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04 Mar 2024 at 01:58
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Bibliography on: Neanderthals


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Wikipedia: Neanderthals or Neandertals — named for the Neandertal region in Germany — were a species or subspecies of archaic human, in the genus Homo. Neanderthals became extinct around 40,000 years ago. They were closely related to modern humans, sharing 99.7% of DNA. Remains left by Neanderthals include bone and stone tools, which are found in Eurasia, from Western Europe to Central and Northern Asia. Neanderthals are generally classified by paleontologists as the species Homo neanderthalensis, having separated from the Homo sapiens lineage 600,000 years ago, but a minority consider them to be a subspecies of Homo sapiens (Homo sapiens neanderthalensis). Several cultural assemblages have been linked to the Neanderthals in Europe. The earliest, the Mousterian stone tool culture, dates to about 160,000 years ago. Late Mousterian artifacts were found in Gorham's Cave on the south-facing coast of Gibraltar. Compared to Homo sapiens, Neanderthals had a lower surface-to-volume ratio, with shorter legs and a bigger body, in conformance with Bergmann's rule, as an energy-loss reduction adaptation to life in a high-latitude (i.e. seasonally cold) climate. Their average cranial capacity was notably larger than typical for modern humans: 1600 cm3 vs. 1250-1400 cm3. The Neanderthal genome project published papers in 2010 and 2014 stating that Neanderthals contributed to the DNA of modern humans, including most humans outside sub-Saharan Africa, as well as a few populations in sub-Saharan Africa, through interbreeding, likely between 50,000 and 60,000 years ago.

Created with PubMed® Query: ( Neanderthal OR Neandertal ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2024-02-29

Hernaiz-García M, Zanolli C, Martín-Francés L, et al (2024)

Masticatory habits of the adult Neanderthal individual BD 1 from La Chaise-de-Vouthon (France).

American journal of biological anthropology [Epub ahead of print].

OBJECTIVES: The analysis of dental wear provides a useful approach for dietary and cultural habit reconstructions of past human populations. The analysis of macrowear patterns can also be used to better understand the individual chewing behavior and to investigate the biomechanical responses during different biting scenarios. The aim of this study is to evaluate the diet and chewing performance of the adult Neanderthal Bourgeois-Delaunay 1 (BD 1) and to investigate the relationship between wear and cementum deposition under mechanical demands.

MATERIALS AND METHODS: The macrowear pattern of BD 1 was analyzed using the occlusal fingerprint analysis method. We propose a new method for the bilateral measurement of the cementum volume along both buccal and lingual sides of the molar root.

RESULTS: BD 1's anterior dentition is more affected by wear compared to the posterior one. The macrowear pattern suggest a normal chewing behavior and a mixed-diet coming from temperate environments. The teeth on the left side of the mandible display greater levels of wear, as well as the buccal side of the molar crowns. The cementum analysis shows higher buccal volume along the molar roots.

DISCUSSION: BD1 could have been preferably chewing on the left side of the mandible. The exploitation of various food resources suggested by the macrowear analysis is compatible with the environmental reconstructions. Finally, the greater wear on the buccal side of the molar occlusal surface and the greater volume of cementum in that side of the molar roots offers a preliminary understanding about the potential correlation between dental wear and cementum deposition.

RevDate: 2024-02-26

Kerdoncuff E, Skov L, Patterson N, et al (2024)

50,000 years of Evolutionary History of India: Insights from ~2,700 Whole Genome Sequences.

bioRxiv : the preprint server for biology pii:2024.02.15.580575.

