@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}, doi = {10.1080/15476286.2024.2417152}, pmid = {39508203}, issn = {1555-8584}, 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 {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}, doi = {10.1371/journal.pone.0306676}, 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 {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 = {}, doi = {10.1093/molbev/msae200}, pmid = {39431545}, issn = {1537-1719}, support = {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 {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 = {Humans ; *Microscopy/methods/trends/instrumentation ; Animals ; Photons ; }, 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 {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 = {}, number = {}, pages = {}, pmid = {39443791}, issn = {1476-4687}, 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 {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 ; }, 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}, doi = {10.1098/rspb.2024.1562}, 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 {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 = {}, doi = {10.1242/dev.202997}, 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 {pmid39378102, year = {2024}, author = {Laporte, D and Sagot, I}, title = {Microtubule reorganization and quiescence: an intertwined relationship.}, journal = {Physiology (Bethesda, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1152/physiol.00036.2024}, pmid = {39378102}, issn = {1548-9221}, support = {ANR-21-CE13-0023-01//Agence Nationale de la Recherche (ANR)/ ; }, abstract = {Quiescence is operationally defined as a reversible proliferation arrest. This cellular state is central for both organism development and homeostasis, its dysregulation causing 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 at 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 {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 {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}, doi = {10.1016/j.tig.2024.06.003}, pmid = {38971670}, issn = {0168-9525}, 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 {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 = {}, doi = {10.1242/bio.061720}, 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 {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 {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 {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 {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 {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 {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 {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}, 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 {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 {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 {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}, 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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 ; Benchmarking ; 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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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}, doi = {10.1146/annurev-genet-033123-095833}, 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 ; }, 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 {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 {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 {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 {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}, 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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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}, 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 {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 {pmid9990861, year = {1998}, author = {Girault, JA and Labesse, G and Mornon, JP and Callebaut, I}, title = {Janus kinases and focal adhesion kinases play in the 4.1 band: a superfamily of band 4.1 domains important for cell structure and signal transduction.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {4}, number = {12}, pages = {751-769}, pmid = {9990861}, issn = {1076-1551}, mesh = {Amino Acid Sequence ; Animals ; Cell Adhesion Molecules/*chemistry/genetics/*metabolism ; Cytoskeletal Proteins/chemistry ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Humans ; Membrane Proteins/*chemistry ; Molecular Sequence Data ; *Neuropeptides ; Phylogeny ; Protein-Tyrosine Kinases/*chemistry/genetics/*metabolism ; *Signal Transduction ; }, abstract = {The band 4.1 domain was first identified in the red blood cell protein band 4.1, and subsequently in ezrin, radixin, and moesin (ERM proteins) and other proteins, including tumor suppressor merlin/schwannomin, talin, unconventional myosins VIIa and X, and protein tyrosine phosphatases. Recently, the presence of a structurally related domain has been demonstrated in the N-terminal region of two groups of tyrosine kinases: the focal adhesion kinases (FAK) and the Janus kinases (JAK). Additional proteins containing the 4.1/JEF (JAK, ERM, FAK) domain include plant kinesin-like calmodulin-binding proteins (KCBP) and a number of uncharacterized open reading frames identified by systematic DNA sequencing. Phylogenetic analysis of amino acid sequences suggests that band 4.1/JEF domains can be grouped in several families that have probably diverged early during evolution. Hydrophobic cluster analysis indicates that the band 4.1/JEF domains might consist of a duplicated module of approximately 140 residues and a central hinge region. A conserved property of the domain is its capacity to bind to the membrane-proximal region of the C-terminal cytoplasmic tail of proteins with a single transmembrane segment. Many proteins with band 4.1/JEF domains undergo regulated intra- or intermolecular homotypic interactions. Additional properties common to band 4.1/JEF domains of several proteins are binding of phosphoinositides and regulation by GTPases of the Rho family. Many proteins with band 4. 1/JEF domains are associated with the actin-based cytoskeleton and are enriched at points of contact with other cells or the extracellular matrix, from which they can exert control over cell growth. Thus, proteins with band 4.1/JEF domain are at the crossroads between cytoskeletal organization and signal transduction in multicellular organisms. Their importance is underlined by the variety of diseases that can result from their mutations.}, } @article {pmid9949831, year = {1998}, author = {Green, DR and Amarante-Mendes, GP}, title = {The point of no return: mitochondria, caspases, and the commitment to cell death.}, journal = {Results and problems in cell differentiation}, volume = {24}, number = {}, pages = {45-61}, doi = {10.1007/978-3-540-69185-3_3}, pmid = {9949831}, issn = {0080-1844}, mesh = {Animals ; *Apoptosis/genetics ; *Caspases ; Humans ; *Mitochondria ; Models, Biological ; Oncogenes ; }, abstract = {Apoptosis is a specialized mode of cell death finely regulated at the molecular level and conserved throughout evolution. In many instances during normal development or in order to maintain the homeostasis of a multicellular organism, a strategic intracellular program is initiated ensuring the fate of unwanted cells. Interference with this program has been implicated in many pathologies, particularly in cancer and autoimmune diseases. What is most important, from the organism's point of view, is that the dismissal of the outcast cells is accomplished serenely, i.e., the dying cells resign their existence without causing an inflammatory reaction. Therefore, the ability to manipulate the cell death machinery is an obvious goal of medical research. Here, we debate the idea of the point-of-no-return and propose models for the role of "initiator" and "executioner" caspases in the death program. We argue that, in many circumstances, the cells are committed to die before the execution phase of apoptosis starts. This commitment event is coordinated by the mitochondria and can be blocked by anti-apoptotic oncogenes.}, } @article {pmid9880549, year = {1999}, author = {Hallmann, A}, title = {Enzymes in the extracellular matrix of Volvox: an inducible, calcium-dependent phosphatase with a modular composition.}, journal = {The Journal of biological chemistry}, volume = {274}, number = {3}, pages = {1691-1697}, doi = {10.1074/jbc.274.3.1691}, pmid = {9880549}, issn = {0021-9258}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Western ; Calcium/*metabolism ; Chlorophyta/*enzymology ; Enzyme Induction ; Enzyme Inhibitors/pharmacology ; Extracellular Matrix/*enzymology ; Glycosylation ; Molecular Sequence Data ; Organophosphorus Compounds/metabolism ; Phosphoric Monoester Hydrolases/*biosynthesis/chemistry/*genetics/isolation & purification/*metabolism ; Protein Conformation ; Rabbits ; Substrate Specificity ; }, abstract = {The volvocine algae provide the unique opportunity for exploring development of an extracellular matrix. Volvox is the most advanced member of this family and represents the simplest multicellular organism, with differentiated cells, a complete division of labor, and a complex extracellular matrix, which serves structural and enzymatic functions. In Volvox carteri a glycosylated extracellular phosphatase was identified, which is partially released from the extracellular matrix into the growth medium. The phosphatase is synthesized in response to inorganic phosphate starvation and is strictly calcium-dependent. The metalloenzyme has been purified to homogeneity and characterized. Its gene and cDNA have been cloned. Comparisons of genomic and cDNA sequences revealed an extremely intron-rich gene (32 introns). With an apparent molecular mass of 160 kDa the Volvox extracellular phosphatase is the largest phosphatase cloned, with no sequence similarity to any other phosphatase. This enzyme exhibits a modular composition. There are two large domains and a small one. The large domains are highly homologous to each other and therefore most likely originated from gene duplication and fusion. At least one EF-hand motif for calcium binding was identified in this extracellular protein. Volvox extracellular phosphatase is the first calcium-dependent extracellular phosphatase to be cloned.}, } @article {pmid9818725, year = {1998}, author = {Rayner, TF and Stark, MJ}, title = {Identification and characterization of the KlCMD1 gene encoding Kluyveromyces lactis calmodulin.}, journal = {Yeast (Chichester, England)}, volume = {14}, number = {9}, pages = {869-875}, doi = {10.1002/(SICI)1097-0061(19980630)14:9<869::AID-YEA278>3.0.CO;2-U}, pmid = {9818725}, issn = {0749-503X}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Base Sequence ; Calmodulin/chemistry/*genetics ; Genes, Fungal ; Humans ; Kluyveromyces/*genetics ; Molecular Sequence Data ; Phylogeny ; Saccharomyces cerevisiae/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The KlCMD1 gene was isolated from a Kluyveromyces lactis genomic library as a suppressor of the Saccharomyces cerevisiae temperature-sensitive mutant spc110-124, an allele previously shown to be suppressed by elevated copy number of the S. cerevisiae calmodulin gene CMD1. The KlCMD1 gene encodes a polypeptide which is 95% identical to S. cerevisiae calmodulin and 55% identical to calmodulin from Schizosaccharomyces pombe. Complementation of a S. cerevisiae cdm1 deletion mutant by KlCMD1 demonstrates that this gene encodes a functional calmodulin homologue. Multiple sequence alignment of calmodulins from yeast and multicellular eukaryotes shows that the K. lactis and S. cerevisiae calmodulins are considerably more closely related to each other than to other calmodulins, most of which have four functional Ca2+-binding EF hand domains. Thus like its S. cerevisiae counterpart Cmd1p, the KlCMD1 product is predicted to form only three Ca2+-binding motifs.}, } @article {pmid9797404, year = {1998}, author = {Bhattacharya, D and Weber, K and An, SS and Berning-Koch, W}, title = {Actin phylogeny identifies Mesostigma viride as a flagellate ancestor of the land plants.}, journal = {Journal of molecular evolution}, volume = {47}, number = {5}, pages = {544-550}, doi = {10.1007/pl00006410}, pmid = {9797404}, issn = {0022-2844}, mesh = {Actins/*genetics ; Base Sequence ; Chlorophyta/*genetics ; DNA Primers ; DNA, Complementary ; Molecular Sequence Data ; *Phylogeny ; }, abstract = {Green algae and land plants trace their evolutionary history to a unique common ancestor. This "green lineage" is phylogenetically subdivided into two distinct assemblages, the Chlorophyta and the Streptophyta. The Chlorophyta includes the Chlorophyceae, Trebouxiophyceae, Ulvophyceae, and Prasinopohyceae, whereas the Streptophyta includes the Charophyceae plus the bryophytes, ferns, and all other multicellular land plants (Embryophyta). The Prasinophyceae is believed to contain the earliest divergences within the green lineage. Phylogenetic analyses using rDNA sequences identify the prasinophytes as a paraphyletic taxon that diverges at the base of the Chlorophyta. rDNA analyses, however, provide ambiguous results regarding the identity of the flagellate ancestor of the Streptophyta. We have sequenced the actin-encoding cDNAs from Scherffelia dubia (Prasinophyceae), Coleochaete scutata, Spirogyra sp. (Charophyceae), and the single-copy actin gene from Mesostigma viride (Prasinophyceae). Phylogenetic analyses show Mesostigma to be the earliest divergence within the Streptophyta and provide direct evidence for a scaly, biflagellate, unicellular ancestor for this lineage. This result is supported by the existence of two conserved actin-coding region introns (positions 20-3, 152-1), and one intron in the 5'-untranslated region of the actin gene shared by Mesostigma and the embryophytes.}, } @article {pmid9795100, year = {1998}, author = {Ikuta, T and Sogawa, N and Ariga, H and Ikemura, T and Matsumoto, K}, title = {Structural analysis of mouse tenascin-X: evolutionary aspects of reduplication of FNIII repeats in the tenascin gene family.}, journal = {Gene}, volume = {217}, number = {1-2}, pages = {1-13}, doi = {10.1016/s0378-1119(98)00355-2}, pmid = {9795100}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Cell Line ; Conserved Sequence ; Crosses, Genetic ; *Evolution, Molecular ; Exons ; *Gene Duplication ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Molecular Sequence Data ; *Phylogeny ; Protein Isoforms/chemistry/genetics ; Repetitive Sequences, Nucleic Acid ; Sequence Alignment ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Stem Cells/metabolism ; Tenascin/chemistry/*genetics ; Transcription Factors/metabolism ; }, abstract = {Tenascin-X (TNX) is an extracellular matrix glycoprotein involved in both primary structural functions and modulating cellular activities in multicellular organisms. We determined the 67977bp nucleotide sequence of the entire mouse tenascin-X (Tnx) gene, which also includes the last exon of Creb-rp and Cyp21. We compared it with the orthologous human locus. Conservation of both position and orientation of the three functionally unrelated genes at this position was found. Comparison also revealed that introns 1, 4 and 6 of Tnx are highly conserved between species. The sequence showed that mouse Tnx contains 43 exons separated by 42 introns. The deduced amino-acid sequence (4114 residues) revealed that mouse Tnx has a primary structure characteristic of tenascins, which consists of a signal peptide and four heptad repeats followed by 18.5 epidermal growth factor-like (EGF) repeats, 31 fibronectin type III-like (FNIII) repeats, and a region homologous to fibrinogen. cDNA clones generated by alternative splicing of eight consecutive FNIII repeats (M15-M22) as well as a proximal FNIII repeat (M3) were also identified. The FNIII motifs that were subject to alternative splicing were assigned to the group of recently reduplicated FNIII repeats because they have a high level of amino-acid sequence similarity. We also analyzed the evolution of FNIII repeats in TNX.}, } @article {pmid9766962, year = {1998}, author = {Huai, H and Woodruff, RC}, title = {Clusters of new identical mutants and the fate of underdominant mutations.}, journal = {Genetica}, volume = {102-103}, number = {1-6}, pages = {489-505}, pmid = {9766962}, issn = {0016-6707}, mesh = {Alleles ; Animals ; *Biological Evolution ; Cluster Analysis ; Genetics, Population ; Genotype ; Germ Cells/physiology ; Heterozygote ; Humans ; Mathematical Computing ; Meiosis ; Mitosis ; *Models, Genetic ; *Mutation ; Probability ; Selection, Genetic ; }, abstract = {Given favorable environmental and demographic conditions, premeiotic clusters of identical mutations can produce a broad distribution of the initial frequency of underdominant alleles. Because of these clusters, new underdominant mutations may not necessarily be as rare in a population as previously assumed. The fixation of underdominant mutations, especially those with low heterozygous fitness, is increased when mutations appear in a cluster due to a genetic change that occurred before germline differentiation. Most restrictions on the fixation of underdominant mutations in a single population, such as strong genetic drift, weak selection against mutant heterozygotes, isolated population structure, inbreeding, meiotic drive, and selection in favor of mutant homozygotes can be relaxed or even dropped. Instead, the fate of strong underdominant mutations is determined mainly by ecological and genetic factors that affect the cluster size distribution of new premeiotic mutations. Accumulation of reproductive isolation by the fixation of underdominant mutations becomes more feasible with clusters, and mutation is not always the weakest force during this evolutionary process. The large mean and variance of reproductive success in many multicellular species make it possible that even underdominant mutations with very low heterozygous fitness could contribute substantially to reproductive isolation.}, } @article {pmid9766961, year = {1998}, author = {Furusawa, M and Doi, H}, title = {Asymmetrical DNA replication promotes evolution: disparity theory of evolution.}, journal = {Genetica}, volume = {102-103}, number = {1-6}, pages = {333-347}, pmid = {9766961}, issn = {0016-6707}, mesh = {Animals ; *Biological Evolution ; DNA/chemistry ; *DNA Replication ; Genetic Variation ; Genome ; Humans ; *Models, Genetic ; *Mutagenesis ; *Mutation ; Nucleic Acid Conformation ; Replication Origin ; }, abstract = {Heredity is guaranteed by faithful DNA replication whereas evolution depends upon errors accompanying DNA replication. This contradiction existing between heredity and evolution cannot be resolved in an individual organism, but only in terms of a population, in that a delicate balance exists between wild type and variants in a population which is necessary for the survival of the species. Namely, there seems to be a key in the mechanism of DNA replication to solve some problems of evolution. DNA is replicated semiconservatively using the leading and discontinuous lagging strands. According to our 'disparity theory of evolution', the existence of a sufficient fidelity difference between the leading and lagging strands is advantageous in terms of evolution, because the diversity of genotypes is enlarged but genotypes that have occurred in the past are guaranteed. In theory, by artificially increasing the fidelity difference between the leading and lagging strand ('disparity mutator'), evolution is accelerated while avoiding the extinction of the population. Using a disparity mutator, we should be able to improve living things, including multicellular organisms, within constrained conditions. A double-stranded algorithm, which mimics the structure and replication manner of DNA, is promising for solving optimization problems.}, } @article {pmid9714748, year = {1998}, author = {Cetkovic, H and Müller, IM and Müller, WE and Gamulin, V}, title = {Characterization and phylogenetic analysis of a cDNA encoding the Fes/FER related, non-receptor protein-tyrosine kinase in the marine sponge sycon raphanus.}, journal = {Gene}, volume = {216}, number = {1}, pages = {77-84}, doi = {10.1016/s0378-1119(98)00320-5}, pmid = {9714748}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Animals ; DNA, Complementary/chemistry/*genetics ; Molecular Sequence Data ; Phylogeny ; Porifera/chemistry/*enzymology/*genetics ; Protein-Tyrosine Kinases/genetics ; Proto-Oncogene Proteins/*genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {In search of ancient versions of phylogenetically conserved genes/proteins, which are typical for multicellular animals, we have decided to analyse marine sponges (Porifera), the most ancient and most primitive metazoan organisms. We report here the complete nucleotide sequence of Sycon raphanus cDNA coding for a 879 aa long protein, which displays high overall similarity in primary structure and organization of domains with non-receptor tyrosine kinases (TKs) from the Fes/FER family. The encoded protein, which we named Fes/FER_SR, has a highly conserved, 260 aa long tyrosine kinase domain at the C-terminus. Amino-terminal to the catalytic domain is an 85 aa long SH2 domain. The N-terminus is over 500 aa long and displays homology only with N-terminal domains of protein-tyrosine kinases (PTKs) from the Fes/FER family. Mammalian Fes/FER proteins show around 58% overall homology with Fes/FER_SR (identity and similarity) and lower homology was found with Drosophila melanogaster Fps (FER) protein (49%). Homologies in TK, SH2 and N-terminal domains are on average 78%, 65% and 49%, respectively. Fes/FER_SR shows next to best homology with the Abl family of non-receptor PTKs, while Src-related PTKs from the fresh-water sponge Spongilla lacustris are related only distantly to Fes/FER_SR. Phylogenetic analysis shows that the S. raphanus TK is indeed the most ancient known member of the Fes/FER family of non-receptor PTKs. The role of these PTKs in signal transduction in higher animals is still enigmatic; they are present in the nucleus as well as in the cytoplasm and FER is found in all cell types examined. The function of Fes/FER_SR in sponge, the most primitive multicellular animal which lacks specialized organ systems, remains to be elucidated.}, } @article {pmid9694578, year = {1998}, author = {Reincke, M}, title = {Mutations in adrenocortical tumors.