and contains several conserved putative transcription factor binding sites. A TATA box, however, was lacking. Using a dual fluorescent reporter system and transient transfection assays, we have analysed the bovine intergenic region between TWINKLE and MRPL43. This small genomic fragment showed a bidirectional promoter activity. As the TWINKLE/MRPL43 bidirectional promoter tested was highly conserved, it is likely that the results we obtained here in cattle may be extended to the other species.}, } @article {pmid24361339, year = {2014}, author = {Bersini, S and Jeon, JS and Moretti, M and Kamm, RD}, title = {In vitro models of the metastatic cascade: from local invasion to extravasation.}, journal = {Drug discovery today}, volume = {19}, number = {6}, pages = {735-742}, pmid = {24361339}, issn = {1878-5832}, support = {R21 CA140096/CA/NCI NIH HHS/United States ; R33 CA174550/CA/NCI NIH HHS/United States ; R33 CA174550-01/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Humans ; Microfluidic Analytical Techniques/*methods ; Neoplasm Invasiveness/*pathology ; Neoplasms/blood/diagnosis ; Neoplastic Cells, Circulating/*pathology ; Signal Transduction/physiology ; }, abstract = {A crucial event in the metastatic cascade is the extravasation of circulating cancer cells from blood capillaries to the surrounding tissues. The past 5 years have been characterized by a significant evolution in the development of in vitro extravasation models, which moved from traditional transmigration chambers to more sophisticated microfluidic devices, enabling the study of complex cell-cell and cell-matrix interactions in multicellular, controlled environments. These advanced assays could be applied to screen easily and rapidly a broad spectrum of molecules inhibiting cancer cell endothelial adhesion and extravasation, thus contributing to the design of more focused in vivo tests.}, } @article {pmid24360576, year = {2014}, author = {Charoen, KM and Fallica, B and Colson, YL and Zaman, MH and Grinstaff, MW}, title = {Embedded multicellular spheroids as a biomimetic 3D cancer model for evaluating drug and drug-device combinations.}, journal = {Biomaterials}, volume = {35}, number = {7}, pages = {2264-2271}, pmid = {24360576}, issn = {1878-5905}, support = {R01 CA149561/CA/NCI NIH HHS/United States ; T32 EB006359/EB/NIBIB NIH HHS/United States ; T32EB006359/EB/NIBIB NIH HHS/United States ; T32 GM008541/GM/NIGMS NIH HHS/United States ; R25 CA153955/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/*therapeutic use ; *Biomimetics ; Cell Line, Tumor ; Drug Evaluation, Preclinical ; *Equipment and Supplies ; Humans ; *Imaging, Three-Dimensional ; *Microspheres ; Neoplasms/drug therapy/*pathology/therapy ; }, abstract = {Multicellular aggregates of cells, termed spheroids, are of interest for studying tumor behavior and for evaluating the response of pharmacologically active agents. Spheroids more faithfully reproduce the tumor macrostructure found in vivo compared to classical 2D monolayers. We present a method for embedding spheroids within collagen gels followed by quantitative and qualitative whole spheroid and single cell analyses enabling characterization over the length scales from molecular to macroscopic. Spheroid producing and embedding capabilities are demonstrated for U2OS and MDA-MB-231 cell lines, of osteosarcoma and breast adenocarcinoma origin, respectively. Finally, using the MDA-MB-231 tumor model, the chemotherapeutic response between paclitaxel delivery as a bolus dose, as practiced in the clinic, is compared to delivery within an expansile nanoparticle. The expansile nanoparticle delivery route provides a superior outcome and the results mirror those observed in a murine xenograft model. These findings highlight the synergistic beneficial results that may arise from the use of a drug delivery system, and the need to evaluate both drug candidates and delivery systems in the research and preclinical screening phases of a new cancer therapy development program.}, } @article {pmid24353202, year = {2014}, author = {Woods, HA}, title = {Mosaic physiology from developmental noise: within-organism physiological diversity as an alternative to phenotypic plasticity and phenotypic flexibility.}, journal = {The Journal of experimental biology}, volume = {217}, number = {Pt 1}, pages = {35-45}, doi = {10.1242/jeb.089698}, pmid = {24353202}, issn = {1477-9145}, mesh = {Acclimatization/*physiology ; Allostasis/*physiology ; Animals ; Biodiversity ; Biological Evolution ; Environment ; Homeostasis/*physiology ; Stochastic Processes ; *Stress, Physiological ; }, abstract = {A key problem in organismal biology is to explain the origins of functional diversity. In the context of organismal biology, functional diversity describes the set of phenotypes, across scales of biological organization and through time, that a single genotype, or genome, or organism, can produce. Functional diversity encompasses many phenomena: differences in cell types within organisms; physiological and morphological differences among tissues and organs; differences in performance; morphological shifts in external phenotype; and changes in behavior. How can single genomes produce so many different phenotypes? Modern biology proposes two general mechanisms. The first is developmental programs, by which single cells and their single genomes diversify, via relatively deterministic processes, into the sets of cell types, tissues and organs that we see in most multicellular organisms. The second general mechanism is phenotypic modification stemming from interactions between organisms and their environments - modifications known either as phenotypic plasticity or as phenotypic flexibility, depending on the time scale of the response and the degree of reversibility. These two diversity-generating mechanisms are related because phenotypic modifications may sometimes arise as a consequence of environments influencing developmental programs. Here, I propose that functional diversity also arises via a third fundamental mechanism: stochastic developmental events giving rise to mosaics of physiological diversity within individual organisms. In biological systems, stochasticity stems from the inherently random actions of small numbers of molecules interacting with one another. Although stochastic effects occur in many biological contexts, available evidence suggests that they can be especially important in gene networks, specifically as a consequence of low transcript numbers in individual cells. I briefly review known mechanisms by which organisms control such stochasticity, and how they may use it to create adaptive functional diversity. I then fold this idea into modern thinking on phenotypic plasticity and flexibility, proposing that multicellular organisms exhibit 'mosaic physiology'. Mosaic physiology refers to sets of diversified phenotypes, within individual organisms, that carry out related functions at the same time, but that are distributed in space. Mosaic physiology arises from stochasticity-driven differentiation of cells, early during cell diversification, which is then amplified by cell division and growth into macroscopic phenotypic modules (cells, tissues, organs) making up the physiological systems of later life stages. Mosaic physiology provides a set of standing, diversified phenotypes, within single organisms, that raise the likelihood of the organism coping well with novel environmental challenges. These diversified phenotypes can be distinct, akin to polyphenisms at the organismal level; or they can be continuously distributed, creating a kind of standing, simultaneously expressed reaction norm of physiological capacities.}, } @article {pmid24349132, year = {2013}, author = {Kuwayama, H and Miyanaga, Y and Urushihara, H and Ueda, M}, title = {A RabGAP regulates life-cycle duration via trimeric G-protein cascades in Dictyostelium discoideum.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e81811}, pmid = {24349132}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans ; Cell Proliferation ; Dictyostelium/*genetics/metabolism ; GTPase-Activating Proteins/*genetics/metabolism ; Gene Deletion ; Gene Expression Regulation ; Genetic Complementation Test ; Humans ; Life Cycle Stages/*genetics ; Microtubule-Associated Proteins/*genetics/metabolism ; Molecular Sequence Data ; Protein Binding ; Protein Multimerization ; Protozoan Proteins/*genetics/metabolism ; Sequence Alignment ; Signal Transduction ; Two-Hybrid System Techniques ; }, abstract = {BACKGROUND: The life-cycle of cellular slime molds comprises chronobiologically regulated processes. During the growth phase, the amoeboid cells proliferate at a definite rate. Upon starvation, they synthesize cAMP as both first and second messengers in signalling pathways and form aggregates, migrating slugs, and fruiting bodies, consisting of spores and stalk cells, within 24 h. In Dictyostelium discoideum, because most growth-specific events cease during development, proliferative and heterochronic mutations are not considered to be interrelated and no genetic factor governing the entire life-cycle duration has ever been identified.

Using yeast 2-hybrid library screening, we isolated a Dictyostelium discoideum RabGAP, Dd Rbg-3, as a candidate molecule by which the Dictyostelium Gα2 subunit directs its effects. Rab GTPase-activating protein, RabGAP, acts as a negative regulator of Rab small GTPases, which orchestrate the intracellular membrane trafficking involved in cell proliferation. Deletion mutants of Dd rbg-3 exhibited an increased growth rate and a shortened developmental period, while an overexpression mutant demonstrated the opposite effects. We also show that Dd Rbg-3 interacts with 2 Gα subunits in an activity-dependent manner in vitro. Furthermore, both human and Caenorhabditis elegans rbg-3 homologs complemented the Dd rbg-3-deletion phenotype in D. discoideum, indicating that similar pathways may be generally conserved in multicellular organisms.

CONCLUSIONS/SIGNIFICANCE: Our findings suggest that Dd Rbg-3 acts as a key element regulating the duration of D. discoideum life-span potentially via trimeric G-protein cascades.}, } @article {pmid24349103, year = {2013}, author = {Arakaki, Y and Kawai-Toyooka, H and Hamamura, Y and Higashiyama, T and Noga, A and Hirono, M and Olson, BJ and Nozaki, H}, title = {The simplest integrated multicellular organism unveiled.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e81641}, pmid = {24349103}, issn = {1932-6203}, mesh = {*Biological Evolution ; Chlorophyta/classification/physiology/*ultrastructure ; Cytoplasm/physiology/ultrastructure ; Extracellular Matrix/physiology/ultrastructure ; Flagella/physiology/ultrastructure ; *Phylogeny ; Protoplasts/physiology/ultrastructure ; Species Specificity ; }, abstract = {Volvocine green algae represent the "evolutionary time machine" model lineage for studying multicellularity, because they encompass the whole range of evolutionary transition of multicellularity from unicellular Chlamydomonas to >500-celled Volvox. Multicellular volvocalean species including Gonium pectorale and Volvox carteri generally have several common morphological features to survive as integrated multicellular organisms such as "rotational asymmetry of cells" so that the cells become components of the individual and "cytoplasmic bridges between protoplasts in developing embryos" to maintain the species-specific form of the multicellular individual before secretion of new extracellular matrix (ECM). However, these morphological features have not been studied in the four-celled colonial volvocine species Tetrabaena socialis that is positioned in the most basal lineage within the colonial or multicellular volvocine greens. Here we established synchronous cultures of T. socialis and carried out immunofluorescence microscopic and ultrastructural observations to elucidate these two morphological attributes. Based on immunofluorescence microscopy, four cells of the mature T. socialis colony were identical in morphology but had rotational asymmetry in arrangement of microtubular rootlets and separation of basal bodies like G. pectorale and V. carteri. Ultrastructural observations clearly confirmed the presence of cytoplasmic bridges between protoplasts in developing embryos of T. socialis even after the formation of new flagella in each daughter protoplast within the parental ECM. Therefore, these two morphological attributes might have evolved in the common four-celled ancestor of the colonial volvocine algae and contributed to the further increase in cell number and complexity of the multicellular individuals of this model lineage. T. socialis is one of the simplest integrated multicellular organisms in which four identical cells constitute the individual.}, } @article {pmid24339376, year = {2014}, author = {Kramer, S}, title = {RNA in development: how ribonucleoprotein granules regulate the life cycles of pathogenic protozoa.}, journal = {Wiley interdisciplinary reviews. RNA}, volume = {5}, number = {2}, pages = {263-284}, doi = {10.1002/wrna.1207}, pmid = {24339376}, issn = {1757-7012}, mesh = {Apicomplexa/genetics/*metabolism ; Cytoplasmic Granules/genetics/metabolism ; Gene Expression Regulation/*physiology ; Oocytes/metabolism ; Protozoan Proteins/genetics/*metabolism ; RNA, Protozoan/genetics/*metabolism ; Ribonucleoproteins/genetics/*metabolism ; Trypanosoma/genetics/*metabolism ; }, abstract = {Ribonucleoprotein (RNP) granules are important posttranscriptional regulators of messenger RNA (mRNA) fate. Several types of RNP granules specifically regulate gene expression during development of multicellular organisms and are commonly referred to as germ granules. The function of germ granules is not entirely understood and probably diverse, but it is generally agreed that one main function is posttranscriptional regulation of gene expression during early development, when transcription is silent. One example is the translational repression of maternally derived mRNAs in oocytes. Here, I hope to show that the need for regulation of gene expression by RNP granules is not restricted to animal development, but plays an equally important role during the development of pathogenic protozoa. Apicomplexa and Trypanosomatidae have complex life cycles with frequent host changes. The need to quickly adapt gene expression to a new environment as well as the ability to suppress translation to survive latencies is critical for successful completion of life cycles. Posttranscriptional gene regulation is not necessarily simpler in protozoa. Apicomplexa surprise with the presence of micro RNA (miRNAs) and upstream open reading frames (µORFs). Trypanosomes have an unusually large repertoire of different RNP granule types. A better understanding of RNP granules in protozoa may help to gain insight into the evolutionary origin of RNP granules: Trypanosomes for example have two types of granules with interesting similarities to animal germ granules.}, } @article {pmid24336809, year = {2014}, author = {Ofer, D and Linial, M}, title = {NeuroPID: a predictor for identifying neuropeptide precursors from metazoan proteomes.}, journal = {Bioinformatics (Oxford, England)}, volume = {30}, number = {7}, pages = {931-940}, doi = {10.1093/bioinformatics/btt725}, pmid = {24336809}, issn = {1367-4811}, mesh = {Amino Acid Sequence ; Animals ; *Artificial Intelligence ; Databases, Genetic ; Insecta ; Molecular Sequence Data ; Neuropeptides/*analysis/chemistry ; Protein Precursors/analysis ; Proteome/*analysis/chemistry ; Sequence Alignment ; Sequence Homology, Amino Acid ; *Software ; Support Vector Machine ; }, abstract = {MOTIVATION: The evolution of multicellular organisms is associated with increasing variability of molecules governing behavioral and physiological states. This is often achieved by neuropeptides (NPs) that are produced in neurons from a longer protein, named neuropeptide precursor (NPP). The maturation of NPs occurs through a sequence of proteolytic cleavages. The difficulty in identifying NPPs is a consequence of their diversity and the lack of applicable sequence similarity among the short functionally related NPs.

RESULTS: Herein, we describe Neuropeptide Precursor Identifier (NeuroPID), a machine learning scheme that predicts metazoan NPPs. NeuroPID was trained on hundreds of identified NPPs from the UniProtKB database. Some 600 features were extracted from the primary sequences and processed using support vector machines (SVM) and ensemble decision tree classifiers. These features combined biophysical, chemical and informational-statistical properties of NPs and NPPs. Other features were guided by the defining characteristics of the dibasic cleavage sites motif. NeuroPID reached 89-94% accuracy and 90-93% precision in cross-validation blind tests against known NPPs (with an emphasis on Chordata and Arthropoda). NeuroPID also identified NPP-like proteins from extensively studied model organisms as well as from poorly annotated proteomes. We then focused on the most significant sets of features that contribute to the success of the classifiers. We propose that NPPs are attractive targets for investigating and modulating behavior, metabolism and homeostasis and that a rich repertoire of NPs remains to be identified.

AVAILABILITY: NeuroPID source code is freely available at http://www.protonet.cs.huji.ac.il/neuropid}, } @article {pmid24333018, year = {2014}, author = {Dunin-Horkawicz, S and Kopec, KO and Lupas, AN}, title = {Prokaryotic ancestry of eukaryotic protein networks mediating innate immunity and apoptosis.}, journal = {Journal of molecular biology}, volume = {426}, number = {7}, pages = {1568-1582}, doi = {10.1016/j.jmb.2013.11.030}, pmid = {24333018}, issn = {1089-8638}, mesh = {Amino Acid Sequence ; Apoptosis/genetics/*physiology ; Computational Biology ; Eukaryotic Cells/cytology/metabolism ; Immunity, Innate/genetics/*physiology ; Molecular Sequence Data ; Prokaryotic Cells/cytology/metabolism ; Proteins/*chemistry/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {Protein domains characteristic of eukaryotic innate immunity and apoptosis have many prokaryotic counterparts of unknown function. By reconstructing interactomes computationally, we found that bacterial proteins containing these domains are part of a network that also includes other domains not hitherto associated with immunity. This network is connected to the network of prokaryotic signal transduction proteins, such as histidine kinases and chemoreceptors. The network varies considerably in domain composition and degree of paralogy, even between strains of the same species, and its repetitive domains are often amplified recently, with individual repeats sharing up to 100% sequence identity. Both phenomena are evidence of considerable evolutionary pressure and thus compatible with a role in the "arms race" between host and pathogen. In order to investigate the relationship of this network to its eukaryotic counterparts, we performed a cluster analysis of organisms based on a census of its constituent domains across all fully sequenced genomes. We obtained a large central cluster of mainly unicellular organisms, from which multicellular organisms radiate out in two main directions. One is taken by multicellular bacteria, primarily cyanobacteria and actinomycetes, and plants form an extension of this direction, connected via the basal, unicellular cyanobacteria. The second main direction is taken by animals and fungi, which form separate branches with a common root in the α-proteobacteria of the central cluster. This analysis supports the notion that the innate immunity networks of eukaryotes originated from their endosymbionts and that increases in the complexity of these networks accompanied the emergence of multicellularity.}, } @article {pmid24313842, year = {2014}, author = {Urano, D and Jones, AM}, title = {Heterotrimeric G protein-coupled signaling in plants.}, journal = {Annual review of plant biology}, volume = {65}, number = {}, pages = {365-384}, pmid = {24313842}, issn = {1545-2123}, support = {R01 GM065989/GM/NIGMS NIH HHS/United States ; R01GM065989/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/metabolism ; Heterotrimeric GTP-Binding Proteins/*metabolism ; Models, Molecular ; Plant Proteins/*metabolism ; Plants/*metabolism ; Protein Structure, Secondary ; Signal Transduction ; }, abstract = {Investigators studying G protein-coupled signaling--often called the best-understood pathway in the world owing to intense research in medical fields--have adopted plants as a new model to explore the plasticity and evolution of G signaling. Much research on plant G signaling has not disappointed. Although plant cells have most of the core elements found in animal G signaling, differences in network architecture and intrinsic properties of plant G protein elements make G signaling in plant cells distinct from the animal paradigm. In contrast to animal G proteins, plant G proteins are self-activating, and therefore regulation of G activation in plants occurs at the deactivation step. The self-activating property also means that plant G proteins do not need and therefore do not have typical animal G protein-coupled receptors. Targets of activated plant G proteins, also known as effectors, are unlike effectors in animal cells. The simpler repertoire of G signal elements in Arabidopsis makes G signaling easier to manipulate in a multicellular context.}, } @article {pmid24307687, year = {2014}, author = {Suga, H and Torruella, G and Burger, G and Brown, MW and Ruiz-Trillo, I}, title = {Earliest Holozoan expansion of phosphotyrosine signaling.}, journal = {Molecular biology and evolution}, volume = {31}, number = {3}, pages = {517-528}, pmid = {24307687}, issn = {1537-1719}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Animals ; Choanoflagellata/*enzymology ; Evolution, Molecular ; Mesomycetozoea/enzymology ; Models, Molecular ; Phosphotyrosine/*metabolism ; Phylogeny ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/chemistry ; *Signal Transduction ; }, abstract = {Phosphotyrosine (pTyr) signaling is involved in development and maintenance of metazoans' multicellular body through cell-to-cell communication. Tyrosine kinases (TKs), tyrosine phosphatases, and other proteins relaying the signal compose the cascade. Domain architectures of the pTyr signaling proteins are diverse in metazoans, reflecting their complex intercellular communication. Previous studies had shown that the metazoan-type TKs, as well as other pTyr signaling proteins, were already diversified in the common ancestor of metazoans, choanoflagellates, and filastereans (which are together included in the clade Holozoa) whereas they are absent in fungi and other nonholozoan lineages. However, the earliest-branching holozoans Ichthyosporea and Corallochytrea, as well as the two fungi-related amoebae Fonticula and Nuclearia, have not been studied. Here, we analyze the complete genome sequences of two ichthyosporeans and Fonticula, and RNAseq data of three additional ichthyosporeans, one corallochytrean, and Nuclearia. Both the ichthyosporean and corallochytrean genomes encode a large variety of receptor TKs (RTKs) and cytoplasmic TKs (CTKs), as well as other pTyr signaling components showing highly complex domain architectures. However, Nuclearia and Fonticula have no TK, and show much less diversity in other pTyr signaling components. The CTK repertoires of both Ichthyosporea and Corallochytrea are similar to those of Metazoa, Choanoflagellida, and Filasterea, but the RTK sets are totally different from each other. The complex pTyr signaling equipped with positive/negative feedback mechanism likely emerged already at an early stage of holozoan evolution, yet keeping a high evolutionary plasticity in extracellular signal reception until the co-option of the system for cell-to-cell communication in metazoans.}, } @article {pmid24307295, year = {2013}, author = {Tischer, S and Reineck, M and Söding, J and Münder, S and Böttger, A}, title = {Eph receptors and ephrin class B ligands are expressed at tissue boundaries in Hydra vulgaris.}, journal = {The International journal of developmental biology}, volume = {57}, number = {9-10}, pages = {759-765}, doi = {10.1387/ijdb.130158ab}, pmid = {24307295}, issn = {1696-3547}, mesh = {Amino Acid Sequence ; Animals ; Cell Adhesion/*physiology ; Ephrins/*biosynthesis ; Epithelial Cells/metabolism ; Hydra ; Phylogeny ; Protein Structure, Tertiary ; Receptors, Eph Family/*biosynthesis ; Sequence Alignment ; Signal Transduction ; }, abstract = {Eph receptors and ephrins are important players in axon guidance, cell sorting and boundary formation. Both the receptors and the ligands are integrated transmembrane proteins and signalling is bidirectional. The prevalent outcome of signal transduction is repulsion of adjacent cells or cell populations. Eph/ephrins have been identified in all multicellular animals from human to sponge, their functions however appear to have been altered during evolution. Here we have identified four Eph receptors and three class B ligands in the cnidarian Hydra vulgaris, indicating that those are the evolutionary older ones. In situ hybridisation experiments revealed a striking complementarity of expression of receptors and ligands in tentacles and in developing buds. This suggests that the original function of ephrin signalling may have been in epithelial cell adhesion and the formation of tissue boundaries.}, } @article {pmid24301834, year = {2014}, author = {Urbisz, AZ and Lai, YT and Swiątek, P}, title = {Barbronia weberi (Clitellata, Hirudinida, Salifidae) has ovary cords of the Erpobdella type.}, journal = {Journal of morphology}, volume = {275}, number = {5}, pages = {479-488}, doi = {10.1002/jmor.20229}, pmid = {24301834}, issn = {1097-4687}, mesh = {Animals ; Female ; Leeches/classification/physiology/*ultrastructure ; Oocytes/cytology/physiology/ultrastructure ; Ovary/anatomy & histology/physiology ; Phylogeny ; }, abstract = {The organization of the ovaries in representative of the Salifidae (Hirudinida, Erpobdelliformes) was studied at the ultrastructural level for the first time. Like in other leeches, the ovaries of Barbronia weberi are composed of an outer envelope (i.e., an ovisac made up of two coelomic epithelia, muscle cells, and connective tissue) and several internal units, which are broadly similar to the ovary cords found in representatives of the Erpobdellidae. There are usually 6-8 ovary cords that are twisted or cambered with a narrow apical part and a broader, irregularly shaped distal end in each ovisac of B. weberi. Each ovary cord is built from somatic and germ-line cells and the latter tend to form multicellular cysts that are equipped with a central cytoplasmic core (cytophore). There are two morphologically different subpopulations of germ-line cells: oocytes and more numerous nurse cells. Growing oocytes form protuberances on the ovary cord surface and eventually detach from the cord and float freely in the ovisac lumen, whereas the other components of germ-line cysts (i.e., nurse cells and cytophore) degenerate. It should be pointed out that there is a prominent gradient of germ-cell development along the long axis of the cord. The somatic cells form the ovary cord envelope (the so-called spongiosa cells) and also penetrate the spaces between germ-line cells. Both kinds of the somatic cells, that is, those forming the cord envelope and the somatic cells that are associated with oocytes (follicular cells) have a well-developed system of intercellular channels. Additionally, one prominent somatic cell, the apical cell, was found at the apical tip of each ovary cord. Because the aforementioned features of ovary cords found in B. weberi are very similar (with a few minor exceptions) to the ovary cords that have been described in Erpobdella octoculata and E. johanssoni, we propose the term "ovary cords of the Erpobdella type" for them. Our results support a close phylogenetic relationship between Salifidae and Erpobdellidae.}, } @article {pmid24298060, year = {2014}, author = {Covo, S and Puccia, CM and Argueso, JL and Gordenin, DA and Resnick, MA}, title = {The sister chromatid cohesion pathway suppresses multiple chromosome gain and chromosome amplification.}, journal = {Genetics}, volume = {196}, number = {2}, pages = {373-384}, pmid = {24298060}, issn = {1943-2631}, support = {Z01 ES065073//Intramural NIH HHS/United States ; 1Z01ES065073/ES/NIEHS NIH HHS/United States ; }, mesh = {Aneuploidy ; Cell Cycle Proteins/deficiency/genetics ; Chromatids/*genetics/metabolism ; Chromosomal Proteins, Non-Histone/deficiency/genetics ; *Chromosome Aberrations ; Chromosomes, Fungal/*genetics/metabolism ; Copper Sulfate/toxicity ; DNA Copy Number Variations ; DNA Damage ; Diploidy ; Drug Resistance, Fungal/genetics ; Gene Amplification ; Mutation ; Saccharomyces cerevisiae/drug effects/*genetics/metabolism ; Cohesins ; }, abstract = {Gain or loss of chromosomes resulting in aneuploidy can be important factors in cancer and adaptive evolution. Although chromosome gain is a frequent event in eukaryotes, there is limited information on its genetic control. Here we measured the rates of chromosome gain in wild-type yeast and sister chromatid cohesion (SCC) compromised strains. SCC tethers the newly replicated chromatids until anaphase via the cohesin complex. Chromosome gain was measured by selecting and characterizing copper-resistant colonies that emerged due to increased copies of the metallothionein gene CUP1. Although all defective SCC diploid strains exhibited increased rates of chromosome gain, there were 15-fold differences between them. Of all mutants examined, a hypomorphic mutation at the cohesin complex caused the highest rate of chromosome gain while disruption of WPL1, an important regulator of SCC and chromosome condensation, resulted in the smallest increase in chromosome gain. In addition to defects in SCC, yeast cell type contributed significantly to chromosome gain, with the greatest rates observed for homozygous mating-type diploids, followed by heterozygous mating type, and smallest in haploids. In fact, wpl1-deficient haploids did not show any difference in chromosome gain rates compared to wild-type haploids. Genomic analysis of copper-resistant colonies revealed that the "driver" chromosome for which selection was applied could be amplified to over five copies per diploid cell. In addition, an increase in the expected driver chromosome was often accompanied by a gain of a small number of other chromosomes. We suggest that while chromosome gain due to SCC malfunction can have negative effects through gene imbalance, it could also facilitate opportunities for adaptive changes. In multicellular organisms, both factors could lead to somatic diseases including cancer.}, } @article {pmid24296535, year = {2014}, author = {Fatica, A and Bozzoni, I}, title = {Long non-coding RNAs: new players in cell differentiation and development.}, journal = {Nature reviews. Genetics}, volume = {15}, number = {1}, pages = {7-21}, pmid = {24296535}, issn = {1471-0064}, support = {GGP11149/TI_/Telethon/Italy ; }, mesh = {Animals ; Cell Differentiation/*genetics/physiology ; Cytoplasm/genetics ; Dosage Compensation, Genetic/*genetics ; Gene Expression Regulation, Developmental/*genetics ; Genomic Imprinting/*genetics ; Mammals/*genetics/growth & development ; *Models, Genetic ; Models, Molecular ; Muscles/physiology ; Organogenesis/*genetics ; RNA, Long Noncoding/*genetics ; Species Specificity ; }, abstract = {Genomes of multicellular organisms are characterized by the pervasive expression of different types of non-coding RNAs (ncRNAs). Long ncRNAs (lncRNAs) belong to a novel heterogeneous class of ncRNAs that includes thousands of different species. lncRNAs have crucial roles in gene expression control during both developmental and differentiation processes, and the number of lncRNA species increases in genomes of developmentally complex organisms, which highlights the importance of RNA-based levels of control in the evolution of multicellular organisms. In this Review, we describe the function of lncRNAs in developmental processes, such as in dosage compensation, genomic imprinting, cell differentiation and organogenesis, with a particular emphasis on mammalian development.}, } @article {pmid24295300, year = {2013}, author = {Balklava, Z and Sztul, E}, title = {Studying membrane trafficking in the worm C. elegans by RNA interference.}, journal = {Methods in cell biology}, volume = {118}, number = {}, pages = {51-68}, doi = {10.1016/B978-0-12-417164-0.00004-5}, pmid = {24295300}, issn = {0091-679X}, mesh = {Animals ; Biological Transport ; Caenorhabditis elegans/cytology/genetics/*metabolism ; Caenorhabditis elegans Proteins/*genetics/metabolism ; Cell Membrane/metabolism ; Escherichia coli ; *Gene Knockdown Techniques ; Gene Transfer Techniques ; Green Fluorescent Proteins ; Membrane Transport Proteins/genetics/metabolism ; Microscopy, Fluorescence ; *RNA Interference ; }, abstract = {A powerful approach to gain understanding of molecular machinery responsible for membrane trafficking is through inactivation of gene function by RNA interference (RNAi). RNAi-mediated gene silencing occurs when a double-stranded RNA is introduced into cells and targets a complementary mRNA for degradation. The subsequent lack of mRNA prevents the synthesis of the corresponding protein and ultimately causes depletion of a particular gene product from the cell. The effects of such depletion can then by analyzed by functional, morphological, and biochemical assays. RNAi-mediated knockdowns of numerous gene products in cultured cells of mammalian and other species origins have provided significant new insight into traffic regulation and represent standard approaches in current cell biology. However, RNAi in the multicellular nematode Caenorhabditis elegans model allows RNAi studies within the context of a whole organism, and thus provides an unprecedented opportunity to explore effects of specific trafficking regulators within the context of distinct developmental stages and diverse cell types. In addition, various transgenic C. elegans strains have been developed that express marker proteins tagged with fluorescent proteins to facilitate the analysis of trafficking within the secretory and endocytic pathways. This chapter provides a detailed description of a basic RNAi approach that can be used to analyze the function of any gene of interest in secretory and endosomal trafficking in C. elegans.}, } @article {pmid24293008, year = {2013}, author = {McCormack, R and de Armas, L and Shiratsuchi, M and Podack, ER}, title = {Killing machines: three pore-forming proteins of the immune system.}, journal = {Immunologic research}, volume = {57}, number = {1-3}, pages = {268-278}, pmid = {24293008}, issn = {1559-0755}, support = {F31 AI106290/AI/NIAID NIH HHS/United States ; P01 CA109094/CA/NCI NIH HHS/United States ; R01 CA039201/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/immunology ; Complement Membrane Attack Complex ; Extracellular Space/immunology/microbiology/virology ; Humans ; Immunity/*physiology ; Intracellular Space/immunology/microbiology ; Neoplasms/metabolism ; Pore Forming Cytotoxic Proteins/*physiology ; Virus Diseases/immunology/metabolism ; }, abstract = {The evolution of early multicellular eukaryotes 400-500 million years ago required a defensive strategy against microbial invasion. Pore-forming proteins containing the membrane-attack-complex-perforin (MACPF) domain were selected as the most efficient means to destroy bacteria or virally infected cells. The mechanism of pore formation by the MACPF domain is distinctive in that pore formation is purely physical and unspecific. The MACPF domain polymerizes, refolds, and inserts itself into bilayer membranes or bacterial outer cell walls. The displacement of surface lipid/carbohydrate molecules by the polymerizing MACPF domain creates clusters of large, water-filled holes that destabilize the barrier function and provide access for additional anti-bacterial or anti-viral effectors to sensitive sites that complete the destruction of the invader via enzymatic or chemical attack. The highly efficient mechanism of anti-microbial defense by a combined physical and chemical strategy using pore-forming MACPF-proteins has been retargeted during evolution of vertebrates and mammals for three purposes: (1) to kill extracellular bacteria C9/polyC9 evolved in conjunction with complement, (2) to kill virus infected and cancer cells perforin-1/polyperforin-1 CTL evolved targeted by NK and CTL, and (3) to kill intracellular bacteria transmembrane perforin-2/putative polyperforin-2 evolved targeted by phagocytic and nonphagocytic cells. Our laboratory has been involved in the discovery and description of each of the three pore-formers that will be reviewed here.}, } @article {pmid24287596, year = {2013}, author = {Boughalmi, M and Pagnier, I and Aherfi, S and Colson, P and Raoult, D and La Scola, B}, title = {First isolation of a giant virus from wild Hirudo medicinalis leech: Mimiviridae isolation in Hirudo medicinalis.}, journal = {Viruses}, volume = {5}, number = {12}, pages = {2920-2930}, pmid = {24287596}, issn = {1999-4915}, mesh = {Acanthamoeba/growth & development ; Animals ; Cluster Analysis ; DNA, Viral/chemistry/genetics ; France ; Hirudo medicinalis/*virology ; Microscopy, Electron ; Mimiviridae/classification/genetics/*isolation & purification ; Phylogeny ; Sequence Analysis, DNA ; Sequence Homology ; Tunisia ; }, abstract = {Giant viruses and amoebae are common in freshwater, where they can coexist with other living multicellular organisms. We screened leeches from the species Hirudo medicinalis for giant viruses. We analyzed five H. medicinalis obtained from Tunisia (3) and France (2). The leeches were decontaminated and then dissected to remove internal parts for co-culture with Acanthamoeba polyphaga. The genomes of isolated viruses were sequenced on a 454 Roche instrument, and a comparative genomics analysis was performed. One Mimivirus was isolated and the strain was named Hirudovirus. The genome assembly generated two scaffolds, which were 1,155,382 and 25,660 base pairs in length. Functional annotations were identified for 47% of the genes, which corresponds to 466 proteins. The presence of Mimividae in the same ecological niche as wild Hirudo may explain the presence of the mimivirus in the digestive tract of the leech, and several studies have already shown that viruses can persist in the digestive tracts of leeches fed contaminated blood. As leeches can be used medically and Mimiviruses have the potential to be an infectious agent in humans, patients treated with leeches should be surveyed to investigate a possible connection.}, } @article {pmid24277850, year = {2013}, author = {de Mendoza, A and Sebé-Pedrós, A and Šestak, MS and Matejcic, M and Torruella, G and Domazet-Loso, T and Ruiz-Trillo, I}, title = {Transcription factor evolution in eukaryotes and the assembly of the regulatory toolkit in multicellular lineages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {50}, pages = {E4858-66}, pmid = {24277850}, issn = {1091-6490}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Cell Differentiation/*genetics ; Computational Biology ; Embryonic Development/*genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; Gene Expression Regulation, Developmental/*genetics ; Genomics/methods ; Statistics, Nonparametric ; Transcription Factors/*genetics ; }, abstract = {Transcription factors (TFs) are the main players in transcriptional regulation in eukaryotes. However, it remains unclear what role TFs played in the origin of all of the different eukaryotic multicellular lineages. In this paper, we explore how the origin of TF repertoires shaped eukaryotic evolution and, in particular, their role into the emergence of multicellular lineages. We traced the origin and expansion of all known TFs through the eukaryotic tree of life, using the broadest possible taxon sampling and an updated phylogenetic background. Our results show that the most complex multicellular lineages (i.e., those with embryonic development, Metazoa and Embryophyta) have the most complex TF repertoires, and that these repertoires were assembled in a stepwise manner. We also show that a significant part of the metazoan and embryophyte TF toolkits evolved earlier, in their respective unicellular ancestors. To gain insights into the role of TFs in the development of both embryophytes and metazoans, we analyzed TF expression patterns throughout their ontogeny. The expression patterns observed in both groups recapitulate those of the whole transcriptome, but reveal some important differences. Our comparative genomics and expression data reshape our view on how TFs contributed to eukaryotic evolution and reveal the importance of TFs to the origins of multicellularity and embryonic development.}, } @article {pmid24277716, year = {2014}, author = {Bessa, J and Luengo, M and Rivero-Gil, S and Ariza-Cosano, A and Maia, AH and Ruiz-Ruano, FJ and Caballero, P and Naranjo, S and Carvajal, JJ and Gómez-Skarmeta, JL}, title = {A mobile insulator system to detect and disrupt cis-regulatory landscapes in vertebrates.}, journal = {Genome research}, volume = {24}, number = {3}, pages = {487-495}, pmid = {24277716}, issn = {1549-5469}, mesh = {Animals ; Animals, Genetically Modified ; DNA Transposable Elements/*genetics ; *Enhancer Elements, Genetic ; Fluorescence ; Genes, Reporter/physiology ; Genome ; Humans ; *Insulator Elements ; Mice ; Mutagenesis, Insertional/*methods ; Vertebrates/*genetics ; Zebrafish/genetics ; }, abstract = {In multicellular organisms, cis-regulation controls gene expression in space and time. Despite the essential implication of cis-regulation in the development and evolution of organisms and in human diseases, our knowledge about regulatory sequences largely derives from analyzing their activity individually and outside their genomic context. Indeed, the contribution of these sequences to the expression of their target genes in their genomic context is still largely unknown. Here we present a novel genetic screen designed to visualize and interrupt gene regulatory landscapes in vertebrates. In this screen, based on the random insertion of an engineered Tol2 transposon carrying a strong insulator separating two fluorescent reporter genes, we isolated hundreds of zebrafish lines containing insertions that disrupt the cis-regulation of tissue-specific expressed genes. We therefore provide a new easy-to-handle tool that will help to disrupt and chart the regulatory activity spread through the vast noncoding regions of the vertebrate genome.}, } @article {pmid24277295, year = {2014}, author = {Leducq, JB}, title = {Ecological genomics of adaptation and speciation in fungi.}, journal = {Advances in experimental medicine and biology}, volume = {781}, number = {}, pages = {49-72}, doi = {10.1007/978-94-007-7347-9_4}, pmid = {24277295}, issn = {0065-2598}, mesh = {Adaptation, Biological/*physiology ; *Ecosystem ; *Evolution, Molecular ; Fungi/*physiology ; *Gene-Environment Interaction ; Genome, Fungal/*physiology ; Humans ; *Metagenomics ; Quantitative Trait Loci/physiology ; }, abstract = {Fungi play a central role in both ecosystems and human societies. This is in part because they have adopted a large diversity of life history traits to conquer a wide variety of ecological niches. Here, I review recent fungal genomics studies that explored the molecular origins and the adaptive significance of this diversity. First, macro-ecological genomics studies revealed that fungal genomes were highly remodelled during their evolution. This remodelling, in terms of genome organization and size, occurred through the proliferation of non-coding elements, gene compaction, gene loss and the expansion of large families of adaptive genes. These features vary greatly among fungal clades, and are correlated with different life history traits such as multicellularity, pathogenicity, symbiosis, and sexual reproduction. Second, micro-ecological genomics studies, based on population genomics, experimental evolution and quantitative trait loci approaches, have allowed a deeper exploration of early evolutionary steps of the above adaptations. Fungi, and especially budding yeasts, were used intensively to characterize early mutations and chromosomal rearrangements that underlie the acquisition of new adaptive traits allowing them to conquer new ecological niches and potentially leading to speciation. By uncovering the ecological factors and genomic modifications that underline adaptation, these studies showed that Fungi are powerful models for ecological genomics (eco-genomics), and that this approach, so far mainly developed in a few model species, should be expanded to the whole kingdom.}, } @article {pmid24261447, year = {2013}, author = {Niklas, KJ and Cobb, ED and Crawford, DR}, title = {The evo-devo of multinucleate cells, tissues, and organisms, and an alternative route to multicellularity.}, journal = {Evolution & development}, volume = {15}, number = {6}, pages = {466-474}, doi = {10.1111/ede.12055}, pmid = {24261447}, issn = {1525-142X}, mesh = {*Biological Evolution ; Cell Division ; Eukaryota/classification/cytology/*genetics/growth & development ; Plants/metabolism ; Viridiplantae/classification/*cytology/*genetics/growth & development ; }, abstract = {Multinucleate cells, tissues, or organisms occur in 60 families of land plants and in five otherwise diverse algal lineages (Rhodophyceae, Xanthophyceae, Chlorophyceae, Ulvophyceae, and Charophyceae). Inspection of a morphospace constructed out of eight developmental processes reveals a large number of possible variants of multinucleate cells and organisms that, with two exceptions, are represented by one or more plant species in one or more clades. Thus, most of these permutations of developmental processes exist in nature. Inspection of the morphospace also shows how the siphonous body plan (a multinucleate cell with the capacity for indeterminate growth in size) can theoretically serve as the direct progenitor of a multicellular organism by a process similar to segregative cell division observed in siphonocladean algae. Using molecular phylogenies of algal clades, different evolutionary scenarios are compared to see how the multicellular condition may have evolved from a multinucleate unicellular progenitor. We also show that the siphonous progenitor of a multicellular organism has previously passed through the alignment-of-fitness phase (in which genetic similarity among cells/nuclei minimizes internal genomic conflict) and the export-of-fitness phase (in which genetically similar cells/nuclei collaborate to achieve a reproductively integrated multicellular organism). All that is theoretically required is the evolutionary acquisition of the capacity to compartmentalize its cytoplasm.}, } @article {pmid24256402, year = {2013}, author = {Gleason, EJ and Kramer, EM}, title = {Conserved roles for Polycomb Repressive Complex 2 in the regulation of lateral organ development in Aquilegia x coerulea 'Origami'.}, journal = {BMC plant biology}, volume = {13}, number = {}, pages = {185}, pmid = {24256402}, issn = {1471-2229}, mesh = {Aquilegia/genetics/*growth & development/*metabolism ; *Conserved Sequence ; *Crosses, Genetic ; Down-Regulation/genetics ; Flowers/anatomy & histology/genetics ; Gene Expression Regulation, Plant ; Gene Silencing ; Genetic Association Studies ; *Organogenesis/genetics ; Phenotype ; Plant Leaves/genetics ; Plant Proteins/metabolism ; Plant Viruses/physiology ; Polycomb Repressive Complex 2/genetics/*metabolism ; }, abstract = {BACKGROUND: Epigenetic regulation is necessary for maintaining gene expression patterns in multicellular organisms. The Polycomb Group (PcG) proteins form several complexes with important and deeply conserved epigenetic functions in both the plant and animal kingdoms. One such complex, the Polycomb Repressive Complex 2 (PRC2), is critical to many developmental processes in plants including the regulation of major developmental transitions. In addition, PRC2 restricts the expression domain of various transcription factor families in Arabidopsis, including the class I KNOX genes and several of the ABCE class MADS box genes. While the functions of these transcription factors are known to be deeply conserved, whether or not their regulation by PRC2 is similarly conserved remains an open question.

RESULTS: Here we use virus-induced gene silencing (VIGS) to characterize the function of the PRC2 complex in lateral organ development of Aquilegia x coerulea 'Origami', a member of the lower eudicot order Ranunculales. Leaves with PRC2 down-regulation displayed a range of phenotypes including ruffled or curled laminae, additional lobing, and an increased frequency of higher order branching. Sepals and petals were also affected, being narrowed, distorted, or, in the case of the sepals, exhibiting partial homeotic transformation. Many of the petal limbs also had a particularly intense yellow coloration due to an accumulation of carotenoid pigments. We show that the A. x coerulea floral MADS box genes AGAMOUS1 (AqAG1), APETALA3-3 (AqAP3-3) and SEPALLATA3 (AqSEP3) are up-regulated in many tissues, while expression of the class I KNOX genes and several candidate genes involved in carotenoid production or degradation are largely unaffected.

CONCLUSIONS: PRC2 targeting of several floral MADS box genes may be conserved in dicots, but other known targets do not appear to be. In the case of the type I KNOX genes, this may reflect a regulatory shift associated with the evolution of compound leaves.}, } @article {pmid24252439, year = {2014}, author = {Ågren, JA}, title = {Evolutionary transitions in individuality: insights from transposable elements.}, journal = {Trends in ecology & evolution}, volume = {29}, number = {2}, pages = {90-96}, doi = {10.1016/j.tree.2013.10.007}, pmid = {24252439}, issn = {1872-8383}, mesh = {Animals ; Arabidopsis/genetics ; Behavior, Animal ; *Biological Evolution ; *DNA Transposable Elements ; Genetic Fitness ; Genome ; Individuality ; Reproduction/genetics ; Selection, Genetic ; Social Behavior ; }, abstract = {The history of life has been characterised by evolutionary transitions in individuality, the grouping together of independently replicating units into new larger wholes: genes to chromosomes, chromosomes in genomes, up to three genomes in cells, and cells in multicellular organisms that form groups and societies. Central to understanding these transitions is to determine what prevents selfish behaviour at lower levels from disrupting the functionality of higher levels. Here, I review work on transposable elements, a common source of disruption at the genome level, in light of the evolutionary transitions framework, and argue that the rapid influx of data on transposons from whole-genome sequencing has created a rich data source to incorporate into the study of evolutionary transitions in individuality.}, } @article {pmid24240534, year = {2013}, author = {Pietra, S and Gustavsson, A and Kiefer, C and Kalmbach, L and Hörstedt, P and Ikeda, Y and Stepanova, AN and Alonso, JM and Grebe, M}, title = {Arabidopsis SABRE and CLASP interact to stabilize cell division plane orientation and planar polarity.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {2779}, pmid = {24240534}, issn = {2041-1723}, mesh = {Alleles ; Amino Acid Sequence ; Arabidopsis/*cytology/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Base Sequence ; Cell Division/*physiology ; Cell Polarity/physiology ; Chromosomes, Plant ; Gene Expression Regulation, Plant/*physiology ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Microtubule-Associated Proteins/genetics/*metabolism ; Phylogeny ; }, abstract = {The orientation of cell division and the coordination of cell polarity within the plane of the tissue layer (planar polarity) contribute to shape diverse multicellular organisms. The root of Arabidopsis thaliana displays regularly oriented cell divisions, cell elongation and planar polarity providing a plant model system to study these processes. Here we report that the SABRE protein, which shares similarity with proteins of unknown function throughout eukaryotes, has important roles in orienting cell division and planar polarity. SABRE localizes at the plasma membrane, endomembranes, mitotic spindle and cell plate. SABRE stabilizes the orientation of CLASP-labelled preprophase band microtubules predicting the cell division plane, and of cortical microtubules driving cell elongation. During planar polarity establishment, sabre is epistatic to clasp at directing polar membrane domains of Rho-of-plant GTPases. Our findings mechanistically link SABRE to CLASP-dependent microtubule organization, shedding new light on the function of SABRE-related proteins in eukaryotes.}, } @article {pmid24231534, year = {2013}, author = {Griffiths, JG and Bonser, SP}, title = {Is sex advantageous in adverse environments? A test of the abandon-ship hypothesis.}, journal = {The American naturalist}, volume = {182}, number = {6}, pages = {718-725}, doi = {10.1086/673476}, pmid = {24231534}, issn = {1537-5323}, mesh = {Adaptation, Biological ; Animals ; Population Dynamics ; Reproduction ; *Stress, Physiological ; Trifolium/*physiology ; }, abstract = {Understanding the evolution and maintenance of sexual reproduction remains a long-standing challenge in evolutionary biology. Stress often induces sexual reproduction in facultatively sexual species (those species capable of both sexual and asexual reproduction). The abandon-ship hypothesis predicts higher allocation to sex under stress to allow low-fitness individuals to recombine their genotype, potentially increasing offspring fitness. However, effective tests of the abandon-ship hypothesis, particularly in multicellular organisms, are lacking. Here we test the abandon-ship hypothesis, using cyanogenic and acyanogenic defense phenotypes of the short-lived perennial herb Trifolium repens. Cyanogenesis provides an effective defense against herbivores and is under relatively simple genetic control (plants dominant for cyanogenesis at two alleles express the defended phenotype). Thus, maladapted individuals can acquire adaptive defense alleles for their offspring in a single episode of sexual reproduction. Plants were grown under high- and low-herbivory treatments (plants were exposed to herbivorous snails) and a control treatment (no herbivory). Herbivores reduced growth and fitness in all treated plants, but herbivory induced higher sexual allocation only in maladapted (acyanogenic) individuals. Overall, our results support the abandon-ship hypothesis.}, } @article {pmid24228734, year = {2013}, author = {Adrian, AB and Comeron, JM}, title = {The Drosophila early ovarian transcriptome provides insight to the molecular causes of recombination rate variation across genomes.}, journal = {BMC genomics}, volume = {14}, number = {}, pages = {794}, pmid = {24228734}, issn = {1471-2164}, support = {RC2GM092501/GM/NIGMS NIH HHS/United States ; T32 GM082729/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chromatin/genetics ; *DNA Breaks, Double-Stranded ; Drosophila melanogaster/genetics ; Female ; *Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genome, Insect ; Meiosis/*genetics ; Ovary/metabolism ; *Recombination, Genetic ; }, abstract = {BACKGROUND: Evidence in yeast indicates that gene expression is correlated with recombination activity and double-strand break (DSB) formation in some hotspots. Studies of nucleosome occupancy in yeast and mice also suggest that open chromatin influences the formation of DSBs. In Drosophila melanogaster, high-resolution recombination maps show an excess of DSBs within annotated transcripts relative to intergenic sequences. The impact of active transcription on recombination landscapes, however, remains unexplored in a multicellular organism. We then investigated the transcription profile during early meiosis in D. melanogaster females to obtain a glimpse at the relevant transcriptional dynamics during DSB formation, and test the specific hypothesis that DSBs preferentially target transcriptionally active genomic regions.

RESULTS: Our study of transcript profiles of early- and late-meiosis using mRNA-seq revealed, 1) significant differences in gene expression, 2) new genes and exons, 3) parent-of-origin effects on transcription in early-meiosis stages, and 4) a nonrandom genomic distribution of transcribed genes. Importantly, genomic regions that are more actively transcribed during early meiosis show higher rates of recombination, and we ruled out DSB preference for genic regions that are not transcribed.

CONCLUSIONS: Our results provide evidence in a multicellular organism that transcription during the initial phases of meiosis increases the likelihood of DSB and give insight into the molecular determinants of recombination rate variation across the D. melanogaster genome. We propose that a model where variation in gene expression plays a role altering the recombination landscape across the genome could provide a molecular, heritable and plastic mechanism to observed patterns of recombination variation, from the high level of intra-specific variation to the known influence of environmental factors and stress conditions.}, } @article {pmid24226773, year = {2013}, author = {Arpaia, N and Campbell, C and Fan, X and Dikiy, S and van der Veeken, J and deRoos, P and Liu, H and Cross, JR and Pfeffer, K and Coffer, PJ and Rudensky, AY}, title = {Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.}, journal = {Nature}, volume = {504}, number = {7480}, pages = {451-455}, pmid = {24226773}, issn = {1476-4687}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R37 AI034206/AI/NIAID NIH HHS/United States ; T32 GM007739/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R37AI034206/AI/NIAID NIH HHS/United States ; T32A1007621//PHS HHS/United States ; T32 CA009149/CA/NCI NIH HHS/United States ; T32 AI007621/AI/NIAID NIH HHS/United States ; }, mesh = {Acetylation ; Animals ; Butyrates/*metabolism ; *Cell Differentiation ; Cytokines/metabolism ; Dendritic Cells/immunology/metabolism ; Enhancer Elements, Genetic/genetics ; Fermentation ; Forkhead Transcription Factors/genetics/metabolism ; Histone Deacetylases/metabolism ; Inflammation Mediators/metabolism ; Intestinal Mucosa/cytology/immunology/*metabolism/microbiology ; Intestines/cytology/immunology/*microbiology ; Introns/genetics ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred C57BL ; Starch/metabolism ; *Symbiosis ; T-Lymphocytes, Regulatory/*cytology/immunology/*metabolism ; }, abstract = {Intestinal microbes provide multicellular hosts with nutrients and confer resistance to infection. The delicate balance between pro- and anti-inflammatory mechanisms, essential for gut immune homeostasis, is affected by the composition of the commensal microbial community. Regulatory T cells (Treg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine. Although specific members of the commensal microbial community have been found to potentiate the generation of anti-inflammatory Treg or pro-inflammatory T helper 17 (TH17) cells, the molecular cues driving this process remain elusive. Considering the vital metabolic function afforded by commensal microorganisms, we reasoned that their metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells. We tested this hypothesis by exploring the effect of microbial metabolites on the generation of anti-inflammatory Treg cells. We found that in mice a short-chain fatty acid (SCFA), butyrate, produced by commensal microorganisms during starch fermentation, facilitated extrathymic generation of Treg cells. A boost in Treg-cell numbers after provision of butyrate was due to potentiation of extrathymic differentiation of Treg cells, as the observed phenomenon was dependent on intronic enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic Treg-cell differentiation. In addition to butyrate, de novo Treg-cell generation in the periphery was potentiated by propionate, another SCFA of microbial origin capable of histone deacetylase (HDAC) inhibition, but not acetate, which lacks this HDAC-inhibitory activity. Our results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.}, } @article {pmid24222650, year = {2014}, author = {Bertrand, S and Iwema, T and Escriva, H}, title = {FGF signaling emerged concomitantly with the origin of Eumetazoans.}, journal = {Molecular biology and evolution}, volume = {31}, number = {2}, pages = {310-318}, doi = {10.1093/molbev/mst222}, pmid = {24222650}, issn = {1537-1719}, mesh = {Amino Acid Sequence ; Animals ; Eukaryota/classification/*metabolism ; Evolution, Molecular ; Fibroblast Growth Factors/chemistry/*genetics/metabolism ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Receptors, Fibroblast Growth Factor/metabolism ; Sequence Alignment ; *Signal Transduction ; }, abstract = {Complex metazoan bodies require cell-to-cell communication for development, a process often mediated by signaling molecules binding to specific receptors. Relatively few signaling pathways have been recruited during evolution to build multicellular animals from unicellular zygotes. Of these few signaling pathways, one of particular importance is the receptor tyrosine kinase (RTK) pathway. In metazoans, fibroblast growth factors (FGFs) bind to receptors in the RTK family, but the origin of the FGF gene family has so far remained a mystery. Here we show that extant bona fide FGFs most likely originated from proteins bearing an FGF-like domain that arose in a choanoflagellate/metazoan ancestor. We found orthologous genes closely related to FGF in choanoflagellates as well as in many metazoans such as sponges, acoels, protostomes, or nonvertebrate deuterostomes. We also show that these genes have a common evolutionary history with Retinitis Pigmentosa 1 (RP1). Even if some metazoan signaling pathways emerged long before multicellularity, we show that FGFs, like their receptors, originated in a eumetazoan ancestor.}, } @article {pmid24218634, year = {2013}, author = {Harmston, N and Baresic, A and Lenhard, B}, title = {The mystery of extreme non-coding conservation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {368}, number = {1632}, pages = {20130021}, pmid = {24218634}, issn = {1471-2970}, support = {MC_UP_1102/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Conserved Sequence/*genetics ; DNA, Intergenic/*genetics ; *Evolution, Molecular ; Genome/*genetics ; *Models, Genetic ; Selection, Genetic ; }, abstract = {Regions of several dozen to several hundred base pairs of extreme conservation have been found in non-coding regions in all metazoan genomes. The distribution of these elements within and across genomes has suggested that many have roles as transcriptional regulatory elements in multi-cellular organization, differentiation and development. Currently, there is no known mechanism or function that would account for this level of conservation at the observed evolutionary distances. Previous studies have found that, while these regions are under strong purifying selection, and not mutational coldspots, deletion of entire regions in mice does not necessarily lead to identifiable changes in phenotype during development. These opposing findings lead to several questions regarding their functional importance and why they are under strong selection in the first place. In this perspective, we discuss the methods and techniques used in identifying and dissecting these regions, their observed patterns of conservation, and review the current hypotheses on their functional significance.}, } @article {pmid24213153, year = {2014}, author = {Lenartowski, R and Suwińska, A and Prusińska, J and Gumowski, K and Lenartowska, M}, title = {Molecular cloning and transcriptional activity of a new Petunia calreticulin gene involved in pistil transmitting tract maturation, progamic phase, and double fertilization.}, journal = {Planta}, volume = {239}, number = {2}, pages = {437-454}, pmid = {24213153}, issn = {1432-2048}, mesh = {Amino Acid Sequence ; Base Sequence ; Calcium/*metabolism ; Calcium-Binding Proteins/genetics/metabolism ; Calreticulin/*genetics/metabolism ; DNA, Complementary/chemistry/genetics ; DNA, Plant/chemistry/genetics ; Flowers/cytology/genetics/physiology ; Gene Expression ; *Gene Expression Regulation, Plant ; Homeostasis ; Molecular Sequence Data ; Petunia/cytology/*genetics/physiology ; Phylogeny ; Plant Proteins/genetics/metabolism ; Pollen/cytology/genetics/physiology ; Pollination ; Protein Structure, Tertiary ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {Calreticulin (CRT) is a highly conserved and ubiquitously expressed Ca[2+]-binding protein in multicellular eukaryotes. As an endoplasmic reticulum-resident protein, CRT plays a key role in many cellular processes including Ca[2+] storage and release, protein synthesis, and molecular chaperoning in both animals and plants. CRT has long been suggested to play a role in plant sexual reproduction. To begin to address this possibility, we cloned and characterized the full-length cDNA of a new CRT gene (PhCRT) from Petunia. The deduced amino acid sequence of PhCRT shares homology with other known plant CRTs, and phylogenetic analysis indicates that the PhCRT cDNA clone belongs to the CRT1/CRT2 subclass. Northern blot analysis and fluorescent in situ hybridization were used to assess PhCRT gene expression in different parts of the pistil before pollination, during subsequent stages of the progamic phase, and at fertilization. The highest level of PhCRT mRNA was detected in the stigma-style part of the unpollinated pistil 1 day before anthesis and during the early stage of the progamic phase, when pollen is germinated and tubes outgrow on the stigma. In the ovary, PhCRT mRNA was most abundant after pollination and reached maximum at the late stage of the progamic phase, when pollen tubes grow into the ovules and fertilization occurs. PhCRT mRNA transcripts were seen to accumulate predominantly in transmitting tract cells of maturing and receptive stigma, in germinated pollen/growing tubes, and at the micropylar region of the ovule, where the female gametophyte is located. From these results, we suggest that PhCRT gene expression is up-regulated during secretory activity of the pistil transmitting tract cells, pollen germination and outgrowth of the tubes, and then during gamete fusion and early embryogenesis.}, } @article {pmid24210433, year = {2013}, author = {Miller, PW and Clarke, DN and Weis, WI and Lowe, CJ and Nelson, WJ}, title = {The evolutionary origin of epithelial cell-cell adhesion mechanisms.}, journal = {Current topics in membranes}, volume = {72}, number = {}, pages = {267-311}, pmid = {24210433}, issn = {1063-5823}, support = {U01 GM094663/GM/NIGMS NIH HHS/United States ; R01 GM035527/GM/NIGMS NIH HHS/United States ; GM007276/GM/NIGMS NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; R37 GM035527/GM/NIGMS NIH HHS/United States ; GM035527/GM/NIGMS NIH HHS/United States ; R01 GM056169/GM/NIGMS NIH HHS/United States ; GM56169/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/chemistry/metabolism ; Allosteric Regulation ; Animals ; *Biological Evolution ; Cadherins/genetics/metabolism ; Caenorhabditis elegans/metabolism ; Cell Adhesion ; Chickens/metabolism ; Dictyostelium/metabolism ; Drosophila/metabolism ; Epithelial Cells/cytology/*metabolism ; Extracellular Matrix/metabolism ; Genome ; Mammals/metabolism ; Protein Binding ; Protein Isoforms/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Xenopus laevis/metabolism ; Zebrafish/metabolism ; }, abstract = {A simple epithelium forms a barrier between the outside and the inside of an organism, and is the first organized multicellular tissue found in evolution. We examine the relationship between the evolution of epithelia and specialized cell-cell adhesion proteins comprising the classical cadherin/β-catenin/α-catenin complex (CCC). A review of the divergent functional properties of the CCC in metazoans and non-metazoans, and an updated phylogenetic coverage of the CCC using recent genomic data reveal: (1) The core CCC likely originated before the last common ancestor of unikonts and their closest bikont sister taxa. (2) Formation of the CCC may have constrained sequence evolution of the classical cadherin cytoplasmic domain and β-catenin in metazoa. (3) The α-catenin-binding domain in β-catenin appears to be the favored mutation site for disrupting β-catenin function in the CCC. (4) The ancestral function of the α/β-catenin heterodimer appears to be an actin-binding module. In some metazoan groups, more complex functions of α-catenin were gained by sequence divergence in the non-actin-binding (N-, M-) domains. (5) Allosteric regulation of α-catenin may have evolved for more complex regulation of the actin cytoskeleton.}, } @article {pmid24200356, year = {2013}, author = {Villa, F and Villa, S and Gelain, A and Cappitelli, F}, title = {Sub-lethal activity of small molecules from natural sources and their synthetic derivatives against biofilm forming nosocomial pathogens.}, journal = {Current topics in medicinal chemistry}, volume = {13}, number = {24}, pages = {3184-3204}, doi = {10.2174/15680266113136660225}, pmid = {24200356}, issn = {1873-4294}, mesh = {Anti-Bacterial Agents/chemical synthesis/*chemistry/*pharmacology ; Aquatic Organisms ; Bacteria/chemistry ; Biofilms/drug effects ; Biological Products/chemistry ; Computer Simulation ; Cross Infection/drug therapy/*microbiology ; Drug Design ; High-Throughput Screening Assays/*methods ; Humans ; Plant Extracts/chemistry/pharmacology ; Small Molecule Libraries/*chemical synthesis/*pharmacology ; }, abstract = {Nowadays, the patient safety is seriously jeopardized by the emergence and spread of nosocomial pathogens in the form of biofilm that is resistant to traditional and affordable antimicrobials. Although advances in organic synthesis have extended the lifetime of classic antibiotics through synthetic modifications, the search of innovative antibiofilm compounds from natural sources can provide new templates, novel targets and unique mechanisms that should have advantages over known antimicrobial agents. Testing sub-lethal concentrations of crude extracts and/or isolated compounds from plants and microorganisms is critical to acting on mechanisms subtler than the killing activity, e.g. those influencing the multicellular behavior, offering an elegant way to develop novel antimicrobial-free antibiofilm strategies. Herein we discussed the search and biological activity of small molecules from natural sources and their synthetic derivatives able to modulate biofilm genesis of nosocomial pathogens through non-microbicidal mechanisms (sub-lethal concentrations). The present work offers an overview about the approaches applied to the discovery of lead small molecules including a) conventional drug design methods like screening of chemical compounds obtained from nature and b) computer- aided drug design approaches. Finally, a classification (not exhaustive but representative) based on the natural origin of small molecules and their synthetic derivatives was reported. The information presented in this review should be of interest to a broad range of disciplines and represents an effort to summarize experimental research and advances in this field.}, } @article {pmid24195722, year = {2013}, author = {Zaritsky, A and Manor, N and Wolf, L and Ben-Jacob, E and Tsarfaty, I}, title = {Benchmark for multi-cellular segmentation of bright field microscopy images.}, journal = {BMC bioinformatics}, volume = {14}, number = {}, pages = {319}, pmid = {24195722}, issn = {1471-2105}, mesh = {Algorithms ; Animals ; Cell Movement/*physiology ; Cytological Techniques/*methods/standards ; Dogs ; HEK293 Cells ; Humans ; Image Processing, Computer-Assisted/*methods/standards ; Madin Darby Canine Kidney Cells ; Microscopy/*methods/standards ; }, abstract = {BACKGROUND: Multi-cellular segmentation of bright field microscopy images is an essential computational step when quantifying collective migration of cells in vitro. Despite the availability of various tools and algorithms, no publicly available benchmark has been proposed for evaluation and comparison between the different alternatives.

DESCRIPTION: A uniform framework is presented to benchmark algorithms for multi-cellular segmentation in bright field microscopy images. A freely available set of 171 manually segmented images from diverse origins was partitioned into 8 datasets and evaluated on three leading designated tools.

CONCLUSIONS: The presented benchmark resource for evaluating segmentation algorithms of bright field images is the first public annotated dataset for this purpose. This annotated dataset of diverse examples allows fair evaluations and comparisons of future segmentation methods. Scientists are encouraged to assess new algorithms on this benchmark, and to contribute additional annotated datasets.}, } @article {pmid24193369, year = {2013}, author = {Ratcliff, WC and Herron, MD and Howell, K and Pentz, JT and Rosenzweig, F and Travisano, M}, title = {Experimental evolution of an alternating uni- and multicellular life cycle in Chlamydomonas reinhardtii.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {2742}, pmid = {24193369}, issn = {2041-1723}, mesh = {Animals ; *Biological Evolution ; Chlamydomonas reinhardtii/*cytology/*genetics/physiology ; Molecular Sequence Data ; }, abstract = {The transition to multicellularity enabled the evolution of large, complex organisms, but early steps in this transition remain poorly understood. Here we show that multicellular complexity, including development from a single cell, can evolve rapidly in a unicellular organism that has never had a multicellular ancestor. We subject the alga Chlamydomonas reinhardtii to conditions that favour multicellularity, resulting in the evolution of a multicellular life cycle in which clusters reproduce via motile unicellular propagules. While a single-cell genetic bottleneck during ontogeny is widely regarded as an adaptation to limit among-cell conflict, its appearance very early in this transition suggests that it did not evolve for this purpose. Instead, we find that unicellular propagules are adaptive even in the absence of intercellular conflict, maximizing cluster-level fecundity. These results demonstrate that the unicellular bottleneck, a trait essential for evolving multicellular complexity, can arise rapidly via co-option of the ancestral unicellular form.}, } @article {pmid24188247, year = {2013}, author = {Costantini, M and Alvarez-Valin, F and Costantini, S and Cammarano, R and Bernardi, G}, title = {Compositional patterns in the genomes of unicellular eukaryotes.}, journal = {BMC genomics}, volume = {14}, number = {}, pages = {755}, pmid = {24188247}, issn = {1471-2164}, mesh = {Base Composition ; DNA/chemistry/metabolism ; Eukaryota/classification/*genetics ; *Genome ; Isochores/chemistry/genetics ; Models, Genetic ; Phylogeny ; }, abstract = {BACKGROUND: The genomes of multicellular eukaryotes are compartmentalized in mosaics of isochores, large and fairly homogeneous stretches of DNA that belong to a small number of families characterized by different average GC levels, by different gene concentration (that increase with GC), different chromatin structures, different replication timing in the cell cycle, and other different properties. A question raised by these basic results concerns how far back in evolution the compartmentalized organization of the eukaryotic genomes arose.

RESULTS: In the present work we approached this problem by studying the compositional organization of the genomes from the unicellular eukaryotes for which full sequences are available, the sample used being representative. The average GC levels of the genomes from unicellular eukaryotes cover an extremely wide range (19%-60% GC) and the compositional patterns of individual genomes are extremely different but all genomes tested show a compositional compartmentalization.