India has been underrepresented in whole genome sequencing studies. We generated 2,762 high coverage genomes from India - including individuals from most geographic regions, speakers of all major languages, and tribal and caste groups - providing a comprehensive survey of genetic variation in India. With these data, we reconstruct the evolutionary history of India through space and time at fine scales. We show that most Indians derive ancestry from three ancestral groups related to ancient Iranian farmers, Eurasian Steppe pastoralists and South Asian hunter-gatherers. We uncover a common source of Iranian-related ancestry from early Neolithic cultures of Central Asia into the ancestors of Ancestral South Indians (ASI), Ancestral North Indians (ANI), Austro-asiatic-related and East Asian-related groups in India. Following these admixtures, India experienced a major demographic shift towards endogamy, resulting in extensive homozygosity and identity-by-descent sharing among individuals. At deep time scales, Indians derive around 1-2% of their ancestry from gene flow from archaic hominins, Neanderthals and Denisovans. By assembling the surviving fragments of archaic ancestry in modern Indians, we recover ~1.5 Gb (or 50%) of the introgressing Neanderthal and ~0.6 Gb (or 20%) of the introgressing Denisovan genomes, more than any other previous archaic ancestry study. Moreover, Indians have the largest variation in Neanderthal ancestry, as well as the highest amount of population-specific Neanderthal segments among worldwide groups. Finally, we demonstrate that most of the genetic variation in Indians stems from a single major migration out of Africa that occurred around 50,000 years ago, with minimal contribution from earlier migration waves. Together, these analyses provide a detailed view of the population history of India and underscore the value of expanding genomic surveys to diverse groups outside Europe.

RevDate: 2024-02-24
CmpDate: 2024-02-23

Schmidt P, Iovita R, Charrié-Duhaut A, et al (2024)

Ochre-based compound adhesives at the Mousterian type-site document complex cognition and high investment.

Science advances, 10(8):eadl0822.

Ancient adhesives used in multicomponent tools may be among our best material evidences of cultural evolution and cognitive processes in early humans. African Homo sapiens is known to have made compound adhesives from naturally sticky substances and ochre, a technical behavior proposed to mark the advent of elaborate cognitive processes in our species. Foragers of the European Middle Paleolithic also used glues, but evidence of ochre-based compound adhesives is unknown. Here, we present evidence of this kind. Bitumen was mixed with high loads of goethite ochre to make compound adhesives at the type-site of the Mousterian, Le Moustier (France). Ochre loads were so high that they lowered the adhesive's performance in classical hafting situations where stone implements are glued to handles. However, when used as handheld grips on cutting or scraping tools, a behavior known from Neanderthals, high-ochre adhesives present a real benefit, improving their solidity and rigidity. Our findings help understand the implications of Pleistocene adhesive making.

RevDate: 2024-02-21

Pablos A, JL Arsuaga (2024)

Metatarsals and foot phalanges from the Sima de los Huesos Middle Pleistocene site (Atapuerca, Burgos, Spain).

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

This study provides a complete, updated and illustrated inventory, as well as a comprehensive study, of the metatarsals and foot phalanges (forefoot) recovered from the Middle Pleistocene site of Sima de los Huesos (SH, Atapuerca, Spain) in comparison to other Homo comparative samples, both extant and fossils. This current updated review has established a minimum number of individuals (MNI) of 17, which represent 58.6% of the 29 dental individuals identified within the SH sample. An exclusive or autoapomorphic combination of traits can be recognized within the SH hominin foot sample. A few traits appear primitive or plesiomorphic when compared with earlier Homo individuals and other recent modern humans. There are other metrical and morphological traits that SH hominins and Neandertals have in common that sometimes represent shared derived traits in this evolutionary line, most of which are probably related to robusticity. Furthermore, some exclusive autoapomorphic traits are observed in the SH sample: a very broad first metatarsal, long and broad hallucal proximal foot phalanges and possibly extremely robust lateral distal foot phalanges compared to those of Neandertals and modern humans. In these last traits, the SH metatarsals and pedal phalanges are even more robust than in Neandertals. They are herein named as "hyper-Neandertal" traits, which could suggest a slight gracilization process in this evolutionary line, at least in the hallux toe. Finally, some paleobiological inferences are made in relation to body size (stature and body mass) and some associations are proposed within the SH sample.

RevDate: 2024-02-21

Cerrito P, Nava A, Radovčić D, et al (2024)

Correction: 'Dental cementum virtual histology of Neanderthal teeth from Krapina (Croatia, 130-120 kyr): an informed estimate of age, sex and adult stressors' (2022), by Cerrito et al.