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {30}, number = {6-7}, pages = {447-455}, doi = {10.1055/s-2007-978913}, pmid = {9694578}, issn = {0018-5043}, mesh = {Adrenal Cortex Neoplasms/*genetics ; Cytogenetics ; Genes, Tumor Suppressor ; Humans ; *Mutation ; Neoplastic Syndromes, Hereditary/genetics ; Oncogenes ; }, abstract = {Silent and incidentally detected adrenocortical neoplasms are the most frequent abnormality of the adrenal cortex. The prevalence of these lesions in the general population is around 1%, increases with age and reaches 6% in the seventh decade of life. Primary adrenocortical carcinoma, on the other hand, a highly malignant tumor, is rare with an incidence of 1.7 cases per million per year. Recent progress has been achieved in the understanding of adrenocortical tumorigenesis by mapping and identification of genes responsible for hereditary tumor syndromes like the Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Carney complex and the Multiple Endocrine Neoplasia Type I. Investigation of the clonal composition of adrenal tumors demonstrates that adrenal carcinomas are generally monoclonal, whereas adrenal adenoma may be polyclonal in approximately 25% of cases. These adenomas may have a multicellular origin under the putative action of extra-adrenal and local growth factors. Oncogenes and tumor suppressor genes involved in adrenal carcinomas include mutations in the p53 tumor suppressor gene and rearrangements of the chromosomal locus 11 p15.5 associated with IGF II hyperexpression. Constitutive activation of the ACTH receptor-G protein-cAMP signal cascade does not play a role in adrenal tumor formation. Conversely, deletions of the ACTH receptor gene have been recently found in undifferentiated adenomas and in aggressive adrenocortical carcinomas. This indicates that the signaling pathways responsible for adrenocortical tumor formation are different from that of other endocrine neoplasms like pituitary and thyroid adenomas.}, } @article {pmid9608055, year = {1998}, author = {Kruse, M and Leys, SP and Müller, IM and Müller, WE}, title = {Phylogenetic position of the Hexactinellida within the phylum Porifera based on the amino acid sequence of the protein kinase C from Rhabdocalyptus dawsoni.}, journal = {Journal of molecular evolution}, volume = {46}, number = {6}, pages = {721-728}, doi = {10.1007/pl00006353}, pmid = {9608055}, issn = {0022-2844}, mesh = {*Amino Acid Sequence ; Animals ; Catalysis ; Cloning, Molecular ; DNA, Complementary/isolation & purification ; Evolution, Molecular ; Molecular Sequence Data ; *Phylogeny ; Porifera/*enzymology/*genetics ; Protein Kinase C/chemistry/*genetics ; Protein Structure, Tertiary ; Sequence Analysis ; }, abstract = {Recent analyses of genes encoding proteins typical for multicellularity, especially adhesion molecules and receptors, favor the conclusion that all metazoan phyla, including the phylum Porifera (sponges), are of monophyletic origin. However, none of these data includes cDNA encoding a protein from the sponge class Hexactinellida. We have now isolated and characterized the cDNA encoding a protein kinase C, belonging to the C subfamily (cPKC), from the hexactinellid sponge Rhabdocalyptus dawsoni. The two conserved regions, the regulatory part with the pseudosubstrate site, the two zinc fingers, and the C2 domain, as well as the catalytic domain were used for phylogenetic analyses. Sequence alignment and construction of a phylogenetic tree from the catalytic domains revealed that the yeast Saccharomyces cerevisiae and the protozoan Trypanosoma brucei are at the base of the tree, while the hexactinellid R. dawsoni branches off first among the metazoan sequences; the other two classes of the Porifera, the Calcarea (the sequence from Sycon raphanus was used) and the Demospongiae (sequences from Geodia cydonium and Suberites domuncula were used), branch off later. The statistically robust tree also shows that the two cPKC sequences from the higher invertebrates Drosophila melanogaster and Lytechinus pictus are most closely related to the calcareous sponge. This finding was also confirmed by comparing the regulatory part of the kinase gene. We suggest, that (i) within the phylum Porifera, the class Hexactinellida diverged first from a common ancestor to the Calcarea and the Demospongiae, which both appeared later, and (ii) the higher invertebrates are more closely related to the calcareous sponges.}, } @article {pmid9520435, year = {1998}, author = {Maleszka, R and de Couet, HG and Miklos, GL}, title = {Data transferability from model organisms to human beings: insights from the functional genomics of the flightless region of Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {95}, number = {7}, pages = {3731-3736}, pmid = {9520435}, issn = {0027-8424}, mesh = {Animals ; *Biological Evolution ; Caenorhabditis elegans/genetics ; Drosophila/*genetics ; Gene Deletion ; *Genes, Insect ; Genome, Fungal ; *Genome, Human ; Humans ; *Models, Genetic ; Molecular Sequence Data ; Saccharomyces cerevisiae/genetics ; }, abstract = {At what biological levels are data from single-celled organisms akin to a Rosetta stone for multicellular ones? To examine this question, we characterized a saturation-mutagenized 67-kb region of the Drosophila genome by gene deletions, transgenic rescues, phenotypic dissections, genomic and cDNA sequencing, bio-informatic analysis, reverse transcription-PCR studies, and evolutionary comparisons. Data analysis using cDNA/genomic DNA alignments and bio-informatic algorithms revealed 12 different predicted proteins, most of which are absent from bacterial databases, half of which are absent from Saccharomyces cerevisiae, and nearly all of which have relatives in Caenorhabditis elegans and Homo sapiens. Gene order is not evolutionarily conserved; the closest relatives of these genes are scattered throughout the yeast, nematode, and human genomes. Most gene expression is pleiotropic, and deletion studies reveal that a morphological phenotype is seldom observed when these genes are removed from the genome. These data pinpoint some general bottlenecks in functional genomics, and they reveal the acute emerging difficulties with data transferability above the levels of genes and proteins, especially with complex human phenotypes. At these higher levels the Rosetta stone analogy has almost no applicability. However, newer transgenic technologies in Drosophila and Mus, combined with coherency pattern analyses of gene networks, and synthetic neural modeling, offer insights into organismal function. We conclude that industrially scaled robogenomics in model organisms will have great impact if it can be realistically linked to epigenetic analyses of human variation and to phenotypic analyses of human diseases in different genetic backgrounds.}, } @article {pmid9569639, year = {1998}, author = {Benassi, V and Frey, F and Carton, Y}, title = {A new specific gene for wasp cellular immune resistance in Drosophila.}, journal = {Heredity}, volume = {80 (Pt 3)}, number = {}, pages = {347-352}, doi = {10.1046/j.1365-2540.1998.00303.x}, pmid = {9569639}, issn = {0018-067X}, mesh = {Animals ; Crosses, Genetic ; Drosophila melanogaster/*genetics/*immunology/parasitology ; Female ; Male ; Models, Genetic ; Sex Chromosomes ; Wasps/immunology/*pathogenicity ; }, abstract = {Larvae of Drosophila melanogaster produce a haemocytic reaction against eggs of the parasitoid, Asobara tabida, which leads to the formation of a multicellular capsule surrounding the foreign object. The same phenomenon was observed with the parasitoid, Leptopilina boulardi. Concerning the resistance of D. melanogaster to L. boulardi, a single major segregating locus with the resistant allele dominant to the susceptible one was found. The host strain susceptible to this parasitoid species was found to be highly immune reactive against the eggs of A. tabida. The inheritance of the capacity to encapsulate A. tabida was analysed by comparing reciprocal crosses made using inbred resistant and susceptible parental strains. We conclude that differences in the encapsulation capacity are inherited autosomally, with the reactive phenotype showing complete dominance over the non-reactive one. These data suggest the existence of two independent gene systems, each being concerned with the recognition of one species only.}, } @article {pmid9562423, year = {1998}, author = {Gomez-Escobar, N and Lewis, E and Maizels, RM}, title = {A novel member of the transforming growth factor-beta (TGF-beta) superfamily from the filarial nematodes Brugia malayi and B. pahangi.}, journal = {Experimental parasitology}, volume = {88}, number = {3}, pages = {200-209}, doi = {10.1006/expr.1998.4248}, pmid = {9562423}, issn = {0014-4894}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Brugia malayi/*chemistry/genetics ; Brugia pahangi/*chemistry/genetics ; DNA, Helminth/chemistry/isolation & purification ; Exons ; Female ; Gene Expression ; Male ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; RNA, Messenger/analysis ; Sequence Alignment ; Transforming Growth Factor beta/chemistry/*genetics ; }, abstract = {Transforming growth factor-beta (TGF-beta) superfamily genes encode products controlling pattern formation, cell differentiation, and immune-mediated inflammation. Members of this superfamily are known in multicellular organisms from mammals to the model nematode Caenorhabditis elegans. Using PCR with oligonucleotides complementary to highly conserved motifs in the TGF-beta superfamily, we first isolated a genomic clone from the filarial nematode Brugia malayi. This gene, termed Bm-tgh-1 (TGF-beta homolog-1), spans 2.5 kb of genomic DNA and contains seven exons. Transcripts of this gene are poorly represented in cDNA libraries, but a full-length cDNA was isolated by RACE from B. pahangi (Bp-tgh-1). The tgh-1 genes from the two species are >98% identical at the nucleotide and amino acid levels, differing at 18/1576 base pairs and 5/428 amino acids; all nonsynonymous substitutions are in the long N-terminal propeptide. They show a high level of similarity throughout all seven exons to a C. elegans gene on cosmid T25F10. Homology to other members of the TGF-beta superfamily is restricted to the C-terminal domain which contains the mature active protein. Key features shared with other members of the superfamily include the tetrabasic proteolytic cleavage site to release an active C-terminal peptide, seven cysteines arrayed in identical fashion, and conserved sequence motifs. tgh-1 is most similar to the BMP-1 subfamily involved in developmental signaling in nematodes, insects, and vertebrates. RT-PCR on first-strand cDNA from both Brugia species, with primers specific to the 3' end, showed that tgh-1 is not expressed in the microfilarial stage, but is detectable in the mosquito-derived infective larvae and is maximal in maturing parasites around the time of molting in the mammalian host. Adult parasites show a relatively low level of expression. The identification of tgh-1, and its preferential expression in developing parasites, suggests that it may be involved in key developmental events in the complex filarial life cycle.}, } @article {pmid9507443, year = {1998}, author = {Lee, TH}, title = {Cytokine networks in the pathogenesis of bronchial asthma: implications for therapy.}, journal = {Journal of the Royal College of Physicians of London}, volume = {32}, number = {1}, pages = {56-64}, pmid = {9507443}, issn = {0035-8819}, mesh = {Animals ; Asthma/*etiology/metabolism/*therapy ; Cytokines/genetics/metabolism/*physiology ; Humans ; }, abstract = {Bronchial asthma is characterised by a multicellular inflammatory process in the airways. The bronchial inflammation is orchestrated by a network of cytokines and growth factors which includes those encoded by the GM-CSF/IL-4/IL-5 gene cluster on chromosome 5. Their cellular origins are diverse and include both inflammatory and structural cells in the airways. The efficacy of glucocorticoids in the therapy of bronchial asthma may include the ability to disrupt these cytokine networks. The failure of glucocorticoids to provide benefit in some asthmatic patients may be caused by an excess of pro-inflammatory transcription factors which sequester the glucocorticoid receptor (GR), thereby preventing it from exerting its anti-inflammatory effects. Progress is being made in the elucidation of the molecular regulation of the transcription of TH2 cytokine genes. These novel insights may provide future strategies for therapeutic intervention in asthma.}, } @article {pmid9484905, year = {1997}, author = {Baker, ME}, title = {Steroid receptor phylogeny and vertebrate origins.}, journal = {Molecular and cellular endocrinology}, volume = {135}, number = {2}, pages = {101-107}, doi = {10.1016/s0303-7207(97)00207-4}, pmid = {9484905}, issn = {0303-7207}, mesh = {Animals ; Evolution, Molecular ; Humans ; Phylogeny ; Receptors, Steroid/*genetics ; Vertebrates/*genetics ; }, abstract = {Vertebrates appear about 500 million years ago in the fossil record. This is only 25-50 million years after the great explosion of multicellular invertebrate body plans in the early Cambrian. On a geological time scale, this interval is a 'blink of an eye', suggesting that the evolution of regulatory genes is likely to be important in the origins of vertebrates. Here we present evidence for a role of steroid receptors in this process based on a phylogenetic analysis suggesting that receptors for androgens, glucocorticoids, mineralocorticoids, and progesterone evolved from an ancestral steroid receptor gene by two successive duplications over a brief time that could have coincided with the origins of vertebrates. Moreover, the duplications of these steroid receptors may be additional evidence for the two duplications on a genome-scale that have been proposed to be important in the evolution of vertebrates. The two successive duplications of steroid receptor genes and their subsequent sequence divergence leading to steroid-specific receptors that regulate growth, development, reproduction and homeostasis in vertebrates may have been one of the events important in vertebrate survival after the Cambrian during global extinctions that occurred about 440 and 370 million years ago.}, } @article {pmid9458335, year = {1998}, author = {Trosko, JE and Ruch, RJ}, title = {Cell-cell communication in carcinogenesis.}, journal = {Frontiers in bioscience : a journal and virtual library}, volume = {3}, number = {}, pages = {d208-36}, doi = {10.2741/a275}, pmid = {9458335}, issn = {1093-9946}, support = {CA21104/CA/NCI NIH HHS/United States ; CA57612/CA/NCI NIH HHS/United States ; P42 ES04911-09/ES/NIEHS NIH HHS/United States ; }, mesh = {Cell Communication/*physiology ; Connexins/genetics ; Gap Junctions/*physiology ; Humans ; Models, Biological ; Mutation ; Neoplasms/genetics/*physiopathology/therapy ; Oncogene Proteins/genetics ; Tumor Suppressor Proteins/genetics ; }, abstract = {To explain the complex carcinogenic process by which a single normal cell in human beings can be converted to an invasive and metastatic cancer cell, a number of experimental findings, epidemiological observations and their associated hypothesis/theories have been integrated in this review. All cancers have been generally viewed as the result of a disruption of the homeostatic regulation of a cell's ability to respond appropriately to extra-cellular signals of the body which trigger intra-cellular signal transducting mechanisms which modulate gap junctional intercellular communication between the cells within a tissue. Normal homeostatic control of these three forms of cell communication determines whether: (a) the cell remains quiescent (Go); (b) enters into the cell proliferation phase; (c) is induced to differentiate; (d) is committed to apoptose; or (e) if it is already differentiated, it can adaptively respond. During the evolution from single cell organisms to multicellular organisms, new cellular/biological functions appeared, namely, the control of cell proliferation ("contact inhibition"), the appearance of the process of differentiation from committed stem cells of the various tissues and the need for programmed cell death or apoptosis. Interestingly, cancer cells have been characterized as cells: (a) having been derived from a stem-like cell; (b) without their ability to control cell growth or without the ability to contact inhibit; (c) which can not terminally differentiate under normal conditions; and (d) having altered ability to apoptosis under normal conditions. During that evolutionary transition from the single cell organism to the multicellular organism, many new genes appeared to accompany these new cellular functions. One of these new genes was the gene coding for a membrane associated protein channel (the gap junction) which between coupled cells, allowed the passive transfer on ions and small molecular weight molecules. A family of over a dozen of these highly evolutionarily-conserved genes (the connexin genes) coded for the connexin proteins. A hexameric unit of these connexins in one cell (a connexon) couples with a corresponding connexon in a contiguous cell to join the cytoplasms. This serves to synchronize either the metabolic or electrotonic functions of cells within a tissue. Most normal cells within solid tissues have functional gap junctional intercellular communication (GJIC) (exceptions are free-standing cells such as red blood cells, neutrophils, and several, if not all, the stem cells). On the other hand, the cancer cells of solid tissues appear to have either dysfunctional homologous or heterologous GJIC. Therefore, among the many differences between a cancer cell and its normal parental cell, the carcinogenic process involves the transition from a normal, GJIC-competent cell to one that is defective in GJIC. The review examines how GJIC can be either transiently or stably modulated by endogenous or exogenesis chemicals or by oncogenes and tumor suppressor genes at the transcriptional, translational, or posttranslational levels. It also uses the gap junction as the biological structure to facilitate cellular/tissue homeostasis to be the integrator for the "stem cell" theory, "disease of differentiation theory", "initiation/promotion/progression" concepts, nature and nurture concept of carcinogenesis, the mutation/ epigenetic theories of carcinogenesis, and the oncogene/ tumor suppressor gene theories of carcinogenesis. From this background, implications to cancer prevention and cancer therapy are generated.}, } @article {pmid9428609, year = {1997}, author = {Tazi, J and Rossi, F and Labourier, E and Gallouzi, I and Brunel, C and Antoine, E}, title = {DNA topoisomerase I: customs officer at the border between DNA and RNA worlds?.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {75}, number = {11-12}, pages = {786-800}, doi = {10.1007/s001090050168}, pmid = {9428609}, issn = {0946-2716}, mesh = {Animals ; DNA Topoisomerases, Type I/genetics/*physiology ; Evolution, Molecular ; Humans ; Models, Chemical ; *RNA Splicing ; }, abstract = {DNA topoisomerase I is required for the normal development of multicellular organisms, probably because it plays a role in controlling gene activity, in addition to its function in relieving tortional stress during DNA replication and transcription. The discovery of DNA topoisomerase I as a specific kinase that phosphorylates serine-arginine rich (SR) splicing factors may provide new insights into their precise function in regulating gene expression. It is clear that the splicing factors phosphorylated by DNA topoisomerase I can modulate gene expression by changing the splicing pattern of structural genes. Studies of the splicing mechanism suggest that the phosphorylation of serine residues of SR proteins contribute to their activity. As this phosphorylation can be accomplished by several kinases, it remains to be determined whether phosphorylation by DNA topoisomerase I protein kinase is the limiting step in regulating this process. The availability of specific inhibitors of DNA topoisomerase I, structurally related to the alkaloid camptothecin, have made it possible to address this question experimentally. These inhibitors, which hold great promise as antineoplastic drugs, lead to specific inhibition of SR protein phosphorylation in cultured cells. This observation will hopefully lead to improved understanding of the mechanism by which these drugs act at cellular level.}, } @article {pmid9315669, year = {1997}, author = {Kooistra, R and Vreeken, K and Zonneveld, JB and de Jong, A and Eeken, JC and Osgood, CJ and Buerstedde, JM and Lohman, PH and Pastink, A}, title = {The Drosophila melanogaster RAD54 homolog, DmRAD54, is involved in the repair of radiation damage and recombination.}, journal = {Molecular and cellular biology}, volume = {17}, number = {10}, pages = {6097-6104}, pmid = {9315669}, issn = {0270-7306}, mesh = {Amino Acid Sequence ; Animals ; DNA Damage ; DNA Helicases ; DNA Repair/*physiology ; DNA-Binding Proteins/*genetics/physiology ; *Drosophila Proteins ; Drosophila melanogaster/embryology/*genetics/growth & development ; *Egg Proteins ; Eye/embryology ; Female ; Gene Expression Regulation, Developmental ; Genes, Insect/genetics/physiology ; Larva/drug effects/radiation effects ; Male ; Methyl Methanesulfonate/pharmacology ; Mitosis/genetics ; Molecular Sequence Data ; Mutagenesis ; Mutagens/pharmacology ; RNA, Messenger/analysis ; Recombination, Genetic/*physiology ; Sequence Homology, Amino Acid ; }, abstract = {The RAD54 gene of Saccharomyces cerevisiae plays a crucial role in recombinational repair of double-strand breaks in DNA. Here the isolation and functional characterization of the RAD54 homolog of the fruit fly Drosophila melanogaster, DmRAD54, are described. The putative Dmrad54 protein displays 46 to 57% identity to its homologs from yeast and mammals. DmRAD54 RNA was detected at all stages of fly development, but an increased level was observed in early embryos and ovarian tissue. To determine the function of DmRAD54, a null mutant was isolated by random mutagenesis. DmRADS4-deficient flies develop normally, but the females are sterile. Early development appears normal, but the eggs do not hatch, indicating an essential role for DmRAD54 in development. The larvae of mutant flies are highly sensitive to X rays and methyl methanesulfonate. Moreover, this mutant is defective in X-ray-induced mitotic recombination as measured by a somatic mutation and recombination test. These phenotypes are consistent with a defect in the repair of double-strand breaks and imply that the RAD54 gene is crucial in repair and recombination in a multicellular organism. The results also indicate that the recombinational repair pathway is functionally conserved in evolution.}, } @article {pmid9288632, year = {1997}, author = {Ko, HM and Choi, C and Park, CS and Juhng, SW}, title = {Analysis of clonality by X chromosome inactivation in uterine cervix cancer.