CONCLUSIONS: The average GC range of the genomes of unicellular eukaryotes is very broad (as broad as that of prokaryotes) and individual compositional patterns cover a very broad range from very narrow to very complex. Both features are not surprising for organisms that are very far from each other both in terms of phylogenetic distances and of environmental life conditions. Most importantly, all genomes tested, a representative sample of all supergroups of unicellular eukaryotes, are compositionally compartmentalized, a major difference with prokaryotes.}, } @article {pmid24184688, year = {2014}, author = {Päri, M and Kuusksalu, A and Lopp, A and Kjaer, KH and Justesen, J and Kelve, M}, title = {Enzymatically active 2',5'-oligoadenylate synthetases are widely distributed among Metazoa, including protostome lineage.}, journal = {Biochimie}, volume = {97}, number = {}, pages = {200-209}, doi = {10.1016/j.biochi.2013.10.015}, pmid = {24184688}, issn = {1638-6183}, mesh = {2',5'-Oligoadenylate Synthetase/*classification/genetics/metabolism ; Ambystoma mexicanum/classification/genetics/*metabolism ; Amino Acid Sequence ; Animals ; Biological Evolution ; Choanoflagellata/classification/*enzymology/genetics ; Molecular Sequence Data ; Mytilus/classification/*enzymology/genetics ; Nucleotidyltransferases/classification/genetics/metabolism ; *Phylogeny ; Porifera/classification/*enzymology/genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {2',5'-Oligoadenylate synthetases (OASs) belong to the nucleotidyl transferase family together with poly(A) polymerases, CCA-adding enzymes and the recently discovered cyclic-GMP-AMP synthase (cGAS). Mammalian OASs have been thoroughly characterized as components of the interferon-induced antiviral system. The OAS activity and the respective genes were also discovered in marine sponges where the interferon system is absent. In this study the recombinant OASs from several multicellular animals and their closest unicellular relative, a choanoflagellate, were expressed in a bacterial expression system and their enzymatic activities were examined. We demonstrated 2-5A synthesizing activities of OASs from the marine sponge Tedania ignis, a representative of the phylogenetically oldest metazoan phylum (Porifera), from an invertebrate of the protostome lineage, the mollusk Mytilus californianus (Mollusca), and from a vertebrate species, a cartilaginous fish Leucoraja erinacea (Chordata). However, the expressed proteins from an amphibian, the salamander Ambystoma mexicanum (Chordata), and from a protozoan, the marine choanoflagellate Monosiga brevicollis (Choanozoa), did not show 2-5A synthesizing activity. Differently from other studied OASs, OAS from the marine sponge T. ignis was able to catalyze the formation of oligomers having both 2',5'- and 3',5'-phosphodiester linkages. Our data suggest that OASs from sponges and evolutionarily higher animals have similar activation mechanisms which still include different affinities and possibly different structural requirements for the activating RNAs. Considering their 2'- and 3'-specificities, sponge OASs could represent a link between evolutionarily earlier nucleotidyl transferases and 2'-specific OASs from higher animals.}, } @article {pmid24153409, year = {2014}, author = {Phatarphekar, A and Buss, JM and Rokita, SE}, title = {Iodotyrosine deiodinase: a unique flavoprotein present in organisms of diverse phyla.}, journal = {Molecular bioSystems}, volume = {10}, number = {1}, pages = {86-92}, pmid = {24153409}, issn = {1742-2051}, support = {R01 DK084186/DK/NIDDK NIH HHS/United States ; T32 GM080189/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Catalytic Domain ; Diiodotyrosine/metabolism ; Evolution, Molecular ; Gene Expression Regulation, Enzymologic ; Halogenation ; Iodide Peroxidase/chemistry/*genetics/*metabolism ; Iodides/metabolism ; Mice ; Protein Conformation ; Thyroid Hormones/*biosynthesis ; Tyrosine/*metabolism ; }, abstract = {Iodide is required for thyroid hormone synthesis in mammals and other vertebrates. The role of both iodide and iodinated tyrosine derivatives is currently unknown in lower organisms, yet the presence of a key enzyme in iodide conservation, iodotyrosine deiodinase (IYD), is suggested by genomic data from a wide range of multicellular organisms as well as some bacteria. A representative set of these genes has now been expressed, and the resulting enzymes all catalyze reductive deiodination of diiodotyrosine with kcat/Km values within a single order of magnitude. This implies a physiological presence of iodotyrosines (or related halotyrosines) and a physiological role for their turnover. At least for Metazoa, IYD should provide a new marker for tracing the evolutionary development of iodinated amino acids as regulatory signals through the tree of life.}, } @article {pmid24147855, year = {2014}, author = {Svoronos, AA and Tejavibulya, N and Schell, JY and Shenoy, VB and Morgan, JR}, title = {Micro-mold design controls the 3D morphological evolution of self-assembling multicellular microtissues.}, journal = {Tissue engineering. Part A}, volume = {20}, number = {7-8}, pages = {1134-1144}, pmid = {24147855}, issn = {1937-335X}, support = {R01EB008664/EB/NIBIB NIH HHS/United States ; }, mesh = {Equipment Design ; Fibroblasts/drug effects ; Humans ; Tissue Engineering/*instrumentation/*methods ; Transforming Growth Factor beta1/pharmacology ; }, abstract = {When seeded into nonadhesive micro-molds, cells self-assemble three-dimensional (3D) multicellular microtissues via the action of cytoskeletal-mediated contraction and cell-cell adhesion. The size and shape of the tissue is a function of the cell type and the size, shape, and obstacles of the micro-mold. In this article, we used human fibroblasts to investigate some of the elements of mold design and how they can be used to guide the morphological changes that occur as a 3D tissue self-organizes. In a loop-ended dogbone mold with two nonadhesive posts, fibroblasts formed a self-constrained tissue whose tension induced morphological changes that ultimately caused the tissue to thin and rupture. Increasing the width of the dogbone's connecting rod increased the stability, whereas increasing its length decreased the stability. Mapping the rupture points showed that the balance of cell volume between the toroid and connecting rod regions of the dogbone tissue controlled the point of rupture. When cells were treated with transforming growth factor-β1, dogbones ruptured sooner due to increased cell contraction. In mold designs to form tissues with more complex shapes such as three interconnected toroids or a honeycomb, obstacle design controlled tension and tissue morphology. When the vertical posts were changed to cones, they became tension modulators that dictated when and where tension was released in a large self-organizing tissue. By understanding how elements of mold design control morphology, we can produce better models to study organogenesis, examine 3D cell mechanics, and fabricate building parts for tissue engineering.}, } @article {pmid24145419, year = {2013}, author = {Oud, B and Guadalupe-Medina, V and Nijkamp, JF and de Ridder, D and Pronk, JT and van Maris, AJ and Daran, JM}, title = {Genome duplication and mutations in ACE2 cause multicellular, fast-sedimenting phenotypes in evolved Saccharomyces cerevisiae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {45}, pages = {E4223-31}, pmid = {24145419}, issn = {1091-6490}, mesh = {Benzenesulfonates ; Chitinases ; DNA-Binding Proteins/*genetics ; *Directed Molecular Evolution ; Flow Cytometry ; Frameshift Mutation/genetics ; Gene Duplication/*genetics ; Genetic Engineering/*methods ; *Phenotype ; Reverse Transcriptase Polymerase Chain Reaction ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/*genetics ; Sequence Analysis, DNA ; Transcription Factors/*genetics ; }, abstract = {Laboratory evolution of the yeast Saccharomyces cerevisiae in bioreactor batch cultures yielded variants that grow as multicellular, fast-sedimenting clusters. Knowledge of the molecular basis of this phenomenon may contribute to the understanding of natural evolution of multicellularity and to manipulating cell sedimentation in laboratory and industrial applications of S. cerevisiae. Multicellular, fast-sedimenting lineages obtained from a haploid S. cerevisiae strain in two independent evolution experiments were analyzed by whole genome resequencing. The two evolved cell lines showed different frameshift mutations in a stretch of eight adenosines in ACE2, which encodes a transcriptional regulator involved in cell cycle control and mother-daughter cell separation. Introduction of the two ace2 mutant alleles into the haploid parental strain led to slow-sedimenting cell clusters that consisted of just a few cells, thus representing only a partial reconstruction of the evolved phenotype. In addition to single-nucleotide mutations, a whole-genome duplication event had occurred in both evolved multicellular strains. Construction of a diploid reference strain with two mutant ace2 alleles led to complete reconstruction of the multicellular-fast sedimenting phenotype. This study shows that whole-genome duplication and a frameshift mutation in ACE2 are sufficient to generate a fast-sedimenting, multicellular phenotype in S. cerevisiae. The nature of the ace2 mutations and their occurrence in two independent evolution experiments encompassing fewer than 500 generations of selective growth suggest that switching between unicellular and multicellular phenotypes may be relevant for competitiveness of S. cerevisiae in natural environments.}, } @article {pmid24142536, year = {2013}, author = {Schaible, R and Sussman, M}, title = {FOXO in aging: did evolutionary diversification of FOXO function distract it from prolonging life?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {12}, pages = {1101-1110}, doi = {10.1002/bies.201300078}, pmid = {24142536}, issn = {1521-1878}, mesh = {Aging/genetics/*physiology ; Animals ; Evolution, Molecular ; Forkhead Transcription Factors/genetics/*physiology ; Humans ; Longevity/genetics/*physiology ; }, abstract = {In this paper we contrast the simple role of FOXO in the seemingly non-aging Hydra with its more diversified function in multicellular eukaryotes that manifest aging and limited life spans. From this comparison we develop the concept that, whilst once devoted to life-prolonging cell-renewal (in Hydra), evolutionary accumulation of coupled functionality in FOXO has since 'distracted' it from this role. Seen in this light, aging may not be the direct cost of competing functions, such as reproduction or growth, but the result of a shift in emphasis in a protein, which is accompanied by advantages such as greater organismal complexity and adaptability, but also disadvantages such as reduced regeneration capacity. Studying the role of FOXO in non-aging organisms might, therefore, illuminate the path to extend life span in aging organisms.}, } @article {pmid24139735, year = {2013}, author = {Yant, L and Hollister, JD and Wright, KM and Arnold, BJ and Higgins, JD and Franklin, FCH and Bomblies, K}, title = {Meiotic adaptation to genome duplication in Arabidopsis arenosa.}, journal = {Current biology : CB}, volume = {23}, number = {21}, pages = {2151-2156}, pmid = {24139735}, issn = {1879-0445}, support = {1 F32 GM105293/GM/NIGMS NIH HHS/United States ; 1 F32 GM096699/GM/NIGMS NIH HHS/United States ; F32 GM105293/GM/NIGMS NIH HHS/United States ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; F32 GM096699/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/*genetics/metabolism ; Chromosome Segregation ; *Evolution, Molecular ; *Genome, Plant ; Genome-Wide Association Study ; *Meiosis ; Molecular Sequence Data ; *Polyploidy ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Whole genome duplication (WGD) is a major factor in the evolution of multicellular eukaryotes, yet by doubling the number of homologs, WGD severely challenges reliable chromosome segregation, a process conserved across kingdoms. Despite this, numerous genome-duplicated (polyploid) species persist in nature, indicating early problems can be overcome. Little is known about which genes are involved--only one has been molecularly characterized. To gain new insights into the molecular basis of adaptation to polyploidy, we investigated genome-wide patterns of differentiation between natural diploids and tetraploids of Arabidopsis arenosa, an outcrossing relative of A. thaliana. We first show that diploids are not preadapted to polyploid meiosis. We then use a genome scanning approach to show that although polymorphism is extensively shared across ploidy levels, there is strong ploidy-specific differentiation in 39 regions spanning 44 genes. These are discrete, mostly single-gene peaks of sharply elevated differentiation. Among these peaks are eight meiosis genes whose encoded proteins coordinate a specific subset of early meiotic functions, suggesting these genes comprise a polygenic solution to WGD-associated chromosome segregation challenges. Our findings indicate that even conserved meiotic processes can be capable of nimble evolutionary shifts when required.}, } @article {pmid24133452, year = {2013}, author = {Mohanty, A and McBride, HM}, title = {Emerging roles of mitochondria in the evolution, biogenesis, and function of peroxisomes.}, journal = {Frontiers in physiology}, volume = {4}, number = {}, pages = {268}, pmid = {24133452}, issn = {1664-042X}, abstract = {In the last century peroxisomes were thought to have an endosymbiotic origin. Along with mitochondria and chloroplasts, peroxisomes primarily regulate their numbers through the growth and division of pre-existing organelles, and they house specific machinery for protein import. These features were considered unique to endosymbiotic organelles, prompting the idea that peroxisomes were key cellular elements that helped facilitate the evolution of multicellular organisms. The functional similarities to mitochondria within mammalian systems expanded these ideas, as both organelles scavenge peroxide and reactive oxygen species, both organelles oxidize fatty acids, and at least in higher eukaryotes, the biogenesis of both organelles is controlled by common nuclear transcription factors of the PPAR family. Over the last decade it has been demonstrated that the fission machinery of both organelles is also shared, and that both organelles act as critical signaling platforms for innate immunity and other pathways. Taken together it is clear that the mitochondria and peroxisomes are functionally coupled, regulating cellular metabolism and signaling through a number of common mechanisms. However, recent work has focused primarily on the role of the ER in the biogenesis of peroxisomes, potentially overshadowing the critical importance of the mitochondria as a functional partner. In this review, we explore the mechanisms of functional coupling of the peroxisomes to the mitochondria/ER networks, providing some new perspectives on the potential contribution of the mitochondria to peroxisomal biogenesis.}, } @article {pmid24128845, year = {2013}, author = {Bae, J and Jeong, S and Lee, JY and Lee, HJ and Choi, BH and Kim, JE and Choi, I and Chun, T}, title = {Molecular cloning and expression analysis of pig CD138.}, journal = {Research in veterinary science}, volume = {95}, number = {3}, pages = {1021-1025}, doi = {10.1016/j.rvsc.2013.09.010}, pmid = {24128845}, issn = {1532-2661}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Western/veterinary ; Cloning, Molecular ; Flow Cytometry/veterinary ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment/veterinary ; Swine/genetics ; Syndecan-1/*genetics/physiology ; Tissue Distribution ; }, abstract = {CD138 (syndecan-1) interacts with various components of the extracellular matrix and associates with the actin cytoskeleton. In this study, we cloned pig CD138 cDNA and determined its complete cDNA sequence. Pig CD138 cDNA contained an open reading frame (930 bp) encoding 309 amino acids with five well conserved putative glycosaminoglycan attachment sites, a putative cleavage site for matrix metalloproteinases, and conserved motifs involved in signal transduction among mammalian species. Pig CD138 mRNA was detected in various tissues, including lymphoid and non-lymphoid organs, indicating the multicellular functions of CD138 in pigs. Western blot and flow cytometry analyses detected an approximate 35 kDa pig CD138 protein expressed on the cell surface. Further immunohistochemistry analysis revealed that CD138 expression was mainly observed in submucosa and lamina propria of the pig small intestine. Further study will be necessary to define the functional importance of CD138 during specific infectious diseases in pigs.}, } @article {pmid24125648, year = {2013}, author = {Morino, Y and Okada, K and Niikura, M and Honda, M and Satoh, N and Wada, H}, title = {A genome-wide survey of genes encoding transcription factors in the Japanese pearl oyster, Pinctada fucata: I. homeobox genes.}, journal = {Zoological science}, volume = {30}, number = {10}, pages = {851-857}, doi = {10.2108/zsj.30.851}, pmid = {24125648}, issn = {0289-0003}, mesh = {Animals ; Gene Expression Regulation/physiology ; Genes, Homeobox/*genetics ; *Genome ; Phylogeny ; Pinctada/*genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Homeobox genes are involved in various aspects of the development of multicellular animals, including anterior-posterior patterning of the body plan. We performed a genomic survey of homeobox genes in the Japanese pearl oyster, Pinctada fucata, and annotated 92 homeobox-containing genes and five homeobox-less Pax genes. This species possesses 10 or 11 Hox genes. We annotated another homeobox genes that cover 77 out of the 111 gene families identified in the amphioxus genome. Investigation of these repertoires of homeobox genes will shed new light on the comparatively less well-understood lophotrochozoan development.}, } @article {pmid24120560, year = {2013}, author = {Smith, ME and Gryganskyi, A and Bonito, G and Nouhra, E and Moreno-Arroyo, B and Benny, G}, title = {Phylogenetic analysis of the genus Modicella reveals an independent evolutionary origin of sporocarp-forming fungi in the Mortierellales.}, journal = {Fungal genetics and biology : FG & B}, volume = {61}, number = {}, pages = {61-68}, doi = {10.1016/j.fgb.2013.10.001}, pmid = {24120560}, issn = {1096-0937}, mesh = {Cluster Analysis ; DNA, Fungal/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Fungi/*classification/*genetics ; Molecular Sequence Data ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Most studies of tissue differentiation and development have focused on animals and plants but many fungi form multi-cellular aggregations of spore-bearing tissue known as fruiting bodies or sporocarps. The ability to form sporocarps has arisen independently in several different evolutionary lineages of fungi. Evolutionary relationships of most sporocarp-forming fungi are well known, but the enigmatic zygomycete genus Modicella contains two species of sporocarp-forming fungi for which the phylogenetic affinities have not been explored based on molecular data. Species of Modicella have an uncertain trophic mode and have alternatively been considered members of the order Endogonales (which contains documented species of sporocarp-forming fungi) or the order Mortierellales (which contains no previously documented species of sporocarp-forming fungi). In this study we perform phylogenetic analyses based on ribosomal DNA of Modicella malleola from the Northern Hemisphere and Modicella reniformis from the Southern Hemisphere to determine the evolutionary affinities of the genus Modicella. Our analyses indicate that Modicella is a monophyletic genus of sporocarp-forming fungi nested within the Mortierellales, a group of microfungi with no previously documented sporocarp-forming species. Because Modicella is distantly related to all other known sporocarp-forming fungi, we infer that this lineage has independently evolved the ability form sporocarps. We conclude that the genus Modicella should be a high priority for comparative genomics studies to further elucidate the process of sporocarp formation in fungi.}, } @article {pmid24118120, year = {2013}, author = {Vijendravarma, RK and Kawecki, TJ}, title = {Epistasis and maternal effects in experimental adaptation to chronic nutritional stress in Drosophila.}, journal = {Journal of evolutionary biology}, volume = {26}, number = {12}, pages = {2566-2580}, doi = {10.1111/jeb.12248}, pmid = {24118120}, issn = {1420-9101}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Drosophila/genetics/*physiology ; *Epistasis, Genetic ; Female ; *Nutritional Status ; *Stress, Physiological ; }, abstract = {Based on ecological and metabolic arguments, some authors predict that adaptation to novel, harsh environments should involve alleles showing negative (diminishing return) epistasis and/or that it should be mediated in part by evolution of maternal effects. Although the first prediction has been supported in microbes, there has been little experimental support for either prediction in multicellular eukaryotes. Here we use a line-cross design to study the genetic architecture of adaptation to chronic larval malnutrition in a population of Drosophila melanogaster that evolved on an extremely nutrient-poor larval food for 84 generations. We assayed three fitness-related traits (developmental rate, adult female weight and egg-to-adult viability) under the malnutrition conditions in 14 crosses between this selected population and a nonadapted control population originally derived from the same base population. All traits showed a pattern of negative epistasis between alleles improving performance under malnutrition. Furthermore, evolutionary changes in maternal traits accounted for half of the 68% increase in viability and for the whole of 8% reduction in adult female body weight in the selected population (relative to unselected controls). These results thus support both of the above predictions and point to the importance of nonadditive effects in adaptive microevolution.}, } @article {pmid24109602, year = {2014}, author = {Mukherjee, K and Korithoski, B and Kolaczkowski, B}, title = {Ancient origins of vertebrate-specific innate antiviral immunity.}, journal = {Molecular biology and evolution}, volume = {31}, number = {1}, pages = {140-153}, pmid = {24109602}, issn = {1537-1719}, support = {R21 AI101571/AI/NIAID NIH HHS/United States ; AI101571-02/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; *Immunity, Innate ; Molecular Sequence Data ; Open Reading Frames ; *Phylogeny ; Protein Conformation ; RNA Helicases/genetics/immunology ; RNA, Viral/genetics ; RNA-Binding Proteins/genetics/metabolism ; Receptors, Pattern Recognition/genetics/immunology ; Sequence Alignment ; Vertebrates/classification/*immunology/*virology ; }, abstract = {Animals deploy various molecular sensors to detect pathogen infections. RIG-like receptor (RLR) proteins identify viral RNAs and initiate innate immune responses. The three human RLRs recognize different types of RNA molecules and protect against different viral pathogens. The RLR protein family is widely thought to have originated shortly before the emergence of vertebrates and rapidly diversified through a complex process of domain grafting. Contrary to these findings, here we show that full-length RLRs and their downstream signaling molecules were present in the earliest animals, suggesting that the RLR-based immune system arose with the emergence of multicellularity. Functional differentiation of RLRs occurred early in animal evolution via simple gene duplication followed by modifications of the RNA-binding pocket, many of which may have been adaptively driven. Functional analysis of human and ancestral RLRs revealed that the ancestral RLR displayed RIG-1-like RNA-binding. MDA5-like binding arose through changes in the RNA-binding pocket following the duplication of the ancestral RLR, which may have occurred either early in Bilateria or later, after deuterostomes split from protostomes. The sensitivity and specificity with which RLRs bind different RNA structures has repeatedly adapted throughout mammalian evolution, suggesting a long-term evolutionary arms race with viral RNA or other molecules.}, } @article {pmid24106029, year = {2013}, author = {Rehorek, SJ and Grand-Pierre, AE and Cummings, JR and Jewell, B and Constantine, J and Hillenius, WJ}, title = {A re-examination and re-evaluation of salamander orbital glands.}, journal = {Anatomical record (Hoboken, N.J. : 2007)}, volume = {296}, number = {11}, pages = {1789-1796}, doi = {10.1002/ar.22782}, pmid = {24106029}, issn = {1932-8494}, mesh = {Animals ; Biological Evolution ; Environment ; Female ; Harderian Gland/*anatomy & histology ; Male ; Nasolabial Fold/*anatomy & histology ; Nasolacrimal Duct/*anatomy & histology ; North America ; Orbit/*anatomy & histology ; Phylogeny ; Terminology as Topic ; Caudata/*anatomy & histology ; }, abstract = {The amphibian integument contains numerous multicellular glands. Although two of these, the nasolabial and orbital glands and the associated nasolacrimal duct (NLD), have historically received considerable attention, interpretation of the original observations can be problematic in the context of current literature. Salamanders, in particular, are frequently regarded as at least indicative of aspects of the morphology of the common ancestor to all extant tetrapods; hence, an understanding of these glands in salamanders might prove to be informative about their evolution. For this study, the orbitonasal region of salamanders from three families was histologically examined. Three themes emerged: (1) examination of the effect of phylogeny on the nasolabial gland and NLD revealed a combination of features that may be unique to plethodontid salamanders, and may be correlated to their nose-tapping behavior by which substances are moved into the vomeronasal organ; (2) ecology appears to impact the relative development of the orbital glands, but not necessarily the nasolabial gland, with smaller glands being present in the aquatic species; (3) the nomenclature of the salamander orbital gland remains problematic, especially in light of comparative studies, as several alternate possibilities are viable. From this nomenclatural conundrum, however, it could be concluded that there may be a global pattern in the location of tetrapod orbital gland development. Molecular questions in terms of ontogeny and genetic homology affect the nature of the debate on orbital gland nomenclature. These observations suggest that rather than reflecting an ancestral condition, salamanders may instead represent a case of specialized, convergent evolution.}, } @article {pmid24098140, year = {2013}, author = {Frédéric, MY and Lundin, VF and Whiteside, MD and Cueva, JG and Tu, DK and Kang, SY and Singh, H and Baillie, DL and Hutter, H and Goodman, MB and Brinkman, FS and Leroux, MR}, title = {Identification of 526 conserved metazoan genetic innovations exposes a new role for cofactor E-like in neuronal microtubule homeostasis.}, journal = {PLoS genetics}, volume = {9}, number = {10}, pages = {e1003804}, pmid = {24098140}, issn = {1553-7404}, support = {R01 NS047715/NS/NINDS NIH HHS/United States ; R01NS047715/NS/NINDS NIH HHS/United States ; BMB173007/CAPMC/CIHR/Canada ; }, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/genetics/metabolism ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Homeostasis ; Humans ; Metabolic Networks and Pathways/genetics ; Microtubule-Associated Proteins/*genetics/metabolism ; Microtubules/*genetics/metabolism ; Neurons/*metabolism ; Phylogeny ; Placozoa/genetics ; }, abstract = {The evolution of metazoans from their choanoflagellate-like unicellular ancestor coincided with the acquisition of novel biological functions to support a multicellular lifestyle, and eventually, the unique cellular and physiological demands of differentiated cell types such as those forming the nervous, muscle and immune systems. In an effort to understand the molecular underpinnings of such metazoan innovations, we carried out a comparative genomics analysis for genes found exclusively in, and widely conserved across, metazoans. Using this approach, we identified a set of 526 core metazoan-specific genes (the 'metazoanome'), approximately 10% of which are largely uncharacterized, 16% of which are associated with known human disease, and 66% of which are conserved in Trichoplax adhaerens, a basal metazoan lacking neurons and other specialized cell types. Global analyses of previously-characterized core metazoan genes suggest a prevalent property, namely that they act as partially redundant modifiers of ancient eukaryotic pathways. Our data also highlights the importance of exaptation of pre-existing genetic tools during metazoan evolution. Expression studies in C. elegans revealed that many metazoan-specific genes, including tubulin folding cofactor E-like (TBCEL/coel-1), are expressed in neurons. We used C. elegans COEL-1 as a representative to experimentally validate the metazoan-specific character of our dataset. We show that coel-1 disruption results in developmental hypersensitivity to the microtubule drug paclitaxel/taxol, and that overexpression of coel-1 has broad effects during embryonic development and perturbs specialized microtubules in the touch receptor neurons (TRNs). In addition, coel-1 influences the migration, neurite outgrowth and mechanosensory function of the TRNs, and functionally interacts with components of the tubulin acetylation/deacetylation pathway. Together, our findings unveil a conserved molecular toolbox fundamental to metazoan biology that contains a number of neuronally expressed and disease-related genes, and reveal a key role for TBCEL/coel-1 in regulating microtubule function during metazoan development and neuronal differentiation.}, } @article {pmid24085781, year = {2013}, author = {Kozubowski, L and Yadav, V and Chatterjee, G and Sridhar, S and Yamaguchi, M and Kawamoto, S and Bose, I and Heitman, J and Sanyal, K}, title = {Ordered kinetochore assembly in the human-pathogenic basidiomycetous yeast Cryptococcus neoformans.}, journal = {mBio}, volume = {4}, number = {5}, pages = {e00614-13}, pmid = {24085781}, issn = {2150-7511}, support = {R37AI39115-15/AI/NIAID NIH HHS/United States ; R01 AI039115/AI/NIAID NIH HHS/United States ; R01 AI050113/AI/NIAID NIH HHS/United States ; R37 AI039115/AI/NIAID NIH HHS/United States ; R01AI50113-10/AI/NIAID NIH HHS/United States ; }, mesh = {Chromosomes, Fungal/genetics/metabolism ; Cryptococcosis/*microbiology ; Cryptococcus neoformans/*cytology/genetics/*metabolism ; Fungal Proteins/genetics/metabolism ; Humans ; Kinetochores/*metabolism ; Mitosis ; }, abstract = {UNLABELLED: Kinetochores facilitate interaction between chromosomes and the spindle apparatus. The formation of a metazoan trilayered kinetochore is an ordered event in which inner, middle, and outer layers assemble during disassembly of the nuclear envelope during mitosis. The existence of a similar strong correlation between kinetochore assembly and nuclear envelope breakdown in unicellular eukaryotes is unclear. Studies in the hemiascomycetous budding yeasts Saccharomyces cerevisiae and Candida albicans suggest that an ordered kinetochore assembly may not be evolutionarily conserved. Here, we utilized high-resolution time-lapse microscopy to analyze the localization patterns of a series of putative kinetochore proteins in the basidiomycetous budding yeast Cryptococcus neoformans, a human pathogen. Strikingly, similar to most metazoa but atypical of yeasts, the centromeres are not clustered but positioned adjacent to the nuclear envelope in premitotic C. neoformans cells. The centromeres gradually coalesce to a single cluster as cells progress toward mitosis. The mitotic clustering of centromeres seems to be dependent on the integrity of the mitotic spindle. To study the dynamics of the nuclear envelope, we followed the localization of two marker proteins, Ndc1 and Nup107. Fluorescence microscopy of the nuclear envelope and components of the kinetochore, along with ultrastructure analysis by transmission electron microscopy, reveal that in C. neoformans, the kinetochore assembles in an ordered manner prior to mitosis in concert with a partial opening of the nuclear envelope. Taken together, the results of this study demonstrate that kinetochore dynamics in C. neoformans is reminiscent of that of metazoans and shed new light on the evolution of mitosis in eukaryotes.

IMPORTANCE: Successful propagation of genetic material in progeny is essential for the survival of any organism. A proper kinetochore-microtubule interaction is crucial for high-fidelity chromosome segregation. An error in this process can lead to loss or gain of chromosomes, a common feature of most solid cancers. Several proteins assemble on centromere DNA to form a kinetochore. However, significant differences in the process of kinetochore assembly exist between unicellular yeasts and multicellular metaozoa. Here, we examined the key events that lead to formation of a proper kinetochore in a basidiomycetous budding yeast, Cryptococcus neoformans. We found that, during the progression of the cell cycle, nonclustered centromeres gradually clustered and kinetochores assembled in an ordered manner concomitant with partial opening of the nuclear envelope in this organism. These events have higher similarity to mitotic events of metazoans than to those previously described in other yeasts.}, } @article {pmid24085520, year = {2013}, author = {Khokhlov, AN}, title = {Impairment of regeneration in aging: appropriateness or stochastics?.}, journal = {Biogerontology}, volume = {14}, number = {6}, pages = {703-708}, doi = {10.1007/s10522-013-9468-x}, pmid = {24085520}, issn = {1573-6768}, mesh = {Aging/*pathology ; Animals ; Cell Proliferation ; Cellular Senescence ; Humans ; *Models, Biological ; *Regeneration ; Stochastic Processes ; }, abstract = {There is a viewpoint that suppression of the proliferative capacity of cells and impairment of the regeneration of tissues and organs in aging are a consequence of specially arisen during evolution mechanisms that reduce the risk of malignant transformation and, thus, protect against cancer. We believe that the restriction of cell proliferation in an aging multicellular organism is not a consequence of implementing a special program of aging. Apparently, such a program does not exist at all and aging is only a "byproduct" of the program of development, implementation of which in higher organisms suggests the need for the emergence of cell populations with very low or even zero proliferative activity, which determines the limited capacity of relevant organs and tissues to regenerate. At the same time, it is the presence of highly differentiated cell populations, barely able or completely unable to reproduce (neurons, cardiomyocytes, hepatocytes), that ensures the normal functioning of the higher animals and humans. Apparently, the impairment of regulatory processes, realized at the neurohumoral level, still plays the main role in the mechanisms of aging of multicellular organisms, not just the accumulation of macromolecular defects in individual cells. It seems that the quality of the cells themselves does not worsen with age as much as reliability of the organism control over cells, organs and tissues, which leads to an increase in the probability of death.}, } @article {pmid24081281, year = {2013}, author = {Nogueira, A and Ottra, JH and Guimarães, E and Machado, SR and Lohmann, LG}, title = {Trichome structure and evolution in Neotropical lianas.}, journal = {Annals of botany}, volume = {112}, number = {7}, pages = {1331-1350}, pmid = {24081281}, issn = {1095-8290}, mesh = {Bignoniaceae/*anatomy & histology/ultrastructure ; *Biological Evolution ; Likelihood Functions ; Phylogeny ; Trichomes/*anatomy & histology/ultrastructure ; *Tropical Climate ; }, abstract = {BACKGROUND AND AIMS: Trichomes are epidermal outgrowths generally associated with protection against herbivores and/or desiccation that are widely distributed from ferns to angiosperms. Patterns of topological variation and morphological evolution of trichomes are still scarce in the literature, preventing valid comparisons across taxa. This study integrates detailed morphoanatomical data and the evolutionary history of the tribe Bignonieae (Bignoniaceae) in order to gain a better understanding of current diversity and evolution of trichome types.

METHODS: Two sampling schemes were used to characterize trichome types: (1) macromorphological characterization of all 105 species currently included in Bignonieae; and (2) micromorphological characterization of 16 selected species. Individual trichome morphotypes were coded as binary in each vegetative plant part, and trichome density and size were coded as multistate. Ancestral character state reconstructions were conducted using maximum likelihood (ML) assumptions.

KEY RESULTS: Two main functional trichome categories were found: non-glandular and glandular. In glandular trichomes, three morphotypes were recognized: peltate (Pg), stipitate (Sg) and patelliform/cupular (P/Cg) trichomes. Non-glandular trichomes were uniseriate, uni- or multicellular and simple or branched. Pg and P/Cg trichomes were multicellular and non-vascularized with three clearly distinct cell layers. Sg trichomes were multicellular, uniseriate and long-stalked. ML ancestral character state reconstructions suggested that the most recent common ancestor (MRCA) of Bignonieae probably had non-glandular, Pg and P/Cg trichomes, with each trichome type presenting alternative histories of appearance on the different plant parts. For example, the MRCA of Bignonieae probably had non-glandular trichomes on the stems, prophylls, petiole, petiolule and leaflet veins while P/Cg trichomes were restricted to leaflet blades. Sg trichomes were not present in the MRCA of Bignonieae independently of the position of these trichomes. These trichomes had at least eight independent origins in tribe.

CONCLUSIONS: The patterns of trichome evolution indicate that most morphotypes are probably homologous in Bignonieae and could be treated under the same name based on its morphological similarity and common evolutionary history, in spite of the plethora of names that have been previously designated in the literature. The trichome descriptions presented here will facilitate comparisons across taxa, allowing inferences on the relationsthips between trichome variants and future studies about their functional properties.}, } @article {pmid24080887, year = {2013}, author = {Gómez-Lus, ML and Corcuera, MT and Gómez-Lus, R and Sánchez-Serrano, C and Gómez-Aguado, F and Alonso, MJ and Prieto, J}, title = {[Structural dynamics of Legionella pneumophila and Legionella bozemanii colony/biofilm].}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {26}, number = {3}, pages = {214-219}, pmid = {24080887}, issn = {1988-9518}, mesh = {Biofilms/*growth & development ; Culture Media ; Humans ; Image Processing, Computer-Assisted ; Legionella/*growth & development/physiology ; Legionella pneumophila/*growth & development/physiology ; Legionnaires' Disease/microbiology ; Microscopy, Electron, Transmission ; Paraffin Embedding ; Plastic Embedding ; Species Specificity ; }, abstract = {OBJECTIVES: The genus Legionella includes very pleomorphic species responsible for disease outbreaks in humans. The appearance of such has great importance to develop artificial biofilms in aquatic ecosystems. The aim of this work was to study the dynamics of growth and evolution of the internal structure of colonies of representative species of the genus as static biofilm model.

METHODS: Isolated colonies of Legionella pneumophila and Legionella bozemanii grown in specific media for three and fifteen days were processed for histological methods and embedded in paraffin and epoxy resin for analysis by light microscopy, electron microscopy and image analysis. RESULTS. In colonies of both species were observed and defined specific architectural patterns, based on stratification and evolve over time. The strata differ in the amount of extracellular matrix, the morphology and population density and the proportion of dead cells. The internal structure of three days colonies showed large differences between L. pneumophila (two layers) and L. bozemanii (four layers). However, in the fifteen days colonies of both species evolved towards a common unique pattern formed by three layers. In both species the growth was also found within the culture medium, although this phenomenon was more intense in L. bozemanii with unique, central and larger invasions.

CONCLUSIONS: Our results demonstrate that Legionella colonies on solid culture media are a good model of static biofilm with a complex structural dynamics characterized by the presence of morphological and functional subpopulations. We bring here an histological approach model, allowing, in further research, detailed studies in evolutionary adaptations in multicellular communities to adverse media and to antimicrobials in Legionella species of clinical interest.}, } @article {pmid24080405, year = {2014}, author = {Murcha, MW and Wang, Y and Narsai, R and Whelan, J}, title = {The plant mitochondrial protein import apparatus - the differences make it interesting.}, journal = {Biochimica et biophysica acta}, volume = {1840}, number = {4}, pages = {1233-1245}, doi = {10.1016/j.bbagen.2013.09.026}, pmid = {24080405}, issn = {0006-3002}, mesh = {Membrane Transport Proteins/*physiology ; Mitochondria/genetics/*metabolism ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Plant Proteins/genetics/*metabolism ; Plants/*metabolism/ultrastructure ; Protein Transport/physiology ; Saccharomyces cerevisiae/*metabolism/ultrastructure ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {BACKGROUND: Mitochondria play essential roles in the life and death of almost all eukaryotic cells, ranging from single-celled to multi-cellular organisms that display tissue and developmental differentiation. As mitochondria only arose once in evolution, much can be learned from studying single celled model systems such as yeast and applying this knowledge to other organisms. However, two billion years of evolution have also resulted in substantial divergence in mitochondrial function between eukaryotic organisms.

SCOPE OF REVIEW: Here we review our current understanding of the mechanisms of mitochondrial protein import between plants and yeast (Saccharomyces cerevisiae) and identify a high level of conservation for the essential subunits of plant mitochondrial import apparatus. Furthermore, we investigate examples whereby divergence and acquisition of functions have arisen and highlight the emerging examples of interactions between the import apparatus and components of the respiratory chain.

MAJOR CONCLUSIONS: After more than three decades of research into the components and mechanisms of mitochondrial protein import of plants and yeast, the differences between these systems are examined. Specifically, expansions of the small gene families that encode the mitochondrial protein import apparatus in plants are detailed, and their essential role in seed viability is revealed.

GENERAL SIGNIFICANCE: These findings point to the essential role of the inner mitochondrial protein translocases in Arabidopsis, establishing their necessity for seed viability and the crucial role of mitochondrial biogenesis during germination. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.}, } @article {pmid24068653, year = {2013}, author = {de Paula, WB and Agip, AN and Missirlis, F and Ashworth, R and Vizcay-Barrena, G and Lucas, CH and Allen, JF}, title = {Female and male gamete mitochondria are distinct and complementary in transcription, structure, and genome function.}, journal = {Genome biology and evolution}, volume = {5}, number = {10}, pages = {1969-1977}, pmid = {24068653}, issn = {1759-6653}, mesh = {Adenosine Triphosphate/biosynthesis ; Aging/genetics ; Animals ; *Biological Evolution ; DNA, Mitochondrial/*genetics ; Electron Transport/genetics ; Female ; Free Radicals/metabolism ; Germ Cells/metabolism ; Male ; Mitochondria/genetics/metabolism ; Oocytes/*metabolism ; Oxygen/metabolism ; Spermatozoa/*metabolism ; *Transcription, Genetic ; Zebrafish/metabolism ; }, abstract = {Respiratory electron transport in mitochondria is coupled to ATP synthesis while generating mutagenic oxygen free radicals. Mitochondrial DNA mutation then accumulates with age, and may set a limit to the lifespan of individual, multicellular organisms. Why is this mutation not inherited? Here we demonstrate that female gametes-oocytes-have unusually small and simple mitochondria that are suppressed for DNA transcription, electron transport, and free radical production. By contrast, male gametes-sperm-and somatic cells of both sexes transcribe mitochondrial genes for respiratory electron carriers and produce oxygen free radicals. This germ-line division between mitochondria of sperm and egg is observed in both the vinegar fruitfly and the zebrafish-species spanning a major evolutionary divide within the animal kingdom. We interpret these findings as an evidence that oocyte mitochondria serve primarily as genetic templates, giving rise, irreversibly and in each new generation, to the familiar energy-transducing mitochondria of somatic cells and male gametes. Suppressed mitochondrial metabolism in the female germ line may therefore constitute a mechanism for increasing the fidelity of mitochondrial DNA inheritance.}, } @article {pmid24067914, year = {2013}, author = {Weis, WI and Nelson, WJ and Dickinson, DJ}, title = {Evolution and cell physiology. 3. Using Dictyostelium discoideum to investigate mechanisms of epithelial polarity.}, journal = {American journal of physiology. Cell physiology}, volume = {305}, number = {11}, pages = {C1091-5}, pmid = {24067914}, issn = {1522-1563}, support = {GM-035527/GM/NIGMS NIH HHS/United States ; GM-56169/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Physiological Phenomena/physiology ; Cell Polarity/*physiology ; Dictyostelium/cytology/*physiology ; Epithelial Cells/*physiology ; *Evolution, Molecular ; Humans ; }, abstract = {In Metazoa, a polarized epithelium forms a single-cell-layered barrier that separates the outside from the inside of the organism. In tubular epithelia, the apical side of the cell is constricted relative to the basal side, forming a wedge-shaped cell that can pack into a tube. Apical constriction is mediated by actomyosin activity. In higher animals, apical actomyosin is connected between cells by specialized cell-cell junctions that contain a classical cadherin, the Wnt signaling protein β-catenin, and the actin-binding protein α-catenin. The molecular mechanisms that lead to selective accumulation of myosin at the apical surface of cells are poorly understood. We found that the nonmetazoan Dictyostelium discoideum forms a polarized epithelium that surrounds the stalk tube at the tip of the multicellular fruiting body. Although D. discoideum lacks a cadherin homolog, it expresses homologs of β- and α-catenin. Both catenins are essential for formation of the tip epithelium, polarized protein secretion, and proper multicellular morphogenesis. Myosin localizes apically in tip epithelial cells, and it appears that constriction of this epithelial tube is required for proper morphogenesis. Localization of myosin II is controlled by the protein IQGAP1 and its binding partners cortexillins I and II, which function downstream of α- and β-catenin to exclude myosin from the basolateral cortex and promote apical accumulation of myosin. These studies show that the function of catenins in cell polarity predates the evolution of Wnt signaling and classical cadherins, and that apical localization of myosin is a morphogenetic mechanism conserved from nonmetazoans to vertebrates.}, } @article {pmid24066281, year = {2013}, author = {Bozzaro, S and Buracco, S and Peracino, B}, title = {Iron metabolism and resistance to infection by invasive bacteria in the social amoeba Dictyostelium discoideum.}, journal = {Frontiers in cellular and infection microbiology}, volume = {3}, number = {}, pages = {50}, pmid = {24066281}, issn = {2235-2988}, mesh = {Cation Transport Proteins/metabolism ; Dictyostelium/*metabolism/*microbiology ; Homeostasis ; Iron/*metabolism ; Legionella/*metabolism ; Mycobacterium/*metabolism ; }, abstract = {Dictyostelium cells are forest soil amoebae, which feed on bacteria and proliferate as solitary cells until bacteria are consumed. Starvation triggers a change in life style, forcing cells to gather into aggregates to form multicellular organisms capable of cell differentiation and morphogenesis. As a soil amoeba and a phagocyte that grazes on bacteria as the obligate source of food, Dictyostelium could be a natural host of pathogenic bacteria. Indeed, many pathogens that occasionally infect humans are hosted for most of their time in protozoa or free-living amoebae, where evolution of their virulence traits occurs. Due to these features and its amenability to genetic manipulation, Dictyostelium has become a valuable model organism for studying strategies of both the host to resist infection and the pathogen to escape the defense mechanisms. Similarly to higher eukaryotes, iron homeostasis is crucial for Dictyostelium resistance to invasive bacteria. Iron is essential for Dictyostelium, as both iron deficiency or overload inhibit cell growth. The Dictyostelium genome shares with mammals many genes regulating iron homeostasis. Iron transporters of the Nramp (Slc11A) family are represented with two genes, encoding Nramp1 and Nramp2. Like the mammalian ortholog, Nramp1 is recruited to phagosomes and macropinosomes, whereas Nramp2 is a membrane protein of the contractile vacuole network, which regulates osmolarity. Nramp1 and Nramp2 localization in distinct compartments suggests that both proteins synergistically regulate iron homeostasis. Rather than by absorption via membrane transporters, iron is likely gained by degradation of ingested bacteria and efflux via Nramp1 from phagosomes to the cytosol. Nramp gene disruption increases Dictyostelium sensitivity to infection, enhancing intracellular growth of Legionella or Mycobacteria. Generation of mutants in other "iron genes" will help identify genes essential for iron homeostasis and resistance to pathogens.}, } @article {pmid24048930, year = {2014}, author = {Wanninger, A and Wollesen, T}, title = {Methods in brain development of molluscs.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1082}, number = {}, pages = {117-125}, doi = {10.1007/978-1-62703-655-9_8}, pmid = {24048930}, issn = {1940-6029}, mesh = {Animals ; Brain/cytology/embryology/*growth & development ; Immunohistochemistry/instrumentation/*methods ; *Mollusca ; Vibration ; }, abstract = {Representatives of the phylum Mollusca have long been important models in neurobiological research. Recently, the routine application of immunocytochemistry in combination with confocal laser scanning microscopy has allowed fast generation of highly detailed reconstructions of neural structures of even the smallest multicellular animals, including early developmental stages. As a consequence, large-scale comparative analyses of neurogenesis-an important prerequisite for inferences concerning the evolution of animal nervous systems-are now possible in a reasonable amount of time. Herein, we describe immunocytochemical staining protocols for both whole-mount preparations of developmental stages-usually 70-300 μm in size-as well as for vibratome sections of complex brains. Although our procedures have been optimized for marine molluscs, they may easily be adapted for other (marine) organisms by the creative neurobiologist.}, } @article {pmid24043797, year = {2013}, author = {Sebé-Pedrós, A and Ariza-Cosano, A and Weirauch, MT and Leininger, S and Yang, A and Torruella, G and Adamski, M and Adamska, M and Hughes, TR and Gómez-Skarmeta, JL and Ruiz-Trillo, I}, title = {Early evolution of the T-box transcription factor family.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {40}, pages = {16050-16055}, pmid = {24043797}, issn = {1091-6490}, support = {206883/ERC_/European Research Council/International ; MOP-111007/CAPMC/CIHR/Canada ; }, mesh = {Animals ; *Evolution, Molecular ; Fetal Proteins/*genetics ; Histocytochemistry ; Mesomycetozoea/*genetics ; Microarray Analysis ; Multigene Family/*genetics ; *Phenotype ; *Phylogeny ; Protein Binding ; Real-Time Polymerase Chain Reaction ; Species Specificity ; T-Box Domain Proteins/*genetics ; Xenopus/*genetics ; Brachyury Protein ; }, abstract = {Developmental transcription factors are key players in animal multicellularity, being members of the T-box family that are among the most important. Until recently, T-box transcription factors were thought to be exclusively present in metazoans. Here, we report the presence of T-box genes in several nonmetazoan lineages, including ichthyosporeans, filastereans, and fungi. Our data confirm that Brachyury is the most ancient member of the T-box family and establish that the T-box family diversified at the onset of Metazoa. Moreover, we demonstrate functional conservation of a homolog of Brachyury of the protist Capsaspora owczarzaki in Xenopus laevis. By comparing the molecular phenotype of C. owczarzaki Brachyury with that of homologs of early branching metazoans, we define a clear difference between unicellular holozoan and metazoan Brachyury homologs, suggesting that the specificity of Brachyury emerged at the origin of Metazoa. Experimental determination of the binding preferences of the C. owczarzaki Brachyury results in a similar motif to that of metazoan Brachyury and other T-box classes. This finding suggests that functional specificity between different T-box classes is likely achieved by interaction with alternative cofactors, as opposed to differences in binding specificity.}, } @article {pmid24037739, year = {2013}, author = {Huang, J}, title = {Horizontal gene transfer in eukaryotes: the weak-link model.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {10}, pages = {868-875}, pmid = {24037739}, issn = {1521-1878}, mesh = {Animals ; Eukaryota/*genetics ; Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genes, Bacterial ; Mitochondria/genetics ; *Models, Genetic ; Phylogeny ; Plastids/genetics ; Symbiosis/genetics ; }, abstract = {The significance of horizontal gene transfer (HGT) in eukaryotic evolution remains controversial. Although many eukaryotic genes are of bacterial origin, they are often interpreted as being derived from mitochondria or plastids. Because of their fixed gene pool and gene loss, however, mitochondria and plastids alone cannot adequately explain the presence of all, or even the majority, of bacterial genes in eukaryotes. Available data indicate that no insurmountable barrier to HGT exists, even in complex multicellular eukaryotes. In addition, the discovery of both recent and ancient HGT events in all major eukaryotic groups suggests that HGT has been a regular occurrence throughout the history of eukaryotic evolution. A model of HGT is proposed that suggests both unicellular and early developmental stages as likely entry points for foreign genes into multicellular eukaryotes.}, } @article {pmid24037214, year = {2013}, author = {Lee, YS and Krishnan, A and Zhu, Q and Troyanskaya, OG}, title = {Ontology-aware classification of tissue and cell-type signals in gene expression profiles across platforms and technologies.}, journal = {Bioinformatics (Oxford, England)}, volume = {29}, number = {23}, pages = {3036-3044}, pmid = {24037214}, issn = {1367-4811}, support = {P50 GM071508/GM/NIGMS NIH HHS/United States ; R01 GM071966/GM/NIGMS NIH HHS/United States ; R01 HG005998/HG/NHGRI NIH HHS/United States ; T32 HG003284/HG/NHGRI NIH HHS/United States ; }, mesh = {Bayes Theorem ; Cells/*classification ; Computational Biology/*methods ; *Databases, Factual ; Gene Expression Profiling/*methods ; *High-Throughput Nucleotide Sequencing ; Humans ; Models, Statistical ; Oligonucleotide Array Sequence Analysis/*methods ; Organ Specificity ; }, abstract = {MOTIVATION: Leveraging gene expression data through large-scale integrative analyses for multicellular organisms is challenging because most samples are not fully annotated to their tissue/cell-type of origin. A computational method to classify samples using their entire gene expression profiles is needed. Such a method must be applicable across thousands of independent studies, hundreds of gene expression technologies and hundreds of diverse human tissues and cell-types.

RESULTS: We present Unveiling RNA Sample Annotation (URSA) that leverages the complex tissue/cell-type relationships and simultaneously estimates the probabilities associated with hundreds of tissues/cell-types for any given gene expression profile. URSA provides accurate and intuitive probability values for expression profiles across independent studies and outperforms other methods, irrespective of data preprocessing techniques. Moreover, without re-training, URSA can be used to classify samples from diverse microarray platforms and even from next-generation sequencing technology. Finally, we provide a molecular interpretation for the tissue and cell-type models as the biological basis for URSA's classifications.}, } @article {pmid24032108, year = {2013}, author = {Barteneva, NS and Maltsev, N and Vorobjev, IA}, title = {Microvesicles and intercellular communication in the context of parasitism.}, journal = {Frontiers in cellular and infection microbiology}, volume = {3}, number = {}, pages = {49}, pmid = {24032108}, issn = {2235-2988}, mesh = {Animals ; *Cell Communication ; Exosomes/*metabolism ; *Host-Parasite Interactions ; Humans ; Parasites/*physiology ; }, abstract = {There is a rapidly growing body of evidence that production of microvesicles (MVs) is a universal feature of cellular life. MVs can incorporate microRNA (miRNA), mRNA, mtDNA, DNA and retrotransposons, camouflage viruses/viral components from immune surveillance, and transfer cargo between cells. These properties make MVs an essential player in intercellular communication. Increasing evidence supports the notion that MVs can also act as long-distance vehicles for RNA molecules and participate in metabolic synchronization and reprogramming eukaryotic cells including stem and germinal cells. MV ability to carry on DNA and their general distribution makes them attractive candidates for horizontal gene transfer, particularly between multi-cellular organisms and their parasites; this suggests important implications for the co-evolution of parasites and their hosts. In this review, we provide current understanding of the roles played by MVs in intracellular pathogens and parasitic infections. We also discuss the possible role of MVs in co-infection and host shifting.}, } @article {pmid24030493, year = {2013}, author = {Dejosez, M and Ura, H and Brandt, VL and Zwaka, TP}, title = {Safeguards for cell cooperation in mouse embryogenesis shown by genome-wide cheater screen.}, journal = {Science (New York, N.Y.)}, volume = {341}, number = {6153}, pages = {1511-1514}, doi = {10.1126/science.1241628}, pmid = {24030493}, issn = {1095-9203}, support = {P01 GM81627/GM/NIGMS NIH HHS/United States ; R01 GM077442/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Cell Transdifferentiation/genetics ; Cellular Reprogramming/genetics ; DNA Topoisomerases, Type I/genetics ; Down-Regulation ; Embryonic Development/*genetics ; Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Genome-Wide Association Study ; Induced Pluripotent Stem Cells/metabolism ; Mice ; Mutation ; Receptors, Odorant/genetics ; Tumor Suppressor Protein p53/genetics ; }, abstract = {Ensuring cooperation among formerly autonomous cells has been a central challenge in the evolution of multicellular organisms. One solution is monoclonality, but this option still leaves room for exploitative behavior, as it does not eliminate genetic and epigenetic variability. We therefore hypothesized that embryonic development must be protected by robust regulatory mechanisms that prevent aberrant clones from superseding wild-type cells. Using a genome-wide screen in murine induced pluripotent stem cells, we identified a network of genes (centered on p53, topoisomerase 1, and olfactory receptors) whose down-regulation caused the cells to replace wild-type cells in vitro and in the mouse embryo--without perturbing normal development. These genes thus appear to fulfill an unexpected role in fostering cell cooperation.}, } @article {pmid24026343, year = {2014}, author = {Perera, PI and Ordoñez, CA and Lopez-Lavalle, LA and Dedicova, B}, title = {A milestone in the doubled haploid pathway of cassava: a milestone in the doubled haploid pathway of cassava (Manihot esculenta Crantz): cellular and molecular assessment of anther-derived structures.}, journal = {Protoplasma}, volume = {251}, number = {1}, pages = {233-246}, pmid = {24026343}, issn = {1615-6102}, mesh = {Amplified Fragment Length Polymorphism Analysis ; Cells, Cultured ; Flow Cytometry ; *Haploidy ; Manihot/*cytology/*genetics/growth & development ; Microsatellite Repeats/genetics ; }, abstract = {This study was aimed at inducing androgenesis in cultured anthers of cassava (Manihot esculenta Crantz) to develop a protocol for the production of doubled haploids. Microspore reprogramming was induced in cassava by cold or heat stress of anthers. Since the anthers contain both haploid microspores and diploid somatic cells, it was essential to verify the origin of anther-derived calli. The origin of anther-derived calli was assessed by morphological screening followed by histological analysis and flow cytometry (FCM). Additionally, simple sequence repeat (SSR) and amplified fragmented length polymorphism (AFLP) assays were used for the molecular identification of the microspore-derived calli. The study clearly demonstrated the feasibility of producing microspore-derived calli using heat- or cold-pretreated anthers. Histological studies revealed reprogramming of the developmental pathway of microspores by symmetrical division of the nucleus. Flow cytometry analysis revealed different ploidy level cell types including haploids, which confirmed their origin from the microspores. The SSR and AFLP marker assays independently confirmed the histological and FCM results of a haploid origin of the calli at the DNA level. The presence of multicellular microspores in the in vitro system indicated a switch of developmental program, which constitutes a crucial step in the design of protocols for the regeneration of microspore-derived embryos and plants. This is the first detailed report of calli, embryos, and abnormal shoots originated from the haploid cells in cassava, leading to the development of a protocol for the production of doubled haploid plants in cassava.}, } @article {pmid24021397, year = {2013}, author = {González-Forero, M and Gavrilets, S}, title = {Evolution of manipulated behavior.}, journal = {The American naturalist}, volume = {182}, number = {4}, pages = {439-451}, doi = {10.1086/671932}, pmid = {24021397}, issn = {1537-5323}, mesh = {Animals ; *Biological Evolution ; Helping Behavior ; Insecta/*physiology ; Models, Biological ; *Selection, Genetic ; Social Behavior ; }, abstract = {Many social behaviors are triggered by social partners. For example, cells in a multicellular organism often become soma via extrinsically regulated differentiation, while individuals in a eusocial colony often become helpers via extrinsic caste determination. One explanation for social triggering is that it informs when it is beneficial to express the behavior. Alternatively, social triggering can represent manipulation where social partners partially or completely control the focal individual's behavior. For instance, caste determination in primitively eusocial taxa is typically accomplished via differential feeding or dominance hierarchies, suggesting some manipulation. However, selection would favor resistance if manipulation is detrimental to manipulated parties, and the outcome of the manipulation conflict remains intricate. We analyze the coevolution of manipulation and resistance in a simple but general setting. We show that, despite possible resistance, manipulated behavior can be established under less stringent conditions than spontaneous (i.e., nonmanipulated) behavior because of resistance costs. The existence of this advantage might explain why primitive eusocial behavior tends to be triggered socially and coercively. We provide a simple condition for the advantage of manipulated behavior that may help infer whether a socially triggered behavior is manipulated. We illustrate our analysis with a hypothetical example of maternal manipulation relevant to primitive eusociality.}, } @article {pmid24012879, year = {2013}, author = {Münder, S and Tischer, S and Grundhuber, M and Büchels, N and Bruckmeier, N and Eckert, S and Seefeldt, CA and Prexl, A and Käsbauer, T and Böttger, A}, title = {Notch-signalling is required for head regeneration and tentacle patterning in Hydra.}, journal = {Developmental biology}, volume = {383}, number = {1}, pages = {146-157}, doi = {10.1016/j.ydbio.2013.08.022}, pmid = {24012879}, issn = {1095-564X}, mesh = {Animals ; Bromodeoxyuridine ; DNA Primers/genetics ; Dipeptides ; Extremities/*physiology ; Head/*physiology ; Hydra/*physiology ; In Situ Hybridization ; Microscopy, Confocal ; Receptors, Notch/*metabolism ; Regeneration/*physiology ; Signal Transduction/*physiology ; }, abstract = {Local self-activation and long ranging inhibition provide a mechanism for setting up organising regions as signalling centres for the development of structures in the surrounding tissue. The adult hydra hypostome functions as head organiser. After hydra head removal it is newly formed and complete heads can be regenerated. The molecular components of this organising region involve Wnt-signalling and β-catenin. However, it is not known how correct patterning of hypostome and tentacles are achieved in the hydra head and whether other signals in addition to HyWnt3 are needed for re-establishing the new organiser after head removal. Here we show that Notch-signalling is required for re-establishing the organiser during regeneration and that this is due to its role in restricting tentacle activation. Blocking Notch-signalling leads to the formation of irregular head structures characterised by excess tentacle tissue and aberrant expression of genes that mark the tentacle boundaries. This indicates a role for Notch-signalling in defining the tentacle pattern in the hydra head. Moreover, lateral inhibition by HvNotch and its target HyHes are required for head regeneration and without this the formation of the β-catenin/Wnt dependent head organiser is impaired. Work on prebilaterian model organisms has shown that the Wnt-pathway is important for setting up signalling centres for axial patterning in early multicellular animals. Our data suggest that the integration of Wnt-signalling with Notch-Delta activity was also involved in the evolution of defined body plans in animals.}, } @article {pmid24003001, year = {2013}, author = {Ivancevic, AM and Walsh, AM and Kortschak, RD and Adelson, DL}, title = {Jumping the fine LINE between species: horizontal transfer of transposable elements in animals catalyses genome evolution.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {12}, pages = {1071-1082}, doi = {10.1002/bies.201300072}, pmid = {24003001}, issn = {1521-1878}, mesh = {Animals ; DNA Transposable Elements/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome/*genetics ; Retroelements/*genetics ; }, abstract = {Horizontal transfer (HT) is the transmission of genetic material between non-mating species, a phenomenon thought to occur rarely in multicellular eukaryotes. However, many transposable elements (TEs) are not only capable of HT, but have frequently jumped between widely divergent species. Here we review and integrate reported cases of HT in retrotransposons of the BovB family, and DNA transposons, over a broad range of animals spanning all continents. Our conclusions challenge the paradigm that HT in vertebrates is restricted to infective long terminal repeat (LTR) retrotransposons or retroviruses. This raises the possibility that other non-LTR retrotransposons, such as L1 or CR1 elements, believed to be only vertically transmitted, can horizontally transfer between species. Growing evidence indicates that the process of HT is much more general across different TEs and species than previously believed, and that it likely shapes eukaryotic genomes and catalyses genome evolution.}, } @article {pmid23986111, year = {2013}, author = {Brown, MW and Sharpe, SC and Silberman, JD and Heiss, AA and Lang, BF and Simpson, AG and Roger, AJ}, title = {Phylogenomics demonstrates that breviate flagellates are related to opisthokonts and apusomonads.}, journal = {Proceedings. Biological sciences}, volume = {280}, number = {1769}, pages = {20131755}, pmid = {23986111}, issn = {1471-2954}, support = {MOP-62809//Canadian Institutes of Health Research/Canada ; }, mesh = {Ecosystem ; Estuaries ; Eukaryota/*classification/*genetics/ultrastructure ; Evolution, Molecular ; Genes, rRNA ; Geologic Sediments ; Molecular Sequence Data ; *Phylogeny ; RNA, Protozoan/genetics/metabolism ; Sequence Analysis, RNA ; }, abstract = {Most eukaryotic lineages belong to one of a few major groups. However, several protistan lineages have not yet been robustly placed in any of these groups. Both the breviates and apusomonads are two such lineages that appear to be related to the Amoebozoa and Opisthokonta (i.e. the 'unikonts' or Amorphea); however, their precise phylogenetic positions remain unclear. Here, we describe a novel microaerophilic breviate, Pygsuia biforma gen. nov. sp. nov., isolated from a hypoxic estuarine sediment. Ultrastructurally, this species resembles the breviate genera Breviata and Subulatomonas but has two cell morphologies, adherent and swimming. Phylogenetic analyses of the small sub-unit rRNA gene show that Pygsuia is the sister to the other breviates. We constructed a 159-protein supermatrix, including orthologues identified in RNA-seq data from Pygsuia. Phylogenomic analyses of this dataset show that breviates, apusomonads and Opisthokonta form a strongly supported major eukaryotic grouping we name the Obazoa. Although some phylogenetic methods disagree, the balance of evidence suggests that the breviate lineage forms the deepest branch within Obazoa. We also found transcripts encoding a nearly complete integrin adhesome from Pygsuia, indicating that this protein complex involved in metazoan multicellularity may have evolved earlier in eukaryote evolution than previously thought.}, } @article {pmid23980147, year = {2013}, author = {Alessandri, K and Sarangi, BR and Gurchenkov, VV and Sinha, B and Kießling, TR and Fetler, L and Rico, F and Scheuring, S and Lamaze, C and Simon, A and Geraldo, S and Vignjevic, D and Doméjean, H and Rolland, L and Funfak, A and Bibette, J and Bremond, N and Nassoy, P}, title = {Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {37}, pages = {14843-14848}, pmid = {23980147}, issn = {1091-6490}, mesh = {Alginates ; Animals ; Biomechanical Phenomena ; Capsules ; Cell Count ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Disease Progression ; Elasticity ; Glucuronic Acid ; HeLa Cells ; Hexuronic Acids ; Humans ; Mechanotransduction, Cellular ; Mice ; Microfluidic Analytical Techniques/instrumentation ; Neoplasm Invasiveness/*pathology/*physiopathology ; Spheroids, Cellular/*pathology/*physiology ; Tumor Microenvironment ; }, abstract = {Deciphering the multifactorial determinants of tumor progression requires standardized high-throughput preparation of 3D in vitro cellular assays. We present a simple microfluidic method based on the encapsulation and growth of cells inside permeable, elastic, hollow microspheres. We show that this approach enables mass production of size-controlled multicellular spheroids. Due to their geometry and elasticity, these microcapsules can uniquely serve as quantitative mechanical sensors to measure the pressure exerted by the expanding spheroid. By monitoring the growth of individual encapsulated spheroids after confluence, we dissect the dynamics of pressure buildup toward a steady-state value, consistent with the concept of homeostatic pressure. In turn, these confining conditions are observed to increase the cellular density and affect the cellular organization of the spheroid. Postconfluent spheroids exhibit a necrotic core cemented by a blend of extracellular material and surrounded by a rim of proliferating hypermotile cells. By performing invasion assays in a collagen matrix, we report that peripheral cells readily escape preconfined spheroids and cell-cell cohesivity is maintained for freely growing spheroids, suggesting that mechanical cues from the surrounding microenvironment may trigger cell invasion from a growing tumor. Overall, our technology offers a unique avenue to produce in vitro cell-based assays useful for developing new anticancer therapies and to investigate the interplay between mechanics and growth in tumor evolution.}, } @article {pmid23978389, year = {2013}, author = {Nishihama, R and Kohchi, T}, title = {Evolutionary insights into photoregulation of the cell cycle in the green lineage.}, journal = {Current opinion in plant biology}, volume = {16}, number = {5}, pages = {630-637}, doi = {10.1016/j.pbi.2013.07.006}, pmid = {23978389}, issn = {1879-0356}, mesh = {Biological Evolution ; Cell Cycle/radiation effects ; Chlorophyta/genetics/growth & development/radiation effects ; Cytokinins/metabolism ; Embryophyta/genetics/growth & development/radiation effects ; *Gene Expression Regulation, Plant ; Indoleacetic Acids/metabolism ; Light ; Photoreceptors, Plant/genetics/metabolism ; *Plant Development ; Plant Growth Regulators/metabolism ; Plants/genetics/*radiation effects ; *Signal Transduction ; }, abstract = {Plant growth depends solely on light energy, which drives photosynthesis. Thus, linking growth control to light signals during certain developmental events, such as seed or spore germination and organ formation, is a crucial feature that plants evolved to use energy efficiently. How light controls the cell cycle depends on growth habitats, body plans (unicellular vs. multicellular), and photosensors. For example, the photosensors mediating light signaling to promote cell division appear to differ between green algae and land plants. In this review, we focus on cell-cycle regulation by light and discuss the transition of its molecular mechanisms during evolution. Recent advances show that light-dependent cell-cycle control involves global changes in transcription of cell-cycle genes, and is mediated by auxin and cytokinin.}, } @article {pmid23959164, year = {2013}, author = {Izumi, H and Sagulenko, E and Webb, RI and Fuerst, JA}, title = {Isolation and diversity of planctomycetes from the sponge Niphates sp., seawater, and sediment of Moreton Bay, Australia.}, journal = {Antonie van Leeuwenhoek}, volume = {104}, number = {4}, pages = {533-546}, doi = {10.1007/s10482-013-0003-5}, pmid = {23959164}, issn = {1572-9699}, mesh = {Animals ; Australia ; Bacteria/*classification/*genetics/ultrastructure ; Bays/microbiology ; Geologic Sediments/microbiology ; Phylogeny ; Porifera/*microbiology/ultrastructure ; RNA, Ribosomal, 16S ; Seawater/microbiology ; }, abstract = {Planctomycetes are ubiquitous in marine environment and were reported to occur in association with multicellular eukaryotic organisms such as marine macroalgae and invertebrates. Here, we investigate planctomycetes associated with the marine sponge Niphates sp. from the sub-tropical Australian coast by assessing their diversity using culture-dependent and -independent approaches based on the 16S rRNA gene. The culture-dependent approach resulted in the isolation of a large collection of diverse planctomycetes including some novel lineages of Planctomycetes from the sponge as well as sediment and seawater of Moreton Bay where this sponge occurs. The characterization of these novel planctomycetes revealed that cells of one unique strain do not possess condensed nucleoids, a phenotype distinct from other planctomycetes. In addition, a culture-independent clone library approach identified unique planctomycete 16S rRNA gene sequences closely related to other sponge-derived sequences. The analysis of tissue of the sponge Niphates sp. showed that the mesohyl of the sponge is almost devoid of microbial cells, indicating this species is in the group of 'low microbial abundant' (LMA) sponges. The unique planctomycete 16S rRNA gene sequences identified in this study were phylogenetically closely related to sequences from LMA sponges in other published studies. This study has revealed new insights into the diversity of planctomycetes in the marine environment and the association of planctomycetes with marine sponges.}, } @article {pmid23946353, year = {2013}, author = {Boavida, LC and Qin, P and Broz, M and Becker, JD and McCormick, S}, title = {Arabidopsis tetraspanins are confined to discrete expression domains and cell types in reproductive tissues and form homo- and heterodimers when expressed in yeast.}, journal = {Plant physiology}, volume = {163}, number = {2}, pages = {696-712}, pmid = {23946353}, issn = {1532-2548}, mesh = {Amino Acid Sequence ; Animals ; Arabidopsis/*cytology/genetics/*metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Cell Membrane/metabolism ; Gene Expression Regulation, Plant ; Germ Cells, Plant/cytology/metabolism ; Green Fluorescent Proteins/metabolism ; Molecular Sequence Data ; *Organ Specificity ; Phylogeny ; *Protein Multimerization ; Protein Transport ; Reproduction/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Saccharomyces cerevisiae/*metabolism ; Sequence Alignment ; Subcellular Fractions/metabolism ; Tetraspanins/chemistry/genetics/*metabolism ; }, abstract = {Tetraspanins are evolutionary conserved transmembrane proteins present in all multicellular organisms. In animals, they are known to act as central organizers of membrane complexes and thought to facilitate diverse biological processes, such as cell proliferation, movement, adhesion, and fusion. The genome of Arabidopsis (Arabidopsis thaliana) encodes 17 members of the tetraspanin family; however, little is known about their functions in plant development. Here, we analyzed their phylogeny, protein topology, and domain structure and surveyed their expression and localization patterns in reproductive tissues. We show that, despite their low sequence identity with metazoan tetraspanins, plant tetraspanins display the typical structural topology and most signature features of tetraspanins in other multicellular organisms. Arabidopsis tetraspanins are expressed in diverse tissue domains or cell types in reproductive tissues, and some accumulate at the highest levels in response to pollination in the transmitting tract and stigma, male and female gametophytes and gametes. Arabidopsis tetraspanins are preferentially targeted to the plasma membrane, and they variously associate with specialized membrane domains, in a polarized fashion, to intercellular contacts or plasmodesmata. A membrane-based yeast (Saccharomyces cerevisiae) two-hybrid system established that tetraspanins can physically interact, forming homo- and heterodimer complexes. These results, together with a likely genetic redundancy, suggest that, similar to their metazoan counterparts, plant tetraspanins might be involved in facilitating intercellular communication, whose functions might be determined by the composition of tetraspanin complexes and their binding partners at the cell surface of specific cell types.}, } @article {pmid23945682, year = {2013}, author = {Stewart, AJ and Plotkin, JB}, title = {The evolution of complex gene regulation by low-specificity binding sites.}, journal = {Proceedings. Biological sciences}, volume = {280}, number = {1768}, pages = {20131313}, pmid = {23945682}, issn = {1471-2954}, mesh = {Binding Sites ; *Evolution, Molecular ; *Gene Expression Regulation ; *Gene Regulatory Networks ; Models, Genetic ; Mutation ; }, abstract = {Requirements for gene regulation vary widely both within and among species. Some genes are constitutively expressed, whereas other genes require complex regulatory control. Transcriptional regulation is often controlled by a module of multiple transcription factor binding sites that, in combination, mediate the expression of a target gene. Here, we study how such regulatory modules evolve in response to natural selection. Using a population-genetic model, we show that complex regulatory modules which contain a larger number of binding sites must employ binding motifs that are less specific, on average, compared with smaller regulatory modules. This effect is extremely general, and it holds regardless of the selected binding logic that a module experiences. We attribute this phenomenon to the inability of stabilizing selection to maintain highly specific sites in large regulatory modules. Our analysis helps to explain broad empirical trends in the Saccharomyces cerevisiae regulatory network: those genes with a greater number of distinct transcriptional regulators feature less-specific binding motifs, compared with genes with fewer regulators. Our results also help to explain empirical trends in module size and motif specificity across species, ranging from prokaryotes to single-cellular and multi-cellular eukaryotes.}, } @article {pmid23943356, year = {2013}, author = {Dick, SA and Megeney, LA}, title = {Cell death proteins: an evolutionary role in cellular adaptation before the advent of apoptosis.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {11}, pages = {974-983}, doi = {10.1002/bies.201300052}, pmid = {23943356}, issn = {1521-1878}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adaptation, Physiological/*physiology ; Animals ; Apoptosis/*physiology ; Apoptosis Regulatory Proteins/genetics/*physiology ; Caspases/metabolism ; Cell Differentiation ; Eukaryota/cytology/metabolism ; Evolution, Molecular ; Phosphatidylserines/metabolism ; Signal Transduction ; }, abstract = {Programmed cell death (PCD) or apoptosis is a broadly conserved phenomenon in metazoans, whereby activation of canonical signal pathways induces an ordered dismantling and death of a cell. Paradoxically, the constituent proteins and pathways of PCD (most notably the metacaspase/caspase protease mediated signal pathways) have been demonstrated to retain non-death functions across all phyla including yeast, nematodes, drosophila, and mammals. The ancient conservation of both death and non-death functions of PCD proteins raises an interesting evolutionary conundrum: was the primordial intent of these factors to induce cell death or to regulate other cellular adaptations? Here, we propose the hypothesis that apoptotic behavior of PCD proteins evolved or were co-opted from core non-death functions.}, } @article {pmid23942320, year = {2013}, author = {Suga, H and Chen, Z and de Mendoza, A and Sebé-Pedrós, A and Brown, MW and Kramer, E and Carr, M and Kerner, P and Vervoort, M and Sánchez-Pons, N and Torruella, G and Derelle, R and Manning, G and Lang, BF and Russ, C and Haas, BJ and Roger, AJ and Nusbaum, C and Ruiz-Trillo, I}, title = {The Capsaspora genome reveals a complex unicellular prehistory of animals.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {2325}, pmid = {23942320}, issn = {2041-1723}, support = {HG003067-05/HG/NHGRI NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; HG003067-09/HG/NHGRI NIH HHS/United States ; 206883/ERC_/European Research Council/International ; HG003067-07/HG/NHGRI NIH HHS/United States ; HG003067-06/HG/NHGRI NIH HHS/United States ; HG003067-10/HG/NHGRI NIH HHS/United States ; HG003067-08/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/genetics ; Base Sequence ; Biological Evolution ; Cell Adhesion/genetics ; Choanoflagellata/*genetics/metabolism ; Evolution, Molecular ; Genome ; Intercellular Signaling Peptides and Proteins/*genetics/metabolism ; Mesomycetozoea/*genetics ; Mitochondria/genetics ; Phylogeny ; Protein Structure, Tertiary/genetics ; Sequence Analysis, DNA ; Signal Transduction/genetics ; Transcription, Genetic/genetics ; }, abstract = {To reconstruct the evolutionary origin of multicellular animals from their unicellular ancestors, the genome sequences of diverse unicellular relatives are essential. However, only the genome of the choanoflagellate Monosiga brevicollis has been reported to date. Here we completely sequence the genome of the filasterean Capsaspora owczarzaki, the closest known unicellular relative of metazoans besides choanoflagellates. Analyses of this genome alter our understanding of the molecular complexity of metazoans' unicellular ancestors showing that they had a richer repertoire of proteins involved in cell adhesion and transcriptional regulation than previously inferred only with the choanoflagellate genome. Some of these proteins were secondarily lost in choanoflagellates. In contrast, most intercellular signalling systems controlling development evolved later concomitant with the emergence of the first metazoans. We propose that the acquisition of these metazoan-specific developmental systems and the co-option of pre-existing genes drove the evolutionary transition from unicellular protists to metazoans.}, } @article {pmid23932204, year = {2013}, author = {Small, ID and Rackham, O and Filipovska, A}, title = {Organelle transcriptomes: products of a deconstructed genome.}, journal = {Current opinion in microbiology}, volume = {16}, number = {5}, pages = {652-658}, doi = {10.1016/j.mib.2013.07.011}, pmid = {23932204}, issn = {1879-0364}, mesh = {Animals ; Chloroplasts/*genetics/physiology ; Mitochondria/*genetics/physiology ; Plant Cells/*physiology ; Plants/genetics ; *Transcriptome ; }, abstract = {Genetic drift and mutational pressure have shaped the evolution of mitochondrial and chloroplast genomes, giving rise to mechanisms that regulate their gene expression, which often differ from those in their prokaryotic ancestors. Advances in next generation sequencing technologies have enabled highly detailed characterization of organelle transcriptomes and the discovery of new transcripts and mechanisms for controlling gene expression. Here we discuss the common features of organelle transcriptomes that stem from their prokaryotic origin and some of the new innovations that are unique to organelles of multicellular organisms.}, } @article {pmid23913097, year = {2013}, author = {Tarver, JE and Sperling, EA and Nailor, A and Heimberg, AM and Robinson, JM and King, BL and Pisani, D and Donoghue, PC and Peterson, KJ}, title = {miRNAs: small genes with big potential in metazoan phylogenetics.}, journal = {Molecular biology and evolution}, volume = {30}, number = {11}, pages = {2369-2382}, doi = {10.1093/molbev/mst133}, pmid = {23913097}, issn = {1537-1719}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Conserved Sequence ; *Evolution, Molecular ; Gene Regulatory Networks ; Genome ; Humans ; MicroRNAs/*genetics/*metabolism ; *Phylogeny ; Secondary Metabolism/genetics ; Species Specificity ; }, abstract = {microRNAs (miRNAs) are a key component of gene regulatory networks and have been implicated in the regulation of virtually every biological process found in multicellular eukaryotes. What makes them interesting from a phylogenetic perspective is the high conservation of primary sequence between taxa, their accrual in metazoan genomes through evolutionary time, and the rarity of secondary loss in most metazoan taxa. Despite these properties, the use of miRNAs as phylogenetic markers has not yet been discussed within a clear conceptual framework. Here we highlight five properties of miRNAs that underlie their utility in phylogenetics: 1) The processes of miRNA biogenesis enable the identification of novel miRNAs without prior knowledge of sequence; 2) The continuous addition of miRNA families to metazoan genomes through evolutionary time; 3) The low level of secondary gene loss in most metazoan taxa; 4) The low substitution rate in the mature miRNA sequence; and 5) The small probability of convergent evolution of two miRNAs. Phylogenetic analyses using both Bayesian and parsimony methods on a eumetazoan miRNA data set highlight the potential of miRNAs to become an invaluable new tool, especially when used as an additional line of evidence, to resolve previously intractable nodes within the tree of life.}, } @article {pmid23910661, year = {2013}, author = {Ho, HI and Hirose, S and Kuspa, A and Shaulsky, G}, title = {Kin recognition protects cooperators against cheaters.}, journal = {Current biology : CB}, volume = {23}, number = {16}, pages = {1590-1595}, pmid = {23910661}, issn = {1879-0445}, support = {CA125123/CA/NCI NIH HHS/United States ; AI036211/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R01 GM098276/GM/NIGMS NIH HHS/United States ; R01 GM084992/GM/NIGMS NIH HHS/United States ; RR024574/RR/NCRR NIH HHS/United States ; }, mesh = {*Biological Evolution ; Dictyostelium/cytology/*genetics ; Membrane Proteins/*genetics/metabolism ; Microscopy, Fluorescence ; Organisms, Genetically Modified/genetics ; Phenotype ; Protozoan Proteins/*genetics/metabolism ; Reproduction ; Spores, Protozoan/cytology/genetics ; }, abstract = {The evolution of sociality and altruism is enigmatic because cooperators are constantly threatened by cheaters who benefit from cooperation without incurring its full cost [1, 2]. Kin recognition is the ability to recognize and cooperate with genetically close relatives. It has also been proposed as a potential mechanism that limits cheating [3, 4], but there has been no direct experimental support for that possibility. Here we show that kin recognition protects cooperators against cheaters. The social amoebae Dictyostelium discoideum cooperate by forming multicellular aggregates that develop into fruiting bodies of viable spores and dead stalk cells. Cheaters preferentially differentiate into spores while their victims die as stalk cells in chimeric aggregates. We engineered syngeneic cheaters and victims that differed only in their kin-recognition genes, tgrB1 and tgrC1, and in a single cheater allele and found that the victims escaped exploitation by different types of nonkin cheaters. This protection depends on kin-recognition-mediated segregation because it is compromised when we disrupt strain segregation. These findings provide direct evidence for the role of kin recognition in cheater control and suggest a mechanism for the maintenance of stable cooperative systems.}, } @article {pmid23902772, year = {2013}, author = {Garner, JM and Fan, M and Yang, CH and Du, Z and Sims, M and Davidoff, AM and Pfeffer, LM}, title = {Constitutive activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor κB signaling in glioblastoma cancer stem cells regulates the Notch pathway.}, journal = {The Journal of biological chemistry}, volume = {288}, number = {36}, pages = {26167-26176}, pmid = {23902772}, issn = {1083-351X}, support = {R01 CA133322/CA/NCI NIH HHS/United States ; R01 CA140346/CA/NCI NIH HHS/United States ; CA133322/CA/NCI NIH HHS/United States ; 21766//PHS HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival/genetics ; Gene Expression Regulation, Neoplastic/genetics ; Glioblastoma/genetics/*metabolism/pathology ; Humans ; Mice ; NF-kappa B/genetics/*metabolism ; Neoplasm Proteins/genetics/*metabolism ; Neoplastic Stem Cells/*metabolism/pathology ; Receptors, Notch/genetics/*metabolism ; STAT3 Transcription Factor/*biosynthesis/genetics ; *Signal Transduction ; Spheroids, Cellular/metabolism/pathology ; Up-Regulation/genetics ; }, abstract = {Malignant gliomas are locally aggressive, highly vascular tumors that have a dismal prognosis, and present therapies provide little improvement in the disease course and outcome. Many types of malignancies, including glioblastoma, originate from a population of cancer stem cells (CSCs) that are able to initiate and maintain tumors. Although CSCs only represent a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance drives tumorigenesis. Therefore, it is imperative to identify pathways associated with CSCs to devise strategies to selectively target them. In this study, we describe a novel relationship between glioblastoma CSCs and the Notch pathway, which involves the constitutive activation of STAT3 and NF-κB signaling. Glioma CSCs were isolated and maintained in vitro using an adherent culture system, and the biological properties were compared with the traditional cultures of CSCs grown as multicellular spheres under nonadherent culture conditions. Interestingly, both adherent and spheroid glioma CSCs show constitutive activation of the STAT3/NF-κB signaling pathway and up-regulation of STAT3- and NF-κB-dependent genes. Gene expression profiling also identified components of the Notch pathway as being deregulated in glioma CSCs, and the deregulated expression of these genes was sensitive to treatment with STAT3 and NF-κB inhibitors. This finding is particularly important because Notch signaling appears to play a key role in CSCs in a variety of cancers and controls cell fate determination, survival, proliferation, and the maintenance of stem cells. The constitutive activation of STAT3 and NF-κB signaling pathways that leads to the regulation of Notch pathway genes in glioma CSCs identifies novel therapeutic targets for the treatment of glioma.}, } @article {pmid23899506, year = {2013}, author = {Schallenberg-Rüdinger, M and Lenz, H and Polsakiewicz, M and Gott, JM and Knoop, V}, title = {A survey of PPR proteins identifies DYW domains like those of land plant RNA editing factors in diverse eukaryotes.}, journal = {RNA biology}, volume = {10}, number = {9}, pages = {1549-1556}, pmid = {23899506}, issn = {1555-8584}, mesh = {Acanthamoeba castellanii/genetics/metabolism ; Embryophyta/*genetics/metabolism ; *Eukaryota ; Naegleria/genetics ; Nitella/genetics/metabolism ; Organelles/genetics/metabolism ; Phylogeny ; Physarum polycephalum/genetics/metabolism ; Plant Proteins/genetics/*metabolism ; Prokaryotic Cells/metabolism ; Protein Structure, Tertiary ; *RNA Editing ; RNA-Binding Proteins/genetics/*metabolism ; }, abstract = {The pentatricopeptide repeat modules of PPR proteins are key to their sequence-specific binding to RNAs. Gene families encoding PPR proteins are greatly expanded in land plants where hundreds of them participate in RNA maturation, mainly in mitochondria and chloroplasts. Many plant PPR proteins contain additional carboxyterminal domains and have been identified as essential factors for specific events of C-to-U RNA editing, which is abundant in the two endosymbiotic plant organelles. Among those carboxyterminal domain additions to plant PPR proteins, the so-called DYW domain is particularly interesting given its similarity to cytidine deaminases. The frequency of organelle C-to-U RNA editing and the diversity of DYW-type PPR proteins correlate well in plants and both were recently identified outside of land plants, in the protist Naegleria gruberi. Here we present a systematic survey of PPR protein genes and report on the identification of additional DYW-type PPR proteins in the protists Acanthamoeba castellanii, Malawimonas jakobiformis, and Physarum polycephalum. Moreover, DYW domains were also found in basal branches of multi-cellular lineages outside of land plants, including the alga Nitella flexilis and the rotifers Adineta ricciae and Philodina roseola. Intriguingly, the well-characterized and curious patterns of mitochondrial RNA editing in the slime mold Physarum also include examples of C-to-U changes. Finally, we identify candidate sites for mitochondrial RNA editing in Malawimonas, further supporting a link between DYW-type PPR proteins and C-to-U editing, which may have remained hitherto unnoticed in additional eukaryote lineages.}, } @article {pmid23894089, year = {2013}, author = {Rainer, PP and Primessnig, U and Harenkamp, S and Doleschal, B and Wallner, M and Fauler, G and Stojakovic, T and Wachter, R and Yates, A and Groschner, K and Trauner, M and Pieske, BM and von Lewinski, D}, title = {Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.}, journal = {Heart (British Cardiac Society)}, volume = {99}, number = {22}, pages = {1685-1692}, doi = {10.1136/heartjnl-2013-304163}, pmid = {23894089}, issn = {1468-201X}, support = {F 3517/FWF_/Austrian Science Fund FWF/Austria ; P 19118/FWF_/Austrian Science Fund FWF/Austria ; W 1226/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Aged ; Animals ; Atrial Fibrillation/*blood/*etiology ; Bile Acids and Salts/*blood/chemistry/*pharmacology/physiology ; Cardiac Electrophysiology ; Female ; Heart Atria/*drug effects ; Humans ; Male ; Mice ; Myocytes, Cardiac/*drug effects/*physiology ; Taurocholic Acid/pharmacology ; Ursodeoxycholic Acid/pharmacology ; }, abstract = {OBJECTIVE: High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation (AF) and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids.

METHODS AND RESULTS: Multicellular human atrial preparations ('trabeculae') were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with AF and ECG parameters analysed. Additionally, we conducted electrophysiological studies in murine myocytes. Taurocholic acid (TCA) concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300 µM TCA, p<0.01) while ursodeoxycholic acid did not. Patients with AF had significantly decreased serum levels of ursodeoxycholic acid conjugates and increased levels of non-ursodeoxycholic bile acids. In isolated myocytes, TCA depolarised the resting membrane potential, enhanced Na(+)/Ca(2+) exchanger (NCX) tail current density and induced afterdepolarisations. Inhibition of NCX prevented arrhythmias in atrial trabeculae.