Journal of the Royal Society, Interface, 21(211):20240069.

RevDate: 2024-02-20

Liu S, Luo H, Zhang P, et al (2024)

Adaptive Selection of Cis-regulatory Elements in the Han Chinese.

Molecular biology and evolution pii:7611635 [Epub ahead of print].

Cis-regulatory elements (CREs) have an important role in human adaptation to the living environment. However, the lag in population genomic cohort studies and epigenomic studies, hinders the research in the adaptive analysis of CREs in human populations. In this study, we collected 4,013 unrelated individuals and performed a comprehensive analysis of adaptive selection of genome-wide CREs in the Han Chinese. In total, 12.34% of genomic regions are under the influence of adaptive selection, where 1.00% of enhancers and 2.06% of promoters are under positive selection, and 0.06% of enhancers and 0.02% of promoters are under balancing selection. Gene ontology enrichment analysis of these CREs under adaptive selection reveals that many positive selections in the Han Chinese occur in pathways involved in cell-cell adhesion processes, and many balancing selections are related to immune processes. Two classes of adaptive CREs related to cell adhesion were in-depth analysed, one is the adaptive enhancers derived from neanderthal introgression, leads to lower hyaluronidase level in skin, and brings better performance on UV-radiation resistance to the Han Chinese. Another one is the CREs regulating wound healing, and the results suggest the positive selection inhibits coagulation and promotes angiogenesis and wound healing in the Han Chinese. Finally, we found that many pathogenic alleles, such as risky alleles of type 2 diabetes or schizophrenia, remain in the population due to the hitchhiking effect of positive selections. Our findings will help deepen our understanding of the adaptive evolution of genome regulation in the Han Chinese.

RevDate: 2024-02-20

Yousefi M, Jouladeh-Roudbar A, A Kafash (2024)

Mapping endemic freshwater fish richness to identify high-priority areas for conservation: An ecoregion approach.

Ecology and evolution, 14(2):e10970.

Freshwater ecosystems are experiencing accelerating global biodiversity loss. Thus, knowing where these unique ecosystems' species richness reaches a peak can facilitate their conservation planning. By hosting more than 290 freshwater fishes, Iran is a major freshwater fish hotspot in the Middle East. Considering the accelerating rate of biodiversity loss, there is an urgent need to identify species-rich areas and understand the mechanisms driving biodiversity distribution. In this study, we gathered distribution records of all endemic freshwater fishes of Iran (85 species) to develop their richness map and determine the most critical drivers of their richness patterns from an ecoregion approach. We performed a generalized linear model (GLM) with quasi-Poisson distribution to identify contemporary and historical determinants of endemic freshwater fish richness. We also quantified endemic fish similarity among the 15 freshwater ecoregions of Iran. Results showed that endemic freshwater fish richness is highest in the Zagros Mountains while a moderate level of richness was observed between Zagros and Alborz Mountains. High, moderate, and low richness of endemic freshwater fish match with Upper Tigris & Euphrates, Namak, and Kavir & Lut Deserts ecoregions respectively. Kura - South Caspian Drainages and Caspian Highlands were the most similar ecoregions and Orumiyeh was the most unique ecoregion according to endemic fish presence. Precipitation and precipitation change velocity since the Last Glacial Maximum were the most important predictors of endemic freshwater fish richness. Areas identified to have the highest species richness have high priority for the conservation of freshwater fish in Iran, therefore, should be considered in future protected areas development.

RevDate: 2024-02-20
CmpDate: 2024-02-20

Dehay C, WB Huttner (2024)

Development and evolution of the primate neocortex from a progenitor cell perspective.

Development (Cambridge, England), 151(4):.