}, journal = {Journal of Korean medical science}, volume = {12}, number = {4}, pages = {322-326}, doi = {10.3346/jkms.1997.12.4.322}, pmid = {9288632}, issn = {1011-8934}, mesh = {Carcinoma in Situ/*genetics/pathology ; Carcinoma, Squamous Cell/*genetics/pathology ; Disease Progression ; *Dosage Compensation, Genetic ; Female ; Humans ; Neoplasm Invasiveness ; Paraffin Embedding ; Polymerase Chain Reaction/*methods ; Receptors, Androgen/*genetics ; Uterine Cervical Neoplasms/*genetics/pathology ; }, abstract = {The determination of a unicellular or a multicellular origin of a tumor is an important due for understanding its etiology. To investigate this issue, we performed clonality assay of cervix cancer using polymerase chain reaction based on highly polymorphic locus of the androgen receptor gene, in which methylation of DNA correlates with inactivation of X chromosome. DNA samples were obtained from formalin-fixed, paraffin-embedded tissue of 20 invasive epidermoid carcinomas and 10 carcinoma in situ. Seven of ten carcinoma in situ, heterozygous for the androgen receptor locus, were monoclonal pattern. Among twenty invasive epidermoid carcinomas, eighteen of which showed heterozygous, twelve were monoclonal pattern and six were polyclonal pattern. We conclude that carcinoma in situ arises from a single cell. In invasive epidermoid carcinoma, most cases were monoclonal, although some cases were polyclonal. These suggest that invasive carcinoma of the cervix does not always arise from a single cell, but may arise from several cells with different mechanisms.}, } @article {pmid9223263, year = {1997}, author = {Ayala, FJ}, title = {Vagaries of the molecular clock.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {94}, number = {15}, pages = {7776-7783}, pmid = {9223263}, issn = {0027-8424}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Glycerolphosphate Dehydrogenase/*genetics ; Species Specificity ; Superoxide Dismutase/*genetics ; }, abstract = {The hypothesis of the molecular evolutionary clock asserts that informational macromolecules (i.e., proteins and nucleic acids) evolve at rates that are constant through time and for different lineages. The clock hypothesis has been extremely powerful for determining evolutionary events of the remote past for which the fossil and other evidence is lacking or insufficient. I review the evolution of two genes, Gpdh and Sod. In fruit flies, the encoded glycerol-3-phosphate dehydrogenase (GPDH) protein evolves at a rate of 1.1 x 10(-10) amino acid replacements per site per year when Drosophila species are compared that diverged within the last 55 million years (My), but a much faster rate of approximately 4.5 x 10(-10) replacements per site per year when comparisons are made between mammals (approximately 70 My) or Dipteran families (approximately 100 My), animal phyla (approximately 650 My), or multicellular kingdoms (approximately 1100 My). The rate of superoxide dismutase (SOD) evolution is very fast between Drosophila species (16.2 x 10(-10) replacements per site per year) and remains the same between mammals (17.2) or Dipteran families (15.9), but it becomes much slower between animal phyla (5.3) and still slower between the three kingdoms (3.3). If we assume a molecular clock and use the Drosophila rate for estimating the divergence of remote organisms, GPDH yields estimates of 2,500 My for the divergence between the animal phyla (occurred approximately 650 My) and 3,990 My for the divergence of the kingdoms (occurred approximately 1,100 My). At the other extreme, SOD yields divergence times of 211 My and 224 My for the animal phyla and the kingdoms, respectively. It remains unsettled how often proteins evolve in such erratic fashion as GPDH and SOD.}, } @article {pmid9204761, year = {1997}, author = {Wilson, PG and Borisy, GG}, title = {Evolution of the multi-tubulin hypothesis.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {19}, number = {6}, pages = {451-454}, doi = {10.1002/bies.950190603}, pmid = {9204761}, issn = {0265-9247}, mesh = {Animals ; Evolution, Molecular ; Humans ; Microtubules/*chemistry/genetics/ultrastructure ; Tubulin/*chemistry/genetics/ultrastructure ; }, abstract = {Microtubules are organized into diverse cellular structures in multicellular organisms. How is such diversity generated? Although highly conserved overall, variable regions within alpha- and beta-tubulins show divergence from other alpha- and beta-tubulins in the same species, but show conservation among different species. Such conservation raises the question of whether diversity in tubulin structure mediates diversity in microtubule organization. Recent studies probing the function of beta-tubulin isotypes in axonemes of insects suggest that tubulin structure, through interactions with extrinsic proteins, can direct the architecture and supramolecular organization of microtubules.}, } @article {pmid9180159, year = {1997}, author = {Thorsen, F and Visted, T and Lehtolainen, P and Ylä-Herttuala, S and Bjerkvig, R}, title = {Release of replication-deficient retroviruses from a packaging cell line: interaction with glioma tumor spheroids in vitro.}, journal = {International journal of cancer}, volume = {71}, number = {5}, pages = {874-880}, doi = {10.1002/(sici)1097-0215(19970529)71:5<874::aid-ijc28>3.0.co;2-6}, pmid = {9180159}, issn = {0020-7136}, mesh = {Animals ; Brain/cytology ; Cell Aggregation ; Cell Line ; Cell Survival ; Coculture Techniques ; DNA/analysis ; Escherichia coli/genetics ; Flow Cytometry ; Glioma/*metabolism ; Humans ; Mice ; Rabbits ; Rats ; Retroviridae/*physiology ; Spheroids, Cellular/*metabolism ; *Transfection ; Tumor Cells, Cultured ; *Virus Replication ; beta-Galactosidase/genetics ; }, abstract = {The present study describes how various growth conditions affect gene expression and virus production from a retroviral packaging cell line (Liz 9), grown as monolayers and as multicellular spheroids. In addition, to study the direct interaction between packaging cells and tumor tissue of glioma origin, Liz 9 spheroids were confronted with tumor spheroids derived from a human glioma cell line, GaMg. The results show a progressive gene transfer into the tumor tissue, with 9% transfection efficacy after 5 days of co-culture. In comparison, no gene transfer was observed when the Liz 9 spheroids were confronted with normal brain-cell aggregates. The Liz 9 spheroids established from early-passage cultures (passages 7-14) showed limited growth during 28 days, whereas those initiated from late-passage monolayer cultures (passages 39-49) showed extensive growth. Flow-cytometric DNA profiles of monolayers and of spheroids indicated no difference in cell-cycle distribution or ploidy between early and late passages. A cell-viability assay using scanning confocal microscopy revealed mostly viable cells in the Liz 9 spheroids, with only a few dead cells scattered within the structures. The lacZ-gene expression was maintained in early- and in late-passage cultures. In comparison, in Liz 9 early-passage monolayers, the virus titer was 3.1 x 10(4) +/- 0.4 x 10(4) CFU/ml, whereas no virus titer was found in late-passage cultures. The virus titer from the Liz 9 spheroids was found to be between 10(3) and 10(4) CFU/ml. It is concluded that the virus production from packaging cells may vary, depending on passage number and tissue-culture conditions. In the present study, this is demonstrated by a complete loss in virus titer during prolonged culture of packaging cells. In addition, the 3-dimensional confrontation system described allows direct visualization of how packaging cells interact with tumor tissue. Thus, the co-culture system represents a model for studying the efficiency of packaging cells in transfecting heterogeneous tumor tissue in vitro.}, } @article {pmid9194029, year = {1997}, author = {Inoue, S and Takaoka, K and Endo, T and Mizuno, S and Ogawa, Y and Yoshida, M and Ohnuma, T}, title = {In vitro confirmation of newly established lung cancer cell lines using flow cytometry and multicellular tumor spheroids.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {17}, number = {1}, pages = {85-101}, doi = {10.1016/s0169-5002(97)00652-1}, pmid = {9194029}, issn = {0169-5002}, mesh = {Antigens, Neoplasm/analysis ; Carcinoembryonic Antigen/analysis ; Carcinoma, Squamous Cell/immunology ; Flow Cytometry/*methods ; Histocytochemistry ; Humans ; Immunohistochemistry ; Karyotyping ; Lung/chemistry/immunology/pathology ; Lung Neoplasms/diagnosis/genetics/*pathology ; Microscopy, Electron ; Phosphopyruvate Hydratase/analysis ; Photography ; Spheroids, Cellular/*pathology ; Tumor Cells, Cultured/cytology/*pathology/ultrastructure ; }, abstract = {We report on a simplified method of cytomorphological in vitro confirmation of newly established lung cancer cell lines by using multicellular tumor spheroids (MTS) and flow cytometry (FCM). Eleven cell lines were established from 11 patients with lung cancer. The MTS were produced by culturing cells in agar-coated dish. Cytomorphological studies were made using smears of crushed MTS and frozen sections of MTS. The MTS were fixed doubly with paraformaldehyde and osmic acid for scanning and transmission electron microscopy. Bivariate fluorescence of fluorescein isothyocyanate (FITC, tumor associated antigen, TAA) and propidium iodide (DNA) were measured by FCM. The MTS grew anchorage-independently. Cytopathological and electron microscopic findings of MTS were similar to those of the original clinical specimens. The DNA index and TAA were useful in evaluating the presence or absence of contamination by cells of non-tumor origin. The new cell lines satisfied a minimum of four conditions to confirm their establishment: (a) they originated from humans, (b) they were cytomorphologically identified with specimens from primary lesions, (c) they showed tumorigenicity, and (d) they were free from contamination by cells of different origin. From these findings, the establishment of new cell lines can be confirmed in vitro by using MTS and FCM.}, } @article {pmid9140449, year = {1997}, author = {Heim, S and Teixeira, MR and Dietrich, CU and Pandis, N}, title = {Cytogenetic polyclonality in tumors of the breast.}, journal = {Cancer genetics and cytogenetics}, volume = {95}, number = {1}, pages = {16-19}, doi = {10.1016/s0165-4608(96)00322-6}, pmid = {9140449}, issn = {0165-4608}, mesh = {Breast Neoplasms/*genetics ; *Chromosome Aberrations ; Female ; Humans ; }, abstract = {Cytogenetically unrelated clones are found in half of all carcinomas of the breast and also in the epithelial fraction of many benign breast tumors. The chromosomal aberrations thus detected are clearly nonrandom and appear to be the same as those often seen in other tumors as sole karyotypic anomalies. Clonal chromosome abnormalities are not found in histologically normal breast tissue. Cytogenetically unrelated clones may be found in both primary tumors and secondary lesions, be it within the same breast (multifocal carcinomas), in the contralateral breast (bilateral carcinomas), or in lymph node or other metastases. The aberrations are present in topologically separate tumor domains and may confer on the cells that harbor them different types of cancer-specific behavior, such as the ability to metastasize and invade locally. Whereas the available evidence thus strongly indicates that the cells carrying clonal karyotypic aberrations all are part of the neoplastic parenchyma, it is less certain whether cytogenetic polyclonality actually signifies a multicellular tumor origin, although we think that this is the explanation that best accommodates the cytogenetic data. But even if it should eventually be shown that the seemingly unrelated clones have some submicroscopic tumorigenic mutation in common, the observed karyotypic heterogeneity is remarkable and goes far beyond what one has become accustomed to from most other tumor types. To understand how the various clones interact during mammary carcinogenesis will be a major task in future breast cancer research.}, } @article {pmid9100369, year = {1997}, author = {Pancer, Z and Kruse, M and Müller, I and Müller, WE}, title = {On the origin of Metazoan adhesion receptors: cloning of integrin alpha subunit from the sponge Geodia cydonium.}, journal = {Molecular biology and evolution}, volume = {14}, number = {4}, pages = {391-398}, doi = {10.1093/oxfordjournals.molbev.a025775}, pmid = {9100369}, issn = {0737-4038}, mesh = {Animals ; Base Sequence ; Cloning, Molecular ; DNA, Complementary ; Integrins/chemistry/*genetics ; Membrane Glycoproteins ; Membrane Proteins/*genetics ; Molecular Sequence Data ; Platelet Glycoprotein GPIb-IX Complex ; Porifera/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {Integrins are prominent receptors known from vertebrates and the higher phyla of invertebrates. Until now, no evidence has been provided for the existence of integrins in the lowest Metazoa, the sponges (Porifera). We have isolated and characterized a cDNA clone encoding the alpha subunit of integrin from the marine sponge Geodia cydonium (GCINTEG). The open reading frame encodes a polypeptide of 1,086 residues (118 kDa). The intracellular domain features the sequence Tyr-Phe-x-Gly-Phe-Phe-x-Arg, which is different in one residue from the characteristic consensus pattern for integrin alpha subunits. We conclude that sponges, the oldest multicellular animal phylum, already utilize the structural elements which are required for a tuned and controlled interaction among cells, and between cells and the extracellular matrix.}, } @article {pmid9147129, year = {1997}, author = {Ramponi, G and Stefani, M}, title = {Structural, catalytic, and functional properties of low M(r), phosphotyrosine protein phosphatases. Evidence of a long evolutionary history.}, journal = {The international journal of biochemistry & cell biology}, volume = {29}, number = {2}, pages = {279-292}, doi = {10.1016/s1357-2725(96)00109-4}, pmid = {9147129}, issn = {1357-2725}, mesh = {Amino Acid Sequence ; Animals ; Cattle ; Evolution, Molecular ; Humans ; Molecular Sequence Data ; *Protein Tyrosine Phosphatases/chemistry/genetics/metabolism ; }, abstract = {The PTPase family comprises a number of classes of functionally and structurally unrelated enzymes; it represents an important component of the protein-tyrosine phosphorylation/dephosphorylation machinery, which regulates the level of tyrosine phosphorylation of a number of intracellular proteins. A wealth of recently reported data indicates growing interest in a group of PTPases characterized by low (near 20 kDa) molecular weight and high sequence homology (low M(r), PTPases). These enzymes are present in organisms spanning the philogenetic scale, from prokaryotes to yeast and mammals. The sequence homology of the low M(r), PTPases with other classes of PTPases is limited to the active site sequence CXXXXXRS/T, containing the Cys and Arg residues involved in enzyme catalysis found in all PTPases. The X-ray structural data of three enzymes belonging to different classes of PTPases, a bovine liver low M(r), PTPase isoenzyme, PTP1B, and Yersinia PTPase, show that all these enzymes maintain the same active site and overall catalytic mechanism, though displaying different chain foldings and topologies, supporting convergent evolution. Limited findings on the in vivo function of the low M(r), PTPases are presently available; however, an involvement of the mammalian enzymes in the membrane growth factor receptor signal transduction is emerging. The distribution of these enzymes in philogenetically distant unicellular and multicellular organisms supports their participation in important cell functions.}, } @article {pmid9107136, year = {1996}, author = {Wakahara, M}, title = {Heterochrony and neotenic salamanders: possible clues for understanding the animal development and evolution.}, journal = {Zoological science}, volume = {13}, number = {6}, pages = {765-776}, doi = {10.2108/zsj.13.765}, pmid = {9107136}, issn = {0289-0003}, mesh = {Animals ; *Biological Evolution ; Gene Expression Regulation, Developmental ; Models, Genetic ; Urodela/*genetics/growth & development ; }, abstract = {A synthesis of developmental genetics with evolutionary genetics is now making possible to understand significant evolutionary changes in multicellular organisms. The key concept for unifying the two must be heterochrony. Heterochrony causes evolutionary modifications due to changes in timing and/or rate of development. The heterochrony is conventionally categorized into three patterns as neoteny (retardation in somatic development), progenesis (acceleration in gonadal development), and direct development (acceleration in somatic development, resulting in lack of larval or tadpole stages). A lot of species showing neoteny are known in urodeles, but not in anurans. Neotenic urodeles are also divided into three categories; permanent or obligate, "inducible" obligate and facultative neotenies. Hynobius retardatus, a specific population of which had been reported to show neoteny but is believed to be extinct at present, has become to be used for experimental analysis of heterochronic expression of several adult characters during its ontogeny. Gonadal maturation and a transition of globin subunits from larval to adult types have been shown to occur independently on the morphological metamorphosis in H. retardatus. Mechanisms underlying the heterochrony, including morphogenetic clock, heterochronic genes in Drosophila and C. elegans, temporal colinearity in Hox gene complex in mice, and atavistic transformation induced by altered expression of Hox genes are discussed in terms of current molecular biology.}, } @article {pmid8995053, year = {1996}, author = {Marinets, A and Müller, M and Johnson, PJ and Kulda, J and Scheiner, O and Wiedermann, G and Duchêne, M}, title = {The sequence and organization of the core histone H3 and H4 genes in the early branching amitochondriate protist Trichomonas vaginalis.}, journal = {Journal of molecular evolution}, volume = {43}, number = {6}, pages = {563-571}, pmid = {8995053}, issn = {0022-2844}, support = {AI11942/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Blotting, Southern ; Cloning, Molecular ; DNA, Complementary/genetics ; Genome ; Histones/*genetics/physiology ; Molecular Sequence Data ; *Phylogeny ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Trichomonas vaginalis/*genetics/physiology ; }, abstract = {Among the unicellular protists, several of which are parasitic, some of the most divergent eukaryotic species are found. The evolutionary distances between protists are so large that even slowly evolving proteins like histones are strongly divergent. In this study we isolated cDNA and genomic histone H3 and H4 clones from Trichomonas vaginalis. Two histone H3 and three histone H4 genes were detected on three genomic clones with one complete H3 and two complete H4 sequences. H3 and H4 genes were divergently transcribed with very short intergenic regions of only 194 bp, which contained T. vaginalis-specific as well as histone-specific putative promoter elements. Southern blot analysis showed that there may be several more histone gene pairs. The two complete histone H4 genes were different on the nucleotide level but encoded the same amino acid sequence. Comparison of the amino acid sequences of the T. vaginalis H3 and H4 histones with sequences from animals, fungi, and plants as well as other protists revealed a significant divergence not only from the sequences in multicellular organisms but especially from the sequences in other protists like Entamoeba histolytica, Trypanosoma cruzi, and Leishmania infantum.}, } @article {pmid9119208, year = {1996}, author = {Altukhov, IuP and Korochkin, LI and Rychkov, IuG}, title = {[Hereditary biochemical diversity in the processes of evolution and individual development].}, journal = {Genetika}, volume = {32}, number = {11}, pages = {1450-1473}, pmid = {9119208}, issn = {0016-6758}, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Biological Evolution ; Gene Expression Regulation, Developmental/*physiology ; *Genetic Variation ; Genome ; Heterozygote ; Humans ; Polymorphism, Genetic ; }, abstract = {Results of long-term studies of Russian authors on regularities of expression of hereditary biochemical diversity in evolution and development are reviewed. Primary attention is given to the concepts of genetic monomorphism and genetic stability of population systems, principles of adaptive gene pool structure and optimum genetic diversity, historical and conservation genetics, the concept of the multilevel gene expression, and temporal regulation of ontogenetic functioning of gene clusters coding for enzymes. A universal genetic approach to the problems of evolution and ontogeny is proposed. A population is regarded as a superorganism whose key property is the hierarchic structure of its genetic stability from the stability of monomorphic genes via stability of polymorphic gene frequencies in a multilevel population system to the stability of the total amount of gene diversity in this system. A multicellular organism is also regarded as a developing hierarchical system of populations of cells and genes interacting in a nonrandom fashion. This maintains stability of metabolic processes and is expressed in consistent correlations between monogenic and polygenic morphophysiological characters. Properties of both organisms are determined by the adaptive heterozygosity optimum, the disturbance of which has negative consequences for both individuals and populations. On the basis of these results and the concept on the common nature of evolutionary and ontogenetic processes, the following conclusions are drawn: genetic processes can be either favorable or adverse for developing organisms and populations; the state of genetic processes can be determined by analysis of gene diversity and their deviations from the optimum, taking into account the adaptive gene pool structure; and negative hazardous consequences of extreme external effects at both the individual and population levels can be detected by methods of biochemical genetics in specially planned monitoring programs. Knowledge of normal processes of realization of hereditary information in evolution of populations and in ontogeny opens up new perspectives in detection of unfavorable processes and their correction. This approach proved promising both for preventive and clinical medicine and for exploitation and artificial reproduction of biological resources.}, } @article {pmid8980520, year = {1996}, author = {Vogel, H and Fischer, S and Valentin, K}, title = {A model for the evolution of the plastid sec apparatus inferred from secY gene phylogeny.