CONCLUSIONS: High TCA concentrations induce arrhythmias in adult human atria while ursodeoxycholic acid does not. AF is associated with higher serum levels of non-ursodeoxycholic bile acid conjugates and low levels of ursodeoxycholic acid conjugates. These data suggest that higher levels of toxic (arrhythmogenic) and low levels of protective bile acids create a milieu with a decreased arrhythmic threshold and thus may facilitate arrhythmic events.}, } @article {pmid23885060, year = {2013}, author = {Blackstone, NW}, title = {Evolution and cell physiology. 2. The evolution of cell signaling: from mitochondria to Metazoa.}, journal = {American journal of physiology. Cell physiology}, volume = {305}, number = {9}, pages = {C909-15}, doi = {10.1152/ajpcell.00216.2013}, pmid = {23885060}, issn = {1522-1563}, mesh = {Animals ; *Biological Evolution ; Cell Physiological Phenomena/*physiology ; Humans ; Mitochondria/*physiology ; Signal Transduction/*physiology ; }, abstract = {The history of life is a history of levels-of-selection transitions. Each transition requires mechanisms that mediate conflict among the lower-level units. In the origins of multicellular eukaryotes, cell signaling is one such mechanism. The roots of cell signaling, however, may extend to the previous major transition, the origin of eukaryotes. Energy-converting protomitochondria within a larger cell allowed eukaryotes to transcend the surface-to-volume constraints inherent in the design of prokaryotes. At the same time, however, protomitochondria can selfishly allocate energy to their own replication. Metabolic signaling may have mediated this principal conflict in several ways. Variation of the protomitochondria was constrained by stoichiometry and strong metabolic demand (state 3) exerted by the protoeukaryote. Variation among protoeukaryotes was increased by the sexual stage of the life cycle, triggered by weak metabolic demand (state 4), resulting in stochastic allocation of protomitochondria to daughter cells. Coupled with selection, many selfish protomitochondria could thus be removed from the population. Hence, regulation of states 3 and 4, as, for instance, provided by the CO2/soluble adenylyl cyclase/cAMP pathway in mitochondria, was critical for conflict mediation. Subsequently, as multicellular eukaryotes evolved, metabolic signaling pathways employed by eukaryotes to mediate conflict within cells could now be co-opted into conflict mediation between cells. For example, in some fungi, the CO2/soluble adenylyl cyclase/cAMP pathway regulates the transition from yeast to forms with hyphae. In animals, this pathway regulates the maturation of sperm. While the particular features (sperm and hyphae) are distinct, both may involve between-cell conflicts that required mediation.}, } @article {pmid23864594, year = {2013}, author = {Noble, LM and Andrianopoulos, A}, title = {Reproductive competence: a recurrent logic module in eukaryotic development.}, journal = {Proceedings. Biological sciences}, volume = {280}, number = {1766}, pages = {20130819}, pmid = {23864594}, issn = {1471-2954}, mesh = {*Adaptation, Physiological ; Animals ; Ascomycota/*physiology ; Life Cycle Stages ; Plant Physiological Phenomena ; Reproduction ; }, abstract = {Developmental competence is the ability to differentiate in response to an appropriate stimulus, as first elaborated by Waddington in relation to organs and tissues. Competence thresholds operate at all levels of biological systems from the molecular (e.g. the cell cycle) to the ontological (e.g. metamorphosis and reproduction). Reproductive competence, an organismal process, is well studied in mammals (sexual maturity) and plants (vegetative phase change), though far less than later stages of terminal differentiation. The phenomenon has also been documented in multiple species of multicellular fungi, mostly in early, disparate literature, providing a clear example of physiological differentiation in the absence of morphological change. This review brings together data on reproductive competence in Ascomycete fungi, particularly the model filamentous fungus Aspergillus nidulans, contrasting mechanisms within Unikonts and plants. We posit reproductive competence is an elementary logic module necessary for coordinated development of multicellular organisms or functional units. This includes unitary multicellular life as well as colonial species both unicellular and multicellular (e.g. social insects such as ants). We discuss adaptive hypotheses for developmental and reproductive competence systems and suggest experimental work to address the evolutionary origins, generality and genetic basis of competence in the fungal kingdom.}, } @article {pmid23861491, year = {2013}, author = {Awan, AR and Manfredo, A and Pleiss, JA}, title = {Lariat sequencing in a unicellular yeast identifies regulated alternative splicing of exons that are evolutionarily conserved with humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {31}, pages = {12762-12767}, pmid = {23861491}, issn = {1091-6490}, support = {R01 GM098634/GM/NIGMS NIH HHS/United States ; GM098634/GM/NIGMS NIH HHS/United States ; }, mesh = {Alternative Splicing/*genetics ; *Evolution, Molecular ; Exons/*genetics ; Humans ; Schizosaccharomyces/*genetics ; *Sequence Analysis, DNA ; }, abstract = {Alternative splicing is a potent regulator of gene expression that vastly increases proteomic diversity in multicellular eukaryotes and is associated with organismal complexity. Although alternative splicing is widespread in vertebrates, little is known about the evolutionary origins of this process, in part because of the absence of phylogenetically conserved events that cross major eukaryotic clades. Here we describe a lariat-sequencing approach, which offers high sensitivity for detecting splicing events, and its application to the unicellular fungus, Schizosaccharomyces pombe, an organism that shares many of the hallmarks of alternative splicing in mammalian systems but for which no previous examples of exon-skipping had been demonstrated. Over 200 previously unannotated splicing events were identified, including examples of regulated alternative splicing. Remarkably, an evolutionary analysis of four of the exons identified here as subject to skipping in S. pombe reveals high sequence conservation and perfect length conservation with their homologs in scores of plants, animals, and fungi. Moreover, alternative splicing of two of these exons have been documented in multiple vertebrate organisms, making these the first demonstrations of identical alternative-splicing patterns in species that are separated by over 1 billion y of evolution.}, } @article {pmid23856377, year = {2014}, author = {Day, BJ}, title = {Antioxidant therapeutics: Pandora's box.}, journal = {Free radical biology & medicine}, volume = {66}, number = {}, pages = {58-64}, pmid = {23856377}, issn = {1873-4596}, support = {R01 HL084469/HL/NHLBI NIH HHS/United States ; U54 ES015678/ES/NIEHS NIH HHS/United States ; R01 ES012504/ES/NIEHS NIH HHS/United States ; HL59602/HL/NHLBI NIH HHS/United States ; HL075523/HL/NHLBI NIH HHS/United States ; R01 ES017582/ES/NIEHS NIH HHS/United States ; HL084469/HL/NHLBI NIH HHS/United States ; R01 HL075523/HL/NHLBI NIH HHS/United States ; ES015678/ES/NIEHS NIH HHS/United States ; ES017582/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antioxidants/pharmacology/*therapeutic use ; Catalase/metabolism ; Humans ; Oxidative Stress/*drug effects ; Oxygen/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Superoxide Dismutase/metabolism ; }, abstract = {Evolution has favored the utilization of dioxygen (O2) in the development of complex multicellular organisms. O2 is actually a toxic mutagenic gas that is highly oxidizing and combustible. It is thought that plants are largely to blame for polluting the earth's atmosphere with O2 owing to the development of photosynthesis by blue-green algae over 2 billion years ago. The rise of the plants and atmospheric O2 levels placed evolutionary stress on organisms to adapt or become extinct. This implies that all the surviving creatures on our planet are mutants that have adapted to the "abnormal biology" of O2. Much of the adaptation to the presence of O2 in biological systems comes from well-coordinated antioxidant and repair systems that focus on converting O2 to its most reduced form, water (H2O), and the repair and replacement of damaged cellular macromolecules. Biological systems have also harnessed O2's reactive properties for energy production, xenobiotic metabolism, and host defense and as a signaling messenger and redox modulator of a number of cell signaling pathways. Many of these systems involve electron transport systems and offer many different mechanisms by which antioxidant therapeutics can alternatively produce an antioxidant effect without directly scavenging oxygen-derived reactive species. It is likely that each agent will have a different set of mechanisms that may change depending on the model of oxidative stress, organ system, or disease state. An important point is that all biological processes of aerobes have coevolved with O2 and this creates a Pandora's box for trying to understand the mechanism(s) of action of antioxidants being developed as therapeutic agents.}, } @article {pmid23850579, year = {2013}, author = {Lv, J and Yang, T and Yang, H and Li, Z and Qin, P and Zhang, X and Liang, X and Li, J and Chen, Q}, title = {Identification of myb genes in Euplotes aediculatus may indicate an early evolutionary process.}, journal = {Gene}, volume = {530}, number = {2}, pages = {266-272}, doi = {10.1016/j.gene.2013.06.072}, pmid = {23850579}, issn = {1879-0038}, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Euplotes/*genetics ; *Genes, myb ; Genomic Library ; Humans ; Molecular Sequence Data ; Multigene Family ; Oncogene Proteins v-myb/classification/*genetics ; Phylogeny ; Plants/genetics ; Protozoan Proteins/classification/*genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {The myb gene family encodes proteins characterized by a highly conserved DNA-binding domain and functions as transcription regulators. There are three myb genes in animals with three Myb-motif repeats, namely c-myb, A-myb, and B-myb. By contrast, plants possess an abundance of myb genes, the majority of which are of the type R2R3 (with two Myb-motifs). Few plant myb genes are of the type R1R2R3. Five new myb members in Euplotes were recently identified through degenerate polymerase chain reaction, which suggests that the myb gene is also a multi-member family in the unicellular protist kingdom as in other multi-cellular eukaryotes. The entire gene family further shows the presence of both R1R2R3- and R2R3-type myb. The phylogenic analysis provides concrete new evidence for the evolution of myb genes.}, } @article {pmid23850535, year = {2013}, author = {Marijuán, PC and del Moral, R and Navarro, J}, title = {On eukaryotic intelligence: signaling system's guidance in the evolution of multicellular organization.}, journal = {Bio Systems}, volume = {114}, number = {1}, pages = {8-24}, doi = {10.1016/j.biosystems.2013.06.005}, pmid = {23850535}, issn = {1872-8324}, mesh = {*Biological Evolution ; Cell Communication/*physiology ; Cell Cycle/*physiology ; Cytoskeleton/*physiology ; Eukaryotic Cells/*cytology/*physiology ; *Models, Biological ; Signal Transduction/*physiology ; }, abstract = {Communication with the environment is an essential characteristic of the living cell, even more when considering the origins and evolution of multicellularity. A number of changes and tinkering inventions were necessary in the evolutionary transition between prokaryotic and eukaryotic cells, which finally made possible the appearance of genuine multicellular organisms. In the study of this process, however, the transformations experimented by signaling systems themselves have been rarely object of analysis, obscured by other more conspicuous biological traits: incorporation of mitochondria, segregated nucleus, introns/exons, flagellum, membrane systems, etc. Herein a discussion of the main avenues of change from prokaryotic to eukaryotic signaling systems and a review of the signaling resources and strategies underlying multicellularity will be attempted. In the expansion of prokaryotic signaling systems, four main systemic resources were incorporated: molecular tools for detection of solutes, molecular tools for detection of solvent (Donnan effect), the apparatuses of cell-cycle control, and the combined system endocytosis/cytoskeleton. The multiple kinds of enlarged, mixed pathways that emerged made possible the eukaryotic revolution in morphological and physiological complexity. The massive incorporation of processing resources of electro-molecular nature, derived from the osmotic tools counteracting the Donnan effect, made also possible the organization of a computational tissue with huge information processing capabilities: the nervous system. In the central nervous systems of vertebrates, and particularly in humans, neurons have achieved both the highest level of molecular-signaling complexity and the highest degree of information-processing adaptability. Theoretically, it can be argued that there has been an accelerated pace of evolutionary change in eukaryotic signaling systems, beyond the other general novelties introduced by eukaryotic cells in their handling of DNA processes. Under signaling system's guidance, the whole processes of transcription, alternative splicing, mobile elements, and other elements of domain recombination have become closely intertwined and have propelled the differentiation capabilities of multicellular tissues and morphologies. An amazing variety of signaling and self-construction strategies have emerged out from the basic eukaryotic design of multicellular complexity, in millions and millions of new species evolved. This design can also be seen abstractly as a new kind of quasi-universal problem-solving 'engine' implemented at the biomolecular scale-providing the fundamentals of eukaryotic 'intelligence'. Analyzing in depth the problem-solving intelligence of eukaryotic cells would help to establish an integrative panorama of their information processing organization, and of their capability to handle the morphological and physiological complexity associated. Whether an informational updating of the venerable "cell theory" is feasible or not, becomes, at the time being - right in the middle of the massive data deluge/revolution from omic disciplines - a matter to careful consider.}, } @article {pmid23846861, year = {2014}, author = {Lintilhac, PM}, title = {The problem of morphogenesis: unscripted biophysical control systems in plants.}, journal = {Protoplasma}, volume = {251}, number = {1}, pages = {25-36}, pmid = {23846861}, issn = {1615-6102}, mesh = {Animals ; Cell Wall/*physiology ; Evolution, Molecular ; Plant Cells/physiology ; Plant Development/genetics/*physiology ; *Plant Physiological Phenomena ; }, abstract = {The relative simplicity of plant developmental systems, having evolved within the universal constraints imposed by the plant cell wall, may allow us to outline a consistent developmental narrative that is not currently possible in the animal kingdom. In this article, I discuss three aspects of the development of the mature form in plants, approaching them in terms of the role played by the biophysics and mechanics of the cell wall during growth. First, I discuss axis extension in terms of a loss of stability-based model of cell wall stress relaxation and I introduce the possibility that cell wall stress relaxation can be modeled as a binary switch. Second, I consider meristem shape and surface conformation as a controlling element in the morphogenetic circuitry of plant organogenesis at the apex. Third, I approach the issue of reproductive differentiation and propose that the multicellular sporangium, a universal feature of land plants, acts as a stress-mechanical lens, focusing growth-induced stresses to create a geometrically precise mechanical singularity that can serve as an inducing developmental signal triggering the initiation of reproductive differentiation. Lastly, I offer these three examples of biophysically integrated control processes as entry points into a narrative that provides an independent, nongenetic context for understanding the evolution of the apoplast and the morphogenetic ontogeny of multicellular land plants.}, } @article {pmid23835507, year = {2013}, author = {Reinders, J and Mirouze, M and Nicolet, J and Paszkowski, J}, title = {Parent-of-origin control of transgenerational retrotransposon proliferation in Arabidopsis.}, journal = {EMBO reports}, volume = {14}, number = {9}, pages = {823-828}, pmid = {23835507}, issn = {1469-3178}, mesh = {Arabidopsis/*genetics ; *Epigenesis, Genetic ; Mutation ; Retroelements/*genetics ; }, abstract = {Retrotransposons are ubiquitous mobile genetic elements constituting a major part of eukaryotic genomes. Yet, monitoring retrotransposition and subsequent copy number increases in multicellular eukaryotes is intrinsically difficult. By following the transgenerational accumulation of a newly activated retrotransposon EVADE (EVD) in Arabidopsis, we noticed fast expansion of activated elements transmitted through the paternal germ line but suppression when EVD-active copies are maternally inherited. This parent-of-origin effect on EVD proliferation was still observed when gametophytes carried mutations for key epigenetic regulators previously shown to restrict EVD mobility. Therefore, the main mechanism preventing active EVD proliferation seems to act through epigenetic control in sporophytic tissues in the mother plant. In consequence, once activated, this retrotransposon proliferates in plant populations owing to suppressed epigenetic control during paternal transmission. This parental gateway might contribute to the occasional bursts of retrotransposon mobilization deduced from the genome sequences of many plant species.}, } @article {pmid23831049, year = {2013}, author = {Verbeni, M and Sánchez, O and Mollica, E and Siegl-Cachedenier, I and Carleton, A and Guerrero, I and Ruiz i Altaba, A and Soler, J}, title = {Morphogenetic action through flux-limited spreading.}, journal = {Physics of life reviews}, volume = {10}, number = {4}, pages = {457-475}, doi = {10.1016/j.plrev.2013.06.004}, pmid = {23831049}, issn = {1873-1457}, mesh = {Animals ; Drosophila melanogaster/embryology ; Epithelium/metabolism ; Hedgehog Proteins/metabolism ; *Models, Biological ; *Morphogenesis ; Movement ; Neural Tube/cytology/metabolism ; Nonlinear Dynamics ; Signal Transduction ; Wings, Animal/embryology ; }, abstract = {A central question in biology is how secreted morphogens act to induce different cellular responses within a group of cells in a concentration-dependent manner. Modeling morphogenetic output in multicellular systems has so far employed linear diffusion, which is the normal type of diffusion associated with Brownian processes. However, there is evidence that at least some morphogens, such as Hedgehog (Hh) molecules, may not freely diffuse. Moreover, the mathematical analysis of such models necessarily implies unrealistic instantaneous spreading of morphogen molecules, which are derived from the assumptions of Brownian motion in its continuous formulation. A strict mathematical model considering Fick's diffusion law predicts morphogen exposure of the whole tissue at the same time. Such a strict model thus does not describe true biological patterns, even if similar and attractive patterns appear as results of applying such simple model. To eliminate non-biological behaviors from diffusion models we introduce flux-limited spreading (FLS), which implies a restricted velocity for morphogen propagation and a nonlinear mechanism of transport. Using FLS and focusing on intercellular Hh-Gli signaling, we model a morphogen gradient and highlight the propagation velocity of morphogen particles as a new key biological parameter. This model is then applied to the formation and action of the Sonic Hh (Shh) gradient in the vertebrate embryonic neural tube using our experimental data on Hh spreading in heterologous systems together with published data. Unlike linear diffusion models, FLS modeling predicts concentration fronts and the evolution of gradient dynamics and responses over time. In addition to spreading restrictions by extracellular binding partners, we suggest that the constraints imposed by direct bridges of information transfer such as nanotubes or cytonemes underlie FLS. Indeed, we detect and measure morphogen particle velocity in such cell extensions in different systems.}, } @article {pmid23826714, year = {2013}, author = {Ajawatanawong, P and Baldauf, SL}, title = {Evolution of protein indels in plants, animals and fungi.}, journal = {BMC evolutionary biology}, volume = {13}, number = {}, pages = {140}, pmid = {23826714}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Fungi/classification/*genetics ; Humans ; *INDEL Mutation ; Molecular Sequence Data ; Phylogeny ; Proteins/*genetics ; Sequence Alignment ; Viridiplantae/classification/*genetics ; }, abstract = {BACKGROUND: Insertions/deletions (indels) in protein sequences are useful as drug targets, protein structure predictors, species diagnostics and evolutionary markers. However there is limited understanding of indel evolutionary patterns. We sought to characterize indel patterns focusing first on the major groups of multicellular eukaryotes.

RESULTS: Comparisons of complete proteomes from a taxonically broad set of primarily Metazoa, Fungi and Viridiplantae yielded 299 substantial (>250aa) universal, single-copy (in-paralog only) proteins, from which 901 simple (present/absent) and 3,806 complex (multistate) indels were extracted. Simple indels are mostly small (1-7aa) with a most frequent size class of 1aa. However, even these simple looking indels show a surprisingly high level of hidden homoplasy (multiple independent origins). Among the apparently homoplasy-free simple indels, we identify 69 potential clade-defining indels (CDIs) that may warrant closer examination. CDIs show a very uneven taxonomic distribution among Viridiplante (13 CDIs), Fungi (40 CDIs), and Metazoa (0 CDIs). An examination of singleton indels shows an excess of insertions over deletions in nearly all examined taxa. This excess averages 2.31 overall, with a maximum observed value of 7.5 fold.

CONCLUSIONS: We find considerable potential for identifying taxon-marker indels using an automated pipeline. However, it appears that simple indels in universal proteins are too rare and homoplasy-rich to be used for pure indel-based phylogeny. The excess of insertions over deletions seen in nearly every genome and major group examined maybe useful in defining more realistic gap penalties for sequence alignment. This bias also suggests that insertions in highly conserved proteins experience less purifying selection than do deletions.}, } @article {pmid23817070, year = {2013}, author = {Gauthier, NP and Soufi, B and Walkowicz, WE and Pedicord, VA and Mavrakis, KJ and Macek, B and Gin, DY and Sander, C and Miller, ML}, title = {Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments.}, journal = {Nature methods}, volume = {10}, number = {8}, pages = {768-773}, pmid = {23817070}, issn = {1548-7105}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; U54 CA148967/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Cell Line ; Coculture Techniques/methods ; Humans ; Isotope Labeling/methods ; Lysine/*metabolism ; Mice ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Organisms, Genetically Modified ; Proteome/*biosynthesis/genetics ; Proteomics/*methods ; RNA, Messenger/chemistry/genetics ; Sequence Analysis, DNA ; Tandem Mass Spectrometry ; }, abstract = {We report a technique to selectively and continuously label the proteomes of individual cell types in coculture, named cell type-specific labeling using amino acid precursors (CTAP). Through transgenic expression of exogenous amino acid biosynthesis enzymes, vertebrate cells overcome their dependence on supplemented essential amino acids and can be selectively labeled through metabolic incorporation of amino acids produced from heavy isotope-labeled precursors. When testing CTAP in several human and mouse cell lines, we could differentially label the proteomes of distinct cell populations in coculture and determine the relative expression of proteins by quantitative mass spectrometry. In addition, using CTAP we identified the cell of origin of extracellular proteins secreted from cells in coculture. We believe that this method, which allows linking of proteins to their cell source, will be useful in studies of cell-cell communication and potentially for discovery of biomarkers.}, } @article {pmid23816391, year = {2013}, author = {Strand, MR and Burke, GR}, title = {Polydnavirus-wasp associations: evolution, genome organization, and function.}, journal = {Current opinion in virology}, volume = {3}, number = {5}, pages = {587-594}, doi = {10.1016/j.coviro.2013.06.004}, pmid = {23816391}, issn = {1879-6265}, support = {F32 AI096552/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; *Genome, Viral ; Polydnaviridae/*genetics/physiology ; Proviruses/*genetics/physiology ; Wasps/*virology ; }, abstract = {Viruses replicate to produce virions that transfer the viral genome among hosts, while endogenous viral elements (EVEs) are DNA sequences derived from viruses that integrate into the germline of multicellular organisms and are thereafter inherited like host alleles. Viruses in the family Polydnaviridae are specifically associated with insects called parasitoid wasps and exhibit many traits associated with other viruses. Polydnavirus genomes also persist as EVEs. In this short review we discuss polydnavirus evolution, compare polydnaviruses to other known EVEs of ancient origin, and examine some of the functional similarities polydnaviruses share with phage-like gene transfer agents (GTAs) from prokaryotes.}, } @article {pmid23809699, year = {2013}, author = {Raff, EC and Andrews, ME and Turner, FR and Toh, E and Nelson, DE and Raff, RA}, title = {Contingent interactions among biofilm-forming bacteria determine preservation or decay in the first steps toward fossilization of marine embryos.}, journal = {Evolution & development}, volume = {15}, number = {4}, pages = {243-256}, doi = {10.1111/ede.12028}, pmid = {23809699}, issn = {1525-142X}, mesh = {Aerobiosis ; Anaerobiosis ; Animals ; Artemia/physiology ; Bacteria/*metabolism ; Bacterial Physiological Phenomena ; *Biofilms ; Biological Evolution ; Cytoplasm/metabolism ; *Fossils ; Gammaproteobacteria/metabolism ; Larva ; Lipids/analysis ; Sea Urchins/physiology ; Seawater/*microbiology ; Water Microbiology ; }, abstract = {Fossils of soft tissues provide important records of early animals and embryos, and there is substantial evidence for a role for microbes in soft tissue fossilization. We are investigating the initial events in interactions of bacteria with freshly dead tissue, using marine embryos as a model system. We previously found that microbial invasion can stabilize embryo tissue that would otherwise disintegrate in hours or days by generating a bacterial pseudomorph, a three dimensional biofilm that both replaces the tissue and replicates its morphology. In this study, we sampled seawater at different times and places near Sydney, Australia, and determined the range and frequency of different taphonomic outcomes. Although destruction was most common, bacteria in 35% of seawater samples yielded morphology‐preserving biofilms. We could replicate the taphonomic pathways seen with seawater bacterial communities using single cultured strains of marine gammaproteobacteria. Each given species reproducibly generated a consistent taphonomic outcome and we identified species that yielded each of the distinct pathways produced by seawater bacterial communities. Once formed,bacterial pseudomorphs are stable for over a year and resist attack by other bacteria and destruction by proteases and other lytic enzymes. Competition studies showed that the initial action of a pseudomorphing strain can be blocked by a strain that destroys tissues. Thus embryo preservation in nature may depend on contingent interactions among bacterial species that determine if pseudomorphing occurs.We used Artemia nauplius larvae to show that bacterial biofilm replacement of tissue is not restricted to embryos, but is relevant for preservation of small multicellular organisms. We present a model for bacterial self‐assembly of large‐scale three‐dimensional tissue pseudomorphs, based on smallscaleinteractions among individual bacterial cells to form local biofilms at structural boundaries within the tissue. Localbiofilms then conjoin to generate the pseudomorph.}, } @article {pmid23808329, year = {2013}, author = {Bosch, TC}, title = {Cnidarian-microbe interactions and the origin of innate immunity in metazoans.}, journal = {Annual review of microbiology}, volume = {67}, number = {}, pages = {499-518}, doi = {10.1146/annurev-micro-092412-155626}, pmid = {23808329}, issn = {1545-3251}, mesh = {Animals ; Bacteria/growth & development ; Cnidaria/genetics/*immunology/*microbiology ; Humans ; *Immunity, Innate ; *Microbiota ; Receptors, Pattern Recognition/genetics/immunology ; Symbiosis ; }, abstract = {Most epithelia in animals are colonized by microbial communities. These resident microbes influence fitness and thus ecologically important traits of their hosts, ultimately forming a metaorganism consisting of a multicellular host and a community of associated microorganisms. Recent discoveries in the cnidarian Hydra show that components of the innate immune system as well as transcriptional regulators of stem cells are involved in maintaining homeostasis between animals and their resident microbiota. Here I argue that components of the innate immune system with its host-specific antimicrobial peptides and a rich repertoire of pattern recognition receptors evolved in early-branching metazoans because of the need to control the resident beneficial microbes, not because of invasive pathogens. I also propose a mutual intertwinement between the stem cell regulatory machinery of the host and the resident microbiota composition, such that disturbances in one trigger a restructuring and resetting of the other.}, } @article {pmid23782883, year = {2013}, author = {Romeralo, M and Skiba, A and Gonzalez-Voyer, A and Schilde, C and Lawal, H and Kedziora, S and Cavender, JC and Glöckner, G and Urushihara, H and Schaap, P}, title = {Analysis of phenotypic evolution in Dictyostelia highlights developmental plasticity as a likely consequence of colonial multicellularity.}, journal = {Proceedings. Biological sciences}, volume = {280}, number = {1764}, pages = {20130976}, pmid = {23782883}, issn = {1471-2954}, support = {090276//Wellcome Trust/United Kingdom ; BB/D013453/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/E016308/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/G020426/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Chemotactic Factors/physiology ; Cyclic AMP/analogs & derivatives/metabolism/pharmacology ; Dictyosteliida/*cytology/drug effects/*physiology ; Multifactorial Inheritance ; Phenotype ; Phototropism ; Phylogeny ; Proteins/genetics ; Thionucleotides/pharmacology ; }, abstract = {Colony formation was the first step towards evolution of multicellularity in many macroscopic organisms. Dictyostelid social amoebas have used this strategy for over 600 Myr to form fruiting structures of increasing complexity. To understand in which order multicellular complexity evolved, we measured 24 phenotypic characters over 99 dictyostelid species. Using phylogenetic comparative methods, we show that the last common ancestor (LCA) of Dictyostelia probably erected small fruiting structures directly from aggregates. It secreted cAMP to coordinate fruiting body morphogenesis, and another compound to mediate aggregation. This phenotype persisted up to the LCAs of three of the four major groups of Dictyostelia. The group 4 LCA co-opted cAMP for aggregation and evolved much larger fruiting structures. However, it lost encystation, the survival strategy of solitary amoebas that is retained by many species in groups 1-3. Large structures, phototropism and a migrating intermediate 'slug' stage coevolved as evolutionary novelties within most groups. Overall, dictyostelids show considerable plasticity in the size and shape of multicellular structures, both within and between species. This probably reflects constraints placed by colonial life on developmental control mechanisms, which, depending on local cell density, need to direct from 10 to a million cells into forming a functional fructification.}, } @article {pmid23776247, year = {2013}, author = {Shih, PM and Matzke, NJ}, title = {Primary endosymbiosis events date to the later Proterozoic with cross-calibrated phylogenetic dating of duplicated ATPase proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {30}, pages = {12355-12360}, pmid = {23776247}, issn = {1091-6490}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Adenosine Triphosphatases/classification/*metabolism ; Calibration ; *Phylogeny ; *Symbiosis ; }, abstract = {Chloroplasts and mitochondria descended from bacterial ancestors, but the dating of these primary endosymbiosis events remains very uncertain, despite their importance for our understanding of the evolution of both bacteria and eukaryotes. All phylogenetic dating in the Proterozoic and before is difficult: Significant debates surround potential fossil calibration points based on the interpretation of the Precambrian microbial fossil record, and strict molecular clock methods cannot be expected to yield accurate dates over such vast timescales because of strong heterogeneity in rates. Even with more sophisticated relaxed-clock analyses, nodes that are distant from fossil calibrations will have a very high uncertainty in dating. However, endosymbiosis events and gene duplications provide some additional information that has never been exploited in dating; namely, that certain nodes on a gene tree must represent the same events, and thus must have the same or very similar dates, even if the exact date is uncertain. We devised techniques to exploit this information: cross-calibration, in which node date calibrations are reused across a phylogeny, and cross-bracing, in which node date calibrations are formally linked in a hierarchical Bayesian model. We apply these methods to proteins with ancient duplications that have remained associated and originated from plastid and mitochondrial endosymbionts: the α and β subunits of ATP synthase and its relatives, and the elongation factor thermo unstable. The methods yield reductions in dating uncertainty of 14-26% while only using date calibrations derived from phylogenetically unambiguous Phanerozoic fossils of multicellular plants and animals. Our results suggest that primary plastid endosymbiosis occurred ∼900 Mya and mitochondrial endosymbiosis occurred ∼1,200 Mya.}, } @article {pmid23767751, year = {2013}, author = {Roper, M and Dayel, MJ and Pepper, RE and Koehl, MA}, title = {Cooperatively generated stresslet flows supply fresh fluid to multicellular choanoflagellate colonies.}, journal = {Physical review letters}, volume = {110}, number = {22}, pages = {228104}, doi = {10.1103/PhysRevLett.110.228104}, pmid = {23767751}, issn = {1079-7114}, mesh = {Choanoflagellata/chemistry/*physiology ; Flagella/chemistry/*physiology ; Hydrodynamics ; *Models, Biological ; Stress, Physiological ; Swimming ; Viscosity ; }, abstract = {The flagellated protozoan Salpingoeca rosetta is one of the closest relatives of multicellular animals. Unicellular S. rosetta can be induced to form multicellular colonies, but colonies swim more slowly than individual cells so the advantages conferred by colony formation are uncertain. Here we use theoretical models to show that hydrodynamic cooperation between cells can increase the fluid supply to the colony, an important predictor of feeding rate. Our results suggest that hydrodynamic benefits may have been an important selective factor in the evolution of early multicellular animals.}, } @article {pmid23760641, year = {2013}, author = {Shirokawa, Y and Shimada, M}, title = {Sex allocation pattern of the diatom Cyclotella meneghiniana.}, journal = {Proceedings. Biological sciences}, volume = {280}, number = {1761}, pages = {20130503}, pmid = {23760641}, issn = {1471-2954}, mesh = {Animals ; *Biological Evolution ; Cell Count ; Cell Lineage ; Cell Size ; Diatoms/*cytology/*physiology ; Female ; Game Theory ; Male ; Microfluidic Analytical Techniques ; Reproduction ; Sex Differentiation ; *Sex Ratio ; }, abstract = {Sex allocation is one of the most successful applications of evolutionary game theory. This theory has usually been applied to multicellular organisms; however, conditional sex allocation in unicellular organisms remains an unexplored field of research. Observations at the cellular level are indispensable for an understanding of the phenotypic sex allocation strategy among individuals within clonal unicellular organisms. The diatom Cyclotella meneghiniana, in which the sexes are generated from vegetative cells, is suitable for investigating effects of phenotypic plasticity factors on sex allocation while excluding genetic differences. We designed a microfluidic system that allowed us to trace the fate of individual cells. Sex allocation by individual mother cells was affected by cell lineage, cell size and cell density. Sibling cell pairs tended to differentiate into the same fates (split sex ratio). We found a significant negative correlation between the cell area of the mother cell and sex ratio of the two sibling cells. The male-biased sex ratio declined with higher local cell population density, supporting the fertility insurance hypothesis. Our results characterize multiple non-genetic factors that affect the phenotypic single cell-level sex allocation. Sex allocation in diatoms may provide a model system for testing evolutionary game theory in unicellular organisms.}, } @article {pmid23754817, year = {2013}, author = {Blackstone, NW}, title = {Why did eukaryotes evolve only once? Genetic and energetic aspects of conflict and conflict mediation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {368}, number = {1622}, pages = {20120266}, pmid = {23754817}, issn = {1471-2970}, mesh = {*Biological Evolution ; *Energy Metabolism ; Eukaryota/*genetics/*physiology ; Genetic Variation ; Genome ; Mitochondria ; }, abstract = {According to multi-level theory, evolutionary transitions require mediating conflicts between lower-level units in favour of the higher-level unit. By this view, the origin of eukaryotes and the origin of multicellularity would seem largely equivalent. Yet, eukaryotes evolved only once in the history of life, whereas multicellular eukaryotes have evolved many times. Examining conflicts between evolutionary units and mechanisms that mediate these conflicts can illuminate these differences. Energy-converting endosymbionts that allow eukaryotes to transcend surface-to-volume constraints also can allocate energy into their own selfish replication. This principal conflict in the origin of eukaryotes can be mediated by genetic or energetic mechanisms. Genome transfer diminishes the heritable variation of the symbiont, but requires the de novo evolution of the protein-import apparatus and was opposed by selection for selfish symbionts. By contrast, metabolic signalling is a shared primitive feature of all cells. Redox state of the cytosol is an emergent feature that cannot be subverted by an individual symbiont. Hypothetical scenarios illustrate how metabolic regulation may have mediated the conflicts inherent at different stages in the origin of eukaryotes. Aspects of metabolic regulation may have subsequently been coopted from within-cell to between-cell pathways, allowing multicellularity to emerge repeatedly.}, } @article {pmid23747737, year = {2013}, author = {Häcker, G}, title = {Is there, and should there be, apoptosis in bacteria?.}, journal = {Microbes and infection}, volume = {15}, number = {8-9}, pages = {640-644}, doi = {10.1016/j.micinf.2013.05.005}, pmid = {23747737}, issn = {1769-714X}, mesh = {*Apoptosis ; Bacteria/cytology ; *Bacterial Physiological Phenomena ; }, abstract = {Apoptosis is a well-studied form of cell death in metazoans, where it has a clear role during the life of the (multicellular) animal. Some situations of cell death in unicellular eukaryotes (protozoa and yeast) have also been referred to as apoptosis. In recent years apoptosis has further been identified in bacteria several times. As a bacterial response to external stimuli, apoptosis could be important not only for the bacteria but also to the host. Here I will discuss why I believe that the term apoptosis should be avoided for these situations in bacteria, no matter how interesting the molecular background or how biologically important the underlying mechanism may be.}, } @article {pmid23746639, year = {2013}, author = {Fisher, RM and Cornwallis, CK and West, SA}, title = {Group formation, relatedness, and the evolution of multicellularity.}, journal = {Current biology : CB}, volume = {23}, number = {12}, pages = {1120-1125}, doi = {10.1016/j.cub.2013.05.004}, pmid = {23746639}, issn = {1879-0445}, mesh = {*Biological Evolution ; Eukaryotic Cells/*physiology ; *Evolution, Molecular ; Models, Genetic ; Selection, Genetic ; }, abstract = {The evolution of multicellular organisms represents one of approximately eight major evolutionary transitions that have occurred on earth. The major challenge raised by this transition is to explain why single cells should join together and become mutually dependent, in a way that leads to a more complex multicellular life form that can only replicate as a whole. It has been argued that a high genetic relatedness (r) between cells played a pivotal role in the evolutionary transition from single-celled to multicellular organisms, because it leads to reduced conflict and an alignment of interests between cells. We tested this hypothesis with a comparative study, comparing the form of multicellularity in species where groups are clonal (r = 1) to species where groups are potentially nonclonal (r ≤ 1). We found that species with clonal group formation were more likely to have undergone the major evolutionary transition to obligate multicellularity and had more cell types, a higher likelihood of sterile cells, and a trend toward higher numbers of cells in a group. More generally, our results unify the role of group formation and genetic relatedness across multiple evolutionary transitions and provide an unmistakable footprint of how natural selection has shaped the evolution of life.}, } @article {pmid23738841, year = {2013}, author = {Whitehead, MP and Hooley, P and W Brown, MR}, title = {Horizontal transfer of bacterial polyphosphate kinases to eukaryotes: implications for the ice age and land colonisation.}, journal = {BMC research notes}, volume = {6}, number = {}, pages = {221}, pmid = {23738841}, issn = {1756-0500}, mesh = {Amino Acid Sequence ; Bacteria/*enzymology ; *Gene Transfer, Horizontal ; *Ice ; Molecular Sequence Data ; Phosphotransferases (Phosphate Group Acceptor)/chemistry/genetics/*metabolism ; Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {BACKGROUND: Studies of online database(s) showed that convincing examples of eukaryote PPKs derived from bacteria type PPK1 and PPK2 enzymes are rare and currently confined to a few simple eukaryotes. These enzymes probably represent several separate horizontal transfer events. Retention of such sequences may be an advantage for tolerance to stresses such as desiccation or nutrient depletion for simple eukaryotes that lack more sophisticated adaptations available to multicellular organisms. We propose that the acquisition of encoding sequences for these enzymes by horizontal transfer enhanced the ability of early plants to colonise the land. The improved ability to sequester and release inorganic phosphate for carbon fixation by photosynthetic algae in the ocean may have accelerated or even triggered global glaciation events. There is some evidence for DNA sequences encoding PPKs in a wider range of eukaryotes, notably some invertebrates, though it is unclear that these represent functional genes.Polyphosphate (poly P) is found in all cells, carrying out a wide range of essential roles. Studied mainly in prokaryotes, the enzymes responsible for synthesis of poly P in eukaryotes (polyphosphate kinases PPKs) are not well understood. The best characterised enzyme from bacteria known to catalyse the formation of high molecular weight polyphosphate from ATP is PPK1 which shows some structural similarity to phospholipase D. A second bacterial PPK (PPK2) resembles thymidylate kinase. Recent reports have suggested a widespread distribution of these bacteria type enzymes in eukaryotes.

RESULTS: On - line databases show evidence for the presence of genes encoding PPK1 in only a limited number of eukaryotes. These include the photosynthetic eukaryotes Ostreococcus tauri, O. lucimarinus, Porphyra yezoensis, Cyanidioschyzon merolae and the moss Physcomitrella patens, as well as the amoeboid symbiont Capsaspora owczarzaki and the non-photosynthetic eukaryotes Dictyostelium (3 species), Polysphondylium pallidum and Thecamonas trahens. A second bacterial PPK (PPK2) is found in just two eukaryotes (O. tauri and the sea anemone Nematostella vectensis). There is some evidence for PPK1 and PPK2 encoding sequences in other eukaryotes but some of these may be artefacts of bacterial contamination of gene libraries.

CONCLUSIONS: Evidence for the possible origins of these eukaryote PPK1s and PPK2s and potential prokaryote donors via horizontal gene transfer is presented. The selective advantage of acquiring and maintaining a prokaryote PPK in a eukaryote is proposed to enhance stress tolerance in a changing environment related to the capture and metabolism of inorganic phosphate compounds. Bacterial PPKs may also have enhanced the abilities of marine phytoplankton to sequester phosphate, hence accelerating global carbon fixation.}, } @article {pmid23736899, year = {2013}, author = {Rothballer, A and Kutay, U}, title = {The diverse functional LINCs of the nuclear envelope to the cytoskeleton and chromatin.}, journal = {Chromosoma}, volume = {122}, number = {5}, pages = {415-429}, pmid = {23736899}, issn = {1432-0886}, mesh = {Chromatin/*genetics ; Cytoskeleton/*genetics ; Humans ; Membrane Proteins/genetics/metabolism ; Microtubules/genetics ; Nuclear Envelope/*genetics ; Nuclear Matrix/genetics ; Protein Structure, Tertiary ; }, abstract = {The nuclear envelope (NE) is connected to the different types of cytoskeletal elements by linker of nucleoskeleton and cytoskeleton (LINC) complexes. LINC complexes exist from yeast to humans, and have preserved their general architecture throughout evolution. They are composed of SUN and KASH domain proteins of the inner and the outer nuclear membrane, respectively. These SUN-KASH bridges are used for the transmission of forces across the NE and support diverse biological processes. Here, we review the function of SUN and KASH domain proteins in various unicellular and multicellular species. Specifically, we discuss their influence on nuclear morphology and cytoskeletal organization. Further, emphasis is given on the role of LINC complexes in nuclear anchorage and migration as well as in genome organization.}, } @article {pmid23735467, year = {2013}, author = {Libby, E and B Rainey, P}, title = {A conceptual framework for the evolutionary origins of multicellularity.}, journal = {Physical biology}, volume = {10}, number = {3}, pages = {035001}, doi = {10.1088/1478-3975/10/3/035001}, pmid = {23735467}, issn = {1478-3975}, mesh = {Animals ; *Biological Evolution ; Cell Biology ; Evolution, Molecular ; Humans ; Models, Genetic ; Selection, Genetic ; }, abstract = {The evolution of multicellular organisms from unicellular counterparts involved a transition in Darwinian individuality from single cells to groups. A particular challenge is to understand the nature of the earliest groups, the causes of their evolution, and the opportunities for emergence of Darwinian properties. Here we outline a conceptual framework based on a logical set of possible pathways for evolution of the simplest self-replicating groups. Central to these pathways is the recognition of a finite number of routes by which genetic information can be transmitted between individual cells and groups. We describe the form and organization of each primordial group state and consider factors affecting persistence and evolution of the nascent multicellular forms. Implications arising from our conceptual framework become apparent when attempting to partition fitness effects at individual and group levels. These are discussed with reference to the evolutionary emergence of individuality and its manifestation in extant multicellular life-including those of marginal Darwinian status.}, } @article {pmid23734264, year = {2013}, author = {Wang, L and Mao, Y and Kong, F and Li, G and Ma, F and Zhang, B and Sun, P and Bi, G and Zhang, F and Xue, H and Cao, M}, title = {Complete sequence and analysis of plastid genomes of two economically important red algae: Pyropia haitanensis and Pyropia yezoensis.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e65902}, pmid = {23734264}, issn = {1932-6203}, mesh = {Chloroplast Proteins/classification/*genetics ; Gene Order ; Genome, Plastid/*genetics ; Molecular Sequence Data ; Phylogeny ; Rhodophyta/classification/*genetics ; Sequence Analysis, DNA/*methods ; Species Specificity ; }, abstract = {BACKGROUND: Pyropia haitanensis and P. yezoensis are two economically important marine crops that are also considered to be research models to study the physiological ecology of intertidal seaweed communities, evolutionary biology of plastids, and the origins of sexual reproduction. This plastid genome information will facilitate study of breeding, population genetics and phylogenetics.

PRINCIPAL FINDINGS: We have fully sequenced using next-generation sequencing the circular plastid genomes of P. hatanensis (195,597 bp) and P. yezoensis (191,975 bp), the largest of all the plastid genomes of the red lineage sequenced to date. Organization and gene contents of the two plastids were similar, with 211-213 protein-coding genes (including 29-31 unknown-function ORFs), 37 tRNA genes, and 6 ribosomal RNA genes, suggesting a largest coding capacity in the red lineage. In each genome, 14 protein genes overlapped and no interrupted genes were found, indicating a high degree of genomic condensation. Pyropia maintain an ancient gene content and conserved gene clusters in their plastid genomes, containing nearly complete repertoires of the plastid genes known in photosynthetic eukaryotes. Similarity analysis based on the whole plastid genome sequences showed the distance between P. haitanensis and P. yezoensis (0.146) was much smaller than that of Porphyra purpurea and P. haitanensis (0.250), and P. yezoensis (0.251); this supports re-grouping the two species in a resurrected genus Pyropia while maintaining P. purpurea in genus Porphyra. Phylogenetic analysis supports a sister relationship between Bangiophyceae and Florideophyceae, though precise phylogenetic relationships between multicellular red alage and chromists were not fully resolved.

CONCLUSIONS: These results indicate that Pyropia have compact plastid genomes. Large coding capacity and long intergenic regions contribute to the size of the largest plastid genomes reported for the red lineage. Possessing the largest coding capacity and ancient gene content yet found reveal that Pyropia are more primitive multicellular red algae.}, } @article {pmid23732772, year = {2013}, author = {Martinez, CA and Barr, KA and Kim, AR and Reinitz, J}, title = {A synthetic biology approach to the development of transcriptional regulatory models and custom enhancer design.}, journal = {Methods (San Diego, Calif.)}, volume = {62}, number = {1}, pages = {91-98}, pmid = {23732772}, issn = {1095-9130}, support = {P50 GM081892/GM/NIGMS NIH HHS/United States ; R01 RR07801/RR/NCRR NIH HHS/United States ; R01 GM070444/GM/NIGMS NIH HHS/United States ; R01 GM70444/GM/NIGMS NIH HHS/United States ; R01 RR007801/RR/NCRR NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Binding Sites ; Body Patterning/genetics ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/embryology/*genetics/metabolism ; Embryo, Nonmammalian/cytology/*metabolism/ultrastructure ; *Enhancer Elements, Genetic ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Homeodomain Proteins/genetics/metabolism ; Image Processing, Computer-Assisted/statistics & numerical data ; In Situ Hybridization ; *Models, Genetic ; Protein Binding ; Synthetic Biology/*methods ; Transcription Factors/genetics/metabolism ; Transcription, Genetic ; }, abstract = {Synthetic biology offers novel opportunities for elucidating transcriptional regulatory mechanisms and enhancer logic. Complex cis-regulatory sequences--like the ones driving expression of the Drosophila even-skipped gene--have proven difficult to design from existing knowledge, presumably due to the large number of protein-protein interactions needed to drive the correct expression patterns of genes in multicellular organisms. This work discusses two novel computational methods for the custom design of enhancers that employ a sophisticated, empirically validated transcriptional model, optimization algorithms, and synthetic biology. These synthetic elements have both utilitarian and academic value, including improving existing regulatory models as well as evolutionary questions. The first method involves the use of simulated annealing to explore the sequence space for synthetic enhancers whose expression output fit a given search criterion. The second method uses a novel optimization algorithm to find functionally accessible pathways between two enhancer sequences. These paths describe a set of mutations wherein the predicted expression pattern does not significantly vary at any point along the path. Both methods rely on a predictive mathematical framework that maps the enhancer sequence space to functional output.}, } @article {pmid23730752, year = {2013}, author = {Ratcliff, WC and Pentz, JT and Travisano, M}, title = {Tempo and mode of multicellular adaptation in experimentally evolved Saccharomyces cerevisiae.}, journal = {Evolution; international journal of organic evolution}, volume = {67}, number = {6}, pages = {1573-1581}, doi = {10.1111/evo.12101}, pmid = {23730752}, issn = {1558-5646}, mesh = {Adaptation, Biological/*genetics ; Evolution, Molecular ; Saccharomyces cerevisiae/cytology/*genetics ; *Selection, Genetic ; Time Factors ; }, abstract = {Multicellular complexity is a central topic in biology, but the evolutionary processes underlying its origin are difficult to study and remain poorly understood. Here we use experimental evolution to investigate the tempo and mode of multicellular adaptation during a de novo evolutionary transition to multicellularity. Multicelled "snowflake" yeast evolved from a unicellular ancestor after 7 days of selection for faster settling through liquid media. Over the next 220 days, snowflake yeast evolved to settle 44% more quickly. Throughout the experiment the clusters evolved faster settling by three distinct modes. The number of cells per cluster increased from a mean of 42 cells after 7 days of selection to 114 cells after 227 days. Between days 28 and 65, larger clusters evolved via a twofold increase in the mass of individual cells. By day 227, snowflake yeast evolved to form more hydrodynamic clusters that settle more quickly for their size than ancestral strains. The timing and nature of adaptation in our experiment suggests that costs associated with large cluster size favor novel multicellular adaptations, increasing organismal complexity.}, } @article {pmid23730751, year = {2013}, author = {Simon, B and Fletcher, JA and Doebeli, M}, title = {Towards a general theory of group selection.}, journal = {Evolution; international journal of organic evolution}, volume = {67}, number = {6}, pages = {1561-1572}, doi = {10.1111/j.1558-5646.2012.01835.x}, pmid = {23730751}, issn = {1558-5646}, mesh = {Animals ; Evolution, Molecular ; Markov Chains ; *Models, Genetic ; Population/genetics ; *Selection, Genetic ; }, abstract = {The longstanding debate about the importance of group (multilevel) selection suffers from a lack of formal models that describe explicit selection events at multiple levels. Here, we describe a general class of models for two-level evolutionary processes which include birth and death events at both levels. The models incorporate the state-dependent rates at which these events occur. The models come in two closely related forms: (1) a continuous-time Markov chain, and (2) a partial differential equation (PDE) derived from (1) by taking a limit. We argue that the mathematical structure of this PDE is the same for all models of two-level population processes, regardless of the kinds of events featured in the model. The mathematical structure of the PDE allows for a simple and unambiguous way to distinguish between individual- and group-level events in any two-level population model. This distinction, in turn, suggests a new and intuitively appealing way to define group selection in terms of the effects of group-level events. We illustrate our theory of group selection by applying it to models of the evolution of cooperation and the evolution of simple multicellular organisms, and then demonstrate that this kind of group selection is not mathematically equivalent to individual-level (kin) selection.}, } @article {pmid23728794, year = {2013}, author = {Odon, V and Luke, GA and Roulston, C and de Felipe, P and Ruan, L and Escuin-Ordinas, H and Brown, JD and Ryan, MD and Sukhodub, A}, title = {APE-type non-LTR retrotransposons of multicellular organisms encode virus-like 2A oligopeptide sequences, which mediate translational recoding during protein synthesis.}, journal = {Molecular biology and evolution}, volume = {30}, number = {8}, pages = {1955-1965}, pmid = {23728794}, issn = {1537-1719}, support = {G0901002/MRC_/Medical Research Council/United Kingdom ; BB/E010709/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/E009093/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; C20035/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/H007849/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Genome, Protozoan ; Molecular Sequence Data ; Oligopeptides/chemistry/*genetics ; Open Reading Frames ; Phylogeny ; Protein Biosynthesis/*physiology ; Retroelements/*genetics ; Sequence Alignment ; Trypanosoma/classification/*genetics/*metabolism ; }, abstract = {2A oligopeptide sequences ("2As") mediate a cotranslational recoding event termed "ribosome skipping." Previously we demonstrated the activity of 2As (and "2A-like sequences") within a wide range of animal RNA virus genomes and non-long terminal repeat retrotransposons (non-LTRs) in the genomes of the unicellular organisms Trypanosoma brucei (Ingi) and T. cruzi (L1Tc). Here, we report the presence of 2A-like sequences in the genomes of a wide range of multicellular organisms and, as in the trypanosome genomes, within non-LTR retrotransposons (non-LTRs)-clustering in the Rex1, Crack, L2, L2A, and CR1 clades, in addition to Ingi. These 2A-like sequences were tested for translational recoding activity, and highly active sequences were found within the Rex1, L2, CR1, and Ingi clades. The presence of 2A-like sequences within non-LTRs may not only represent a method of controlling protein biogenesis but also shows some correlation with such apurinic/apyrimidinic DNA endonuclease-type non-LTRs encoding one, rather than two, open reading frames (ORFs). Interestingly, such non-LTRs cluster with closely related elements lacking 2A-like recoding elements but retaining ORF1. Taken together, these observations suggest that acquisition of 2A-like translational recoding sequences may have played a role in the evolution of these elements.}, } @article {pmid23724074, year = {2013}, author = {Zwart, MP and Tromas, N and Elena, SF}, title = {Model-selection-based approach for calculating cellular multiplicity of infection during virus colonization of multi-cellular hosts.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e64657}, pmid = {23724074}, issn = {1932-6203}, mesh = {Caulimovirus/*physiology ; Host-Pathogen Interactions/*physiology ; *Models, Theoretical ; Plants/*virology ; Poisson Distribution ; Tobacco Mosaic Virus/*physiology ; Virus Replication/*physiology ; }, abstract = {The cellular multiplicity of infection (MOI) is a key parameter for describing the interactions between virions and cells, predicting the dynamics of mixed-genotype infections, and understanding virus evolution. Two recent studies have reported in vivo MOI estimates for Tobacco mosaic virus (TMV) and Cauliflower mosaic virus (CaMV), using sophisticated approaches to measure the distribution of two virus variants over host cells. Although the experimental approaches were similar, the studies employed different definitions of MOI and estimation methods. Here, new model-selection-based methods for calculating MOI were developed. Seven alternative models for predicting MOI were formulated that incorporate an increasing number of parameters. For both datasets the best-supported model included spatial segregation of virus variants over time, and to a lesser extent aggregation of virus-infected cells was also implicated. Three methods for MOI estimation were then compared: the two previously reported methods and the best-supported model. For CaMV data, all three methods gave comparable results. For TMV data, the previously reported methods both predicted low MOI values (range: 1.04-1.23) over time, whereas the best-supported model predicted a wider range of MOI values (range: 1.01-2.10) and an increase in MOI over time. Model selection can therefore identify suitable alternative MOI models and suggest key mechanisms affecting the frequency of coinfected cells. For the TMV data, this leads to appreciable differences in estimated MOI values.}, } @article {pmid23702537, year = {2013}, author = {Himmel, HM}, title = {Drug-induced functional cardiotoxicity screening in stem cell-derived human and mouse cardiomyocytes: effects of reference compounds.}, journal = {Journal of pharmacological and toxicological methods}, volume = {68}, number = {1}, pages = {97-111}, doi = {10.1016/j.vascn.2013.05.005}, pmid = {23702537}, issn = {1873-488X}, mesh = {Animals ; Dimethyl Sulfoxide/chemistry ; Electric Impedance ; High-Throughput Screening Assays/methods ; Humans ; Induced Pluripotent Stem Cells/*cytology ; Mice ; Myocardial Contraction/*drug effects ; Myocytes, Cardiac/*drug effects/metabolism ; Reproducibility of Results ; Solvents/chemistry ; Species Specificity ; Time Factors ; Toxicity Tests/*methods ; }, abstract = {INTRODUCTION: Early prediction of drug-induced functional cardiotoxicity requires robust in-vitro systems suitable for medium/high throughput and easily accessible cardiomyocytes with defined reproducible properties. The xCELLigence Cardio system uses 96-well plates with interdigitated electrodes that detect the impedance changes of rhythmic contractions of stem cell-derived cardiomyocyte (SC-CM) layers. Here, we report on our initial screening experience in comparison to established (multi)cellular and in-vivo models.

METHODS: Impedance signals from human iPSC-CM (iCells™) and mouse eSC-CM (Cor.At™) were analyzed for contraction amplitude (CA) and duration, rise/fall time, beating rate (BR) and irregularity.

RESULTS: Following solution exchange, impedance signals re-approximated steady-state conditions after about 2 (Cor.At™) and 3h (iCells™); these time points were used to analyze drug effects. The solvent DMSO (≤1%) hardly influenced contraction parameters in Cor.At™, whereas in iCells™ DMSO (>0.1%) reduced CA and enhanced BR. The selective hERG K⁺ channel blockers E-4031 and dofetilide reduced CA and accelerated BR (≥30 nM) according to the analysis software. The latter, however, was due to burst-like contractions (300 nM) that could be detected only by visual inspection of recordings, and were more pronounced in Cor.At™ as in iCells™. In cardiac myocytes and tissue preparations, however, E4031 and dofetilide have been reported to increase cell shortening and contractile force and to reduce BR. Compounds (pentamidine, HMR1556, ATX2, TTX, and verapamil) with other mechanisms of action were also investigated; their effects differed partially between cell lines (e.g. TTX) and compared to established (multi)cellular models (e.g. HMR1556, ouabain).

CONCLUSION: Mouse and human stem cell-derived cardiomyocytes respond differently to drugs and these responses occasionally also differ from those originating from established in-vitro and in-vivo models. Hence, drug-induced cardiotoxic effects may be detected with this system, however, the predictive or even translational value of results is considered limited and not yet firmly established.}, } @article {pmid23700149, year = {2014}, author = {Henriksen, K and Karsdal, MA and Martin, TJ}, title = {Osteoclast-derived coupling factors in bone remodeling.}, journal = {Calcified tissue international}, volume = {94}, number = {1}, pages = {88-97}, doi = {10.1007/s00223-013-9741-7}, pmid = {23700149}, issn = {1432-0827}, mesh = {Animals ; Bone Remodeling/*genetics/physiology ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Osteoblasts/cytology/metabolism ; Osteoclasts/cytology/*metabolism ; Osteogenesis/physiology ; }, abstract = {In the bone remodeling process that takes place throughout the skeleton at bone multicellular units, intercellular communication processes are crucial. The osteoblast lineage has long been known to program osteoclast formation and hence resorption, but the preservation of bone mass and integrity requires tight control of remodeling. This needs local controls that ensure availability of mesenchymal precursors and the provision of local signals that promote differentiation through the osteoblast lineage. Some signals can come from growth factors released from resorbed bone matrix, and there is increasing evidence that the osteoclast lineage itself produces factors that can either enhance or inhibit osteoblast differentiation and hence bone formation. A number of such factors have been identified from predominantly in vitro experiments. The coupling of bone formation to resorption is increasingly recognized as a complex, dynamic process that results from the input of many local factors of cell and matrix origin that can either promote or inhibit bone formation.}, } @article {pmid23690618, year = {2013}, author = {Pires, ND and Yi, K and Breuninger, H and Catarino, B and Menand, B and Dolan, L}, title = {Recruitment and remodeling of an ancient gene regulatory network during land plant evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {23}, pages = {9571-9576}, pmid = {23690618}, issn = {1091-6490}, support = {BBS/E/J/0000A241/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Bryopsida/*genetics ; *Evolution, Molecular ; Gene Expression Regulation, Plant/genetics ; Gene Regulatory Networks/*genetics ; Molecular Sequence Data ; Multigene Family/*genetics ; Phylogeny ; Plant Roots/genetics/physiology ; Sequence Alignment ; Species Specificity ; }, abstract = {The evolution of multicellular organisms was made possible by the evolution of underlying gene regulatory networks. In animals, the core of gene regulatory networks consists of kernels, stable subnetworks of transcription factors that are highly conserved in distantly related species. However, in plants it is not clear when and how kernels evolved. We show here that RSL (ROOT HAIR DEFECTIVE SIX-LIKE) transcription factors form an ancient land plant kernel controlling caulonema differentiation in the moss Physcomitrella patens and root hair development in the flowering plant Arabidopsis thaliana. Phylogenetic analyses suggest that RSL proteins evolved in aquatic charophyte algae or in early land plants, and have been conserved throughout land plant radiation. Genetic and transcriptional analyses in loss of function A. thaliana and P. patens mutants suggest that the transcriptional interactions in the RSL kernel were remodeled and became more hierarchical during the evolution of vascular plants. We predict that other gene regulatory networks that control development in derived groups of plants may have originated in the earliest land plants or in their ancestors, the Charophycean algae.}, } @article {pmid23690137, year = {2013}, author = {Kutchko, KM and Siltberg-Liberles, J}, title = {Metazoan innovation: from aromatic amino acids to extracellular signaling.}, journal = {Amino acids}, volume = {45}, number = {2}, pages = {359-367}, pmid = {23690137}, issn = {1438-2199}, support = {P20 GM103432/GM/NIGMS NIH HHS/United States ; P20 RR016474/RR/NCRR NIH HHS/United States ; }, mesh = {Amino Acids, Aromatic/*chemistry/*metabolism ; Animals ; Eukaryota/enzymology/*metabolism ; Evolution, Molecular ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Phylogeny ; Sequence Alignment ; Signal Transduction ; Tyrosine/*metabolism ; }, abstract = {Tyrosine depletion in metazoan proteins was recently explained to be due to the appearance of tyrosine kinases in Metazoa. Here, we present a complementary explanation for the depletion of tyrosine, stating the importance of tyrosine in signaling not only as a phosphorylation target but also as a precursor for catecholamines and hormones. Molecules (dopamine, norepinephrine, and epinephrine, and to a lesser extent serotonin and melatonin) critical to metazoan multicellular signaling are also greatly dependent on a supply of tyrosine. These signaling molecules are synthesized in two highly linked pathways specific to metazoans. In addition, the shikimate pathway that non-metazoans use to synthesize the aromatic amino acids is not present in metazoans. These important pathway changes have occurred between Metazoa and other eukaryotes, causing significant changes to tyrosine metabolism and rendering tyrosine crucial for extracellular signaling. In addition, the evolutionary and functional linkage between these two pathways and the resulting implications for neuropathology are discussed.}, } @article {pmid23671590, year = {2013}, author = {Lenart, A and Dudkiewicz, M and Grynberg, M and Pawłowski, K}, title = {CLCAs - a family of metalloproteases of intriguing phylogenetic distribution and with cases of substituted catalytic sites.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e62272}, pmid = {23671590}, issn = {1932-6203}, mesh = {Amino Acid Motifs/genetics ; Amino Acid Sequence ; Archaeal Proteins/genetics ; Bacterial Proteins/genetics ; Databases, Protein ; Genome, Human/*genetics ; Humans ; Metalloproteases/classification/*genetics ; Molecular Sequence Data ; Multigene Family/*genetics ; *Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {The zinc-dependent metalloproteases with His-Glu-x-x-His (HExxH) active site motif, zincins, are a broad group of proteins involved in many metabolic and regulatory functions, and found in all forms of life. Human genome contains more than 100 genes encoding proteins with known zincin-like domains. A survey of all proteins containing the HExxH motif shows that approximately 52% of HExxH occurrences fall within known protein structural domains (as defined in the Pfam database). Domain families with majority of members possessing a conserved HExxH motif include, not surprisingly, many known and putative metalloproteases. Furthermore, several HExxH-containing protein domains thus identified can be confidently predicted to be putative peptidases of zincin fold. Thus, we predict zincin-like fold for eight uncharacterised Pfam families. Besides the domains with the HExxH motif strictly conserved, and those with sporadic occurrences, intermediate families are identified that contain some members with a conserved HExxH motif, but also many homologues with substitutions at the conserved positions. Such substitutions can be evolutionarily conserved and non-random, yet functional roles of these inactive zincins are not known. The CLCAs are a novel zincin-like protease family with many cases of substituted active sites. We show that this allegedly metazoan family has a number of bacterial and archaeal members. An extremely patchy phylogenetic distribution of CLCAs in prokaryotes and their conserved protein domain composition strongly suggests an evolutionary scenario of horizontal gene transfer (HGT) from multicellular eukaryotes to bacteria, providing an example of eukaryote-derived xenologues in bacterial genomes. Additionally, in a protein family identified here as closely homologous to CLCA, the CLCA_X (CLCA-like) family, a number of proteins is found in phages and plasmids, supporting the HGT scenario.}, } @article {pmid23665876, year = {2013}, author = {Hall, DW and Fox, S and Kuzdzal-Fick, JJ and Strassmann, JE and Queller, DC}, title = {The rate and effects of spontaneous mutation on fitness traits in the social amoeba, Dictyostelium discoideum.}, journal = {G3 (Bethesda, Md.)}, volume = {3}, number = {7}, pages = {1115-1127}, pmid = {23665876}, issn = {2160-1836}, mesh = {Dictyostelium/*genetics ; Evolution, Molecular ; *Genetic Fitness ; Mutation/*genetics ; Mutation Rate ; Saccharomyces cerevisiae/genetics ; }, abstract = {We performed a mutation accumulation (MA) experiment in the social amoeba Dictyostelium discoideum to estimate the rate and distribution of effects of spontaneous mutations affecting eight putative fitness traits. We found that the per-generation mutation rate for most fitness components is 0.0019 mutations per haploid genome per generation or larger. This rate is an order of magnitude higher than estimates for fitness components in the unicellular eukaryote Saccharomyces cerevisiae, even though the base-pair substitution rate is two orders of magnitude lower. The high rate of fitness-altering mutations observed in this species may be partially explained by a large mutational target relative to S. cerevisiae. Fitness-altering mutations also may occur primarily at simple sequence repeats, which are common throughout the genome, including in coding regions, and may represent a target that is particularly likely to give fitness effects upon mutation. The majority of mutations had deleterious effects on fitness, but there was evidence for a substantial fraction, up to 40%, being beneficial for some of the putative fitness traits. Competitive ability within the multicellular slug appears to be under weak directional selection, perhaps reflecting the fact that slugs are sometimes, but not often, comprised of multiple clones in nature. Evidence for pleiotropy among fitness components across MA lines was absent, suggesting that mutations tend to act on single fitness components.}, } @article {pmid23662577, year = {2013}, author = {Teriukova, NP and Blinova, GI and Ivanov, VA}, title = {[Zajdela hepatoma cells cultured in vitro].}, journal = {Tsitologiia}, volume = {55}, number = {1}, pages = {36-44}, pmid = {23662577}, issn = {0041-3771}, mesh = {Animals ; Antibodies, Neoplasm/immunology ; *Antigens, Neoplasm/biosynthesis/immunology ; *Carcinoma, Hepatocellular/immunology/metabolism/pathology ; Cell Line, Tumor ; *Liver Neoplasms/immunology/metabolism/pathology ; Male ; Rabbits ; Rats ; *Spheroids, Cellular/immunology/metabolism/pathology ; }, abstract = {Two continuous cell lines, monolayer (ZH-ad) and suspension (ZH-fl), which doffer in the level of cell differentiation and tumorigenicity, were obtained from explants of ascitic Zajdela hepatoma. Using tumor-specific rabbit immune serum tumor-associated antigens were detected in the fraction of plasma membrane of ZH-fl cells, synthesis of that was reduced or suppressed in ZH-ad cells. Intraperitoneal injection of ZH-fl cells as few as 0.5 - 10(6) cells/rat was enough for development of ascites tumor, while minimal dose for ZH-ad cells increase to 20 - 10(6) cells. Three types of generated clones were revealed by means of clonogenic analysis of ZH-fl cells: nonadhesive sphere colonies and two types of monolayer clones ranging in proliferative potential, shape of colonies and cell composition. When the spherical colonies had reached a critical size they disintegrated with dissociation of single cells or islets of various sizes, part of which attached to the plate to form a monolayer. Three clonal cell lines were obtained: IC - as a result of expansion of sphere clone cells, 4G and 10E - from monolayer clones. Our results demonstrate a clonogenic origin of multicellular islets of ascetic hepatoma Zajdela.}, } @article {pmid23645554, year = {2013}, author = {Bhattacharya, D and Pelletreau, KN and Price, DC and Sarver, KE and Rumpho, ME}, title = {Genome analysis of Elysia chlorotica Egg DNA provides no evidence for horizontal gene transfer into the germ line of this Kleptoplastic Mollusc.}, journal = {Molecular biology and evolution}, volume = {30}, number = {8}, pages = {1843-1852}, pmid = {23645554}, issn = {1537-1719}, mesh = {Animals ; Computational Biology/methods ; *DNA ; Databases, Nucleic Acid ; Gastropoda/*genetics/metabolism ; *Gene Transfer, Horizontal ; *Genomics ; Germ Cells/*metabolism ; Transcription, Genetic ; }, abstract = {The sea slug Elysia chlorotica offers a unique opportunity to study the evolution of a novel function (photosynthesis) in a complex multicellular host. Elysia chlorotica harvests plastids (absent of nuclei) from its heterokont algal prey, Vaucheria litorea. The "stolen" plastids are maintained for several months in cells of the digestive tract and are essential for animal development. The basis of long-term maintenance of photosynthesis in this sea slug was thought to be explained by extensive horizontal gene transfer (HGT) from the nucleus of the alga to the animal nucleus, followed by expression of algal genes in the gut to provide essential plastid-destined proteins. Early studies of target genes and proteins supported the HGT hypothesis, but more recent genome-wide data provide conflicting results. Here, we generated significant genome data from the E. chlorotica germ line (egg DNA) and from V. litorea to test the HGT hypothesis. Our comprehensive analyses fail to provide evidence for alga-derived HGT into the germ line of the sea slug. Polymerase chain reaction analyses of genomic DNA and cDNA from different individual E. chlorotica suggest, however, that algal nuclear genes (or gene fragments) are present in the adult slug. We suggest that these nucleic acids may derive from and/or reside in extrachromosomal DNAs that are made available to the animal through contact with the alga. These data resolve a long-standing issue and suggest that HGT is not the primary reason underlying long-term maintenance of photosynthesis in E. chlorotica. Therefore, sea slug photosynthesis is sustained in as yet unexplained ways that do not appear to endanger the animal germ line through the introduction of dozens of foreign genes.}, } @article {pmid23634722, year = {2013}, author = {Aguilera, F and McDougall, C and Degnan, BM}, title = {Origin, evolution and classification of type-3 copper proteins: lineage-specific gene expansions and losses across the Metazoa.}, journal = {BMC evolutionary biology}, volume = {13}, number = {}, pages = {96}, pmid = {23634722}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Catechol Oxidase/chemistry/*genetics/metabolism ; Copper/metabolism ; Eukaryota/chemistry/classification/*genetics ; *Evolution, Molecular ; *Gene Deletion ; *Gene Duplication ; Hemocyanins/chemistry/*genetics/metabolism ; Humans ; Molecular Sequence Data ; Monophenol Monooxygenase/chemistry/*genetics/metabolism ; Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment ; Species Specificity ; }, abstract = {BACKGROUND: Tyrosinases, tyrosinase-related proteins, catechol oxidases and hemocyanins comprise the type-3 copper protein family and are involved in a variety of biological processes, including pigment formation, innate immunity and oxygen transport. Although this family is present in the three domains of life, its origin and early evolution are not well understood. Previous analyses of type-3 copper proteins largely have focussed on specific animal and plant phyla.

RESULTS: Here, we combine genomic, phylogenetic and structural analyses to show that the original type-3 copper protein possessed a signal peptide and may have been secreted (we designate proteins of this type the α subclass). This ancestral type-3 copper protein gene underwent two duplication events, the first prior to the divergence of the unikont eukaryotic lineages and the second before the diversification of animals. The former duplication gave rise to a cytosolic form (β) and the latter to a membrane-bound form (γ). Structural comparisons reveal that the active site of α and γ forms are covered by aliphatic amino acids, and the β form has a highly conserved aromatic residue in this position. The subsequent evolution of this gene family in modern lineages of multicellular eukaryotes is typified by the loss of one or more of these three subclasses and the lineage-specific expansion of one or both of the remaining subclasses.

CONCLUSIONS: The diversity of type-3 copper proteins in animals and other eukaryotes is consistent with two ancient gene duplication events leading to α, β and γ subclasses, followed by the differential loss and expansion of one or more of these subclasses in specific kingdoms and phyla. This has led to many lineage-specific type-3 copper protein repertoires and in some cases the independent evolution of functionally-classified tyrosinases and hemocyanins. For example, the oxygen-carrying hemocyanins in arthropods evolved from a β-subclass tyrosinase, whilst hemocyanins in molluscs and urochordates evolved independently from an α-subclass tyrosinase. Minor conformational changes at the active site of α, β and γ forms can produce type-3 copper proteins with capacities to either carry oxygen (hemocyanins), oxidize diphenols (catechol oxidase) or o-hydroxylate monophenols (tyrosinases) and appear to underlie some functional convergences.}, } @article {pmid23615877, year = {2013}, author = {Tarabichi, M and Antoniou, A and Saiselet, M and Pita, JM and Andry, G and Dumont, JE and Detours, V and Maenhaut, C}, title = {Systems biology of cancer: entropy, disorder, and selection-driven evolution to independence, invasion and "swarm intelligence".}, journal = {Cancer metastasis reviews}, volume = {32}, number = {3-4}, pages = {403-421}, pmid = {23615877}, issn = {1573-7233}, mesh = {Animals ; Cell Transformation, Neoplastic ; Humans ; Neoplasm Metastasis ; Neoplasms/*etiology/*pathology ; *Systems Biology ; }, abstract = {Our knowledge of the biology of solid cancer has greatly progressed during the last few years, and many excellent reviews dealing with the various aspects of this biology have appeared. In the present review, we attempt to bring together these subjects in a general systems biology narrative. It starts from the roles of what we term entropy of signaling and noise in the initial oncogenic events, to the first major transition of tumorigenesis: the independence of the tumor cell and the switch in its physiology, i.e., from subservience to the organism to its own independent Darwinian evolution. The development after independence involves a constant dynamic reprogramming of the cells and the emergence of a sort of collective intelligence leading to invasion and metastasis and seldom to the ultimate acquisition of immortality through inter-individual infection. At each step, the probability of success is minimal to infinitesimal, but the number of cells possibly involved and the time scale account for the relatively high occurrence of tumorigenesis and metastasis in multicellular organisms.}, } @article {pmid23613593, year = {2013}, author = {Pechkovsky, A and Lahav, M and Bitman, E and Salzberg, A and Kleinberger, T}, title = {E4orf4 induces PP2A- and Src-dependent cell death in Drosophila melanogaster and at the same time inhibits classic apoptosis pathways.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {19}, pages = {E1724-33}, pmid = {23613593}, issn = {1091-6490}, mesh = {Animals ; *Apoptosis ; Caspases/metabolism ; Conserved Sequence ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/*metabolism ; Female ; *Gene Expression Regulation, Enzymologic ; Male ; Models, Genetic ; Phenotype ; Phosphoprotein Phosphatases/*metabolism ; Photoreceptor Cells, Invertebrate/physiology ; Transgenes ; Viral Proteins/*genetics/metabolism ; Wings, Animal/physiology ; src-Family Kinases/*metabolism ; }, abstract = {The adenovirus E4orf4 protein regulates the progression of viral infection, and when expressed alone in mammalian tissue culture cells it induces protein phosphatase 2A (PP2A)-B55- and Src-dependent cell death, which is more efficient in oncogene-transformed cells than in normal cells. This form of cell death is caspase-independent, although it interacts with classic caspase-dependent apoptosis. PP2A-B55-dependent E4orf4-induced toxicity is highly conserved in evolution from yeast to mammalian cells. In this work we investigated E4orf4-induced cell death in a whole multicellular organism, Drosophila melanogaster. We show that E4orf4 induced low levels of cell killing, caused by both caspase-dependent and -independent mechanisms. Drosophila PP2A-B55 (twins/abnormal anaphase resolution) and Src64B contributed additively to this form of cell death. Our results provide insight into E4orf4-induced cell death, demonstrating that in parallel to activating caspase-dependent apoptosis, E4orf4 also inhibited this form of cell death induced by the proapoptotic genes reaper, head involution defective, and grim. The combination of both induction and inhibition of caspase-dependent cell death resulted in low levels of tissue damage that may explain the inefficient cell killing induced by E4orf4 in normal cells in tissue culture. Furthermore, E4orf4 inhibited JNK-dependent cell killing as well. However, JNK inhibition did not impede E4orf4-induced toxicity and even enhanced it, indicating that E4orf4-induced cell killing is a distinctive form of cell death that differs from both JNK- and Rpr/Hid/Grim-induced forms of cell death.}, } @article {pmid23611907, year = {2013}, author = {Gyawali, R and Lin, X}, title = {Prezygotic and postzygotic control of uniparental mitochondrial DNA inheritance in Cryptococcus neoformans.}, journal = {mBio}, volume = {4}, number = {2}, pages = {e00112-13}, pmid = {23611907}, issn = {2150-7511}, support = {R01 AI097599/AI/NIAID NIH HHS/United States ; }, mesh = {Cryptococcus neoformans/*genetics ; DNA, Mitochondrial/*genetics ; Genes, Mating Type, Fungal ; *Genes, Mitochondrial ; Time Factors ; }, abstract = {UNLABELLED: Uniparental inheritance of mitochondrial DNA is pervasive in nonisogamic higher eukaryotes during sexual reproduction, and postzygotic and/or prezygotic factors are shown to be important in ensuring such an inheritance pattern. Although the fungus Cryptococcus neoformans undergoes sexual production with isogamic partners of opposite mating types a and α, most progeny derived from such mating events inherit the mitochondrial DNA (mtDNA) from the a parent. The homeodomain protein complex Sxi1α/Sxi2a, formed in the zygote after a-α cell fusion, was previously shown to play a role in this uniparental mtDNA inheritance. Here, we defined the timing of the establishment of the mtDNA inheritance pattern during the mating process and demonstrated a critical role in determining the mtDNA inheritance pattern by a prezygotic factor, Mat2. Mat2 is the key transcription factor that governs the pheromone sensing and response pathway, and it is critical for the early mating events that lead to cell fusion and zygote formation. We show that Mat2 governs mtDNA inheritance independently of the postzygotic factors Sxi1α/Sxi2a, and the cooperation between these prezygotic and postzygotic factors helps to achieve stricter uniparental mitochondrial inheritance in this eukaryotic microbe.