The generation of neurons in the developing neocortex is a major determinant of neocortex size. Crucially, the increase in cortical neuron numbers in the primate lineage, notably in the upper-layer neurons, contributes to increased cognitive abilities. Here, we review major evolutionary changes affecting the apical progenitors in the ventricular zone and focus on the key germinal zone constituting the foundation of neocortical neurogenesis in primates, the outer subventricular zone (OSVZ). We summarize characteristic features of the OSVZ and its key stem cell type, the basal (or outer) radial glia. Next, we concentrate on primate-specific and human-specific genes, expressed in OSVZ-progenitors, the ability of which to amplify these progenitors by targeting the regulation of the cell cycle ultimately underlies the evolutionary increase in upper-layer neurons. Finally, we address likely differences in neocortical development between present-day humans and Neanderthals that are based on human-specific amino acid substitutions in proteins operating in cortical progenitors.

RevDate: 2024-02-17

Voinescu CD, Mozere M, Genovese G, et al (2024)

A Neanderthal haplotype introgressed into the human genome confers protection against membranous nephropathy.

Kidney international pii:S0085-2538(24)00073-5 [Epub ahead of print].

Class 2 HLA and PLA2R1 alleles are exceptionally strong genetic risk factors for membranous nephropathy (MN), leading, through an unknown mechanism, to a targeted autoimmune response. Introgressed archaic haplotypes (introduced from an archaic human genome into the modern human genome) might influence phenotypes through gene dysregulation. Here, we investigated the genomic region surrounding the PLA2R1 gene. We reconstructed the phylogeny of Neanderthal and modern haplotypes in this region and calculated the probability of the observed clustering being the result of introgression or common descent. We imputed variants for the participants in our previous genome-wide association study and we compared the distribution of Neanderthal variants between MN cases and controls. The region associated with the lead MN risk locus in the PLA2R1 gene was confirmed and showed that, within a 507 kb region enriched in introgressed sequence, a stringently defined 105 kb haplotype, intersecting the coding regions for PLA2R1 and ITGB6, is inherited from Neanderthals. Thus, introgressed Neanderthal haplotypes overlapping PLA2R1 are differentially represented in MN cases and controls, with enrichment In controls suggesting a protective effect.

RevDate: 2024-02-17

Zeberg H, Jakobsson M, S Pääbo (2024)

The genetic changes that shaped Neandertals, Denisovans, and modern humans.

Cell pii:S0092-8674(23)01403-4 [Epub ahead of print].

Modern human ancestors diverged from the ancestors of Neandertals and Denisovans about 600,000 years ago. Until about 40,000 years ago, these three groups existed in parallel, occasionally met, and exchanged genes. A critical question is why modern humans, and not the other two groups, survived, became numerous, and developed complex cultures. Here, we discuss genetic differences among the groups and some of their functional consequences. As more present-day genome sequences become available from diverse groups, we predict that very few, if any, differences will distinguish all modern humans from all Neandertals and Denisovans. We propose that the genetic basis of what constitutes a modern human is best thought of as a combination of genetic features, where perhaps none of them is present in each and every present-day individual.

RevDate: 2024-02-12

Yaghmouri M, P Izadi (2024)

Role of the Neanderthal Genome in Genetic Susceptibility to COVID-19: 3p21.31 Locus in the Spotlight.

Biochemical genetics [Epub ahead of print].

Since the outbreak of COVID-19, genome-wide association studies have tried to discover the role of genetic predisposition in the clinical variability of this viral infection. The findings of various investigations have led to several loci for COVID-19 genetic susceptibility. Among candidate regions, the 3p21.31 locus has been in the spotlight among scientists, as it can increase the risk of severe COVID-19 by almost two fold. In addition to its substantial association with COVID-19 severity, this locus is related to some common diseases, such as diabetes, malignancies, and coronary artery disease. This locus also harbors evolutionary traces of Neanderthal genomes, which is believed to be the underlying reason for its association with COVID-19 severity. Additionally, the inheritance of this locus from Neanderthals seems to be under positive selection. This review aims to summarize a collection of evidence on the 3p21.31 locus and its impact on COVID-19 outcomes by focusing on the risk variants originated from the Neanderthal genome. Moreover, we discuss candidate genes at this locus and the possible mechanisms by which they influence the progression of COVID-19 symptoms. Better insights into human genetic susceptibility to newly emerging diseases such as COVID-19 and its evolutionary origin can provide fundamentals for risk assessment of different populations as well as the development of personalized prevention and treatments based on genomic medicine.