}, journal = {Plant molecular biology}, volume = {32}, number = {4}, pages = {685-692}, pmid = {8980520}, issn = {0167-4412}, mesh = {Cloning, Molecular ; *Evolution, Molecular ; Gene Expression Regulation ; Genes/*genetics ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Plant Proteins/*genetics ; Plastids/*genetics ; RNA, Messenger/analysis ; Rhodophyta/*genetics ; SEC Translocation Channels ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {Plastids possess a bacteria-like sec apparatus that is involved in protein import into the thylakoid lumen. We have analyzed one of the genes essential for this process, secY. A secY gene from the unicellular red alga Cyanidium caldarium was found to be transcriptionally active, demonstrating for the first time that secY is functional in a plastid. Unlike the situation seen in bacteria the C. caldarium gene is transcribed monocistronically, despite the fact that it is part of a large ribosomal gene cluster that resembles bacterial spc operons. A molecular phylogeny is presented for 8 plastid-encoded secY genes, four of which have not been published yet. In this analysis plastid secY genes fall into two classes. One of these, comprising of genes from multicellular red algae and Cryptophyta, clusters in a neighbour-joining tree with a cyanobacterial counterpart. Separated from the aforesaid are secY genes from Chromophyta, Glaucocystophyta and a unicellular red alga. All plastid and cyanobacterial sequences are located on the same branch, separated from bacterial homologues. We postulate that the two classes of secY genes are paralogous, i.e. their gene products are involved in different protein translocation processes. Based on this assumption a model for the evolution of the plastid sec apparatus is presented.}, } @article {pmid8876205, year = {1996}, author = {Ayala, FJ and Barrio, E and Kwiatowski, J}, title = {Molecular clock or erratic evolution? A tale of two genes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {93}, number = {21}, pages = {11729-11734}, pmid = {8876205}, issn = {0027-8424}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/enzymology/genetics ; Diptera/enzymology/genetics ; Drosophila/classification/enzymology/genetics ; Drosophilidae/classification/enzymology/genetics ; *Evolution, Molecular ; Genetic Variation ; Glycerolphosphate Dehydrogenase/chemistry/*genetics ; Humans ; Mice ; Molecular Sequence Data ; *Phylogeny ; Rabbits ; Saccharomyces cerevisiae/enzymology/genetics ; Schizosaccharomyces/enzymology/genetics ; Sequence Homology, Amino Acid ; Superoxide Dismutase/chemistry/*genetics ; *Time ; }, abstract = {We have investigated the evolution of glycerol-3-phosphate dehydrogenase (Gpdh). The rate of amino acid replacements is 1 x 10(-10)/site/year when Drosophila species are compared. The rate is 2.7 times greater when Drosophila and Chymomyza species are compared; and about 5 times greater when any of those species are compared with the medfly Ceratitis capitata. This rate of 5 x 10(-10)/site/year is also the rate observed in comparisons between mammals, or between different animal phyla, or between the three multicellular kingdoms. We have also studied the evolution of Cu,Zn superoxide dismutase (Sod). The rate of amino acid replacements is about 17 x 10(-10)/site/year when comparisons are made between dipterans or between mammals, but only 5 x 10(-10) when animal phyla are compared, and only 3 x 10(-10) when the multicellular kingdoms are compared. The apparent decrease by about a factor of 5 in the rate of SOD evolution as the divergence between species increases can be consistent with the molecular clock hypothesis by assuming the covarion hypothesis (namely, that the number of amino acids that can change is constant, but the set of such amino acids changes from time to time and from lineage to lineage). However, we know of no model consistent with the molecular clock hypothesis that would account for the increase in the rate of GPDH evolution as the divergence between species increases.}, } @article {pmid8865666, year = {1996}, author = {Pawlowski, J and Montoya-Burgos, JI and Fahrni, JF and Wüest, J and Zaninetti, L}, title = {Origin of the Mesozoa inferred from 18S rRNA gene sequences.}, journal = {Molecular biology and evolution}, volume = {13}, number = {8}, pages = {1128-1132}, doi = {10.1093/oxfordjournals.molbev.a025675}, pmid = {8865666}, issn = {0737-4038}, mesh = {Animals ; Biological Evolution ; Ciliophora/genetics ; Invertebrates/classification/*physiology ; Male ; Models, Biological ; Models, Genetic ; Molecular Sequence Data ; Nematoda ; Parasites/classification/genetics/physiology ; *Phylogeny ; *RNA, Ribosomal, 18S ; Saccharomyces cerevisiae/genetics ; Sequence Alignment ; Sequence Homology, Nucleic Acid ; }, abstract = {The phylum Mesozoa comprises small, simply organized wormlike parasites of marine invertebrates and is composed of two classes, the Rhombozoa and the Orthonectida. The origin of Mesozoa is uncertain; they are classically considered either as degenerate turbellarians or as primitive multicellular animals related to ciliated protists. In order to precisely determine the phylogenetic position of this group we sequenced the complete 18S rRNA gene of one rhombozoid, Dicyema sp., and one orthonectid, Rhopalura ophiocomae. The sequence analysis shows that the Mesozoa branch early in the animal evolution, closely to nematodes and myxozoans. Our data indicate probably separate origins of rhombozoids and orthonectids, suggesting that their placement in the same phylum needs to be revised.}, } @article {pmid8798342, year = {1996}, author = {Kruse, M and Gamulin, V and Cetkovic, H and Pancer, Z and Müller, IM and Müller, WE}, title = {Molecular evolution of the metazoan protein kinase C multigene family.}, journal = {Journal of molecular evolution}, volume = {43}, number = {4}, pages = {374-383}, pmid = {8798342}, issn = {0022-2844}, support = {RG-33/96-M/RG/CSR NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Catalysis ; *Evolution, Molecular ; Molecular Sequence Data ; Multigene Family/*genetics ; Phylogeny ; Porifera/enzymology/*genetics ; Protein Kinase C/*genetics ; Protein Serine-Threonine Kinases/genetics ; Sequence Homology, Amino Acid ; }, abstract = {Protein kinases C (PKCs) comprise closely related Ser/Thr kinases, ubiquitously present in animal tissues; they respond to second messengers, e.g., Ca2+ and/or diacylglycerol, to express their activities. Two PKCs have been sequenced from Geodia cydonium, a member of the lowest multicellular animals, the sponges (Porifera). One sponge G. cydonium PKC, GCPKC1, belongs to the "novel" (Ca2+-independent) PKC (nPKC) subfamily while the second one, GCPKC2, has the hallmarks of the "conventional" (Ca2+-dependent) PKC (cPKC) subfamily. The alignment of the Ser/Thr catalytic kinase domains, of the predicted aa sequences for these cDNAs with respective segments from previously reported sequences, revealed highest homology to PKCs from animals but also distant relationships to Ser/Thr kinases from protozoa, plants, and bacteria. However, a comparison of the complete structures of the sponge PKCs, which are-already-identical to those of nPKCs and cPKCs from higher metazoa, with the structures of protozoan, plant, and bacterial Ser/Thr kinases indicates that the metazoan PKCs have to be distinguished from the nonmetazoan enzymes. These data indicate that metazoan PKCs have a universal common ancestor which they share with the nonmetazoan Ser/Thr kinases with respect to the kinase domain, but they differ from them in overall structural composition.}, } @article {pmid9035677, year = {1996}, author = {Haas, I and Koldovsky, P}, title = {[Expression of cellular antigen of hypopharyngeal carcinoma in different culture conditions].}, journal = {Laryngo- rhino- otologie}, volume = {75}, number = {9}, pages = {543-547}, doi = {10.1055/s-2007-997630}, pmid = {9035677}, issn = {0935-8943}, mesh = {Adult ; Biomarkers, Tumor/*genetics ; Carcinoma, Squamous Cell/genetics/*pathology ; Cell Division/physiology ; Culture Media ; Epithelium/pathology ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Hypopharyngeal Neoplasms/genetics/*pathology ; Immunoenzyme Techniques ; Male ; Middle Aged ; Spheroids, Cellular/pathology ; Tumor Cells, Cultured/*pathology ; }, abstract = {BACKGROUND: The need to improve therapy regimes, determine prognosis, and study biological properties of tumors extracorporally led to development of different experimental systems. In order to approach the in vivo situation, specific properties of the tumors of origin should be retained by the cells in culture over relatively long periods. However, culture conditions may change expression of cellular antigens.

METHODS: Cryosections of a hypopharyngeal carcinoma were compared in this respect with different cultivation systems (2-dimensional monolayers [ML], 3-dimensional multicellular tumor spheroids [MTS] and substrate cultures on Gelita) in regard to expression of cytokeratins (CK) 1, 7, 10, 14, 18 and 19, vimentin, neurofilament (NF) kD200 and 68, ganglioside GD2, oncogene products (P53 mutant and wild), and membrane-associated antigens (HLA-ABC and -DR, epidermal growth factor receptor EGFR).

RESULTS: Semiquantitative immunohistochemical methods revealed differences in expression of CK1, 14 and 19, GD2, and P53 mutant between these systems.

CONCLUSION: Pronounced expression of markers in MTS compared to original biopsy and monolayer emphasizes the importance of cell-cell contact and 3-dimensionality or metabolic stress. However, weak marker expression within substrate cultures may reflect loose cell-cell contact observed. In these experiments, the antigenic configuration of MTS resembled the one of the original tumor more than the other culture systems: monolayer and growth on substrate. As vimentin and NF are not expressed by healthy epithelial cells of adults, occurrence of intratumoral vimentin and NF could point to derepression of early differentiation antigens.}, } @article {pmid8703085, year = {1996}, author = {Waterborg, JH and Robertson, AJ}, title = {Common features of analogous replacement histone H3 genes in animals and plants.}, journal = {Journal of molecular evolution}, volume = {43}, number = {3}, pages = {194-206}, pmid = {8703085}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Animals ; Databases, Factual ; *Evolution, Molecular ; *Genes ; *Genes, Plant ; Histones/*genetics ; Humans ; Introns ; Invertebrates ; Mammals ; Molecular Sequence Data ; *Phylogeny ; RNA, Messenger/biosynthesis ; Sequence Homology, Amino Acid ; Transcription, Genetic ; }, abstract = {Phylogenetic analysis of histone H3 protein sequences demonstrates the independent origin of the replacement histone H3 genes in animals and in plants. Multiple introns in the replacement histone H3 genes of animals in a pattern distinct from that in plant replacement H3 genes supports this conclusion. It is suggested that replacement H3 genes arose at the same time that, independently, multicellular forms of animals and of plants evolved. Judged by the degree of invariant and functionally constrained amino acid positions, histones H3 and H4, which form together the tetramer kernel of the nucleosome, have co-evolved with equal rates of sequence divergence. Residues 31 and 87 in histone H3 are the only residues that consistently changed across each gene duplication event that created functional replacement histone H3 variant forms. Once changed, these residues have remained invariant across divergent speciation. This suggests that they are required to allow replacement histone H3 to participate in the assembly of nucleosomes in non-S-phase cells. The abundant occurrence of polypyrimidine sequences in the introns of all replacement H3 genes, and the replacement of an intron by a polypyrimidine motif upstream of the alfalfa replacement H3 gene, suggests a function. It is speculated that they may contribute to the characteristic cell-cycle-independent pattern of replacement histone H3 genes by binding nucleosome-excluding proteins.}, } @article {pmid8760489, year = {1996}, author = {Michod, RE}, title = {Cooperation and conflict in the evolution of individuality. II. Conflict mediation.}, journal = {Proceedings. Biological sciences}, volume = {263}, number = {1372}, pages = {813-822}, doi = {10.1098/rspb.1996.0121}, pmid = {8760489}, issn = {0962-8452}, support = {GM-19949/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Conflict, Psychological ; Gene Deletion ; *Genetic Variation ; Genotype ; Humans ; Mathematics ; *Models, Genetic ; Models, Psychological ; Personality ; Recombination, Genetic ; Reproduction ; *Selection, Genetic ; }, abstract = {Evolutionary transitions in the units of selection require the promotion of cooperation and the regulation of conflict among the lower level units. For multicellular organisms to emerge as a new unit of selection, the selfish tendencies of their component cells had to be controlled. Theoretical results indicate organisms may regulate this internal conflict and competition in several ways: by reducing the somatic mutation rate, by sequestering cells in a germ line and by directly reducing the benefits to cell of defecting.}, } @article {pmid8796186, year = {1996}, author = {Lachmann, M and Jablonka, E}, title = {The inheritance of phenotypes: an adaptation to fluctuating environments.}, journal = {Journal of theoretical biology}, volume = {181}, number = {1}, pages = {1-9}, doi = {10.1006/jtbi.1996.0109}, pmid = {8796186}, issn = {0022-5193}, support = {GM 28016/GM/NIGMS NIH HHS/United States ; }, mesh = {*Adaptation, Physiological ; Animals ; *Biological Evolution ; *Environment ; *Models, Genetic ; *Phenotype ; }, abstract = {We discuss simple models for the evolution of rates of spontaneous and induced heritable phenotypic variations in a periodically fluctuating environment with a cycle length between two and 100 generations. For the simplest case, the optimal spontaneous transition rate between two states is approximately 1/n (where n is the cycle length). It is also shown that selection for the optimal transition rate under these conditions is surprisingly strong. When n is small, this means that the heritable variations are produced by non-classical inheritance systems, including non-DNA inheritance systems. Thus, it is predicted that in genes controlling adaptation to such environments, non-classical genetic effects are likely to be observed. We argue that the evolution of spontaneous and induced heritable transitions played an important role in the evolution of ontogenies of both unicellular and multicellular organisms. The existence of a machinery for producing induced heritable phenotypic variations introduces a "Lamarckian" factor into evolution.}, } @article {pmid8654977, year = {1996}, author = {Hobmayer, E and Hatta, M and Fischer, R and Fujisawa, T and Holstein, TW and Sugiyama, T}, title = {Identification of a Hydra homologue of the beta-catenin/plakoglobin/armadillo gene family.}, journal = {Gene}, volume = {172}, number = {1}, pages = {155-159}, doi = {10.1016/0378-1119(96)00162-x}, pmid = {8654977}, issn = {0378-1119}, mesh = {Amino Acid Sequence ; Animals ; Armadillo Domain Proteins ; Biological Evolution ; Cloning, Molecular ; Cytoskeletal Proteins/*genetics ; DNA, Complementary ; Desmoplakins ; *Drosophila Proteins ; Hydra/*genetics ; Molecular Sequence Data ; *Multigene Family ; Proteins/*genetics ; Sequence Homology, Amino Acid ; *Trans-Activators ; beta Catenin ; gamma Catenin ; }, abstract = {The beta-catenin/plakoglobin/armadillo gene family encodes a group of highly conserved proteins which play important roles in cadherin-mediated cell adhesion and in signal transduction mechanisms involved in regulating development. This gene family previously had been isolated only from higher metazoans. Here, we describe the isolation and characterization of a beta-catenin (beta Ctn) homologue from Hydra magnipapillata, a diploblastic lower metazoan. Comparison of the putative amino acid (aa) sequence of Hydra beta Ctn, with its homologues in higher metazoans, shows that a repeating 42-aa motif present in its central domain is highly conserved throughout the metazoa. This suggests that beta Ctn appeared very early in metazoan evolution, possibly when primitive multicellular animals started to form epithelial cell layers.}, } @article {pmid8724539, year = {1996}, author = {Yin, JA and Jowitt, SN}, title = {Clonality switch in acute myeloid leukemia.}, journal = {Leukemia & lymphoma}, volume = {22}, number = {1-2}, pages = {125-130}, doi = {10.3109/10428199609051739}, pmid = {8724539}, issn = {1042-8194}, mesh = {Adult ; Anemia, Refractory, with Excess of Blasts/*pathology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Blast Crisis/pathology ; Bone Marrow/pathology ; Clone Cells/*pathology ; Cyclophosphamide/administration & dosage ; Cytarabine/administration & dosage ; Daunorubicin/administration & dosage ; Disease Progression ; Dosage Compensation, Genetic ; Female ; Hematopoiesis ; Heterozygote ; Humans ; Leukemia, Myeloid, Acute/drug therapy/*pathology ; Neoplastic Stem Cells/*pathology ; Prednisolone/administration & dosage ; Remission Induction ; Thioguanine/administration & dosage ; Vincristine/administration & dosage ; }, abstract = {We have previously described a case of clonality switch in a female patient with acute myeloid leukemia (AML) by X-chromosome inactivation analysis. She presented with refractory anemia with excess blasts in transformation but soon progressed to overt AML. Following induction chemotherapy, she went into complete remission but later relapsed into a second myelodysplastic phase. Analysis of her X-linked DNA polymorphism patterns at presentation and relapse showed that hematopoiesis was clonal, but the genotypes of the two clones was different. She remains clinically well and has a virtually normal blood count more than 5 years from presentation. We now report an update of this unique case and discuss the implications of this finding within the context of a multicellular origin of leukemia.}, } @article {pmid8849902, year = {1996}, author = {Kumar, S and Balczarek, KA and Lai, ZC}, title = {Evolution of the hedgehog gene family.}, journal = {Genetics}, volume = {142}, number = {3}, pages = {965-972}, pmid = {8849902}, issn = {0016-6731}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biological Evolution ; DNA ; *Drosophila Proteins ; Hedgehog Proteins ; Humans ; Molecular Sequence Data ; Phylogeny ; Proteins/chemistry/*genetics ; Sequence Homology, Amino Acid ; *Trans-Activators ; }, abstract = {Effective intercellular communication is an important feature in the development of multicellular organisms. Secreted hedgehog (hh) protein is essential for both long- and short-range cellular signaling required for body pattern formation in animals. In a molecular evolutionary study, we find that the vertebrate homologs of the Drosophila hh gene arose by two gene duplications: the first gave rise to Desert hh, whereas the second produced the Indian and Sonic hh genes. Both duplications occurred before the emergence of vertebrates and probably before the evolution of chordates. The amino-terminal fragment of the hh precursor, crucial in long- and short-range intercellular communication, evolves two to four times slower than the carboxyl-terminal fragment in both Drosophila hh and its vertebrate homologues, suggesting conservation of mechanism of hh action in animals. A majority of amino acid substitutions in the amino- and carboxyl-terminal fragments are conservative, but the carboxyl-terminal domain has undergone extensive insertion-deletion events while maintaining its autocleavage protease activity. Our results point to similarity of evolutionary constraints among sites of Drosophila and vertebrate hh homologs and suggest some future directions for understanding the role of hh genes in the evolution of developmental complexity in animals.}, } @article {pmid8692049, year = {1996}, author = {Kozlov, AP}, title = {Gene competition and the possible evolutionary role of tumours.}, journal = {Medical hypotheses}, volume = {46}, number = {2}, pages = {81-84}, doi = {10.1016/s0306-9877(96)90005-5}, pmid = {8692049}, issn = {0306-9877}, mesh = {Animals ; *Biological Evolution ; Gene Expression Regulation, Neoplastic ; Humans ; Models, Genetic ; Multigene Family ; Neoplasms/*genetics/pathology ; Oncogenes ; }, abstract = {The evolutionary role of tumours might consist of providing the conditions for the expression of evolutionary new genes and thus in providing the material for the origin of new cell types. To approach this concept the principle of gene competition is essential. With an increase in gene number in the genomes of the evolving multicellular organisms the enforcement of gene competition should take place. Therefore, the pre-existing cell types possess limited possibilities for the expression of evolutionary new genes. Like evolutionary new genes originated from extra copies (duplicates) of old genes, evolutionary new cell types had to originate from extra cells which were not functionally necessary to the organism. Tumours could have supplied the evolving multicellular organisms with extra cells for the expression of originating evolutionary new genes. Of course, on the basis of this proposal only tumours at the earlier stages of progression are considered to be meaningful, or some kind of tumour-like processes, but not malignant tumours at late stages of progression. The evolutionary new genes originate in the DNA of germ line cells but not in DNA of tumour cells. Until the moment of their expression in the tumour cells these genes could stay silent. After the expression of these genes tumour cells should acquire the function in the organism, differentiate and lose their previous autonomy. The organisms with a new cell type should then be selected against their fitness and competitive abilities.}, } @article {pmid8570613, year = {1996}, author = {Hallmann, A and Sumper, M}, title = {The Chlorella hexose/H+ symporter is a useful selectable marker and biochemical reagent when expressed in Volvox.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {93}, number = {2}, pages = {669-673}, pmid = {8570613}, issn = {0027-8424}, mesh = {Amino Sugars ; Animals ; Base Sequence ; Biological Transport ; *Carbohydrate Metabolism ; Carrier Proteins/*genetics ; Chlorella/*genetics ; Cloning, Molecular ; Darkness ; Deoxyglucose/metabolism ; *Genetic Markers ; Glucosamine/metabolism ; Glucose/metabolism ; Membrane Proteins/*genetics ; Molecular Sequence Data ; *Monosaccharide Transport Proteins ; Polymerase Chain Reaction ; Selection, Genetic ; Sequence Analysis, DNA ; Symporters ; Transformation, Genetic ; Volvocida/*genetics ; }, abstract = {The multicellular obligately photoautotrophic alga Volvox is composed of only two types of cells, somatic and reproductive. Therefore, Volvox provides the simplest model system for the study of multicellularity. Metabolic labeling experiments using radioactive precursors are crucial for the detection of stage- and cell-type-specific proteins, glycoproteins, lipids, and carbohydrates. However, wild-type Volvox lacks import systems for sugars or amino acids. To circumvent this problem, the hexose/H+ symporter (HUP1) gene from the unicellular alga Chlorella was placed under the control of the constitutive Volvox beta-tubulin promoter. The corresponding transgenic Volvox strain synthesized the sugar transporter in a functional state and was able to efficiently incorporate 14C from labeled glucose or glucosamine. Sensitivity toward the toxic glucose/mannose analogue 2-deoxy-glucose increased by orders of magnitude in transformants. Thus we report the successful transformation of Volvox with a gene of heterologous origin. The chimeric gene may be selected for in either a positive or a negative manner, because transformants exhibit both prolonged survival in the dark in the presence of glucose and greatly increased sensitivity to the toxic sugar 2-deoxyglucose. The former trait may make the gene useful as a dominant selectable marker for use in transformation studies, whereas the latter trait may make it useful in development of a gene-targeting system.