IMPORTANCE: Mitochondrial DNA is inherited uniparentally from the maternal parent in the majority of eukaryotes. Studies done on higher eukaryotes such as mammals have shown that the transmission of parental mitochondrial DNA is controlled at both the prefertilization and postfertilization stages to achieve strict uniparental inheritance. However, the molecular mechanisms underlying such uniparental mitochondrial inheritance have been investigated in detail mostly in anisogamic multicellular eukaryotes. Here, we show that in a simple isogamic microbe, Cryptococcus neoformans, the mitochondrial inheritance is controlled at the prezygotic level as well as the postzygotic level by regulators that are critical for sexual development. Furthermore, the cooperation between these two levels of control ensures stricter uniparental mitochondrial inheritance, echoing what has been observed in higher eukaryotes. Thus, the investigation of uniparental mitochondrial inheritance in this eukaryotic microbe could help advance our understanding of the convergent evolution of this widespread phenomenon in the eukaryotic domain.}, } @article {pmid23597031, year = {2013}, author = {Taylor-Brown, E and Hurd, H}, title = {The first suicides: a legacy inherited by parasitic protozoans from prokaryote ancestors.}, journal = {Parasites & vectors}, volume = {6}, number = {}, pages = {108}, pmid = {23597031}, issn = {1756-3305}, mesh = {*Apoptosis ; Bacteria/genetics ; Biological Evolution ; Leishmania/genetics/*physiology ; Mitochondria/metabolism ; Phenotype ; Plasmodium/genetics/*physiology ; Trypanosoma/genetics/*physiology ; }, abstract = {It is more than 25 years since the first report that a protozoan parasite could die by a process resulting in a morphological phenotype akin to apoptosis. Since then these phenotypes have been observed in many unicellular parasites, including trypanosomatids and apicomplexans, and experimental evidence concerning the molecular pathways that are involved is growing. These observations support the view that this form of programmed cell death is an ancient one that predates the evolution of multicellularity. Here we review various hypotheses that attempt to explain the origin of apoptosis, and look for support for these hypotheses amongst the parasitic protists as, with the exception of yeast, most of the work on death mechanisms in unicellular organisms has focussed on them. We examine the role that addiction modules may have played in the original eukaryote cell and the part played by mitochondria in the execution of present day cells, looking for examples from Leishmania spp. Trypanosoma spp. and Plasmodium spp. In addition, the expanding knowledge of proteases, nucleases and other molecules acting in protist execution pathways has enabled comparisons to be made with extant Archaea and bacteria and with biochemical pathways that evolved in metazoans. These comparisons lend support to the original sin hypothesis but also suggest that present-day death pathways may have had multifaceted beginnings.}, } @article {pmid23586987, year = {2013}, author = {Omura, T}, title = {Contribution of cytochrome P450 to the diversification of eukaryotic organisms.}, journal = {Biotechnology and applied biochemistry}, volume = {60}, number = {1}, pages = {4-8}, doi = {10.1002/bab.1099}, pmid = {23586987}, issn = {1470-8744}, mesh = {Animals ; Biocatalysis ; *Biological Evolution ; Cytochrome P-450 Enzyme System/genetics/*metabolism ; Eukaryota/*enzymology/metabolism ; }, abstract = {Emergence of eukaryotic cells in the ancient world of prokaryotic life was dependent on P450 as the synthesis of sterols, an essential constituent of the plasma membrane, required a P450-catalyzed reaction. As the ancestral monocellular eukaryotic organisms evolved into multicellular eukaryotes, and then diversified to plants, fungi, and animals with different body organizations and metabolic activities, many novel compounds were created in order to meet the requirements for increasing complex metabolic activities of a wide variety of eukaryotic organisms. Many new P450s, created by gene duplication and mutation, contributed to the synthesis of those novel compounds in animals, plants, and fungi, and supported the diversification of the eukaryotes. Many secondary metabolites of plants, which protect the plants from the predation by herbivorous animals, were also synthesized by P450-catalyzed reactions. The herbivorous animals detoxified the noxious foreign compounds in the plants by P450. This "chemical warfare" between animals and plants is particularly evident in plants-insects interaction, and contributed to the coevolution and diversification of both plants and insects. The interaction between flowering plants and insect pollinators, which contributed to their coevolution, also depends on various plant compounds synthesized by P450-catalyzed reactions. P450 has made highly important contributions to the evolution and diversification of eukaryotic organisms.}, } @article {pmid23577236, year = {2013}, author = {Gresham, D}, title = {A sticky solution.}, journal = {eLife}, volume = {2}, number = {}, pages = {e00655}, pmid = {23577236}, issn = {2050-084X}, support = {R01 GM107466/GM/NIGMS NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; Monosaccharide Transport Proteins/*metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; Sucrose/*metabolism ; beta-Fructofuranosidase/*metabolism ; }, abstract = {Selection favours single-celled mutants that stick together when a sugar needed for growth is in short supply, suggesting that multicellular life may have evolved as a by-product of selection for more efficient usage of resources.}, } @article {pmid23577233, year = {2013}, author = {Koschwanez, JH and Foster, KR and Murray, AW}, title = {Improved use of a public good selects for the evolution of undifferentiated multicellularity.}, journal = {eLife}, volume = {2}, number = {}, pages = {e00367}, pmid = {23577233}, issn = {2050-084X}, support = {P50 GM068763/GM/NIGMS NIH HHS/United States ; GM06873/GM/NIGMS NIH HHS/United States ; K25GM085806/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological ; Biological Transport ; Cell Division ; *Evolution, Molecular ; Gene Expression Regulation, Fungal ; Genotype ; Hydrolysis ; Monosaccharide Transport Proteins/genetics/*metabolism ; Mutation ; Phenotype ; Saccharomyces cerevisiae/genetics/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Sucrose/*metabolism ; beta-Fructofuranosidase/genetics/*metabolism ; }, abstract = {We do not know how or why multicellularity evolved. We used the budding yeast, Saccharomyces cerevisiae, to ask whether nutrients that must be digested extracellularly select for the evolution of undifferentiated multicellularity. Because yeast use invertase to hydrolyze sucrose extracellularly and import the resulting monosaccharides, single cells cannot grow at low cell and sucrose concentrations. Three engineered strategies overcame this problem: forming multicellular clumps, importing sucrose before hydrolysis, and increasing invertase expression. We evolved populations in low sucrose to ask which strategy they would adopt. Of 12 successful clones, 11 formed multicellular clumps through incomplete cell separation, 10 increased invertase expression, none imported sucrose, and 11 increased hexose transporter expression, a strategy we had not engineered. Identifying causal mutations revealed genes and pathways, which frequently contributed to the evolved phenotype. Our study shows that combining rational design with experimental evolution can help evaluate hypotheses about evolutionary strategies. DOI:http://dx.doi.org/10.7554/eLife.00367.001.}, } @article {pmid23569284, year = {2013}, author = {Nguyen, DH and Stapleton, SC and Yang, MT and Cha, SS and Choi, CK and Galie, PA and Chen, CS}, title = {Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {17}, pages = {6712-6717}, pmid = {23569284}, issn = {1091-6490}, support = {UH2 EB017103/EB/NIBIB NIH HHS/United States ; T32 HL007954/HL/NHLBI NIH HHS/United States ; R01 GM104287/GM/NIGMS NIH HHS/United States ; HL007954/HL/NHLBI NIH HHS/United States ; R01 EB000262/EB/NIBIB NIH HHS/United States ; EB00262/EB/NIBIB NIH HHS/United States ; CA101871/CA/NCI NIH HHS/United States ; EB08396/EB/NIBIB NIH HHS/United States ; R01 EB008396/EB/NIBIB NIH HHS/United States ; R25 CA101871/CA/NCI NIH HHS/United States ; UH3 EB017103/EB/NIBIB NIH HHS/United States ; R01 DE016525/DE/NIDCR NIH HHS/United States ; }, mesh = {Biomimetics/*methods ; Cell Polarity/physiology ; Dimethylpolysiloxanes ; Fingolimod Hydrochloride ; Fluorescent Antibody Technique ; Human Umbilical Vein Endothelial Cells ; Humans ; Indoles/pharmacology ; Lysophospholipids/metabolism ; Microfluidics/*methods ; *Models, Biological ; Morphogenesis/drug effects/*physiology ; Neovascularization, Physiologic/drug effects/*physiology ; Propylene Glycols/pharmacology ; Pseudopodia/physiology ; Pyrroles/pharmacology ; Sphingosine/analogs & derivatives/metabolism/pharmacology ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors ; }, abstract = {Angiogenesis is a complex morphogenetic process whereby endothelial cells from existing vessels invade as multicellular sprouts to form new vessels. Here, we have engineered a unique organotypic model of angiogenic sprouting and neovessel formation that originates from preformed artificial vessels fully encapsulated within a 3D extracellular matrix. Using this model, we screened the effects of angiogenic factors and identified two distinct cocktails that promoted robust multicellular endothelial sprouting. The angiogenic sprouts in our system exhibited hallmark structural features of in vivo angiogenesis, including directed invasion of leading cells that developed filopodia-like protrusions characteristic of tip cells, following stalk cells exhibiting apical-basal polarity, and lumens and branches connecting back to the parent vessels. Ultimately, sprouts bridged between preformed channels and formed perfusable neovessels. Using this model, we investigated the effects of angiogenic inhibitors on sprouting morphogenesis. Interestingly, the ability of VEGF receptor 2 inhibition to antagonize filopodia formation in tip cells was context-dependent, suggesting a mechanism by which vessels might be able to toggle between VEGF-dependent and VEGF-independent modes of angiogenesis. Like VEGF, sphingosine-1-phosphate also seemed to exert its proangiogenic effects by stimulating directional filopodial extension, whereas matrix metalloproteinase inhibitors prevented sprout extension but had no impact on filopodial formation. Together, these results demonstrate an in vitro 3D biomimetic model that reconstitutes the morphogenetic steps of angiogenic sprouting and highlight the potential utility of the model to elucidate the molecular mechanisms that coordinate the complex series of events involved in neovascularization.}, } @article {pmid23563970, year = {2013}, author = {Grau-Bové, X and Sebé-Pedrós, A and Ruiz-Trillo, I}, title = {A genomic survey of HECT ubiquitin ligases in eukaryotes reveals independent expansions of the HECT system in several lineages.}, journal = {Genome biology and evolution}, volume = {5}, number = {5}, pages = {833-847}, pmid = {23563970}, issn = {1759-6653}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Animals ; Eukaryota/classification/*genetics ; *Evolution, Molecular ; Genome ; *Phylogeny ; Protein Structure, Tertiary ; Ubiquitin-Protein Ligases/classification/*genetics ; Ubiquitination/genetics ; }, abstract = {The posttranslational modification of proteins by the ubiquitination pathway is an important regulatory mechanism in eukaryotes. To date, however, studies on the evolutionary history of the proteins involved in this pathway have been restricted to E1 and E2 enzymes, whereas E3 studies have been focused mainly in metazoans and plants. To have a wider perspective, here we perform a genomic survey of the HECT family of E3 ubiquitin-protein ligases, an important part of this posttranslational pathway, in genomes from representatives of all major eukaryotic lineages. We classify eukaryotic HECTs and reconstruct, by phylogenetic analysis, the putative repertoire of these proteins in the last eukaryotic common ancestor (LECA). Furthermore, we analyze the diversity and complexity of protein domain architectures of HECTs along the different extant eukaryotic lineages. Our data show that LECA had six different HECTs and that protein expansion and N-terminal domain diversification shaped HECT evolution. Our data reveal that the genomes of animals and unicellular holozoans considerably increased the molecular and functional diversity of their HECT system compared with other eukaryotes. Other eukaryotes, such as the Apusozoa Thecanomas trahens or the Heterokonta Phytophthora infestans, independently expanded their HECT repertoire. In contrast, plant, excavate, rhodophyte, chlorophyte, and fungal genomes have a more limited enzymatic repertoire. Our genomic survey and phylogenetic analysis clarifies the origin and evolution of different HECT families among eukaryotes and provides a useful phylogenetic framework for future evolutionary studies of this regulatory pathway.}, } @article {pmid23562785, year = {2013}, author = {Premachandra, HK and De Zoysa, M and Nikapitiya, C and Lee, Y and Wickramaarachchi, WD and Whang, I and Lee, J}, title = {Molluskan fasciclin-1 domain-containing protein: molecular characterizationand gene expression analysis of fasciclin 1-like protein from disk abalone (Haliotis discus discus).}, journal = {Gene}, volume = {522}, number = {2}, pages = {219-225}, doi = {10.1016/j.gene.2013.03.053}, pmid = {23562785}, issn = {1879-0038}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Cell Adhesion ; Cell Adhesion Molecules, Neuronal/chemistry/*genetics/metabolism ; Cloning, Molecular ; Gastropoda/*genetics/immunology/metabolism/microbiology ; Gene Expression ; Hemocytes/metabolism ; Listeria monocytogenes ; Molecular Sequence Data ; Phylogeny ; RNA, Messenger/genetics/metabolism ; Sequence Analysis, DNA ; Vibrio parahaemolyticus/physiology ; }, abstract = {Cell-to-cell contacts play a key role in multicellular systems and organisms. Fasciclin-1 (FAS-1) is a lipid-linked membrane associated glycoprotein that is a member of a newly recognized family of cell adhesion molecules sharing features with the immunoglobulins, cadherins, integrins, and selectins. Here, we report the identification and molecular characterization of a novel FAS-1 domain-containing cDNA from disk abalone (Haliotis discus discus), including its gene expression profile and immune response to bacterial stimuli and tissue injuries. Designated as Abfac1, the 909bp open reading frame (ORF) encodes 303 amino acid (aa) residues with a predicted molecular mass of 33kDa and isoelectric (pI) value of 4.9. The aa sequence contains two FAS-1 domains and three conserved regions, FRa motif, H-box, and FRb motif. Phylogenetic analysis showed the closest relation to Jellyfish cell adhesion protein. In healthy abalone, Abfac1 expression is highest in hepatopancreas followed by mantle and lowest in digestive gland. In immune-stimulated abalones, relative Abfac1 mRNA expression was increased in hemocytes by ~11-fold at 48h after the Vibrio parahaemolyticus infection, by 3.1-fold at 6h after the Listeria monocytogenes infection and by ~9-fold at 6h after the LPS injection. Similarly, tissue injuries caused significant increase of relative mRNA expression by 3.5-fold in hemocytes and by ~10-fold in mantle at 12h post-injury. These results suggest that the novel member of the FAS-1 domain-containing protein family, Abfac1, may be involved in immune response and cell adhesion in disk abalone.}, } @article {pmid23551947, year = {2013}, author = {Sadrieh, A and Mann, SA and Subbiah, RN and Domanski, L and Taylor, JA and Vandenberg, JI and Hill, AP}, title = {Quantifying the origins of population variability in cardiac electrical activity through sensitivity analysis of the electrocardiogram.}, journal = {The Journal of physiology}, volume = {591}, number = {17}, pages = {4207-4222}, pmid = {23551947}, issn = {1469-7793}, mesh = {*Action Potentials ; Data Interpretation, Statistical ; Electrocardiography ; Heart/*physiology ; Heart Rate ; Humans ; Ion Transport ; *Models, Cardiovascular ; Myocytes, Cardiac/metabolism/physiology ; Potassium Channels/metabolism ; }, abstract = {Altered function of ion channels in the heart can increase the risk of sudden arrhythmic death. Hundreds of genetic variants exist in these cardiac ion channel genes. The challenge is how to interpret the effects of multiple conductance perturbations on the complex multi-variable cardiac electrical system? In theory, sensitivity analysis can address this question. However, to date this approach has been restricted by computational overheads to analysis of isolated cells, which has limited extrapolation to physiologically relevant scales. The goal of this study was to extend existing sensitivity analyses to electrocardiogram (ECG) signals derived from multicellular systems and quantify the contribution of ionic conductances to emergent properties of the ECG. To achieve this, we have developed a highly parallelised simulation environment using unconventional high performance computing architectures to analyse the emergent electrical properties of a multicellular system. This has permitted the first systematic analysis of the molecular basis of the T wave amplitude, revealing important but distinct roles for delayed rectifier and inward rectifier K(+) currents. In addition to quantifying how interactions between multiple ion channels influence ECG parameters we show that these sensitivities are dynamic functions of heart rate. This study provides a significant advance in our understanding both of how individual ion conductances define ECG signals and of epistatic modification of cardiac electrical phenotypes. The parallelised simulation environment we have developed removes the computational roadblock that has limited this approach and so provides the framework for future analysis of more complex tissue and whole organ systems.}, } @article {pmid23551562, year = {2013}, author = {Gardiner, J}, title = {The evolution and diversification of plant microtubule-associated proteins.}, journal = {The Plant journal : for cell and molecular biology}, volume = {75}, number = {2}, pages = {219-229}, doi = {10.1111/tpj.12189}, pmid = {23551562}, issn = {1365-313X}, mesh = {Animals ; Arabidopsis/genetics ; Bryopsida/genetics ; Chlamydomonas reinhardtii/genetics ; *Evolution, Molecular ; Genome, Plant ; Magnoliopsida/genetics ; Microtubule-Associated Proteins/genetics/metabolism/*physiology ; Microtubules/chemistry/metabolism ; Oryza/genetics ; Plant Proteins/*genetics ; }, abstract = {Plant evolution is marked by major advances in structural characteristics that facilitated the highly successful colonization of dry land. Underlying these advances is the evolution of genes encoding specialized proteins that form novel microtubular arrays of the cytoskeleton. This review investigates the evolution of plant families of microtubule-associated proteins (MAPs) through the recently sequenced genomes of Arabidopsis thaliana, Oryza sativa, Selaginella moellendorffii, Physcomitrella patens, Volvox carteri and Chlamydomonas reinhardtii. The families of MAPs examined are AIR9, CLASP, CRIPT, MAP18, MOR1, TON, EB1, AtMAP70, SPR2, SPR1, WVD2 and MAP65 families (abbreviations are defined in the footnote to Table 1). Conjectures are made regarding the evolution of MAPs in plants in relation to the evolution of multicellularity, oriented cell division and vasculature. Angiosperms in particular have high numbers of proteins that are involved in promotion of helical growth or its suppression, and novel plant microtubular structures may have acted as a catalyst for the development of novel plant MAPs. Comparisons of plant MAP gene families with those of animals show that animals may have more flexibility in the structure of their microtubule cytoskeletons than plants, but with both plants and animals possessing many MAP splice variants.}, } @article {pmid23510136, year = {2013}, author = {Hoekstra, LA and Montooth, KL}, title = {Inducing extra copies of the Hsp70 gene in Drosophila melanogaster increases energetic demand.}, journal = {BMC evolutionary biology}, volume = {13}, number = {}, pages = {68}, pmid = {23510136}, issn = {1471-2148}, mesh = {Animals ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/*genetics/growth & development/*metabolism ; Energy Metabolism/*genetics ; *Evolution, Molecular ; *Gene Dosage ; HSP70 Heat-Shock Proteins/*genetics/metabolism ; Larva/genetics/growth & development/metabolism ; Temperature ; }, abstract = {BACKGROUND: Mutations that increase gene expression are predicted to increase energy allocation to transcription, translation and protein function. Despite an appreciation that energetic tradeoffs may constrain adaptation, the energetic costs of increased gene expression are challenging to quantify and thus easily ignored when modeling the evolution of gene expression, particularly for multicellular organisms. Here we use the well-characterized, inducible heat-shock response to test whether expressing additional copies of the Hsp70 gene increases energetic demand in Drosophila melanogaster.

RESULTS: We measured metabolic rates of larvae with different copy numbers of the Hsp70 gene to quantify energy expenditure before, during, and after exposure to 36°C, a temperature known to induce robust expression of Hsp70. We observed a rise in metabolic rate within the first 30 minutes of 36°C exposure above and beyond the increase in routine metabolic rate at 36°C. The magnitude of this increase in metabolic rate was positively correlated with Hsp70 gene copy number and reflected an increase as great as 35% of the 22°C metabolic rate. Gene copy number also affected Hsp70 mRNA levels as early as 15 minutes after larvae were placed at 36°C, demonstrating that gene copy number affects transcript abundance on the same timescale as the metabolic effects that we observed. Inducing Hsp70 also had lasting physiological costs, as larvae had significantly depressed metabolic rate when returned to 22°C after induction.

CONCLUSIONS: Our results demonstrate both immediate and persistent energetic consequences of gene copy number in a multicellular organism. We discuss these consequences in the context of existing literature on the pleiotropic effects of variation in Hsp70 copy number, and argue that the increased energetic demand of expressing extra copies of Hsp70 may contribute to known tradeoffs in physiological performance of extra-copy larvae. Physiological costs of mutations that greatly increase gene expression, such as these, may constrain their utility for adaptive evolution.}, } @article {pmid23504484, year = {2013}, author = {Ciarletta, P and Ambrosi, D and Maugin, GA and Preziosi, L}, title = {Mechano-transduction in tumour growth modelling.}, journal = {The European physical journal. E, Soft matter}, volume = {36}, number = {3}, pages = {23}, pmid = {23504484}, issn = {1292-895X}, mesh = {Animals ; Cell Proliferation ; Humans ; *Mechanotransduction, Cellular ; *Models, Biological ; Neoplasms/*pathology ; Thermodynamics ; }, abstract = {The evolution of biological systems is strongly influenced by physical factors, such as applied forces, geometry or the stiffness of the micro-environment. Mechanical changes are particularly important in solid tumour development, as altered stromal-epithelial interactions can provoke a persistent increase in cytoskeletal tension, driving the gene expression of a malignant phenotype. In this work, we propose a novel multi-scale treatment of mechano-transduction in cancer growth. The avascular tumour is modelled as an expanding elastic spheroid, whilst growth may occur both as a volume increase and as a mass production within a cell rim. Considering the physical constraints of an outer healthy tissue, we derive the thermo-dynamical requirements for coupling growth rate, solid stress and diffusing biomolecules inside a heterogeneous tumour. The theoretical predictions successfully reproduce the stress-dependent growth curves observed by in vitro experiments on multicellular spheroids.}, } @article {pmid23503846, year = {2013}, author = {Collén, J and Porcel, B and Carré, W and Ball, SG and Chaparro, C and Tonon, T and Barbeyron, T and Michel, G and Noel, B and Valentin, K and Elias, M and Artiguenave, F and Arun, A and Aury, JM and Barbosa-Neto, JF and Bothwell, JH and Bouget, FY and Brillet, L and Cabello-Hurtado, F and Capella-Gutiérrez, S and Charrier, B and Cladière, L and Cock, JM and Coelho, SM and Colleoni, C and Czjzek, M and Da Silva, C and Delage, L and Denoeud, F and Deschamps, P and Dittami, SM and Gabaldón, T and Gachon, CM and Groisillier, A and Hervé, C and Jabbari, K and Katinka, M and Kloareg, B and Kowalczyk, N and Labadie, K and Leblanc, C and Lopez, PJ and McLachlan, DH and Meslet-Cladiere, L and Moustafa, A and Nehr, Z and Nyvall Collén, P and Panaud, O and Partensky, F and Poulain, J and Rensing, SA and Rousvoal, S and Samson, G and Symeonidi, A and Weissenbach, J and Zambounis, A and Wincker, P and Boyen, C}, title = {Genome structure and metabolic features in the red seaweed Chondrus crispus shed light on evolution of the Archaeplastida.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {13}, pages = {5247-5252}, pmid = {23503846}, issn = {1091-6490}, mesh = {Base Sequence ; Chondrus/*genetics ; *Evolution, Molecular ; *Genes, Plant ; MicroRNAs/genetics ; Molecular Sequence Data ; Plant Proteins/genetics ; RNA, Plant/genetics ; }, abstract = {Red seaweeds are key components of coastal ecosystems and are economically important as food and as a source of gelling agents, but their genes and genomes have received little attention. Here we report the sequencing of the 105-Mbp genome of the florideophyte Chondrus crispus (Irish moss) and the annotation of the 9,606 genes. The genome features an unusual structure characterized by gene-dense regions surrounded by repeat-rich regions dominated by transposable elements. Despite its fairly large size, this genome shows features typical of compact genomes, e.g., on average only 0.3 introns per gene, short introns, low median distance between genes, small gene families, and no indication of large-scale genome duplication. The genome also gives insights into the metabolism of marine red algae and adaptations to the marine environment, including genes related to halogen metabolism, oxylipins, and multicellularity (microRNA processing and transcription factors). Particularly interesting are features related to carbohydrate metabolism, which include a minimalistic gene set for starch biosynthesis, the presence of cellulose synthases acquired before the primary endosymbiosis showing the polyphyly of cellulose synthesis in Archaeplastida, and cellulases absent in terrestrial plants as well as the occurrence of a mannosylglycerate synthase potentially originating from a marine bacterium. To explain the observations on genome structure and gene content, we propose an evolutionary scenario involving an ancestral red alga that was driven by early ecological forces to lose genes, introns, and intergenetic DNA; this loss was followed by an expansion of genome size as a consequence of activity of transposable elements.}, } @article {pmid23499811, year = {2013}, author = {Mokhtar, M}, title = {Investigating the properties of bio-chemical networks of artificial organisms with opposing behaviours.}, journal = {Bio Systems}, volume = {112}, number = {2}, pages = {73-84}, doi = {10.1016/j.biosystems.2013.03.011}, pmid = {23499811}, issn = {1872-8324}, mesh = {Algorithms ; Animals ; Biological Evolution ; Cell Communication ; Eukaryotic Cells/*metabolism ; *Gene Regulatory Networks ; Homeostasis ; Humans ; *Metabolic Networks and Pathways ; Models, Biological ; Prokaryotic Cells/*metabolism ; Signal Transduction ; }, abstract = {Organisms, be it singled-celled organisms or multi-cellular organisms, are constantly faced with opposing objectives requiring different sets of behaviours. These behaviours can be classified into two, predatory behaviours or anti-prey behaviours, with one set of behaviours causing an opposite effect to the other. A healthy organism aims to achieve its equilibrium state or to be in homeostasis. Homeostasis is achieved when a balance between the two opposing behaviours is created and maintained. This raises some questions: is there an innate mechanism that encodes for these categories of behaviours? Is there also an innate mechanism(s) that resolves conflicts and allows switching between these two opposing behaviours? If we consider artificial organisms as single-celled organisms, how do the organisms' gene regulatory network, metabolic network and/or signalling network (their biochemical networks) maintain homeostasis of the organisms? This paper investigates the properties of the networks of best evolved artificial organisms, in order to help answer these questions, and guide the evolutionary development of controllers for artificial systems.}, } @article {pmid23494299, year = {2013}, author = {Schilde, C and Schaap, P}, title = {The Amoebozoa.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {983}, number = {}, pages = {1-15}, pmid = {23494299}, issn = {1940-6029}, support = {BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amoebozoa/classification/cytology/physiology ; Biological Evolution ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dictyostelium/*cytology/physiology ; Morphogenesis ; Phylogeny ; Protozoan Proteins/metabolism ; Signal Transduction ; Spores, Protozoan/cytology/physiology ; }, abstract = {The model organism Dictyostelium discoideum is a member of the Amoebozoa, one of the six major -divisions of eukaryotes. Amoebozoa comprise a wide variety of amoeboid and flagellate organisms with single cells measuring from 5 μm to several meters across. They have adopted many different life styles and sexual behaviors and can live in all but the most extreme environments. This chapter provides an overview of Amoebozoan diversity and compares roads towards multicellularity within the Amoebozoa with inventions of multicellularity in other protist divisions. The chapter closes with a scenario for the evolution of Dictyostelid multicellularity from an Amoebozoan stress response.}, } @article {pmid23484080, year = {2013}, author = {Lim, JJ and Kim, HJ and Kim, KS and Hong, JY and Lee, DR}, title = {In vitro culture-induced pluripotency of human spermatogonial stem cells.}, journal = {BioMed research international}, volume = {2013}, number = {}, pages = {143028}, pmid = {23484080}, issn = {2314-6141}, mesh = {Animals ; Antigens, Differentiation/*biosynthesis ; Cells, Cultured ; Embryoid Bodies/cytology/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology/*metabolism ; Male ; Mice ; Mice, SCID ; Spermatogonia/cytology/*metabolism ; }, abstract = {Unipotent spermatogonial stem cells (SSCs) can be transformed into ESC-like cells that exhibit pluripotency in vitro. However, except for mouse models, their characterization and their origins have remained controversies in other models including humans. This controversy has arisen primarily from the lack of the direct induction of ESC-like cells from well-characterized SSCs. Thus, the aim of the present study was to find and characterize pluripotent human SSCs in in vitro cultures of characterized SSCs. Human testicular tissues were dissociated and plated onto gelatin/laminin-coated dishes to isolate SSCs. In the presence of growth factors SSCs formed multicellular clumps after 2-4 weeks of culture. At passages 1 and 5, the clumps were dissociated and were then analyzed using markers of pluripotent cells. The number of SSEA-4-positive cells was extremely low but increased gradually up to ~ 10% in the SSC clumps during culture. Most of the SSEA-4-negative cells expressed markers for SSCs, and some cells coexpressed markers of both pluripotent and germ cells. The pluripotent cells formed embryoid bodies and teratomas that contained derivatives of the three germ layers in SCID mice. These results suggest that the pluripotent cells present within the clumps were derived directly from SSCs during in vitro culture.}, } @article {pmid23481191, year = {2013}, author = {Hulpiau, P and Gul, IS and van Roy, F}, title = {New insights into the evolution of metazoan cadherins and catenins.}, journal = {Progress in molecular biology and translational science}, volume = {116}, number = {}, pages = {71-94}, doi = {10.1016/B978-0-12-394311-8.00004-2}, pmid = {23481191}, issn = {1878-0814}, mesh = {Animals ; *Biological Evolution ; Cadherins/*genetics/metabolism ; Catenins/*genetics/metabolism ; }, abstract = {E-Cadherin and β-catenin are the best studied representatives of the superfamilies of transmembrane cadherins and intracellular armadillo catenins, respectively. However, in over 600 million years of multicellular animal evolution, these two superfamilies have diversified remarkably both structurally and functionally. Although their basic building blocks, respectively, the cadherin repeat domain and the armadillo repeat domain, predate metazoans, the specific and complex domain compositions of the different family members and their functional roles in cell adhesion and signaling appear to be key features for the emergence of multicellular animal life. Basal animals such as placozoans and sponges have a limited number of distinct cadherins and catenins. The origin of vertebrates, in particular, coincided with a large increase in the number of cadherins and armadillo proteins, including modern "classical" cadherins, protocadherins, and plakophilins. Also, α-catenins increased. This chapter introduces the many different family members and describes the putative evolutionary relationships between them.}, } @article {pmid23471616, year = {2013}, author = {Römling, U and Galperin, MY and Gomelsky, M}, title = {Cyclic di-GMP: the first 25 years of a universal bacterial second messenger.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {77}, number = {1}, pages = {1-52}, pmid = {23471616}, issn = {1098-5557}, support = {//Intramural NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Bacteria/classification/genetics/metabolism/*pathogenicity ; *Bacterial Physiological Phenomena ; Cyclic GMP/*analogs & derivatives/chemistry/genetics/metabolism ; Eukaryotic Cells/metabolism/microbiology ; *Gene Expression Regulation, Bacterial ; Humans ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Second Messenger Systems/genetics/*physiology ; }, abstract = {Twenty-five years have passed since the discovery of cyclic dimeric (3'→5') GMP (cyclic di-GMP or c-di-GMP). From the relative obscurity of an allosteric activator of a bacterial cellulose synthase, c-di-GMP has emerged as one of the most common and important bacterial second messengers. Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Cyclic di-GMP plays key roles in lifestyle changes of many bacteria, including transition from the motile to the sessile state, which aids in the establishment of multicellular biofilm communities, and from the virulent state in acute infections to the less virulent but more resilient state characteristic of chronic infectious diseases. From a practical standpoint, modulating c-di-GMP signaling pathways in bacteria could represent a new way of controlling formation and dispersal of biofilms in medical and industrial settings. Cyclic di-GMP participates in interkingdom signaling. It is recognized by mammalian immune systems as a uniquely bacterial molecule and therefore is considered a promising vaccine adjuvant. The purpose of this review is not to overview the whole body of data in the burgeoning field of c-di-GMP-dependent signaling. Instead, we provide a historic perspective on the development of the field, emphasize common trends, and illustrate them with the best available examples. We also identify unresolved questions and highlight new directions in c-di-GMP research that will give us a deeper understanding of this truly universal bacterial second messenger.}, } @article {pmid23468928, year = {2013}, author = {Hamaji, T and Smith, DR and Noguchi, H and Toyoda, A and Suzuki, M and Kawai-Toyooka, H and Fujiyama, A and Nishii, I and Marriage, T and Olson, BJ and Nozaki, H}, title = {Mitochondrial and plastid genomes of the colonial green alga Gonium pectorale give insights into the origins of organelle DNA architecture within the volvocales.}, journal = {PloS one}, volume = {8}, number = {2}, pages = {e57177}, pmid = {23468928}, issn = {1932-6203}, mesh = {Chlorophyta/classification/*genetics ; Gene Order ; *Genome, Mitochondrial ; *Genome, Plastid ; Phylogeny ; Volvox/classification/genetics ; }, abstract = {Volvocalean green algae have among the most diverse mitochondrial and plastid DNAs (mtDNAs and ptDNAs) from the eukaryotic domain. However, nearly all of the organelle genome data from this group are restricted to unicellular species, like Chlamydomonas reinhardtii, and presently only one multicellular species, the ∼4,000-celled Volvox carteri, has had its organelle DNAs sequenced. The V. carteri organelle genomes are repeat rich, and the ptDNA is the largest plastome ever sequenced. Here, we present the complete mtDNA and ptDNA of the colonial volvocalean Gonium pectorale, which is comprised of ∼16 cells and occupies a phylogenetic position closer to that of V. carteri than C. reinhardtii within the volvocine line. The mtDNA and ptDNA of G. pectorale are circular-mapping AT-rich molecules with respective lengths and coding densities of 16 and 222.6 kilobases and 73 and 44%. They share some features with the organelle DNAs of V. carteri, including palindromic repeats within the plastid compartment, but show more similarities with those of C. reinhardtii, such as a compact mtDNA architecture and relatively low organelle DNA intron contents. Overall, the G. pectorale organelle genomes raise several interesting questions about the origin of linear mitochondrial chromosomes within the Volvocales and the relationship between multicellularity and organelle genome expansion.}, } @article {pmid23455615, year = {2013}, author = {Iida, H and Ota, S and Inouye, I}, title = {Cleavage, incomplete inversion, and cytoplasmic bridges in Gonium pectorale (Volvocales, Chlorophyta).}, journal = {Journal of plant research}, volume = {126}, number = {5}, pages = {699-707}, pmid = {23455615}, issn = {1618-0860}, mesh = {Biological Evolution ; *Cell Division ; Chlorophyta/*embryology/ultrastructure ; Cytoplasm/ultrastructure ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Species Specificity ; Time-Lapse Imaging ; }, abstract = {Multicellularity arose several times in evolution of eukaryotes. The volvocine algae have full range of colonial organization from unicellular to colonies, and thus these algae are well-known models for examining the evolution and mechanisms of multicellularity. Gonium pectorale is a multicellular species of Volvocales and is thought to be one of the first small colonial organisms among the volvocine algae. In these algae, a cytoplasmic bridge is one of the key traits that arose during the evolution of multicellularity. Here, we observed the inversion process and the cytoplasmic bridges in G. pectorale using time-lapse, fluorescence, and electron microscopy. The cytoplasmic bridges were located in the middle region of the cell in 2-, 4-, 8-, and 16-celled stages and in inversion stages. However, there were no cytoplasmic bridges in the mature adult stage. Cytoplasmic bridges and cortical microtubules in G. pectorale suggest that a mechanism of kinesin-microtubule machinery similar to that in other volvocine algae is responsible for inversion in this species.}, } @article {pmid23454078, year = {2013}, author = {Jeltsch, A}, title = {Oxygen, epigenetic signaling, and the evolution of early life.}, journal = {Trends in biochemical sciences}, volume = {38}, number = {4}, pages = {172-176}, doi = {10.1016/j.tibs.2013.02.001}, pmid = {23454078}, issn = {0968-0004}, mesh = {Animals ; Cell Differentiation ; DNA/*chemistry ; DNA Methylation ; *Epigenesis, Genetic ; *Evolution, Molecular ; Genomic Instability ; Origin of Life ; Oxygen/*chemistry ; Phylogeny ; *Signal Transduction ; }, abstract = {After approximately 3 billion years of unicellular life on Earth, multicellular animals appeared some 600 million years ago, followed by the rapid emergence of most animal phyla during the Cambrian radiation. This evolutionary jump was paralleled by an increase in atmospheric oxygen, which I propose allowed the generation of epigenetic signaling systems that are essential for cellular differentiation in animals. Epigenetic signaling is based on the reversible deposition of chemically stable marks in DNA and histone proteins, with methylation of cytosine and lysine residues, respectively, playing a central role. Recent evidence indicates that the removal of such methyl groups critically depends on oxygenases. Hence, reversible epigenetic systems could only appear after accumulation of oxygen in the atmosphere.}, } @article {pmid23449590, year = {2013}, author = {Sakakibara, K and Ando, S and Yip, HK and Tamada, Y and Hiwatashi, Y and Murata, T and Deguchi, H and Hasebe, M and Bowman, JL}, title = {KNOX2 genes regulate the haploid-to-diploid morphological transition in land plants.}, journal = {Science (New York, N.Y.)}, volume = {339}, number = {6123}, pages = {1067-1070}, doi = {10.1126/science.1230082}, pmid = {23449590}, issn = {1095-9203}, mesh = {Bryopsida/*anatomy & histology/genetics/*growth & development ; *Diploidy ; Gene Deletion ; Genes, Plant/*physiology ; Germ Cells, Plant/*growth & development ; *Haploidy ; Homeodomain Proteins/genetics/*physiology ; }, abstract = {Unlike animals, land plants undergo an alternation of generations, producing multicellular bodies in both haploid (1n: gametophyte) and diploid (2n: sporophyte) generations. Plant body plans in each generation are regulated by distinct developmental programs initiated at either meiosis or fertilization, respectively. In mosses, the haploid gametophyte generation is dominant, whereas in vascular plants-including ferns, gymnosperms, and angiosperms-the diploid sporophyte generation is dominant. Deletion of the class 2 KNOTTED1-LIKE HOMEOBOX (KNOX2) transcription factors in the moss Physcomitrella patens results in the development of gametophyte bodies from diploid embryos without meiosis. Thus, KNOX2 acts to prevent the haploid-specific body plan from developing in the diploid plant body, indicating a critical role for the evolution of KNOX2 in establishing an alternation of generations in land plants.}, } @article {pmid23448886, year = {2013}, author = {Solari, CA and Kessler, JO and Goldstein, RE}, title = {A general allometric and life-history model for cellular differentiation in the transition to multicellularity.}, journal = {The American naturalist}, volume = {181}, number = {3}, pages = {369-380}, doi = {10.1086/669151}, pmid = {23448886}, issn = {1537-5323}, support = {BB/F021844/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Biological Evolution ; Body Size/physiology ; Cell Differentiation/*physiology ; Chlorophyta/*growth & development ; Fertility/physiology ; Genetic Fitness/genetics/*physiology ; Germ Cells/*cytology ; *Models, Biological ; Reproduction/genetics/physiology ; }, abstract = {The transition from unicellular, to colonial, to larger multicellular organisms has benefits, costs, and requirements. Here we present a model inspired by the volvocine green algae that explains the dynamics involved in the unicellular-multicellular transition using life-history theory and allometry. We model the two fitness components (fecundity and viability) and compare the fitness of hypothetical colonies of different sizes with varying degrees of cellular differentiation to understand the general principles that underlie the evolution of multicellularity. We argue that germ-soma separation may have evolved to counteract the increasing costs and requirements of larger multicellular colonies. The model shows that the cost of investing in soma decreases with size. For lineages such as the Volvocales, as reproduction costs increase with size for undifferentiated colonies, soma specialization benefits the colony indirectly by decreasing such costs and directly by helping reproductive cells acquire resources for their metabolic needs. Germ specialization is favored once soma evolves and takes care of vegetative functions. To illustrate the model, we use some allometric relationships measured in Volvocales. Our analysis shows that the cost of reproducing an increasingly larger group has likely played an important role in the transition to multicellularity and cellular differentiation.}, } @article {pmid23441759, year = {2013}, author = {Xu, R and Rudd, TR and Hughes, AJ and Siligardi, G and Fernig, DG and Yates, EA}, title = {Analysis of the fibroblast growth factor receptor (FGFR) signalling network with heparin as coreceptor: evidence for the expansion of the core FGFR signalling network.}, journal = {The FEBS journal}, volume = {280}, number = {10}, pages = {2260-2270}, doi = {10.1111/febs.12201}, pmid = {23441759}, issn = {1742-4658}, mesh = {Binding Sites ; Circular Dichroism/methods ; Cloning, Molecular ; Evolution, Molecular ; Fibroblast Growth Factor 7/genetics/metabolism ; Fibroblast Growth Factors/genetics/*metabolism ; Genetic Vectors/genetics/metabolism ; Heparin/*metabolism ; Heparitin Sulfate/metabolism ; Humans ; Multiprotein Complexes/metabolism ; Protein Binding ; Protein Interaction Mapping/methods ; Protein Structure, Secondary ; Receptor, Fibroblast Growth Factor, Type 1/metabolism ; Receptor, Fibroblast Growth Factor, Type 2/*metabolism ; *Signal Transduction ; }, abstract = {The evolution of the fibroblast growth factor (FGF)-FGF receptor (FGFR) signalling system has closely followed that of multicellular organisms. The abilities of nine FGFs (FGF-1 to FGF-9; examples of FGF subfamilies 1, 4, 7, 8, and 9) and seven FGFRs or isoforms (FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, FGFR3c, and FGFR4) to support signalling in the presence of heparin, a proxy for the cellular heparan sulfate coreceptor, were assembled into a network. A connection between two FGFRs was defined as their mutual ability to signal with a particular FGF. The network contained a core of four receptors (FGFR1c, FGFR2c, FGFR3c, and FGFR4) with complete connectivity and high redundancy. Analysis of the wider network indicated that neither FGF-3 nor FGF-7 was well connected to this core of four receptors, and that divergence of a precursor of FGF subgroups 1, 4 and 9 from FGF subgroup 8 may have allowed expansion from a three-member FGFR core signalling system to the four-member core network. This increases by four-fold the number of possible signalling combinations. Synchrotron radiation CD spectra of the FGFs with heparin revealed no overall common structural change, suggesting the existence of distinct heparin-binding sites throughout the FGFs. The approach provides a potential method of identifying agents capable of influencing particular FGF-FGFR combinations, or areas of the signalling network, for experimental or therapeutic purposes.}, } @article {pmid23437009, year = {2013}, author = {Suvorova, ES and Croken, M and Kratzer, S and Ting, LM and Conde de Felipe, M and Balu, B and Markillie, ML and Weiss, LM and Kim, K and White, MW}, title = {Discovery of a splicing regulator required for cell cycle progression.}, journal = {PLoS genetics}, volume = {9}, number = {2}, pages = {e1003305}, pmid = {23437009}, issn = {1553-7404}, support = {AI93220/AI/NIAID NIH HHS/United States ; P30AI051519/AI/NIAID NIH HHS/United States ; RC4 AI092801/AI/NIAID NIH HHS/United States ; R01 AI089885/AI/NIAID NIH HHS/United States ; R01AI087625/AI/NIAID NIH HHS/United States ; R01 AI077662/AI/NIAID NIH HHS/United States ; R01 AI095094/AI/NIAID NIH HHS/United States ; P30 AI051519/AI/NIAID NIH HHS/United States ; 1S10RR019352/RR/NCRR NIH HHS/United States ; R01 AI087625/AI/NIAID NIH HHS/United States ; RC4AI092801/AI/NIAID NIH HHS/United States ; T32GM007491/GM/NIGMS NIH HHS/United States ; 1S10RR021056/RR/NCRR NIH HHS/United States ; R01AI077662/AI/NIAID NIH HHS/United States ; R56 AI093220/AI/NIAID NIH HHS/United States ; S10 RR019352/RR/NCRR NIH HHS/United States ; T32 GM007491/GM/NIGMS NIH HHS/United States ; R01AI095094/AI/NIAID NIH HHS/United States ; S10 RR021056/RR/NCRR NIH HHS/United States ; R01AI089885/AI/NIAID NIH HHS/United States ; }, mesh = {Alternative Splicing/*genetics ; Cell Cycle/*genetics ; Conserved Sequence/genetics ; G1 Phase/genetics ; Gene Expression Regulation ; Humans ; Mutation ; Nucleotide Motifs/genetics ; *RNA, Messenger/genetics/metabolism ; *RNA-Binding Proteins/genetics/metabolism ; Sequence Homology, Amino Acid ; Temperature ; *Toxoplasma/genetics/metabolism ; }, abstract = {In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.}, } @article {pmid23431170, year = {2013}, author = {Chang, H and Nathans, J}, title = {Responses of hair follicle-associated structures to loss of planar cell polarity signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {10}, pages = {E908-17}, pmid = {23431170}, issn = {1091-6490}, support = {//Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Body Patterning/physiology ; Cell Polarity/*physiology ; Female ; Frizzled Receptors/deficiency/genetics/physiology ; Hair Follicle/*cytology/growth & development/physiology ; Merkel Cells/physiology ; Mice ; Mice, Knockout ; Muscle, Smooth/cytology ; Nerve Endings/ultrastructure ; Pregnancy ; Sebaceous Glands/cytology ; Signal Transduction/physiology ; Skin/cytology/innervation ; }, abstract = {The mammalian hair follicle unit consists of a central follicle and a series of associated structures: sebaceous glands, arrector pili muscles, Merkel cells, and sensory nerve endings. The architecture of this multicellular structure is highly polarized with respect to the body axes. Previous work has implicated Frizzled6 (Fz6)-mediated planar cell polarity (PCP) signaling in the initial specification of hair follicle orientation. Here we investigate the origin of polarity information among structures within the hair follicle unit. Merkel cell clusters appear to have direct access to Fz6-based polarity information, and they lose polarity in the absence of Fz6. By contrast, the other follicle-associated structures likely derive some or all of their polarity cues from hair follicles, and as a result, their orientations closely match that of their associated follicle. These experiments reveal the interplay between global and local sources of polarity information for coordinating the spatial arrangement of diverse multicellular structures. They also highlight the utility of mammalian skin as a system for quantitative analyses of biological polarity.}, } @article {pmid23425690, year = {2013}, author = {Hsieh, JC and Van Den Berg, D and Kang, H and Hsieh, CL and Lieber, MR}, title = {Large chromosome deletions, duplications, and gene conversion events accumulate with age in normal human colon crypts.}, journal = {Aging cell}, volume = {12}, number = {2}, pages = {269-279}, pmid = {23425690}, issn = {1474-9726}, support = {R01 CA100504/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/*genetics/pathology ; *Chromosome Deletion ; *Chromosome Duplication ; Chromosomes ; Colon/*metabolism/pathology ; DNA Copy Number Variations ; DNA Methylation ; Female ; *Gene Conversion ; Genome, Human ; Humans ; Loss of Heterozygosity ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; }, abstract = {Little is known about the types and numbers of mutations that may accumulate in normal human cells with age. Such information would require obtaining enough DNA from a single cell to accurately carry out reliable analysis despite extensive amplification; and complete genomic coverage under these circumstances is difficult. We have compared colon crypts, which are putatively clonal and contain ~2000 cells each, to determine how much somatic genetic variation occurs in vivo (without ex vivo cell culturing). Using high-density SNP microarrays, we find that chromosome deletions, duplications, and gene conversions were significantly more frequent in colons from the older individuals. These changes affected lengths ranging from 73 kb to 46 Mb. Although detection requires progeny of a single mutant stem cell to reach niche dominance over neighboring stem cells, none of the deletions appear likely to confer a selective advantage. Mutations can become fixed randomly during stem cell evolution through neutral drift in normal human crypts. The fact that chromosomal changes are detected in individual crypts with increasing age suggests that either such changes accumulate with age or single stem cell dominance increases with age, and the former is more likely. This progressive genome-wide divergence of human somatic cells with age has implications for aging and disease in multicellular organisms.}, } @article {pmid23419129, year = {2013}, author = {Fairclough, SR and Chen, Z and Kramer, E and Zeng, Q and Young, S and Robertson, HM and Begovic, E and Richter, DJ and Russ, C and Westbrook, MJ and Manning, G and Lang, BF and Haas, B and Nusbaum, C and King, N}, title = {Premetazoan genome evolution and the regulation of cell differentiation in the choanoflagellate Salpingoeca rosetta.}, journal = {Genome biology}, volume = {14}, number = {2}, pages = {R15}, pmid = {23419129}, issn = {1474-760X}, support = {R01 GM089977/GM/NIGMS NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; T32 HG 00047/HG/NHGRI NIH HHS/United States ; R01 HG004164/HG/NHGRI NIH HHS/United States ; }, mesh = {Choanoflagellata/*genetics/physiology ; Cytokinesis/genetics ; *Evolution, Molecular ; *Genome, Protozoan ; Protozoan Proteins/genetics/metabolism ; Septins/genetics/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Metazoan multicellularity is rooted in mechanisms of cell adhesion, signaling, and differentiation that first evolved in the progenitors of metazoans. To reconstruct the genome composition of metazoan ancestors, we sequenced the genome and transcriptome of the choanoflagellate Salpingoeca rosetta, a close relative of metazoans that forms rosette-shaped colonies of cells.

RESULTS: A comparison of the 55 Mb S. rosetta genome with genomes from diverse opisthokonts suggests that the origin of metazoans was preceded by a period of dynamic gene gain and loss. The S. rosetta genome encodes homologs of cell adhesion, neuropeptide, and glycosphingolipid metabolism genes previously found only in metazoans and expands the repertoire of genes inferred to have been present in the progenitors of metazoans and choanoflagellates. Transcriptome analysis revealed that all four S. rosetta septins are upregulated in colonies relative to single cells, suggesting that these conserved cytokinesis proteins may regulate incomplete cytokinesis during colony development. Furthermore, genes shared exclusively by metazoans and choanoflagellates were disproportionately upregulated in colonies and the single cells from which they develop.

CONCLUSIONS: The S. rosetta genome sequence refines the catalog of metazoan-specific genes while also extending the evolutionary history of certain gene families that are central to metazoan biology. Transcriptome data suggest that conserved cytokinesis genes, including septins, may contribute to S. rosetta colony formation and indicate that the initiation of colony development may preferentially draw upon genes shared with metazoans, while later stages of colony maturation are likely regulated by genes unique to S. rosetta.}, } @article {pmid23402598, year = {2013}, author = {Lerche, K and Hallmann, A}, title = {Stable nuclear transformation of Eudorina elegans.}, journal = {BMC biotechnology}, volume = {13}, number = {}, pages = {11}, pmid = {23402598}, issn = {1472-6750}, mesh = {Cell Nucleus/*metabolism ; Chlamydomonas reinhardtii/genetics ; Chlorophyta/genetics/*metabolism ; Genes, Reporter ; Genetic Engineering ; Kanamycin Kinase/genetics/metabolism ; Luciferases/genetics/metabolism ; Paromomycin/pharmacology ; Plasmids/genetics/metabolism ; Promoter Regions, Genetic ; Streptomyces/genetics ; Transformation, Genetic/drug effects ; Volvox/genetics ; }, abstract = {BACKGROUND: A fundamental step in evolution was the transition from unicellular to differentiated, multicellular organisms. Volvocine algae have been used for several decades as a model lineage to investigate the evolutionary aspects of multicellularity and cellular differentiation. There are two well-studied volvocine species, a unicellular alga (Chlamydomonas reinhardtii) and a multicellular alga with differentiated cell types (Volvox carteri). Species with intermediate characteristics also exist, which blur the boundaries between unicellularity and differentiated multicellularity. These species include the globular alga Eudorina elegans, which is composed of 16-32 cells. However, detailed molecular analyses of E. elegans require genetic manipulation. Unfortunately, genetic engineering has not yet been established for Eudorina, and only limited DNA and/or protein sequence information is available.

RESULTS: Here, we describe the stable nuclear transformation of E. elegans by particle bombardment using both a chimeric selectable marker and reporter genes from different heterologous sources. Transgenic algae resistant to paromomycin were achieved using the aminoglycoside 3'-phosphotransferase VIII (aphVIII) gene of Streptomyces rimosus, an actinobacterium, under the control of an artificial promoter consisting of two V. carteri promoters in tandem. Transformants exhibited an increase in resistance to paromomycin by up to 333-fold. Co-transformation with non-selectable plasmids was achieved with a rate of 50 - 100%. The luciferase (gluc) gene from the marine copepod Gaussia princeps, which previously was engineered to match the codon usage of C. reinhardtii, was used as a reporter gene. The expression of gluc was mediated by promoters from C. reinhardtii and V. carteri. Heterologous heat shock promoters induced an increase in luciferase activity (up to 600-fold) at elevated temperatures. Long-term stability and both constitutive and inducible expression of the co-bombarded gluc gene was demonstrated by transcription analysis and bioluminescence assays.

CONCLUSIONS: Heterologous flanking sequences, including promoters, work in E. elegans and permit both constitutive and inducible expression of heterologous genes. Stable nuclear transformation of E. elegans is now routine. Thus, we show that genetic engineering of a species is possible even without the resources of endogenous genes and promoters.}, } @article {pmid23398683, year = {2013}, author = {Schultheiss, KP and Craddock, BP and Tong, M and Seeliger, M and Miller, WT}, title = {Metazoan-like signaling in a unicellular receptor tyrosine kinase.}, journal = {BMC biochemistry}, volume = {14}, number = {}, pages = {4}, pmid = {23398683}, issn = {1471-2091}, support = {CA58530/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cell Line ; Choanoflagellata/*enzymology/metabolism ; Mice ; Molecular Sequence Data ; Phosphorylation ; Protein Structure, Tertiary ; Protozoan Proteins/chemistry/genetics/*metabolism ; Receptor Protein-Tyrosine Kinases/chemistry/genetics/*metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid ; *Signal Transduction ; Transfection ; }, abstract = {BACKGROUND: Receptor tyrosine kinases (RTKs) are crucial components of signal transduction systems in multicellular animals. Surprisingly, numerous RTKs have been identified in the genomes of unicellular choanoflagellates and other protists. Here, we report the first biochemical study of a unicellular RTK, namely RTKB2 from Monosiga brevicollis.

RESULTS: We cloned, expressed, and purified the RTKB2 kinase, and showed that it is enzymatically active. The activity of RTKB2 is controlled by autophosphorylation, as in metazoan RTKs. RTKB2 possesses six copies of a unique domain (designated RM2) in its C-terminal tail. An isolated RM2 domain (or a synthetic peptide derived from the RM2 sequence) served as a substrate for RTKB2 kinase. When phosphorylated, the RM2 domain bound to the Src homology 2 domain of MbSrc1 from M. brevicollis. NMR structural studies of the RM2 domain indicated that it is disordered in solution.

CONCLUSIONS: Our results are consistent with a model in which RTKB2 activation stimulates receptor autophosphorylation within the RM2 domains. This leads to recruitment of Src-like kinases (and potentially other M. brevicollis proteins) and further phosphorylation, which may serve to increase or dampen downstream signals. Thus, crucial features of signal transduction circuitry were established prior to the evolution of metazoans from their unicellular ancestors.}, } @article {pmid23397797, year = {2012}, author = {Gilbert, SF and Sapp, J and Tauber, AI}, title = {A symbiotic view of life: we have never been individuals.}, journal = {The Quarterly review of biology}, volume = {87}, number = {4}, pages = {325-341}, doi = {10.1086/668166}, pmid = {23397797}, issn = {0033-5770}, mesh = {Animals ; Humans ; *Symbiosis ; }, abstract = {The notion of the "biological individual" is crucial to studies of genetics, immunology, evolution, development, anatomy, and physiology. Each of these biological subdisciplines has a specific conception of individuality, which has historically provided conceptual contexts for integrating newly acquired data. During the past decade, nucleic acid analysis, especially genomic sequencing and high-throughput RNA techniques, has challenged each of these disciplinary definitions by finding significant interactions of animals and plants with symbiotic microorganisms that disrupt the boundaries that heretofore had characterized the biological individual. Animals cannot be considered individuals by anatomical or physiological criteria because a diversity of symbionts are both present and functional in completing metabolic pathways and serving other physiological functions. Similarly, these new studies have shown that animal development is incomplete without symbionts. Symbionts also constitute a second mode of genetic inheritance, providing selectable genetic variation for natural selection. The immune system also develops, in part, in dialogue with symbionts and thereby functions as a mechanism for integrating microbes into the animal-cell community. Recognizing the "holobiont"--the multicellular eukaryote plus its colonies of persistent symbionts--as a critically important unit of anatomy, development, physiology, immunology, and evolution opens up new investigative avenues and conceptually challenges the ways in which the biological subdisciplines have heretofore characterized living entities.}, } @article {pmid23395845, year = {2014}, author = {Benito, N and Fernández-Ruiz, A and Makarov, VA and Makarova, J and Korovaichuk, A and Herreras, O}, title = {Spatial modules of coherent activity in pathway-specific LFPs in the hippocampus reflect topology and different modes of presynaptic synchronization.}, journal = {Cerebral cortex (New York, N.Y. : 1991)}, volume = {24}, number = {7}, pages = {1738-1752}, doi = {10.1093/cercor/bht022}, pmid = {23395845}, issn = {1460-2199}, mesh = {Animals ; Bicuculline/pharmacology ; Electric Stimulation ; Evoked Potentials/drug effects/*physiology ; Excitatory Amino Acid Antagonists/pharmacology ; Female ; Functional Laterality ; GABA-A Receptor Antagonists/pharmacology ; Hippocampus/*cytology/physiology ; *Models, Neurological ; Nerve Net/drug effects/*physiology ; Neurons/*cytology/drug effects/physiology ; Perforant Pathway/physiology ; Presynaptic Terminals/drug effects/*physiology ; Quinoxalines/pharmacology ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Ongoing network activity often manifests as irregular fluctuations in local field potentials (LFPs), a complex mixture of multicellular synaptic currents of varying locations and extensions. Among other conditions, for synchronously firing presynaptic units to generate sizable postsynaptic LFPs, their axonal territories should overlap. We have taken advantage of anatomical regularity of the rat hippocampus and combined multiple linear recordings and spatial discrimination techniques to separate pathway-specific LFPs with enough spatial resolution to discriminate postsynaptic regions of varying activation, and to investigate their presynaptic origin, chemical nature, and spatial extension. We identified 6 main excitatory and inhibitory LFP generators with different synaptic territories in principal cells and hippocampal subfields matching anatomical pathways. Some recognized pathways did not contribute notably to LFPs. Each showed different septo-temporal spatial modules over which the field potential fluctuations were synchronous. These modules were explained by either the strong overlap of synaptic territories of coactivated afferent neurons (e.g., CA3 clusters for CA1 Schaffer LFPs), or widespread coalescence of postsynaptic territories (granule cell somatic inhibition). We also show evidence that distinct modes of afferent synchronization generate stereotyped spatial patterns of synchronous LFPs in one pathway. Thus, studying spatial coherence of pathway-specific LFPs provides remote access to the dynamics of afferent populations.}, } @article {pmid23393190, year = {2013}, author = {Sanges, R and Hadzhiev, Y and Gueroult-Bellone, M and Roure, A and Ferg, M and Meola, N and Amore, G and Basu, S and Brown, ER and De Simone, M and Petrera, F and Licastro, D and Strähle, U and Banfi, S and Lemaire, P and Birney, E and Müller, F and Stupka, E}, title = {Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development.}, journal = {Nucleic acids research}, volume = {41}, number = {6}, pages = {3600-3618}, pmid = {23393190}, issn = {1362-4962}, support = {TGM11SB2/TI_/Telethon/Italy ; }, mesh = {Animals ; Base Sequence ; Conserved Sequence ; Dogs ; *Enhancer Elements, Genetic ; Fishes/genetics ; *Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Genes, Homeobox ; Genetic Loci ; Genome ; Humans ; Mammals/genetics ; Mice ; Synteny ; Transcription, Genetic ; Urochordata/*genetics ; Vertebrates/*genetics ; }, abstract = {Co-option of cis-regulatory modules has been suggested as a mechanism for the evolution of expression sites during development. However, the extent and mechanisms involved in mobilization of cis-regulatory modules remains elusive. To trace the history of non-coding elements, which may represent candidate ancestral cis-regulatory modules affirmed during chordate evolution, we have searched for conserved elements in tunicate and vertebrate (Olfactores) genomes. We identified, for the first time, 183 non-coding sequences that are highly conserved between the two groups. Our results show that all but one element are conserved in non-syntenic regions between vertebrate and tunicate genomes, while being syntenic among vertebrates. Nevertheless, in all the groups, they are significantly associated with transcription factors showing specific functions fundamental to animal development, such as multicellular organism development and sequence-specific DNA binding. The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. We refer to the elements as 'Olfactores conserved non-coding elements'.}, } @article {pmid23388496, year = {2013}, author = {Eickel, N and Kaiser, G and Prado, M and Burda, PC and Roelli, M and Stanway, RR and Heussler, VT}, title = {Features of autophagic cell death in Plasmodium liver-stage parasites.}, journal = {Autophagy}, volume = {9}, number = {4}, pages = {568-580}, pmid = {23388496}, issn = {1554-8635}, mesh = {Amino Acid Sequence ; Animals ; *Autophagy ; Conserved Sequence ; Databases, Protein ; Evolution, Molecular ; Gene Knockout Techniques ; Genetic Complementation Test ; Green Fluorescent Proteins/metabolism ; Hep G2 Cells ; Humans ; *Life Cycle Stages ; Lipid Metabolism ; Liver/*parasitology ; Mice ; Molecular Sequence Data ; Parasites/*cytology/*growth & development/ultrastructure ; Phagosomes/metabolism/ultrastructure ; Plasmodium berghei/*cytology/*growth & development/ultrastructure ; Protein Transport ; Protozoan Proteins/metabolism ; Saccharomyces cerevisiae/metabolism ; Schizonts/cytology/metabolism/ultrastructure ; Sequence Homology, Amino Acid ; Vacuoles/metabolism ; }, abstract = {Analyzing molecular determinants of Plasmodium parasite cell death is a promising approach for exploring new avenues in the fight against malaria. Three major forms of cell death (apoptosis, necrosis and autophagic cell death) have been described in multicellular organisms but which cell death processes exist in protozoa is still a matter of debate. Here we suggest that all three types of cell death occur in Plasmodium liver-stage parasites. Whereas typical molecular markers for apoptosis and necrosis have not been found in the genome of Plasmodium parasites, we identified genes coding for putative autophagy-marker proteins and thus concentrated on autophagic cell death. We characterized the Plasmodium berghei homolog of the prominent autophagy marker protein Atg8/LC3 and found that it localized to the apicoplast. A relocalization of PbAtg8 to autophagosome-like vesicles or vacuoles that appear in dying parasites was not, however, observed. This strongly suggests that the function of this protein in liver-stage parasites is restricted to apicoplast biology.}, } @article {pmid23386364, year = {2013}, author = {Caicci, F and Gasparini, F and Rigon, F and Zaniolo, G and Burighel, P and Manni, L}, title = {The oral sensory structures of Thaliacea (Tunicata) and consideration of the evolution of hair cells in Chordata.}, journal = {The Journal of comparative neurology}, volume = {521}, number = {12}, pages = {2756-2771}, doi = {10.1002/cne.23313}, pmid = {23386364}, issn = {1096-9861}, mesh = {Afferent Pathways/physiology ; Animals ; Axons/ultrastructure ; *Biological Evolution ; Chordata/*anatomy & histology ; Cilia/ultrastructure ; Hair Cells, Auditory/*physiology/ultrastructure ; Mechanoreceptors/*physiology/ultrastructure ; Microscopy, Electron ; Mouth/physiology ; Urochordata/*anatomy & histology ; }, abstract = {We analyzed the mouth of three species, representative of the three orders of the class Thaliacea (Tunicata)--Pyrosoma atlanticum (Pyrosomatida), Doliolum nationalis (Doliolida), and Thalia democratica (Salpida)--to verify the presence of mechanoreceptors, particularly hair cells. In vertebrates, hair cells are well-known mechanoreceptors of the inner ear and lateral line, typically exhibiting an apical hair bundle composed of a cilium and stereovilli but lacking an axon. For a long time, hair cells were thought to be exclusive to vertebrates. However, evidence of a mechanosensory organ (the coronal organ) employing hair cells in the mouth of tunicates, considered the sister group of vertebrates, suggests that tunicate and vertebrate hair cells may share a common origin. This study on thaliaceans, a tunicate group not yet investigated, shows that both P. atlanticum and D. nationalis possess a coronal organ, in addition to sensory structures containing peripheral neurons (i.e., cupular organs and triads of sensory cells). In contrast, in T. democratica, we did not recognize any oral multicellular sensory organ. We hypothesize that in T. democratica, hair cells were secondarily lost, concomitantly with the loss of branchial fissures, the acquisition of a feeding mechanism based on muscle activity, and a mechanosensory apparatus based on excitable epithelia. Our data are consistent with the hypothesis that hair cells were present in the common ancestor of tunicates and vertebrates, from which hair cells progressively evolved.}, } @article {pmid23385589, year = {2013}, author = {Niu, N and Liang, W and Yang, X and Jin, W and Wilson, ZA and Hu, J and Zhang, D}, title = {EAT1 promotes tapetal cell death by regulating aspartic proteases during male reproductive development in rice.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {1445}, pmid = {23385589}, issn = {2041-1723}, mesh = {Amino Acid Sequence ; Aspartic Acid Proteases/*metabolism ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors/chemistry/genetics/metabolism ; Cell Death ; Chromosomes, Plant/genetics ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Models, Biological ; Molecular Sequence Data ; Mutation/genetics ; Organ Specificity ; Oryza/*cytology/*enzymology/genetics/ultrastructure ; Phenotype ; Phylogeny ; Physical Chromosome Mapping ; Plant Proteins/*chemistry/genetics/metabolism ; Pollen/*cytology/*enzymology/ultrastructure ; Protein Binding ; Reproduction ; Saccharomyces cerevisiae/cytology/metabolism ; }, abstract = {Programmed cell death is essential for the development of multicellular organisms, yet pathways of plant programmed cell death and its regulation remain elusive. Here we report that ETERNAL TAPETUM 1, a basic helix-loop-helix transcription factor conserved in land plants, positively regulates programmed cell death in tapetal cells in rice anthers. eat1 exhibits delayed tapetal cell death and aborted pollen formation. ETERNAL TAPETUM 1 directly regulates the expression of OsAP25 and OsAP37, which encode aspartic proteases that induce programmed cell death in both yeast and plants. Expression and genetic analyses revealed that ETERNAL TAPETUM 1 acts downstream of TAPETUM DEGENERATION RETARDATION, another positive regulator of tapetal programmed cell death, and that ETERNAL TAPETUM 1 can also interact with the TAPETUM DEGENERATION RETARDATION protein. This study demonstrates that ETERNAL TAPETUM 1 promotes aspartic proteases triggering plant programmed cell death, and reveals a dynamic regulatory cascade in male reproductive development in rice.}, } @article {pmid23383067, year = {2013}, author = {Senatore, A and Monteil, A and van Minnen, J and Smit, AB and Spafford, JD}, title = {NALCN ion channels have alternative selectivity filters resembling calcium channels or sodium channels.}, journal = {PloS one}, volume = {8}, number = {1}, pages = {e55088}, pmid = {23383067}, issn = {1932-6203}, mesh = {*Alternative Splicing ; Amino Acid Sequence ; Animals ; Calcium Channels/*chemistry/genetics ; Conserved Sequence ; Evolution, Molecular ; Gene Expression Regulation ; Humans ; Ion Channels ; Membrane Proteins ; Molecular Sequence Data ; Phylogeny ; Porosity ; Protein Isoforms/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Snails ; Sodium Channels/*chemistry/*genetics/metabolism ; }, abstract = {NALCN is a member of the family of ion channels with four homologous, repeat domains that include voltage-gated calcium and sodium channels. NALCN is a highly conserved gene from simple, extant multicellular organisms without nervous systems such as sponges and placozoans and mostly remains a single gene compared to the calcium and sodium channels which diversified into twenty genes in humans. The single NALCN gene has alternatively-spliced exons at exons 15 or exon 31 that splices in novel selectivity filter residues that resemble calcium channels (EEEE) or sodium channels (EKEE or EEKE). NALCN channels with alternative calcium, (EEEE) and sodium, (EKEE or EEKE) -selective pores are conserved in simple bilaterally symmetrical animals like flatworms to non-chordate deuterostomes. The single NALCN gene is limited as a sodium channel with a lysine (K)-containing pore in vertebrates, but originally NALCN was a calcium-like channel, and evolved to operate as both a calcium channel and sodium channel for different roles in many invertebrates. Expression patterns of NALCN-EKEE in pond snail, Lymnaea stagnalis suggest roles for NALCN in secretion, with an abundant expression in brain, and an up-regulation in secretory organs of sexually-mature adults such as albumen gland and prostate. NALCN-EEEE is equally abundant as NALCN-EKEE in snails, but is greater expressed in heart and other muscle tissue, and 50% less expressed in the brain than NALCN-EKEE. Transfected snail NALCN-EEEE and NALCN-EKEE channel isoforms express in HEK-293T cells. We were not able to distinguish potential NALCN currents from background, non-selective leak conductances in HEK293T cells. Native leak currents without expressing NALCN genes in HEK-293T cells are NMDG(+) impermeant and blockable with 10 µM Gd(3+) ions and are indistinguishable from the hallmark currents ascribed to mammalian NALCN currents expressed in vitro by Lu et al. in Cell. 2007 Apr 20;129(2):371-83.}, } @article {pmid23379554, year = {2013}, author = {Gusachenko, ON and Zenkova, MA and Vlassov, VV}, title = {Nucleic acids in exosomes: disease markers and intercellular communication molecules.}, journal = {Biochemistry. Biokhimiia}, volume = {78}, number = {1}, pages = {1-7}, doi = {10.1134/S000629791301001X}, pmid = {23379554}, issn = {1608-3040}, mesh = {Animals ; Biomarkers/analysis/metabolism ; Cell Adhesion Molecules/analysis/*metabolism ; Cell Communication ; Exosomes/*metabolism ; Humans ; Nucleic Acids/*metabolism ; }, abstract = {The term "exosomes" is currently used to describe specific vesicular structures of endosomal origin produced by the majority of eukaryotic cells. These natural vesicles have been under study for more than two decades. Nevertheless, a real splash of scientific interest in studies on exosomes took place only during recent years, when the concept of the role and functions of exosomes in multicellular organisms was essentially reconsidered. The major role in this was played by the discovery of exosomal mRNA and miRNA in 2007, which stimulated the idea of regulatory and communicative role of exosomes in the organism and also encouraged considering exosomes and other vesicles as potential biomarkers. The present review summarizes the up to date knowledge on the composition and probable physiological functions of nucleic acids released by different cells as components of exosomes. We also touch upon the problem of using these data in clinical diagnosis.}, } @article {pmid23375108, year = {2013}, author = {Clarke, M and Lohan, AJ and Liu, B and Lagkouvardos, I and Roy, S and Zafar, N and Bertelli, C and Schilde, C and Kianianmomeni, A and Bürglin, TR and Frech, C and Turcotte, B and Kopec, KO and Synnott, JM and Choo, C and Paponov, I and Finkler, A and Heng Tan, CS and Hutchins, AP and Weinmeier, T and Rattei, T and Chu, JS and Gimenez, G and Irimia, M and Rigden, DJ and Fitzpatrick, DA and Lorenzo-Morales, J and Bateman, A and Chiu, CH and Tang, P and Hegemann, P and Fromm, H and Raoult, D and Greub, G and Miranda-Saavedra, D and Chen, N and Nash, P and Ginger, ML and Horn, M and Schaap, P and Caler, L and Loftus, BJ}, title = {Genome of Acanthamoeba castellanii highlights extensive lateral gene transfer and early evolution of tyrosine kinase signaling.}, journal = {Genome biology}, volume = {14}, number = {2}, pages = {R11}, pmid = {23375108}, issn = {1474-760X}, support = {281633/ERC_/European Research Council/International ; BB/E016308/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Acanthamoeba castellanii/*genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genome, Protozoan ; Introns ; Protein-Tyrosine Kinases/*genetics/metabolism ; Protozoan Proteins/*genetics/metabolism ; *Signal Transduction ; }, abstract = {BACKGROUND: The Amoebozoa constitute one of the primary divisions of eukaryotes, encompassing taxa of both biomedical and evolutionary importance, yet its genomic diversity remains largely unsampled. Here we present an analysis of a whole genome assembly of Acanthamoeba castellanii (Ac) the first representative from a solitary free-living amoebozoan.

RESULTS: Ac encodes 15,455 compact intron-rich genes, a significant number of which are predicted to have arisen through inter-kingdom lateral gene transfer (LGT). A majority of the LGT candidates have undergone a substantial degree of intronization and Ac appears to have incorporated them into established transcriptional programs. Ac manifests a complex signaling and cell communication repertoire, including a complete tyrosine kinase signaling toolkit and a comparable diversity of predicted extracellular receptors to that found in the facultatively multicellular dictyostelids. An important environmental host of a diverse range of bacteria and viruses, Ac utilizes a diverse repertoire of predicted pattern recognition receptors, many with predicted orthologous functions in the innate immune systems of higher organisms.