RevDate: 2024-02-05

Russo G, Milks A, Leder D, et al (2024)

Author Correction: First direct evidence of lion hunting and the early use of a lion pelt by Neanderthals.

Scientific reports, 14(1):2772 pii:10.1038/s41598-024-52963-y.

RevDate: 2024-02-01

Curry A (2024)

In Europe, an early, cold dawn for modern humans.

Science (New York, N.Y.), 383(6682):468-469.

Moderns made mysterious ice age artifacts-implying overlap with Neanderthals.

RevDate: 2024-01-31

Pederzani S, Britton K, Trost M, et al (2024)

Stable isotopes show Homo sapiens dispersed into cold steppes ~45,000 years ago at Ilsenhöhle in Ranis, Germany.

Nature ecology & evolution [Epub ahead of print].

The spread of Homo sapiens into new habitats across Eurasia ~45,000 years ago and the concurrent disappearance of Neanderthals represents a critical evolutionary turnover in our species' history. 'Transitional' technocomplexes, such as the Lincombian-Ranisian-Jerzmanowician (LRJ), characterize the European record during this period but their makers and evolutionary significance have long remained unclear. New evidence from Ilsenhöhle in Ranis, Germany, now provides a secure connection of the LRJ to H. sapiens remains dated to ~45,000 years ago, making it one of the earliest forays of our species to central Europe. Using many stable isotope records of climate produced from 16 serially sampled equid teeth spanning ~12,500 years of LRJ and Upper Palaeolithic human occupation at Ranis, we review the ability of early humans to adapt to different climate and habitat conditions. Results show that cold climates prevailed across LRJ occupations, with a temperature decrease culminating in a pronounced cold excursion at ~45,000-43,000 cal BP. Directly dated H. sapiens remains confirm that humans used the site even during this very cold phase. Together with recent evidence from the Initial Upper Palaeolithic, this demonstrates that humans operated in severe cold conditions during many distinct early dispersals into Europe and suggests pronounced adaptability.

RevDate: 2024-01-31

Mylopotamitaki D, Weiss M, Fewlass H, et al (2024)

Homo sapiens reached the higher latitudes of Europe by 45,000 years ago.

Nature [Epub ahead of print].

The Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe[1]. Local hybridization between the two groups occurred[2], but not on all occasions[3]. Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups[4]. One such technocomplex for which the makers are unknown is the Lincombian-Ranisian-Jerzmanowician (LRJ), which has been described in northwestern and central Europe[5-8]. Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated with an LRJ assemblage at the site Ilsenhöhle in Ranis (Germany). These human remains are among the earliest directly dated Upper Palaeolithic H. sapiens remains in Eurasia. We show that early H. sapiens associated with the LRJ were present in central and northwestern Europe long before the extinction of late Neanderthals in southwestern Europe. Our results strengthen the notion of a patchwork of distinct human populations and technocomplexes present in Europe during this transitional period.

RevDate: 2024-01-31

Janivara R, Hazra U, Pfennig A, et al (2024)

Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men.

bioRxiv : the preprint server for biology pii:2024.01.12.575396.

Androgenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics of male pattern baldness comes from individuals of European descent. Here, we examined a novel dataset comprising 2,136 men from Ghana, Nigeria, Senegal, and South Africa that were genotyped using a custom array. We first tested how genetic predictions of baldness generalize from Europe to Africa, finding that polygenic scores from European GWAS yielded AUC statistics that ranged from 0.513 to 0.546, indicating that genetic predictions of baldness in African populations performed notably worse than in European populations. Subsequently, we conducted the first African GWAS of androgenetic alopecia, focusing on self-reported baldness patterns at age 45. After correcting for present age, population structure, and study site, we identified 266 moderately significant associations, 51 of which were independent (p-value < 10 [-5] , r [2] < 0.2). Most baldness associations were autosomal, and the X chromosomes does not appear to have a large impact on baldness in African men. Finally, we examined the evolutionary causes of continental differences in genetic architecture. Although Neanderthal alleles have previously been associated with skin and hair phenotypes, we did not find evidence that European-ascertained baldness hits were enriched for signatures of ancient introgression. Most loci that are associated with androgenetic alopecia are evolving neutrally. However, multiple baldness-associated SNPs near the EDA2R and AR genes have large allele frequency differences between continents. Collectively, our findings illustrate how evolutionary history contributes to the limited portability of genetic predictions across ancestries.