}, } @article {pmid8541419, year = {1995}, author = {Katayama, T and Wada, H and Furuya, H and Satoh, N and Yamamoto, M}, title = {Phylogenetic position of the dicyemid mesozoa inferred from 18S rDNA sequences.}, journal = {The Biological bulletin}, volume = {189}, number = {2}, pages = {81-90}, doi = {10.2307/1542458}, pmid = {8541419}, issn = {0006-3185}, mesh = {Animals ; Base Sequence ; DNA Primers ; DNA, Ribosomal/*genetics ; Invertebrates/*classification/genetics ; Molecular Sequence Data ; Mollusca/parasitology ; Phylogeny ; RNA, Ribosomal, 18S/*genetics ; Sequence Homology, Nucleic Acid ; Symbiosis ; }, abstract = {The dicyemid mesozoa, obligate symbionts in the cephalopod kidney, are simply organized multicellular animals. They have long been the subject of phylogenetic debates. Some authors have suggested that dicyemids represent an offshoot from an early metazoan ancestor. Other workers considered them to be degenerated progeny of higher metazoa, possibly parasitic trematodes. We determined the almost complete nucleotide sequences of 18S rDNA in two species of dicyemid, Dicyema orientale and Dicyema acuticephalum, isolated purely from cephalopod urine. We compared these sequences with sequences determined in the present study from three flatworm species, as well as with a variety of eukaryote sequences obtained from databases. The phylogenetic trees reconstructed with the use of the neighbor-joining, maximum-parsimony, and maximum-likelihood methods indicated that the dicyemids belong among the triploblastic animals (Bilateria). However, we cannot firmly establish the position of the dicyemids within the Bilateria because we cannot ignore the problem of long branch attraction between the myxozoans, dicyemids, nematodes, and acoel flatworms. The present results favor the hypothesis that the dicyemids do not represent an early divergent metazoan group, but rather a group degenerated from a triploblastic ancestor.}, } @article {pmid7565716, year = {1995}, author = {Zhou, K and Takegawa, K and Emr, SD and Firtel, RA}, title = {A phosphatidylinositol (PI) kinase gene family in Dictyostelium discoideum: biological roles of putative mammalian p110 and yeast Vps34p PI 3-kinase homologs during growth and development.}, journal = {Molecular and cellular biology}, volume = {15}, number = {10}, pages = {5645-5656}, pmid = {7565716}, issn = {0270-7306}, support = {CA60559/CA/NCI NIH HHS/United States ; }, mesh = {1-Phosphatidylinositol 4-Kinase ; Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; Conserved Sequence ; Dictyostelium/*enzymology/genetics/growth & development ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Fungal ; Genes, Fungal/*genetics ; Mammals/genetics ; Molecular Sequence Data ; Multigene Family/*genetics ; Phosphatidylinositol 3-Kinases ; Phosphotransferases (Alcohol Group Acceptor)/genetics/*physiology ; Phylogeny ; RNA, Antisense/genetics ; *Saccharomyces cerevisiae Proteins ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; }, abstract = {Three groups of phosphatidylinositol (PI) kinases convert PI into PI(3)phosphate, PI(4)phosphate, PI(4,5) bisphosphate, and PI(3,4,5)trisphosphate. These phosphoinositides have been shown to function in vesicle-mediated protein sorting, and they serve as second-messenger signaling molecules for regulating cell growth. To further elucidate the mechanism of regulation and function of phosphoinositides, we cloned genes encoding five putative PI kinases from Dictyostelium discoideum. Database analysis indicates that D. discoideum PIK1 (DdPIK1), -2, and -3 are most closely related to the mammalian p110 PI 3-kinase, DdPIK5 is closest to the yeast Vps34p PI 3-kinase, and DdPIK4 is most homologous to PI 4-kinases. Together with other known PI kinases, a superfamily of PI kinase genes has been defined, with all of the encoded proteins sharing a common highly conserved catalytic core domain. DdPIK1, -2, and -3 may have redundant functions because disruption of any single gene had no effect on D. discoideum growth or development. However, strains in which both of the two most highly related genes, DdPIK1 and DdPIK2, were disrupted showed both growth and developmental defects, while double knockouts of DdPIK1 and DdPIK3 and DdPIK2 and DdPIK3 appear to be lethal. The delta Ddpik1 delta Ddpik2 null cells were smaller than wild-type cells and grew slowly both in association with bacteria and in axenic medium when attached to petri plates but were unable to grow in suspension in axenic medium. When delta Ddpik1 delta Ddpik2 null cells were plated for multicellular development, they formed aggregates having multiple tips and produced abnormal fruiting bodies. Antisense expression of DdPIK5 (a putative homolog of the Saccharomyces cerevisiae VPS34) led to a defect in the growth of D. discoideum cells on bacterial lawns and abnormal development. DdPIK5 complemented the temperature-sensitive growth defect of a Schizosaccharomyces pombe delta Svps34 mutant strain, suggesting DdPIK5 encodes a functional homolog of yeast Vps34p. These observations indicate that in D. discoideum, different PI kinases regulate distinct cellular processes, including cell growth, development, and protein trafficking.}, } @article {pmid7666445, year = {1995}, author = {Newfeld, SJ and Gelbart, WM}, title = {Identification of two Drosophila TGF-beta family members in the grasshopper Schistocerca americana.}, journal = {Journal of molecular evolution}, volume = {41}, number = {2}, pages = {155-160}, pmid = {7666445}, issn = {0022-2844}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Biological Evolution ; Bone Morphogenetic Proteins ; *Drosophila Proteins ; Drosophila melanogaster/*genetics ; Gene Dosage ; Genes, Insect/*genetics ; Grasshoppers/*genetics ; Hominidae/genetics ; Humans ; Insect Hormones/*genetics ; Molecular Sequence Data ; Proteins/genetics ; RNA, Messenger/analysis ; Sequence Alignment ; Sequence Homology, Amino Acid ; Transforming Growth Factor beta/*genetics ; }, abstract = {Intercellular signaling molecules of the transforming growth factor-beta (TGF-beta) superfamily are required for pattern formation in many multicellular organisms. The decapentaplegic (dpp) gene of Drosophila melanogaster has several developmental roles. To improve our understanding of the evolutionary diversification of this large family we identified dpp in the grasshopper Schistocerca americana. S. americana diverged from D. melanogaster approximately 350 million years ago, utilizes a distinct developmental program, and has a 60-fold-larger genome than D. melanogaster. Our analyses indicate a single dpp locus in D. melanogaster and S. americana, suggesting that dpp copy number does not correlate with increasing genome size. Another TGF-beta superfamily member, the D. melanogaster gene 60A, is also present in only one copy in each species. Comparison of homologous sequences from D. melanogaster, S. americana, and H. sapiens, representing roughly 900 million years of evolutionary distance, reveals significant constraint on sequence divergence for both dpp and 60A. In the signaling portion of the dpp protein, the amino acid identity between these species exceeds 74%. Our results for the TGF-beta superfamily are consistent with current hypotheses describing gene duplication and diversification as a frequent response to high levels of selective pressure on individual family members.}, } @article {pmid8590468, year = {1995}, author = {Bouget, FY and Kerbourc'h, C and Liaud, MF and Loiseaux de Goër, S and Quatrano, RS and Cerff, R and Kloareg, B}, title = {Structural features and phylogeny of the actin gene of Chondrus crispus (Gigartinales, Rhodophyta).}, journal = {Current genetics}, volume = {28}, number = {2}, pages = {164-172}, pmid = {8590468}, issn = {0172-8083}, mesh = {Actins/*genetics ; Amino Acid Sequence ; Base Sequence ; Blotting, Southern ; DNA, Complementary ; Molecular Sequence Data ; *Phylogeny ; Rhodophyta/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {We have characterized the cDNA and genomic sequences that encode actin from the multicellular red alga Chondrus crispus. Southern-blot analysis indicates that the C. crispus actin gene (ChAc) is present as a single copy. Northern analysis shows that, like the GapA gene, the actin gene is well expressed in gametophytes but weakly in protoplasts. Compared to actin genes of animals, fungi, green plants and oomycetes, that of C. crispus displays a higher evolutionary rate and does not show any of the amino-acid signatures characteristic of the other lineages. As previously described for GapA, ChAc is interrupted by a single intron at the beginning of the coding region. The site of initiation of transcription was characterized by RNAse protection. The promoter region displays a CAAT box but lacks a canonical TATA motif. Other noticeable features, such as a high content of pyrimidines as well as a 14-nt motif found in both the 5'-untranslated region and the intron, were observed.}, } @article {pmid7597031, year = {1995}, author = {Escalante, AA and Ayala, FJ}, title = {Evolutionary origin of Plasmodium and other Apicomplexa based on rRNA genes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {92}, number = {13}, pages = {5793-5797}, pmid = {7597031}, issn = {0027-8424}, support = {GM42397/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apicomplexa/classification/*genetics/pathogenicity ; *Biological Evolution ; Disease Vectors ; Fungi/genetics ; *Genes, Protozoan ; Humans ; Insect Vectors ; Molecular Sequence Data ; Phylogeny ; Plants/genetics ; Plasmodium/classification/*genetics/pathogenicity ; RNA, Ribosomal/*genetics ; }, abstract = {We have explored the evolutionary history of the Apicomplexa and two related protistan phyla, Dinozoa and Ciliophora, by comparing the nucleotide sequences of small subunit ribosomal RNA genes. We conclude that the Plasmodium lineage, to which the malarial parasites belong, diverged from other apicomplexan lineages (piroplasmids and coccidians) several hundred million years ago, perhaps even before the Cambrian. The Plasmodium radiation, which gave rise to several species parasitic to humans, occurred approximately 129 million years ago; Plasmodium parasitism of humans has independently arisen several times. The origin of apicomplexans (Plasmodium), dinoflagellates, and ciliates may be > 1 billion years old, perhaps older than the three multicellular kingdoms of animals, plants, and fungi. Digenetic parasitism independently evolved several times in the Apicomplexa.}, } @article {pmid7739382, year = {1995}, author = {Claudianos, C and Campbell, HD}, title = {The novel flightless-I gene brings together two gene families, actin-binding proteins related to gelsolin and leucine-rich-repeat proteins involved in Ras signal transduction.}, journal = {Molecular biology and evolution}, volume = {12}, number = {3}, pages = {405-414}, doi = {10.1093/oxfordjournals.molbev.a040215}, pmid = {7739382}, issn = {0737-4038}, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/genetics ; *Drosophila Proteins ; Drosophila melanogaster/genetics ; Gelsolin/*genetics ; Genes, ras/*genetics ; Humans ; Leucine/*chemistry ; Mice ; Microfilament Proteins/*genetics ; Molecular Sequence Data ; Phylogeny ; Proteins/*genetics ; Repetitive Sequences, Nucleic Acid ; Sequence Alignment ; Signal Transduction/*genetics ; }, abstract = {The Drosophila melanogaster gene flightless-I, involved in gastrulation and muscle degeneration, has Caenorhabditis elegans and human homologues. In these highly conserved genes, two previously known gene families have been brought together, families encoding the actin-binding proteins related to gelsolin and the leucine-rich-repeat (LRR) group of proteins involved in protein-protein interactions. Both these gene families exhibit characteristics of molecular changes involving replication slippage and exon shuffling. Phylogenetic analyses of 19 amino acid sequences of 6 related protein types indicate that actin-associated proteins related to gelsolin are monophyletic to a common ancestor and include flightless proteins. Conversely, comparison of 24 amino acid sequences of LRR proteins including the flightless proteins indicates that flightless proteins are members of a structurally related subgroup. Included in the flightless cluster are human and mouse rsp-1 proteins involved in suppressing v-Ras transformation of cells and the membrane-associated yeast (Saccharomyces cerevisae) adenylate cyclase whose analogous LRRs are required for interaction with Ras proteins. There is a strong possibility that ligands for this group could be related and that flightless may have a similar role in Ras signal transduction. It is hypothesized that an ancestral monomeric gelsolin precursor protein has undergone at least four independent gene reorganization events to account for the structural diversity of the extant family of gelsolin-related proteins and that gene duplication and exon shuffling events occurred prior to or at the beginning of multicellular life, resulting in the evolution of some members of the family soon after the appearance of actin-type proteins.}, } @article {pmid7708828, year = {1994}, author = {Ewald, PW}, title = {Evolution of mutation rate and virulence among human retroviruses.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {346}, number = {1317}, pages = {333-41; discussion 341-3}, doi = {10.1098/rstb.1994.0150}, pmid = {7708828}, issn = {0962-8436}, mesh = {Biological Evolution ; Humans ; Mutation ; Retroviridae/*genetics/*pathogenicity ; Virulence ; }, abstract = {High mutation rates are generally considered to be detrimental to the fitness of multicellular organisms because mutations untune finely tuned biological machinery. However, high mutation rates may be favoured by a need to evade an immune system that has been strongly stimulated to recognize those variants that reproduced earlier during the infection. HIV infections conform to this situation because they are characterized by large numbers of viruses that are continually breaking latency and large numbers that are actively replicating throughout a long period of infection. To be transmitted, HIVs are thus generally exposed to an immune system that has been activated to destroy them in response to prior viral replication in the individual. Increases in sexual contact should contribute to this predicament by favouring evolution toward relatively high rates of replication early during infection. Because rapid replication and high mutation rate probably contribute to rapid progression of infections to AIDS, the interplay of sexual activity, replication rate, and mutation rate helps explain why HIV-1 has only recently caused a lethal pandemic, even though molecular data suggest that it may have been present in humans for more than a century. This interplay also offers an explanation for geographic differences in progression to cancer found among infections due to the other major group of human retroviruses, human T-cell lymphotropic viruses (HTLV). Finally, it suggests ways in which we can use natural selection as a tool to control the AIDS pandemic and prevent similar pandemics from arising in the future.}, } @article {pmid7923079, year = {1994}, author = {Gorunova, L and Mertens, F and Mandahl, N and Jonsson, N and Persson, B and Heim, S and Mitelman, F}, title = {Cytogenetic heterogeneity in a clear cell hidradenoma of the skin.}, journal = {Cancer genetics and cytogenetics}, volume = {77}, number = {1}, pages = {26-32}, doi = {10.1016/0165-4608(94)90144-9}, pmid = {7923079}, issn = {0165-4608}, mesh = {Acrospiroma/*genetics/pathology ; Aged ; *Chromosome Aberrations ; Humans ; Karyotyping ; Male ; Skin Neoplasms/*genetics/pathology ; }, abstract = {Short-term cultures from a clear cell hidradenoma, a benign skin tumor for which no chromosome data exist, were cytogenetically analyzed. A total of eight unrelated aberrant clones were identified. The karyotypic profiles of two separately processed parts of the sample--a tumor nodule and seemingly normal adjacent dermal tissue--were different. Characteristic for the tumor nodule was a single abnormal clonal population consisting of three subclones: 46,XY,der(2)inv(2)(p13q23)t(2;9)(p13;q22), der(9)t(2;9)(q23;q22),t(11;19)(q21;p13),t(12;19)(q24;p13)/46,idem, inv(1)(p32q44)/92,idemx2. The adjacent tissue contained, in addition to the clone found in the tumor nodule, a spectrum of unrelated clones, the largest of which also showed clonal evolution: 45-47,XY,t(3;6)(p25;p25),t(12;17)(q15;q12),-17,+r(17)x2 [cp]/45-47,idem,inv(5)(p15q22)/90-94,idemx2. The remaining six clones found in this part were small and had simpler numerical or structural aberrations. The multiclonal pattern observed in this hidradenoma seems to reflect both cytogenetic convergence and divergence during neoplastic progression. The presence of unrelated clones may be an indication that the tumor was of multicellular origin.}, } @article {pmid8090766, year = {1994}, author = {Thompson-Stewart, D and Karpen, GH and Spradling, AC}, title = {A transposable element can drive the concerted evolution of tandemly repetitious DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {91}, number = {19}, pages = {9042-9046}, pmid = {8090766}, issn = {0027-8424}, support = {/HHMI/Howard Hughes Medical Institute/United States ; GM27875/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; *DNA Transposable Elements ; Drosophila melanogaster/*genetics ; Gene Conversion ; *Repetitive Sequences, Nucleic Acid ; }, abstract = {Recombination and conversion have been proposed to drive the concerted evolution of tandemly repeated DNA sequences. However, specific correction events within the repeated genes of multicellular organisms have not been observed directly, so their nature has remained speculative. We investigated whether the excision of transposable P elements from tandemly repeated sequences would induce unequal gene conversion. Genetically marked elements located in a subtelomeric repeat were mobilized, and the structure of the region was analyzed in progeny. We observed that the number of repeats was frequently altered. Decreases were more common than increases, and this bias probably resulted from intrinsic mechanisms governing P element-induced double-strand break repair. Our results suggest that transposable elements play an important role in the evolution of repetitious DNA.}, } @article {pmid8078481, year = {1994}, author = {Prade, RA and Timberlake, WE}, title = {The Penicillium chrysogenum and Aspergillus nidulans wetA developmental regulatory genes are functionally equivalent.}, journal = {Molecular & general genetics : MGG}, volume = {244}, number = {5}, pages = {539-547}, pmid = {8078481}, issn = {0026-8925}, support = {GM37886/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Aspergillus nidulans/*genetics/physiology ; Base Sequence ; Conserved Sequence ; DNA Mutational Analysis ; DNA Primers ; DNA, Fungal/genetics ; Fungal Proteins/chemistry/genetics ; *Gene Expression Regulation, Fungal ; *Genes, Fungal ; Genes, Regulator ; Molecular Sequence Data ; Morphogenesis ; Penicillium chrysogenum/*genetics/physiology ; Phylogeny ; Promoter Regions, Genetic ; Spores, Fungal/cytology/*growth & development ; }, abstract = {Aspergillus nidulans and Penicillium chrysogenum are related fungi that reproduce asexually by forming multicellular conidiophores and uninucleate conidia. In A. nidulans, spore maturation is controlled by the wetA (AwetA) regulatory gene. We cloned a homologous gene (PwetA) from P. chrysogenum to determine if spore maturation is regulated by a similar mechanism in this species. The PwetA and AwetA genes are similar in structure and functional organization. The inferred polypeptides share 77% overall amino acid sequence similarity, with several regions having > 85% similarity. The genes also had significant, local sequence similarities in their 5' flanking regions, including conserved binding sites for the product of the regulatory gene abaA. PwetA fully complemented an A. nidulans wetA deletion mutation, demonstrating that PwetA and its 5' regulatory sequences function normally in A. nidulans. These results indicate that the mechanisms controlling sporulation in A. nidulans and P. chrysogenum are evolutionarily conserved.}, } @article {pmid7840899, year = {1994}, author = {Gamulin, V and Rinkevich, B and Schäcke, H and Kruse, M and Müller, IM and Müller, WE}, title = {Cell adhesion receptors and nuclear receptors are highly conserved from the lowest metazoa (marine sponges) to vertebrates.}, journal = {Biological chemistry Hoppe-Seyler}, volume = {375}, number = {9}, pages = {583-588}, doi = {10.1515/bchm3.1994.375.9.583}, pmid = {7840899}, issn = {0177-3593}, mesh = {Amino Acid Sequence ; Animals ; Cell Adhesion Molecules/*metabolism ; Conserved Sequence ; Galectins ; Hemagglutinins/chemistry/genetics ; Lectins/chemistry/*genetics ; Mammals ; Molecular Sequence Data ; Porifera/*genetics ; Protein-Tyrosine Kinases/genetics ; Receptors, Cell Surface/chemistry/*genetics ; Receptors, Cytoplasmic and Nuclear/chemistry/*genetics ; Sequence Homology, Amino Acid ; Vertebrates/*metabolism ; }, abstract = {The shift from unicellular life to multicellular, integrated organisms has been accompanied by the acquisition of adhesion proteins/receptors. Recently we succeeded to clone some genes coding for such proteins from the lowest multicellular animals, the marine sponges (model: the siliceous sponge Geodia cydonium). G. cydonium contains e.g. several lectins; cDNAs for two of them were cloned. Both lectins have a framework sequence of 38 conserved amino acids which are characteristic for the carbohydrate binding site of vertebrate S-type lectins. Next, the cDNA coding for a receptor tyrosine kinase of class II was isolated and characterized. The deduced aa sequence shows two characteristic domains; (i) the tyrosine kinase domain and (ii) an immunoglobulin-like domain. The latter part displays high homology to the vertebrate type immunoglobulin domain. This result together with the lectin data demonstrates that binding domains of such adhesion proteins are not recent achievements of higher animals but exist already in animals (sponges) which have diverged from other organisms about 800 million years ago. Considering the fact that during embryogenesis of sponges a typical anteroposterior organization pattern is seen a 'home-otic' organ-like transformation has been postulated. The subsequent search for genes provided with the homeodomain-like sequence was successful. These data support the view that the kingdom Animalia is of monophyletic origin.