CONCLUSIONS: Our analysis highlights the important role of LGT in the biology of Ac and in the diversification of microbial eukaryotes. The early evolution of a key signaling facility implicated in the evolution of metazoan multicellularity strongly argues for its emergence early in the Unikont lineage. Overall, the availability of an Ac genome should aid in deciphering the biology of the Amoebozoa and facilitate functional genomic studies in this important model organism and environmental host.}, } @article {pmid23374161, year = {2013}, author = {Ng, TP and Saltin, SH and Davies, MS and Johannesson, K and Stafford, R and Williams, GA}, title = {Snails and their trails: the multiple functions of trail-following in gastropods.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {88}, number = {3}, pages = {683-700}, doi = {10.1111/brv.12023}, pmid = {23374161}, issn = {1469-185X}, mesh = {Animals ; Behavior, Animal/*physiology ; Gastropoda/*physiology ; Motor Activity/*physiology ; Mucus/*physiology ; }, abstract = {Snails are highly unusual among multicellular animals in that they move on a layer of costly mucus, leaving behind a trail that can be followed and utilized for various purposes by themselves or by other animals. Here we review more than 40 years of experimental and theoretical research to try to understand the ecological and evolutionary rationales for trail-following in gastropods. Data from over 30 genera are currently available, representing a broad taxonomic range living in both aquatic and terrestrial environments. The emerging picture is that the production of mucus trails, which initially was an adaptation to facilitate locomotion and/or habitat extension, has evolved to facilitate a multitude of additional functions. Trail-following supports homing behaviours, and provides simple mechanisms for self-organisation in groups of snails, promoting aggregation and thus relieving desiccation and predation pressures. In gastropods that copulate, trail-following is an important component in mate-searching, either as an alternative, or in addition to the release of water- or air-borne pheromones. In some species, this includes a capacity of males not only to identify trails of conspecifics but also to discriminate between trails laid by females and males. Notably, trail discrimination seems important as a pre-zygotic barrier to mating in some snail species. As production of a mucus trail is the most costly component of snail locomotion, it is also tempting to speculate that evolution has given rise to various ways to compensate for energy losses. Some snails, for example, increase energy intake by eating particles attached to the mucus of trails that they follow, whereas others save energy through reducing the production of their own mucus by moving over previously laid mucus trails. Trail-following to locate a prey item or a mate is also a way to save energy. While the rationale for trail-following in many cases appears clear, the basic mechanisms of trail discrimination, including the mechanisms by which many snails determine the polarity of the trail, are yet to be experimentally determined. Given the multiple functions of trail-following we propose that future studies should adopt an integrated approach, taking into account the possibility of the simultaneous occurrence of many selectively advantageous roles of trail-following behaviour in gastropods. We also believe that future opportunities to link phenotypic and genotypic traits will make possible a new generation of research projects in which gastropod trail-following, its multitude of functions and evolutionary trade-offs can be further elucidated.}, } @article {pmid23369575, year = {2013}, author = {Oczypok, EA and Oury, TD and Chu, CT}, title = {It's a cell-eat-cell world: autophagy and phagocytosis.}, journal = {The American journal of pathology}, volume = {182}, number = {3}, pages = {612-622}, pmid = {23369575}, issn = {1525-2191}, support = {R01 NS065789/NS/NINDS NIH HHS/United States ; HL095495/HL/NHLBI NIH HHS/United States ; NS065789/NS/NINDS NIH HHS/United States ; AG026389/AG/NIA NIH HHS/United States ; T32 HL094295/HL/NHLBI NIH HHS/United States ; NS059806/NS/NINDS NIH HHS/United States ; R56 NS065789/NS/NINDS NIH HHS/United States ; R01 AG026389/AG/NIA NIH HHS/United States ; R21 HL095495/HL/NHLBI NIH HHS/United States ; P01 NS059806/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Autophagy ; Cells/cytology/*metabolism ; Homeostasis ; Humans ; Models, Biological ; *Phagocytosis ; Reactive Oxygen Species/metabolism ; }, abstract = {The process of cellular eating, or the phagocytic swallowing of one cell by another, is an ancient manifestation of the struggle for life itself. Following the endosymbiotic origin of eukaryotic cells, increased cellular and then multicellular complexity was accompanied by the emergence of autophagic mechanisms for self-digestion. Heterophagy and autophagy function not only to protect the nutritive status of cells, but also as defensive responses against microbial pathogens externally or the ill effects of damaged proteins and organelles within. Because of the key roles played by phagocytosis and autophagy in a wide range of acute and chronic human diseases, pathologists have played similarly key roles in elucidating basic regulatory phases for both processes. Studies in diverse organ systems (including the brain, liver, kidney, lung, and muscle) have defined key roles for these lysosomal pathways in infection control, cell death, inflammation, cancer, neurodegeneration, and mitochondrial homeostasis. The literature reviewed here exemplifies the role of pathology in defining leading-edge questions for continued molecular and pathophysiological investigations into all forms of cellular digestion.}, } @article {pmid23363998, year = {2012}, author = {Zhong, M and Kawaguchi, R and Kassai, M and Sun, H}, title = {Retina, retinol, retinal and the natural history of vitamin A as a light sensor.}, journal = {Nutrients}, volume = {4}, number = {12}, pages = {2069-2096}, pmid = {23363998}, issn = {2072-6643}, support = {R01 EY018144/EY/NEI NIH HHS/United States ; R01EY018144/EY/NEI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Biological Transport ; Humans ; *Light ; Opsins/*metabolism ; Receptors, G-Protein-Coupled/metabolism ; Retina/*physiology ; Retinaldehyde/*physiology ; Vision, Ocular/*physiology ; Vitamin A/*physiology ; }, abstract = {Light is both the ultimate energy source for most organisms and a rich information source. Vitamin A-based chromophore was initially used in harvesting light energy, but has become the most widely used light sensor throughout evolution from unicellular to multicellular organisms. Vitamin A-based photoreceptor proteins are called opsins and have been used for billions of years for sensing light for vision or the equivalent of vision. All vitamin A-based light sensors for vision in the animal kingdom are G-protein coupled receptors, while those in unicellular organisms are light-gated channels. This first major switch in evolution was followed by two other major changes: the switch from bistable to monostable pigments for vision and the expansion of vitamin A's biological functions. Vitamin A's new functions such as regulating cell growth and differentiation from embryogenesis to adult are associated with increased toxicity with its random diffusion. In contrast to bistable pigments which can be regenerated by light, monostable pigments depend on complex enzymatic cycles for regeneration after every photoisomerization event. Here we discuss vitamin A functions and transport in the context of the natural history of vitamin A-based light sensors and propose that the expanding functions of vitamin A and the choice of monostable pigments are the likely evolutionary driving forces for precise, efficient, and sustained vitamin A transport.}, } @article {pmid23362301, year = {2013}, author = {Niklas, KJ}, title = {Biophysical and size-dependent perspectives on plant evolution.}, journal = {Journal of experimental botany}, volume = {64}, number = {15}, pages = {4817-4827}, doi = {10.1093/jxb/ers379}, pmid = {23362301}, issn = {1460-2431}, mesh = {*Biological Evolution ; Biomechanical Phenomena ; *Biophysics ; Ecosystem ; Embryophyta/anatomy & histology/genetics ; Fossils ; Phenotype ; Plants/*anatomy & histology/genetics ; }, abstract = {Physical laws and processes have profoundly influenced plant evolution. Their effects are invariably size dependent and thus subject to scaling as well as biophysical analyses even though these effects differ depending upon the fluid (water or air) in which plants evolve. Although organisms cannot obviate the effects of physical laws and processes, the consequences of these effects can be altered by ontogenetic or phylogenetic alterations in geometry, shape, or orientation as well as in body size. These assertions are examined using theoretical insights and empirical data drawn from extant and fossil plants pertinent to four evolutionary transitions: (1) the evolution of multicellularity, (2) the transition from an aquatic to an aerial habitat, (3) the evolution of vascular tissues, and (4) the evolution of secondary growth by the independent acquisition of cambia. This examination shows how physical laws limit phenotypic expression, but how they also simultaneously provide alternative, potentially adaptive possibilities.}, } @article {pmid23360999, year = {2013}, author = {Ringrose, JH and van den Toorn, HW and Eitel, M and Post, H and Neerincx, P and Schierwater, B and Altelaar, AF and Heck, AJ}, title = {Deep proteome profiling of Trichoplax adhaerens reveals remarkable features at the origin of metazoan multicellularity.}, journal = {Nature communications}, volume = {4}, number = {}, pages = {1408}, pmid = {23360999}, issn = {2041-1723}, mesh = {Animals ; *Biological Evolution ; Databases, Protein ; Ion Exchange ; Phosphorylation ; Phosphotransferases/metabolism ; Phosphotyrosine/metabolism ; Placozoa/*cytology/*metabolism ; Protein Processing, Post-Translational ; Proteome/*metabolism ; Proteomics/*methods ; Receptors, Notch/metabolism ; Signal Transduction ; }, abstract = {Genome sequencing of arguably the simplest known animal, Trichoplax adhaerens, uncovered a rich array of transcription factor and signalling pathway genes. Although the existence of such genes allows speculation about the presence of complex regulatory events, it does not reveal the level of actual protein expression and functionalization through posttranslational modifications. Using high-resolution mass spectrometry, we here semi-quantify 6,516 predicted proteins, revealing evidence of horizontal gene transfer and the presence at the protein level of nodes important in animal signalling pathways. Moreover, our data demonstrate a remarkably high activity of tyrosine phosphorylation, in line with the hypothesized burst of tyrosine-regulated signalling at the instance of animal multicellularity. Together, this Trichoplax proteomics data set offers significant new insight into the mechanisms underlying the emergence of metazoan multicellularity and provides a resource for interested researchers.}, } @article {pmid23355006, year = {2013}, author = {Schmith, A and Groth, M and Ratka, J and Gatz, S and Spaller, T and Siol, O and Glöckner, G and Winckler, T}, title = {Conserved gene regulatory function of the carboxy-terminal domain of dictyostelid C-module-binding factor.}, journal = {Eukaryotic cell}, volume = {12}, number = {3}, pages = {460-468}, pmid = {23355006}, issn = {1535-9786}, mesh = {Base Sequence ; Conserved Sequence ; Dictyostelium/*genetics/metabolism ; Gene Expression Regulation ; Genes, Protozoan ; Molecular Sequence Data ; Mutation ; Phylogeny ; Protein Structure, Tertiary ; Protozoan Proteins/*chemistry/genetics/*metabolism ; Sequence Analysis, RNA ; Transcription Factors/*chemistry/genetics/*metabolism ; Transcription, Genetic ; Transcriptome ; }, abstract = {C-module-binding factor A (CbfA) is a jumonji-type transcription regulator that is important for maintaining the expression and mobility of the retrotransposable element TRE5-A in the social amoeba Dictyostelium discoideum. CbfA-deficient cells have lost TRE5-A retrotransposition, are impaired in the ability to feed on bacteria, and do not enter multicellular development because of a block in cell aggregation. In this study, we performed Illumina RNA-seq of growing CbfA mutant cells to obtain a list of CbfA-regulated genes. We demonstrate that the carboxy-terminal domain of CbfA alone is sufficient to mediate most CbfA-dependent gene expression. The carboxy-terminal domain of CbfA from the distantly related social amoeba Polysphondylium pallidum restored the expression of CbfA-dependent genes in the D. discoideum CbfA mutant, indicating a deep conservation in the gene regulatory function of this domain in the dictyostelid clade. The CbfA-like protein CbfB displays ∼25% sequence identity with CbfA in the amino-terminal region, which contains a JmjC domain and two zinc finger regions and is thought to mediate chromatin-remodeling activity. In contrast to CbfA proteins, where the carboxy-terminal domains are strictly conserved in all dictyostelids, CbfB proteins have completely unrelated carboxy-terminal domains. Outside the dictyostelid clade, CbfA-like proteins with the CbfA-archetypical JmjC/zinc finger arrangement and individual carboxy-terminal domains are prominent in filamentous fungi but are not found in yeasts, plants, and metazoans. Our data suggest that two functional regions of the CbfA-like proteins evolved at different rates to allow the occurrence of species-specific adaptation processes during genome evolution.}, } @article {pmid23352078, year = {2013}, author = {Marshall, WL and Berbee, ML}, title = {Comparative morphology and genealogical delimitation of cryptic species of sympatric isolates of Sphaeroforma (Ichthyosporea, Opisthokonta).}, journal = {Protist}, volume = {164}, number = {2}, pages = {287-311}, doi = {10.1016/j.protis.2012.12.002}, pmid = {23352078}, issn = {1618-0941}, mesh = {Animals ; Cell Wall/ultrastructure ; Cluster Analysis ; DNA, Protozoan/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; DNA, Ribosomal Spacer/chemistry/genetics ; Mesomycetozoea/*classification/*cytology/genetics ; Microscopy ; Molecular Sequence Data ; Organelles/ultrastructure ; Phylogeny ; RNA, Protozoan/genetics ; Sequence Analysis, DNA ; Spores, Protozoan/cytology ; }, abstract = {Of the ancient clades of unicellular relatives of the multicellular animals, ichthyosporea are among the easiest to collect, cultivate, and analyze at the population level. Once identified, species can be correlated with their animal hosts and geographical ranges. However, the spherical stages common to many ichthyosporea provide little basis for morphological species identification. This study of the genus Sphaeroforma is the first to apply patterns of genetic discontinuity to delimit species among any of the unicellular 'holozoa.' Sequences of three loci from 148 sympatric isolates, along with type cultures, provided concordant support for new species "Sphaeroforma nootkatensis" and "Sphaeroforma gastrica," and for formally describing 'Pseudoperkinsus tapetis,' as "Sphaeroforma tapetis". We document light and electron microscopic characters that distinguish the genus but not its species. "S. tapetis" sometimes had brief amoeboid or plasmodial motile stages and endospore release through pores. Unlike closely related Creolimax, Sphaeroforma lacked a central vacuole but had multiple peripheral nucleoli. Like distantly related eccrinales, Sphaeroforma cell walls had pores and a calyx. Analyses of allele frequencies in "S. tapetis" indicated geographical differentiation but no host specificity. Accurate molecular identification of species will increase the feasibility and reliability of further studies of Sphaeroforma in its natural habit.}, } @article {pmid23349899, year = {2013}, author = {Szczesny, P and Mykowiecka, A and Pawłowski, K and Grynberg, M}, title = {Distinct protein classes in human red cell proteome revealed by similarity of phylogenetic profiles.}, journal = {PloS one}, volume = {8}, number = {1}, pages = {e54471}, pmid = {23349899}, issn = {1932-6203}, mesh = {Bacteria ; Erythrocytes/*chemistry ; Eukaryotic Cells ; Evolution, Molecular ; Humans ; *Phylogeny ; Proteins/*classification/isolation & purification ; *Proteome ; }, abstract = {The minimal set of proteins necessary to maintain a vertebrate cell forms an interesting core of cellular machinery. The known proteome of human red blood cell consists of about 1400 proteins. We treated this protein complement of one of the simplest human cells as a model and asked the questions on its function and origins. The proteome was mapped onto phylogenetic profiles, i.e. vectors of species possessing homologues of human proteins. A novel clustering approach was devised, utilising similarity in the phylogenetic spread of homologues as distance measure. The clustering based on phylogenetic profiles yielded several distinct protein classes differing in phylogenetic taxonomic spread, presumed evolutionary history and functional properties. Notably, small clusters of proteins common to vertebrates or Metazoa and other multicellular eukaryotes involve biological functions specific to multicellular organisms, such as apoptosis or cell-cell signaling, respectively. Also, a eukaryote-specific cluster is identified, featuring GTP-ase signalling and ubiquitination. Another cluster, made up of proteins found in most organisms, including bacteria and archaea, involves basic molecular functions such as oxidation-reduction and glycolysis. Approximately one third of erythrocyte proteins do not fall in any of the clusters, reflecting the complexity of protein evolution in comparison to our simple model. Basically, the clustering obtained divides the proteome into old and new parts, the former originating from bacterial ancestors, the latter from inventions within multicellular eukaryotes. Thus, the model human cell proteome appears to be made up of protein sets distinct in their history and biological roles. The current work shows that phylogenetic profiles concept allows protein clustering in a way relevant both to biological function and evolutionary history.}, } @article {pmid23349118, year = {2013}, author = {Beall, CM}, title = {Human adaptability studies at high altitude: research designs and major concepts during fifty years of discovery.}, journal = {American journal of human biology : the official journal of the Human Biology Council}, volume = {25}, number = {2}, pages = {141-147}, doi = {10.1002/ajhb.22355}, pmid = {23349118}, issn = {1520-6300}, mesh = {*Acclimatization ; Adaptation, Physiological ; Altitude ; *Biological Evolution ; Cold Temperature ; Humans ; Oxygen/*metabolism ; Research Design ; }, abstract = {OBJECTIVES: This report presents a perspective on the broad research trends in the biology of human populations at high-altitude and their contributions to the improved understanding of evolution and adaptation. A focus is on the research that has occurred over the past 50 years of anthropological fieldwork on the Andean, Tibetan, and, to a lesser extent, the East African plateaus.

METHODS: With an emphasis on fieldwork studies, this report presents and illustrates major concepts and research designs in published high-altitude studies.

RESULTS: Early use of a single population-multiple stress research design focused on Andean Quechua, sometimes in comparison with European or admixed Andean-European samples. That design identified physical and sociocultural environmental factors including cold and under nutrition as well as high-altitude hypobaric hypoxia. Researchers accumulated evidence supporting the hypothesis of four modes of adaptation to a complex Andean highland environment: cultural, acclimatization, developmental, and genetic. The discovery that Andean biological patterns were not replicated among Tibetan highlanders stimulated research on the extent and origins of the contrasts. It also shifted emphasis to a multiple population - single stress study design. The discovery of oxygen-homeostasis-associated genetic loci and traits in all multicellular animals has transformed high-altitude research. Paradoxically, genomic analyses identifying the pertinent biological pathways are likely to return interest to environmental factors other than hypoxia.

CONCLUSIONS: Details of the proximate mechanisms, the biochemical, and physiological processes underlying the three modes of biological adaptation are accumulating. Better understanding of oxygen-homeostasis processes leads to questions about crossadaptation with other environmental factors. The particulars of the ultimate mechanisms, the evolutionary, and microevolutionary history underlying the population differences are also emerging. For example, similar hemoglobin phenotypes among Tibetan and Ethiopian Amhara highlanders associate with different genetic loci and the variants at those loci are present in most populations regardless of altitude. Continuing fieldwork is urgent because modernization and migration are changing the traditional ways of life and patterns of exposure to the environment among highlanders everywhere.}, } @article {pmid23335919, year = {2012}, author = {Amaral-Zettler, LA}, title = {Eukaryotic diversity at pH extremes.}, journal = {Frontiers in microbiology}, volume = {3}, number = {}, pages = {441}, pmid = {23335919}, issn = {1664-302X}, abstract = {Extremely acidic (pH < 3) and extremely alkaline (pH > 9) environments support a diversity of single-cell and to a lesser extent, multicellular eukaryotic life. This study compared alpha and beta diversity in eukaryotic communities from seven diverse aquatic environments with pH values ranging from 2 to 11 using massively-parallel pyrotag sequencing targeting the V9 hypervariable region of the 18S ribosomal RNA (rRNA) gene. A total of 946 operational taxonomic units (OTUs) were recovered at a 6% cut-off level (94% similarity) across the sampled environments. Hierarchical clustering of the samples segregated the communities into acidic and alkaline groups. Similarity percentage (SIMPER) analysis followed by indicator OTU analysis (IOA) and non-metric multidimensional scaling (NMDS) were used to determine which characteristic groups of eukaryotic taxa typify acidic or alkaline extremes and the extent to which pH explains eukaryotic community structure in these environments. Spain's Rio Tinto yielded the fewest observed OTUs while Nebraska Sandhills alkaline lakes yielded the most. Distinct OTUs, including metazoan OTUs, numerically dominated pH extreme sites. Indicator OTUs included the diatom Pinnularia and unidentified opisthokonts (Fungi and Filasterea) in the extremely acidic environments, and the ciliate Frontonia across the extremely alkaline sites. Inferred from NMDS, pH explained only a modest fraction of the variation across the datasets, indicating that other factors influence the underlying community structure in these environments. The findings from this study suggest that the ability for eukaryotes to adapt to pH extremes over a broad range of values may be rare, but further study of taxa that can broadly adapt across diverse acidic and alkaline environments, respectively present good models for understanding adaptation and should be targeted for future investigations.}, } @article {pmid23333946, year = {2013}, author = {Suga, H and Ruiz-Trillo, I}, title = {Development of ichthyosporeans sheds light on the origin of metazoan multicellularity.}, journal = {Developmental biology}, volume = {377}, number = {1}, pages = {284-292}, pmid = {23333946}, issn = {1095-564X}, support = {206883/ERC_/European Research Council/International ; }, mesh = {Animals ; Animals, Genetically Modified ; Base Sequence ; *Biological Evolution ; Cell Nucleus Division/drug effects ; Eukaryota/*cytology/drug effects/genetics/*growth & development/ultrastructure ; Giant Cells/cytology/drug effects ; Models, Biological ; Molecular Sequence Data ; Morpholinos/pharmacology ; RNA Interference/drug effects ; Transformation, Genetic/drug effects ; }, abstract = {To understand the mechanisms involved in the transition from protists to multicellular animals (metazoans), studying unicellular relatives of metazoans is as important as studying metazoans themselves. However, investigations remain poor on the closest unicellular (or colonial) relatives of Metazoa, i.e., choanoflagellates, filastereans and ichthyosporeans. Molecular-level analyses on these protists have been severely limited by the lack of transgenesis tools. Their genomes, however, contain several key genes encoding proteins important for metazoan development and multicellularity, including those involved in cell-cell communication, cell proliferation, cell differentiation, and tissue growth control. Tools to analyze their functions in a molecular level are awaited. Here we report techniques of cell transformation and gene silencing developed for the first time in a close relative of metazoans, the ichthyosporean Creolimax fragrantissima. We propose C. fragrantissima as a model organism to investigate the origin of metazoan multicellularity. By transgenesis, we demonstrate that its colony develops from a fully-grown multinucleate syncytium, in which nuclear divisions are strictly synchronized. It has been hypothesized that metazoan multicellular development initially occurred in the course of evolution through successive rounds of cell division, which were not necessarily be synchronized, or alternatively through cell aggregation. Our findings point to another possible mechanism for the evolution of animal multicellularity, namely, cellularization of a syncytium in which nuclear divisions are synchronized. We believe that further studies on the development of ichthyosporeans by the use of our methodologies will provide novel insights into the origin of metazoan multicellularity.}, } @article {pmid23331916, year = {2013}, author = {Niklas, KJ and Newman, SA}, title = {The origins of multicellular organisms.}, journal = {Evolution & development}, volume = {15}, number = {1}, pages = {41-52}, doi = {10.1111/ede.12013}, pmid = {23331916}, issn = {1525-142X}, mesh = {Animals ; *Biological Evolution ; Body Patterning ; Cell Communication ; Cell Differentiation ; Cell Lineage ; Chlamydomonas/physiology ; Chlorophyta/physiology ; Developmental Biology ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Genome ; Genotype ; Phylogeny ; Species Specificity ; }, abstract = {Multicellularity has evolved in several eukaryotic lineages leading to plants, fungi, and animals. Theoretically, in each case, this involved (1) cell-to-cell adhesion with an alignment-of-fitness among cells, (2) cell-to-cell communication, cooperation, and specialization with an export-of-fitness to a multicellular organism, and (3) in some cases, a transition from "simple" to "complex" multicellularity. When mapped onto a matrix of morphologies based on developmental and physical rules for plants, these three phases help to identify a "unicellular ⇒ colonial ⇒ filamentous (unbranched ⇒ branched) ⇒ pseudoparenchymatous ⇒ parenchymatous" morphological transformation series that is consistent with trends observed within each of the three major plant clades. In contrast, a more direct "unicellular ⇒ colonial or siphonous ⇒ parenchymatous" series is observed in fungal and animal lineages. In these contexts, we discuss the roles played by the cooptation, expansion, and subsequent diversification of ancestral genomic toolkits and patterning modules during the evolution of multicellularity. We conclude that the extent to which multicellularity is achieved using the same toolkits and modules (and thus the extent to which multicellularity is homologous among different organisms) differs among clades and even among some closely related lineages.}, } @article {pmid23329689, year = {2013}, author = {Tian, X and Strassmann, JE and Queller, DC}, title = {Dictyostelium development shows a novel pattern of evolutionary conservation.}, journal = {Molecular biology and evolution}, volume = {30}, number = {4}, pages = {977-984}, doi = {10.1093/molbev/mst007}, pmid = {23329689}, issn = {1537-1719}, mesh = {Animals ; Biological Evolution ; Conserved Sequence ; Dictyostelium/*genetics/metabolism/physiology ; Gene Expression ; *Gene Expression Regulation, Developmental ; Genes, Protozoan ; Models, Genetic ; Sequence Analysis, RNA ; }, abstract = {von Baer's law states that early stages of animal development are the most conserved. More recent evidence supports a modified "hourglass" pattern in which an early but somewhat later stage is most conserved. Both patterns have been explained by the relative complexity of either temporal or spatial interactions; the greatest conservation and lowest evolvability occur at the time of the most complex interactions, because these cause larger effects that are harder for selection to alter. This general kind of explanation might apply universally across independent multicellular systems, as supported by the recent finding of the hourglass pattern in plants. We use RNA-seq expression data from the development of the slime mold Dictyostelium to demonstrate that it does not follow either of the two canonical patterns but instead tends to show the strongest conservation and weakest evolvability late in development. We propose that this is consistent with a version of the spatial constraints model, modified for organisms that never achieve a high degree of developmental modularity.}, } @article {pmid23327985, year = {2013}, author = {Donley, N and Thayer, MJ}, title = {DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability.}, journal = {Seminars in cancer biology}, volume = {23}, number = {2}, pages = {80-89}, pmid = {23327985}, issn = {1096-3650}, support = {R01 CA131967/CA/NCI NIH HHS/United States ; T32 GM071338/GM/NIGMS NIH HHS/United States ; CA104693/CA/NCI NIH HHS/United States ; CA131967/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA Replication/*genetics ; DNA Replication Timing/genetics/*physiology ; Epigenesis, Genetic/physiology ; Gene Expression Regulation, Neoplastic ; Genomic Instability/*genetics ; Humans ; Models, Biological ; Neoplasms/*genetics ; Time Factors ; }, abstract = {Normal cellular division requires that the genome be faithfully replicated to ensure that unaltered genomic information is passed from one generation to the next. DNA replication initiates from thousands of origins scattered throughout the genome every cell cycle; however, not all origins initiate replication at the same time. A vast amount of work over the years indicates that different origins along each eukaryotic chromosome are activated in early, middle or late S phase. This temporal control of DNA replication is referred to as the replication-timing program. The replication-timing program represents a very stable epigenetic feature of chromosomes. Recent evidence has indicated that the replication-timing program can influence the spatial distribution of mutagenic events such that certain regions of the genome experience increased spontaneous mutagenesis compared to surrounding regions. This influence has helped shape the genomes of humans and other multicellular organisms and can affect the distribution of mutations in somatic cells. It is also becoming clear that the replication-timing program is deregulated in many disease states, including cancer. Aberrant DNA replication timing is associated with changes in gene expression, changes in epigenetic modifications and an increased frequency of structural rearrangements. Furthermore, certain replication timing changes can directly lead to overt genomic instability and may explain unique mutational signatures that are present in cells that have undergone the recently described processes of "chromothripsis" and "kataegis". In this review, we will discuss how the normal replication timing program, as well as how alterations to this program, can contribute to the evolution of the genomic landscape in normal and cancerous cells.}, } @article {pmid23319343, year = {2012}, author = {Hernández-Hernández, V and Niklas, KJ and Newman, SA and Benítez, M}, title = {Dynamical patterning modules in plant development and evolution.}, journal = {The International journal of developmental biology}, volume = {56}, number = {9}, pages = {661-674}, doi = {10.1387/ijdb.120027mb}, pmid = {23319343}, issn = {1696-3547}, mesh = {*Biological Evolution ; Epigenesis, Genetic ; Gene Expression Regulation, Plant ; Plant Development/*genetics ; Plants/*genetics ; }, abstract = {Broad comparative studies at the level of developmental processes are necessary to fully understand the evolution of development and phenotypes. The concept of dynamical patterning modules (DPMs) provides a framework for studying developmental processes in the context of wide comparative analyses. DPMs are defined as sets of ancient, conserved gene products and molecular networks, in conjunction with the physical morphogenetic and patterning processes they mobilize in the context of multicellularity. The theoretical framework based on DPMs originally postulated that each module generates a key morphological motif of the basic animal body plans and organ forms. Here, we use a previous definition of the plant multicellular body plan and describe the basic DPMs underlying the main features of plant development. For each DPM, we identify characteristic molecules and molecular networks, and when possible, the physical processes they mobilize. We then briefly review the phyletic distribution of these molecules across the various plant lineages. Although many of the basic plant DPMs are significantly different from those of animals, the framework established by a DPM perspective on plant development is essential for comparative analyses aiming to provide a truly mechanistic explanation for organic development across all plant and animal lineages.}, } @article {pmid23315654, year = {2013}, author = {Parfrey, LW and Lahr, DJ}, title = {Multicellularity arose several times in the evolution of eukaryotes (response to DOI 10.1002/bies.201100187).}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {4}, pages = {339-347}, doi = {10.1002/bies.201200143}, pmid = {23315654}, issn = {1521-1878}, mesh = {Animals ; *Cell Polarity ; Dictyostelium/*cytology ; Epithelial Cells/*physiology ; Humans ; }, abstract = {The cellular slime mold Dictyostelium has cell-cell connections similar in structure, function, and underlying molecular mechanisms to animal epithelial cells. These similarities form the basis for the proposal that multicellularity is ancestral to the clade containing animals, fungi, and Amoebozoa (including Dictyostelium): Amorphea (formerly "unikonts"). This hypothesis is intriguing and if true could precipitate a paradigm shift. However, phylogenetic analyses of two key genes reveal patterns inconsistent with a single origin of multicellularity. A single origin in Amorphea would also require loss of multicellularity in each of the many unicellular lineages within this clade. Further, there are numerous other origins of multicellularity within eukaryotes, including three within Amorphea, that are not characterized by these structural and mechanistic similarities. Instead, convergent evolution resulting from similar selective pressures for forming multicellular structures with motile and differentiated cells is the most likely explanation for the observed similarities between animal and dictyostelid cell-cell connections.}, } @article {pmid23313713, year = {2013}, author = {Völgyi, B and Kovács-Oller, T and Atlasz, T and Wilhelm, M and Gábriel, R}, title = {Gap junctional coupling in the vertebrate retina: variations on one theme?.}, journal = {Progress in retinal and eye research}, volume = {34}, number = {}, pages = {1-18}, doi = {10.1016/j.preteyeres.2012.12.002}, pmid = {23313713}, issn = {1873-1635}, mesh = {Animals ; Connexins/metabolism/physiology ; Electrical Synapses/physiology ; Gap Junctions/*physiology ; Retina/cytology/*physiology ; Vertebrates/*physiology ; }, abstract = {Gap junctions connect cells in the bodies of all multicellular organisms, forming either homologous or heterologous (i.e. established between identical or different cell types, respectively) cell-to-cell contacts by utilizing identical (homotypic) or different (heterotypic) connexin protein subunits. Gap junctions in the nervous system serve electrical signaling between neurons, thus they are also called electrical synapses. Such electrical synapses are particularly abundant in the vertebrate retina where they are specialized to form links between neurons as well as glial cells. In this article, we summarize recent findings on retinal cell-to-cell coupling in different vertebrates and identify general features in the light of the evergrowing body of data. In particular, we describe and discuss tracer coupling patterns, connexin proteins, junctional conductances and modulatory processes. This multispecies comparison serves to point out that most features are remarkably conserved across the vertebrate classes, including (i) the cell types connected via electrical synapses; (ii) the connexin makeup and the conductance of each cell-to-cell contact; (iii) the probable function of each gap junction in retinal circuitry; (iv) the fact that gap junctions underlie both electrical and/or tracer coupling between glial cells. These pan-vertebrate features thus demonstrate that retinal gap junctions have changed little during the over 500 million years of vertebrate evolution. Therefore, the fundamental architecture of electrically coupled retinal circuits seems as old as the retina itself, indicating that gap junctions deeply incorporated in retinal wiring from the very beginning of the eye formation of vertebrates. In addition to hard wiring provided by fast synaptic transmitter-releasing neurons and soft wiring contributed by peptidergic, aminergic and purinergic systems, electrical coupling may serve as the 'skeleton' of lateral processing, enabling important functions such as signal averaging and synchronization.}, } @article {pmid23313199, year = {2013}, author = {Okuyama, H and Yoshida, T and Endo, H and Nakayama, M and Nonomura, N and Nishimura, K and Inoue, M}, title = {Involvement of heregulin/HER3 in the primary culture of human urothelial cancer.}, journal = {The Journal of urology}, volume = {190}, number = {1}, pages = {302-310}, doi = {10.1016/j.juro.2012.12.106}, pmid = {23313199}, issn = {1527-3792}, mesh = {Blotting, Western ; Carcinoma, Transitional Cell/drug therapy/*pathology ; Cell Proliferation ; Humans ; Immunohistochemistry ; Molecular Targeted Therapy ; Neuregulin-1/*pharmacology ; Polymerase Chain Reaction/methods ; Receptor, ErbB-3/genetics/*metabolism ; Sensitivity and Specificity ; Signal Transduction ; Spheroids, Cellular/drug effects ; Transplantation, Heterologous ; Tumor Cells, Cultured/*drug effects ; Urinary Bladder Neoplasms/drug therapy/*pathology ; }, abstract = {PURPOSE: We previously established a novel method of human colorectal cancer primary culture. This method, termed the cancer tissue originated spheroid method, involves the preparation of multicellular spheroids of primary cancer cells that are cultured so that cell-cell contact is maintained. We applied this method to human urothelial cancer.

MATERIALS AND METHODS: Cancer tissue originated spheroids were prepared from xenografts or primary human bladder urothelial cancer tumors following the same protocol used for human colorectal cancer. Cancer tissue originated spheroids were characterized using immunohistochemistry, Western blot and polymerase chain reaction.

RESULTS: We established a xenograft from a primary bladder urothelial cancer, and isolated and cultured cancer tissue originated spheroids from the xenograft tumor. Cancer tissue originated spheroids retained the characteristics of the original tumor and those of the xenograft. Heregulin promoted cancer tissue originated spheroid growth, and inhibitors of PI3K and mTOR inhibited heregulin induced growth, as did lapatinib but not erlotinib. We also prepared cancer tissue originated spheroids from primary bladder urothelial cancer. The success rate of establishing primary cancer tissue originated spheroids from nonmuscle invasive urothelial cancer was 90.7% and that from muscle invasive cancer was 68.2%. The overall success rate was 84.2%. Heregulin promoted the growth of primary cancer tissue originated spheroids from 4 of 7 patients.

CONCLUSIONS: We report a method of establishing primary cultures of human urothelial cancer cells. Growth stimulation by heregulin in cancer tissue originated spheroids from xenografts and primary tumors suggests the possibility of molecular targeting therapy against HER3 signaling for human urothelial cancer. The cancer tissue originated spheroid method might be useful for selecting patients for molecular targeting drugs such as lapatinib.}, } @article {pmid23312067, year = {2013}, author = {Dawson, SC and Paredez, AR}, title = {Alternative cytoskeletal landscapes: cytoskeletal novelty and evolution in basal excavate protists.}, journal = {Current opinion in cell biology}, volume = {25}, number = {1}, pages = {134-141}, pmid = {23312067}, issn = {1879-0410}, support = {R01 AI077571/AI/NIAID NIH HHS/United States ; }, mesh = {Actins/metabolism ; Animals ; *Biological Evolution ; Cytoskeleton/*metabolism ; Eukaryota/*cytology/genetics/ultrastructure ; Genome/genetics ; Humans ; Microtubules/metabolism ; Phylogeny ; Proteins/metabolism ; Species Specificity ; }, abstract = {Microbial eukaryotes encompass the majority of eukaryotic evolutionary and cytoskeletal diversity. The cytoskeletal complexity observed in multicellular organisms appears to be an expansion of components present in genomes of diverse microbial eukaryotes such as the basal lineage of flagellates, the Excavata. Excavate protists have complex and diverse cytoskeletal architectures and life cycles-essentially alternative cytoskeletal 'landscapes'-yet still possess conserved microtubule-associated and actin-associated proteins. Comparative genomic analyses have revealed that a subset of excavates, however, lack many canonical actin-binding proteins central to actin cytoskeleton function in other eukaryotes. Overall, excavates possess numerous uncharacterized and 'hypothetical' genes, and may represent an undiscovered reservoir of novel cytoskeletal genes and cytoskeletal mechanisms. The continued development of molecular genetic tools in these complex microbial eukaryotes will undoubtedly contribute to our overall understanding of cytoskeletal diversity and evolution.}, } @article {pmid23300255, year = {2013}, author = {Smith, DR and Hamaji, T and Olson, BJ and Durand, PM and Ferris, P and Michod, RE and Featherston, J and Nozaki, H and Keeling, PJ}, title = {Organelle genome complexity scales positively with organism size in volvocine green algae.}, journal = {Molecular biology and evolution}, volume = {30}, number = {4}, pages = {793-797}, doi = {10.1093/molbev/mst002}, pmid = {23300255}, issn = {1537-1719}, mesh = {Chlamydomonas reinhardtii/cytology/*genetics ; Evolution, Molecular ; Genetic Drift ; Genetic Variation ; *Genome, Mitochondrial ; Genome, Plant ; *Genome, Plastid ; Mitochondria/*genetics ; Models, Genetic ; Plastids/*genetics ; Volvocida/cytology/genetics ; }, abstract = {It has been argued that for certain lineages, noncoding DNA expansion is a consequence of the increased random genetic drift associated with long-term escalations in organism size. But a lack of data has prevented the investigation of this hypothesis in most plastid-bearing protists. Here, using newly sequenced mitochondrial and plastid genomes, we explore the relationship between organelle DNA noncoding content and organism size within volvocine green algae. By looking at unicellular, colonial, and differentiated multicellular algae, we show that organelle DNA complexity scales positively with species size and cell number across the volvocine lineage. Moreover, silent-site genetic diversity data suggest that the volvocine species with the largest cell numbers and most bloated organelle genomes have the smallest effective population sizes. Together, these findings support the view that nonadaptive processes, like random genetic drift, promote the expansion of noncoding regions in organelle genomes.}, } @article {pmid23299670, year = {2013}, author = {Bogaert, KA and Arun, A and Coelho, SM and De Clerck, O}, title = {Brown algae as a model for plant organogenesis.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {959}, number = {}, pages = {97-125}, doi = {10.1007/978-1-62703-221-6_6}, pmid = {23299670}, issn = {1940-6029}, mesh = {Organogenesis/genetics/*physiology ; Phaeophyceae/genetics/*physiology ; }, abstract = {Brown algae are an extremely interesting, but surprisingly poorly explored, group of organisms. They are one of only five eukaryotic lineages to have independently evolved complex multicellularity, which they express through a wide variety of morphologies ranging from uniseriate branched filaments to complex parenchymatous thalli with multiple cell types. Despite their very distinct evolutionary history, brown algae and land plants share a striking amount of developmental features. This has led to an interest in several aspects of brown algal development, including embryogenesis, polarity, cell cycle, asymmetric cell division and a putative role for plant hormone signalling. This review describes how investigations using brown algal models have helped to increase our understanding of the processes controlling early embryo development, in particular polarization, axis formation and asymmetric cell division. Additionally, the diversity of life cycles in the brown lineage and the emergence of Ectocarpus as a powerful model organism, are affording interesting insights on the molecular mechanisms underlying haploid-diploid life cycles. The use of these and other emerging brown algal models will undoubtedly add to our knowledge on the mechanisms that regulate development in multicellular photosynthetic organisms.}, } @article {pmid23291162, year = {2013}, author = {Duncan, O and van der Merwe, MJ and Daley, DO and Whelan, J}, title = {The outer mitochondrial membrane in higher plants.}, journal = {Trends in plant science}, volume = {18}, number = {4}, pages = {207-217}, doi = {10.1016/j.tplants.2012.12.004}, pmid = {23291162}, issn = {1878-4372}, mesh = {Arabidopsis/genetics/*metabolism/physiology ; Arabidopsis Proteins/genetics/metabolism ; Biological Evolution ; Lipids ; Membrane Proteins/genetics/*metabolism ; Mitochondria/*metabolism ; Mitochondrial Membranes/*metabolism ; Mitochondrial Proteins/genetics/metabolism ; Phylogeny ; Protein Transport ; Proteome ; Signal Transduction ; Stress, Physiological ; }, abstract = {The acquisition and integration of intracellular organelles, such as mitochondria and plastids, were important steps in the emergence of complex multicellular life. Although the outer membranes of these organelles have lost many of the functions of their free-living bacterial ancestor, others were acquired during organellogenesis. To date, the biological roles of these proteins have not been systematically characterized. In this review, we discuss the evolutionary origins and functions of outer membrane mitochondrial (OMM) proteins in Arabidopsis thaliana. Our analysis, using phylogenetic inference, indicates that several OMM proteins either acquired novel functional roles or were recruited from other subcellular localizations during evolution in Arabidopsis. These observations suggest the existence of novel communication routes and functions between organelles within plant cells.}, } @article {pmid23289572, year = {2013}, author = {Ross, L and Hardy, NB and Okusu, A and Normark, BB}, title = {Large population size predicts the distribution of asexuality in scale insects.}, journal = {Evolution; international journal of organic evolution}, volume = {67}, number = {1}, pages = {196-206}, doi = {10.1111/j.1558-5646.2012.01784.x}, pmid = {23289572}, issn = {1558-5646}, mesh = {Animals ; Evolution, Molecular ; Extinction, Biological ; Hemiptera/*genetics ; Models, Theoretical ; Parthenogenesis/*genetics ; Phylogeny ; Population/genetics ; }, abstract = {Understanding why some organisms reproduce by sexual reproduction while others can reproduce asexually remains an important unsolved problem in evolutionary biology. Simple demography suggests that asexuals should outcompete sexually reproducing organisms, because of their higher intrinsic rate of increase. However, the majority of multicellular organisms have sexual reproduction. The widely accepted explanation for this apparent contradiction is that asexual lineages have a higher extinction rate. A number of models have indicated that population size might play a crucial role in the evolution of asexuality. The strength of processes that lead to extinction of asexual species is reduced when population sizes get very large, so that the long-term advantage of sexual over asexual reproduction may become negligible. Here, we use a comparative approach using scale insects (Coccoidea, Hemiptera) to show that asexuality is indeed more common in species with larger population density and geographic distribution and we also show that asexual species tend to be more polyphagous. We discuss the implication of our findings for previously observed patterns of asexuality in agricultural pests.}, } @article {pmid23281188, year = {2013}, author = {Harrison, F}, title = {Bacterial cooperation in the wild and in the clinic: are pathogen social behaviours relevant outside the laboratory?.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {35}, number = {2}, pages = {108-112}, pmid = {23281188}, issn = {1521-1878}, mesh = {Animals ; Bacteria/growth & development/*pathogenicity ; Bacterial Secretion Systems/*physiology ; Biological Evolution ; Host-Pathogen Interactions ; Humans ; Laboratories ; Microbial Consortia/*physiology ; Microbial Interactions/*physiology ; Selection, Genetic ; Virulence ; Virulence Factors/physiology ; }, abstract = {Individual bacterial cells can communicate via quorum sensing, cooperate to harvest nutrients from their environment, form multicellular biofilms, compete over resources and even kill one another. When the environment that bacteria inhabit is an animal host, these social behaviours mediate virulence. Over the last decade, much attention has focussed on the ecology, evolution and pathology of bacterial cooperation, and the possibility that it could be exploited or destabilised to treat infections. But how far can we really extrapolate from theoretical predictions and laboratory experiments to make inferences about 'cooperative' behaviours in hosts and reservoirs? To determine the likely importance and evolution of cooperation 'in the wild', several questions must be addressed. A recent paper that reports the dynamics of bacterial cooperation and virulence in a field experiment provides an excellent nucleus for bringing together key empirical and theoretical results which help us to frame - if not completely to answer - these questions.}, } @article {pmid24833059, year = {2013}, author = {Gramzow, L and Theißen, G}, title = {Phylogenomics of MADS-Box Genes in Plants - Two Opposing Life Styles in One Gene Family.}, journal = {Biology}, volume = {2}, number = {3}, pages = {1150-1164}, pmid = {24833059}, issn = {2079-7737}, abstract = {The development of multicellular eukaryotes, according to their body plan, is often directed by members of multigene families that encode transcription factors. MADS (for MINICHROMOSOME MAINTENANCE1, AGAMOUS, DEFICIENS and SERUM RESPONSE FACTOR)-box genes form one of those families controlling nearly all major aspects of plant development. Knowing the complete complement of MADS-box genes in sequenced plant genomes will allow a better understanding of the evolutionary patterns of these genes and the association of their evolution with the evolution of plant morphologies. Here, we have applied a combination of automatic and manual annotations to identify the complete set of MADS-box genes in 17 plant genomes. Furthermore, three plant genomes were reanalyzed and published datasets were used for four genomes such that more than 2,600 genes from 24 species were classified into the two types of MADS-box genes, Type I and Type II. Our results extend previous studies, highlighting the remarkably different evolutionary patterns of Type I and Type II genes and provide a basis for further studies on the evolution and function of MADS-box genes.}, } @article {pmid24769743, year = {2013}, author = {Torday, JS}, title = {Evolutionary biology redux.}, journal = {Perspectives in biology and medicine}, volume = {56}, number = {4}, pages = {455-484}, doi = {10.1353/pbm.2013.0038}, pmid = {24769743}, issn = {1529-8795}, mesh = {Aging ; Animals ; *Biological Evolution ; Cell Communication ; Gene Expression Regulation ; Homeostasis ; Humans ; Models, Biological ; Phylogeny ; Selection, Genetic ; Signal Transduction ; }, abstract = {This article offers a novel, enlightened concept for determining the mechanism of evolution. It is based on homeostasis, which distinguishes life from non-life and as such is the universal mechanism for the evolution of all living organisms. This view of evolution is logical, mechanistic, non-scalar, predictive, testable, and falsifiable, and it illuminates the epistemological relationships between physics and biology, ontogeny and phylogeny, development and aging, ultimate and proximate causation, health and disease. In addition to validating Haeckel's biogenetic law and Lamarckian epigenetics, reflecting the enabling value of the cellular approach, this perspective also expresses the evolutionary process at the cell-molecular level, since the mechanism of cell communication itself is universal in biology, in keeping with a Kuhnian paradigm shift. This approach may even elucidate the nature and evolution of consciousness as a manifestation of the cellular continuum from unicellular to multicellular life. We need such a functional genomic mechanism for the process of evolution if we are to make progress in biology and medicine. Like Copernican heliocentrism, a cellular approach to evolution may fundamentally change humankind's perceptions about our place in the universe.}, } @article {pmid23214131, year = {2012}, author = {Kikulska, A and Mlacki, M and Wilanowski, T}, title = {[The role of LSF/Grainyhead transcription factors in development and function of epidermal barrier in animals].}, journal = {Postepy biochemii}, volume = {58}, number = {1}, pages = {69-78}, pmid = {23214131}, issn = {0032-5422}, mesh = {Animals ; Apoptosis/genetics ; Cell Proliferation ; DNA-Binding Proteins/metabolism ; Disease Models, Animal ; Epidermis/embryology/*metabolism ; Gene Expression ; Humans ; Neoplasms/genetics ; Neural Tube Defects/genetics ; Transcription Factors/genetics/*metabolism ; Wound Healing/genetics ; }, abstract = {The LSF/Grainyhead family of transcription factors consists of proteins whose structure and functions have been preserved in the course of eukaryotic evolution--from primitive unicellular life forms to complex multicellular organisms. In the latter, these factors display tissue specificity and are active mainly in the covering epithelium. The roles of GRH factors are associated with regulation of expression of genes essential for correct differentiation and functioning of the epithelia of ectodermal origin. The Grh gene expression profiles are diverse and variable, especially during embryonic development. Research on the role of GRHL transcription factors is carried out on cellular and organismal level. In experimental animals, aberrant Grh gene expression leads to many diseases, including failure of epidermal wound healing and neural tube defects. Changes of these genes' expression levels are also linked to carcinogenesis. GRHL transcription factors participate in signaling pathways involved in cellular proliferation and apoptosis.}, } @article {pmid23211014, year = {2013}, author = {Sun, BF and Xiao, JH and He, SM and Liu, L and Murphy, RW and Huang, DW}, title = {Multiple ancient horizontal gene transfers and duplications in lepidopteran species.}, journal = {Insect molecular biology}, volume = {22}, number = {1}, pages = {72-87}, doi = {10.1111/imb.12004}, pmid = {23211014}, issn = {1365-2583}, mesh = {Animals ; Biological Evolution ; Bombyx/genetics ; Expressed Sequence Tags ; *Gene Transfer, Horizontal ; Genome, Insect ; Lepidoptera/*genetics/metabolism ; Phylogeny ; Selection, Genetic ; }, abstract = {Eukaryotic horizontal gene transfer (HGT) events are increasingly being discovered yet few reports have summarized multiple occurrences in a wide range of species. We systematically investigated HGT events in the order Lepidoptera by employing a series of filters. Bombyx mori, Danaus plexippus and Heliconius melpomene had 13, 12 and 12 HGTs, respectively, from bacteria and fungi. These HGTs contributed a total of 64 predicted genes: 22 to B. mori, 22 to D. plexippus and 20 to H. melpomene. Several new genes were generated by post-transfer duplications. Post-transfer duplication of a suite of functional HGTs has rarely been reported in higher organisms. The distributional patterns of paralogues for certain genes differed in the three species, indicating potential independent duplication or loss events. All of these HGTs had homologues expressed in some other lepidopterans, indicating ancient transfer events. Most HGTs were involved in the metabolism of sugar and amino acids. These HGTs appeared to have experienced amelioration, purifying selection and accelerated evolution to adapt to the background genome of the recipient. The discovery of ancient, massive HGTs and duplications in lepidopterans and their adaptive evolution provides further insights into the evolutionary significance of the events from donors to multicellular host recipients.}, } @article {pmid23209170, year = {2013}, author = {Chevin, LM and Gallet, R and Gomulkiewicz, R and Holt, RD and Fellous, S}, title = {Phenotypic plasticity in evolutionary rescue experiments.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {368}, number = {1610}, pages = {20120089}, pmid = {23209170}, issn = {1471-2970}, mesh = {*Adaptation, Physiological ; Animals ; Bacteria ; *Biological Evolution ; Competitive Behavior ; Environment ; Extinction, Biological ; Genetic Fitness/physiology ; Mutation ; *Phenotype ; Plants ; Population Density ; Population Dynamics ; Selection, Genetic ; Stress, Physiological ; }, abstract = {Population persistence in a new and stressful environment can be influenced by the plastic phenotypic responses of individuals to this environment, and by the genetic evolution of plasticity itself. This process has recently been investigated theoretically, but testing the quantitative predictions in the wild is challenging because (i) there are usually not enough population replicates to deal with the stochasticity of the evolutionary process, (ii) environmental conditions are not controlled, and (iii) measuring selection and the inheritance of traits affecting fitness is difficult in natural populations. As an alternative, predictions from theory can be tested in the laboratory with controlled experiments. To illustrate the feasibility of this approach, we briefly review the literature on the experimental evolution of plasticity, and on evolutionary rescue in the laboratory, paying particular attention to differences and similarities between microbes and multicellular eukaryotes. We then highlight a set of questions that could be addressed using this framework, which would enable testing the robustness of theoretical predictions, and provide new insights into areas that have received little theoretical attention to date.}, } @article {pmid23206384, year = {2013}, author = {Tarnita, CE and Taubes, CH and Nowak, MA}, title = {Evolutionary construction by staying together and coming together.}, journal = {Journal of theoretical biology}, volume = {320}, number = {}, pages = {10-22}, doi = {10.1016/j.jtbi.2012.11.022}, pmid = {23206384}, issn = {1095-8541}, support = {R01 GM078986/GM/NIGMS NIH HHS/United States ; R01GM078986/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Eukaryotic Cells/physiology ; *Models, Biological ; *Origin of Life ; }, abstract = {The evolutionary trajectory of life on earth is one of increasing size and complexity. Yet the standard equations of evolutionary dynamics describe mutation and selection among similar organisms that compete on the same level of organization. Here we begin to outline a mathematical theory that might help to explore how evolution can be constructive, how natural selection can lead from lower to higher levels of organization. We distinguish two fundamental operations, which we call 'staying together' and 'coming together'. Staying together means that individuals form larger units by not separating after reproduction, while coming together means that independent individuals form aggregates. Staying together can lead to specialization and division of labor, but the developmental program must evolve in the basic unit. Coming together can be creative by combining units with different properties. Both operations have been identified in the context of multicellularity, but they have been treated very similarly. Here we point out that staying together and coming together can be found at every level of biological construction and moreover that they face different evolutionary problems. The distinction is particularly clear in the context of cooperation and defection. For staying together the stability of cooperation takes the form of a developmental error threshold, while coming together leads to evolutionary games and requires a mechanism for the evolution of cooperation. We use our models to discuss simple aspects of the evolution of protocells, eukarya, multi-cellularity and animal societies.}, } @article {pmid23201916, year = {2013}, author = {Bailey, M and Christoforidou, Z and Lewis, M}, title = {Evolution of immune systems: specificity and autoreactivity.}, journal = {Autoimmunity reviews}, volume = {12}, number = {6}, pages = {643-647}, doi = {10.1016/j.autrev.2012.10.007}, pmid = {23201916}, issn = {1873-0183}, mesh = {Adaptive Immunity ; Animals ; *Biological Evolution ; Humans ; *Immune System ; }, abstract = {Multicellularity evolved well before 600 million years ago, and all multicellular animals have evolved since then with the need to protect against pathogens. There is no reason to expect their immune systems to be any less sophisticated than ours. The vertebrate system, based on rearranging immunoglobulin-superfamily domains, appears to have evolved partly as a result of chance insertion of RAG genes by horizontal transfer. Remarkably sophisticated systems for expansion of immunological repertoire have evolved in parallel in many groups of organisms. Vaccination of invertebrates against commercially important pathogens has been empirically successful, and suggests that the definition of an adaptive and innate immune system should no longer depend on the presence of memory and specificity, since these terms are hard to define in themselves. The evolution of randomly-created immunological repertoire also carries with it the potential for generating autoreactive specificities and consequent autoimmune damage. While invertebrates may use systems analogous to ours to control autoreactive specificities, they may have evolved alternative mechanisms which operate either at the level of individuals-within-populations rather than cells-within-individuals, by linking self-reactive specificities to regulatory pathways and non-self-reactive to effector pathways.}, } @article {pmid23194272, year = {2012}, author = {Armengaud, J and Christie-Oleza, JA and Clair, G and Malard, V and Duport, C}, title = {Exoproteomics: exploring the world around biological systems.}, journal = {Expert review of proteomics}, volume = {9}, number = {5}, pages = {561-575}, doi = {10.1586/epr.12.52}, pmid = {23194272}, issn = {1744-8387}, mesh = {Bacteria/isolation & purification/pathogenicity ; Cell Line ; Computational Biology ; *Extracellular Space/chemistry/metabolism ; High-Throughput Screening Assays/methods ; Humans ; Mass Spectrometry/methods ; *Peptides/chemistry/isolation & purification/metabolism ; *Proteins/classification/isolation & purification/metabolism ; Proteomics/*methods ; }, abstract = {The term 'exoproteome' describes the protein content that can be found in the extracellular proximity of a given biological system. These proteins arise from cellular secretion, other protein export mechanisms or cell lysis, but only the most stable proteins in this environment will remain in abundance. It has been shown that these proteins reflect the physiological state of the cells in a given condition and are indicators of how living systems interact with their environments. High-throughput proteomic approaches based on a shotgun strategy, and high-resolution mass spectrometers, have modified the authors' view of exoproteomes. In the present review, the authors describe how these new approaches should be exploited to obtain the maximum useful information from a sample, whatever its origin. The methodologies used for studying secretion from model cell lines derived from eukaryotic, multicellular organisms, virulence determinants of pathogens and environmental bacteria and their relationships with their habitats are illustrated with several examples. The implication of such data, in terms of proteogenomics and the discovery of novel protein functions, is discussed.}, } @article {pmid23188094, year = {2012}, author = {Gupta, GD and Kale, A and Kumar, V}, title = {Molecular evolution of translin superfamily proteins within the genomes of eubacteria, archaea and eukaryotes.}, journal = {Journal of molecular evolution}, volume = {75}, number = {5-6}, pages = {155-167}, pmid = {23188094}, issn = {1432-1432}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Archaea/genetics ; Carrier Proteins/chemistry/genetics/metabolism ; DNA-Binding Proteins/chemistry/*genetics/metabolism ; Eubacterium/genetics ; Eukaryota/genetics ; *Evolution, Molecular ; *Genome ; Humans ; Models, Molecular ; Molecular Sequence Data ; *Multigene Family ; Phylogeny ; Protein Conformation ; RNA-Binding Proteins/chemistry/*genetics/metabolism ; Sequence Alignment ; }, abstract = {Translin and its interacting partner protein, TRAX, are members of the translin superfamily. These proteins are involved in mRNA regulation and in promoting RISC activity by removing siRNA passenger strand cleavage products, and have been proposed to play roles in DNA repair and recombination. Both homomeric translin and heteromeric translin-TRAX complex bind to ssDNA and RNA; however, the heteromeric complex is a key activator in siRNA-mediated silencing in human and drosophila. The residues critical for RNase activity of the complex reside in TRAX sequence. Both translin and TRAX are well conserved in eukaryotes. In present work, a single translin superfamily protein is detected in Chloroflexi eubacteria, in the known phyla of archaea and in some unicellular eukaryotes. The prokaryotic proteins essentially share unique sequence motifs with eukaryotic TRAX, while the proteins possessing both the unique sequences and conserved indels of TRAX or translin can be identified from protists. Intriguingly, TRAX protein in all the known genomes of extant Chloroflexi share high sequence similarity and conserved indels with the archaeal protein, suggesting occurrence of TRAX at least at the time of Chloroflexi divergence as well as evolutionary relationship between Chloroflexi and archaea. The mirror phylogeny in phylogenetic tree, constructed using diverse translin and TRAX sequences, indicates gene duplication event leading to evolution of translin in unicellular eukaryotes, prior to divergence of multicellular eukayrotes. Since Chloroflexi has been debated to be near the last universal common ancestor, the present analysis indicates that TRAX may be useful to understand the tree of life.}, } @article {pmid23185420, year = {2012}, author = {Turnbull, C and Wilson, PD and Hoggard, S and Gillings, M and Palmer, C and Smith, S and Beattie, D and Hussey, S and Stow, A and Beattie, A}, title = {Primordial enemies: fungal pathogens in thrips societies.}, journal = {PloS one}, volume = {7}, number = {11}, pages = {e49737}, pmid = {23185420}, issn = {1932-6203}, mesh = {Animals ; Antifungal Agents/metabolism ; Behavior, Animal ; Biological Evolution ; Cordyceps/*pathogenicity/physiology ; Female ; Fungi/*pathogenicity/physiology ; Insecta ; Linear Models ; Male ; Thysanoptera/*microbiology ; }, abstract = {Microbial pathogens are ancient selective agents that have driven many aspects of multicellular evolution, including genetic, behavioural, chemical and immune defence systems. It appears that fungi specialised to attack insects were already present in the environments in which social insects first evolved and we hypothesise that if the early stages of social evolution required antifungal defences, then covariance between levels of sociality and antifungal defences might be evident in extant lineages, the defences becoming stronger with group size and increasing social organisation. Thus, we compared the activity of cuticular antifungal compounds in thrips species (Insecta: Thysanoptera) representing a gradient of increasing group size and sociality: solitary, communal, social and eusocial, against the entomopathogen Cordyceps bassiana. Solitary and communal species showed little or no activity. In contrast, the social and eusocial species killed this fungus, suggesting that the evolution of sociality has been accompanied by sharp increases in the effectiveness of antifungal compounds. The antiquity of fungal entomopathogens, demonstrated by fossil finds, coupled with the unequivocal response of thrips colonies to them shown here, suggests two new insights into the evolution of thrips sociality: First, traits that enabled nascent colonies to defend themselves against microbial pathogens should be added to those considered essential for social evolution. Second, limits to the strength of antimicrobials, through resource constraints or self-antibiosis, may have been overcome by increase in the numbers of individuals secreting them, thus driving increases in colony size. If this is the case for social thrips, then we may ask: did antimicrobial traits and microbes such as fungal entomopathogens play an integral part in the evolution of insect sociality in general?}, } @article {pmid23180579, year = {2013}, author = {Mukherjee, K and Campos, H and Kolaczkowski, B}, title = {Evolution of animal and plant dicers: early parallel duplications and recurrent adaptation of antiviral RNA binding in plants.}, journal = {Molecular biology and evolution}, volume = {30}, number = {3}, pages = {627-641}, pmid = {23180579}, issn = {1537-1719}, mesh = {Adaptation, Biological/genetics ; Amino Acid Sequence ; Animals ; Bayes Theorem ; Catalytic Domain ; Conserved Sequence ; *Evolution, Molecular ; Gene Duplication ; Likelihood Functions ; Models, Genetic ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Plant Proteins/chemistry/*genetics ; Plants/enzymology/genetics ; Protein Binding ; RNA Interference ; Ribonuclease III/chemistry/*genetics ; Selection, Genetic ; Sequence Analysis, Protein ; Surface Properties ; }, abstract = {RNA interference (RNAi) is a eukaryotic molecular system that serves two primary functions: 1) gene regulation and 2) protection against selfish elements such as viruses and transposable DNA. Although the biochemistry of RNAi has been detailed in model organisms, very little is known about the broad-scale patterns and forces that have shaped RNAi evolution. Here, we provide a comprehensive evolutionary analysis of the Dicer protein family, which carries out the initial RNA recognition and processing steps in the RNAi pathway. We show that Dicer genes duplicated and diversified independently in early animal and plant evolution, coincident with the origins of multicellularity. We identify a strong signature of long-term protein-coding adaptation that has continually reshaped the RNA-binding pocket of the plant Dicer responsible for antiviral immunity, suggesting an evolutionary arms race with viral factors. We also identify key changes in Dicer domain architecture and sequence leading to specialization in either gene-regulatory or protective functions in animal and plant paralogs. As a whole, these results reveal a dynamic picture in which the evolution of Dicer function has driven elaboration of parallel RNAi functional pathways in animals and plants.}, } @article {pmid23179353, year = {2012}, author = {Tang, YH and Han, SP and Kassahn, KS and Skarshewski, A and Rothnagel, JA and Smith, R}, title = {Complex evolutionary relationships among four classes of modular RNA-binding splicing regulators in eukaryotes: the hnRNP, SR, ELAV-like and CELF proteins.}, journal = {Journal of molecular evolution}, volume = {75}, number = {5-6}, pages = {214-228}, pmid = {23179353}, issn = {1432-1432}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; CCAAT-Enhancer-Binding Protein-delta/chemistry/genetics ; Cluster Analysis ; Computational Biology ; Consensus Sequence ; ELAV Proteins/chemistry/genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; Heterogeneous-Nuclear Ribonucleoproteins/genetics ; Humans ; Molecular Sequence Data ; Nuclear Proteins/genetics ; Phylogeny ; *RNA Splicing ; RNA-Binding Proteins/*genetics ; Sequence Alignment ; Serine-Arginine Splicing Factors ; }, abstract = {Alternative RNA splicing in multicellular organisms is regulated by a large group of proteins of mainly unknown origin. To predict the functions of these proteins, classification of their domains at the sequence and structural level is necessary. We have focused on four groups of splicing regulators, the heterogeneous nuclear ribonucleoprotein (hnRNP), serine-arginine (SR), embryonic lethal, abnormal vision (ELAV)-like, and CUG-BP and ETR-like factor (CELF) proteins, that show increasing diversity among metazoa. Sequence and phylogenetic analyses were used to obtain a broader understanding of their evolutionary relationships. Surprisingly, when we characterised sequence similarities across full-length sequences and conserved domains of ten metazoan species, we found some hnRNPs were more closely related to SR, ELAV-like and CELF proteins than to other hnRNPs. Phylogenetic analyses and the distribution of the RRM domains suggest that these proteins diversified before the last common ancestor of the metazoans studied here through domain acquisition and duplication to create genes of mixed evolutionary origin. We propose that these proteins were derived independently rather than through the expansion of a single protein family. Our results highlight inconsistencies in the current classification system for these regulators, which does not adequately reflect their evolutionary relationships, and suggests that a domain-based classification scheme may have more utility.}, } @article {pmid23165352, year = {2013}, author = {Jolliffe, AK and Derry, WB}, title = {The TP53 signaling network in mammals and worms.}, journal = {Briefings in functional genomics}, volume = {12}, number = {2}, pages = {129-141}, doi = {10.1093/bfgp/els047}, pmid = {23165352}, issn = {2041-2657}, support = {MOP 79495//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Caenorhabditis elegans/*metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; Evolution, Molecular ; Humans ; Mammals/*metabolism ; *Signal Transduction ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {The nematode worm Caenorhabditis elegans has been an invaluable model organism for studying the molecular mechanisms that govern cell fate, from fundamental aspects of multicellular development to programmed cell death (apoptosis). The transparency of this organism permits visualization of cells in living animals at high resolution. The powerful genetics and functional genomics tools available in C. elegans allow for detailed analysis of gene function, including genes that are frequently deregulated in human diseases such as cancer. The TP53 protein is a critical suppressor of tumor formation in vertebrates, and the TP53 gene is mutated in over 50% of human cancers. TP53 suppresses malignancy by integrating a variety of cellular stresses that direct it to activate transcription of genes that help to repair the damage or trigger apoptotic death if the damage is beyond repair. The TP53 paralogs, TP63 and TP73, have distinct roles in development as well as overlapping functions with TP53 in apoptosis and repair, which complicates their analysis in vertebrates. C. elegans contains a single TP53 family member, cep-1, that shares properties of all three vertebrate genes and thus offers a simple system in which to study the biological functions of this important gene family. This review summarizes major advances in our understanding of the TP53 family using C. elegans as a model organism.}, } @article {pmid23163752, year = {2013}, author = {Belaidi, AA and Schwarz, G}, title = {Metal insertion into the molybdenum cofactor: product-substrate channelling demonstrates the functional origin of domain fusion in gephyrin.}, journal = {The Biochemical journal}, volume = {450}, number = {1}, pages = {149-157}, doi = {10.1042/BJ20121078}, pmid = {23163752}, issn = {1470-8728}, mesh = {Alternative Splicing ; Apoproteins/chemistry/genetics/metabolism ; Carrier Proteins/*chemistry/genetics/metabolism ; Coenzymes/*chemistry/metabolism ; Membrane Proteins/*chemistry/genetics/metabolism ; Metalloproteins/*chemistry/metabolism ; Molybdenum/*chemistry/metabolism ; Molybdenum Cofactors ; Protein Processing, Post-Translational ; Protein Structure, Tertiary ; Pteridines/*chemistry/metabolism ; Recombinant Proteins/chemistry/genetics/metabolism ; }, abstract = {The complexity of eukaryotic multicellular organisms relies on evolutionary developments that include compartmentalization, alternative splicing, protein domain fusion and post-translational modification. Mammalian gephyrin uniquely exemplifies these processes by combining two enzymatic functions within the biosynthesis of the Moco (molybdenum cofactor) in a multidomain protein. It also undergoes extensive alternative splicing, especially in neurons, where it also functions as a scaffold protein at inhibitory synapses. Two out of three gephyrin domains are homologous to bacterial Moco-synthetic proteins (G and E domain) while being fused by a third gephyrin-specific central C domain. In the present paper, we have established the in vitro Moco synthesis using purified components and demonstrated an over 300-fold increase in Moco synthesis for gephyrin compared with the isolated G domain, which synthesizes adenylylated molybdopterin, and E domain, which catalyses the metal insertion at physiological molybdate concentrations in an ATP-dependent manner. We show that the C domain impacts the catalytic efficacy of gephyrin, suggesting an important structural role in product-substrate channelling as depicted by a structural model that is in line with a face-to-face orientation of both active sites. Our functional studies demonstrate the evolutionary advantage of domain fusion in metabolic proteins, which can lead to the development of novel functions in higher eukaryotes.}, } @article {pmid23139082, year = {2013}, author = {Koonin, EV and Csuros, M and Rogozin, IB}, title = {Whence genes in pieces: reconstruction of the exon-intron gene structures of the last eukaryotic common ancestor and other ancestral eukaryotes.}, journal = {Wiley interdisciplinary reviews. RNA}, volume = {4}, number = {1}, pages = {93-105}, doi = {10.1002/wrna.1143}, pmid = {23139082}, issn = {1757-7012}, mesh = {Alternative Splicing ; Animals ; Biological Evolution ; Conserved Sequence/genetics ; Eukaryota/*genetics ; Evolution, Molecular ; Exons/*genetics ; Genome ; Humans ; Introns/*genetics ; Spliceosomes/genetics ; }, abstract = {In eukaryotes, protein-coding sequences are interrupted by non-coding sequences known as introns. During mRNA maturation, introns are excised by the spliceosome and the coding regions, exons, are spliced to form the mature coding region. The intron densities widely differ between eukaryotic lineages, from 6 to 7 introns per kb of coding sequence in vertebrates, some invertebrates and green plants, to only a few introns across the entire genome in many unicellular eukaryotes. Evolutionary reconstructions using maximum likelihood methods suggest intron-rich ancestors for each major group of eukaryotes. For the last common ancestor of animals, the highest intron density of all extant and extinct eukaryotes was inferred, at 120-130% of the human intron density. Furthermore, an intron density within 53-74% of the human values was inferred for the last eukaryotic common ancestor. Accordingly, evolution of eukaryotic genes in all lines of descent involved primarily intron loss, with substantial gain only at the bases of several branches including plants and animals. These conclusions have substantial biological implications indicating that the common ancestor of all modern eukaryotes was a complex organism with a gene architecture resembling those in multicellular organisms. Alternative splicing most likely initially appeared as an inevitable result of splicing errors and only later was employed to generate structural and functional diversification of proteins.}, } @article {pmid23136763, year = {2012}, author = {Kotolupov, VA and Isaeva, VV}, title = {[Cells in the system of multicelular organisms from positions of non-linear dynamics].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {48}, number = {5}, pages = {517-526}, pmid = {23136763}, issn = {0044-4529}, mesh = {Adaptation, Biological/*physiology ; Animals ; Apoptosis/*physiology ; Cell Differentiation/*physiology ; Homeostasis/*physiology ; *Models, Biological ; *Nonlinear Dynamics ; }, abstract = {The organism physiological systems forming a hierarchic network with mutual dependence and subordination can be considered as systems with non-linear dynamics including positive and negative feedbacks. In the course of evolution there occurred selection of robust, flexible, modular systems capable for adaptive self-organization by non-linear interaction of components, which leads to formation of the ordered in space and time robust and plastic organization of the whole. Cells of multicellular organisms are capable for coordinated "social" behavior with formation of ordered cell assemblies, which provides a possibility of morphological and functional variability correlating with manifestations of the large spectrum of adaptive reactions. The multicellular organism is the multilevel system with hierarchy of numerous subsystems capable for adaptive self-organization; disturbance of their homeostasis can lead to pathological changes. The healthy organism regulates homeostasis, self-renewal, differentiation, and apoptosis of cells serving its parts and construction blocks by preserving its integrity and controlling behavior of cells. The systemic approach taking into account biological regularities of the appearance and development of functions in evolution of multicellular organisms opens new possibilities for diagnostics and treatment of many diseases.}, } @article {pmid23134060, year = {2013}, author = {Glöckner, G and Noegel, AA}, title = {Comparative genomics in the Amoebozoa clade.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {88}, number = {1}, pages = {215-225}, doi = {10.1111/j.1469-185X.2012.00248.x}, pmid = {23134060}, issn = {1469-185X}, mesh = {Amoebozoa/*genetics ; Animals ; *Biological Evolution ; *Genome ; *Genomics ; Phylogeny ; }, abstract = {Amoeboid life forms can be found throughout the evolutionary tree. The greatest proportion of these life forms is found in the Amoebozoa clade, one of the six major eukaryote evolutionary branches. Despite its common origin this clade exhibits a wide diversity of lifestyles including free-living and parasitic species and species with multicellular and multinucleate life stages. In this group, development, cooperation, and social behaviour can be studied in addition to traits common to unicellular organisms. To date, only a few Amoebozoa genomes have been sequenced completely, however a number of expressed sequence tags (ESTs) and complete and draft genomes have become available recently for several species that represent some of the major evolutionary lineages in this clade. This resource allows us to compare and analyse the evolutionary history and fate of branch-specific genes if properly exploited. Despite the large evolutionary time scale since the emergence of the major groups the genomic organization in Amoebozoa has retained common features. The number of Amoebozoa-specific genetic inventions seems to be rather small. The emergence of subgroups is accompanied by gene and domain losses and acquisitions of bacterial gene material. The sophisticated developmental cycles of Myxogastria and Dictyosteliida likely have a common origin and are deeply rooted in amoebozoan evolution. In this review we describe initial approaches to comparative genomics in Amoebozoa, summarize recent findings, and identify goals for further studies.}, } @article {pmid23133603, year = {2012}, author = {Jami, SK and Clark, GB and Ayele, BT and Ashe, P and Kirti, PB}, title = {Genome-wide comparative analysis of annexin superfamily in plants.}, journal = {PloS one}, volume = {7}, number = {11}, pages = {e47801}, pmid = {23133603}, issn = {1932-6203}, mesh = {Amino Acid Motifs ; Annexins/genetics/*metabolism ; Arabidopsis/genetics ; Bayes Theorem ; Binding Sites ; Calcium/chemistry ; Chromosomes/ultrastructure ; Databases, Genetic ; Exons ; *Genome-Wide Association Study ; Introns ; Likelihood Functions ; Multigene Family ; Oryza/genetics ; Phylogeny ; Plants/*genetics ; Protein Structure, Tertiary ; }, abstract = {Most annexins are calcium-dependent, phospholipid-binding proteins with suggested functions in response to environmental stresses and signaling during plant growth and development. They have previously been identified and characterized in Arabidopsis and rice, and constitute a multigene family in plants. In this study, we performed a comparative analysis of annexin gene families in the sequenced genomes of Viridiplantae ranging from unicellular green algae to multicellular plants, and identified 149 genes. Phylogenetic studies of these deduced annexins classified them into nine different arbitrary groups. The occurrence and distribution of bona fide type II calcium binding sites within the four annexin domains were found to be different in each of these groups. Analysis of chromosomal distribution of annexin genes in rice, Arabidopsis and poplar revealed their localization on various chromosomes with some members also found on duplicated chromosomal segments leading to gene family expansion. Analysis of gene structure suggests sequential or differential loss of introns during the evolution of land plant annexin genes. Intron positions and phases are well conserved in annexin genes from representative genomes ranging from Physcomitrella to higher plants. The occurrence of alternative motifs such as K/R/HGD was found to be overlapping or at the mutated regions of the type II calcium binding sites indicating potential functional divergence in certain plant annexins. This study provides a basis for further functional analysis and characterization of annexin multigene families in the plant lineage.}, } @article {pmid23129619, year = {2012}, author = {Sung, W and Tucker, AE and Doak, TG and Choi, E and Thomas, WK and Lynch, M}, title = {Extraordinary genome stability in the ciliate Paramecium tetraurelia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {47}, pages = {19339-19344}, pmid = {23129619}, issn = {1091-6490}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Substitution/genetics ; DNA-Directed DNA Polymerase/metabolism ; Genome, Protozoan/*genetics ; Genomic Instability/*genetics ; Mitochondria/genetics ; Mutation Rate ; Paramecium tetraurelia/enzymology/*genetics ; Reproduction/genetics ; }, abstract = {Mutation plays a central role in all evolutionary processes and is also the basis of genetic disorders. Established base-substitution mutation rates in eukaryotes range between ∼5 × 10(-10) and 5 × 10(-8) per site per generation, but here we report a genome-wide estimate for Paramecium tetraurelia that is more than an order of magnitude lower than any previous eukaryotic estimate. Nevertheless, when the mutation rate per cell division is extrapolated to the length of the sexual cycle for this protist, the measure obtained is comparable to that for multicellular species with similar genome sizes. Because Paramecium has a transcriptionally silent germ-line nucleus, these results are consistent with the hypothesis that natural selection operates on the cumulative germ-line replication fidelity per episode of somatic gene expression, with the germ-line mutation rate per cell division evolving downward to the lower barrier imposed by random genetic drift. We observe ciliate-specific modifications of widely conserved amino acid sites in DNA polymerases as one potential explanation for unusually high levels of replication fidelity.}, } @article {pmid23128987, year = {2013}, author = {Bloemendal, S and Kück, U}, title = {Cell-to-cell communication in plants, animals, and fungi: a comparative review.}, journal = {Die Naturwissenschaften}, volume = {100}, number = {1}, pages = {3-19}, pmid = {23128987}, issn = {1432-1904}, mesh = {Animals ; Cell Communication/*physiology ; Fungi/*physiology ; *Plant Physiological Phenomena ; Plants/virology ; }, abstract = {Cell-to-cell communication is a prerequisite for differentiation and development in multicellular organisms. This communication has to be tightly regulated to ensure that cellular components such as organelles, macromolecules, hormones, or viruses leave the cell in a precisely organized way. During evolution, plants, animals, and fungi have developed similar ways of responding to this biological challenge. For example, in higher plants, plasmodesmata connect adjacent cells and allow communication to regulate differentiation and development. In animals, two main general structures that enable short- and long-range intercellular communication are known, namely gap junctions and tunneling nanotubes, respectively. Finally, filamentous fungi have also developed specialized structures called septal pores that allow intercellular communication via cytoplasmic flow. This review summarizes the underlying mechanisms for intercellular communication in these three eukaryotic groups and discusses its consequences for the regulation of differentiation and developmental processes.}, } @article {pmid23109712, year = {2013}, author = {Gest, N and Gautier, H and Stevens, R}, title = {Ascorbate as seen through plant evolution: the rise of a successful molecule?.}, journal = {Journal of experimental botany}, volume = {64}, number = {1}, pages = {33-53}, doi = {10.1093/jxb/ers297}, pmid = {23109712}, issn = {1460-2431}, mesh = {Antioxidants/metabolism ; Ascorbic Acid/*metabolism ; *Biological Evolution ; Biological Transport ; Origin of Life ; Plants/*metabolism ; }, abstract = {Ascorbate is a widespread and efficient antioxidant that has multiple functions in plants, traditionally associated with the reactions of photosynthesis. This review aims to look at ascorbate from an evolutionary perspective. Cyanobacteria, algae, and bryophytes contain lower concentrations of ascorbate than higher plants, where the molecule accumulates in high concentrations in both photosynthetic and non-photosynthetic organs and tissues. This increase in ascorbate concentration is paralleled by an increase in the number of isoforms of ascorbate peroxidase and the ascorbate regenerating enzymes mono- and dehydroascorbate reductase. One way of understanding the rise in ascorbate concentrations is to consider ascorbate as a molecule among others that has been subject to selection pressures during evolution, due to its cost or benefit for the cell and the organism. Ascorbate has a low cost in terms of synthesis and toxicity, and its benefits include protection of the glutathione pool and proper functioning of a range of enzymes. The hypothesis presented here is that these features would have favoured increasing roles for the molecule in the development and growth of multicellular organisms. This review then focuses on this diversity of roles for ascorbate in both photosynthetic and non-photosynthetic tissues of higher plants, including fruits and seeds, as well as further functions the molecule may possess by looking at other species. The review also highlights one of the trade-offs of domestication, which has often reduced or diluted ascorbate content in the quest for increased fruit growth and yield, with unknown consequences for the corresponding functional diversity, particularly in terms of stress resistance and adaptive responses to the environment.}, } @article {pmid23109363, year = {2013}, author = {Ríos-Barrera, LD and Riesgo-Escovar, JR}, title = {Regulating cell morphogenesis: the Drosophila Jun N-terminal kinase pathway.}, journal = {Genesis (New York, N.Y. : 2000)}, volume = {51}, number = {3}, pages = {147-162}, doi = {10.1002/dvg.22354}, pmid = {23109363}, issn = {1526-968X}, mesh = {Animals ; Drosophila/*enzymology/genetics/growth & development ; Gene Expression Regulation, Developmental ; JNK Mitogen-Activated Protein Kinases/genetics/*metabolism ; *MAP Kinase Signaling System ; Morphogenesis/*genetics ; }, abstract = {The Jun-N-terminal Kinase pathway (JNK), known also as stress activated protein kinase pathway (SAPK), is an eukaryotic evolutionarily conserved signaling pathway. From a purported evolutionarily "ancient" function as stress mediator, it evolved in multicellular eukaryotes to permanent roles in development, without leaving its original function. In Drosophila melanogaster, it is required for follicle cell morphogenesis, embryonic dorsal closure, pupal thoracic closure and genital disc rotation closure, all processes with requisite cell shape changes. Besides, it is activated during wound healing and in response to stress (UV irradiation, oxidative stress) where it may signal cell death or proliferation. Despite these varied roles, it has a conserved core of molecules that follow the MAPKKK/MAPKK/MAPK logic of mitogen activated protein kinases pathways. Regulation of the JNK pathway appears majorly negative, with phosphatases, transcription factors and proteins of novel structure "holding back" on JNK activation in different tissues. This particular mode of regulation may hark back to the pathway's origin as stress detector and responder, implying readiness to respond, from which the developmental roles may have evolved as conditions demanding obligate and predicted stress responses (i.e., embryonic dorsal closure viewed as a "wound of development").}, } @article {pmid23108939, year = {2012}, author = {Baluška, F}, title = {Rethinking origins of multicellularity: convergent evolution of epithelia in plants.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {12}, pages = {1085}, doi = {10.1002/bies.201200134}, pmid = {23108939}, issn = {1521-1878}, mesh = {Animals ; *Cell Polarity ; Dictyostelium/*cytology ; Epithelial Cells/*physiology ; Humans ; }, } @article {pmid23103169, year = {2012}, author = {Qian, W and Ma, D and Xiao, C and Wang, Z and Zhang, J}, title = {The genomic landscape and evolutionary resolution of antagonistic pleiotropy in yeast.}, journal = {Cell reports}, volume = {2}, number = {5}, pages = {1399-1410}, pmid = {23103169}, issn = {2211-1247}, support = {R01 GM067030/GM/NIGMS NIH HHS/United States ; R01 GM103232/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; *Biological Evolution ; Gene Deletion ; Gene Expression Regulation, Fungal ; Genetic Pleiotropy/*genetics ; Genetics, Population ; *Genome ; *Models, Genetic ; Saccharomyces cerevisiae/*genetics ; }, abstract = {Antagonistic pleiotropy (AP), or genetic tradeoff, is an important concept that is frequently invoked in theories of aging, cancer, genetic disease, and other common phenomena. However, the prevalence of AP, which genes are subject to AP, and to what extent and how AP may be resolved remain unclear. By measuring the fitness difference between the wild-type and null alleles of ~5,000 nonessential genes in yeast, we found that in any given environment, yeast expresses hundreds of genes that harm rather than benefit the organism, demonstrating widespread AP. Nonetheless, under sufficient selection, AP is often resolvable through regulatory evolution, primarily by trans-acting changes, although in one case we also detected a cis-acting change and localized its causal mutation. However, AP is resolved more slowly in smaller populations, predicting more unresolved AP in multicellular organisms than in yeast. These findings provide an empirical foundation for AP-dependent theories and have broad biomedical and evolutionary implications.}, } @article {pmid23093189, year = {2012}, author = {Yue, J and Hu, X and Sun, H and Yang, Y and Huang, J}, title = {Widespread impact of horizontal gene transfer on plant colonization of land.}, journal = {Nature communications}, volume = {3}, number = {}, pages = {1152}, pmid = {23093189}, issn = {2041-1723}, mesh = {Biological Evolution ; Bryopsida/genetics/physiology ; Gene Transfer, Horizontal/*genetics/physiology ; Genes, Plant/genetics/physiology ; Multigene Family/genetics/physiology ; Phylogeny ; Plant Development/genetics/physiology ; Plant Physiological Phenomena/genetics ; Plants/*genetics ; Sequence Alignment ; }, abstract = {In complex multicellular eukaryotes such as animals and plants, horizontal gene transfer is commonly considered rare with very limited evolutionary significance. Here we show that horizontal gene transfer is a dynamic process occurring frequently in the early evolution of land plants. Our genome analyses of the moss Physcomitrella patens identified 57 families of nuclear genes that were acquired from prokaryotes, fungi or viruses. Many of these gene families were transferred to the ancestors of green or land plants. Available experimental evidence shows that these anciently acquired genes are involved in some essential or plant-specific activities such as xylem formation, plant defence, nitrogen recycling as well as the biosynthesis of starch, polyamines, hormones and glutathione. These findings suggest that horizontal gene transfer had a critical role in the transition of plants from aquatic to terrestrial environments. On the basis of these findings, we propose a model of horizontal gene transfer mechanism in nonvascular and seedless vascular plants.}, } @article {pmid23084775, year = {2012}, author = {Guerriero, G}, title = {Putative chitin synthases from Branchiostoma floridae show extracellular matrix-related domains and mosaic structures.}, journal = {Genomics, proteomics & bioinformatics}, volume = {10}, number = {4}, pages = {197-207}, pmid = {23084775}, issn = {2210-3244}, support = {M 1315/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Chitin/chemistry/metabolism ; Chitin Synthase/*chemistry/*genetics/metabolism ; Chordata, Nonvertebrate/*enzymology/*genetics ; Computational Biology ; Discoidins ; Extracellular Matrix/chemistry/*metabolism ; Glycosyltransferases/chemistry/metabolism ; Lectins ; Models, Molecular ; Molecular Sequence Data ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Protozoan Proteins ; }, abstract = {The transition from unicellular to multicellular life forms requires the development of a specialized structural component, the extracellular matrix (ECM). In Metazoans, there are two main supportive systems, which are based on chitin and collagen/hyaluronan, respectively. Chitin is the major constituent of fungal cell walls and arthropod exoskeleton. However, presence of chitin/chitooligosaccharides has been reported in lower chordates and during specific stages of vertebrate development. In this study, the occurrence of chitin synthases (CHSs) was investigated with a bioinformatics approach in the cephalochordate Branchiostoma floridae, in which the presence of chitin was initially reported in the skeletal rods of the pharyngeal gill basket. Twelve genes coding for proteins containing conserved amino acid residues of processive glycosyltransferases from GT2 family were found and 10 of them display mosaic structures with novel domains never reported previously in a chitin synthase. In particular, the presence of a discoidin (DS) and a sterile alpha motif (SAM) domain was found in nine identified proteins. Sequence analyses and homology modelling suggest that these domains might interact with the extracellular matrix and mediate protein-protein interaction. The multi-domain putative chitin synthases from B. floridae constitute an emblematic example of the explosion of domain innovation and shuffling which predate Metazoans.}, } @article {pmid23083808, year = {2012}, author = {Ramsdale, M}, title = {Programmed cell death in the cellular differentiation of microbial eukaryotes.}, journal = {Current opinion in microbiology}, volume = {15}, number = {6}, pages = {646-652}, doi = {10.1016/j.mib.2012.09.005}, pmid = {23083808}, issn = {1879-0364}, mesh = {*Apoptosis ; *Autophagy ; *Cell Differentiation ; Eukaryota/*physiology ; Signal Transduction ; }, abstract = {Programmed cell death (PCD) is a ubiquitous feature of multicellular and unicellular organisms. Eukaryotic microbes use PCD to regulate the development of specialized cells and structures. Many different types of PCD occur, ranging from apoptosis-like cell death, programmed necrosis and autophagic death. An overview of cell death pathways is undertaken, highlighting new elements in the PCD molecular machinery. Examples of PCD in cellular differentiation are explored alongside evolutionary scenarios that could initiate and maintain PCD in microbes, including the evolution of multicellularity. The finding that defects in PCD can lead to antimicrobial drug resistance is also considered. Greater understanding of PCD and its role in differentiation offers new hope for discovery of therapeutic agents that manipulate endogenous cell suicide pathways.}, } @article {pmid23077252, year = {2012}, author = {Sung, W and Ackerman, MS and Miller, SF and Doak, TG and Lynch, M}, title = {Drift-barrier hypothesis and mutation-rate evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {45}, pages = {18488-18492}, pmid = {23077252}, issn = {1091-6490}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cell Division/genetics ; Chlamydomonas reinhardtii/*genetics ; Entomoplasmataceae/*genetics ; *Genetic Drift ; Genome Size/genetics ; Genome, Bacterial/genetics ; Genome, Plant/genetics ; *Models, Genetic ; *Mutation Rate ; *Reproductive Isolation ; Species Specificity ; }, abstract = {Mutation dictates the tempo and mode of evolution, and like all traits, the mutation rate is subject to evolutionary modification. Here, we report refined estimates of the mutation rate for a prokaryote with an exceptionally small genome and for a unicellular eukaryote with a large genome. Combined with prior results, these estimates provide the basis for a potentially unifying explanation for the wide range in mutation rates that exists among organisms. Natural selection appears to reduce the mutation rate of a species to a level that scales negatively with both the effective population size (N(e)), which imposes a drift barrier to the evolution of molecular refinements, and the genomic content of coding DNA, which is proportional to the target size for deleterious mutations. As a consequence of an expansion in genome size, some microbial eukaryotes with large N(e) appear to have evolved mutation rates that are lower than those known to occur in prokaryotes, but multicellular eukaryotes have experienced elevations in the genome-wide deleterious mutation rate because of substantial reductions in N(e).}, } @article {pmid23066508, year = {2012}, author = {Hadfield, MG}, title = {Molecular clue links bacteria to the origin of animals.}, journal = {eLife}, volume = {1}, number = {}, pages = {e00242}, pmid = {23066508}, issn = {2050-084X}, mesh = {Bacteroidetes/classification/*metabolism ; Biological Evolution ; Choanoflagellata/*drug effects/growth & development/ultrastructure ; Feeding Behavior ; Lipid Metabolism ; Lipids/biosynthesis/*pharmacology ; Morphogenesis/*drug effects ; Phylogeny ; }, abstract = {Bacteria have a role in the formation of colonies by a species of single-celled organisms whose ancestors gave rise to the animals, which suggests that bacteria might also have influenced the origin of multicellularity in animals.}, } @article {pmid23066504, year = {2012}, author = {Alegado, RA and Brown, LW and Cao, S and Dermenjian, RK and Zuzow, R and Fairclough, SR and Clardy, J and King, N}, title = {A bacterial sulfonolipid triggers multicellular development in the closest living relatives of animals.}, journal = {eLife}, volume = {1}, number = {}, pages = {e00013}, pmid = {23066504}, issn = {2050-084X}, support = {T32 HG000047/HG/NHGRI NIH HHS/United States ; R01 GM086258/GM/NIGMS NIH HHS/United States ; F32 GM086054/GM/NIGMS NIH HHS/United States ; F32 GM089018/GM/NIGMS NIH HHS/United States ; T32 HG00047/HG/NHGRI NIH HHS/United States ; R01 GM099533/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteroidetes/classification/*metabolism ; Biological Evolution ; Choanoflagellata/*drug effects/growth & development/ultrastructure ; Feeding Behavior ; Lipid Metabolism ; Lipids/biosynthesis/*pharmacology ; Morphogenesis/*drug effects ; Phylogeny ; }, abstract = {Bacterially-produced small molecules exert profound influences on animal health, morphogenesis, and evolution through poorly understood mechanisms. In one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta, we find that rosette colony development is induced by the prey bacterium Algoriphagus machipongonensis and its close relatives in the Bacteroidetes phylum. Here we show that a rosette inducing factor (RIF-1) produced by A. machipongonensis belongs to the small class of sulfonolipids, obscure relatives of the better known sphingolipids that play important roles in signal transmission in plants, animals, and fungi. RIF-1 has extraordinary potency (femtomolar, or 10(-15) M) and S. rosetta can respond to it over a broad dynamic range-nine orders of magnitude. This study provides a prototypical example of bacterial sulfonolipids triggering eukaryotic morphogenesis and suggests molecular mechanisms through which bacteria may have contributed to the evolution of animals.DOI:http://dx.doi.org/10.7554/eLife.00013.001.}, } @article {pmid23066074, year = {2012}, author = {Newman, SA}, title = {Physico-genetic determinants in the evolution of development.}, journal = {Science (New York, N.Y.)}, volume = {338}, number = {6104}, pages = {217-219}, doi = {10.1126/science.1222003}, pmid = {23066074}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Body Patterning/*genetics ; Chimerism/embryology ; Cleavage Stage, Ovum ; Invertebrates/embryology ; Mutation ; *Physical Phenomena ; Vertebrates/embryology ; }, abstract = {Animal bodies and the embryos that generate them exhibit an assortment of stereotypic morphological motifs that first appeared more than half a billion years ago. During development, cells arrange themselves into tissues with interior cavities and multiple layers with immiscible boundaries, containing patterned arrangements of cell types. These tissues go on to elongate, fold, segment, and form appendages. Their motifs are similar to the outcomes of physical processes generic to condensed, chemically excitable, viscoelastic materials, although the embryonic mechanisms that generate them are typically much more complex. I propose that the origins of animal development lay in the mobilization of physical organizational effects that resulted when certain gene products of single-celled ancestors came to operate on the spatial scale of multicellular aggregates.}, } @article {pmid23058793, year = {2013}, author = {Karpov, SA and Mikhailov, KV and Mirzaeva, GS and Mirabdullaev, IM and Mamkaeva, KA and Titova, NN and Aleoshin, VV}, title = {Obligately phagotrophic aphelids turned out to branch with the earliest-diverging fungi.}, journal = {Protist}, volume = {164}, number = {2}, pages = {195-205}, doi = {10.1016/j.protis.2012.08.001}, pmid = {23058793}, issn = {1618-0941}, mesh = {Amino Acid Sequence ; Eukaryota/*classification/*genetics ; Evolution, Molecular ; Microalgae/parasitology ; Molecular Sequence Data ; *Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {Reconstructing the early evolution of fungi and metazoans, two of the kingdoms of multicellular eukaryotes thriving on earth, is a challenging task for biologists. Among extant organisms having characters intermediate between fungi and hypothetical protistan ancestors, from which both fungi and metazoans are believed to have evolved, aphelids are unfairly neglected. The phylogenetic position of these microalgal endoparasites remained uncertain, since no nucleotide sequence data have been reported to date. Aphelids resemble some primitive zoosporic fungi in life cycle, but, unlike fungi, they live by phagotrophy. Here we present a phylogeny, in which a cultured aphelid species, Amoeboaphelidium protococcarum, forms a monophyletic group with Rozella and microsporidia as a sister group to Fungi. We also report a non-canonical nuclear genetic code in A. protococcarum.}, } @article {pmid23057749, year = {2012}, author = {Mallarino, R and Abzhanov, A}, title = {Paths less traveled: evo-devo approaches to investigating animal morphological evolution.}, journal = {Annual review of cell and developmental biology}, volume = {28}, number = {}, pages = {743-763}, pmid = {23057749}, issn = {1530-8995}, support = {R21 DE021535/DE/NIDCR NIH HHS/United States ; 1R21DE021535-01/DE/NIDCR NIH HHS/United States ; }, mesh = {Adaptation, Biological/genetics ; Animal Fins/physiology ; Animals ; Beak/physiology ; *Biological Evolution ; Genetic Speciation ; Models, Biological ; Morphogenesis/*genetics ; Phylogeny ; }, abstract = {One of the chief aims of modern biology is to understand the causes and mechanisms of morphological evolution. Multicellular animals display a stunning diversity of shapes and sizes of their bodies and individual suborganismal structures, much of it important to their survival. What is the most efficient way to study the evolution of morphological diversity? The old-new field of evolutionary developmental biology (evo-devo) can be particularly useful for understanding the origins of animal forms, as it aims to consolidate advances from disparate fields such as phylogenetics, genomics, morphometrics, cell biology, and developmental biology. We analyze the structure of some of the most successful recent evo-devo studies, which we see as having three distinct but highly interdependent components: (a) morphometrics, (b) identification of candidate mechanisms, and (c) functional experiments. Our case studies illustrate how multifarious evo-devo approaches taken within the three-winged evo-devo research program explain developmental mechanisms for morphological evolution across different phylogenetic scales.}, } @article {pmid23056439, year = {2012}, author = {Saxer, G and Havlak, P and Fox, SA and Quance, MA and Gupta, S and Fofanov, Y and Strassmann, JE and Queller, DC}, title = {Whole genome sequencing of mutation accumulation lines reveals a low mutation rate in the social amoeba Dictyostelium discoideum.}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e46759}, pmid = {23056439}, issn = {1932-6203}, support = {T15 LM007093/LM/NLM NIH HHS/United States ; 5T15LM007093-17/LM/NLM NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Dictyostelium/*genetics ; Genome/*genetics ; Mutation ; }, abstract = {Spontaneous mutations play a central role in evolution. Despite their importance, mutation rates are some of the most elusive parameters to measure in evolutionary biology. The combination of mutation accumulation (MA) experiments and whole-genome sequencing now makes it possible to estimate mutation rates by directly observing new mutations at the molecular level across the whole genome. We performed an MA experiment with the social amoeba Dictyostelium discoideum and sequenced the genomes of three randomly chosen lines using high-throughput sequencing to estimate the spontaneous mutation rate in this model organism. The mitochondrial mutation rate of 6.76×10(-9), with a Poisson confidence interval of 4.1×10(-9) - 9.5×10(-9), per nucleotide per generation is slightly lower than estimates for other taxa. The mutation rate estimate for the nuclear DNA of 2.9×10(-11), with a Poisson confidence interval ranging from 7.4×10(-13) to 1.6×10(-10), is the lowest reported for any eukaryote. These results are consistent with low microsatellite mutation rates previously observed in D. discoideum and low levels of genetic variation observed in wild D. discoideum populations. In addition, D. discoideum has been shown to be quite resistant to DNA damage, which suggests an efficient DNA-repair mechanism that could be an adaptation to life in soil and frequent exposure to intracellular and extracellular mutagenic compounds. The social aspect of the life cycle of D. discoideum and a large portion of the genome under relaxed selection during vegetative growth could also select for a low mutation rate. This hypothesis is supported by a significantly lower mutation rate per cell division in multicellular eukaryotes compared with unicellular eukaryotes.}, } @article {pmid23053625, year = {2013}, author = {Funayama, N}, title = {The stem cell system in demosponges: suggested involvement of two types of cells: archeocytes (active stem cells) and choanocytes (food-entrapping flagellated cells).}, journal = {Development genes and evolution}, volume = {223}, number = {1-2}, pages = {23-38}, pmid = {23053625}, issn = {1432-041X}, mesh = {Animals ; Cell Differentiation ; Cell Movement ; Humans ; Porifera/*cytology ; *Stem Cells ; }, abstract = {Major questions about stem cell systems include what type(s) of stem cells are involved (unipotent/totipotent/pluripotent/multipotent stem cells) and how the self-renewal and differentiation of stem cells are regulated. Sponges, the sister group of all other animals and probably the earliest branching multicellular lineage of extant animals, are thought to possess totipotent stem cells. This review introduces what is known about the stem cells in sponges based on histological studies and also on recent molecular biological studies that have started to reveal the molecular and cellular mechanisms of the stem cell system in sponges (mainly in demosponges). The currently proposed model of the stem cell system in demosponges is described, and the possible applicability of this model to other classes of sponges is discussed. Finally, a possible scenario of the evolution of stem cells, including how migrating stem cells arose in the urmetazoan (the last common ancestor of metazoans) and the evolutionary origin of germ line cells in the urbilaterian (the last common ancestor of bilaterians), are discussed.}, } @article {pmid23046654, year = {2012}, author = {Cellier, MF}, title = {Nramp: from sequence to structure and mechanism of divalent metal import.}, journal = {Current topics in membranes}, volume = {69}, number = {}, pages = {249-293}, doi = {10.1016/B978-0-12-394390-3.00010-0}, pmid = {23046654}, issn = {1063-5823}, mesh = {Animals ; Bacteria/metabolism/pathogenicity ; Bacterial Proteins/chemistry/classification/metabolism ; Cation Transport Proteins/chemistry/classification/*metabolism ; Evolution, Molecular ; Ferrous Compounds/*metabolism ; Gene Expression Regulation ; Humans ; Iron Overload/metabolism/pathology ; Manganese/*metabolism ; Mice ; Parkinson Disease/metabolism/pathology ; Phylogeny ; Plasma Membrane Neurotransmitter Transport Proteins/chemistry/classification/metabolism ; Protein Structure, Tertiary ; Tuberculosis/genetics/metabolism/pathology ; }, abstract = {Mn and Fe are important for energy metabolism and oxidative stress resistance and cells maintain adequate stores for survival and prevention of toxicity. Membrane permeases of the natural resistance-associated macrophage protein (Nramp) family importing protons and divalent metals are conserved from bacteria to man. Nramp hydrophobic core relates structurally to a superfamily of cation-driven carriers with inverted symmetry. Molecular phylogeny and sequence features support Nramp pseudo-symmetric three-dimensional (3D) model, and remote ancestry to the LeuT superfamily. Genetic analyses suggest conservation of Nramp sequence marks the transition from a phylogenetic out-group and may relate to divalent metal selectivity. Three phylogroups of bacterial proton-dependent manganese transporters (MntH) demonstrate specific patterns of sequence conservation suggesting functional constraints linked to ecological or taxonomical distributions, which may contribute to bacterial virulence. Nramp 3D model is supported experimentally by transmembrane topology and structure-function studies of Escherichia coli and mouse homologs as well as peptide structure analyses. Eukaryotic Nramps are required for Mn and Fe homeostasis, contributing in multicellular organisms to subcellular and systemic metal traffic and intercellular signaling. Nramps are subjected to elaborate regulation including developmental control of gene expression, protein subcellular targeting, dynamic metallo-dependent control of messenger RNA and protein stability and trafficking. Several human pathologies may result from defects in Nramp-dependent Fe(2+) or Mn(2+) transport, including iron overload, neurodegenerative diseases and innate susceptibility to infectious diseases.}, } @article {pmid23046428, year = {2012}, author = {Yasumura, Y and Pierik, R and Fricker, MD and Voesenek, LA and Harberd, NP}, title = {Studies of Physcomitrella patens reveal that ethylene-mediated submergence responses arose relatively early in land-plant evolution.}, journal = {The Plant journal : for cell and molecular biology}, volume = {72}, number = {6}, pages = {947-959}, doi = {10.1111/tpj.12005}, pmid = {23046428}, issn = {1365-313X}, support = {BB/F020759/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Base Sequence ; Biological Evolution ; Bryopsida/*genetics/physiology ; Droughts ; Ethylenes/*metabolism ; *Gene Expression Regulation, Plant ; Molecular Sequence Data ; Mutation ; Phylogeny ; Plant Growth Regulators/*metabolism ; Plant Leaves/genetics/physiology ; Plant Proteins/*genetics ; Plant Shoots/genetics/physiology ; Receptors, Cell Surface/*genetics ; Sequence Analysis, DNA ; Stress, Physiological ; Water/physiology ; }, abstract = {Colonization of the land by multicellular green plants was a fundamental step in the evolution of life on earth. Land plants evolved from fresh-water aquatic algae, and the transition to a terrestrial environment required the acquisition of developmental plasticity appropriate to the conditions of water availability, ranging from drought to flood. Here we show that extant bryophytes exhibit submergence-induced developmental plasticity, suggesting that submergence responses evolved relatively early in the evolution of land plants. We also show that a major component of the bryophyte submergence response is controlled by the phytohormone ethylene, using a perception mechanism that has subsequently been conserved throughout the evolution of land plants. Thus a plant environmental response mechanism with major ecological and agricultural importance probably had its origins in the very earliest stages of the colonization of the land.}, } @article {pmid23045965, year = {2012}, author = {Edwards, J}, title = {Single-domain β-thymosins: the family history.}, journal = {Annals of the New York Academy of Sciences}, volume = {1269}, number = {}, pages = {7-15}, doi = {10.1111/j.1749-6632.2012.06684.x}, pmid = {23045965}, issn = {1749-6632}, mesh = {Amino Acid Sequence ; Animals ; Birds/genetics ; Evolution, Molecular ; Fishes/genetics ; Gene Duplication/genetics/physiology ; Molecular Sequence Data ; Reptiles/genetics ; Sequence Homology, Amino Acid ; Synteny/genetics ; Thymosin/chemistry/genetics/*metabolism ; Zebrafish/genetics ; }, abstract = {Evolution probably invented the β-thymosin domain in a single-celled close relative of multicellular animals. Expansion from single genes to the small family of monomeric β-thymosins of present-day vertebrates may have started with a very ancient duplication, before the rounds of whole-genome duplications. In land vertebrates and fish, this family consists of the descendants of five genes of their jawed vertebrate common ancestor. Identifying this common ancestry depends on the genes possessing conserved sets of flanking sequences, as the relationships are not recognizable from amino-acid sequences. One of these genes has given rise both to a group of fish β-thymosins and to a hitherto unrecognized group of β-thymosins of birds and reptiles. The resulting classification may prove useful in relation to the β-thymosins of model organisms, such as the zebrafish, and for identifying important noncoding sequence elements, exemplified here by a conserved sequence in the 3'untranslated region of transcripts from the β4 subfamily.}, } @article {pmid23037702, year = {2012}, author = {Watari, A}, title = {[Nature of cancer explored from the perspective of the functional evolution of proto-oncogenes].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {132}, number = {10}, pages = {1165-1170}, doi = {10.1248/yakushi.12-00204}, pmid = {23037702}, issn = {1347-5231}, mesh = {Animals ; Biological Evolution ; Neoplasms/*genetics ; Oncogenes/physiology ; Proto-Oncogenes/*physiology ; p21-Activated Kinases/genetics ; }, abstract = {The products of proto-oncogene play critical roles in the development or maintenance of multicellular societies in animals via strict regulatory systems. When these regulatory systems are disrupted, proto-oncogenes can become oncogenes, and thereby induce cell transformation and carcinogenesis. To understand the molecular basis for development of the regulatory system of proto-oncogenes during evolution, we screened for ancestral proto-oncogenes from the unicellular choanoflagellate Monosiga ovata (M. ovata) by monitoring their transforming ability in mammalian cells; consequently, we isolated a Pak gene ortholog, which encodes a serine/threonine kinase as a 'primitive oncogene'. We also cloned Pak orthologs from fungi and the multicellular sponge Ephydatia fluviatilis, and compared their regulatory features with that of M. ovata Pak (MoPak). MoPak is constitutively active and induces cell transformation in mammalian cells. In contrast, Pak orthologs from multicellular animals are strictly regulated. Analyses of Pak mutants revealed that structural alterations in the auto-inhibitory domain (AID) are responsible for the enhanced kinase activity and the oncogenic activity of MoPak. Furthermore, we show that Rho family GTPases-mediated regulatory system of Pak kinase is conserved throughout the evolution from unicellular to multicellular animals, but the MoPak is more sensitive to the Rho family GTPases-mediated activation than multicellular Pak. These results show that maturation of AID function was required for the development of the strict regulatory system of the Pak proto-oncogene, and support the potential link between the development of the regulatory system of proto-oncogenes and the evolution of multicellularity. Further analysis of oncogenic functions of proto-oncogene orthologs in the unicellular genes would provide some insights into the mechanisms of the destruction of multicellular society in cancer.}, } @article {pmid23024606, year = {2012}, author = {Mallick, B and Ghosh, Z}, title = {Probing Evolutionary Biography of MicroRNAs and Associated Factors.}, journal = {Current genomics}, volume = {13}, number = {2}, pages = {144-152}, pmid = {23024606}, issn = {1875-5488}, abstract = {Intergenic DNA, often described as "playground of evolution", harbors a plethora of cis and trans regulatory elements in the form of non-coding RNAs (ncRNAs). The evolution of the silencing mechanism mediated by microRNAs (miRNAs), an important class of ncRNA, involves the proliferation of miRNA biogenesis and effector proteins, continuing innovation of novel families by the diversification of established families and spawning additional paralogous family members. Such evolving miRNA pathways for spatiotemporal regulation of the transcriptome have shaped the evolution of eukaryotic genomes and contributed to the complexity of multicellular organisms. Here, we focus on the emergence of new target specificity of the miRNAs along with the proliferation of core biogenesis and effector modules and show how this has contributed to generate diverse miRNA regulatory pathways.}, } @article {pmid23016975, year = {2012}, author = {Satoh, N and Tagawa, K and Takahashi, H}, title = {How was the notochord born?.}, journal = {Evolution & development}, volume = {14}, number = {1}, pages = {56-75}, doi = {10.1111/j.1525-142X.2011.00522.x}, pmid = {23016975}, issn = {1525-142X}, mesh = {Animals ; Body Patterning/genetics ; Chordata/embryology/*genetics/metabolism ; *Evolution, Molecular ; Fetal Proteins/genetics/metabolism ; Gastrula/embryology/metabolism ; Gene Expression Regulation, Developmental ; Genes, Developmental/genetics ; Invertebrates/embryology/genetics/metabolism ; Notochord/*embryology/metabolism ; Phylogeny ; T-Box Domain Proteins/genetics/metabolism ; Transcription, Genetic ; Wnt Signaling Pathway ; Brachyury Protein ; }, abstract = {More than 550 million years ago, chordates originated from a common ancestor shared with nonchordate deuterostomes by developing a novel type of larva, the "tadpole larva." The notochord is the supporting organ of the larval tail and the most prominent feature of chordates; indeed, phylum Chordata is named after this organ. In this review, we discuss the molecular mechanisms involved in the formation of the notochord over the course of chordate evolution with a special emphasis on a member of T-box gene family, Brachyury. Comparison of the decoded genome of a unicellular choanoflagellate with the genomes of sponge and cnidarians suggests that T-box gene family arose at the time of the evolution of multicellular animals. Gastrulation is a morphogenetic movement that is essential for the formation of two- or three-germ-layered embryos. Brachyury is transiently expressed in the blastopore (bp) region, where it confers on cells the ability to undergo invagination. This process is involved in the formation of the archenteron in all metazoans. This is a "primary" function of Brachyury. During the evolution of chordates, Brachyury gained an additional expression domain at the dorsal midline region of the bp. In this new expression domain, Brachyury served its "secondary" function, recruiting another set of target genes to form a dorsal axial organ, notochord. The Wnt/β-catenin, BMP/Nodal, and FGF-signaling pathways are involved in the transcriptional activation of Brachyury. We discuss the molecular mechanisms of Brachyury secondary function in the context of the dorsal-ventral (D-V) inversion theory and the aboral-dorsalization hypothesis. Although the scope of this review requires some degree of oversimplification of Brachyury function, it is beneficial to facilitate studies on the notochord formation, a central evolutionary developmental biology problem in the history of metazoan evolution, pointed out first by Alexander Kowalevsky.}, } @article {pmid23013032, year = {2012}, author = {Natochin, IuV and Felitsyn, SB and Klimova, EV and Shakhmatova, EI}, title = {[K+/Na+ in the animal extracellular fluid at weathering of granitoids and problem of the origin of life].}, journal = {Zhurnal evoliutsionnoi biokhimii i fiziologii}, volume = {48}, number = {4}, pages = {409-416}, pmid = {23013032}, issn = {0044-4529}, mesh = {Animals ; *Biological Evolution ; Eukaryota/chemistry/metabolism ; Extracellular Fluid/chemistry/metabolism ; Hemolymph/chemistry/metabolism ; *Origin of Life ; *Potassium/blood/chemistry/metabolism ; Prokaryotic Cells/chemistry/metabolism ; *Sodium/blood/chemistry/metabolism ; Water/chemistry ; }, abstract = {Leaching of granitoids of the paleoproterozoic age was performed from several seconds to 360 days in water solutions (pH < 6.0) in the oxygen or argon medium. Under these conditions the entrance of K+ into the solution has been shown to occur at the higher rate than that of Na+. The obtained data are considered as evidence in favor of a possibility of the existence at the earlier stages of the Earth geologic history of water reservoirs with predominance of K+ over Na+. The K+/Na+ ratio exceeding 1 has been shown in prokaryotes, in cells and tissues of the free living and parasitic species of invertebrate and vertebrate animals. At the same time in the extracellular fluid of the fresh water, marine, and terrestrial animals, in which the Na+ concentration varies from 13 to 482 mmol/l, the K+/Na+ ratio is preserved at the level of 0.034 +/- 0.001. These results are discussed in connection with the problem of origin of protocells and of concentration ratios of monovalent cations in water phases of multicellular organisms.}, } @article {pmid22996257, year = {2013}, author = {Yang, C and Ye, Z}, title = {Trichomes as models for studying plant cell differentiation.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {70}, number = {11}, pages = {1937-1948}, pmid = {22996257}, issn = {1420-9071}, mesh = {Arabidopsis/*cytology/genetics/metabolism ; Cell Cycle/physiology ; *Cell Differentiation ; Cotton Fiber ; Gene Expression Regulation, Plant ; Models, Biological ; Plant Cells/metabolism/ultrastructure ; Plant Epidermis/*cytology/genetics/metabolism ; }, abstract = {Trichomes, originating from epidermal cells, are present on nearly all terrestrial plants. They exist in diverse forms, are readily accessible, and serve as an excellent model system for analyzing the molecular mechanisms in plant cell differentiation, including cell fate choices, cell cycle control, and cell morphogenesis. In Arabidopsis, two regulatory models have been identified that function in parallel in trichome formation; the activator-inhibitor model and the activator-depletion model. Cotton fiber, a similar unicellular structure, is controlled by some functional homologues of Arabidopsis trichome-patterning genes. Multicellular trichomes, as in tobacco and tomato, may form through a distinct pathway from unicellular trichomes. Recent research has shown that cell cycle control participates in trichome formation. In this review, we summarize the molecular mechanisms involved in the formation of unicellular and multicellular trichomes, and discuss the integration of the cell cycle in its initiation and morphogenesis.}, } @article {pmid22993722, year = {2012}, author = {Koonin, EV and Wolf, YI}, title = {Evolution of microbes and viruses: a paradigm shift in evolutionary biology?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {2}, number = {}, pages = {119}, pmid = {22993722}, issn = {2235-2988}, mesh = {Adaptation, Biological ; Archaea/*genetics ; Bacteria/*genetics ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genetic Variation ; Selection, Genetic ; Viruses/*genetics ; }, abstract = {When Charles Darwin formulated the central principles of evolutionary biology in the Origin of Species in 1859 and the architects of the Modern Synthesis integrated these principles with population genetics almost a century later, the principal if not the sole objects of evolutionary biology were multicellular eukaryotes, primarily animals and plants. Before the advent of efficient gene sequencing, all attempts to extend evolutionary studies to bacteria have been futile. Sequencing of the rRNA genes in thousands of microbes allowed the construction of the three- domain "ribosomal Tree of Life" that was widely thought to have resolved the evolutionary relationships between the cellular life forms. However, subsequent massive sequencing of numerous, complete microbial genomes revealed novel evolutionary phenomena, the most fundamental of these being: (1) pervasive horizontal gene transfer (HGT), in large part mediated by viruses and plasmids, that shapes the genomes of archaea and bacteria and call for a radical revision (if not abandonment) of the Tree of Life concept, (2) Lamarckian-type inheritance that appears to be critical for antivirus defense and other forms of adaptation in prokaryotes, and (3) evolution of evolvability, i.e., dedicated mechanisms for evolution such as vehicles for HGT and stress-induced mutagenesis systems. In the non-cellular part of the microbial world, phylogenomics and metagenomics of viruses and related selfish genetic elements revealed enormous genetic and molecular diversity and extremely high abundance of viruses that come across as the dominant biological entities on earth. Furthermore, the perennial arms race between viruses and their hosts is one of the defining factors of evolution. Thus, microbial phylogenomics adds new dimensions to the fundamental picture of evolution even as the principle of descent with modification discovered by Darwin and the laws of population genetics remain at the core of evolutionary biology.}, } @article {pmid22992464, year = {2012}, author = {Macro, L and Jaiswal, JK and Simon, SM}, title = {Dynamics of clathrin-mediated endocytosis and its requirement for organelle biogenesis in Dictyostelium.}, journal = {Journal of cell science}, volume = {125}, number = {Pt 23}, pages = {5721-5732}, pmid = {22992464}, issn = {1477-9137}, support = {R01 GM087977/GM/NIGMS NIH HHS/United States ; 5R01GM087977-03/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptor Protein Complex 2/metabolism ; Clathrin/*metabolism ; Dictyostelium/*cytology/*metabolism ; Endocytosis/*physiology ; Organelle Biogenesis ; Saccharomyces cerevisiae ; }, abstract = {The protein clathrin mediates one of the major pathways of endocytosis from the extracellular milieu and plasma membrane. In single-cell eukaryotes, such as Saccharomyces cerevisiae, the gene encoding clathrin is not an essential gene, raising the question of whether clathrin conveys specific advantages for multicellularity. Furthermore, in contrast to mammalian cells, endocytosis in S. cerevisiae is not dependent on either clathrin or adaptor protein 2 (AP2), an endocytic adaptor molecule. In this study, we investigated the requirement for components of clathrin-mediated endocytosis (CME) in another unicellular organism, the amoeba Dictyostelium. We identified a heterotetrameric AP2 complex in Dictyostelium that is similar to that which is found in higher eukaryotes. By simultaneously imaging fluorescently tagged clathrin and AP2, we found that, similar to higher eukaryotes, these proteins colocalized to membrane puncta that move into the cell together. In addition, the contractile vacuole marker protein, dajumin-green fluorescent protein (GFP), is trafficked via the cell membrane and internalized by CME in a clathrin-dependent, AP2-independent mechanism. This pathway is distinct from other endocytic mechanisms in Dictyostelium. Our finding that CME is required for the internalization of contractile vacuole proteins from the cell membrane explains the contractile vacuole biogenesis defect in Dictyostelium cells lacking clathrin. Our results also suggest that the machinery for CME and its role in organelle maintenance appeared early during eukaryotic evolution. We hypothesize that dependence of endocytosis on specific components of the CME pathway evolved later, as demonstrated by internalization independent of AP2 function.}, } @article {pmid22977115, year = {2013}, author = {Bezginov, A and Clark, GW and Charlebois, RL and Dar, VU and Tillier, ER}, title = {Coevolution reveals a network of human proteins originating with multicellularity.}, journal = {Molecular biology and evolution}, volume = {30}, number = {2}, pages = {332-346}, pmid = {22977115}, issn = {1537-1719}, mesh = {Animals ; *Biological Evolution ; Cell Communication/*physiology ; Ciliary Motility Disorders/genetics/metabolism ; Cluster Analysis ; Databases, Protein ; Female ; Gene Expression ; Humans ; Male ; Mutation ; Neoplasms/genetics/metabolism ; Protein Binding ; Protein Interaction Mapping ; Protein Interaction Maps ; Proteins/*genetics/*metabolism ; }, abstract = {Protein interaction networks play central roles in biological systems, from simple metabolic pathways through complex programs permitting the development of organisms. Multicellularity could only have arisen from a careful orchestration of cellular and molecular roles and responsibilities, all properly controlled and regulated. Disease reflects a breakdown of this organismal homeostasis. To better understand the evolution of interactions whose dysfunction may be contributing factors to disease, we derived the human protein coevolution network using our MatrixMatchMaker algorithm and using the Orthologous MAtrix project (OMA) database as a source for protein orthologs from 103 eukaryotic genomes. We annotated the coevolution network using protein-protein interaction data, many functional data sources, and we explored the evolutionary rates and dates of emergence of the proteins in our data set. Strikingly, clustering based only on the topology of the coevolution network partitions it into two subnetworks, one generally representing ancient eukaryotic functions and the other functions more recently acquired during animal evolution. That latter subnetwork is enriched for proteins with roles in cell-cell communication, the control of cell division, and related multicellular functions. Further annotation using data from genetic disease databases and cancer genome sequences strongly implicates these proteins in both ciliopathies and cancer. The enrichment for such disease markers in the animal network suggests a functional link between these coevolving proteins. Genetic validation corroborates the recruitment of ancient cilia in the evolution of multicellularity.}, } @article {pmid22977071, year = {2012}, author = {Booth, W and Smith, CF and Eskridge, PH and Hoss, SK and Mendelson, JR and Schuett, GW}, title = {Facultative parthenogenesis discovered in wild vertebrates.}, journal = {Biology letters}, volume = {8}, number = {6}, pages = {983-985}, pmid = {22977071}, issn = {1744-957X}, mesh = {Agkistrodon/*physiology ; Animals ; *Biological Evolution ; Female ; Gene Frequency ; Genotype ; Microsatellite Repeats/genetics ; North America ; Parthenogenesis/*physiology ; }, abstract = {Facultative parthenogenesis (FP)-asexual reproduction by bisexual species-has been documented in a variety of multi-cellular organisms but only recently in snakes, varanid lizards, birds and sharks. Unlike the approximately 80 taxa of unisexual reptiles, amphibians and fishes that exist in nature, FP has yet to be documented in the wild. Based on captive documentation, it appears that FP is widespread in squamate reptiles (snakes, lizards and amphisbaenians), and its occurrence in nature seems inevitable, yet the task of detecting FP in wild individuals has been deemed formidable. Here we show, using microsatellite DNA genotyping and litter characteristics, the first cases of FP in wild-collected pregnant females and their offspring of two closely related species of North American pitviper snakes-the copperhead (Agkistrodon contortrix) and cottonmouth (Agkistrodon piscivorus). Our findings support the view that non-hybrid origins of parthenogenesis, such as FP, are more common in squamates than previously thought. With this confirmation, FP can no longer be viewed as a rare curiosity outside the mainstream of vertebrate evolution. Future research on FP in squamate reptiles related to proximate control of induction, reproductive competence of parthenogens and population genetics modelling is warranted.}, } @article {pmid22975005, year = {2012}, author = {Niccoli, T and Partridge, L}, title = {Ageing as a risk factor for disease.}, journal = {Current biology : CB}, volume = {22}, number = {17}, pages = {R741-52}, doi = {10.1016/j.cub.2012.07.024}, pmid = {22975005}, issn = {1879-0445}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {*Aging ; Autophagy ; Cardiovascular Diseases/epidemiology/pathology ; DNA Damage ; Humans ; Life Expectancy ; Mitochondria/physiology ; Neoplasms/epidemiology/pathology ; Neurodegenerative Diseases/epidemiology/pathology ; Risk Factors ; Signal Transduction ; Time Factors ; }, abstract = {Age is the main risk factor for the prevalent diseases of developed countries: cancer, cardiovascular disease and neurodegeneration. The ageing process is deleterious for fitness, but can nonetheless evolve as a consequence of the declining force of natural selection at later ages, attributable to extrinsic hazards to survival: ageing can then occur as a side-effect of accumulation of mutations that lower fitness at later ages, or of natural selection in favour of mutations that increase fitness of the young but at the cost of a higher subsequent rate of ageing. Once thought of as an inexorable, complex and lineage-specific process of accumulation of damage, ageing has turned out to be influenced by mechanisms that show strong evolutionary conservation. Lowered activity of the nutrient-sensing insulin/insulin-like growth factor/Target of Rapamycin signalling network can extend healthy lifespan in yeast, multicellular invertebrates, mice and, possibly, humans. Mitochondrial activity can also promote ageing, while genome maintenance and autophagy can protect against it. We discuss the relationship between evolutionarily conserved mechanisms of ageing and disease, and the associated scientific challenges and opportunities.}, } @article {pmid22975003, year = {2012}, author = {Boehm, T}, title = {Evolution of vertebrate immunity.}, journal = {Current biology : CB}, volume = {22}, number = {17}, pages = {R722-32}, doi = {10.1016/j.cub.2012.07.003}, pmid = {22975003}, issn = {1879-0445}, mesh = {Adaptation, Physiological ; Animals ; *Biological Evolution ; Humans ; Immune System Diseases/epidemiology ; Immune System Phenomena ; Models, Immunological ; Vertebrates/*immunology ; }, abstract = {All multicellular organisms protect themselves against pathogens using sophisticated immune defenses. Functionally interconnected humoral and cellular facilities maintain immune homeostasis in the absence of overt infection and regulate the initiation and termination of immune responses directed against pathogens. Immune responses of invertebrates, such as flies, are innate and usually stereotyped; those of vertebrates, encompassing species as diverse as jawless fish and humans, are additionally adaptive, enabling more rapid and efficient immune reactivity upon repeated encounters with a pathogen. Many of the attributes historically defining innate and adaptive immunity are in fact common to both, blurring their functional distinction and emphasizing shared ancestry and co-evolution. These findings provide indications of the evolutionary forces underlying the origin of somatic diversification of antigen receptors and contribute to our understanding of the complex phenotypes of human immune disorders. Moreover, informed by phylogenetic considerations and inspired by improved knowledge of functional networks, new avenues emerge for innovative therapeutic strategies.}, } @article {pmid22970728, year = {2012}, author = {Yruela, I and Contreras-Moreira, B}, title = {Protein disorder in plants: a view from the chloroplast.}, journal = {BMC plant biology}, volume = {12}, number = {}, pages = {165}, pmid = {22970728}, issn = {1471-2229}, mesh = {Amino Acid Sequence ; Cell Nucleus/genetics/*metabolism ; Chloroplast Proteins/genetics/*metabolism ; Chloroplasts/genetics/*metabolism ; Computational Biology ; Evolution, Molecular ; *Genome, Plant ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; Nuclear Proteins/genetics/metabolism ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants/genetics/*metabolism ; Protein Transport ; Ribosomal Proteins/genetics/metabolism ; }, abstract = {BACKGROUND: The intrinsically unstructured state of some proteins, observed in all living organisms, is essential for basic cellular functions. In this field the available information from plants is limited but it has been reached a point where these proteins can be comprehensively classified on the basis of disorder, function and evolution.