RevDate: 2024-01-26

Jambrina-Enríquez M, Mallol C, Herrera Herrera AV, et al (2024)

Microstratigraphic, lipid biomarker and stable isotope study of a middle Palaeolithic combustion feature from Axlor, Spain.

iScience, 27(1):108755.

Archaeological research has increasingly focused on studying combustion features as valuable sources of information regarding past technological and cultural aspects. The use of microstratigraphic and biomolecular techniques enables the identification of combustion residues and substrate components, and infer about past fire-related activities and the environments. Our study conducted on a combustion feature (Level N, ∼100 Ka) at the Axlor cave, a Middle Paleolithic site in northern Iberia, exemplifies the interdisciplinary approach to combustion features. Micromorphological features revealed depositional activities associated with occupations such as hearth rake-out and trampling. Through molecular (n-alkanes, n-alcohols, and n-fatty acids) and isotopic analysis (δ[13]C16:0 and δ[13]C18:0), we infer the good preservation of organic matter, the contributions of non-ruminant fats, and the dead-wood gathering strategies by Neanderthal groups. By combining microstratigraphic and biomolecular approaches, our study significantly contributes to the advancement of our current understanding of Neanderthal pyrotechnology.

RevDate: 2024-01-23

Bailey SE, Davies TW, Imbrasas MD, et al (2024)

New Neanderthal remains from Axlor cave (Dima, Biscay, northern Iberian Peninsula).

Journal of human evolution, 187:103483 pii:S0047-2484(23)00162-8 [Epub ahead of print].

RevDate: 2024-01-24
CmpDate: 2024-01-24

Peyrégne S, Slon V, J Kelso (2024)

More than a decade of genetic research on the Denisovans.

Nature reviews. Genetics, 25(2):83-103.

Denisovans, a group of now extinct humans who lived in Eastern Eurasia in the Middle and Late Pleistocene, were first identified from DNA sequences just over a decade ago. Only ten fragmentary remains from two sites have been attributed to Denisovans based entirely on molecular information. Nevertheless, there has been great interest in using genetic data to understand Denisovans and their place in human history. From the reconstruction of a single high-quality genome, it has been possible to infer their population history, including events of admixture with other human groups. Additionally, the identification of Denisovan DNA in the genomes of present-day individuals has provided insights into the timing and routes of dispersal of ancient modern humans into Asia and Oceania, as well as the contributions of archaic DNA to the physiology of present-day people. In this Review, we synthesize more than a decade of research on Denisovans, reconcile controversies and summarize insights into their population history and phenotype. We also highlight how our growing knowledge about Denisovans has provided insights into our own evolutionary history.

RevDate: 2024-01-22

Massé L, d'Incau E, Souron A, et al (2024)

Unraveling the Life History of Past Populations through Hypercementosis: Insights into Cementum Apposition Patterns and Possible Etiologies Using Micro-CT and Confocal Microscopy.

Biology, 13(1): pii:biology13010043.

The "teeth-as-tools" hypothesis posits that Neanderthals used their anterior teeth as a tool or a third hand for non-dietary purposes. These non- or para-masticatory activities (e.g., tool-making or food preparation prior to ingestion) have also been described in other past and extant human populations, and other Primates. Cementum is the mineralized tissue that covers the tooth root surface and anchors it to the alveolar bone. Under certain conditions (e.g., mechanical stress, infection), its production becomes excessive (i.e., beyond the physiological state) and is called 'hypercementosis'. Several studies in dental anthropology have established a correlation between the teeth-as-tools and hypercementosis. The present work aims to characterize the different patterns of cementum apposition on archeological teeth and discuss their supposed etiology. Using microtomography and confocal microscopy, the patterns of cementum apposition (i.e., thickness, location, and surface characteristics) were analyzed in 35 hypercementotic teeth (Sains-en-Gohelle, France; 7th-17th c. A.D.). Four groups were identified with distinct hypercementosis patterns: (1) impacted, (2) infected, (3) hypofunctional, and (4) hyperfunctional teeth. Characterizing hypercementosis can contribute to documenting the oral health status (paleopathology) and/or masticatory activity of individuals, even from isolated teeth. This has implications for the study of fossil hominins, particularly Neanderthals, known for their use of anterior teeth as tools and frequent and substantial occurrence of hypercementosis.