}, } @article {pmid7787792, year = {1994}, author = {Müller, WE and Müller, IM and Gamulin, V}, title = {On the monophyletic evolution of the metazoa.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {27}, number = {9}, pages = {2083-2096}, pmid = {7787792}, issn = {0100-879X}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; *Biological Evolution ; Cloning, Molecular ; DNA, Complementary/genetics ; Humans ; Lectins/genetics ; Molecular Sequence Data ; Porifera/*genetics ; Protein-Tyrosine Kinases/genetics ; Receptor Protein-Tyrosine Kinases/genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; }, abstract = {1. The shift from unicellular life to multicellular, integrated organisms has been accompanied by the acquisition of adhesion proteins. Recently we succeeded in cloning some genes coding for such proteins from the lowest multicellular animals, the marine sponges (model: the siliceous sponge Geodia cydonium). 2. G. cydonium contains several lectins and cDNA for two of them (termed LECT-1 and LECT-2) was cloned. Both lectins have a framework sequence of 38 conserved amino acids which are characteristic for the carbohydrate-binding site of vertebrate S-type lectins. Next, we have isolated and characterized a cDNA coding for a receptor tyrosine kinase of class II (GCTK). The deduced amino acid sequence shows two characteristic domains: i) the tyrosine kinase domain and ii) an immunoglobulin-like domain. The latter part shows high homology to the vertebrate type immunoglobulin domain. This result, together with the lectin data, demonstrates that binding domains of such adhesion proteins are not recent achievements of higher animals but exist already in animals (sponges) which have diverged from other organisms about 800 million years ago. 3. Considering the fact that during embryogenesis of sponges a typical anteroposterior organization pattern is seen, a "homeotic" organ-like transformation has been postulated. The subsequent search for genes provided with the homeodomain sequence was successful. The deduced amino acid sequence of G. cydonium showed high homology to chicken and to the Antennapedia sequence from Drosophila melanogaster. 4. These data support the view that the kingdom Animalia is of monophyletic origin.}, } @article {pmid7803760, year = {1994}, author = {Magnuson, NS and Beck, T and Vahidi, H and Hahn, H and Smola, U and Rapp, UR}, title = {The Raf-1 serine/threonine protein kinase.}, journal = {Seminars in cancer biology}, volume = {5}, number = {4}, pages = {247-253}, pmid = {7803760}, issn = {1044-579X}, mesh = {Animals ; Calcium-Calmodulin-Dependent Protein Kinases/physiology ; Cyclic AMP-Dependent Protein Kinases/physiology ; Genes, ras ; Humans ; Protein Kinase C/physiology ; Protein Serine-Threonine Kinases/*physiology ; Proto-Oncogene Proteins/*physiology ; Proto-Oncogene Proteins c-raf ; Signal Transduction ; }, abstract = {Raf-1 belongs to a family of serine/threonine protein kinases which are highly conserved through evolution in multicellular organisms. Raf-1 kinase has gained much attention due to its function as a critical shuttle enzyme that connects stimulation of growth factor receptors and protein kinase C at the cell membrane to changes in the expression of genes involved in the control of cell growth, differentiation and survival. Regulation of Raf-1 activity is complex and involves Ras, as well as several serine/threonine and tyrosine kinases. Through a series of phosphorylation events, extracellular signals are connected through the Raf-1/MAP kinase pathway to activity-regulation of several oncogene-class transcription factors via phosphorylation of specific serine residues. Under ordinary circumstances, the cascade involving Raf-1 eventually leads to changes in gene expression and protein synthesis. Upon constitutive activation of Raf-1 kinase, as a result of genetic changes, a variety of cell types acquire a transformed phenotype.}, } @article {pmid7632194, year = {1994}, author = {Opitz, JM and de la Cruz, F}, title = {Cholesterol metabolism in the RSH/Smith-Lemli-Opitz syndrome: summary of an NICHD conference.}, journal = {American journal of medical genetics}, volume = {50}, number = {4}, pages = {326-338}, doi = {10.1002/ajmg.1320500406}, pmid = {7632194}, issn = {0148-7299}, mesh = {Abnormalities, Multiple/*metabolism ; Blood-Brain Barrier ; Brain Chemistry ; Cholesterol/*biosynthesis ; Cholesterol, Dietary/therapeutic use ; Dehydrocholesterols/blood ; Face/abnormalities ; Genitalia/abnormalities ; Humans ; Infant, Newborn ; Intellectual Disability/metabolism ; Limb Deformities, Congenital ; Lipid Metabolism, Inborn Errors/*genetics ; Microcephaly/metabolism ; Myelin Sheath/physiology ; National Institutes of Health (U.S.) ; Neonatal Screening ; Oxidoreductases/*deficiency ; *Oxidoreductases Acting on CH-CH Group Donors ; Syndrome ; United States ; }, abstract = {During the evolution of multicellularity and attendant processes of development, cholesterol played a key role in the formation of the plasma membrane and outer mitochondrial membrane of every cell in the organism. Later functions include pivotal involvement in steroid, bile acid, and vitamin D metabolism and myelination of the nervous system. In the CNS myelination does not begin until the third trimester, and subcortical myelination not until after birth. The cholesterol of the cell membrane of the ovum is maternally derived. It is not known when the zygote begins making its own cholesterol during morphogenesis and histogenesis, but it must occur early to keep up with the dramatic rate of cell division in the embryo. Thus, it is a startling surprise that human embryos and fetuses apparently able to synthesize little cholesterol (because of a presumed defect of the delta 5,7-sterol, delta 7-reductase that converts 7-dehydrocholesterol (7-DHC) into cholesterol) frequently live to term and, rarely, may be so mildly affected as to attend school with only mild MR. The discovery by G. Stephen Tint and his co-workers of the apparent 7-DHC reductase deficiency makes the RSH (Smith-Lemli-Opitz) syndrome the first true metabolic malformation syndrome. A teratological animal model which has been known for 30 years now appears applicable to the RSH/SLO syndrome. A multidisciplinary NICHD conference held on September 20-21, 1993 reviewed the numerous implications of this discovery and agreed unanimously that research in this field be given highest priority in order to better understand cholesterol synthesis in the mammalian brain, cholesterol transport from mother to embryo and fetus, pre- and postnatal metabolic compensation in structure and function for a profound block in cholesterol synthesis, the nature of the blood-brain barrier for cholesterol, treatment of affected infants, children, and adults, structure and genetic specification of a 7-DHC reductase enzyme (which has never been purified!) and its evolution, the variability of the syndrome and whether it is genetically homo- or heterogeneous, the population genetics of the RSH syndrome, possible selective advantages (or disadvantages) of heterozygotes, and means of newborn screening, carrier detection, and prenatal diagnosis.}, } @article {pmid8056151, year = {1994}, author = {Parma, J and Duprez, L and Van Sande, J and Paschke, R and Tonacchera, M and Dumont, J and Vassart, G}, title = {Constitutively active receptors as a disease-causing mechanism.}, journal = {Molecular and cellular endocrinology}, volume = {100}, number = {1-2}, pages = {159-162}, doi = {10.1016/0303-7207(94)90296-8}, pmid = {8056151}, issn = {0303-7207}, mesh = {Animals ; Disease/*etiology ; GTP-Binding Proteins/physiology ; Gene Expression Regulation ; Humans ; Mice ; Models, Biological ; Models, Molecular ; Mutation ; Receptors, Cell Surface/genetics/*physiology ; *Signal Transduction ; }, abstract = {Membrane receptors have appeared early in evolution as the means for the unicellular organism to sense its environment. With the emergence of social cellular life in multicellular organisms, membrane receptors have acquired the additional functions of sensing the presence of similar cells (as in the aggregation phenomenon of Dictyostelium discoideum) (Klein et al., 1988) or the presence of the mate (Saccharomyces cerevisiae) (Cross et al., 1988), and to detect endocrine signals emitted by cells in distant tissues. As the latter function is central to homeostasis and regulation of cell growth, the downstream regulatory cascades under receptor control are the subject of intense research with implications in virtually all fields of biomedical science. The impact of the analysis of tyrosine kinase-activated cascades on our understanding of carcinogenesis is but one example of such an advance.}, } @article {pmid8079730, year = {1994}, author = {Kunz, LA and Groebe, K and Mueller-Klieser, W}, title = {Oncogene-associated growth behavior and oxygenation of multicellular spheroids from rat embryo fibroblasts.}, journal = {Advances in experimental medicine and biology}, volume = {345}, number = {}, pages = {359-366}, doi = {10.1007/978-1-4615-2468-7_47}, pmid = {8079730}, issn = {0065-2598}, mesh = {Animals ; Cell Division/genetics ; Cell Line ; Cell Transformation, Neoplastic/*genetics/metabolism/pathology ; Cocarcinogenesis ; Embryo, Mammalian ; Fibroblasts/cytology/metabolism ; Genes, myc ; Genes, ras ; *Oncogenes ; Oxygen Consumption/genetics ; Rats ; }, abstract = {The basis of the present investigation was the establishment of an oncogene-dependent, genetically determined two-stage carcinogenesis in vitro model as multicellular spheroids. Spheroid formation was achieved with four rat embryo fibroblast cell lines, two of which represent the first step of malignant transformation, known as stage of immortalization. The ras-transfected counterparts of these two parental cell clones represent fully transformed phenotypes. The data obtained show that spheroid volume growth and cellular viability reflect the degree of tumorigenicity in vivo of the different fibroblast types investigated. In addition, ras-transfection alters not only the growth kinetics but also the cellular oxygen metabolism. Furthermore, the results demonstrate very clearly that different fibroblast clones at the same stage of malignant transformation may be characterized by an entirely different growth behavior, morphology and metabolic activity in spheroid culture. This is true, although these cells originate from the same primary cells, differ only in the step of immortalization, and were cultured as spheroids under identical environmental conditions.}, } @article {pmid7579522, year = {1994}, author = {Chothia, C}, title = {Protein families in the metazoan genome.}, journal = {Development (Cambridge, England). Supplement}, volume = {}, number = {}, pages = {27-33}, pmid = {7579522}, mesh = {Animals ; *Evolution, Molecular ; Exons ; Introns ; Invertebrates/*genetics ; Molecular Structure ; Multigene Family ; Mutation ; Protein Conformation ; Proteins/*genetics ; }, abstract = {The evolution of development involves the development of new proteins. Estimates based on the initial results of the genome projects, and on the data banks of protein sequences and structures, suggest that the large majority of proteins come from no more than one thousand families. Members of a family are descended from a common ancestor. Protein families evolve by gene duplication and mutation. Mutations change the conformation of the peripheral regions of proteins; i.e. the regions that are involved, at least in part, in their function. If mutations proceed until only 20% of the residues in related proteins are identical, it is common for the conformational changes to affect half the structure. Most of the proteins involved in the interactions of cells, and in their assembly to form multicellular organisms, are mosaic proteins. These are large and have a modular structure, in that they are built of sets of homologous domains that are drawn from a relatively small number of protein families. Patthy's model for the evolution of mosaic proteins describes how they arose through the insertion of introns into genes, gene duplications and intronic recombination. The rates of progress in the genome sequencing projects, and in protein structure analyses, means that in a few years we will have a fairly complete outline description of the molecules responsible for the structure and function of organisms at several different levels of developmental complexity. This should make a major contribution to our understanding of the evolution of development.}, } @article {pmid7906442, year = {1993}, author = {Shenk, MA and Steele, RE}, title = {A molecular snapshot of the metazoan 'Eve'.}, journal = {Trends in biochemical sciences}, volume = {18}, number = {12}, pages = {459-463}, doi = {10.1016/0968-0004(93)90003-6}, pmid = {7906442}, issn = {0968-0004}, mesh = {Animals ; Cell Communication/genetics/physiology ; Cnidaria/*genetics ; Drosophila ; Extracellular Matrix Proteins/genetics/physiology ; Molecular Biology ; *Phylogeny ; Signal Transduction/genetics/physiology ; Transcription Factors/genetics/physiology ; }, abstract = {A description of the molecular make-up of the ancestral multicellular animal is emerging from the growing availability of molecular biological and biochemical data gleaned from the study of modern members of ancient groups of animals. We use the distributions of classes of transcription factors, signal transduction systems and other molecular innovations among metazoan phyla to infer some of the characteristics of the first animals.}, } @article {pmid8243991, year = {1993}, author = {Kaiser, D}, title = {Roland Thaxter's legacy and the origins of multicellular development.}, journal = {Genetics}, volume = {135}, number = {2}, pages = {249-254}, doi = {10.1093/genetics/135.2.249}, pmid = {8243991}, issn = {0016-6731}, mesh = {Animals ; Ascomycota/*growth & development ; Developmental Biology/history ; Dictyostelium/genetics/*growth & development ; History, 19th Century ; Morphogenesis ; Myxococcales/genetics/*growth & development ; Phylogeny ; }, } @article {pmid8219058, year = {1993}, author = {Valentin, K and Kostrzewa, M and Zetsche, K}, title = {Glutamate synthase is plastid-encoded in a red alga: implications for the evolution of glutamate synthases.}, journal = {Plant molecular biology}, volume = {23}, number = {1}, pages = {77-85}, pmid = {8219058}, issn = {0167-4412}, mesh = {Amino Acid Sequence ; *Biological Evolution ; Blotting, Northern ; Blotting, Southern ; Cloning, Molecular ; Glutamate Synthase/*genetics/metabolism ; Molecular Sequence Data ; Plastids/*enzymology ; Rhodophyta/enzymology/*genetics ; Sequence Homology, Amino Acid ; }, abstract = {An actively transcribed gene (glsF) encoding for ferredoxin-dependent glutamate synthase (Fd-GOGAT) was found on the plastid genome of the multicellular red alga Antithamnion sp. Fd-GOGAT is not plastid-encoded in chlorophytic plants, demonstrating that red algal plastid genomes encode for additional functions when compared to those known from green chloroplasts. Moreover, our results suggest that the plant Fd-GOGAT has an endosymbiotic origin. The same may not be true for NADPH-dependent GOGAT. In Antithamnion glsF is flanked upstream by cpcBA and downstream by psaC and is transcribed monocistronically. Implications of these results for the evolution of GOGAT enzymes and the plastid genome are discussed.}, } @article {pmid8219057, year = {1993}, author = {Kostrzewa, M and Zetsche, K}, title = {Organization of plastid-encoded ATPase genes and flanking regions including homologues of infB and tsf in the thermophilic red alga Galdieria sulphuraria.}, journal = {Plant molecular biology}, volume = {23}, number = {1}, pages = {67-76}, pmid = {8219057}, issn = {0167-4412}, mesh = {Adenosine Triphosphatases/*genetics ; Amino Acid Sequence ; Biological Evolution ; Blotting, Northern ; Molecular Sequence Data ; Phylogeny ; Plastids/*enzymology ; Restriction Mapping ; Rhodophyta/enzymology/*genetics ; Sequence Homology, Amino Acid ; Transcription, Genetic ; }, abstract = {We have cloned and sequenced the plastid ATPase operons (atp1 and atp2) and flanking regions from the unicellular red alga Galdieria sulphuraria (Cyanidium caldarium). Six genes (5 atpI, H, G, F, D and A 3) are linked in atp1 encoding ATPase subunits a, c, b, b, delta and alpha, respectively. The atpF gene does not contain an intron and overlaps atpD by 1 bp. As in the genome of chloroplasts from land plants, the cluster is located downstream of rps2, but between this gene and atp1 we found the gene for the prokaryotic translation elongation factor TS. Downstream of atpA, we detected two open reading frames, one encoding a putative transport protein. The genes atpB and atpE, encoding ATPase subunits beta and epsilon, respectively, are linked in atp2, separated by a 2 bp spacer. Upstream of atpB, an uninterrupted orf167 was detected which is homologous to an intron-containing open reading frame in land plant chloroplasts. This orf167 is preceded on the opposite DNA strand by a homologue to initiation factor 2 in prokaryotes. The arrangement of atp1 and atp2 is the same as observed in the multicellular red alga Antithamnion sp., indicating a conserved genome arrangement in the red algal plastid genome. Differences compared to green chloroplast genomes suggest a large phylogenetic distance between red algae and green plants, while similarities in arrangement and sequence to chromophytic ATPase operons support a red algal origin of chlorophyll a/c-containing plastids or alternatively point to a common prokaryotic endosymbiont.}, } @article {pmid8400545, year = {1993}, author = {Hirabayashi, J and Kasai, K}, title = {The family of metazoan metal-independent beta-galactoside-binding lectins: structure, function and molecular evolution.}, journal = {Glycobiology}, volume = {3}, number = {4}, pages = {297-304}, doi = {10.1093/glycob/3.4.297}, pmid = {8400545}, issn = {0959-6658}, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Galactosides/*metabolism ; Galectins ; Hemagglutinins/*classification/genetics/metabolism ; Invertebrates/*chemistry/genetics ; Membrane Glycoproteins/*classification/genetics/metabolism ; Metals/metabolism ; Molecular Sequence Data ; }, abstract = {Animal metal-independent beta-galactoside-binding lectins were initially found in vertebrates, but they have recently been isolated from much lower invertebrates, such as nematode and sponge, as well. Further, an eosinophilic lysophospholipase associated with various inflammatory reactions was very recently found to be a new member of this protein family. It appears that beta-galactoside-binding lectins and some non-lectin proteins form a superfamily whose members are widely distributed from vertebrates to invertebrates. From the viewpoints of protein architecture, the superfamily members can be subdivided into three types; i.e. 'proto type' (the relatively well-studied 14 kDa lectins), 'chimera type' (29-35 kDa lectins also known as epsilon BP/CBP35/Mac2/laminin-binding protein) and 'tandem-repeat type' (a newly found nematode 32 kDa lectin). Comparison of their amino acid sequences and mutagenesis studies have suggested the functional importance of some conservative hydrophilic residues (His44, Asn46, Arg48, Glu71 and Arg73 of human 14 kDa lectin). Several non-charged residues (Gly14, Phe45, Pro47, Phe49, Val59, Trp68, Pro78 and Phe79) are also well conserved, and are probably important to maintain the structural framework of these proteins. A consideration of molecular evolution suggests that lectins belonging to this family probably existed in the Precambrian era. Ubiquitous occurrence of these homologous lectins with shared sugar specificity suggests that they are involved in 'essential minimum' functions of multicellular animals, possibly in cooperation with their partner glycoconjugates.}, } @article {pmid8297931, year = {1993}, author = {Finch, CE}, title = {FRAR course on laboratory approaches to aging. Theories of aging.}, journal = {Aging (Milan, Italy)}, volume = {5}, number = {4}, pages = {277-289}, pmid = {8297931}, issn = {0394-9532}, mesh = {*Aging/genetics/physiology ; Animals ; Biological Evolution ; Diet ; Ecosystem ; Female ; Gene Expression ; Humans ; Male ; *Models, Biological ; Neurosecretory Systems/physiology ; Reproduction ; }, abstract = {This review of gerontological theory cites diverse examples of neural and endocrine involvement in the senescence of mammals and some other multicellular species that suggest fundamental involvement in age-related changes in cell functions. The data support the major hypothesis that age-related changes are generally caused by specific physiological factors that are extrinsic to cells. The success of these manipulations includes retarding or reversing specific age-related changes, and extending the life span. From another perspective, these findings have converted time in the analysis of senescence from an independent variable to a dependent variable. So far, we do not need to hypothesize any new mechanism that is not already known in disease or normal functioning.}, } @article {pmid8346026, year = {1993}, author = {Degnan, BM and Degnan, SM and Naganuma, T and Morse, DE}, title = {The ets multigene family is conserved throughout the Metazoa.}, journal = {Nucleic acids research}, volume = {21}, number = {15}, pages = {3479-3484}, pmid = {8346026}, issn = {0305-1048}, support = {R01-CA53105/CA/NCI NIH HHS/United States ; R01-RR06640/RR/NCRR NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Annelida/genetics ; Binding Sites ; *Biological Evolution ; Chordata, Nonvertebrate/genetics ; *Conserved Sequence ; Crustacea/genetics ; DNA/metabolism ; Echinodermata/genetics ; Invertebrates/*genetics ; Molecular Sequence Data ; Mollusca/genetics ; *Multigene Family ; Nematoda/genetics ; Polymerase Chain Reaction ; Porifera/genetics ; Proto-Oncogene Proteins/chemistry/*genetics ; Proto-Oncogene Proteins c-ets ; *Transcription Factors ; }, abstract = {This study provides the first empirical evidence for the conservation of the ets proto-oncogene transcription factor family throughout the Metazoa. Using the polymerase chain reaction with degenerate primers corresponding to conserved sequences within the ETS DNA-binding domain, we have detected ets genes in a range of lower metazoans, including sponges, ctenophores, anemones, flatworms and nematodes, and in several higher invertebrate metazoans. Many of these sequences are significantly divergent from the original v-ets-1 oncogene, although most can be aligned with recently defined groups within the ets gene family. Multiple ETS domain sequences were detected in a number of the lower metazoan species, providing evidence for the existence of an ets multigene family at the earliest stages of metazoan evolution. In contrast, we were unable to detect any ETS sequences in fungal, plant or several protozoan DNAs. Our findings suggest that the duplication and divergence of ets proto-oncogenes responsible for generating the multigene family occurred concomitantly with the development of metazoan animals. In addition, these data corroborate other recent molecular evidence in providing strong support for the monophyletic origin of all multicellular animals, including sponges.