RESULTS: Our analysis of plant genomes confirms that nuclear-encoded proteins follow the same trend than other multi-cellular eukaryotes; however, chloroplast- and mitochondria- encoded proteins conserve the patterns of Archaea and Bacteria, in agreement with their phylogenetic origin. Based on current knowledge about gene transference from the chloroplast to the nucleus, we report a strong correlation between the rate of disorder of transferred and nuclear-encoded proteins, even for polypeptides that play functional roles back in the chloroplast. We further investigate this trend by reviewing the set of chloroplast ribosomal proteins, one of the most representative transferred gene clusters, finding that the ribosomal large subunit, assembled from a majority of nuclear-encoded proteins, is clearly more unstructured than the small one, which integrates mostly plastid-encoded proteins.

CONCLUSIONS: Our observations suggest that the evolutionary dynamics of the plant nucleus adds disordered segments to genes alike, regardless of their origin, with the notable exception of proteins currently encoded in both genomes, probably due to functional constraints.}, } @article {pmid22970104, year = {2012}, author = {Hoef-Emden, K}, title = {Pitfalls of establishing DNA barcoding systems in protists: the cryptophyceae as a test case.}, journal = {PloS one}, volume = {7}, number = {8}, pages = {e43652}, pmid = {22970104}, issn = {1932-6203}, mesh = {Algorithms ; Base Sequence ; Bayes Theorem ; Cryptophyta/classification/*genetics ; Cyclooxygenase 1/genetics ; *DNA Barcoding, Taxonomic ; Likelihood Functions ; Models, Genetic ; Molecular Sequence Data ; Monte Carlo Method ; Phylogeny ; Ribosome Subunits, Large, Eukaryotic/genetics ; }, abstract = {A DNA barcode is a preferrably short and highly variable region of DNA supposed to facilitate a rapid identification of species. In many protistan lineages, a lack of species-specific morphological characters hampers an identification of species by light or electron microscopy, and difficulties to perform mating experiments in laboratory cultures also do not allow for an identification of biological species. Thus, testing candidate barcode markers as well as establishment of accurately working species identification systems are more challenging than in multicellular organisms. In cryptic species complexes the performance of a potential barcode marker can not be monitored using morphological characters as a feedback, but an inappropriate choice of DNA region may result in artifactual species trees for several reasons. Therefore a priori knowledge of the systematics of a group is required. In addition to identification of known species, methods for an automatic delimitation of species with DNA barcodes have been proposed. The Cryptophyceae provide a mixture of systematically well characterized as well as badly characterized groups and are used in this study to test the suitability of some of the methods for protists. As species identification method the performance of blast in searches against badly to well-sampled reference databases has been tested with COI-5P and 5'-partial LSU rDNA (domains A to D of the nuclear LSU rRNA gene). In addition the performance of two different methods for automatic species delimitation, fixed thresholds of genetic divergence and the general mixed Yule-coalescent model (GMYC), have been examined. The study demonstrates some pitfalls of barcoding methods that have to be taken care of. Also a best-practice approach towards establishing a DNA barcode system in protists is proposed.}, } @article {pmid22969411, year = {2012}, author = {Rabosky, DL and Slater, GJ and Alfaro, ME}, title = {Clade age and species richness are decoupled across the eukaryotic tree of life.}, journal = {PLoS biology}, volume = {10}, number = {8}, pages = {e1001381}, pmid = {22969411}, issn = {1545-7885}, mesh = {*Biodiversity ; Eukaryota/*classification ; Models, Biological ; *Phylogeny ; Species Specificity ; Time Factors ; }, abstract = {Explaining the dramatic variation in species richness across the tree of life remains a key challenge in evolutionary biology. At the largest phylogenetic scales, the extreme heterogeneity in species richness observed among different groups of organisms is almost certainly a function of many complex and interdependent factors. However, the most fundamental expectation in macroevolutionary studies is simply that species richness in extant clades should be correlated with clade age: all things being equal, older clades will have had more time for diversity to accumulate than younger clades. Here, we test the relationship between stem clade age and species richness across 1,397 major clades of multicellular eukaryotes that collectively account for more than 1.2 million described species. We find no evidence that clade age predicts species richness at this scale. We demonstrate that this decoupling of age and richness is unlikely to result from variation in net diversification rates among clades. At the largest phylogenetic scales, contemporary patterns of species richness are inconsistent with unbounded diversity increase through time. These results imply that a fundamentally different interpretative paradigm may be needed in the study of phylogenetic diversity patterns in many groups of organisms.}, } @article {pmid22965912, year = {2013}, author = {Basak, I and Møller, SG}, title = {Emerging facets of plastid division regulation.}, journal = {Planta}, volume = {237}, number = {2}, pages = {389-398}, pmid = {22965912}, issn = {1432-2048}, mesh = {Arabidopsis/chemistry/genetics ; Arabidopsis Proteins/*chemistry/genetics ; Cell Differentiation ; *Cell Division ; Chloroplast Proteins/chemistry/genetics ; Cytosol/chemistry ; Evolution, Molecular ; Intracellular Membranes/chemistry ; Multiprotein Complexes/chemistry/genetics ; Phosphorylation ; Plant Cells/chemistry ; Plastids/*chemistry/genetics ; }, abstract = {Plastids are complex organelles that are integrated into the plant host cell where they differentiate and divide in tune with plant differentiation and development. In line with their prokaryotic origin, plastid division involves both evolutionary conserved proteins and proteins of eukaryotic origin where the host has acquired control over the process. The plastid division apparatus is spatially separated between the stromal and the cytosolic space but where clear coordination mechanisms exist between the two machineries. Our knowledge of the plastid division process has increased dramatically during the past decade and recent findings have not only shed light on plastid division enzymology and the formation of plastid division complexes but also on the integration of the division process into a multicellular context. This review summarises our current knowledge of plastid division with an emphasis on biochemical features, the functional assembly of protein complexes and regulatory features of the overall process.}, } @article {pmid22962278, year = {2012}, author = {Simonin, A and Palma-Guerrero, J and Fricker, M and Glass, NL}, title = {Physiological significance of network organization in fungi.}, journal = {Eukaryotic cell}, volume = {11}, number = {11}, pages = {1345-1352}, pmid = {22962278}, issn = {1535-9786}, mesh = {Biological Transport ; Biomarkers/metabolism ; Carbon/metabolism ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Fluorescence ; Green Fluorescent Proteins/metabolism ; Histones/metabolism ; Hyphae/genetics/*physiology ; Isotope Labeling/methods ; *Metabolic Networks and Pathways ; Neurospora crassa/genetics/*physiology ; Nitrogen/metabolism ; Species Specificity ; Spores, Fungal/physiology ; Time Factors ; }, abstract = {The evolution of multicellularity has occurred in diverse lineages and in multiple ways among eukaryotic species. For plants and fungi, multicellular forms are derived from ancestors that failed to separate following cell division, thus retaining cytoplasmic continuity between the daughter cells. In networked organisms, such as filamentous fungi, cytoplasmic continuity facilitates the long-distance transport of resources without the elaboration of a separate vascular system. Nutrient translocation in fungi is essential for nutrient cycling in ecosystems, mycorrhizal symbioses, virulence, and substrate utilization. It has been proposed that an interconnected mycelial network influences resource translocation, but the theory has not been empirically tested. Here we show, by using mutants that disrupt network formation in Neurospora crassa (Δso mutant, no fusion; ΔPrm-1 mutant, ∼50% fusion), that the translocation of labeled nutrients is adversely affected in homogeneous environments and is even more severely impacted in heterogeneous environments. We also show that the ability to share resources and genetic exchange between colonies (via hyphal fusion) is very limited in mature colonies, in contrast to in young colonies and germlings that readily share nutrients and genetic resources. The differences in genetic/resource sharing between young and mature colonies were associated with variations in colony architecture (hyphal differentiation/diameters, branching patterns, and angles). Thus, the ability to share resources and genetic material between colonies is developmentally regulated and is a function of the age of a colony. This study highlights the necessity of hyphal fusion for efficient nutrient translocation within an N. crassa colony but also shows that established N. crassa colonies do not share resources in a significant manner.}, } @article {pmid22952431, year = {2012}, author = {Harmon, LJ}, title = {An inordinate fondness for eukaryotic diversity.}, journal = {PLoS biology}, volume = {10}, number = {8}, pages = {e1001382}, pmid = {22952431}, issn = {1545-7885}, mesh = {*Biodiversity ; Eukaryota/*genetics ; *Phylogeny ; }, abstract = {Why do some groups of organisms, like beetles, have so many species, and others, like the tuataras, so few? This classic question in evolutionary biology has a deep history and has been studied using both fossils and phylogenetic trees. Phylogeny-based studies have focused on tree balance, which compares the number of species across clades of the same age in the tree. These studies have suggested that rates of speciation and extinction vary tremendously across the tree of life. In this issue, Rabosky et al. report the most ambitious study to date on the differences in species diversity across clades in the tree of life. The authors bring together a tremendously large dataset of multicellular eukaryotes, including all living species of plants, animals, and fungi; they divide these organisms into 1,397 clades, accounting for more than 1.2 million species in total. Rabosky et al. find tremendous variation in diversity across the tree of life. There are old clades with few species, young clades with many species, and everything in between. They also note a peculiar aspect of their data: it is difficult or impossible to predict how many species will be found in a particular clade knowing how long a clade has been diversifying from a common ancestor. This pattern suggests complex dynamics of speciation and extinction in the history of eukaryotes. Rabosky et al.'s paper represents the latest development in our efforts to understand the Earth's biodiversity at the broadest scales.}, } @article {pmid22948853, year = {2012}, author = {Sun, S and Heitman, J}, title = {Should Y stay or should Y go: the evolution of non-recombining sex chromosomes.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {11}, pages = {938-942}, pmid = {22948853}, issn = {1521-1878}, support = {R37 AI039115/AI/NIAID NIH HHS/United States ; R01 AI039115/AI/NIAID NIH HHS/United States ; R37 AI39115/AI/NIAID NIH HHS/United States ; R01 AI50113/AI/NIAID NIH HHS/United States ; R01 AI050113/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/genetics ; Chromosomes, Human, Y/genetics ; *Evolution, Molecular ; Genetic Loci/genetics ; Humans ; Recombination, Genetic/*genetics ; Y Chromosome/*genetics ; }, abstract = {Gradual degradation seems inevitable for non-recombining sex chromosomes. This has been supported by the observation of degenerated non-recombining sex chromosomes in a variety of species. The human Y chromosome has also degenerated significantly during its evolution, and theories have been advanced that the Y chromosome could disappear within the next ~5 million years, if the degeneration rate it has experienced continues. However, recent studies suggest that this is unlikely. Conservative evolutionary forces such as strong purifying selection and intrachromosomal repair through gene conversion balance the degeneration tendency of the Y chromosome and maintain its integrity after an initial period of faster degeneration. We discuss the evidence both for and against the extinction of the Y chromosome. We also discuss potential insights gained on the evolution of sex-determining chromosomes by studying simpler sex-determining chromosomal regions of unicellular and multicellular microorganisms.}, } @article {pmid22948334, year = {2012}, author = {França, GS and Cancherini, DV and de Souza, SJ}, title = {Evolutionary history of exon shuffling.}, journal = {Genetica}, volume = {140}, number = {4-6}, pages = {249-257}, pmid = {22948334}, issn = {1573-6857}, mesh = {Animals ; Cluster Analysis ; Computational Biology/methods ; *Evolution, Molecular ; *Exons ; Humans ; Introns ; Open Reading Frames/genetics ; Plants/genetics ; Protein Interaction Domains and Motifs/genetics ; *Recombination, Genetic ; }, abstract = {Exon shuffling has been characterized as one of the major evolutionary forces shaping both the genome and the proteome of eukaryotes. This mechanism was particularly important in the creation of multidomain proteins during animal evolution, bringing a number of functional genetic novelties. Here, genome information from a variety of eukaryotic species was used to address several issues related to the evolutionary history of exon shuffling. By comparing all protein sequences within each species, we were able to characterize exon shuffling signatures throughout metazoans. Intron phase (the position of the intron regarding the codon) and exon symmetry (the pattern of flanking introns for a given exon or block of adjacent exons) were features used to evaluate exon shuffling. We confirmed previous observations that exon shuffling mediated by phase 1 introns (1-1 exon shuffling) is the predominant kind in multicellular animals. Evidence is provided that such pattern was achieved since the early steps of animal evolution, supported by a detectable presence of 1-1 shuffling units in Trichoplax adhaerens and a considerable prevalence of them in Nematostella vectensis. In contrast, Monosiga brevicollis, one of the closest relatives of metazoans, and Arabidopsis thaliana, showed no evidence of 1-1 exon or domain shuffling above what it would be expected by chance. Instead, exon shuffling events are less abundant and predominantly mediated by phase 0 introns (0-0 exon shuffling) in those non-metazoan species. Moreover, an intermediate pattern of 1-1 and 0-0 exon shuffling was observed for the placozoan T. adhaerens, a primitive animal. Finally, characterization of flanking intron phases around domain borders allowed us to identify a common set of symmetric 1-1 domains that have been shuffled throughout the metazoan lineage.}, } @article {pmid22945313, year = {2012}, author = {Moody, LA and Saidi, Y and Smiles, EJ and Bradshaw, SJ and Meddings, M and Winn, PJ and Coates, JC}, title = {ARABIDILLO gene homologues in basal land plants: species-specific gene duplication and likely functional redundancy.}, journal = {Planta}, volume = {236}, number = {6}, pages = {1927-1941}, pmid = {22945313}, issn = {1432-2048}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/genetics ; Base Sequence ; Bryopsida/cytology/*genetics/growth & development ; Gene Expression Regulation, Plant ; Genes, Reporter ; Genome, Plant/*genetics ; Molecular Sequence Data ; Phenotype ; Phylogeny ; Plant Proteins/*genetics ; Plants, Genetically Modified ; Promoter Regions, Genetic/genetics ; Selaginellaceae/cytology/*genetics/growth & development ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Deletion ; Sequence Homology, Nucleic Acid ; Species Specificity ; }, abstract = {ARABIDILLO proteins regulate multicellular root development in Arabidopsis thaliana. Conserved ARABIDILLO homologues are present throughout land plants, even in early-evolving plants that do not possess complex root architecture, suggesting that ARABIDILLO genes have additional functions. Here, we have cloned and characterised ARABIDILLO gene homologues from two early-evolving land plants, the bryophyte Physcomitrella patens and the lycophyte Selaginella moellendorffii. We show that two of the PHYSCODILLO genes (PHYSCODILLO1A and -1B) exist as a tail-to-tail tandem array of two almost identical 12 kb sequences, while a third related gene (PHYSCODILLO2) is located elsewhere in the Physcomitrella genome. Physcomitrella possesses a very low percentage of tandemly arrayed genes compared with the later-evolving plants whose genomes have been sequenced to date. Thus, PHYSCODILLO1A and -1B genes represent a relatively unusual gene arrangement. PHYSCODILLO promoters are active largely in the haploid gametophyte, with additional activity at the foot of the sporophyte. The pattern of promoter activity is uniform in filamentous and leafy tissues, suggesting pleiotropic gene functions and likely functional redundancy: the latter possibility is confirmed by the lack of discernible phenotype in a physcodillo2 deletion mutant. Interestingly, the pattern of PHYSCODILLO promoter activity in female reproductive organs is strikingly similar to that of an Arabidopsis homologue, suggesting co-option of some PHYSCODILLO functions or regulation into both the sporophyte and gametophyte. In conclusion, our work identifies and characterises some of the earliest-evolving land plant ARABIDILLO homologues. We confirm that all land plant ARABIDILLO genes arose from a single common ancestor and suggest that PHYSCODILLO proteins have novel and pleiotropic functions, some of which may be conserved in later-evolving plants.}, } @article {pmid22933559, year = {2012}, author = {Lenhart, JS and Schroeder, JW and Walsh, BW and Simmons, LA}, title = {DNA repair and genome maintenance in Bacillus subtilis.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {76}, number = {3}, pages = {530-564}, pmid = {22933559}, issn = {1098-5557}, support = {T32 GM007544/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacillus subtilis/*genetics/growth & development/metabolism ; DNA Damage ; *DNA Repair ; *DNA Replication ; *Gene Expression Regulation, Bacterial ; Genome, Bacterial/*genetics ; Mutagenesis ; Spores, Bacterial/physiology ; }, abstract = {From microbes to multicellular eukaryotic organisms, all cells contain pathways responsible for genome maintenance. DNA replication allows for the faithful duplication of the genome, whereas DNA repair pathways preserve DNA integrity in response to damage originating from endogenous and exogenous sources. The basic pathways important for DNA replication and repair are often conserved throughout biology. In bacteria, high-fidelity repair is balanced with low-fidelity repair and mutagenesis. Such a balance is important for maintaining viability while providing an opportunity for the advantageous selection of mutations when faced with a changing environment. Over the last decade, studies of DNA repair pathways in bacteria have demonstrated considerable differences between Gram-positive and Gram-negative organisms. Here we review and discuss the DNA repair, genome maintenance, and DNA damage checkpoint pathways of the Gram-positive bacterium Bacillus subtilis. We present their molecular mechanisms and compare the functions and regulation of several pathways with known information on other organisms. We also discuss DNA repair during different growth phases and the developmental program of sporulation. In summary, we present a review of the function, regulation, and molecular mechanisms of DNA repair and mutagenesis in Gram-positive bacteria, with a strong emphasis on B. subtilis.}, } @article {pmid22930590, year = {2012}, author = {Dickinson, DJ and Nelson, WJ and Weis, WI}, title = {An epithelial tissue in Dictyostelium challenges the traditional origin of metazoan multicellularity.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {10}, pages = {833-840}, pmid = {22930590}, issn = {1521-1878}, support = {R01 GM035527/GM/NIGMS NIH HHS/United States ; R37 GM035527/GM/NIGMS NIH HHS/United States ; GM035527/GM/NIGMS NIH HHS/United States ; R01 GM056169/GM/NIGMS NIH HHS/United States ; GM56169/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *Cell Polarity ; Dictyostelium/*cytology ; Epithelial Cells/metabolism/*physiology ; Epithelium/metabolism ; Humans ; }, abstract = {We hypothesize that aspects of animal multicellularity originated before the divergence of metazoans from fungi and social amoebae. Polarized epithelial tissues are a defining feature of metazoans and contribute to the diversity of animal body plans. The recent finding of a polarized epithelium in the non-metazoan social amoeba Dictyostelium discoideum demonstrates that epithelial tissue is not a unique feature of metazoans, and challenges the traditional paradigm that multicellularity evolved independently in social amoebae and metazoans. An alternative view, presented here, is that the common ancestor of social amoebae, fungi, and animals spent a portion of its life cycle in a multicellular state and possessed molecular machinery necessary for forming an epithelial tissue. Some descendants of this ancestor retained multicellularity, while others reverted to unicellularity. This hypothesis makes testable predictions regarding tissue organization in close relatives of metazoans and provides a novel conceptual framework for studies of early animal evolution.}, } @article {pmid22928977, year = {2012}, author = {Jaiswal, P and Singh, SP and Aiyar, P and Akkali, R and Baskar, R}, title = {Regulation of multiple tip formation by caffeine in cellular slime molds.}, journal = {BMC developmental biology}, volume = {12}, number = {}, pages = {26}, pmid = {22928977}, issn = {1471-213X}, mesh = {1-Methyl-3-isobutylxanthine/pharmacology ; Caffeine/*pharmacology ; Cell Transdifferentiation ; Chemotactic Factors/pharmacology ; Chemotaxis ; Cyclic AMP/metabolism/physiology ; Cyclic Nucleotide Phosphodiesterases, Type 4/genetics/metabolism ; Dictyostelium/*cytology/drug effects/physiology ; Dipeptides/pharmacology ; Gene Expression ; Kinetics ; Lactams/pharmacology ; Phosphodiesterase 4 Inhibitors/*pharmacology ; Protozoan Proteins/genetics/metabolism ; }, abstract = {BACKGROUND: The multicellular slug in Dictyostelium has a single tip that acts as an organising centre patterning the rest of the slug. High adenosine levels at the tip are believed to be responsible for this tip dominance and the adenosine antagonist, caffeine overrides this dominance promoting multiple tip formation.

RESULTS: Caffeine induced multiple tip effect is conserved in all the Dictyostelids tested. Two key components of cAMP relay namely, cAMP phosphodiesterase (Pde4) and adenyl cyclase-A (AcaA) levels get reduced during secondary tip formation in Dictyostelium discoideum. Pharmacological inhibition of cAMP phosphodiesterase also resulted in multiple tips. Caffeine reduces cAMP levels by 16.4, 2.34, 4.71 and 6.30 folds, respectively in D. discoideum, D. aureostipes, D. minutum and Polysphondylium pallidum. We propose that altered cAMP levels, perturbed cAMP gradient and impaired signalling may be the critical factors for the origin of multiple tips in other Dictyostelids as well. In the presence of caffeine, slug cell movement gets impaired and restricted. The cell type specific markers, ecmA (prestalk) and pspA (prespore) cells are not equally contributing during additional tip formation. During additional tip emergence, prespore cells transdifferentiate to compensate the loss of prestalk cells.

CONCLUSION: Caffeine decreases adenyl cyclase-A (AcaA) levels and as a consequence low cAMP is synthesised altering the gradient. Further if cAMP phosphodiesterase (Pde4) levels go down in the presence of caffeine, the cAMP gradient breaks down. When there is no cAMP gradient, directional movement is inhibited and might favour re-differentiation of prespore to prestalk cells.}, } @article {pmid22926916, year = {2012}, author = {Chen, G and Rubinstein, B and Li, R}, title = {Whole chromosome aneuploidy: big mutations drive adaptation by phenotypic leap.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {10}, pages = {893-900}, pmid = {22926916}, issn = {1521-1878}, support = {R01 GM059964/GM/NIGMS NIH HHS/United States ; R01-GM059964/GM/NIGMS NIH HHS/United States ; }, mesh = {Abnormal Karyotype ; Adaptation, Biological/*genetics ; *Aneuploidy ; Animals ; Chromosomal Instability ; Chromosomes/*genetics ; *Evolution, Molecular ; Humans ; Mutagenesis ; Phenotype ; }, abstract = {Despite its widespread existence, the adaptive role of aneuploidy (the abnormal state of having an unequal number of different chromosomes) has been a subject of debate. Cellular aneuploidy has been associated with enhanced resistance to stress, whereas on the organismal level it is detrimental to multicellular species. Certain aneuploid karyotypes are deleterious for specific environments, but karyotype diversity in a population potentiates adaptive evolution. To reconcile these paradoxical observations, this review distinguishes the role of aneuploidy in cellular versus organismal evolution. Further, it proposes a population genetics perspective to examine the behavior of aneuploidy on a populational versus individual level. By altering the copy number of a significant portion of the genome, aneuploidy introduces large phenotypic leaps that enable small cell populations to explore a wide phenotypic landscape, from which adaptive traits can be selected. The production of chromosome number variation can be further increased by stress- or mutation-induced chromosomal instability, fueling rapid cellular adaptation.}, } @article {pmid22925839, year = {2012}, author = {Baars, BJ and Edelman, DB}, title = {Consciousness, biology and quantum hypotheses.}, journal = {Physics of life reviews}, volume = {9}, number = {3}, pages = {285-294}, doi = {10.1016/j.plrev.2012.07.001}, pmid = {22925839}, issn = {1873-1457}, mesh = {Animals ; Biology/*methods ; *Consciousness/physiology ; Evolution, Molecular ; Humans ; *Models, Neurological ; *Quantum Theory ; Wakefulness/physiology ; }, abstract = {Natural phenomena are reducible to quantum events in principle, but quantum mechanics does not always provide the best level of analysis. The many-body problem, chaotic avalanches, materials properties, biological organisms, and weather systems are better addressed at higher levels. Animals are highly organized, goal-directed, adaptive, selectionist, information-preserving, functionally redundant, multicellular, quasi-autonomous, highly mobile, reproducing, dissipative systems that conserve many fundamental features over remarkably long periods of time at the species level. Animal brains consist of massive, layered networks of specialized signaling cells with 10,000 communication points per cell, and interacting up to 1000 Hz. Neurons begin to divide and differentiate very early in gestation, and continue to develop until middle age. Waking brains operate far from thermodynamic equilibrium under delicate homeostatic control, making them extremely sensitive to a range of physical and chemical stimuli, highly adaptive, and able to produce a remarkable range of goal-relevant actions. Consciousness is "a difference that makes a difference" at the level of massive neuronal interactions in the most parallel-interactive anatomical structure of the mammalian brain, the cortico-thalamic (C-T) system. Other brain structures are not established to result in direct conscious experiences, at least in humans. However, indirect extra-cortical influences on the C-T system are pervasive. Learning, brain plasticity and major life adaptations may require conscious cognition. While brains evolved over hundreds of millions of years, and individual brains grow over months, years and decades, conscious events appear to have a duty cycle of ∼100 ms, fading after a few seconds. They can of course be refreshed by inner rehearsal, re-visualization, or attending to recurrent stimulus sources. These very distinctive brain events are needed when animals seek out and cope with new, unpredictable and highly valued life events, such as evading predators, gathering critical information, seeking mates and hunting prey. Attentional selection of conscious events can be observed behaviorally in animals showing coordinated receptor orienting, flexible responding, alertness, emotional reactions, seeking, motivation and curiosity, as well as behavioral surprise and cortical and autonomic arousal. Brain events corresponding to attentional selection are prominent and widespread. Attention generally results in conscious experiences, which may be needed to recruit widespread processing resources in the brain. Many neuronal processes never become conscious, such as the balance system of the inner ear. An air traveler may "see" the passenger cabin tilt downward as the plane tilts to descend for a landing. That visual experience occurs even at night, when the traveler has no external frame of spatial reference. The passenger's body tilt with respect to gravity is detected unconsciously via the hair cells of the vestibular canals, which act as liquid accelerometers. However, that sensory activity is not experienced directly. It only becomes conscious via vision and the body senses. The vestibular sense is therefore quite different from visual perception, which "reports" accurately to a conscious field of experience, so that we can point accurately to a bright star on a dark night. Vestibular input is also precise but unconscious. Conscious cognition is therefore a distinct kind of brain event. Many of its features are well established, and must be accounted for by any adequate theory. No non-biological examples are known. Penrose and Hameroff have proposed that consciousness may be viewed as a fundamental problem in quantum physics. Specifically, their 'orchestrated objective reduction' (Orch-OR) hypothesis posits that conscious states arise from quantum computations in the microtubules of neurons. However, a number of microtubule-associated proteins are found in both plant and animal cells (like neurons) and plants are not generally considered to be conscious. Current quantum-level proposals do not explain the prominent empirical features of consciousness. Notably, they do not distinguish between closely matched conscious and unconscious brain events, as cognitive-biological theories must. About half of the human brain does not support conscious contents directly, yet neurons in these "unconscious" brain regions contain large numbers of microtubules. QM phenomena are famously observer-dependent, but to the best of our knowledge it has not been shown that they require a conscious observer, as opposed to a particle detector. Conscious humans cannot detect quantum events "as such" without the aid of special instrumentation. Instead, we categorize the wavelengths of light into conscious sensory events that neglect their quantum mechanical properties. In science the burden of proof is on the proposer, and this burden has not yet been met by quantum-level proposals. While in the future we may discover quantum effects that bear distinctively on conscious cognition 'as such,' we do not have such evidence today.}, } @article {pmid22920514, year = {2012}, author = {Souza, V and Siefert, JL and Escalante, AE and Elser, JJ and Eguiarte, LE}, title = {The Cuatro Ciénegas Basin in Coahuila, Mexico: an astrobiological Precambrian Park.}, journal = {Astrobiology}, volume = {12}, number = {7}, pages = {641-647}, pmid = {22920514}, issn = {1557-8070}, mesh = {Biological Evolution ; *Ecosystem ; *Exobiology/methods ; Mexico ; Models, Biological ; Time Factors ; *Wilderness ; }, abstract = {The Cuatro Ciénegas Basin (CCB) is a rare oasis in the Chihuahuan Desert in the state of Coahuila, Mexico. It has a biological endemism similar to that of the Galapagos Islands, and its spring-fed ecosystems have very low nutrient content (nitrogen or phosphorous) and are dominated by diverse microbialites. Thus, it has proven to be a distinctive opportunity for the field of astrobiology, as the CCB can be seen as a proxy for an earlier time in Earth's history, in particular the late Precambrian, the biological frontier when prokaryotic life yielded at least partial dominance to eukaryotes and multicellular life. It is a kind of ecological time machine that provides abundant opportunities for collaborative investigations by geochemists, geologists, ecologists, and population biologists in the study of the evolutionary processes that structured Earth-based life, especially in the microbial realm. The CCB is an object of investigation for the identification of biosignatures of past and present biota that can be used in our search for extraterrestrial life. In this review, we summarize CCB research efforts that began with microbial ecology and population biology projects and have since been expanded into broader efforts that involve biogeochemistry, comparative genomics, and assessments of biosignatures. We also propose that, in the future, the CCB is sanctioned as a "Precambrian Park" for astrobiology.}, } @article {pmid22919645, year = {2012}, author = {Salvucci, E}, title = {Selfishness, warfare, and economics; or integration, cooperation, and biology.}, journal = {Frontiers in cellular and infection microbiology}, volume = {2}, number = {}, pages = {54}, pmid = {22919645}, issn = {2235-2988}, mesh = {Biology/*trends ; *Evolution, Molecular ; Humans ; }, abstract = {The acceptance of Darwin's theory of evolution by natural selection is not complete and it has been pointed out its limitation to explain the complex processes that constitute the transformation of species. It is necessary to discuss the explaining power of the dominant paradigm. It is common that new discoveries bring about contradictions that are intended to be overcome by adjusting results to the dominant reductionist paradigm using all sorts of gradations and combinations that are admitted for each case. In addition to the discussion on the validity of natural selection, modern findings represent a challenge to the interpretation of the observations with the Darwinian view of competition and struggle for life as theoretical basis. New holistic interpretations are emerging related to the Net of Life, in which the interconnection of ecosystems constitutes a dynamic and self-regulating biosphere: viruses are recognized as a macroorganism with a huge collection of genes, most unknown that constitute the major planet's gene pool. They play a fundamental role in evolution since their sequences are capable of integrating into the genomes in an "infective" way and become an essential part of multicellular organisms. They have content with "biological sense" i.e., they appear as part of normal life processes and have a serious role as carrier elements of complex genetic information. Antibiotics are cell signals with main effects on general metabolism and transcription on bacterial cells and communities. The hologenome theory considers an organism and all of its associated symbiotic microbes (parasites, mutualists, synergists, amensalists) as a result of symbiopoiesis. Microbes, helmints, that are normally understood as parasites are cohabitants and they have cohabited with their host and drive the evolution and existence of the partners. Each organism is the result of integration of complex systems. The eukaryotic organism is the result of combination of bacterial, virus, and eukaryotic DNA and it is the result of the interaction of its own genome with the genome of its microbiota, and their metabolism are intertwined (as a "superorganism") along evolution. The darwinian paradigm had its origin in the free market theories and concepts of Malthus and Spencer. Then, nature was explained on the basis of market theories moving away from an accurate explanation of natural phenomena. It is necessary to acknowledge the limitations of the dominant dogma. These new interpretations about biological processes, molecules, roles of viruses in nature, and microbial interactions are remarkable points to be considered in order to construct a solid theory adjusted to the facts and with less speculations and tortuous semantic traps.}, } @article {pmid22916027, year = {2012}, author = {Bietenhader, M and Martos, A and Tetaud, E and Aiyar, RS and Sellem, CH and Kucharczyk, R and Clauder-Münster, S and Giraud, MF and Godard, F and Salin, B and Sagot, I and Gagneur, J and Déquard-Chablat, M and Contamine, V and Hermann-Le Denmat, S and Sainsard-Chanet, A and Steinmetz, LM and di Rago, JP}, title = {Experimental relocation of the mitochondrial ATP9 gene to the nucleus reveals forces underlying mitochondrial genome evolution.}, journal = {PLoS genetics}, volume = {8}, number = {8}, pages = {e1002876}, pmid = {22916027}, issn = {1553-7404}, mesh = {Biological Evolution ; Cell Nucleus/enzymology/*genetics ; Fungal Proteins/*genetics/metabolism ; Gene Deletion ; Genes, Mitochondrial ; Genome, Mitochondrial ; Mitochondria/enzymology/*genetics ; Mitochondrial Proton-Translocating ATPases/*genetics/metabolism ; Oxidative Phosphorylation ; Podospora/enzymology/*genetics ; Protein Subunits/genetics/metabolism ; Saccharomyces cerevisiae/enzymology/*genetics ; Saccharomyces cerevisiae Proteins/*genetics/metabolism ; Transgenes ; }, abstract = {Only a few genes remain in the mitochondrial genome retained by every eukaryotic organism that carry out essential functions and are implicated in severe diseases. Experimentally relocating these few genes to the nucleus therefore has both therapeutic and evolutionary implications. Numerous unproductive attempts have been made to do so, with a total of only 5 successes across all organisms. We have taken a novel approach to relocating mitochondrial genes that utilizes naturally nuclear versions from other organisms. We demonstrate this approach on subunit 9/c of ATP synthase, successfully relocating this gene for the first time in any organism by expressing the ATP9 genes from Podospora anserina in Saccharomyces cerevisiae. This study substantiates the role of protein structure in mitochondrial gene transfer: expression of chimeric constructs reveals that the P. anserina proteins can be correctly imported into mitochondria due to reduced hydrophobicity of the first transmembrane segment. Nuclear expression of ATP9, while permitting almost fully functional oxidative phosphorylation, perturbs many cellular properties, including cellular morphology, and activates the heat shock response. Altogether, our study establishes a novel strategy for allotopic expression of mitochondrial genes, demonstrates the complex adaptations required to relocate ATP9, and indicates a reason that this gene was only transferred to the nucleus during the evolution of multicellular organisms.}, } @article {pmid22911953, year = {2012}, author = {Jonker, JL and von Byern, J and Flammang, P and Klepal, W and Power, AM}, title = {Unusual adhesive production system in the barnacle Lepas anatifera: an ultrastructural and histochemical investigation.}, journal = {Journal of morphology}, volume = {273}, number = {12}, pages = {1377-1391}, doi = {10.1002/jmor.20067}, pmid = {22911953}, issn = {1097-4687}, support = {P 21767/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adhesives/chemistry/*isolation & purification/metabolism ; Animals ; Glycoproteins/biosynthesis/chemistry/*isolation & purification ; Secretory Pathway ; Thoracica/*chemistry/*cytology/ultrastructure ; }, abstract = {Adhesives that are naturally produced by marine organisms are potential sources of inspiration in the search for medical adhesives. Investigations of barnacle adhesives are at an early stage but it is becoming obvious that barnacles utilize a unique adhesive system compared to other marine organisms. The current study examined the fine structure and chemistry of the glandular system that produces the adhesive of the barnacle Lepas anatifera. All components for the glue originated from large single-cell glands (70-180 μm). Staining (including immunostaining) showed that L-3,4-dihydroxyphenylalanine and phosphoserine were not present in the glue producing tissues, demonstrating that the molecular adhesion of barnacles differs from all other permanently gluing marine animals studied to date. The glandular tissue and adhesive secretion primarily consisted of slightly acidic proteins but also included some carbohydrate. Adhesive proteins were stored in cytoplasmic granules adjacent to an intracellular drainage canal (ICC); observations implicated both merocrine and apocrine mechanisms in the transport of the secretion from the cell cytoplasm to the ICC. Inside the ICC, the secretion was no longer contained within granules but was a flocculent material which became "clumped" as it traveled through the canal network. Hemocytes were not seen within the adhesive "apparatus" (comprising of the glue producing cells and drainage canals), nor was there any structural mechanism by which additions such as hemocytes could be made to the secretion. The unicellular adhesive gland in barnacles is distinct from multicellular adhesive systems observed in marine animals such as mussels and tubeworms. Because the various components are not physically separated in the apparatus, the barnacle adhesive system appears to utilize completely different and unknown mechanisms for maintaining the liquid state of the glue within the body, as well as unidentified mechanisms for the conversion of extruded glue into hard cement.}, } @article {pmid22903534, year = {2012}, author = {Bosch, TC}, title = {Rethinking the origin of multicellularity: where do epithelia come from? (Comment on DOI 10.1002/bies.201100187).}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {34}, number = {10}, pages = {826-827}, doi = {10.1002/bies.201200104}, pmid = {22903534}, issn = {1521-1878}, mesh = {Animals ; *Cell Polarity ; Dictyostelium/*cytology ; Epithelial Cells/*physiology ; Humans ; }, } @article {pmid22889906, year = {2012}, author = {Jin, J and Pawson, T}, title = {Modular evolution of phosphorylation-based signalling systems.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {367}, number = {1602}, pages = {2540-2555}, pmid = {22889906}, issn = {1471-2970}, support = {MOP-13466//Canadian Institutes of Health Research/Canada ; MOP-57793//Canadian Institutes of Health Research/Canada ; MOP-6849//Canadian Institutes of Health Research/Canada ; }, mesh = {Allosteric Regulation ; Animals ; Binding Sites ; Enzyme Activation ; Eukaryota/chemistry/*enzymology ; *Evolution, Molecular ; Models, Molecular ; Phosphoric Monoester Hydrolases/chemistry ; *Phosphorylation ; Protein Binding ; Protein Kinases/*chemistry ; *Signal Transduction ; Substrate Specificity ; src Homology Domains ; }, abstract = {Phosphorylation sites are formed by protein kinases ('writers'), frequently exert their effects following recognition by phospho-binding proteins ('readers') and are removed by protein phosphatases ('erasers'). This writer-reader-eraser toolkit allows phosphorylation events to control a broad range of regulatory processes, and has been pivotal in the evolution of new functions required for the development of multi-cellular animals. The proteins that comprise this system of protein kinases, phospho-binding targets and phosphatases are typically modular in organization, in the sense that they are composed of multiple globular domains and smaller peptide motifs with binding or catalytic properties. The linkage of these binding and catalytic modules in new ways through genetic recombination, and the selection of particular domain combinations, has promoted the evolution of novel, biologically useful processes. Conversely, the joining of domains in aberrant combinations can subvert cell signalling and be causative in diseases such as cancer. Major inventions such as phosphotyrosine (pTyr)-mediated signalling that flourished in the first multi-cellular animals and their immediate predecessors resulted from stepwise evolutionary progression. This involved changes in the binding properties of interaction domains such as SH2 and their linkage to new domain types, and alterations in the catalytic specificities of kinases and phosphatases. This review will focus on the modular aspects of signalling networks and the mechanism by which they may have evolved.}, } @article {pmid22876786, year = {2012}, author = {Cohen, E and Chor, B}, title = {Detecting phylogenetic signals in eukaryotic whole genome sequences.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {19}, number = {8}, pages = {945-956}, doi = {10.1089/cmb.2012.0122}, pmid = {22876786}, issn = {1557-8666}, mesh = {Algorithms ; Animals ; *Computer Simulation ; Eukaryota/*genetics ; Genetic Speciation ; *Genome ; Humans ; *Models, Genetic ; *Phylogeny ; Proteome/genetics ; Reference Standards ; Sequence Homology, Nucleic Acid ; }, abstract = {Whole genome sequences are a rich source of molecular data, with a potential for the discovery of novel evolutionary information. Yet, many parts of these sequences are not known to be under evolutionary pressure and, thus, are not conserved. Furthermore, a good model for whole genome evolution does not exist. Consequently, it is not a priori clear if a meaningful phylogenetic signal exists and can be extracted from the sequences as a whole. Indeed, very few phylogenies were reconstructed based on these sequences. Prior to this work, only two reconstruction methods were applied to large eukaryotic genomes: the K(r) method (Haubold et al., 2009), which was applied to genomes of rather small diversity (Drosophila species), and the feature frequency profile method (Sims et al., 2009a), which was applied to genomes of moderate diversity (mammals). We investigate the whole genome-based phylogenetic reconstruction question with respect to a much wider taxonomic sample. We apply K(r), FFP, and an alternative alignment-free method, the average common subsequence (ACS) (Ulitsky et al., 2006), to 24 multicellular eukaryotes (vertebrates, invertebrates, and plants). We also apply ACS to the proteome sequences of these 24 taxa. We compare the resulting trees to a standard reference, the National Center for Biotechnology Information (NCBI) taxonomy tree. Trees produced by ACS(AA), based on proteomes, are in complete agreement with the NCBI tree. For the genome-based reconstruction, ACS(DNA) produces trees whose agreement with the NCBI tree is excellent to very good for divergence times up to 800 million years ago, medium at 1 billion years ago, and poor at 1.6 billion years ago. We conclude that whole genomes do carry a clear phylogenetic signal, yet this signal "saturates" with longer divergence times. Furthermore, from the few existing methods, ACS is best capable of detecting this signal.}, } @article {pmid22875808, year = {2012}, author = {Avesson, L and Reimegård, J and Wagner, EG and Söderbom, F}, title = {MicroRNAs in Amoebozoa: deep sequencing of the small RNA population in the social amoeba Dictyostelium discoideum reveals developmentally regulated microRNAs.}, journal = {RNA (New York, N.Y.)}, volume = {18}, number = {10}, pages = {1771-1782}, pmid = {22875808}, issn = {1469-9001}, mesh = {Amoebozoa/*genetics ; Animals ; Base Sequence ; Cluster Analysis ; Dictyostelium/*genetics/growth & development ; Gene Expression Regulation, Developmental ; Genome, Protozoan ; *High-Throughput Nucleotide Sequencing/methods ; MicroRNAs/chemistry/*genetics/isolation & purification ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Protozoan/genetics ; Transfection ; Validation Studies as Topic ; }, abstract = {The RNA interference machinery has served as a guardian of eukaryotic genomes since the divergence from prokaryotes. Although the basic components have a shared origin, silencing pathways directed by small RNAs have evolved in diverse directions in different eukaryotic lineages. Micro (mi)RNAs regulate protein-coding genes and play vital roles in plants and animals, but less is known about their functions in other organisms. Here, we report, for the first time, deep sequencing of small RNAs from the social amoeba Dictyostelium discoideum. RNA from growing single-cell amoebae as well as from two multicellular developmental stages was sequenced. Computational analyses combined with experimental data reveal the expression of miRNAs, several of them exhibiting distinct expression patterns during development. To our knowledge, this is the first report of miRNAs in the Amoebozoa supergroup. We also show that overexpressed miRNA precursors generate miRNAs and, in most cases, miRNA* sequences, whose biogenesis is dependent on the Dicer-like protein DrnB, further supporting the presence of miRNAs in D. discoideum. In addition, we find miRNAs processed from hairpin structures originating from an intron as well as from a class of repetitive elements. We believe that these repetitive elements are sources for newly evolved miRNAs.}, } @article {pmid22857779, year = {2012}, author = {Prem, D and Solís, MT and Bárány, I and Rodríguez-Sanz, H and Risueño, MC and Testillano, PS}, title = {A new microspore embryogenesis system under low temperature which mimics zygotic embryogenesis initials, expresses auxin and efficiently regenerates doubled-haploid plants in Brassica napus.}, journal = {BMC plant biology}, volume = {12}, number = {}, pages = {127}, pmid = {22857779}, issn = {1471-2229}, mesh = {Brassica napus/cytology/*embryology/genetics/growth & development ; *Cold Temperature ; DNA, Plant/analysis ; Desiccation ; Diploidy ; Germination ; Haploidy ; Indoleacetic Acids/*metabolism ; Pollen/cytology/*embryology/genetics/growth & development ; }, abstract = {BACKGROUND: Microspore embryogenesis represents a unique system of single cell reprogramming in plants wherein a highly specialized cell, the microspore, by specific stress treatment, switches its fate towards an embryogenesis pathway. In Brassica napus, a model species for this phenomenon, incubation of isolated microspores at 32°C is considered to be a pre-requisite for embryogenesis induction.