RevDate: 2024-01-12

Borodko DD, Zhenilo SV, FS Sharko (2023)

Search for differentially methylated regions in ancient and modern genomes.

Vavilovskii zhurnal genetiki i selektsii, 27(7):820-828.

Currently, active research is focused on investigating the mechanisms that regulate the development of various pathologies and their evolutionary dynamics. Epigenetic mechanisms, such as DNA methylation, play a significant role in evolutionary processes, as their changes have a faster impact on the phenotype compared to mutagenesis. In this study, we attempted to develop an algorithm for identifying differentially methylated regions associated with metabolic syndrome, which have undergone methylation changes in humans during the transition from a hunter-gatherer to a sedentary lifestyle. The application of existing whole-genome bisulfite sequencing methods is limited for ancient samples due to their low quality and fragmentation, and the approach to obtaining DNA methylation profiles differs significantly between ancient hunter-gatherer samples and modern tissues. In this study, we validated DamMet, an algorithm for reconstructing ancient methylomes. Application of DamMet to Neanderthal and Denisovan genomes showed a moderate level of correlation with previously published methylation profiles and demonstrated an underestimation of methylation levels in the reconstructed profiles by an average of 15-20 %. Additionally, we developed a new Python-based algorithm that allows for the comparison of methylomes in ancient and modern samples, despite the absence of methylation profiles in modern bone tissue within the context of obesity. This analysis involves a two-step data processing approach, where the first step involves the identification and filtration of tissue-specific methylation regions, and the second step focuses on the direct search for differentially methylated regions in specific areas associated with the researcher's target condition. By applying this algorithm to test data, we identified 38 differentially methylated regions associated with obesity, the majority of which were located in promoter regions. The pipeline demonstrated sufficient efficiency in detecting these regions. These results confirm the feasibility of reconstructing DNA methylation profiles in ancient samples and comparing them with modern methylomes. Furthermore, possibilities for further methodological development and the implementation of a new step for studying differentially methylated positions associated with evolutionary processes are discussed.

RevDate: 2024-01-08

Huttner WB, Heide M, Mora-Bermúdez F, et al (2024)

Neocortical neurogenesis in development and evolution-Human-specific features.

The Journal of comparative neurology [Epub ahead of print].

In this review, we focus on human-specific features of neocortical neurogenesis in development and evolution. Two distinct topics will be addressed. In the first section, we discuss the expansion of the neocortex during human evolution and concentrate on the human-specific gene ARHGAP11B. We review the ability of ARHGAP11B to amplify basal progenitors and to expand a primate neocortex. We discuss the contribution of ARHGAP11B to neocortex expansion during human evolution and its potential implications for neurodevelopmental disorders and brain tumors. We then review the action of ARHGAP11B in mitochondria as a regulator of basal progenitor metabolism, and how it promotes glutaminolysis and basal progenitor proliferation. Finally, we discuss the increase in cognitive performance due to the ARHGAP11B-induced neocortical expansion. In the second section, we focus on neocortical development in modern humans versus Neanderthals. Specifically, we discuss two recent findings pointing to differences in neocortical neurogenesis between these two hominins that are due to a small number of amino acid substitutions in certain key proteins. One set of such proteins are the kinetochore-associated proteins KIF18a and KNL1, where three modern human-specific amino acid substitutions underlie the prolongation of metaphase during apical progenitor mitosis. This prolongation in turn is associated with an increased fidelity of chromosome segregation to the apical progenitor progeny during modern human neocortical development, with implications for the proper formation of radial units. Another such key protein is transketolase-like 1 (TKTL1), where a single modern human-specific amino acid substitution endows TKTL1 with the ability to amplify basal radial glia, resulting in an increase in upper-layer neuron generation. TKTL1's ability is based on its action in the pentose phosphate pathway, resulting in increased fatty acid synthesis. The data imply greater neurogenesis during neocortical development in modern humans than Neanderthals due to TKTL1, in particular in the developing frontal lobe.