}, } @article {pmid8507494, year = {1993}, author = {Staiger, C and Doonan, J}, title = {Cell division in plants.}, journal = {Current opinion in cell biology}, volume = {5}, number = {2}, pages = {226-231}, doi = {10.1016/0955-0674(93)90107-2}, pmid = {8507494}, issn = {0955-0674}, mesh = {Cell Cycle/genetics ; Mitosis/*genetics ; *Plants/genetics ; Protein Kinases ; }, abstract = {The past couple of years have seen the isolation and characterization of many of the regulatory genes from plants that are thought to be intimately involved in regulation of the cell division cycle. In addition, characterization of plant-specific aspects of the cell division cycle has provided insight into how spatial and temporal controls may be linked. The comparative lack of cell mobility means that plant organs are historic records of the cell cycles that occurred during their evolution. Differentiated cells retain a capacity for re-entry into the cell cycle, which is probably an adaptation to compensate for the damage that they must tolerate because of a sedentary lifestyle. Understanding how plants cope with such damage and manage to generate such an array of diverse multicellular structures will require a basic comprehension of cell division.}, } @article {pmid8321157, year = {1993}, author = {Chigira, M}, title = {A general model of carcinogenesis (I)--Tumor evolution and gene deletion.}, journal = {Medical hypotheses}, volume = {40}, number = {4}, pages = {223-226}, doi = {10.1016/0306-9877(93)90045-r}, pmid = {8321157}, issn = {0306-9877}, mesh = {Animals ; DNA Repair ; *Gene Deletion ; Genes, Tumor Suppressor ; Humans ; *Models, Genetic ; Mutation ; Neoplasms/*genetics ; }, abstract = {Carcinogenesis is functionally a deletion alteration rather than addition of genetic information. Repressor genes may be more sensitive to 'neutral' mutations of DNA than those of structural genes, since selection pressure for deletion of repressors is extremely low in multicellular organisms. Dysfunction of repressors caused by genomic mutation induces autonomic expression of structural genes which is programmed a priori in each cell. Tumor progression can be explained by this deletion model with abnormal DNA repair. Alteration of DNA repairing units may be the initial mutation in carcinogenesis.}, } @article {pmid8364691, year = {1993}, author = {West, L and Powers, D}, title = {Molecular phylogenetic position of hexactinellid sponges in relation to the Protista and Demospongiae.}, journal = {Molecular marine biology and biotechnology}, volume = {2}, number = {2}, pages = {71-75}, pmid = {8364691}, issn = {1053-6426}, mesh = {Animals ; Base Sequence ; DNA, Ribosomal/chemistry/isolation & purification ; Eukaryota/*classification/genetics ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Porifera/*classification/genetics ; RNA, Ribosomal, 18S/genetics ; }, abstract = {Although it is generally accepted that the first multicellular organisms arose from unicellular ancestors, the phylogenetic relationships linking these groups remain unclear. Anatomical, physiological, and molecular studies of current multicellular organisms with relatively simple body organization suggest key characteristics of the earliest multicellular lineages. Glass sponges, the Hexactinellida, possess cellular characteristics that resemble some unicellular protistan organisms. These unique sponges were abundant in shallow seas of the early Cambrian, but they are currently restricted to polar habitats or very deep regions of the world oceans. Due in part to their relative inaccessibility, their potential significance to the early phylogeny of the eukaryotic kingdoms has been largely overlooked. We used sequences of the 18s ribosomal RNA gene of Farrea occa, a representative of the deep-water hexactinellid sponges, and Coelocarteria singaporense, a representative of the more common demosponges, and compared them with selected ribosomal RNA gene sequences available within the Protista. Using four computational methods for phylogenetic analysis of ribosomal DNA sequences, we found that the hexactinellid sponge-demosponge cluster is most closely related to Volvox and Acanthamoeba.}, } @article {pmid7956040, year = {1993}, author = {Bird, AP}, title = {Functions for DNA methylation in vertebrates.}, journal = {Cold Spring Harbor symposia on quantitative biology}, volume = {58}, number = {}, pages = {281-285}, doi = {10.1101/sqb.1993.058.01.033}, pmid = {7956040}, issn = {0091-7451}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {5-Methylcytosine ; Animals ; Binding Sites ; Biological Evolution ; Cytosine/analogs & derivatives/metabolism ; DNA/genetics/*metabolism ; Genes, Regulator ; Genome ; Methylation ; Transcription, Genetic ; Vertebrates ; }, abstract = {DNA methylation is ancestrally a mechanism for neutralizing potentially damaging DNA elements in the genome. The genomes of most multicellular organisms contain a small fraction of methylated DNA that contains the methylated elements, whereas the organism's own genes remain free of methylation. Vertebrates are exceptional among animals in that their genomes, including genes, are predominantly methylated. They retain the ability to inactivate viral DNA but have recruited the DNA methylation system for new functions. Widespread low-density methylation can contribute to lowering of the level of transcriptional "noise" from cryptic or inappropriate promoters. This may be the major advantage of DNA methylation in these organisms and may be sufficiently beneficial to offset the disadvantage of m5C mutability. The other novel feature of DNA methylation in vertebrates is the capacity to de novo methylate certain CpG islands, causing long-term strong repression. These evolutionary innovations may explain the high complexity of vertebrate organs and cell types.}, } @article {pmid3638476, year = {1986}, author = {Agrell, U}, title = {Draft of a general stochastic theory of cancer and its possible experimental verification with monoclonal multiplication of repairing and immunological systems.}, journal = {Medical hypotheses}, volume = {20}, number = {3}, pages = {261-270}, doi = {10.1016/0306-9877(86)90042-3}, pmid = {3638476}, issn = {0306-9877}, mesh = {Age Factors ; Aging ; Biological Evolution ; *DNA Repair ; Diseases in Twins ; Humans ; Mutation ; Neoplasms/*etiology/genetics/immunology ; Oncogenes ; *Probability ; *Stochastic Processes ; Twins, Monozygotic ; }, abstract = {A general stochastic theory of cancer is outlined by applying to cancer the laws of quantum mechanics instead of the laws of traditional physics, especially with regard to the concept of cause. This theory is combined with the evolutionary theory on the one hand and the mutation theory of aging/death of multicellular beings consisting of somatic cells on the other. The cancer theory centers around the phenomenon of DNA mutating randomly by quantal steps. Because of mutations in the DNA in general as well as in the special DNA which codes for the DNA repairing systems the body is permeated in the course of time - via increasing losses of information in the DNA - with increasingly altered proteins which is observed as aging process. From this process of entropy the concept of the cancer cell is deduced: When the losses of information in a certain cell and also in the repairing and immunological systems have random concordances, cancer as a type of antigens comes into existence. Here the concept of CONCORDANCE OF "BLURRING" is introduced. This CONCORDANCE OF "BLURRING" occurs randomly approximately once among three times 60 000 billion cells, i.e. three human beings. The so-called "oncogenes" are integrated into this theory. It is proposed to test this theory using monozygotic twins both suffering from cancer: By injecting monoclonally multiplied immunological systems, eventually also repair-systems, from the respective other twin, the proposition is that the cancer would be cured in both twins. If this critical experiment is successful, one can cure human beings suffering from cancer by the same procedure, using those systems of their relatives. This treatment would cure the cancer to the extent to which there is a genetic correspondence in the sections of genes coding for these systems.}, } @article {pmid4088951, year = {1985}, author = {Thompson, SA and Johnson, MP and Heidger, PM and Lubaroff, DM}, title = {Characterization of the heterogeneity of R3327 rat prostatic tumors derived from single-cell clones.}, journal = {The Prostate}, volume = {6}, number = {4}, pages = {369-387}, doi = {10.1002/pros.2990060406}, pmid = {4088951}, issn = {0270-4137}, mesh = {Adenocarcinoma/*pathology/ultrastructure ; Animals ; Cell Transformation, Neoplastic/pathology ; Cells, Cultured ; Clone Cells ; Culture Techniques ; DNA, Neoplasm/analysis ; Flow Cytometry ; Male ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Prostatic Neoplasms/*pathology/ultrastructure ; Rats ; }, abstract = {Prostatic adenocarcinoma is characterized by cellular diversity, which is well demonstrated in the Dunning R3327 rat prostatic adenocarcinoma. This heterogeneity may arise from epigenetic influences, ie, cellular adaptation or selection, and/or from genetic changes. To investigate the question of genetic instability, four tissue culture cell lines were derived from single cells isolated from the uncloned late (UCL) passage of the Dunning R3327H prostate cell culture. Each of these clonally derived tissue cultures was injected into castrated and intact young adult male rats for tumor production. Uncloned early (UCE) and UCL passage tissue cultures were also propagated as solid tumors. Tumors and the cultures from which they were derived were examined for evidence of phenotypic and genetic changes using morphological and cytometric methods. Transmission and scanning electron microscopy revealed only slight differences among the cell cultures. A single population of diploid cells was demonstrated in each of the cell cultures by propidium iodide staining and subsequent flow cytometric measurement of DNA content/nucleus. Tumors of unicellular as well as multicellular origin exhibited extreme heterogeneity of histological features, both among animals as well as within a single tumor. Tumors were surveyed and tissue types were characterized and cataloged. Clone 3 was generally better differentiated than the others; tumors from castrated animals were better differentiated than those from intact animals. Flow cytometry revealed multiple hyperdiploid cell populations that were variable from one sample to another. We concluded that changes in genotype as well as phenotype occurred in the tumors derived from single cells. Some of these changes may have occurred in the cells while still in culture.}, } @article {pmid3916708, year = {1985}, author = {Ikemura, T}, title = {Codon usage and tRNA content in unicellular and multicellular organisms.}, journal = {Molecular biology and evolution}, volume = {2}, number = {1}, pages = {13-34}, doi = {10.1093/oxfordjournals.molbev.a040335}, pmid = {3916708}, issn = {0737-4038}, mesh = {Animals ; Biological Evolution ; Codon/*genetics ; Escherichia coli/genetics ; RNA, Messenger/*genetics ; RNA, Transfer/*genetics ; Saccharomyces cerevisiae/genetics ; }, abstract = {Choices of synonymous codons in unicellular organisms are here reviewed, and differences in synonymous codon usages between Escherichia coli and the yeast Saccharomyces cerevisiae are attributed to differences in the actual populations of isoaccepting tRNAs. There exists a strong positive correlation between codon usage and tRNA content in both organisms, and the extent of this correlation relates to the protein production levels of individual genes. Codon-choice patterns are believed to have been well conserved during the course of evolution. Examination of silent substitutions and tRNA populations in Enterobacteriaceae revealed that the evolutionary constraint imposed by tRNA content on codon usage decelerated rather than accelerated the silent-substitution rate, at least insofar as pairs of taxonomically related organisms were examined. Codon-choice patterns of multicellular organisms are briefly reviewed, and diversity in G+C percentage at the third position of codons in vertebrate genes--as well as a possible causative factor in the production of this diversity--is discussed.}, } @article {pmid3902346, year = {1985}, author = {Vinogradov, SN}, title = {The structure of invertebrate extracellular hemoglobins (erythrocruorins and chlorocruorins).}, journal = {Comparative biochemistry and physiology. B, Comparative biochemistry}, volume = {82}, number = {1}, pages = {1-15}, doi = {10.1016/0305-0491(85)90120-8}, pmid = {3902346}, issn = {0305-0491}, support = {HL 25952/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Erythrocruorins/genetics/*metabolism ; Extracellular Space/metabolism ; Hemeproteins/genetics/*metabolism ; Hemoglobins/*metabolism ; Invertebrates/*metabolism ; Macromolecular Substances ; Oxygen/metabolism ; *Phylogeny ; Protein Binding ; Species Specificity ; Structure-Activity Relationship ; }, abstract = {The knowledge accumulated over the last 30 years concerning the subunit structures of the invertebrate extracellular hemoglobins permits us to classify them into four distinct groups. Single-domain, single-subunit hemoglobins consisting of single, heme-binding polypeptide chains which have a molecular mass of ca. 16 KDa. These molecules are found in multicellular parasitic organisms such as the trematodes Dicrocoelium and Fasciolopsis and in a few insects, namely in the adult Anisops and in the larvae of Chironomus and of Buenoa. Two-domain, multi-subunit hemoglobins consisting of 30-37 KDa polypeptide chains each containing two, linearly connected heme-binding domains, which form polymeric aggregates with molecular masses ranging from 250 to 800 KDa. These hemoglobins are found extensively among the carapaced branchiopod crustaceans: Caenestheria, Daphnia and Lepidurus hemoglobins have been found to consist of 10, 16 and 24 two-domain chains, respectively. Judging from their electron microscopic appearances, some of the hemoglobins may possess different molecular symmetries. Multi-domain, multi-subunit hemoglobins consisting of two or more polypeptide chains, each comprising many heme-binding domains of ca. 15-20 KDa each. Examples of this class are found among the carapaceless branchiopod crustaceans, the planorbid snails and the clams from the families Astartidae and Carditidae. Artemia hemoglobin consists of two chains of ca. 125 KDa, each containing 8 heme-binding domains. Planorbis and Helisoma hemoglobins possess a molecular mass of ca. 1700 KDa and consist of 10 chains of 170-200 KDa. Astarte and Cardita hemoglobins appear in electron micrographs as rod-like polymers of variable dimensions, 20-30 nm in diameter and 20-100 nm in length and consist of polypeptide chains of ca. 300 KDa. The crustacean and gastropod hemoglobins vary in their electron microscopic appearance and may possess different molecular symmetries. Single-domain, multi-subunit hemoglobins consisting of aggregates of several small subunits, some of which are disulfide-bonded and not all of which contain heme. These molecules are widely distributed among the annelids and possibly also among the pogonophores. They are characterized by a two-tiered, hexagonal electron microscopic appearance, with a vertex-to-vertex diameter of 30 nm and a height of 20 nm, an acidic isoelectric point, a sedimentation coefficient of 50-60 S and a low iron content of 0.24 +/- 0.03%.(ABSTRACT TRUNCATED AT 400 WORDS)}, } @article {pmid6539911, year = {1984}, author = {Ohama, T and Kumazaki, T and Hori, H and Osawa, S}, title = {Evolution of multicellular animals as deduced from 5S rRNA sequences: a possible early emergence of the Mesozoa.}, journal = {Nucleic acids research}, volume = {12}, number = {12}, pages = {5101-5108}, pmid = {6539911}, issn = {0305-1048}, mesh = {Animals ; Base Sequence ; *Biological Evolution ; Invertebrates/*genetics ; Molecular Weight ; Octopodiformes/genetics ; Phylogeny ; RNA, Ribosomal/*genetics ; Species Specificity ; }, abstract = {The nucleotide sequences of 5S rRNA from a mesozoan Dicyema misakiense and three metazoan species, i.e., an acorn-worm Saccoglossus kowalevskii, a moss-animal Bugula neritina, and an octopus Octopus vulgaris have been determined. A phylogenic tree of multicellular animals has been constructed from 73 5S rRNA sequences available at present including those from the above four sequences. The tree suggests that the mesozoan is the most ancient multicellular animal identified so far, its emergence time being almost the same as that of flagellated or ciliated protozoans. The branching points of planarians and nematodes are a little later than that of the mesozoan but are clearly earlier than other metazoan groups including sponges and jellyfishes. Many metazoan groups seem to have diverged within a relatively short period.}, } @article {pmid6736343, year = {1984}, author = {Moulton-Levy, P and Jackson, CE and Levy, HG and Fialkow, PJ}, title = {Multiple cell origin of traumatically induced keloids.}, journal = {Journal of the American Academy of Dermatology}, volume = {10}, number = {6}, pages = {986-988}, doi = {10.1016/s0190-9622(84)80319-9}, pmid = {6736343}, issn = {0190-9622}, support = {CA16448/CA/NCI NIH HHS/United States ; CA22595/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Blood Cells/enzymology ; Cell Division ; Female ; Fibroblasts/enzymology ; Glucosephosphate Dehydrogenase/*genetics ; Humans ; Isoenzymes/*genetics ; Keloid/*enzymology/genetics/pathology ; Skin/pathology ; }, abstract = {Six keloids from five patients heterozygous for the X-linked glucose-6-phosphate dehydrogenase (G6PD) locus were studied. Both the B and A enzymes were found in the keloids in similar proportions to the normal tissues. This finding indicates that keloids have a multicellular origin and that they do not develop clonally as do most neoplasms.}, } @article {pmid6462202, year = {1984}, author = {Anders, F and Schartl, M and Barnekow, A}, title = {Xiphophorus as an in vivo model for studies on oncogenes.}, journal = {National Cancer Institute monograph}, volume = {65}, number = {}, pages = {97-109}, pmid = {6462202}, issn = {0083-1921}, mesh = {Animals ; Fishes/classification/embryology/*genetics ; Genes, Regulator ; Melanoma/genetics ; Neoplasms, Experimental/chemically induced/genetics ; *Oncogenes ; Pigments, Biological ; }, abstract = {The capacity of Xiphophorus to develop neoplasia can be formally assigned to a "tumor gene" (Tu), which appears to be a normal part of the genome of all individuals. The wild fish have evolved population-specific and cell type-specific systems of regulatory genes (R) for Tu that protect the fish from neoplasia. Hybridization of members of different wild populations in the laboratory followed by treatment of the hybrids with carcinogens led to disintegration of the R systems permitting excessive expression of Tu and thus resulting in neoplasia. Certain hybrids developed neoplasia even spontaneously. Observations on the genuine phenotypic effect of the derepressed Tu in the early embryo indicated an essential normal function of this oncogene in cell differentiation, proliferation and cell-cell communication. Tu appeared to be indispensable in the genome but may also be present in accessory copies. Recently, c-src, the cellular homolog of the Rous sarcoma virus oncogene v-src, was detected in Xiphophorus. The protein product of c-src, pp60c-src, was identified and then examined by its associated kinase activity. This pp60c-src was found in all individuals tested, but, depending on the genotype, its kinase activity was different. The genetic characters of c-src, such as linkage relations, dosage relations, expression, etc., correspond to those of Tu. From a systematic study which showed that pp60c-src was present in all metazoa tested ranging from mammals down to sponges, we concluded that c-src has evolved with the multicellular organization of animals. Neoplasia of animals and humans is a characteristic closely related to this evolution. Our data showed that small aquarium fish, besides being used successfully because they are time-, space-, and money-saving systems for carcinogenicity testing, are also highly suitable for basic studies on neoplasia at the populational, morphological, developmental, cell biological, and molecular levels.}, } @article {pmid6300500, year = {1983}, author = {Collins, SJ and Fialkow, PJ}, title = {Clonal nature of mink cell focus-inducing virus-induced AKR leukemia: studies with X-chromosome inactivation cellular mosaicism.}, journal = {Journal of the National Cancer Institute}, volume = {70}, number = {3}, pages = {529-533}, pmid = {6300500}, issn = {0027-8874}, support = {GM-15253/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Clone Cells ; Electrophoresis, Starch Gel ; Female ; Genetic Markers ; Leukemia Virus, Murine ; Leukemia, Experimental/enzymology/*etiology ; Male ; Mice ; Mice, Inbred AKR/genetics ; *Mosaicism ; Phenotype ; Phosphoglycerate Kinase/analysis/*genetics ; Thymoma/enzymology/*etiology ; *Tumor Virus Infections ; X Chromosome ; }, abstract = {The number of cells from which murine thymic leukemias (thymomas) develop after neonatal injection with a mink cell focus-inducing recombinant virus was studied in AKR mice heterozygous at the X-linked phosphoglycerate kinase (PGK) locus. Because only one of the two X-chromosomes is active in XX somatic cells, thymic leukemias that are clonal should display either type A or type B PGK but not both, whereas those with a multicellular origin may exhibit both enzymes. In 23 of 25 animals studied, thymomas expressed exclusively (11 animals) or predominantly (12 animals) a single enzyme in contrast to normal tissue which expressed both enzyme types in approximately equal ratios. In the 12 thymomas expressing a minor enzyme component, the predominant enzyme in the original tumor always predominated in the thymomas arising in animals transplanted with the original tumors, indicating that this minor PGK component was not contributed by malignant cells. The results indicate that the great majority of recombinant virus-induced AKR leukemias are clonal.