RESULTS: We have developed a new in vitro system at lower temperature (18°C) to efficiently induce microspore embryogenesis throughout two different developmental pathways: one involving the formation of suspensor-like structures (52.4%) and another producing multicellular embryos without suspensor (13.1%); additionally, a small proportion of non-responsive microspores followed a gametophytic-like development (34.4%) leading to mature pollen. The suspensor-like pathway followed at 18°C involved the establishment of asymmetric identities from the first microspore division and an early polarity leading to different cell fates, suspensor and embryo development, which were formed by cells with different organizations and endogenous auxin distribution, similar to zygotic embryogenesis. In addition, a new strategy for germination of microspore derived embryos was developed for achieving more than 90% conversion of embryos to plantlets, with a predominance of spontaneous doubled haploids plants.

CONCLUSION: The present work reveals a novel mechanism for efficient microspore embryogenesis induction in B. napus using continuous low temperature treatment. Results indicated that low temperature applied for longer periods favours an embryogenesis pathway whose first division originates asymmetric cell identities, early polarity establishment and the formation of suspensor-like structures, mimicking zygotic embryogenesis. This new in vitro system provides a convenient tool to analyze in situ the mechanisms underlying different developmental pathways during the microspore reprogramming, breaking or not the cellular symmetry, the establishment of polarity and the developmental embryo patterning, which further produce mature embryos and plants.}, } @article {pmid22857263, year = {2012}, author = {Sterkers, Y and Lachaud, L and Bourgeois, N and Crobu, L and Bastien, P and Pagès, M}, title = {Novel insights into genome plasticity in Eukaryotes: mosaic aneuploidy in Leishmania.}, journal = {Molecular microbiology}, volume = {86}, number = {1}, pages = {15-23}, doi = {10.1111/j.1365-2958.2012.08185.x}, pmid = {22857263}, issn = {1365-2958}, mesh = {Adaptation, Biological ; *Aneuploidy ; Evolution, Molecular ; Genetic Heterogeneity ; Genome Size ; *Genome, Protozoan ; Genomic Instability ; Leishmania/*genetics ; }, abstract = {Leishmania are unicellular eukaryotes that have many markedly original molecular features compared with other uni- or multicellular eukaryotes like yeasts or mammals. Genome plasticity in this parasite has been the subject of many publications, and has been associated with drug resistance or adaptability. Aneuploidy has been suspected by several authors and it is now confirmed using state-of-the-art technologies such as high-throughput DNA sequencing. The analysis of genome contents at the single cell level using fluorescence in situ hybridization (FISH) has brought a new light on the genome organization: within a cell population, every chromosome, in every cell, may be present in at least two ploidy states (being either monosomic, disomic or trisomic), and the chromosomal content varies greatly from cell to cell, thus generating a constitutive intra-strain genomic heterogeneity, here termed 'mosaic aneuploidy'. Mosaic aneuploidy deeply affects the genetics of these organisms, leading, for example, to an extreme degree of intra-strain genomic diversity, as well as to a clearance of heterozygous cells in the population without however affecting genetic heterogeneity. Second, mosaic aneuploidy might be considered as a powerful strategy evolved by the parasite for adapting to modifications of environment conditions as well as for the emergence of drug resistance. On the whole, mosaic aneuploidy may be considered as a novel mechanism for generating phenotypic diversity driven by genomic plasticity.}, } @article {pmid22855327, year = {2012}, author = {Galliot, B}, title = {Preface: the hydra model system.}, journal = {The International journal of developmental biology}, volume = {56}, number = {6-8}, pages = {407-409}, doi = {10.1387/ijdb.120094bg}, pmid = {22855327}, issn = {1696-3547}, mesh = {Animals ; *Hydra/physiology ; Models, Animal ; Models, Biological ; Regeneration ; }, abstract = {The freshwater Hydra polyp emerged as a model system in 1741 when Abraham Trembley not only discovered its amazing regenerative potential, but also demonstrated that experimental manipulations pave the way to research in biology. Since then, Hydra flourished as a potent and fruitful model system to help answer questions linked to cell and developmental biology, as such as the setting up of an organizer to regenerate a complex missing structure, the establishment and maintainance of polarity in a multicellular organism, the development of mathematical models to explain the robust developmental rules observed in this animal, the maintainance of stemness and multipotency in a highly dynamic environment, the plasticity of differentiated cells, to name but a few. However the Hydra model system is not restricted to cell and developmental biology; during the past 270 years it has also been heavily used to investigate the relationships between Hydra and its environment, opening new horizons concerning neurophysiology, innate immunity, ecosystems, ecotoxicology, symbiosis...}, } @article {pmid22842779, year = {2012}, author = {Schippers, JH and Nguyen, HM and Lu, D and Schmidt, R and Mueller-Roeber, B}, title = {ROS homeostasis during development: an evolutionary conserved strategy.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {69}, number = {19}, pages = {3245-3257}, pmid = {22842779}, issn = {1420-9071}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation ; Cell Proliferation ; Glutaredoxins/metabolism ; *Growth and Development ; Homeostasis ; NADPH Oxidases/metabolism ; Plants/metabolism ; Proteins/metabolism ; Reactive Oxygen Species/*metabolism ; Signal Transduction ; Thioredoxins/metabolism ; Yeasts/metabolism ; }, abstract = {The balance between cellular proliferation and differentiation is a key aspect of development in multicellular organisms. Recent studies on Arabidopsis roots revealed distinct roles for different reactive oxygen species (ROS) in these processes. Modulation of the balance between ROS in proliferating cells and elongating cells is controlled at least in part at the transcriptional level. The effect of ROS on proliferation and differentiation is not specific for plants but appears to be conserved between prokaryotic and eukaryotic life forms. The ways in which ROS is received and how it affects cellular functioning is discussed from an evolutionary point of view. The different redox-sensing mechanisms that evolved ultimately result in the activation of gene regulatory networks that control cellular fate and decision-making. This review highlights the potential common origin of ROS sensing, indicating that organisms evolved similar strategies for utilizing ROS during development, and discusses ROS as an ancient universal developmental regulator.}, } @article {pmid22837400, year = {2012}, author = {Nichols, SA and Roberts, BW and Richter, DJ and Fairclough, SR and King, N}, title = {Origin of metazoan cadherin diversity and the antiquity of the classical cadherin/β-catenin complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {32}, pages = {13046-13051}, pmid = {22837400}, issn = {1091-6490}, support = {R01 GM089977/GM/NIGMS NIH HHS/United States ; T32 GM007232/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Cadherins/*genetics ; Choanoflagellata/*genetics ; Computational Biology ; DNA Primers/genetics ; *Evolution, Molecular ; *Genetic Variation ; Genome/genetics ; Genomic Library ; Molecular Sequence Data ; *Phylogeny ; Sequence Analysis, DNA ; beta Catenin/*genetics ; }, abstract = {The evolution of cadherins, which are essential for metazoan multicellularity and restricted to metazoans and their closest relatives, has special relevance for understanding metazoan origins. To reconstruct the ancestry and evolution of cadherin gene families, we analyzed the genomes of the choanoflagellate Salpingoeca rosetta, the unicellular outgroup of choanoflagellates and metazoans Capsaspora owczarzaki, and a draft genome assembly from the homoscleromorph sponge Oscarella carmela. Our finding of a cadherin gene in C. owczarzaki reveals that cadherins predate the divergence of the C. owczarzaki, choanoflagellate, and metazoan lineages. Data from these analyses also suggest that the last common ancestor of metazoans and choanoflagellates contained representatives of at least three cadherin families, lefftyrin, coherin, and hedgling. Additionally, we find that an O. carmela classical cadherin has predicted structural features that, in bilaterian classical cadherins, facilitate binding to the cytoplasmic protein β-catenin and, thereby, promote cadherin-mediated cell adhesion. In contrast with premetazoan cadherin families (i.e., those conserved between choanoflagellates and metazoans), the later appearance of classical cadherins coincides with metazoan origins.}, } @article {pmid22833122, year = {2012}, author = {Aoyama, T and Hiwatashi, Y and Shigyo, M and Kofuji, R and Kubo, M and Ito, M and Hasebe, M}, title = {AP2-type transcription factors determine stem cell identity in the moss Physcomitrella patens.}, journal = {Development (Cambridge, England)}, volume = {139}, number = {17}, pages = {3120-3129}, doi = {10.1242/dev.076091}, pmid = {22833122}, issn = {1477-9129}, mesh = {Arabidopsis Proteins/*metabolism ; Blotting, Southern ; Bryopsida/*cytology/*genetics/growth & development ; Cell Differentiation/*physiology ; Cluster Analysis ; Computational Biology ; Cytokinins/metabolism ; Gene Expression Regulation, Plant/*genetics ; Germ Cells, Plant/growth & development ; Histocytochemistry ; Indoleacetic Acids/metabolism ; Likelihood Functions ; Microscopy, Fluorescence ; Models, Genetic ; Phylogeny ; Plasmids/genetics ; Real-Time Polymerase Chain Reaction ; Species Specificity ; Stem Cells/*physiology ; Transcription Factors/*metabolism ; }, abstract = {Stem cells are formed at particular times and positions during the development of multicellular organisms. Whereas flowering plants form stem cells only in the sporophyte generation, non-seed plants form stem cells in both the sporophyte and gametophyte generations. Although the molecular mechanisms underlying stem cell formation in the sporophyte generation have been extensively studied, only a few transcription factors involved in the regulation of gametophyte stem cell formation have been reported. The moss Physcomitrella patens forms a hypha-like body (protonema) and a shoot-like body (gametophore) from a protonema apical cell and a gametophore apical cell, respectively. These apical cells have stem cell characteristics and are formed as side branches of differentiated protonema cells. Here, we show that four AP2-type transcription factors orthologous to Arabidopsis thaliana AINTEGUMENTA, PLETHORA and BABY BOOM (APB) are indispensable for the formation of gametophore apical cells from protonema cells. Quadruple disruption of all APB genes blocked gametophore formation, even in the presence of cytokinin, which enhances gametophore apical cell formation in the wild type. All APB genes were expressed in emerging gametophore apical cells, but not in protonema apical cells. Heat-shock induction of an APB4 transgene driven by a heat-shock promoter increased the number of gametophores. Expression of all APB genes was induced by auxin but not by cytokinin. Thus, the APB genes function synergistically with cytokinin signaling to determine the identity of the two types of stem cells.}, } @article {pmid22832104, year = {2012}, author = {Sebé-Pedrós, A and Zheng, Y and Ruiz-Trillo, I and Pan, D}, title = {Premetazoan origin of the hippo signaling pathway.}, journal = {Cell reports}, volume = {1}, number = {1}, pages = {13-20}, pmid = {22832104}, issn = {2211-1247}, support = {/HHMI_/Howard Hughes Medical Institute/United States ; 206883/ERC_/European Research Council/International ; R01 EY015708/EY/NEI NIH HHS/United States ; R01EY015708/EY/NEI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Amoeba/metabolism ; Animals ; Drosophila melanogaster/genetics/growth & development/metabolism ; *Evolution, Molecular ; Gene Expression Regulation ; Genomics ; Likelihood Functions ; Molecular Sequence Data ; Protein Serine-Threonine Kinases/chemistry/*genetics/metabolism ; Sequence Alignment ; Signal Transduction/*genetics ; Transcription Factors/metabolism ; }, abstract = {Nonaggregative multicellularity requires strict control of cell number. The Hippo signaling pathway coordinates cell proliferation and apoptosis and is a central regulator of organ size in animals. Recent studies have shown the presence of key members of the Hippo pathway in nonbilaterian animals, but failed to identify this pathway outside Metazoa. Through comparative analyses of recently sequenced holozoan genomes, we show that Hippo pathway components, such as the kinases Hippo and Warts, the coactivator Yorkie, and the transcription factor Scalloped, were already present in the unicellular ancestors of animals. Remarkably, functional analysis of Hippo components of the amoeboid holozoan Capsaspora owczarzaki, performed in Drosophila melanogaster, demonstrate that the growth-regulatory activity of the Hippo pathway is conserved in this unicellular lineage. Our findings show that the Hippo pathway evolved well before the origin of Metazoa and highlight the importance of Hippo signaling as a key developmental mechanism predating the origin of Metazoa.}, } @article {pmid22825600, year = {2012}, author = {Chakraborty, C and Agoramoorthy, G}, title = {Stem cells in the light of evolution.}, journal = {The Indian journal of medical research}, volume = {135}, number = {6}, pages = {813-819}, pmid = {22825600}, issn = {0971-5916}, mesh = {Animals ; *Biological Evolution ; Gene Regulatory Networks ; Humans ; Mammals ; *Regenerative Medicine ; Selection, Genetic ; *Stem Cells/cytology/physiology ; }, abstract = {All organisms depend on stem cells for their survival. As a result, stem cells may be a prerequisite for the evolution of specific characteristics in organisms that include regeneration, multicellularity and coloniality. Stem cells have attracted the attention of biologists and medical scientists for a long time. These provide materials for regenerative medicine. We review in this paper, the link between modern stem cell research and early studies in ancient organisms. It also outlines details on stem cells in the light of evolution with an emphasis on their regeneration potential, coloniality and multicellularity. The information provided might be of use to molecular biologists, medical scientists and developmental biologists who are engaged in integrated research involving the stem cells.}, } @article {pmid22821454, year = {2012}, author = {Sommer, RJ}, title = {Evolution of regulatory networks: nematode vulva induction as an example of developmental systems drift.}, journal = {Advances in experimental medicine and biology}, volume = {751}, number = {}, pages = {79-91}, doi = {10.1007/978-1-4614-3567-9_4}, pmid = {22821454}, issn = {0065-2598}, mesh = {Animals ; Biological Evolution ; Caenorhabditis elegans/genetics/*growth & development/metabolism ; Cell Communication ; Conserved Sequence ; Epidermis/*growth & development/metabolism ; Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Helminth Proteins/genetics/metabolism ; Larva/genetics/*growth & development/metabolism ; Nematoda/genetics/*growth & development/metabolism ; Phenotype ; Phylogeny ; Reproduction/physiology ; Signal Transduction ; }, abstract = {Changes in the developmental processes and developmental mechanisms can result in the modification of morphological structures and in the evolution of phenotypic novelty. But how do developmental processes evolve? One striking finding in modern biology is the confrontation of morphological diversity in multicellular organisms with the conserved blueprint of life-the small number of conserved signaling pathways and transcriptional regulators. Evolutionary developmental biology (evo-devo) tries to explain this discrepancy between macroscopic diversity and molecular uniformity. Selected case studies in evo-devo models allowed detailed insight into the mechanisms of evolutionary changes and might help solving this problem. Here, I compare the formation of vulva development between Caenorhabditis elegans and the evo-devo model Pristionchus pacificus. More than 3 decades of work in C. elegans and 15 years in P. pacificus provide an insight into the molecular mechanisms of developmental change during vulva evolution. C. elegans and P. pacificus differ first, in the type of the signaling system used for vulva induction; second, the cells required for the inductive interactions; third, the logic of the signal system, and finally, the sequence and structure of peptide domains in otherwise conserved proteins. Nonetheless, the vulva is formed from the same three cells in both nematodes. I discuss redundancy as an evolutionary mechanism to explain developmental systems drift, a theory predicting conserved morphological structures to be generated by diverse molecular regulatory networks.}, } @article {pmid22817532, year = {2012}, author = {Skulachev, VP}, title = {What is "phenoptosis" and how to fight it?.}, journal = {Biochemistry. Biokhimiia}, volume = {77}, number = {7}, pages = {689-706}, doi = {10.1134/S0006297912070012}, pmid = {22817532}, issn = {1608-3040}, mesh = {Aging/*genetics ; Animals ; Apoptosis/*genetics ; Biological Evolution ; Caloric Restriction ; *Death ; Genome/genetics ; Humans ; Mitochondria/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Phenoptosis is the death of an organism programmed by its genome. Numerous examples of phenoptosis are described in prokaryotes, unicellular eukaryotes, and all kingdoms of multicellular eukaryotes (animals, plants, and fungi). There are very demonstrative cases of acute phenoptosis when actuation of a specific biochemical or behavioral program results in immediate death. Rapid (taking days) senescence of semelparous plants is described as phenoptosis controlled by already known genes and mediated by toxic phytohormones like abscisic acid. In soya, the death signal is transmitted from beans to leaves via xylem, inducing leaf fall and death of the plant. Mutations in two genes of Arabidopsis thaliana, required for the flowering and subsequent formation of seeds, prevent senescence, strongly prolonging the lifespan of this small semelparous grass that becomes a big bush with woody stem, and initiate substitution of vegetative for sexual reproduction. The death of pacific salmon immediately after spawning is surely programmed. In this case, numerous typical traits of aging, including amyloid plaques in the brain, appear on the time scale of days. There are some indications that slow aging of higher animals and humans is also programmed, being the final step of ontogenesis. It is assumed that stepwise decline of many physiological functions during such aging increases pressure of natural selection on organisms stimulating in this way biological evolution. As a working hypothesis, the biochemical mechanism of slow aging is proposed. It is assumed that mitochondria-generated reactive oxygen species (ROS) is a tool to stimulate apoptosis, an effect decreasing with age the cell number (cellularity) of organs and tissues. A group of SkQ-type substances composed of plastoquinone and a penetrating cation were synthesized to target an antioxidant into mitochondria and to prevent the age-linked rise of the mitochondrial ROS level. Such targeting is due to the fact that mitochondria are the only cellular organelles that are negatively charged compared to the cytosol. SkQs are shown to strongly decrease concentration of ROS in mitochondria, prolong lifespan of fungi, invertebrates, fish, and mammals, and retard appearance of numerous traits of aging. Clinical trials of SkQ1 (plastoquinonyl decyltriphenylphosphonium) have been successfully completed so that the Ministry of Health of the Russian Federation recommends drops of very dilute (0.25 µM) solution of this antioxidant as a medicine to treat the syndrome of dry eye, which was previously considered an incurable disease developing with age. These drops are already available in drugstores. Thus, SkQ1 is the first mitochondria-targeted drug employed in medical practice.}, } @article {pmid22807664, year = {2012}, author = {Crombach, A and Wotton, KR and Cicin-Sain, D and Ashyraliyev, M and Jaeger, J}, title = {Efficient reverse-engineering of a developmental gene regulatory network.}, journal = {PLoS computational biology}, volume = {8}, number = {7}, pages = {e1002589}, pmid = {22807664}, issn = {1553-7358}, mesh = {Animals ; Computational Biology/*methods ; Computer Simulation ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/genetics/growth & development ; Gene Expression ; *Gene Regulatory Networks ; Genes, Insect ; Hybridization, Genetic ; Models, Genetic ; RNA, Messenger/genetics/metabolism ; }, abstract = {Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to discover whether there are rules or regularities governing development and evolution of complex multi-cellular organisms.}, } @article {pmid22806564, year = {2013}, author = {Zhao, J and Lendahl, U and Nistér, M}, title = {Regulation of mitochondrial dynamics: convergences and divergences between yeast and vertebrates.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {70}, number = {6}, pages = {951-976}, pmid = {22806564}, issn = {1420-9071}, mesh = {Animals ; *Biological Evolution ; Cell Line ; Dynamins ; GTP Phosphohydrolases/physiology ; Humans ; Microtubule-Associated Proteins/*metabolism/physiology ; Mitochondrial Dynamics/*physiology ; Mitochondrial Proteins/physiology ; *Models, Biological ; Saccharomyces cerevisiae/*physiology ; Species Specificity ; Vertebrates/*physiology ; }, abstract = {In eukaryotic cells, the shape of mitochondria can be tuned to various physiological conditions by a balance of fusion and fission processes termed mitochondrial dynamics. Mitochondrial dynamics controls not only the morphology but also the function of mitochondria, and therefore is crucial in many aspects of a cell's life. Consequently, dysfunction of mitochondrial dynamics has been implicated in a variety of human diseases including cancer. Several proteins important for mitochondrial fusion and fission have been discovered over the past decade. However, there is emerging evidence that there are as yet unidentified proteins important for these processes and that the fusion/fission machinery is not completely conserved between yeast and vertebrates. The recent characterization of several mammalian proteins important for the process that were not conserved in yeast, may indicate that the molecular mechanisms regulating and controlling the morphology and function of mitochondria are more elaborate and complex in vertebrates. This difference could possibly be a consequence of different needs in the different cell types of multicellular organisms. Here, we review recent advances in the field of mitochondrial dynamics. We highlight and discuss the mechanisms regulating recruitment of cytosolic Drp1 to the mitochondrial outer membrane by Fis1, Mff, and MIEF1 in mammals and the divergences in regulation of mitochondrial dynamics between yeast and vertebrates.}, } @article {pmid22802643, year = {2012}, author = {Lobikin, M and Wang, G and Xu, J and Hsieh, YW and Chuang, CF and Lemire, JM and Levin, M}, title = {Early, nonciliary role for microtubule proteins in left-right patterning is conserved across kingdoms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {31}, pages = {12586-12591}, pmid = {22802643}, issn = {1091-6490}, support = {R01 GM077425/GM/NIGMS NIH HHS/United States ; R01 HL095716/HL/NHLBI NIH HHS/United States ; HL095716/HL/NHLBI NIH HHS/United States ; R01-GM077425/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Blastomeres/cytology/*metabolism ; Body Patterning/*physiology ; Cell Division/*physiology ; HL-60 Cells ; Humans ; Microtubules/*metabolism ; Tubulin/*metabolism ; Xenopus Proteins/*metabolism ; Xenopus laevis ; }, abstract = {Many types of embryos' bodyplans exhibit consistently oriented laterality of the heart, viscera, and brain. Errors of left-right patterning present an important class of human birth defects, and considerable controversy exists about the nature and evolutionary conservation of the molecular mechanisms that allow embryos to reliably orient the left-right axis. Here we show that the same mutations in the cytoskeletal protein tubulin that alter asymmetry in plants also affect very early steps of left-right patterning in nematode and frog embryos, as well as chirality of human cells in culture. In the frog embryo, tubulin α and tubulin γ-associated proteins are required for the differential distribution of maternal proteins to the left or right blastomere at the first cell division. Our data reveal a remarkable molecular conservation of mechanisms initiating left-right asymmetry. The origin of laterality is cytoplasmic, ancient, and highly conserved across kingdoms, a fundamental feature of the cytoskeleton that underlies chirality in cells and multicellular organisms.}, } @article {pmid22796128, year = {2012}, author = {Gleason, EJ and Kramer, EM}, title = {Characterization of Aquilegia Polycomb Repressive Complex 2 homologs reveals absence of imprinting.}, journal = {Gene}, volume = {507}, number = {1}, pages = {54-60}, doi = {10.1016/j.gene.2012.07.004}, pmid = {22796128}, issn = {1879-0038}, mesh = {Aquilegia/*genetics ; Arabidopsis/genetics/metabolism ; Evolution, Molecular ; Gene Expression Regulation, Plant ; Genome, Plant ; *Genomic Imprinting ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Polycomb-Group Proteins ; Repressor Proteins/*genetics ; }, abstract = {Epigenetic regulation is important for maintaining gene expression patterns in multicellular organisms. The Polycomb Group (PcG) proteins form several complexes with important and deeply conserved epigenetic functions in both the plant and animal kingdoms. The plant Polycomb Repressive Complex 2 (PRC2) contains four core proteins, Enhancer of Zeste (E(z)), Suppressor of Zeste 12 (Su(z)12), Extra Sex Combs (ESC), and Multicopy Suppressor of IRA 1 (MSI1), and functions in many developmental transitions. In some plant species, including rice and Arabidopsis, duplications in the core PRC2 proteins allow the formation of PRC2s with distinct developmental functions. In addition, members of the plant specific VEL PHD family have been shown to associate with the PRC2 complex in Arabidopsis and may play a role in targeting the PRC2 to specific loci. Here we examine the evolution and expression of the PRC2 and VEL PHD families in Aquilegia, a member of the lower eudicot order Ranunculales and an emerging model for the investigation of plant ecology, evolution and developmental genetics. We find that Aquilegia has a relatively simple PRC2 with only one homolog of Su(z)12, ESC and MSI1 and two ancient copies of E(z), AqSWN and AqCLF. Aquilegia has four members of the VEL PHD family, three of which appear to be closely related to Arabidopsis proteins known to associate with the PRC2. The PRC2 and VEL PHD family proteins are expressed at a relatively constant level throughout Aquilegia vulgaris development, with the VEL PHD family and MSI1 expressed at higher levels during and after vernalization and in the inflorescence. Both AqSWN and AqCLF are expressed in Aquilegia endosperm but neither copy is imprinted.}, } @article {pmid22792236, year = {2012}, author = {Hosp, J and Sagane, Y and Danks, G and Thompson, EM}, title = {The evolving proteome of a complex extracellular matrix, the Oikopleura house.}, journal = {PloS one}, volume = {7}, number = {7}, pages = {e40172}, pmid = {22792236}, issn = {1932-6203}, mesh = {Animals ; Epithelium/metabolism ; Extracellular Matrix/*metabolism ; Female ; Gene Order ; Genome ; Glycoproteins/genetics/metabolism ; Heparan Sulfate Proteoglycans/metabolism ; Immunity, Innate/genetics ; Male ; Phylogeny ; Protein Transport ; Proteome/*metabolism ; Urochordata/genetics/immunology/*metabolism ; }, abstract = {Extracellular matrices regulate biological processes at the level of cells, tissues, and in some cases, entire multicellular organisms. The subphylum Urochordata exemplifies the latter case, where animals are partially or completely enclosed in "houses" or "tunics". Despite this common strategy, we show that the house proteome of the appendicularian, Oikopleura, has very little in common with the proteome of the sister class, ascidian, Ciona. Of 80 identified house proteins (oikosins), ∼half lack domain modules or similarity to known proteins, suggesting de novo appearance in appendicularians. Gene duplication has been important in generating almost 1/3 of the current oikosin complement, with serial duplications up to 8 paralogs in one family. Expression pattern analyses revealed that individual oikosins are produced from specific fields of cells within the secretory epithelium, but in some cases, migrate up to at least 20 cell diameters in extracellular space to combine in defined house structures. Interestingly, peroxidasin and secretory phospholipase A(2) domains, implicated in innate immune defence are secreted from the anlage associated with the food-concentrating filter, suggesting that this extra-organismal structure may play, in part, such a role in Oikopleura. We also show that sulfation of proteoglycans is required for the hydration and inflation of pre-house rudiments into functional houses. Though correct proportioning in the production of oikosins would seem important in repetitive assembly of the complex house structure, the genomic organization of oikosin loci appears incompatible with common enhancers or locus control regions exerting such a coordinate regulatory role. Thus, though all tunicates employ extracellular matrices based on a cellulose scaffold as a defining feature of the subphylum, they have evolved radically different protein compositions associated with this common underlying structural theme.}, } @article {pmid22768154, year = {2012}, author = {Lizier, NF and Kerkis, A and Gomes, CM and Hebling, J and Oliveira, CF and Caplan, AI and Kerkis, I}, title = {Scaling-up of dental pulp stem cells isolated from multiple niches.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e39885}, pmid = {22768154}, issn = {1932-6203}, mesh = {Biomarkers/metabolism ; Bromodeoxyuridine/metabolism ; Cell Count ; Cell Culture Techniques ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cell Separation/*methods ; Cells, Cultured ; Child ; Chondrogenesis/drug effects ; Culture Media/pharmacology ; Dental Pulp/*cytology ; Embryonic Stem Cells/cytology/drug effects/metabolism ; Gene Expression Regulation/drug effects ; Humans ; Immunophenotyping ; Mesenchymal Stem Cells/cytology/drug effects/metabolism ; Muscle Development/drug effects ; *Stem Cell Niche/drug effects ; Stem Cells/*cytology/drug effects/metabolism/ultrastructure ; Time Factors ; }, abstract = {Dental pulp (DP) can be extracted from child's primary teeth (deciduous), whose loss occurs spontaneously by about 5 to 12 years. Thus, DP presents an easy accessible source of stem cells without ethical concerns. Substantial quantities of stem cells of an excellent quality and at early (2-5) passages are necessary for clinical use, which currently is a problem for use of adult stem cells. Herein, DPs were cultured generating stem cells at least during six months through multiple mechanical transfers into a new culture dish every 3-4 days. We compared stem cells isolated from the same DP before (early population, EP) and six months after several mechanical transfers (late population, LP). No changes, in both EP and LP, were observed in morphology, expression of stem cells markers (nestin, vimentin, fibronectin, SH2, SH3 and Oct3/4), chondrogenic and myogenic differentiation potential, even after cryopreservation. Six hours after DP extraction and in vitro plating, rare 5-bromo-2'-deoxyuridine (BrdU) positive cells were observed in pulp central part. After 72 hours, BrdU positive cells increased in number and were found in DP periphery, thus originating a multicellular population of stem cells of high purity. Multiple stem cell niches were identified in different zones of DP, because abundant expression of nestin, vimentin and Oct3/4 proteins was observed, while STRO-1 protein localization was restricted to perivascular niche. Our finding is of importance for the future of stem cell therapies, providing scaling-up of stem cells at early passages with minimum risk of losing their "stemness".}, } @article {pmid22765842, year = {2012}, author = {Forte, E and Miraldi, F and Chimenti, I and Angelini, F and Zeuner, A and Giacomello, A and Mercola, M and Messina, E}, title = {TGFβ-dependent epithelial-to-mesenchymal transition is required to generate cardiospheres from human adult heart biopsies.}, journal = {Stem cells and development}, volume = {21}, number = {17}, pages = {3081-3090}, pmid = {22765842}, issn = {1557-8534}, support = {R37 HL059502/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Benzamides/pharmacology ; Biomarkers/metabolism ; Biopsy ; Cell Differentiation ; Cells, Cultured ; Dioxoles/pharmacology ; *Epithelial-Mesenchymal Transition ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Myocardial Ischemia/metabolism/pathology ; Myocardium/metabolism/*pathology ; Myocytes, Cardiac/*cytology/metabolism ; Receptor, Notch1/genetics/metabolism ; Receptors, Transforming Growth Factor beta/antagonists & inhibitors ; *Regeneration ; Snail Family Transcription Factors ; Stem Cells/*cytology/metabolism ; Transcription Factors/genetics/metabolism ; Transforming Growth Factor beta/*metabolism/pharmacology ; }, abstract = {Autologous cardiac progenitor cells (CPCs) isolated as cardiospheres (CSps) represent a promising candidate for cardiac regenerative therapy. A better understanding of the origin and mechanisms underlying human CSps formation and maturation is undoubtedly required to enhance their cardiomyogenic potential. Epithelial-to-mesenchymal transition (EMT) is a key morphogenetic process that is implicated in the acquisition of stem cell-like properties in different adult tissues, and it is activated in the epicardium after ischemic injury to the heart. We investigated whether EMT is involved in the formation and differentiation of human CSps, revealing that an up-regulation of the expression of EMT-related genes accompanies CSps formation that is relative to primary explant-derived cells and CSp-derived cells grown in a monolayer. EMT and CSps formation is enhanced in the presence of transforming growth factor β1 (TGFβ1) and drastically blocked by the type I TGFβ-receptor inhibitor SB431452, indicating that TGFβ-dependent EMT is essential for the formation of these niche-like 3D-multicellular clusters. Since TGFβ is activated in the myocardium in response to injury, our data suggest that CSps formation mimics an adaptive mechanism that could potentially be enhanced to increase in vivo or ex vivo regenerative potential of adult CPCs.}, } @article {pmid22726356, year = {2012}, author = {Rehfeld, JF}, title = {Beginnings: a reflection on the history of gastrointestinal endocrinology.}, journal = {Regulatory peptides}, volume = {177 Suppl}, number = {}, pages = {S1-5}, doi = {10.1016/j.regpep.2012.05.087}, pmid = {22726356}, issn = {1873-1686}, mesh = {Animals ; Cell Membrane/chemistry ; Drug Therapy/methods ; Endocrine Glands/chemistry/metabolism ; Endocrinology/history ; Gastrointestinal Hormones/*chemistry/classification/genetics/metabolism ; Gastrointestinal Tract/chemistry/*metabolism ; Genes, Regulator ; History, 20th Century ; History, 21st Century ; Humans ; Neuroendocrine Tumors/chemistry/therapy ; Peptide Hormones/*chemistry/classification/genetics/metabolism ; Phylogeny ; Radioimmunoassay ; }, abstract = {The gut is the largest endocrine organ in the body. Gut hormones share some characteristics: Their structure groups hormones into families, each of which originate from a single gene. A hormone gene is often expressed in multiple peptides due to tandem genes, alternative splicing or differentiated posttranslational processing. By these mechanisms, more than 100 different hormonally active peptides are produced in the gastrointestinal tract. In addition, gut hormones are widely expressed outside the gut. The different cell types often express different products of the same gene and release the peptides in different ways. Consequently, the same peptide may act as a hormone, a local growth factor, or a neurotransmitter. This new biology suggests that gastrointestinal hormones should be conceived as intercellular messengers of major general impact. The following short review is a vignette on steps in the history of gastrointestinal endocrinology from classic studies of digestive juice secretion over peptide chemistry, immunochemistry, and molecular genetics to modern receptor pharmacology and drug development. From shadowy beginnings, gastrointestinal endocrinology has emerged as a central discipline in the understanding of multicellular life and its diseases.}, } @article {pmid22763458, year = {2012}, author = {Steinmetz, PR and Kraus, JE and Larroux, C and Hammel, JU and Amon-Hassenzahl, A and Houliston, E and Wörheide, G and Nickel, M and Degnan, BM and Technau, U}, title = {Independent evolution of striated muscles in cnidarians and bilaterians.}, journal = {Nature}, volume = {487}, number = {7406}, pages = {231-234}, pmid = {22763458}, issn = {1476-4687}, support = {P 21108/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Animals ; *Biological Evolution ; Cnidaria/*anatomy & histology/genetics/metabolism ; Gene Duplication ; Gene Expression Regulation ; Muscle, Striated/metabolism/*physiology ; Myosin Heavy Chains/genetics/metabolism ; Phylogeny ; }, abstract = {Striated muscles are present in bilaterian animals (for example, vertebrates, insects and annelids) and some non-bilaterian eumetazoans (that is, cnidarians and ctenophores). The considerable ultrastructural similarity of striated muscles between these animal groups is thought to reflect a common evolutionary origin. Here we show that a muscle protein core set, including a type II myosin heavy chain (MyHC) motor protein characteristic of striated muscles in vertebrates, was already present in unicellular organisms before the origin of multicellular animals. Furthermore, 'striated muscle' and 'non-muscle' myhc orthologues are expressed differentially in two sponges, compatible with a functional diversification before the origin of true muscles and the subsequent use of striated muscle MyHC in fast-contracting smooth and striated muscle. Cnidarians and ctenophores possess striated muscle myhc orthologues but lack crucial components of bilaterian striated muscles, such as genes that code for titin and the troponin complex, suggesting the convergent evolution of striated muscles. Consistently, jellyfish orthologues of a shared set of bilaterian Z-disc proteins are not associated with striated muscles, but are instead expressed elsewhere or ubiquitously. The independent evolution of eumetazoan striated muscles through the addition of new proteins to a pre-existing, ancestral contractile apparatus may serve as a model for the evolution of complex animal cell types.}, } @article {pmid22751134, year = {2013}, author = {DeGregori, J}, title = {Challenging the axiom: does the occurrence of oncogenic mutations truly limit cancer development with age?.}, journal = {Oncogene}, volume = {32}, number = {15}, pages = {1869-1875}, pmid = {22751134}, issn = {1476-5594}, support = {R01 CA157850/CA/NCI NIH HHS/United States ; R01CA157850/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Aging/*genetics ; Cell Transformation, Neoplastic/*genetics ; DNA Repair/genetics ; Humans ; Models, Biological ; Mutation ; *Mutation Rate ; Neoplasms/*genetics ; Phenotype ; }, abstract = {A widely accepted paradigm in cancer research holds that the development of cancers is rate limited by the occurrence of oncogenic mutations. In particular, the exponential rise in the incidence of most cancers with age is thought to reflect the time required for cells to accumulate the multiple oncogenic mutations needed to confer the cancer phenotype. Here I will argue against the axiom that the occurrence of oncogenic mutations limits cancer incidence with age, based on several observations, including that the rate of mutation accumulation is maximal during ontogeny, oncogenic mutations are frequently detected in normal tissues, the evolution of complex multicellularity was not accompanied by reductions in mutation rates, and that many oncogenic mutations have been shown to impair stem cell activity. Moreover, although evidence that has been used to support the current paradigm includes increased cancer incidence in individuals with inherited DNA repair deficiencies or exposed to mutagens, the pleotropic effects of these contexts could enhance tumorigenesis at multiple levels. I will further argue that age-dependent alteration of selection for oncogenic mutations provides a more plausible explanation for increased cancer incidence in the elderly. Although oncogenic mutations are clearly required for cancer evolution, together these observations counter the common view that age dependence of cancers is largely explained by the time required to accumulate sufficient oncogenic mutations.}, } @article {pmid22749958, year = {2012}, author = {Morris, DJ}, title = {A new model for myxosporean (Myxozoa) development explains the endogenous budding phenomenon, the nature of cell within cell life stages and evolution of parasitism from a cnidarian ancestor.}, journal = {International journal for parasitology}, volume = {42}, number = {9}, pages = {829-840}, doi = {10.1016/j.ijpara.2012.06.001}, pmid = {22749958}, issn = {1879-0135}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; *Models, Biological ; Myxozoa/*cytology/genetics/*growth & development ; Spores, Protozoan/physiology ; }, abstract = {The phylum Myxozoa is composed of endoparasitic species that have predominately been recorded within aquatic vertebrates. The simple body form of a trophic cell containing other cells within it, as observed within these hosts, has provided few clues to relationships with other organisms. In addition, the placement of the group using molecular phylogenies has proved very difficult, although the majority of analyses now suggest that they are cnidarians. There have been relatively few studies of myxozoan stages within invertebrate hosts, even though these exhibit multicellular and sexual stages that may provide clues to myxozoan evolution. Therefore an ultrastructural examination of a myxozoan infection of a freshwater oligochaete was conducted, to reassess and formulate a model for myxozoan development in these hosts. This deemed that meiosis occurs within the oligochaete, but that fertilisation is not immediate. Rather, the resultant haploid germ cell (oocyte) is engulfed by a diploid sporogonic cell (nurse cell) to form a sporoplasm. It is this sporoplasm that infects the fish, resulting in the multicellular stages observed. Fertilisation occurs after the parasites leave the fish and enter the oligochaete host. The nurse cell/oocyte model explains previously conflicting evidence in the literature regarding myxosporean biology, and aligns phenomena considered distinctive to the Myxozoa, such as endogenous budding and cell within cell development, with processes recorded in cnidarians. Finally, the evolutionary origin of the Myxozoa as cnidarian parasites of ova is hypothesised.}, } @article {pmid22734652, year = {2012}, author = {Alvarez-Venegas, R and Avramova, Z}, title = {Evolution of the PWWP-domain encoding genes in the plant and animal lineages.}, journal = {BMC evolutionary biology}, volume = {12}, number = {}, pages = {101}, pmid = {22734652}, issn = {1471-2148}, mesh = {Animals ; Arabidopsis/genetics ; Chlorophyta/genetics ; Humans ; Methyltransferases/*genetics ; Nuclear Proteins/chemistry/*genetics ; Plants/*genetics ; *Protein Structure, Tertiary ; Sea Anemones/*genetics ; }, abstract = {BACKGROUND: Conserved domains are recognized as the building blocks of eukaryotic proteins. Domains showing a tendency to occur in diverse combinations ('promiscuous' domains) are involved in versatile architectures in proteins with different functions. Current models, based on global-level analyses of domain combinations in multiple genomes, have suggested that the propensity of some domains to associate with other domains in high-level architectures increases with organismal complexity. Alternative models using domain-based phylogenetic trees propose that domains have become promiscuous independently in different lineages through convergent evolution and are, thus, random with no functional or structural preferences. Here we test whether complex protein architectures have occurred by accretion from simpler systems and whether the appearance of multidomain combinations parallels organismal complexity. As a model, we analyze the modular evolution of the PWWP domain and ask whether its appearance in combinations with other domains into multidomain architectures is linked with the occurrence of more complex life-forms. Whether high-level combinations of domains are conserved and transmitted as stable units (cassettes) through evolution is examined in the genomes of plant or metazoan species selected for their established position in the evolution of the respective lineages.

RESULTS: Using the domain-tree approach, we analyze the evolutionary origins and distribution patterns of the promiscuous PWWP domain to understand the principles of its modular evolution and its existence in combination with other domains in higher-level protein architectures. We found that as a single module the PWWP domain occurs only in proteins with a limited, mainly, species-specific distribution. Earlier, it was suggested that domain promiscuity is a fast-changing (volatile) feature shaped by natural selection and that only a few domains retain their promiscuity status throughout evolution. In contrast, our data show that most of the multidomain PWWP combinations in extant multicellular organisms (humans or land plants) are present in their unicellular ancestral relatives suggesting they have been transmitted through evolution as conserved linear arrangements ('cassettes'). Among the most interesting biologically relevant results is the finding that the genes of the two plant Trithorax family subgroups (ATX1/2 and ATX3/4/5) have different phylogenetic origins. The two subgroups occur together in the earliest land plants Physcomitrella patens and Selaginella moellendorffii.

CONCLUSION: Gain/loss of a single PWWP domain is observed throughout evolution reflecting dynamic lineage- or species-specific events. In contrast, higher-level protein architectures involving the PWWP domain have survived as stable arrangements driven by evolutionary descent. The association of PWWP domains with the DNA methyltransferases in O. tauri and in the metazoan lineage seems to have occurred independently consistent with convergent evolution. Our results do not support models wherein more complex protein architectures involving the PWWP domain occur with the appearance of more evolutionarily advanced life forms.}, } @article {pmid22730024, year = {2012}, author = {Jones, VA and Dolan, L}, title = {The evolution of root hairs and rhizoids.}, journal = {Annals of botany}, volume = {110}, number = {2}, pages = {205-212}, pmid = {22730024}, issn = {1095-8290}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Biological Evolution ; Bryophyta/genetics/growth & development ; Cell Differentiation/genetics ; Germ Cells, Plant/growth & development ; Phylogeny ; Plant Roots/cytology/*genetics/*growth & development ; Plants/*genetics ; Rhizome/cytology/*genetics/*growth & development ; }, abstract = {BACKGROUND: Almost all land plants develop tip-growing filamentous cells at the interface between the plant and substrate (the soil). Root hairs form on the surface of roots of sporophytes (the multicellular diploid phase of the life cycle) in vascular plants. Rhizoids develop on the free-living gametophytes of vascular and non-vascular plants and on both gametophytes and sporophytes of the extinct rhyniophytes. Extant lycophytes (clubmosses and quillworts) and monilophytes (ferns and horsetails) develop both free-living gametophytes and free-living sporophytes. These gametophytes and sporophytes grow in close contact with the soil and develop rhizoids and root hairs, respectively.

SCOPE: Here we review the development and function of rhizoids and root hairs in extant groups of land plants. Root hairs are important for the uptake of nutrients with limited mobility in the soil such as phosphate. Rhizoids have a variety of functions including water transport and adhesion to surfaces in some mosses and liverworts.

CONCLUSIONS: A similar gene regulatory network controls the development of rhizoids in moss gametophytes and root hairs on the roots of vascular plant sporophytes. It is likely that this gene regulatory network first operated in the gametophyte of the earliest land plants. We propose that later it functioned in sporophytes as the diploid phase evolved a free-living habit and developed an interface with the soil. This transference of gene function from gametophyte to sporophyte could provide a mechanism that, at least in part, explains the increase in morphological diversity of sporophytes that occurred during the radiation of land plants in the Devonian Period.}, } @article {pmid22717455, year = {2012}, author = {Joachim, J and Wirth, M and McKnight, NC and Tooze, SA}, title = {Coiling up with SCOC and WAC: two new regulators of starvation-induced autophagy.}, journal = {Autophagy}, volume = {8}, number = {9}, pages = {1397-1400}, doi = {10.4161/auto.21043}, pmid = {22717455}, issn = {1554-8635}, support = {15153/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Adaptor Proteins, Signal Transducing/*metabolism ; Animals ; *Autophagy ; Caenorhabditis elegans/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Membrane Proteins/*metabolism ; Models, Biological ; Phagosomes/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis ; *Signal Transduction ; Starvation/*pathology ; Ubiquitination ; }, abstract = {Autophagy is a conserved and highly regulated catabolic pathway, transferring cytoplasmic components in autophagosomes to lysosomes for degradation and providing amino acids during starvation. In multicellular organisms autophagy plays an important role for tissue homeostasis, and deregulation of autophagy has been implicated in a broad range of diseases, including cancer and neurodegenerative disorders. In mammals, many aspects of autophagy still need to be fully elucidated: what is the exact hierarchy and relationship between ATG proteins and other factors that lead to the formation and expansion of phagophores? Where does the membrane source for autophagosome formation originate? Which signaling events trigger amino acid starvation-induced autophagy? How are the activities of ULK1/2 and the class III PtdIns3K regulated and linked to each other? To develop therapeutic strategies to manipulate autophagy in human disease, a comprehensive understanding of the molecular protein machinery mediating and regulating autophagy is required.}, } @article {pmid22702725, year = {2012}, author = {Xue, B and Dunker, AK and Uversky, VN}, title = {Orderly order in protein intrinsic disorder distribution: disorder in 3500 proteomes from viruses and the three domains of life.}, journal = {Journal of biomolecular structure & dynamics}, volume = {30}, number = {2}, pages = {137-149}, doi = {10.1080/07391102.2012.675145}, pmid = {22702725}, issn = {1538-0254}, mesh = {Animals ; Binding Sites ; Computational Biology ; Eukaryota/genetics/metabolism ; Evolution, Molecular ; Humans ; Protein Conformation ; Proteins/*chemistry/metabolism ; Proteome/*chemistry ; Viruses/genetics/metabolism ; }, abstract = {Intrinsically disordered proteins and intrinsically disordered protein regions are highly abundant in nature. However, the quantitative and qualitative measures of protein intrinsic disorder in species with known genomes are still not available. Furthermore, although the correlation between high fraction of disordered residues and advanced species has been reported, the details of this correlation and the connection between the disorder content and proteome complexity have not been reported as of yet. To fill this gap, we analysed entire proteomes of 3484 species from three domains of life (archaea, bacteria and eukaryotes) and from viruses. Our analysis revealed that the evolution process is characterized by distinctive patterns of changes in the protein intrinsic disorder content. We are showing here that viruses are characterized by the widest spread of the proteome disorder content (the percentage of disordered residues ranges from 7.3% in human coronavirus NL63 to 77.3% in Avian carcinoma virus). For several organisms, a clear correlation is seen between their disorder contents and habitats. In multicellular eukaryotes, there is a weak correlation between the complexity of an organism (evaluated as a number of different cell types) and its overall disorder content. For both the prokaryotes and eukaryotes, the disorder content is generally independent of the proteome size. However, disorder shows a sharp increase associated with the transition from prokaryotic to eukaryotic cells. This suggests that the increased disorder content in eukaryotic proteomes might be used by nature to deal with the increased cell complexity due to the appearance of the various cellular compartments.}, } @article {pmid22698377, year = {2012}, author = {Tossi, V and Cassia, R and Bruzzone, S and Zocchi, E and Lamattina, L}, title = {ABA says NO to UV-B: a universal response?.}, journal = {Trends in plant science}, volume = {17}, number = {9}, pages = {510-517}, doi = {10.1016/j.tplants.2012.05.007}, pmid = {22698377}, issn = {1878-4372}, mesh = {Abscisic Acid/*physiology/radiation effects ; Amino Acid Sequence ; Animals ; Calcium/physiology ; Humans ; Models, Biological ; Molecular Sequence Data ; Nitric Oxide/*physiology ; Phylogeny ; Plants/metabolism ; Sequence Alignment ; Signal Transduction/*drug effects/radiation effects ; Stress, Physiological/*drug effects/physiology ; *Ultraviolet Rays ; }, abstract = {Abscisic acid (ABA) signaling pathways have been widely characterized in plants, whereas the function of ABA in animals is less well understood. However, recent advances show ABA production by a wide range of lower animals and higher mammals. This enables a new evaluation of ABA signaling pathways in different organisms in response to common environmental stress, such as ultraviolet (UV)-B. In this opinion article, we propose that the induction of common signaling components, such as ABA, nitric oxide (NO) and Ca(2+), in plant and animal cells in response to high doses of UV-B, suggests that the evolution of a general mechanism activated by UV-B is conserved in divergent multicellular organisms challenged by a changing common environment.}, } @article {pmid22690978, year = {2012}, author = {Ni, T and Yue, J and Sun, G and Zou, Y and Wen, J and Huang, J}, title = {Ancient gene transfer from algae to animals: mechanisms and evolutionary significance.}, journal = {BMC evolutionary biology}, volume = {12}, number = {}, pages = {83}, pmid = {22690978}, issn = {1471-2148}, mesh = {Animals ; Choanoflagellata/*genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; Multigene Family ; Phylogeny ; Plants/*genetics ; Plastids/genetics ; }, abstract = {BACKGROUND: Horizontal gene transfer (HGT) is traditionally considered to be rare in multicellular eukaryotes such as animals. Recently, many genes of miscellaneous algal origins were discovered in choanoflagellates. Considering that choanoflagellates are the existing closest relatives of animals, we speculated that ancient HGT might have occurred in the unicellular ancestor of animals and affected the long-term evolution of animals.

RESULTS: Through genome screening, phylogenetic and domain analyses, we identified 14 gene families, including 92 genes, in the tunicate Ciona intestinalis that are likely derived from miscellaneous photosynthetic eukaryotes. Almost all of these gene families are distributed in diverse animals, suggesting that they were mostly acquired by the common ancestor of animals. Their miscellaneous origins also suggest that these genes are not derived from a particular algal endosymbiont. In addition, most genes identified in our analyses are functionally related to molecule transport, cellular regulation and methylation signaling, suggesting that the acquisition of these genes might have facilitated the intercellular communication in the ancestral animal.