}, } @article {pmid7135207, year = {1982}, author = {Jackson, CE and Cerny, JC and Block, MA and Fialkow, PJ}, title = {Probable clonal origin of aldosteronomas versus multicellular origin of parathyroid "adenomas".}, journal = {Surgery}, volume = {92}, number = {5}, pages = {875-879}, pmid = {7135207}, issn = {0039-6060}, support = {AM10206/AM/NIADDK NIH HHS/United States ; CA 16448/CA/NCI NIH HHS/United States ; CA 22595/CA/NCI NIH HHS/United States ; }, mesh = {Adenoma/*pathology ; Adrenal Cortex Neoplasms/genetics/metabolism/*pathology ; Adult ; Aldosterone/*metabolism ; Female ; Genetic Linkage ; Glucosephosphate Dehydrogenase/genetics ; Heterozygote ; Humans ; Hyperaldosteronism/etiology ; Isoenzymes/genetics ; Middle Aged ; Parathyroid Neoplasms/*pathology ; Pedigree ; X Chromosome ; }, abstract = {Adrenocortical adenomas causing hyperaldosteronism in two women heterozygous at the X chromosome-linked glucose-6-phosphate dehydrogenase (G-6-PD) locus exhibited only one G-6-PD isoenzyme. This finding suggests a clonal development for these benign tumors and contrasts with the multicellular origin of parathyroid adenomas reported in three patients from our institution in 1977 and found subsequently in seven other hyperparathyroid women whose cases are reported here. One of these seven patients had hereditary hyperparathyroidism. In this case each of three glands removed showed both A and B G-6-PD isoenzymes in similar ratios as were found in normal tissues. The multicellular origin of hereditary hyperparathyroidism is compatible with the concept of parathyroid lesions being manifestations of the first genetic event in Knudson's two-mutational-event theory for the initiation of cancer. The multicellular origin of sporadic parathyroid tumors suggest that they are caused by some factors stimulating many cells in the parathyroid glands. The young average age of onset of eight cases of parathyroid cancer from five families with hereditary hyperparathyroidism in the literature is also compatible with Knudson's theory. G-6-PD studies of other aldosteronomas, parathyroid tumors, and other endocrine neoplasms may provide important information about the pathogenesis of these conditions.}, } @article {pmid7112116, year = {1982}, author = {Fidler, IJ and Hart, IR}, title = {Biological diversity in metastatic neoplasms: origins and implications.}, journal = {Science (New York, N.Y.)}, volume = {217}, number = {4564}, pages = {998-1003}, doi = {10.1126/science.7112116}, pmid = {7112116}, issn = {0036-8075}, support = {N01-CO-75380/CO/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cell Transformation, Neoplastic/pathology ; Clone Cells ; Humans ; Immunity ; Melanoma/genetics/pathology ; Mice ; Mice, Inbred Strains ; Mutation ; Neoplasm Metastasis/*pathology ; Neoplasms, Experimental/pathology ; Phenotype ; Skin Neoplasms/genetics/pathology ; }, abstract = {Whether neoplasms are unicellular or multicellular in their origin, the process of tumor evolution and progression can rapidly generate biological diversity. Metastases result from the survival and proliferation of specialized subpopulations of cells within the parent tumor. Metastases may have a clonal origin and different metastases may develop from different progenitor cells. However, as with the primary tumor, the origin of metastases is unimportant since the process of tumor evolution and progression can generate biological diversity within and among different metastatic foci.}, } @article {pmid7107068, year = {1982}, author = {Collins, SJ and Fialkow, PJ}, title = {Clonal nature of spontaneous AKR leukemia: studies utilizing the X-linked enzyme phosphoglycerate kinase.}, journal = {International journal of cancer}, volume = {29}, number = {6}, pages = {673-676}, doi = {10.1002/ijc.2910290612}, pmid = {7107068}, issn = {0020-7136}, support = {GM 15253/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Clone Cells ; Female ; Genetic Linkage ; Heterozygote ; Leukemia, Experimental/*genetics ; Male ; Mice ; Mice, Inbred AKR ; Mosaicism ; Neoplasm Transplantation ; Phenotype ; Phosphoglycerate Kinase/*analysis/genetics ; Thymoma/*genetics ; Thymus Neoplasms/*genetics ; X Chromosome ; }, abstract = {AKR mice heterozygous at the X-linked phosphoglycerate kinase (PGK) locus were used in experiments to determine the number of cells from which spontaneous thymic leukemias (thymomas) develop. Because only one of the two X-chromosomes is active in XX somatic cells, thymic leukemias that are clonal should display either type A or type B PGK, but not both, while those that are multicellular in origin may exhibit both enzymes. Spontaneous thymomas from 19 PGK heterozygous animals expressed exclusively (11 tumors) or predominantly (8 tumors) a single enzyme in contrast to non-malignant tissue from these animals which expressed both enzyme types in approximately equal ratios. When primary tumors expressing a single or predominant enzyme type were transplanted, the transplanted tumors invariably displayed the PGK phenotype that predominated in the initial tumor indicating that the minor PGK component was not contributed by malignant cells. These results indicate that spontaneous AKR leukemias are clonal.}, } @article {pmid7043281, year = {1982}, author = {Wintersberger, U}, title = {Chemical carcinogenesis -- the price for DNA - repair?.}, journal = {Die Naturwissenschaften}, volume = {69}, number = {3}, pages = {107-113}, pmid = {7043281}, issn = {0028-1042}, mesh = {Animals ; Base Sequence ; Carcinogens/*pharmacology ; Cell Differentiation ; *Cell Transformation, Neoplastic ; Cell Transformation, Viral ; *DNA Repair ; DNA Replication/drug effects ; Mice ; Retroviridae/genetics ; Teratoma/physiopathology ; Transcription, Genetic/*drug effects ; }, abstract = {This essay examines the possibility of merging the mutation theory of cancer with the hypothesis that cancer is a change in the state of the differentiation of cells. It is suggested that during normal development DNA rearrangements occur, concerning genes which code for differentiation specific cell communication proteins. These proteins are responsible for the proper functioning of growth control in a multicellular organism. DNA-damaging agents - mutagens - induce DNA repair enzymes, some of which may catalyse illegitimate genome rearrangements, thus leading to a change of the balance between growth and differentiation. A cell with a selective advantage may arise and become the origin of a tumor.}, } @article {pmid7031747, year = {1981}, author = {Gensler, HL and Bernstein, H}, title = {DNA damage as the primary cause of aging.}, journal = {The Quarterly review of biology}, volume = {56}, number = {3}, pages = {279-303}, doi = {10.1086/412317}, pmid = {7031747}, issn = {0033-5770}, support = {GM27219/GM/NIGMS NIH HHS/United States ; }, mesh = {*Aging ; Animals ; Brain/metabolism ; Cell Survival ; DNA/*metabolism/radiation effects ; *DNA Repair ; DNA Replication ; DNA, Single-Stranded/metabolism ; Genes ; Models, Biological ; Muscle Development ; Mutation ; Transcription, Genetic ; Ultraviolet Rays ; }, abstract = {DNA damage appears to be ubiquitous in the biological world, as judged by the variety of organisms which have evolved DNA-repair systems. Previously, it was proposed that germ-line DNA of multicellular organisms may be protected from damage, and consequently from aging, by efficient recombinational repair during meiosis. The somatic line, however, may be vulnerable to the accumulation of DNA damage, and hence undergo aging, owing to relatively less repair. Although the DNA lesions most important in aging are not known yet, there is evidence for serveral types of endogenous damage. DNA lesions have been shown to interfere with transcription and replication, and so lead to loss of cell function and death. In mammals, there is a progressive decline of function in many different tissues with increasing age. Deterioration of central nervous system functions appears to be a critical part of the aging process. This may be due to the low DNA repair capacity which is found in postmitotic brain tissue, and which could result in the accumulation of DNA lesions in this tissue. Also reviewed is evidence that species longevity is directly related to tissue DNA-repair capacity and that aging may be accelerated by treatment with DNA-damaging agents, or in individuals with genetically defective repair. Although it has been frequently postulated that somatic mutation may be cause of aging, current evidence suggests that it is probably less important than DNA damage. A prominent theory on the evolution of aging, which attributes special importance to genes that are advantagous in youth but are deleterious later on, is discussed in terms of regulatory genes that reduce DNA repair as cells differentiate to the postmitotic state. Finally, we hypothesize that the factors which determine maximum longevity of individuals in a population are the rate of occurrence of DNA damage, the rate of DNA repair, the degree of cellular redundancy, and the extent of exposure to stress.}, } @article {pmid6172909, year = {1981}, author = {Mustafin, AM}, title = {[One of the possible mechanisms of growth regulation in multicellular organisms and its application to the problems of aging and carcinogenesis].}, journal = {Uspekhi sovremennoi biologii}, volume = {92}, number = {2}, pages = {261-277}, pmid = {6172909}, issn = {0042-1324}, mesh = {*Aging ; Animals ; Biological Evolution ; Cell Cycle ; Cell Differentiation ; Cell Survival ; Cell Transformation, Neoplastic/pathology ; DNA/physiology ; DNA, Neoplasm/physiology ; *Growth ; Growth Substances/physiology ; Humans ; Neoplasms/*etiology/genetics ; Neoplasms, Experimental/*etiology/genetics ; RNA/physiology ; RNA, Neoplasm/physiology ; Regeneration ; }, } @article {pmid7275355, year = {1981}, author = {Reddy, AL and Fialkow, PJ}, title = {Effect of solvents on methylcholanthrene-induced carcinogenesis in mice.}, journal = {International journal of cancer}, volume = {27}, number = {4}, pages = {501-504}, doi = {10.1002/ijc.2910270413}, pmid = {7275355}, issn = {0020-7136}, support = {GM 15253/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Benzene/pharmacology ; Female ; Fibrosarcoma/chemically induced/enzymology/pathology ; Methylcholanthrene ; Mice ; Mice, Inbred BALB C ; Oils/pharmacology ; Phenotype ; Phosphoglycerate Kinase/genetics ; Plants ; Sarcoma, Experimental/chemically induced/enzymology/*pathology ; Solvents/*pharmacology ; }, abstract = {We have shown previously, with X-chromosome linked phosphoglycerate kinase (PGK) cell markers, that the fibrosarcomas induced in mice by subcutaneous injection of 0.2-2.0 mg of methylcholanthrene (MCA) dissolved in olive oil had a multicellular origin. In this study we used a constant dose of MCA injected subcutaneously and compared the effects on tumorigenesis of using benzene or olive oil as the solvents. The benzene and olive oil groups differed in tumor incidence (100% versus 50%), location (muscle versus skin), and type (rhabdomyosarcomas versus fibrosarcomas). Each of the nine olive-oil MCA-induced tumors showed both PGK enzyme types, whereas 13 ot 16 tumors induced by MCA in benzene displayed only a single PGK type. This difference in PGK phenotypes suggests that the MCA-benzene neoplasms arose from one or a few cells. We conclude from these results that the nature of the solvent plays an important role in the type and number of cells from which tumors induced by subcutaneous injection of MCA arise.}, } @article {pmid692174, year = {1978}, author = {Reiner, JM}, title = {Tissue mosaics and clonal mechanisms of atherogenesis.}, journal = {Mechanisms of ageing and development}, volume = {8}, number = {1}, pages = {15-20}, doi = {10.1016/0047-6374(78)90003-9}, pmid = {692174}, issn = {0047-6374}, mesh = {Arteriosclerosis/enzymology/*genetics/pathology ; Cell Count ; Cell Division ; *Clone Cells ; Female ; Genetic Variation ; Glucosephosphate Dehydrogenase/analysis/genetics ; Heterozygote ; Humans ; *Mosaicism ; Probability ; }, abstract = {It is known that atherosclerotic lesions arising in aortae of females heterozygous for the A and B variants of glucose-6-phosphate dehydrogenase are frequently though not invariably of one enzyme type. The occurrence of heterotypic lesions rules out single-cell origin. However, it is possible to analyze the results of such studies in terms of multicellular atherogenic foci. The variance in enzyme proportions in the normal tissue mosaic permits an assessment of clump or patch size. Then an application of geometrical probability permits the derivation of a relation between the proportion of monotypic lesions and the size and cell number of the original atherogenic focus. Comparison with suitable experimental data gives reasonable estimates of these cell numbers. The influence of selection in the cell population on such estimates is considered.}, } @article {pmid74018, year = {1977}, author = {Hildemann, WH and Raison, RL and Cheung, G and Hull, CJ and Akaka, L and Okamoto, J}, title = {Immunological specificity and memory in a scleractinian coral.}, journal = {Nature}, volume = {270}, number = {5634}, pages = {219-223}, doi = {10.1038/270219a0}, pmid = {74018}, issn = {0028-0836}, mesh = {Animals ; Biological Evolution ; Cnidaria/*immunology ; Epitopes ; Graft Rejection ; Histocompatibility Antigens/*analysis/genetics ; *Immunologic Memory ; Polymorphism, Genetic ; }, abstract = {Tissue transplantation immunity with a specific memory component is demonstrated in populations of Montipora. This highly discriminating immunoreactivity derives from extensive allogeneic polymorphism of histocompatibility (H) markers. An H system of immunorecognition is postulated to have originated in multicellular invertebrates probably beginning with coelenterates.}, } @article {pmid982576, year = {1976}, author = {Glasnikova, A and Miklovichova, M}, title = {[Pollen development in the anthers of several cereal strains and hybrids during cultivation in vitro].}, journal = {TSitologiia i genetika}, volume = {10}, number = {5}, pages = {444-449}, pmid = {982576}, issn = {0564-3783}, mesh = {Edible Grain/*growth & development ; Hybridization, Genetic ; In Vitro Techniques ; *Pollen ; Secale/*growth & development ; Species Specificity ; Triticum/*growth & development ; }, abstract = {In order to induce androgenesis in vitro anthers of some cereals were cultivated. The highest number of proembryos was obtained in the hybrid Triticale in F3 generation on Blayder's medium supplemented with 3 and 12% sucrose. Proembryos represented multi-nuclear and multicellular formations which stagnated at the globular stage of development. Origin of roots from calluses was not accompanied by formation of buds. There was no formation of embryos from pollen grains in case of lines Triticum aestivum and Secale cereale.}, } @article {pmid4943851, year = {1971}, author = {Yunis, JJ and Yasmineh, WG}, title = {Heterochromatin, satellite DNA, and cell function. Structural DNA of eucaryotes may support and protect genes and aid in speciation.}, journal = {Science (New York, N.Y.)}, volume = {174}, number = {4015}, pages = {1200-1209}, doi = {10.1126/science.174.4015.1200}, pmid = {4943851}, issn = {0036-8075}, mesh = {Animals ; Biological Evolution ; Cattle ; Cell Nucleus/analysis ; *Chromosomes/analysis ; Congenital Abnormalities/genetics ; *Cytogenetics ; DNA/analysis/*physiology ; Guinea Pigs ; Heterochromatin/analysis/*physiology ; Humans ; Karyotyping ; Meiosis ; Mice ; Mitosis ; Mutation ; Neoplasms/genetics ; Nucleic Acid Hybridization ; Nucleotides/analysis ; Phenotype ; Recombination, Genetic ; Sex Chromosomes ; Species Specificity ; }, abstract = {With the assumption that a portion that comprises some 10 percent of the genomes in higher organisms cannot be without a raison d'être, an extensive review led us to conclude that a certain amount of constitutive heterochromatin is essential in multicellular organisms at two levels of organization, chromosomal and nuclear. At the chromosomal level, constitutive heterochromatin is present around vital areas within the chromosomes. Around the centromeres, for example, heterochromatin is believed to confer protection and strength to the centromeric chromatin. Around secondary constrictions, heterochromatic blocks may ensure against evolutionary change of ribosomal cistrons by decreasing the frequency of crossing-over in these cistrons in meiosis and absorbing the effects of mutagenic agents. During meiosis heterochromatin may aid in the initial alignment of chromosomes prior to synapsis and may facilitate speciation by allowing chromosomal rearrangement and providing, through the species specificity of its DNA, barriers against cross-fertilization. At the nuclear level of organization, constitutive heterochromatin may help maintain the proper spatial relationships necessary for the efficient operation of the cell through the stages of mitosis and meiosis. In the unicellular procaryotes, the presence of a small amount of genetic information in one chromosome obviates the need for constitutive heterochromatin and a nuclear membrane. At higher levels of organization, with an increase in the size of the genome and with evolution of cellular and sexual differentiation, the need for compartmentalization and structural components in the nucleus became imminent. The portion of the genome that was concerned with synthesis of ribosomal RNA was enlarged and localized in specific chromosomes, and the centromere became part of each chromosome when the mitotic spindle was developed in evolution. Concomitant with these changes in the genome, repetitive sequences in the form of constitutive heterochromatin appeared, probably as a result of large-scale duplication. The repetitive DNA's were kept through natural selection because of their importance in preserving these vital regions and in maintaining the structural and functional integrity of the nucleus. The association of satellite (or highly repetitive) DNA with constitutive heterochromatin is understandable, since it stresses the importance of the structural rather than transcriptional roles of these entities. Nuclear satellite DNA's have one property in common despite their species specificity, namely heterochromatization. In this sense the apparent species specificity of satellite DNA may be the result of natural selection for duplicated short polynucleotide segments that are nontranscriptional and can be utilized in specific structural roles.}, } @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 {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 {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 {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 = {}, number = {}, pages = {}, doi = {10.1093/femsre/fuae024}, pmid = {39366767}, issn = {1574-6976}, 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 {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 = {}, doi = {10.1101/2024.05.25.595918}, pmid = {39345370}, issn = {2692-8205}, 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 {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 = {2024}, author = {Kalita, AI and Keller Valsecchi, CI}, title = {Dosage compensation in non-model insects - progress and perspectives.}, journal = {Trends in genetics : TIG}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tig.2024.08.010}, pmid = {39341686}, issn = {0168-9525}, 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 {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 {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}, doi = {10.1098/rsbl.2024.0310}, pmid = {39288812}, issn = {1744-957X}, mesh = {*Symbiosis ; Animals ; *Biological Evolution ; *Reproduction ; Eukaryota/physiology ; Arthropods/microbiology/physiology ; Wolbachia/physiology/genetics ; Toxin-Antitoxin Systems/genetics ; Bacteria/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 {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 {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}, 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 {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 {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 {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 {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 {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 {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 = {*Osteoclasts/metabolism ; Humans ; Animals ; Bone Remodeling ; }, 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}, doi = {10.1146/annurev-cellbio-120123-112853}, pmid = {38985841}, issn = {1530-8995}, 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 {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 {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 {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 {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 {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}, doi = {10.1111/dgd.12935}, 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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 = {RPG-2020-199//Leverhulme Trust/ ; NE/P013678/1//Natural Environment Research Council/ ; //Biosphere Evolution, Transitions and Resilience/ ; //Natural Science Foundation of China/ ; 62220//John Templeton Foundation/ ; GBMF9741//Gordon and Betty Moore Foundation/ ; URF\R\201024//University Research Fellowship to T.W/ ; }, 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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 = {Mice ; Pregnancy ; Humans ; Male ; Female ; Animals ; *Testis/metabolism ; Acetaminophen/toxicity/metabolism ; *Prenatal Exposure Delayed Effects/chemically induced/metabolism ; Leydig Cells/metabolism ; Testosterone/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 {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 {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}, doi = {10.1002/adhm.202302907}, pmid = {37797407}, issn = {2192-2659}, support = {1R011HL150359-01/NH/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 {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 = {Humans ; Mice ; Pregnancy ; Female ; Animals ; *Acetaminophen/toxicity ; Fetal Development ; Osteogenesis ; Bone and Bones ; *Prenatal Exposure Delayed Effects ; }, 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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 {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 = {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 ; 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 ; }, ab