CONCLUSIONS: Our findings provide additional evidence that algal genes in aplastidic eukaryotes are not exclusively derived from historical plastids and thus important for interpreting the evolution of eukaryotic photosynthesis. Most importantly, our data represent the first evidence that more anciently acquired genes might exist in animals and that ancient HGT events have played an important role in animal evolution.}, } @article {pmid22679768, year = {2012}, author = {Savost'ianov, GA}, title = {[The origin of elementary units of multicellularity and development of a spatial organization of cell layers].}, journal = {Izvestiia Akademii nauk. Seriia biologicheskaia}, volume = {}, number = {2}, pages = {164-174}, pmid = {22679768}, issn = {1026-3470}, mesh = {Animals ; Cells/*cytology/ultrastructure ; Computer Simulation ; Epithelium/embryology/ultrastructure ; Humans ; *Models, Biological ; *Morphogenesis ; }, abstract = {The concept of the elementary unit of multicellularity, the histion, which also serves as a morphofunctional unit of cell layers, is introduced. Histions are cell groups formed as a result of division of labor between cells. Cell layers are regarded as regular cell networks (lattices) formed through polymerization of histions. The theory constructed based on this concept allows the composition and structure of a multitude of histions to be calculated; their development to be quantified; and families of topological and geometrical models for the histoarchitecture of cell layers to be constructed, visualized with computer programs, and experimentally verified. In addition, this model can predict previously unknown topological variants of the histoarchitecture of epithelial tissues, as well as their presence in normal development and pathology.}, } @article {pmid22674065, year = {2012}, author = {Harris, TJ}, title = {An introduction to adherens junctions: from molecular mechanisms to tissue development and disease.}, journal = {Sub-cellular biochemistry}, volume = {60}, number = {}, pages = {1-5}, doi = {10.1007/978-94-007-4186-7_1}, pmid = {22674065}, issn = {0306-0225}, mesh = {Adherens Junctions/*physiology ; Animals ; Cadherins/*metabolism ; Catenins/*metabolism ; *Disease ; Humans ; Morphogenesis ; }, abstract = {Adherens junctions (AJs) are fundamental for the development of animal tissues and organs. The core complex is formed from transmembrane cell-cell adhesion molecules, cadherins, and adaptor molecules, the catenins, that link to cytoskeletal and regulatory networks within the cell. This complex can be considered over a wide range of biological organization, from atoms to molecules, protein complexes, molecular networks, cells, tissues, and overall animal development. AJs have also been an integral part of animal evolution, and play central roles in cancer development and pathogen infection. This book addresses major questions encompassing these aspects of AJ biology. How did AJs evolve? How do the cadherins and catenins interact to assemble AJs and mediate adhesion? How do AJs interface with other cellular machinery to couple adhesion with the whole cell? How do AJs affect cell behaviour and multicellular development? How can abnormal AJ activity lead to disease?}, } @article {pmid22664124, year = {2012}, author = {Wang, X and Schröder, HC and Wiens, M and Schloßmacher, U and Müller, WE}, title = {Biosilica: Molecular Biology, Biochemistry and Function in Demosponges as well as its Applied Aspects for Tissue Engineering.}, journal = {Advances in marine biology}, volume = {62}, number = {}, pages = {231-271}, doi = {10.1016/B978-0-12-394283-8.00005-9}, pmid = {22664124}, issn = {0065-2881}, mesh = {Animals ; Cathepsins ; Models, Molecular ; Molecular Biology ; Phylogeny ; Porifera ; *Silicon Dioxide ; *Tissue Engineering ; }, abstract = {Biomineralization, biosilicification in particular (i.e. the formation of biogenic silica, SiO(2)), has become an exciting source of inspiration for the development of novel bionic approaches following 'nature as model'. Siliceous sponges are unique among silica-forming organisms in their ability to catalyze silica formation using a specific enzyme termed silicatein. In this study, we review the present state of knowledge on silicatein-mediated 'biosilica' formation in marine demosponges, the involvement of further molecules in silica metabolism and their potential applications in nano-biotechnology and bio-medicine. While most forms of multicellular life have developed a calcium-based skeleton, a few specialized organisms complement their body plan with silica. Only sponges (phylum Porifera) are able to polymerize silica enzymatically mediated in order to generate massive siliceous skeletal elements (spicules) during a unique reaction, at ambient temperature and pressure. During this biomineralization process (i.e. biosilicification), hydrated, amorphous silica is deposited within highly specialized sponge cells, ultimately resulting in structures that range in size from micrometres to metres. This peculiar phenomenon has been comprehensively studied in recent years, and in several approaches, the molecular background was explored to create tools that might be employed for novel bioinspired biotechnological and biomedical applications. Thus, it was discovered that spiculogenesis is mediated by the enzyme silicatein and starts intracellularly. The resulting silica nanoparticles fuse and subsequently form concentric lamellar layers around a central protein filament, consisting of silicatein and the scaffold protein silintaphin-1. Once the growing spicule is extruded into the extracellular space, it obtains final size and shape. Again, this process is mediated by silicatein and silintaphin-1/silintaphin-1, in combination with other molecules such as galectin and collagen. The molecular toolbox generated so far allows the fabrication of novel micro- and nano-structured composites, contributing to the economical and sustainable synthesis of biomaterials with unique characteristics. In this context, first bioinspired approaches implement recombinant silicatein and silintaphin-1 for applications in the field of biomedicine (biosilica-mediated regeneration of tooth and bone defects) with promising results.}, } @article {pmid22662159, year = {2012}, author = {Coppin, E and Berteaux-Lecellier, V and Bidard, F and Brun, S and Ruprich-Robert, G and Espagne, E and Aït-Benkhali, J and Goarin, A and Nesseir, A and Planamente, S and Debuchy, R and Silar, P}, title = {Systematic deletion of homeobox genes in Podospora anserina uncovers their roles in shaping the fruiting body.}, journal = {PloS one}, volume = {7}, number = {5}, pages = {e37488}, pmid = {22662159}, issn = {1932-6203}, mesh = {Amino Acid Sequence ; Evolution, Molecular ; Fertility/genetics ; Fruiting Bodies, Fungal/*genetics ; *Gene Deletion ; *Genes, Homeobox ; Genotype ; Molecular Sequence Data ; Mutation ; Phenotype ; Podospora/*genetics/metabolism ; Sequence Alignment ; Transcription Factors/chemistry/genetics/metabolism ; }, abstract = {Higher fungi, which comprise ascomycetes and basidiomycetes, play major roles in the biosphere. Their evolutionary success may be due to the extended dikaryotic stage of their life cycle, which is the basis for their scientific name: the Dikarya. Dikaryosis is maintained by similar structures, the clamp in basidiomycetes and the crozier in ascomycetes. Homeodomain transcription factors are required for clamp formation in all basidiomycetes studied. We identified all the homeobox genes in the filamentous ascomycete fungus Podospora anserina and constructed deletion mutants for each of these genes and for a number of gene combinations. Croziers developed normally in these mutants, including those with up to six deleted homeogenes. However, some mutants had defects in maturation of the fruiting body, an effect that could be rescued by providing wild-type maternal hyphae. Analysis of mutants deficient in multiple homeogenes revealed interactions between the genes, suggesting that they operate as a complex network. Similar to their role in animals and plants, homeodomain transcription factors in ascomycetes are involved in shaping multicellular structures.}, } @article {pmid22647940, year = {2012}, author = {Crossin, KL}, title = {Oxygen levels and the regulation of cell adhesion in the nervous system: a control point for morphogenesis in development, disease and evolution?.}, journal = {Cell adhesion & migration}, volume = {6}, number = {1}, pages = {49-58}, pmid = {22647940}, issn = {1933-6926}, mesh = {Animals ; Atmosphere ; Brain Ischemia ; Cell Adhesion ; Cell Proliferation ; *Evolution, Molecular ; Hypoxia, Brain/metabolism/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; *Morphogenesis ; Nervous System/cytology/*metabolism ; Neural Cell Adhesion Molecules/metabolism ; Neural Stem Cells/cytology/metabolism ; Neurogenesis ; Oxygen/*metabolism ; Symbiosis ; Wnt Signaling Pathway ; }, abstract = {In this article, I discuss the hallmarks of hypoxia in vitro and in vivo and review work showing that many types of stem cell proliferate more robustly in lowered oxygen. I then discuss recent studies showing that alterations in the levels and the types of cell and substrate adhesion molecules are a notable response to reduced O(2) levels in both cultured primary neural stem cells and brain tissues in response to hypoxia in vivo. The ability of O(2) levels to regulate adhesion molecule expression is linked to the Wnt signaling pathway, which can control and be controlled by adhesion events. The ability of O(2) levels to influence cell adhesion also has far-reaching implications for development, ischemic trauma and neural regeneration, as well as for cancer and other diseases. Finally I discuss the possibility that the fluctuations in O(2) levels known to have occurred over evolutionary time could, by influencing adhesion systems, have contributed to early symbiotic events in unicellular organisms and to the emergence of multicellularity. It is not my intention to be exhaustive in these domains, which are far from my own field of study. Rather this article is meant to provoke and stimulate thinking about molecular evolution involving O(2) sensing and signaling during eras of geologic and atmospheric change that might inform modern studies on development and disease.}, } @article {pmid22622805, year = {2013}, author = {Colombelli, J and Solon, J}, title = {Force communication in multicellular tissues addressed by laser nanosurgery.}, journal = {Cell and tissue research}, volume = {352}, number = {1}, pages = {133-147}, doi = {10.1007/s00441-012-1445-1}, pmid = {22622805}, issn = {1432-0878}, mesh = {Animals ; Biomechanical Phenomena ; Cell Communication ; Cytoskeleton/metabolism ; Humans ; Laser Capture Microdissection/methods ; Laser Therapy/*methods ; *Mechanotransduction, Cellular ; Morphogenesis ; }, abstract = {Cell contractility is a prominent mechanism driving multicellular tissue development and remodeling. Forces originated by the actomyosin cytoskeleton not only act within the cell body but can also propagate many layers away from the contraction source and grant tissues the ability to organize collectively and to achieve robust remodeling through development. Tissue tension is being thoroughly investigated in model organisms and increasing evidence is revealing the major role played by the communication, dynamics and propagation of cell-to-cell physical forces in multicellular remodeling. Recently, pulsed-laser-based surgery has fostered in vivo experimental studies to investigate intracellular and supracellular forces in action. The technique offers a unique method to perturb mechanical equilibrium in a subpopulation of cells or in a single cell, while the overall tissue remains intact. In particular, improved ablation precision with short laser pulses and the combination of this technique with biophysical models now allow an in-depth understanding of the role of cellular mechanics in tissue morphogenesis. We first characterize laser ablation modes available to perform intracellular, cellular, or multi-cellular ablation via the example of the model monolayer tissue of the amnioserosa of Drosophila by relating subnanosecond laser pulse energy to ablation efficiency and the probability of cavitation bubble formation. We then review recent laser nanosurgery experiments that have been performed in cultured cells and that tackle actomyosin mechanics and provide molecular insights into force-sensing mechanisms. We finally review studies showing the central role of laser ablation in revealing the nature and orientation of forces involved in intracellular contractility and force mechanosensing in tissue development, e.g., axis elongation, branching morphogenesis, or tissue invagination. We discuss the perspectives offered by the technique in force-based cell-cell communication and mechanosensing pathways.}, } @article {pmid22609469, year = {2012}, author = {Nahalka, J}, title = {Glycocodon theory--the first table of glycocodons.}, journal = {Journal of theoretical biology}, volume = {307}, number = {}, pages = {193-204}, doi = {10.1016/j.jtbi.2012.05.010}, pmid = {22609469}, issn = {1095-8541}, mesh = {Amino Acid Sequence ; Campylobacter/enzymology ; Crystallization ; Galectin 3/chemistry ; *Genetic Code ; Glycocalyx/chemistry/genetics ; Glycoproteins/chemistry/metabolism ; Hexosyltransferases/chemistry ; Humans ; Lectins/chemistry ; Membrane Proteins/chemistry ; *Models, Genetic ; Models, Molecular ; Molecular Sequence Data ; Peptides/chemistry/metabolism ; Polysaccharides/chemistry/*genetics ; Pseudomonas syringae/metabolism ; Sequence Alignment ; Ficolins ; }, abstract = {Hydrophobic cellular membranes separate cells from an environment that is generally based on water. Therefore, it is not surprising that hydrophilic glycans and glycoproteins are exposed on the lipidic surface of membranes and that the glycocalyx has evolved in all basic cell types. During the evolution of multicellular life, the surface exposed protein-glycan interactions were taken as the origin of the language of cell-cell communication. The bioinformatics analysis presented here reveals that the amino acid triplets, the glycocodons, can be deduced for each glycan letter (monosaccharide). This theory proposes to distinguish between the "sugar code" (the sugar sequence) and the "glycocode" (evolutionary selected amino acids recognising the mono-sugar). Similarly to genetic code, original glycocodons are related to G, A, V, and D amino acids. Modern glycocodons can be deduced from GAVD-glycocodons using hydropathic similarity. In general, the amino acid triplets can be assembled from one dipeptide that is specific to a monosaccharide plus a polar amino acid. This theory may shed a different light on the reason for WWD conservation in the active sites of oligosaccharyltransferases and for GGQ in the active sites of ribosomes.}, } @article {pmid22608515, year = {2012}, author = {Wang, F and Vandepoele, K and Van Lijsebettens, M}, title = {Tetraspanin genes in plants.}, journal = {Plant science : an international journal of experimental plant biology}, volume = {190}, number = {}, pages = {9-15}, doi = {10.1016/j.plantsci.2012.03.005}, pmid = {22608515}, issn = {1873-2259}, mesh = {Evolution, Molecular ; Genes, Plant/*genetics ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Plants/*genetics/*metabolism ; Tetraspanins/chemistry/*genetics/metabolism ; }, abstract = {Tetraspanins represent a four-transmembrane protein superfamily with a conserved structure and amino acid residues that are present in mammals, insects, fungi and plants. Tetraspanins interact with each other or with other membrane proteins to form tetraspanin-enriched microdomains that play important roles in development, pathogenesis and immune responses via facilitating cell-cell adhesion and fusion, ligand binding and intracellular trafficking. Here, we emphasize evolutionary aspects within the plant kingdom based on genomic sequence information. A phylogenetic tree based on 155 tetraspanin genes of 11 plant species revealed ancient and fast evolving clades. Tetraspanins were only present in multicellular plants, were often duplicated in the plant genomes and predicted by the electronic Fluorescent Pictograph for gene expression analysis to be either functionally redundant or divergent. Tetraspanins contain a large extracellular loop with conserved cysteines that provide the binding sites for the interactions. The Arabidopsis thaliana TETRASPANIN1/TORNADO2/EKEKO has a function in leaf and root patterning and TETRASPANIN3 was identified in the plasmodesmatal proteome, suggesting a role in cell-cell communication during plant development.}, } @article {pmid22608512, year = {2012}, author = {Brown, MW and Kolisko, M and Silberman, JD and Roger, AJ}, title = {Aggregative multicellularity evolved independently in the eukaryotic supergroup Rhizaria.}, journal = {Current biology : CB}, volume = {22}, number = {12}, pages = {1123-1127}, doi = {10.1016/j.cub.2012.04.021}, pmid = {22608512}, issn = {1879-0445}, mesh = {Adaptation, Biological/*physiology ; Base Sequence ; Bayes Theorem ; *Biological Evolution ; DNA, Complementary/genetics ; Genomics/methods ; Likelihood Functions ; Models, Genetic ; Molecular Sequence Data ; *Phylogeny ; Rhizaria/classification/*cytology/*genetics ; Sequence Analysis, DNA ; }, abstract = {Multicellular forms of life have evolved many times, independently giving rise to a diversity of organisms such as animals, plants, and fungi that together comprise the visible biosphere. Yet multicellular life is far more widespread among eukaryotes than just these three lineages. A particularly common form of multicellularity is a social aggregative fruiting lifestyle whereby individual cells associate to form a "fungus-like" sorocarp. This complex developmental process that requires the interaction of thousands of cells working in concert was made famous by the "cellular slime mold"Dictyostelium discoideum, which became an important model organism. Although sorocarpic protistan lineages have been identified in five of the major eukaryote groups, the ubiquitous and globally distributed species Guttulinopsis vulgaris has eluded proper classification. Here we demonstrate, by phylogenomic analyses of a 159-protein data set, that G. vulgaris is a member of Rhizaria and is thus the first member of this eukaryote supergroup known to be capable of aggregative multicellularity.}, } @article {pmid22600736, year = {2012}, author = {Hsu, DW and Chubb, JR and Muramoto, T and Pears, CJ and Mahadevan, LC}, title = {Dynamic acetylation of lysine-4-trimethylated histone H3 and H3 variant biology in a simple multicellular eukaryote.}, journal = {Nucleic acids research}, volume = {40}, number = {15}, pages = {7247-7256}, pmid = {22600736}, issn = {1362-4962}, support = {090904//Wellcome Trust/United Kingdom ; G120/1013/MRC_/Medical Research Council/United Kingdom ; G120/1013(75407)/MRC_/Medical Research Council/United Kingdom ; 081548/Z/06/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Acetylation/drug effects ; Amino Acid Substitution ; Dictyostelium/genetics/growth & development/*metabolism ; Gene Deletion ; Gene Expression ; Histone-Lysine N-Methyltransferase/genetics ; Histones/chemistry/genetics/*metabolism ; Hydroxamic Acids/pharmacology ; Lysine/*metabolism ; Methylation ; }, abstract = {Dynamic acetylation of all lysine-4-trimethylated histone H3 is a complex phenomenon involved in Immediate-early gene induction in metazoan eukaryotes. Higher eukaryotes express repeated copies of three closely related H3 variants, inaccessible to genetic analysis. We demonstrate conservation of these phenomena in Dictyostelium which has three single-copy H3 variant genes. Although dynamic acetylation is targeted to two H3 variants which are K4-trimethylated, K9-acetylation is preferentially targeted to one. In cells lacking Set1 methyltransferase and any detectable K4-trimethylation, dynamic acetylation is lost demonstrating a direct link between the two. Gene replacement to express mutated H3 variants reveals a novel interaction between K4-trimethylation on different variants. Cells expressing only one variant show defects in growth, and in induction of a UV-inducible gene, demonstrating the functional importance of variant expression. These studies confirm that dynamic acetylation targeted to H3K4me3 arose early in evolution and reveal a very high level of specificity of histone variant utilization in a simple multicellular eukaryote.}, } @article {pmid22595987, year = {2012}, author = {Hemmrich, G and Khalturin, K and Boehm, AM and Puchert, M and Anton-Erxleben, F and Wittlieb, J and Klostermeier, UC and Rosenstiel, P and Oberg, HH and Domazet-Loso, T and Sugimoto, T and Niwa, H and Bosch, TC}, title = {Molecular signatures of the three stem cell lineages in hydra and the emergence of stem cell function at the base of multicellularity.}, journal = {Molecular biology and evolution}, volume = {29}, number = {11}, pages = {3267-3280}, doi = {10.1093/molbev/mss134}, pmid = {22595987}, issn = {1537-1719}, mesh = {Animals ; Biological Evolution ; Cell Lineage/*genetics ; Cell Separation ; *Gene Expression Profiling ; Gene Expression Regulation ; Genetic Complementation Test ; Hydra/*cytology/*genetics ; Mice ; Phylogeny ; Staining and Labeling ; Stem Cells/*cytology/*metabolism ; Transcription Factors/genetics/metabolism ; Transcriptome/genetics ; }, abstract = {How distinct stem cell populations originate and whether there is a clear stem cell "genetic signature" remain poorly understood. Understanding the evolution of stem cells requires molecular profiling of stem cells in an animal at a basal phylogenetic position. In this study, using transgenic Hydra polyps, we reveal for each of the three stem cell populations a specific signature set of transcriptions factors and of genes playing key roles in cell type-specific function and interlineage communication. Our data show that principal functions of stem cell genes, such as maintenance of stemness and control of stem cell self-renewal and differentiation, arose very early in metazoan evolution. They are corroborating the view that stem cell types shared common, multifunctional ancestors, which achieved complexity through a stepwise segregation of function in daughter cells.}, } @article {pmid22589468, year = {2012}, author = {Kandasamy, MK and McKinney, EC and Roy, E and Meagher, RB}, title = {Plant vegetative and animal cytoplasmic actins share functional competence for spatial development with protists.}, journal = {The Plant cell}, volume = {24}, number = {5}, pages = {2041-2057}, pmid = {22589468}, issn = {1532-298X}, support = {R01 GM036397/GM/NIGMS NIH HHS/United States ; T32 GM007103/GM/NIGMS NIH HHS/United States ; GM 07103-35/GM/NIGMS NIH HHS/United States ; GM36397-25/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/*classification/genetics/*metabolism ; Archamoebae/genetics/metabolism ; Chlorophyta/genetics/metabolism ; Choanoflagellata/genetics/metabolism ; Ciona intestinalis/genetics/metabolism ; Phylogeny ; }, abstract = {Actin is an essential multifunctional protein encoded by two distinct ancient classes of genes in animals (cytoplasmic and muscle) and plants (vegetative and reproductive). The prevailing view is that each class of actin variants is functionally distinct. However, we propose that the vegetative plant and cytoplasmic animal variants have conserved functional competence for spatial development inherited from an ancestral protist actin sequence. To test this idea, we ectopically expressed animal and protist actins in Arabidopsis thaliana double vegetative actin mutants that are dramatically altered in cell and organ morphologies. We found that expression of cytoplasmic actins from humans and even a highly divergent invertebrate Ciona intestinalis qualitatively and quantitatively suppressed the root cell polarity and organ defects of act8 act7 mutants and moderately suppressed the root-hairless phenotype of act2 act8 mutants. By contrast, human muscle actins were unable to support prominently any aspect of plant development. Furthermore, actins from three protists representing Choanozoa, Archamoeba, and green algae efficiently suppressed all the phenotypes of both the plant mutants. Remarkably, these data imply that actin's competence to carry out a complex suite of processes essential for multicellular development was already fully developed in single-celled protists and evolved nonprogressively from protists to plants and animals.}, } @article {pmid22587123, year = {2012}, author = {Flenner, E and Janosi, L and Barz, B and Neagu, A and Forgacs, G and Kosztin, I}, title = {Kinetic Monte Carlo and cellular particle dynamics simulations of multicellular systems.}, journal = {Physical review. E, Statistical, nonlinear, and soft matter physics}, volume = {85}, number = {3 Pt 1}, pages = {031907}, doi = {10.1103/PhysRevE.85.031907}, pmid = {22587123}, issn = {1550-2376}, mesh = {Animals ; Cell Aggregation/physiology ; Cell Communication/*physiology ; Cell Movement/physiology ; Computer Simulation ; Humans ; *Models, Biological ; Spheroids, Cellular/*physiology ; }, abstract = {Computer modeling of multicellular systems has been a valuable tool for interpreting and guiding in vitro experiments relevant to embryonic morphogenesis, tumor growth, angiogenesis and, lately, structure formation following the printing of cell aggregates as bioink particles. Here we formulate two computer simulation methods: (1) a kinetic Monte Carlo (KMC) and (2) a cellular particle dynamics (CPD) method, which are capable of describing and predicting the shape evolution in time of three-dimensional multicellular systems during their biomechanical relaxation. Our work is motivated by the need of developing quantitative methods for optimizing postprinting structure formation in bioprinting-assisted tissue engineering. The KMC and CPD model parameters are determined and calibrated by using an original computational-theoretical-experimental framework applied to the fusion of two spherical cell aggregates. The two methods are used to predict the (1) formation of a toroidal structure through fusion of spherical aggregates and (2) cell sorting within an aggregate formed by two types of cells with different adhesivities.}, } @article {pmid22581706, year = {2012}, author = {Somorjai, IM and Lohmann, JU and Holstein, TW and Zhao, Z}, title = {Stem cells: a view from the roots.}, journal = {Biotechnology journal}, volume = {7}, number = {6}, pages = {704-722}, doi = {10.1002/biot.201100349}, pmid = {22581706}, issn = {1860-7314}, mesh = {Animals ; Arabidopsis/cytology ; Cell Differentiation/genetics ; Cnidaria/cytology ; DNA Methylation ; Drosophila/cytology ; Epigenesis, Genetic ; Histones/metabolism ; Humans ; Mice ; MicroRNAs ; Stem Cell Niche ; Stem Cells/*cytology/*physiology ; }, abstract = {In both plants and animals, regeneration requires the activation of stem cells. This is possibly related to the origin and requirements of multicellularity. Although long diverged from a common ancestry, plant and animal models such as Arabidopsis, Drosophila and mouse share considerable similarities in stem cell regulation. This includes stem cell niche organisation, epigenetic modification of DNA and histones, and the role of small RNA machinery in differentiation and pluripotency states. Dysregulation of any of these can lead to premature ageing, patterning and specification defects, as well as cancers. Moreover, emerging basal animal and plant systems are beginning to provide important clues concerning the diversity and evolutionary history of stem cell regulatory mechanisms in eukaryotes. This review provides a comparative framework, highlighting both the commonalities and differences among groups, which should promote the intelligent design of artificial stem cell systems, and thereby fuel the field of biomaterials science.}, } @article {pmid22580093, year = {2012}, author = {Gardner, MB and Baumgarth, N and Fell, A and McSorley, SJ and Solnick, JV and Bevins, CL}, title = {Meeting report: a symposium on the evolution of common molecular pathways underlying innate immunity.}, journal = {Microbes and infection}, volume = {14}, number = {9}, pages = {667-671}, doi = {10.1016/j.micinf.2012.04.001}, pmid = {22580093}, issn = {1769-714X}, support = {R01 AI032738/AI/NIAID NIH HHS/United States ; R37 AI032738/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; California ; *Evolution, Molecular ; Humans ; *Immunity, Innate ; Models, Animal ; Models, Biological ; Molecular Biology ; }, abstract = {The University of California, Davis hosted a symposium on innate immunity in January 2012. Professors Bruce Beutler, Jules Hoffmann, Luke O'Neill and Pamela Ronald discussed their research on mechanisms that multicellular organisms use to recognize microbes.}, } @article {pmid22572958, year = {2012}, author = {Batsios, P and Peter, T and Baumann, O and Stick, R and Meyer, I and Gräf, R}, title = {A lamin in lower eukaryotes?.}, journal = {Nucleus (Austin, Tex.)}, volume = {3}, number = {3}, pages = {237-243}, pmid = {22572958}, issn = {1949-1042}, mesh = {Alkyl and Aryl Transferases/chemistry/metabolism ; Animals ; Cell Nucleus/metabolism ; Centrosome/metabolism ; Dictyostelium/metabolism ; Lamins/chemistry/*metabolism ; Nuclear Envelope/metabolism ; Protein Processing, Post-Translational ; Protozoan Proteins/chemistry/*metabolism ; }, abstract = {Lamins are the major components of the nuclear lamina and serve not only as a mechanical support, but are also involved in chromatin organization, epigenetic regulation, transcription and mitotic events. Despite these universal tasks, lamins have so far been found only in metazoans. Yet, recently we have identified Dictyostelium NE81 as the first lamin-like protein in a lower eukaryote. Based on the current knowledge, we draw a model for nuclear envelope organization in Dictyostelium in this Extra View and we review the experimental data that justified this classification. Furthermore we provide unpublished data underscoring the requirement of posttranslational CaaX-box processing for proper protein localization at the nuclear envelope. Sequence comparison of NE81 sequences from four Dictyostelia with bona fide lamins illustrates the evolutional relationship between these proteins. Under certain conditions these usually unicellular social amoebae congregate to form a multicellular body. We propose that the evolution of the lamin-like NE81 went along with the invention of multicellularity.}, } @article {pmid22566026, year = {2012}, author = {Xu, K and Buchsbaum, RJ}, title = {Isolation of mammary epithelial cells from three-dimensional mixed-cell spheroid co-culture.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {62}, pages = {}, pmid = {22566026}, issn = {1940-087X}, mesh = {Animals ; Coculture Techniques/*methods ; Epithelial Cells/cytology ; Humans ; Mammary Glands, Animal/*cytology ; Mammary Glands, Human/*cytology ; Spheroids, Cellular/*cytology ; }, abstract = {While enormous efforts have gone into identifying signaling pathways and molecules involved in normal and malignant cell behaviors(1-2), much of this work has been done using classical two-dimensional cell culture models, which allow for easy cell manipulation. It has become clear that intracellular signaling pathways are affected by extracellular forces, including dimensionality and cell surface tension(3-4). Multiple approaches have been taken to develop three-dimensional models that more accurately represent biologic tissue architecture(3). While these models incorporate multi-dimensionality and architectural stresses, study of the consequent effects on cells is less facile than in two-dimensional tissue culture due to the limitations of the models and the difficulty in extracting cells for subsequent analysis. The important role of the microenvironment around tumors in tumorigenesis and tumor behavior is becoming increasingly recognized(4). Tumor stroma is composed of multiple cell types and extracellular molecules. During tumor development there are bidirectional signals between tumor cells and stromal cells(5). Although some factors participating in tumor-stroma co-evolution have been identified, there is still a need to develop simple techniques to systematically identify and study the full array of these signals(6). Fibroblasts are the most abundant cell type in normal or tumor-associated stromal tissues, and contribute to deposition and maintenance of basement membrane and paracrine growth factors(7). Many groups have used three dimensional culture systems to study the role of fibroblasts on various cellular functions, including tumor response to therapies, recruitment of immune cells, signaling molecules, proliferation, apoptosis, angiogenesis, and invasion(8-15). We have optimized a simple method for assessing the effects of mammary fibroblasts on mammary epithelial cells using a commercially available extracellular matrix model to create three-dimensional cultures of mixed cell populations (co-cultures)(16-22). With continued co-culture the cells form spheroids with the fibroblasts clustering in the interior and the epithelial cells largely on the exterior of the spheroids and forming multi-cellular projections into the matrix. Manipulation of the fibroblasts that leads to altered epithelial cell invasiveness can be readily quantified by changes in numbers and length of epithelial projections(23). Furthermore, we have devised a method for isolating epithelial cells out of three-dimensional co-culture that facilitates analysis of the effects of fibroblast exposure on epithelial behavior. We have found that the effects of co-culture persist for weeks after epithelial cell isolation, permitting ample time to perform multiple assays. This method is adaptable to cells of varying malignant potential and requires no specialized equipment. This technique allows for rapid evaluation of in vitro cell models under multiple conditions, and the corresponding results can be compared to in vivo animal tissue models as well as human tissue samples.}, } @article {pmid22564088, year = {2012}, author = {Noonin, C and Lin, X and Jiravanichpaisal, P and Söderhäll, K and Söderhäll, I}, title = {Invertebrate hematopoiesis: an anterior proliferation center as a link between the hematopoietic tissue and the brain.}, journal = {Stem cells and development}, volume = {21}, number = {17}, pages = {3173-3186}, doi = {10.1089/scd.2012.0077}, pmid = {22564088}, issn = {1557-8534}, mesh = {Animals ; Astacoidea/*cytology/metabolism/physiology ; Brain/*cytology/metabolism/physiology ; Bromodeoxyuridine/metabolism ; Cell Count ; Cell Differentiation ; Cell Nucleus/metabolism ; *Cell Proliferation ; Cells, Cultured ; Gastric Mucosa/metabolism ; *Hematopoiesis ; Hematopoietic System/cytology/metabolism ; Hemocytes/*cytology/metabolism ; Lipopolysaccharides ; Microscopy, Electron, Transmission ; Mitosis ; Reactive Oxygen Species/metabolism ; Staining and Labeling ; Stomach/cytology/physiology ; }, abstract = {During evolution, the innate and adaptive immune systems were developed to protect organisms from non-self substances. The innate immune system is phylogenetically more ancient and is present in most multicellular organisms, whereas adaptive responses are restricted to vertebrates. Arthropods lack the blood cells of the lymphoid lineage and oxygen-carrying erythrocytes, making them suitable model animals for studying the regulation of the blood cells of the innate immune system. Many crustaceans have a long life span and need to continuously synthesize blood cells, in contrast to many insects. The hematopoietic tissue (HPT) of Pacifastacus leniusculus provides a simple model for studying hematopoiesis, because the tissue can be isolated, and the proliferation of stem cells and their differentiation can be studied both in vivo and in vitro. Here, we demonstrate new findings of a physical link between the HPT and the brain. Actively proliferating cells were localized to an anterior proliferation center (APC) in the anterior part of the tissue near the area linking the HPT to the brain, whereas more differentiated cells were detected in the posterior part. The central areas of HPT expand in response to lipopolysaccharide-induced blood loss. Cells isolated from the APC divide rapidly and form cell clusters in vitro; conversely, the cells from the remaining HPT form monolayers, and they can be induced to differentiate in vitro. Our findings offer an opportunity to learn more about invertebrate hematopoiesis and its connection to the central nervous system, thereby obtaining new information about the evolution of different blood and nerve cell lineages.}, } @article {pmid22562152, year = {2012}, author = {Greer, SN and Metcalf, JL and Wang, Y and Ohh, M}, title = {The updated biology of hypoxia-inducible factor.}, journal = {The EMBO journal}, volume = {31}, number = {11}, pages = {2448-2460}, pmid = {22562152}, issn = {1460-2075}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Apoptosis Regulatory Proteins ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Carrier Proteins/metabolism ; Embryonic Development ; Humans ; Hypoxia/*metabolism ; Hypoxia-Inducible Factor 1/antagonists & inhibitors/*metabolism ; Immunity ; Membrane Proteins/metabolism ; Mice ; Oxygen/*metabolism ; Receptors, Notch/metabolism ; Repressor Proteins ; Sirtuin 3/metabolism ; Thyroid Hormones/metabolism ; Thyroid Hormone-Binding Proteins ; }, abstract = {Oxygen is essential for eukaryotic life and is inextricably linked to the evolution of multicellular organisms. Proper cellular response to changes in oxygen tension during normal development or pathological processes, such as cardiovascular disease and cancer, is ultimately regulated by the transcription factor, hypoxia-inducible factor (HIF). Over the past decade, unprecedented molecular insight has been gained into the mammalian oxygen-sensing pathway involving the canonical oxygen-dependent prolyl-hydroxylase domain-containing enzyme (PHD)-von Hippel-Lindau tumour suppressor protein (pVHL) axis and its connection to cellular metabolism. Here we review recent notable advances in the field of hypoxia that have shaped a more complex model of HIF regulation and revealed unique roles of HIF in a diverse range of biological processes, including immunity, development and stem cell biology.}, } @article {pmid22550341, year = {2012}, author = {Suga, H and Dacre, M and de Mendoza, A and Shalchian-Tabrizi, K and Manning, G and Ruiz-Trillo, I}, title = {Genomic survey of premetazoans shows deep conservation of cytoplasmic tyrosine kinases and multiple radiations of receptor tyrosine kinases.}, journal = {Science signaling}, volume = {5}, number = {222}, pages = {ra35}, doi = {10.1126/scisignal.2002733}, pmid = {22550341}, issn = {1937-9145}, support = {206883/ERC_/European Research Council/International ; HG004164/HG/NHGRI NIH HHS/United States ; }, mesh = {Base Sequence ; Cytoplasm/enzymology/*genetics ; Eukaryota/enzymology/*genetics ; *Evolution, Molecular ; Genome/*physiology ; Molecular Sequence Data ; *Phylogeny ; Receptor Protein-Tyrosine Kinases/*genetics ; }, abstract = {The evolution of multicellular metazoans from a unicellular ancestor is one of the most important advances in the history of life. Protein tyrosine kinases play important roles in cell-to-cell communication, cell adhesion, and differentiation in metazoans; thus, elucidating their origins and early evolution is crucial for understanding the origin of metazoans. Although tyrosine kinases exist in choanoflagellates, few data are available about their existence in other premetazoan lineages. To unravel the origin of tyrosine kinases, we performed a genomic and polymerase chain reaction (PCR)-based survey of the genes that encode tyrosine kinases in the two described filasterean species, Capsaspora owczarzaki and Ministeria vibrans, the closest relatives to the Metazoa and Choanoflagellata clades. We present 103 tyrosine kinase-encoding genes identified in the whole genome sequence of C. owczarzaki and 15 tyrosine kinase-encoding genes cloned by PCR from M. vibrans. Through detailed phylogenetic analysis, comparison of the organizations of the protein domains, and resequencing and revision of tyrosine kinase sequences previously found in some whole genome sequences, we demonstrate that the basic repertoire of metazoan cytoplasmic tyrosine kinases was established before the divergence of filastereans from the Metazoa and Choanoflagellata clades. In contrast, the receptor tyrosine kinases diversified extensively in each of the filasterean, choanoflagellate, and metazoan clades. This difference in the divergence patterns between cytoplasmic tyrosine kinases and receptor tyrosine kinases suggests that receptor tyrosine kinases that had been used for receiving environmental cues were subsequently recruited as a communication tool between cells at the onset of metazoan multicellularity.}, } @article {pmid22549587, year = {2012}, author = {Liu, H and Jiang, D and Chi, F and Zhao, B}, title = {The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation.}, journal = {Protein & cell}, volume = {3}, number = {4}, pages = {291-304}, pmid = {22549587}, issn = {1674-8018}, mesh = {Animals ; Cell Differentiation ; Cell Proliferation ; Drosophila ; Drosophila Proteins/*metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/*metabolism ; Mesenchymal Stem Cells/cytology/metabolism ; Neoplastic Stem Cells/cytology/metabolism ; Nuclear Proteins/metabolism ; Protein Serine-Threonine Kinases/*metabolism ; Signal Transduction ; Stem Cells/*cytology/metabolism ; Transcription Factors/metabolism ; }, abstract = {Stem cells and progenitor cells are the cells of origin for multi-cellular organisms and organs. They play key roles during development and their dysregulation gives rise to human diseases such as cancer. The recent development of induced pluripotent stem cell (iPSC) technology which converts somatic cells to stem-like cells holds great promise for regenerative medicine. Nevertheless, the understanding of proliferation, differentiation, and self-renewal of stem cells and organ-specific progenitor cells is far from clear. Recently, the Hippo pathway was demonstrated to play important roles in these processes. The Hippo pathway is a newly established signaling pathway with critical functions in limiting organ size and suppressing tumorigenesis. This pathway was first found to inhibit cell proliferation and promote apoptosis, therefore regulating cell number and organ size in both Drosophila and mammals. However, in several organs, disturbance of the pathway leads to specific expansion of the progenitor cell compartment and manipulation of the pathway in embryonic stem cells strongly affects their self-renewal and differentiation. In this review, we summarize current observations on roles of the Hippo pathway in different types of stem cells and discuss how these findings changed our view on the Hippo pathway in organ development and tumorigenesis.}, } @article {pmid22543423, year = {2013}, author = {Ereskovsky, AV and Renard, E and Borchiellini, C}, title = {Cellular and molecular processes leading to embryo formation in sponges: evidences for high conservation of processes throughout animal evolution.}, journal = {Development genes and evolution}, volume = {223}, number = {1-2}, pages = {5-22}, pmid = {22543423}, issn = {1432-041X}, mesh = {Animals ; *Biological Evolution ; Porifera/classification/cytology/*embryology/physiology ; Reproduction, Asexual ; Signal Transduction ; }, abstract = {The emergence of multicellularity is regarded as one of the major evolutionary events of life. This transition unicellularity/pluricellularity was acquired independently several times (King 2004). The acquisition of multicellularity implies the emergence of cellular cohesion and means of communication, as well as molecular mechanisms enabling the control of morphogenesis and body plan patterning. Some of these molecular tools seem to have predated the acquisition of multicellularity while others are regarded as the acquisition of specific lineages. Morphogenesis consists in the spatial migration of cells or cell layers during embryonic development, metamorphosis, asexual reproduction, growth, and regeneration, resulting in the formation and patterning of a body. In this paper, our aim is to review what is currently known concerning basal metazoans--sponges' morphogenesis from the tissular, cellular, and molecular points of view--and what remains to elucidate. Our review attempts to show that morphogenetic processes found in sponges are as diverse and complex as those found in other animals. In true epithelial sponges (Homoscleromorpha), as well as in others, we find similar cell/layer movements, cellular shape changes involved in major morphogenetic processes such as embryogenesis or larval metamorphosis. Thus, sponges can provide information enabling us to better understand early animal evolution at the molecular level but also at the cell/cell layer level. Indeed, comparison of molecular tools will only be of value if accompanied by functional data and expression studies during morphogenetic processes.}, } @article {pmid22535467, year = {2012}, author = {Wilson, IB}, title = {The class I α1,2-mannosidases of Caenorhabditis elegans.}, journal = {Glycoconjugate journal}, volume = {29}, number = {4}, pages = {173-179}, pmid = {22535467}, issn = {1573-4986}, mesh = {Animals ; Caenorhabditis elegans/*enzymology/metabolism ; Endoplasmic Reticulum/enzymology/metabolism ; Genome, Helminth ; Golgi Apparatus/enzymology/metabolism ; Mannans/chemistry/metabolism ; Mannosidases/*chemistry/classification ; Molecular Sequence Data ; Phylogeny ; Pichia/metabolism ; Polysaccharides/chemistry/metabolism ; }, abstract = {During the biosynthesis of N-glycans in multicellular eukaryotes, glycans with the compositions Man(5)GlcNAc(2-3) are key intermediates. However, to reach this 'decision point', these N-glycans are first processed from Glc(3)Man(9)GlcNAc(2) through to Man(5)GlcNAc(2) by a number of glycosidases, whereby up to four α1-2-linked mannose residues are removed by class I mannosidases (glycohydrolase family 47). Whereas in the yeast Saccharomyces cerevisiae there are maximally three members of this protein family, in higher organisms there are multiple class I mannosidases residing in the endoplasmic reticulum and Golgi apparatus. The genome of the model nematode Caenorhabditis elegans encodes seven members of this protein family, whereby four are predicted to be classical processing mannosidases and three are related proteins with roles in quality control. In this study, cDNAs encoding the four predicted mannosidases were cloned and expressed in Pichia pastoris and the activity of these enzymes, designated MANS-1, MANS-2, MANS-3 and MANS-4, was verified. The first two can, dependent on the incubation time, remove three to four residues from Man(9)GlcNAc(2), whereas the action of the other two results in the appearance of the B isomer of Man(8)GlcNAc(2); together the complementary activities of these enzymes result in processing to Man(5)GlcNAc(2). With these data, another gap is closed in our understanding of the N-glycan biosynthesis pathway of the nematode worm.}, } @article {pmid22534682, year = {2012}, author = {de Almeida, M and de Almeida, CV and Mendes Graner, E and Ebling Brondani, G and Fiori de Abreu-Tarazi, M}, title = {Pre-procambial cells are niches for pluripotent and totipotent stem-like cells for organogenesis and somatic embryogenesis in the peach palm: a histological study.}, journal = {Plant cell reports}, volume = {31}, number = {8}, pages = {1495-1515}, pmid = {22534682}, issn = {1432-203X}, mesh = {Arecaceae/*cytology/*embryology ; Cambium/*cytology ; Cell Count ; Cell Differentiation ; Cell Nucleus/metabolism ; *Organogenesis ; Plant Vascular Bundle/cytology/physiology ; Pluripotent Stem Cells/*cytology/metabolism ; Regeneration/physiology ; Seeds/cytology/embryology ; *Stem Cell Niche ; Totipotent Stem Cells/*cytology/metabolism ; }, abstract = {UNLABELLED: The direct induction of adventitious buds and somatic embryos from explants is a morphogenetic process that is under the influence of exogenous plant growth regulators and its interactions with endogenous phytohormones. We performed an in vitro histological analysis in peach palm (Bactris gasipaes Kunth) shoot apexes and determined that the positioning of competent cells and their interaction with neighboring cells, under the influence of combinations of exogenously applied growth regulators (NAA/BAP and NAA/TDZ), allows the pre-procambial cells (PPCs) to act in different morphogenic pathways to establish niche competent cells. It is likely that there has been a habituation phenomenon during the regeneration and development of the microplants. This includes promoting the tillering of primary or secondary buds due to culturing in the absence of NAA/BAP or NAA/TDZ after a period in the presence of these growth regulators. Histological analyses determined that the adventitious roots were derived from the dedifferentiation of the parenchymal cells located in the basal region of the adventitious buds, with the establishment of rooting pole, due to an auxin gradient. Furthermore, histological and histochemical analyses allowed us to characterize how the PPCs provide niches for multipotent, pluripotent and totipotent stem-like cells for vascular differentiation, organogenesis and somatic embryogenesis in the peach palm. The histological and histochemical analyses also allowed us to detect the unicellular or multicellular origin of somatic embryogenesis. Therefore, our results indicate that the use of growth regulators in microplants can lead to habituation and to different morphogenic pathways leading to potential niche establishment, depending on the positioning of the competent cells and their interaction with neighboring cells.

KEY MESSAGE: Our results indicate that the use of growth regulators in microplants can lead to habituation and to different morphogenic pathways leading to potential niche establishment, depending on the positioning of the competent cells and their interaction with neighboring cells.}, } @article {pmid22517163, year = {2012}, author = {Peters, SE and Gaines, RR}, title = {Formation of the 'Great Unconformity' as a trigger for the Cambrian explosion.}, journal = {Nature}, volume = {484}, number = {7394}, pages = {363-366}, pmid = {22517163}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms/classification/cytology ; *Biological Evolution ; Ecosystem ; Fossils ; Geologic Sediments/*chemistry ; Geology ; History, Ancient ; Hydrogen-Ion Concentration ; North America ; Seawater/chemistry ; Soil/chemistry ; }, abstract = {The transition between the Proterozoic and Phanerozoic eons, beginning 542 million years (Myr) ago, is distinguished by the diversification of multicellular animals and by their acquisition of mineralized skeletons during the Cambrian period. Considerable progress has been made in documenting and more precisely correlating biotic patterns in the Neoproterozoic-Cambrian fossil record with geochemical and physical environmental perturbations, but the mechanisms responsible for those perturbations remain uncertain. Here we use new stratigraphic and geochemical data to show that early Palaeozoic marine sediments deposited approximately 540-480 Myr ago record both an expansion in the area of shallow epicontinental seas and anomalous patterns of chemical sedimentation that are indicative of increased oceanic alkalinity and enhanced chemical weathering of continental crust. These geochemical conditions were caused by a protracted period of widespread continental denudation during the Neoproterozoic followed by extensive physical reworking of soil, regolith and basement rock during the first continental-scale marine transgression of the Phanerozoic. The resultant globally occurring stratigraphic surface, which in most regions separates continental crystalline basement rock from much younger Cambrian shallow marine sedimentary deposits, is known as the Great Unconformity. Although Darwin and others have interpreted this widespread hiatus in sedimentation on the continents as a failure of the geologic record, this palaeogeomorphic surface represents a unique physical environmental boundary condition that affected seawater chemistry during a time of profound expansion of shallow marine habitats. Thus, the formation of the Great Unconformity may have been an environmental trigger for the evolution of biomineralization and the 'Cambrian explosion' of ecologic and taxonomic diversity following the Neoproterozoic emergence of animals.}, } @article {pmid22513108, year = {2012}, author = {Charrier, B and Le Bail, A and de Reviers, B}, title = {Plant Proteus: brown algal morphological plasticity and underlying developmental mechanisms.}, journal = {Trends in plant science}, volume = {17}, number = {8}, pages = {468-477}, doi = {10.1016/j.tplants.2012.03.003}, pmid = {22513108}, issn = {1878-4372}, mesh = {*Adaptation, Biological ; Biological Evolution ; Cell Division ; Environment ; Mechanotransduction, Cellular ; *Morphogenesis ; Phaeophyceae/classification/genetics/*physiology ; Phylogeny ; Signal Transduction ; Species Specificity ; }, abstract = {Brown algae are multicellular photosynthetic marine organisms, ubiquitous on rocky intertidal shores at cold and temperate latitudes. Nevertheless, little is known about many aspects of their biology, particularly their development. Given their phylogenetic distance (1.6 billion years) from other plant organisms (land plants, and green and red algae), brown algae harbor a high, as-yet undiscovered diversity of biological mechanisms governing their development. They also show great morphological plasticity, responding to specific environmental constraints, such as sea currents, reduced light availability, grazer attacks, desiccation and UV exposure. Here, we show that brown algal morphogenesis is rather simple and flexible, and review recent genomic data on the cellular and molecular mechanisms known to date that can possibly account for this developmental strategy.}, } @article {pmid22507701, year = {2012}, author = {Rogozin, IB and Carmel, L and Csuros, M and Koonin, EV}, title = {Origin and evolution of spliceosomal introns.}, journal = {Biology direct}, volume = {7}, number = {}, pages = {11}, pmid = {22507701}, issn = {1745-6150}, support = {Z01LM000073-12/LM/NLM NIH HHS/United States ; //Intramural NIH HHS/United States ; }, mesh = {Alternative Splicing ; Animals ; Base Sequence ; Conserved Sequence ; Eukaryota/chemistry/classification/genetics ; *Evolution, Molecular ; Exons ; Genetics, Population ; Genome ; *Introns ; Phylogeny ; RNA Splice Sites ; Selection, Genetic ; Spliceosomes/chemistry/*genetics ; Untranslated Regions ; }, abstract = {Evolution of exon-intron structure of eukaryotic genes has been a matter of long-standing, intensive debate. The introns-early concept, later rebranded 'introns first' held that protein-coding genes were interrupted by numerous introns even at the earliest stages of life's evolution and that introns played a major role in the origin of proteins by facilitating recombination of sequences coding for small protein/peptide modules. The introns-late concept held that introns emerged only in eukaryotes and new introns have been accumulating continuously throughout eukaryotic evolution. Analysis of orthologous genes from completely sequenced eukaryotic genomes revealed numerous shared intron positions in orthologous genes from animals and plants and even between animals, plants and protists, suggesting that many ancestral introns have persisted since the last eukaryotic common ancestor (LECA). Reconstructions of intron gain and loss using the growing collection of genomes of diverse eukaryotes and increasingly advanced probabilistic models convincingly show that the LECA and the ancestors of each eukaryotic supergroup had intron-rich genes, with intron densities comparable to those in the most intron-rich modern genomes such as those of vertebrates. The subsequent evolution in most lineages of eukaryotes involved primarily loss of introns, with only a few episodes of substantial intron gain that might have accompanied major evolutionary innovations such as the origin of metazoa. The original invasion of self-splicing Group II introns, presumably originating from the mitochondrial endosymbiont, into the genome of the emerging eukaryote might have been a key factor of eukaryogenesis that in particular triggered the origin of endomembranes and the nucleus. Conversely, splicing errors gave rise to alternative splicing, a major contribution to the biological complexity of multicellular eukaryotes. There is no indication that any prokaryote has ever possessed a spliceosome or introns in protein-coding genes, other than relatively rare mobile self-splicing introns. Thus, the introns-first scenario is not supported by any evidence but exon-intron structure of protein-coding genes appears to have evolved concomitantly with the eukaryotic cell, and introns were a major factor of evolution throughout the history of eukaryotes.}, } @article {pmid22474612, year = {2012}, author = {Lammert, E and Axnick, J}, title = {Vascular lumen formation.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {2}, number = {4}, pages = {a006619}, pmid = {22474612}, issn = {2157-1422}, mesh = {Animals ; Blood Vessels/anatomy & histology/*embryology/physiology ; Endothelial Cells/*cytology/*metabolism ; Endothelium, Vascular/*physiology ; Humans ; Invertebrates/physiology ; Neoplasms/blood supply ; Neovascularization, Pathologic/physiopathology ; Neovascularization, Physiologic/physiology ; Signal Transduction ; Vertebrates/physiology ; }, abstract = {The vascular system developed early in evolution. It is required in large multicellular organisms for the transport of nutrients, oxygen, and waste products to and from tissues. The vascular system is composed of hollow tubes, which have a high level of complexity in vertebrates. Vasculogenesis describes the de novo formation of blood vessels, e.g., aorta formation in vertebrate embryogenesis. In contrast, angiogenesis is the formation of blood vessels from preexisting ones, e.g., sprouting of intersomitic blood vessels from the aorta. Importantly, the lumen of all blood vessels in vertebrates is lined and formed by endothelial cells. In both vasculogenesis and angiogenesis, lumen formation takes place in a cord of endothelial cells. It involves a complex molecular mechanism composed of endothelial cell repulsion at the cell-cell contacts within the endothelial cell cords, junctional rearrangement, and endothelial cell shape change. As the vascular system also participates in the course of many diseases, such as cancer, stroke, and myocardial infarction, it is important to understand and make use of the molecular mechanisms of blood vessel formation to better understand and manipulate the pathomechanisms involved.}, } @article {pmid22467866, year = {2012}, author = {Shih, W and Yamada, S}, title = {N-cadherin-mediated cell-cell adhesion promotes cell migration in a three-dimensional matrix.}, journal = {Journal of cell science}, volume = {125}, number = {Pt 15}, pages = {3661-3670}, pmid = {22467866}, issn = {1477-9137}, support = {R01 GM094798/GM/NIGMS NIH HHS/United States ; GM094798/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/metabolism ; Animals ; Cadherins/genetics/metabolism/*physiology ; Cell Adhesion/*physiology ; Cell Line ; Cell Line, Transformed ; Cell Movement/*physiology ; Collagen/chemistry ; Cytoskeleton/metabolism ; Dogs ; Epithelial Cells/*cytology ; Epithelial-Mesenchymal Transition/drug effects/physiology ; Gene Knockdown Techniques ; Hepatocyte Growth Factor/pharmacology ; Madin Darby Canine Kidney Cells ; Stress Fibers/metabolism ; alpha Catenin/metabolism ; }, abstract = {Cancer cells that originate from epithelial tissues typically lose epithelial specific cell-cell junctions, but these transformed cells are not devoid of cell-cell adhesion proteins. Using hepatocyte-growth-factor-treated MDCK cells that underwent a complete epithelial-to-mesenchymal transition, we analyzed cell-cell adhesion between these highly invasive transformed epithelial cells in a three-dimensional (3D) collagen matrix. In a 3D matrix, these transformed cells formed elongated multicellular chains, and migrated faster and more persistently than single cells in isolation. In addition, the cell clusters were enriched with stress-fiber-like actin bundles that provided contractile forces. N-cadherin-knockdown cells failed to form cell-cell junctions or migrate, and the expression of the N-cadherin cytoplasmic or extracellular domain partially rescued the knockdown phenotype. By contrast, the expression of N-cadherin-α-catenin chimera rescued the knockdown phenotype, but individual cells within the cell clusters were less mobile. Together, our findings suggest that a dynamic N-cadherin and actin linkage is required for efficient 3D collective migration.}, } @article {pmid22464976, year = {2012}, author = {Okamoto, K and Nakatsukasa, M and Alié, A and Masuda, Y and Agata, K and Funayama, N}, title = {The active stem cell specific expression of sponge Musashi homolog EflMsiA suggests its involvement in maintaining the stem cell state.}, journal = {Mechanisms of development}, volume = {129}, number = {1-4}, pages = {24-37}, doi = {10.1016/j.mod.2012.03.001}, pmid = {22464976}, issn = {1872-6356}, mesh = {Animals ; Cell Cycle Checkpoints ; Cell Differentiation ; Cell Division ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Gene Expression ; Organ Specificity ; Phylogeny ; Porifera/*cytology/genetics/metabolism ; Protein Transport ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/genetics/*metabolism ; Stem Cells/*physiology ; }, abstract = {A hallmark of stem cells is the ability to sustainably generate stem cells themselves (self-renew) as well as differentiated cells. Although a full understanding of this ability will require clarifying underlying the primordial molecular and cellular mechanisms, how stem cells maintain their stem state and their population in the evolutionarily oldest extant multicellular organisms, sponges, is poorly understood. Here, we report the identification of the first stem cell-specific gene in demosponges, a homolog of Musashi (an evolutionarily conserved RNA binding protein that regulates the stem cell state in various organisms). EflMsiA, a Musashi paralog, is specifically expressed in stem cells (archeocytes) in the freshwater sponge Ephydatia fluviatilis. EflMsiA protein is localized predominantly in the nucleus, with a small fraction in the cytoplasm, in archeocytes. When archeocytes enter M-phase, EflMsiA protein diffuses into the cytoplasm, probably because of the breakdown of the nuclear membrane. In the present study, the existence of two types of M-phase archeocytes [(M)-archeocytes] was revealed by a precise analysis of the expression levels of EflMsiA mRNA and protein. In Type I (M)-archeocytes, presumably archeocytes undergoing self-renewal, the expression levels of EflMsiA mRNA and protein were high. In Type II (M)-archeocytes, presumably archeocytes committed to differentiate (committed archeocytes), the expression levels of EflMsiA mRNA and protein were about 60% and 30% lower than those in Type I (M)-archeocytes. From these results, archeocytes can be molecularly defined for the first time as EflMsiA-mRNA-expressing cells. Furthermore, these findings shed light on the mode of cell division of archeocytes and suggest that archeocytes divide symmetrically for both self-renewal and differentiation.}, } @article {pmid22458243, year = {2012}, author = {Denardi, JD and Oliveira, DM and Paiva, EA}, title = {Glandular trichomes in Connarus suberosus (Connaraceae): distribution, structural organization and probable functions.}, journal = {Revista de biologia tropical}, volume = {60}, number = {1}, pages = {505-513}, doi = {10.15517/rbt.v60i1.2785}, pmid = {22458243}, issn = {0034-7744}, mesh = {Brazil ; Connaraceae/chemistry/classification/*ultrastructure ; Microscopy, Electron ; }, abstract = {Connarus suberosus is a typical species of the Brazilian Cerrado biome, and its inflorescences and young vegetative branches are densely covered by dendritic trichomes. The objective of this study was to report the occurrence of a previously undescribed glandular trichome of this species. The localization, origin and structure of these trichomes were investigated under light, transmission and scanning electron microscopy. Collections were made throughout the year, from five adult specimens of Connarus suberosus near Botucatu, São Paulo, Brazil, including vegetative and reproductive apices, leaves and fruits in different developmental stages, as well as floral buds and flowers at anthesis. Glandular trichomes (GTs) occurred on vegetative and reproductive organs during their juvenile stages. The GTs consisted of a uniseriate, multicellular peduncle, whose cells contain phenolic compounds, as well as a multicellular glandular portion that accumulates lipids. The glandular cell has thin wall, dense cytoplasm (with many mitochondria, plastids and dictyosomes), and a large nucleus with a visible nucleolus. The starch present in the plastids was hydrolyzed during the synthesis phase, reducing the density of the plastid stroma. Some plastids were fused to vacuoles, and some evidence suggested the conversion of plastids into vacuoles. During the final activity stages of the GTs, a darkening of the protoplasm was observed in some of the glandular cells, as a programmed cell death; afterwards, became caducous. The GTs in C. suberosus had a temporal restriction, being limited to the juvenile phase of the organs. Their presence on the exposed surfaces of developing organs and the chemical nature of the reserve products, suggest that these structures are food bodies. Field observations and detailed studies of plant-environment interactions, as well as chemical analysis of the reserve compounds, are still necessary to confirm the role of these GTs as feeding rewards.}, } @article {pmid22456498, year = {2012}, author = {Nussbaum, JC and Locksley, RM}, title = {Infectious (Non)tolerance--frustrated commensalism gone awry?.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {4}, number = {5}, pages = {}, pmid = {22456498}, issn = {1943-0264}, support = {R01 AI030663/AI/NIAID NIH HHS/United States ; R37 AI026918/AI/NIAID NIH HHS/United States ; T32 AI007641/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Communicable Diseases/*microbiology ; Host-Pathogen Interactions/*immunology/physiology ; Humans ; Immune Tolerance/*immunology ; Inflammation/*microbiology ; Mice ; *Models, Biological ; Signal Transduction/*immunology ; Symbiosis/*immunology/physiology ; }, abstract = {Despite advances in medicine, infectious diseases remain major causes of death and disability worldwide. Acute or chronic infectious agents mediate host tissue damage and cause a spectrum of disease as diverse as overwhelming sepsis and shock within hours to persistent tissue inflammation causing organ failure or even cancer over years. Although pathogen exposure can cause disease via host-derived inflammation, pathogens share recognized elements with harmless human commensals. Mouse models and organisms with simpler flora are revealing the dialogue between multicellular hosts and commensal flora. In some instances the persistent inflammation associated with pathogens can be interpreted within a framework of frustrated commensalism in which the host and pathogen cannot complete the requisite dialogue that establishes homeostasis. In contrast, coevolved commensals interact cooperatively with the host immune system, resulting in immunotolerance. Attempts to more thoroughly understand the molecular nature of the dialogue may uncover novel approaches to the control of inflammation and tissue damage.}, } @article {pmid22453942, year = {2012}, author = {Mackrill, JJ}, title = {Ryanodine receptor calcium release channels: an evolutionary perspective.}, journal = {Advances in experimental medicine and biology}, volume = {740}, number = {}, pages = {159-182}, doi = {10.1007/978-94-007-2888-2_7}, pmid = {22453942}, issn = {0065-2598}, mesh = {Animals ; Calcium/metabolism ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Humans ; Protein Structure, Tertiary ; Ryanodine Receptor Calcium Release Channel/chemistry/genetics/*physiology ; }, abstract = {Ryanodine receptors (RyRs), along with the related inositol 1,4,5-trisphosphate receptors (IP(3)Rs), mediate the release of Ca(2+) from intracellular organelles of eukaryotes. As discussed in other chapters, such increases in intracellular Ca(2+) levels act a fundamental second messenger, regulating a diverse array of cellular processes. For over two decades, it has been reported that vertebrates express multiple RYR genes, whereas non-vertebrate multicellular organisms possess a single homologue within their genomes. Recently, the existence of RyR-like channels in unicellular organisms has also been reported. This chapter exploits recent expansions in available genome data to generate an overview of the expression of RyR-like genes in organisms representing a broad range of viral, archaeal, bacterial and eukaryotic taxa. Analyses of the multidomain structures and phylogenetic relationships of these proteins has lead to a model in which, early during eukaryotic evolution, IP(3)R-like ancestral Ca(2+) release channels were converted to RyR proteins via the addition of promiscuous protein domains, possibly via horizontal gene transfer mechanisms.}, } @article {pmid22451943, year = {2012}, author = {Sharp, NP and Agrawal, AF}, title = {Evidence for elevated mutation rates in low-quality genotypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {16}, pages = {6142-6146}, pmid = {22451943}, issn = {1091-6490}, mesh = {Adaptation, Physiological/genetics ; Alleles ; Animals ; Chromosomes, Insect/*genetics ; Crosses, Genetic ; Drosophila melanogaster/*genetics ; Evolution, Molecular ; Female ; Genotype ; Humans ; Male ; *Models, Genetic ; *Mutation Rate ; Stress, Physiological/genetics ; }, abstract = {The deleterious mutation rate plays a key role in a number of important topics in biology, from mating system evolution to human health. Despite this broad significance, the nature and causes of variation in mutation rate are poorly understood, especially in multicellular organisms. We test whether genetic quality, the presence or absence of deleterious alleles, affects the mutation rate in Drosophila melanogaster by using a modified mutation accumulation approach. We find evidence that genotypes constructed to carry deleterious "treatment" alleles on one chromosome during mutation accumulation experience an elevated mutation rate on a different chromosome. Further, this elevation is correlated with the effect of the treatment alleles on phenotypic condition, measured as body mass. Treatment alleles that reduce mass by 10% cause a doubling in the rate of mutational decline. Our results show that mutation rates are sensitive to genetic stress, such that individuals with low-quality genotypes will produce offspring of even lower genetic quality, in a mutational positive feedback loop. This type of variation in mutation rate is expected to alter a variety of predictions based on mutation load theory and accelerate adaptation to new environments. Positive mutational feedback could affect human health by increasing the rate of germline mutation, and possibly somatic mutation, in individuals of poor health because of genetic or environmental stress.}, } @article {pmid22449041, year = {2012}, author = {Oikawa, A and Saito, K}, title = {Metabolite analyses of single cells.}, journal = {The Plant journal : for cell and molecular biology}, volume = {70}, number = {1}, pages = {30-38}, doi = {10.1111/j.1365-313X.2012.04967.x}, pmid = {22449041}, issn = {1365-313X}, mesh = {Mass Spectrometry ; Metabolomics/*methods ; Plant Cells/*metabolism ; Plants/*metabolism ; Single-Cell Analysis/*methods ; }, abstract = {Single-cell analysis is a promising method for understanding not only cellular physiology but also biological mechanisms of multicellular organisms. Although neighboring cells in multicellular organisms originate from the same genomic information, different circumstances around cells or epigenetic differences have different influences on each cell, leading to differing expression of genes, and thus differing levels and dynamics of metabolites, in single cells. However, single-cell analysis is a tough challenge, even with recent technologies, because of the small size of single cells. Unlike genes, metabolites cannot be amplified, and therefore metabolite analysis is another issue. To analyze such a tiny quantity of metabolites in a single cell, various techniques have been tried and developed. Especially in mass spectrometry, marked improvements in both detection sensitivity and ionization techniques have opened up the challenge for the analysis of metabolites in single cells. In this review, we discuss the method for metabolite detection at the level of single cells and recent advancements in technology.}, } @article {pmid22442339, year = {2012}, author = {Schönenberger, J and von Balthazar, M and Takahashi, M and Xiao, X and Crane, PR and Herendeen, PS}, title = {Glandulocalyx upatoiensis, a fossil flower of Ericales (Actinidiaceae/Clethraceae) from the Late Cretaceous (Santonian) of Georgia, USA.}, journal = {Annals of botany}, volume = {109}, number = {5}, pages = {921-936}, pmid = {22442339}, issn = {1095-8290}, mesh = {Actinidiaceae/*anatomy & histology/genetics ; *Biological Evolution ; Clethraceae/*anatomy & histology/genetics ; Flowers/*anatomy & histology/genetics/ultrastructure ; Fossils ; Fruit/anatomy & histology/genetics ; Georgia ; Magnoliopsida/*anatomy & histology/genetics ; Microscopy, Electron, Scanning ; Phylogeny ; Seeds/anatomy & histology/genetics ; }, abstract = {BACKGROUND AND AIMS: Ericales are a major group of extant asterid angiosperms that are well represented in the Late Cretaceous fossil record, mainly by flowers, fruits and seeds. Exceptionally well preserved fossil flowers, here described as Glandulocalyx upatoiensis gen. & sp. nov., from the Santonian of Georgia, USA, yield new detailed evidence of floral structure in one of these early members of Ericales and provide a secure basis for comparison with extant taxa.

METHODS: The floral structure of several fossil specimens was studied by scanning electron microscopy (SEM), light microscopy of microtome thin sections and synchrotron-radiation X-ray tomographic microscopy (SRXTM). For direct comparisons with flowers of extant Ericales, selected floral features of Actinidiaceae and Clethraceae were studied with SEM.

KEY RESULTS: Flowers of G. upatoiensis have five sepals with quincuncial aestivation, five free petals with quincuncial aestivation, 20-28 stamens arranged in a single series, extrorse anther orientation in the bud, ventral anther attachment and a tricarpellate, syncarpous ovary with three free styles and numerous small ovules on axile, protruding-diffuse and pendant placentae. The calyx is characterized by a conspicuous indumentum of large, densely arranged, multicellular and possibly glandular trichomes.

CONCLUSIONS: Comparison with extant taxa provides clear evidence for a relationship with core Ericales comprised of the extant families Actinidiaceae, Roridulaceae, Sarraceniaceae, Clethraceae, Cyrillaceae and Ericaceae. Within this group, the most marked similarities are with extant Actinidiaceae and, to a lesser degree, with Clethraceae. More detailed analyses of the relationships of Glandulocalyx and other Ericales from the Late Cretaceous will require an improved understanding of the morphological features that diagnose particular extant groups defined on the basis of molecular data.}, } @article {pmid22438907, year = {2012}, author = {Koch, BJ and Ryan, JF and Baxevanis, AD}, title = {The diversification of the LIM superclass at the base of the metazoa increased subcellular complexity and promoted multicellular specialization.}, journal = {PloS one}, volume = {7}, number = {3}, pages = {e33261}, pmid = {22438907}, issn = {1932-6203}, support = {//Intramural NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Bayes Theorem ; Evolution, Molecular ; Genetic Speciation ; Genetic Variation ; Humans ; LIM Domain Proteins/chemistry/*classification/*genetics ; Likelihood Functions ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Sequence Homology, Amino Acid ; }, abstract = {BACKGROUND: Throughout evolution, the LIM domain has been deployed in many different domain configurations, which has led to the formation of a large and distinct group of proteins. LIM proteins are involved in relaying stimuli received at the cell surface to the nucleus in order to regulate cell structure, motility, and division. Despite their fundamental roles in cellular processes and human disease, little is known about the evolution of the LIM superclass.

RESULTS: We have identified and characterized all known LIM domain-containing proteins in six metazoans and three non-metazoans. In addition, we performed a phylogenetic analysis on all LIM domains and, in the process, have identified a number of novel non-LIM domains and motifs in each of these proteins. Based on these results, we have formalized a classification system for LIM proteins, provided reasonable timing for class and family origin events; and identified lineage-specific loss events. Our analysis is the first detailed description of the full set of LIM proteins from the non-bilaterian species examined in this study.

CONCLUSION: Six of the 14 LIM classes originated in the stem lineage of the Metazoa. The expansion of the LIM superclass at the base of the Metazoa undoubtedly contributed to the increase in subcellular complexity required for the transition from a unicellular to multicellular lifestyle and, as such, was a critically important event in the history of animal multicellularity.}, } @article {pmid22434426, year = {2012}, author = {Chang, GS and Noegel, AA and Mavrich, TN and Müller, R and Tomsho, L and Ward, E and Felder, M and Jiang, C and Eichinger, L and Glöckner, G and Schuster, SC and Pugh, BF}, title = {Unusual combinatorial involvement of poly-A/T tracts in organizing genes and chromatin in Dictyostelium.}, journal = {Genome research}, volume = {22}, number = {6}, pages = {1098-1106}, pmid = {22434426}, issn = {1549-5469}, support = {R01 HG004160/HG/NHGRI NIH HHS/United States ; R56 HG004160/HG/NHGRI NIH HHS/United States ; HG004160/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Chromatin/*genetics ; Dictyostelium/*genetics ; Genes ; Nucleosomes/*genetics ; Phylogeny ; Poly A/*genetics ; Poly T/*genetics ; Promoter Regions, Genetic ; RNA Polymerase II/genetics ; TATA Box/genetics ; Transcription Factors/genetics ; }, abstract = {Dictyostelium discoideum is an amoebozoa that exists in both a free-living unicellular and a multicellular form. It is situated in a deep branch in the evolutionary tree and is particularly noteworthy in having a very A/T-rich genome. Dictyostelium provides an ideal system to examine the extreme to which nucleotide bias may be employed in organizing promoters, genes, and nucleosomes across a genome. We find that Dictyostelium genes are demarcated precisely at their 5' ends by poly-T tracts and precisely at their 3' ends by poly-A tracts. These tracts are also associated with nucleosome-free regions and are embedded with precisely positioned TATA boxes. Homo- and heteropolymeric tracts of A and T demarcate nucleosome border regions. Together, these findings reveal the presence of a variety of functionally distinct polymeric A/T elements. Strikingly, Dictyostelium chromatin may be organized in di-nucleosome units but is otherwise organized as in animals. This includes a +1 nucleosome in a position that predicts the presence of a paused RNA polymerase II. Indeed, we find a strong phylogenetic relationship between the presence of the NELF pausing factor and positioning of the +1 nucleosome. Pausing and +1 nucleosome positioning may have coevolved in animals.}, } @article {pmid22427962, year = {2012}, author = {Edlund, A and Ek, K and Breitholtz, M and Gorokhova, E}, title = {Antibiotic-induced change of bacterial communities associated with the copepod Nitocra spinipes.}, journal = {PloS one}, volume = {7}, number = {3}, pages = {e33107}, pmid = {22427962}, issn = {1932-6203}, mesh = {Animals ; Anti-Bacterial Agents/*toxicity ; Bacteria/*drug effects/genetics ; Base Sequence ; *Biodiversity ; Chromatography, Liquid ; Cloning, Molecular ; Copepoda/*drug effects/growth & development/*microbiology ; DNA Primers/genetics ; Likelihood Functions ; Models, Genetic ; Molecular Sequence Data ; Oceans and Seas ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Species Specificity ; Sweden ; *Symbiosis ; Tandem Mass Spectrometry ; Water Pollutants, Chemical/*toxicity ; }, abstract = {Environmental pressures, such as physical factors, diet and contaminants may affect interactions between microbial symbionts and their multicellular hosts. Despite obvious relevance, effects of antimicrobial contaminants on host-symbiont relations in non-target aquatic organisms are largely unknown. We show that exposure to antibiotics had negative effects on survival and juvenile development of the copepod Nitocra spinipes and caused significant alterations in copepod-associated bacterial communities. The significant positive correlations between indices of copepod development and bacterial diversity indicate that disruption of the microflora was likely to be an important factor behind retarded juvenile development in the experimental animals. Moreover, as evidenced by ribotype distribution in the bacterial clone libraries, the exposure to antibiotics caused a shift in dominance from Betaproteobacteria to Cardinium bacteria; the latter have been shown to cause reproductive manipulations in various terrestrial arthropods. Thus, in addition to providing evidence that the antibiotic-induced perturbation of the microbial community associates with reductions in fitness-related traits of the host, this study is the first record of a copepod serving as a host for endosymbiotic Cardinium. Taken together, our results suggest that (1) antimicrobial substances and possibly other stressors can affect micobiome and symbiont-mediated interactions in copepods and other hosts, and (2) Cardinium endosymbionts may occur in other copepods and affect reproduction of their hosts.}, } @article {pmid22426243, year = {2012}, author = {Buttigieg, J and Nurse, CA}, title = {Methodologies for studying peripheral O2 chemosensing: past, present, and future.}, journal = {Respiratory physiology & neurobiology}, volume = {181}, number = {2}, pages = {194-201}, doi = {10.1016/j.resp.2012.03.001}, pmid = {22426243}, issn = {1878-1519}, mesh = {Animals ; Chromatography, High Pressure Liquid/methods ; Dogs ; Electrochemical Techniques ; Electrophysiological Phenomena ; Humans ; Mice ; Models, Animal ; *Oxidative Phosphorylation ; Oxygen/analysis/*metabolism ; Patch-Clamp Techniques ; Rabbits ; Rats ; }, abstract = {The reduction of molecular oxygen in individual cells during the process of oxidative phosphorylation is central to oxidative metabolism and bioenergetic homeostasis. As such, any insufficiency in molecular oxygen availability represents a severe threat to sustained life. Thus, as with other similar multicellular organisms, the human body has evolved various peripheral chemosensory pathways that play a key role in sampling arterial PO2 values and initiating corrective reflex responses so as to maintain homeostasis. Research on these peripheral chemosensors can trace their origins to the cross circulation studies of Corneille Heymans in the early 20th century. Since then, it has become increasingly apparent that defects in these chemosensory pathways play a key role in various pathological conditions, e.g. Sudden Infant Death Syndrome (SIDS), and therefore an understanding of the underlying mechanisms is of critical importance. This review aims to discuss the advantages and disadvantages of the various experimental models employed in studying the mechanisms by which acute peripheral chemosensing occurs.}, } @article {pmid22411854, year = {2012}, author = {Moran, Y and Fredman, D and Szczesny, P and Grynberg, M and Technau, U}, title = {Recurrent horizontal transfer of bacterial toxin genes to eukaryotes.}, journal = {Molecular biology and evolution}, volume = {29}, number = {9}, pages = {2223-2230}, pmid = {22411854}, issn = {1537-1719}, support = {P 24858/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Amino Acid Sequence ; Animals ; Bacterial Toxins/chemistry/*genetics/metabolism ; Cnidaria/genetics/metabolism ; Eukaryota/*genetics/metabolism ; Evolution, Molecular ; Gene Expression ; *Gene Transfer, Horizontal ; Molecular Sequence Data ; Phylogeny ; Pore Forming Cytotoxic Proteins/chemistry/genetics/metabolism ; Sequence Alignment ; }, abstract = {In this work, we report likely recurrent horizontal (lateral) gene transfer events of genes encoding pore-forming toxins of the aerolysin family between species belonging to different kingdoms of life. Clustering based on pairwise similarity and phylogenetic analysis revealed several distinct aerolysin sequence groups, each containing proteins from multiple kingdoms of life. These results strongly support at least six independent transfer events between distantly related phyla in the evolutionary history of one protein family and discount selective retention of ancestral genes as a plausible explanation for this patchy phylogenetic distribution. We discuss the possible roles of these proteins and show evidence for a convergent new function in two extant species. We hypothesize that certain gene families are more likely to be maintained following horizontal gene transfer from commensal or pathogenic organism to its host if they 1) can function alone; and 2) are immediately beneficial for the ecology of the organism, as in the case of pore-forming toxins which can be utilized in multicellular organisms for defense and predation.}, } @article {pmid22409430, year = {2012}, author = {Tian, HF and Feng, JM and Wen, JF}, title = {The evolution of cardiolipin biosynthesis and maturation pathways and its implications for the evolution of eukaryotes.}, journal = {BMC evolutionary biology}, volume = {12}, number = {}, pages = {32}, pmid = {22409430}, issn = {1471-2148}, mesh = {Base Sequence ; Bayes Theorem ; Biosynthetic Pathways/*physiology ; Cardiolipins/*biosynthesis/*metabolism ; Eukaryota/*enzymology/genetics/metabolism ; *Evolution, Molecular ; Likelihood Functions ; Membrane Proteins/metabolism/*physiology ; Models, Genetic ; Molecular Sequence Data ; Phospholipases A2, Calcium-Independent/genetics/metabolism ; *Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; Transferases (Other Substituted Phosphate Groups)/metabolism/*physiology ; }, abstract = {BACKGROUND: Cardiolipin (CL) is an important component in mitochondrial inner and bacterial membranes. Its appearance in these two biomembranes has been considered as evidence of the endosymbiotic origin of mitochondria. But CL was reported to be synthesized through two distinct enzymes--CLS_cap and CLS_pld in eukaryotes and bacteria. Therefore, how the CL biosynthesis pathway evolved is an interesting question.

RESULTS: Phylogenetic distribution investigation of CL synthase (CLS) showed: most bacteria have CLS_pld pathway, but in partial bacteria including proteobacteria and actinobacteria CLS_cap pathway has already appeared; in eukaryotes, Supergroup Opisthokonta and Archaeplastida, and Subgroup Stramenopiles, which all contain multicellular organisms, possess CLS_cap pathway, while Supergroup Amoebozoa and Excavata and Subgroup Alveolata, which all consist exclusively of unicellular eukaryotes, bear CLS_pld pathway; amitochondriate protists in any supergroups have neither. Phylogenetic analysis indicated the CLS_cap in eukaryotes have the closest relationship with those of alpha proteobacteria, while the CLS_pld in eukaryotes share a common ancestor but have no close correlation with those of any particular bacteria.

CONCLUSIONS: The first eukaryote common ancestor (FECA) inherited the CLS_pld from its bacterial ancestor (e. g. the bacterial partner according to any of the hypotheses about eukaryote evolution); later, when the FECA evolved into the last eukaryote common ancestor (LECA), the endosymbiotic mitochondria (alpha proteobacteria) brought in CLS_cap, and then in some LECA individuals the CLS_cap substituted the CLS_pld, and these LECAs would evolve into the protist lineages from which multicellular eukaryotes could arise, while in the other LECAs the CLS_pld was retained and the CLS_cap was lost, and these LECAs would evolve into the protist lineages possessing CLS_pld. Besides, our work indicated CL maturation pathway arose after the emergence of eukaryotes probably through mechanisms such as duplication of other genes, and gene duplication and loss occurred frequently at different lineage levels, increasing the pathway diversity probably to fit the complicated cellular process in various cells. Our work also implies the classification putting Stramenopiles and Alveolata together to form Chromalveolata may be unreasonable; the absence of CL synthesis and maturation pathways in amitochondriate protists is most probably due to secondary loss.}, } @article {pmid22399377, year = {2012}, author = {Muñoz-Pinedo, C}, title = {Signaling pathways that regulate life and cell death: evolution of apoptosis in the context of self-defense.}, journal = {Advances in experimental medicine and biology}, volume = {738}, number = {}, pages = {124-143}, doi = {10.1007/978-1-4614-1680-7_8}, pmid = {22399377}, issn = {0065-2598}, support = {08-0621/AICR_/Worldwide Cancer Research/United Kingdom ; }, mesh = {Animals ; Apoptosis/*immunology ; *Biological Evolution ; Granzymes/immunology ; Humans ; Inhibitor of Apoptosis Proteins/immunology ; Mitochondria/immunology ; Receptors, Death Domain/immunology ; Signal Transduction/*immunology ; Stress, Physiological/*immunology ; }, abstract = {Programmed Cell Death is essential for the life cycle of many organisms. Cell death in multicellular organisms can occur as a consequence of massive damage (necrosis) or in a controlled form, through engagement of diverse biochemical programs. The best well known form of programmed cell death is apoptosis. Apoptosis occurs in animals as a consequence of a variety of stimuli including stress and social signals and it plays essential roles in morphogenesis and immune defense. The machinery of apoptosis is well conserved among animals and it is composed of caspases (the proteases which execute cell death), adapter proteins (caspase activators), Bcl-2 family proteins and Inhibitor of Apoptosis Proteins (IAPs). We will describe in this chapter the main apoptotic pathways in animals: the extrinsic (death receptor-mediated), the intrinsic/mitochondrial and the Granzyme B pathway. Other forms of non-apoptotic Programmed Cell Death which occur in animals will also be discussed. We will summarize the current knowledge about apoptotic-like and other forms of cell death in other organisms such as plants and protists.Additionally, we will discuss the hypothesis that apoptosis originated as part of a host defense mechanism. We will explore the similarities between the protein complexes which mediate apoptosis (apoptosomes) and complexes involved in immunity: inflammasomes. Additional functions of apoptotic proteins related to immune function will be summarized, in an effort to explore the evolutionary origins of cell death.}, } @article {pmid22399372, year = {2012}, author = {Misevic, GN and Misevic, N and Popescu, O}, title = {Glyconectin glycans as the self-assembling nano-molecular-velcrosystem mediating self-nonself recognition and adhesion implicated in evolution of multicellularity.}, journal = {Advances in experimental medicine and biology}, volume = {738}, number = {}, pages = {31-45}, doi = {10.1007/978-1-4614-1680-7_3}, pmid = {22399372}, issn = {0065-2598}, mesh = {Animals ; Cell Adhesion/physiology ; *Evolution, Molecular ; Glycoproteins/chemistry/genetics/*metabolism ; Peptidoglycan/chemistry/genetics/*metabolism ; Porifera/*physiology ; }, abstract = {The goal of this chapter is to make a specific contribution about glyconectin glycan as the self-assembling nano-molecular-velcro system mediating initial steps of self-nonself recognition and cell adhesion in Porifera, the first descendants of the most simple primordial multicellular organisms. Two original findings will be described: (i) Velcro like concept based on highly polyvalent and specific intermolecular glycan to glycan associations with extremely low affinity of the single binding site and (ii) novel structures of the large and newly emerging family of glyconectin like glycan molecules. The emphasis will be put on the interdisciplinary approach for studying structure to function relationship at the different size scale levels by combining the knowledge and technologies (instrumentation and methods) of physics, chemistry, biology and mathematics. Applying such strategy which is crossing the boundaries of different science disciplines enabled us to develop a new Atomic Force Microscopy (AFM) based nano-bio-technology and perform the first quantitative measurements of intermolecular binding forces at the single molecular level under physiological conditions. We propose that nano-velcro systems of the glyconectin glycans, which are the constituents on the cell surface that are the most exposed to the environment, were responsible for the molecular self-nonself recognition and adhesion processes that underpinned the emergence of multicellular life forms.}, } @article {pmid22399371, year = {2012}, author = {Nedelcu, AM}, title = {The evolution of self during the transition to multicellularity.}, journal = {Advances in experimental medicine and biology}, volume = {738}, number = {}, pages = {14-30}, doi = {10.1007/978-1-4614-1680-7_2}, pmid = {22399371}, issn = {0065-2598}, mesh = {*Biological Evolution ; Chlorophyta/*physiology ; }, abstract = {The notion of ' self' is intrinsically linked to the concepts of identity and individuality. During evolutionary transitions in individuality-such as, for instance, during the origin of the first cell, the origin of the eukaryotic cell and the origin of multicellular individuals-new kinds of individuals emerged from the interaction of previously independent entities. The question discussed here is: How can new types of individuals with qualities that cannot be reduced to the properties of their parts be created at a higher level? This question is addressed in the context of the transition to multicellularity and using the volvocine green algae-a group of closely related unicellular and multicellular species with various degrees of physiological and reproductive unity-as a model system. In this chapter, we review our framework to addressing the evolution of individuality during the transition to multicellularity, focusing on the reorganization of general life-traits and cellular processes and the cooption of environmentally-induced responses.}, } @article {pmid22394375, year = {2012}, author = {Dittami, SM and Gravot, A and Goulitquer, S and Rousvoal, S and Peters, AF and Bouchereau, A and Boyen, C and Tonon, T}, title = {Towards deciphering dynamic changes and evolutionary mechanisms involved in the adaptation to low salinities in Ectocarpus (brown algae).}, journal = {The Plant journal : for cell and molecular biology}, volume = {71}, number = {3}, pages = {366-377}, doi = {10.1111/j.1365-313X.2012.04982.x}, pmid = {22394375}, issn = {1365-313X}, mesh = {Amino Acids/metabolism ; Anions/metabolism ; Base Sequence ; *Biological Evolution ; Carbohydrate Metabolism ; Cations/metabolism ; Ecosystem ; Fatty Acids, Omega-3/metabolism ; Fresh Water ; Gene Expression Profiling ; Genome, Plant/genetics ; Metabolome/*physiology ; Molecular Sequence Data ; Nitrogen/metabolism ; Oligonucleotide Array Sequence Analysis ; Phaeophyceae/classification/genetics/*physiology ; Phylogeny ; Salinity ; Salt Tolerance/genetics/*physiology ; Sequence Analysis, DNA ; Transcriptome/*physiology ; }, abstract = {Colonizations of freshwater by marine species are rare events, and little information is known about the underlying mechanisms. Brown algae are an independent lineage of photosynthetic and multicellular organisms from which few species inhabit freshwater. As a marine alga that is also found in freshwater, Ectocarpus is of particular interest for studying the transition between these habitats. To gain insights into mechanisms of the transition, we examined salinity tolerance and adaptations to low salinities in a freshwater strain of Ectocarpus on physiological and molecular levels. We show that this isolate belongs to a widely distributed and highly stress-resistant clade, and differed from the genome-sequenced marine strain in its tolerance of low salinities. It also exhibited profound, but reversible, morphological, physiological, and transcriptomic changes when transferred to seawater. Although gene expression profiles were similar in both strains under identical conditions, metabolite and ion profiles differed strongly, the freshwater strain exhibiting e.g. higher cellular contents of amino acids and nitrate, higher contents of n-3 fatty acids, and lower intracellular mannitol and sodium concentrations. Moreover, several stress markers were noted in the freshwater isolate in seawater. This finding suggests that, while high stress tolerance and plasticity may be prerequisites for the colonization of freshwater, genomic alterations have occurred that produced permanent changes in the metabolite profiles to stabilize the transition.}, } @article {pmid22374462, year = {2012}, author = {Kailayangiri, S and Altvater, B and Meltzer, J and Pscherer, S and Luecke, A and Dierkes, C and Titze, U and Leuchte, K and Landmeier, S and Hotfilder, M and Dirksen, U and Hardes, J and Gosheger, G and Juergens, H and Rossig, C}, title = {The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting.}, journal = {British journal of cancer}, volume = {106}, number = {6}, pages = {1123-1133}, pmid = {22374462}, issn = {1532-1827}, mesh = {Adolescent ; Adult ; Animals ; Antigens, Surface/immunology/metabolism ; Bone Neoplasms/immunology/*metabolism/therapy ; Cell Line, Tumor ; Cell Proliferation ; Child ; Coculture Techniques ; Cytotoxicity, Immunologic ; Female ; Gangliosides/immunology/*metabolism ; Granzymes/metabolism ; Humans ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Transplantation ; Receptors, Antigen, T-Cell/biosynthesis/metabolism ; Recombinant Fusion Proteins/biosynthesis/metabolism ; Sarcoma, Ewing/immunology/*metabolism/therapy ; Single-Chain Antibodies/biosynthesis/metabolism ; Spheroids, Cellular/immunology ; T-Lymphocytes/immunology/metabolism/*transplantation ; Young Adult ; }, abstract = {BACKGROUND: Novel treatment strategies are needed to cure disseminated Ewing sarcoma. Primitive neuroectodermal features and a mesenchymal stem cell origin are both compatible with aberrant expression of the ganglioside antigen G(D2) and led us to explore G(D2) immune targeting in this cancer.

METHODS: We investigated G(D2) expression in Ewing sarcoma by immunofluorescence staining. We then assessed the antitumour activity of T cells expressing a chimeric antigen receptor specific for G(D2) against Ewing sarcoma in vitro and in vivo.

RESULTS: Surface G(D2) was detected in 10 out of 10 Ewing sarcoma cell lines and 3 out of 3 primary cell cultures. Moreover, diagnostic biopsies from 12 of 14 patients had uniform G(D2) expression. T cells specifically modified to express the G(D2)-specific chimeric receptor 14. G2a-28ζ efficiently interacted with Ewing sarcoma cells, resulting in antigen-specific secretion of cytokines. Moreover, chimeric receptor gene-modified T cells from healthy donors and from a patient exerted potent, G(D2)-specific cytolytic responses to allogeneic and autologous Ewing sarcoma, including tumour cells grown as multicellular, anchorage-independent spheres. G(D2)-specific T cells further had activity against Ewing sarcoma xenografts.

CONCLUSION: G(D2) surface expression is a characteristic of Ewing sarcomas and provides a suitable target antigen for immunotherapeutic strategies to eradicate micrometastatic cells and prevent relapse in high-risk disease.}, } @article {pmid22360486, year = {2012}, author = {Makepeace, BL and Martin, C and Turner, JD and Specht, S}, title = {Granulocytes in helminth infection -- who is calling the shots?.}, journal = {Current medicinal chemistry}, volume = {19}, number = {10}, pages = {1567-1586}, pmid = {22360486}, issn = {1875-533X}, support = {242131//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Granulocytes/*immunology/*parasitology ; Helminthiasis/*immunology/parasitology ; Helminths/*immunology ; *Host-Parasite Interactions ; Humans ; Intestinal Diseases, Parasitic/*immunology/parasitology ; }, abstract = {Helminths are parasitic organisms that can be broadly described as "worms" due to their elongated body plan, but which otherwise differ in shape, development, migratory routes and the predilection site of the adults and larvae. They are divided into three major groups: trematodes (flukes), which are leaf-shaped, hermaphroditic (except for blood flukes) flatworms with oral and ventral suckers; cestodes (tapeworms), which are segmented, hermaphroditic flatworms that inhabit the intestinal lumen; and nematodes (roundworms), which are dioecious, cylindrical parasites that inhabit intestinal and peripheral tissue sites. Helminths exhibit a sublime co-evolution with the host's immune system that has enabled them to successfully colonize almost all multicellular species present in every geographical environment, including over two billion humans. In the face of this challenge, the host immune system has evolved to strike a delicate balance between attempts to neutralize the infectious assault versus limitation of damage to host tissues. Among the most important cell types during helminthic invasion are granulocytes: eosinophils, neutrophils and basophils. Depending on the specific context, these leukocytes may have pivotal roles in host protection, immunopathology, or facilitation of helminth establishment. This review provides an overview of the function of granulocytes in helminthic infections.}, } @article {pmid22357931, year = {2012}, author = {Kawabe, Y and Weening, KE and Marquay-Markiewicz, J and Schaap, P}, title = {Evolution of self-organisation in Dictyostelia by adaptation of a non-selective phosphodiesterase and a matrix component for regulated cAMP degradation.}, journal = {Development (Cambridge, England)}, volume = {139}, number = {7}, pages = {1336-1345}, pmid = {22357931}, issn = {1477-9129}, support = {BB/G020426/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/D013453/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 090276/WT_/Wellcome Trust/United Kingdom ; BB/E016308/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {3',5'-Cyclic-AMP Phosphodiesterases/genetics/*physiology ; Cloning, Molecular ; Cyclic AMP/metabolism ; Cysteine/chemistry ; Developmental Biology/methods ; Dictyostelium ; Gene Expression Regulation, Developmental ; Genetic Complementation Test ; Models, Biological ; Phenotype ; Phylogeny ; Promoter Regions, Genetic ; Protein Isoforms ; Protein Structure, Tertiary ; }, abstract = {Dictyostelium discoideum amoebas coordinate aggregation and morphogenesis by secreting cyclic adenosine monophosphate (cAMP) pulses that propagate as waves through fields of cells and multicellular structures. To retrace how this mechanism for self-organisation evolved, we studied the origin of the cAMP phosphodiesterase PdsA and its inhibitor PdiA, which are essential for cAMP wave propagation. D. discoideum and other species that use cAMP to aggregate reside in group 4 of the four major groups of Dictyostelia. We found that groups 1-3 express a non-specific, low affinity orthologue of PdsA, which gained cAMP selectivity and increased 200-fold in affinity in group 4. A low affinity group 3 PdsA only partially restored aggregation of a D. discoideum pdsA-null mutant, but was more effective at restoring fruiting body morphogenesis. Deletion of a group 2 PdsA gene resulted in disruption of fruiting body morphogenesis, but left aggregation unaffected. Together, these results show that groups 1-3 use a low affinity PdsA for morphogenesis that is neither suited nor required for aggregation. PdiA belongs to a family of matrix proteins that are present in all Dictyostelia and consist mainly of cysteine-rich repeats. However, in its current form with several extensively modified repeats, PdiA is only present in group 4. PdiA is essential for initiating spiral cAMP waves, which, by organising large territories, generate the large fruiting structures that characterise group 4. We conclude that efficient cAMP-mediated aggregation in group 4 evolved by recruitment and adaptation of a non-selective phosphodiesterase and a matrix component into a system for regulated cAMP degradation.}, } @article {pmid22353663, year = {2011}, author = {Zaina, S and Lund, G}, title = {Epigenetics: a tool to understand diet-related cardiovascular risk?.}, journal = {Journal of nutrigenetics and nutrigenomics}, volume = {4}, number = {5}, pages = {261-274}, doi = {10.1159/000334584}, pmid = {22353663}, issn = {1661-6758}, mesh = {Animals ; Atherosclerosis/genetics ; Cardiovascular Diseases/*genetics ; DNA/metabolism ; DNA Methylation ; *Diet ; *Epigenesis, Genetic ; *Epigenomics ; Genetic Variation ; Humans ; Models, Biological ; Models, Genetic ; Nutritional Sciences ; Risk Factors ; Transcription, Genetic ; }, abstract = {Cardiovascular disease (CVD) is a leading cause of mortality and is projected to hold its grim record as developing countries increase their wealth. Since specific nutritional habits are important risk factors for CVD, it is imperative to understand how ingredients of risk-associated diets convert a healthy cellular transcriptional program into a pathological one. Epigenetics has enriched our view of the genome by showing that DNA-associated regulatory proteins and RNAs, together with chemical modifications of the DNA itself, determine which parts of the DNA chain are transcribed or silent in a given phase of a cell's life. This complex biological entity--the epigenome--accounts for the enormous phenotypic diversity within a multicellular organism despite its unicellular origin. Crucially, the epigenome can be modified by diet and other exogenous factors, thus suggesting that epigenetic mechanisms might underlie pathological responses to CVD risk factors. Here, we will review the current knowledge of epigenetic mechanisms in diet-gene interactions and propose ways in which epigenetics might clarify the impact of genetic variants on CVD risk.}, } @article {pmid22328715, year = {2012}, author = {Yang, D and Zhong, F and Li, D and Liu, Z and Wei, H and Jiang, Y and He, F}, title = {General trends in the utilization of structural factors contributing to biological complexity.}, journal = {Molecular biology and evolution}, volume = {29}, number = {8}, pages = {1957-1968}, doi = {10.1093/molbev/mss064}, pmid = {22328715}, issn = {1537-1719}, mesh = {Animals ; Databases, Protein ; *Evolution, Molecular ; Genome/genetics ; Humans ; Protein Structure, Tertiary ; Proteins/*chemistry/*genetics ; Proteome/genetics/metabolism ; Species Specificity ; }, abstract = {During evolution, proteins containing newly emerged domains and the increasing proportion of multidomain proteins in the full genome-encoded proteome (GEP) have substantially contributed to increasing biological complexity. However, it is not known how these two potential structural factors are preferentially utilized at given physiological states. Here, we classified proteins according to domain number and domain age and explored the general trends across species for the utilization of proteins from GEP to various certain-state proteomes (CSPs, i.e., all the proteins expressed at certain physiological states). We found that multidomain proteins or only older domain-containing proteins are significantly overrepresented in CSPs compared with GEP, which is a trend that is stronger in multicellular organisms than in unicellular organisms. Interestingly, the strengths of overrepresentation decreased during evolution of multicellular eukaryotes. When comparing across CSPs, we found that multidomain proteins are more overrepresented in complex tissues than in simpler ones, whereas no difference among proteins with domains of different ages is evident between complex and simple tissues. Thus, biological complexity under certain conditions is more significantly realized by diverse domain organization than by the emergence of new types of domain. In addition, we found that multidomain or only older domain-containing proteins tend to evolve slowly and generally are under stronger purifying selection, which may partly result from their general overrepresentation trends in CSPs.}, } @article {pmid22326743, year = {2012}, author = {Cai, X}, title = {Evolutionary genomics reveals the premetazoan origin of opposite gating polarity in animal-type voltage-gated ion channels.}, journal = {Genomics}, volume = {99}, number = {4}, pages = {241-245}, doi = {10.1016/j.ygeno.2012.01.007}, pmid = {22326743}, issn = {1089-8646}, mesh = {Amino Acid Sequence ; Animals ; Biophysics ; Calcium Channels/*genetics ; Choanoflagellata/*genetics ; Cyclic Nucleotide-Gated Cation Channels/genetics ; *Evolution, Molecular ; Genomics/methods ; Molecular Sequence Data ; Nucleotides, Cyclic/genetics ; Phylogeny ; Potassium Channels, Voltage-Gated/*genetics ; Protein Structure, Tertiary/genetics ; Sequence Alignment ; Sodium Channels/*genetics ; }, abstract = {Electrical signaling in animals ensures the rapid and accurate transmission of information, often carried by voltage-gated Na(+), Ca(2+) and K(+) channels that are activated by membrane depolarization. In heart and neurons, a distinct type of ion channel called the hyperpolarization-activated, cyclic nucleotide-regulated (HCN) channel is activated by membrane hyperpolarization. Recent genomic studies have revealed that animal-type voltage-gated Na(+) channels (Liebeskind BJ, et al. 2011.