RevDate: 2024-01-08
CmpDate: 2024-01-05

Levinstein Hallak K, S Rosset (2024)

Dating ancient splits in phylogenetic trees, with application to the human-Neanderthal split.

BMC genomic data, 25(1):4.

BACKGROUND: We tackle the problem of estimating species TMRCAs (Time to Most Recent Common Ancestor), given a genome sequence from each species and a large known phylogenetic tree with a known structure (typically from one of the species). The number of transitions at each site from the first sequence to the other is assumed to be Poisson distributed, and only the parity of the number of transitions is observed. The detailed phylogenetic tree contains information about the transition rates in each site. We use this formulation to develop and analyze multiple estimators of the species' TMRCA. To test our methods, we use mtDNA substitution statistics from the well-established Phylotree as a baseline for data simulation such that the substitution rate per site mimics the real-world observed rates.

RESULTS: We evaluate our methods using simulated data and compare them to the Bayesian optimizing software BEAST2, showing that our proposed estimators are accurate for a wide range of TMRCAs and significantly outperform BEAST2. We then apply the proposed estimators on Neanderthal, Denisovan, and Chimpanzee mtDNA genomes to better estimate their TMRCA with modern humans and find that their TMRCA is substantially later, compared to values cited recently in the literature.

CONCLUSIONS: Our methods utilize the transition statistics from the entire known human mtDNA phylogenetic tree (Phylotree), eliminating the requirement to reconstruct a tree encompassing the specific sequences of interest. Moreover, they demonstrate notable improvement in both running speed and accuracy compared to BEAST2, particularly for earlier TMRCAs like the human-Chimpanzee split. Our results date the human - Neanderthal TMRCA to be [Formula: see text] years ago, considerably later than values cited in other recent studies.

RevDate: 2023-12-19

Palancar CA, Bastir M, Rosas A, et al (2023)

Modern human atlas ranges of motion and Neanderthal estimations.

Journal of human evolution, 187:103482 pii:S0047-2484(23)00161-6 [Epub ahead of print].

RevDate: 2023-12-19

Zhao H, Liu LL, Sun J, et al (2023)

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression.

Science China. Life sciences [Epub ahead of print].

Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution.

RevDate: 2023-12-14

Velazquez-Arcelay K, Colbran LL, McArthur E, et al (2023)

Archaic Introgression Shaped Human Circadian Traits.

Genome biology and evolution, 15(12):.

When the ancestors of modern Eurasians migrated out of Africa and interbred with Eurasian archaic hominins, namely, Neanderthals and Denisovans, DNA of archaic ancestry integrated into the genomes of anatomically modern humans. This process potentially accelerated adaptation to Eurasian environmental factors, including reduced ultraviolet radiation and increased variation in seasonal dynamics. However, whether these groups differed substantially in circadian biology and whether archaic introgression adaptively contributed to human chronotypes remain unknown. Here, we traced the evolution of chronotype based on genomes from archaic hominins and present-day humans. First, we inferred differences in circadian gene sequences, splicing, and regulation between archaic hominins and modern humans. We identified 28 circadian genes containing variants with potential to alter splicing in archaics (e.g., CLOCK, PER2, RORB, and RORC) and 16 circadian genes likely divergently regulated between present-day humans and archaic hominins, including RORA. These differences suggest the potential for introgression to modify circadian gene expression. Testing this hypothesis, we found that introgressed variants are enriched among expression quantitative trait loci for circadian genes. Supporting the functional relevance of these regulatory effects, we found that many introgressed alleles have associations with chronotype. Strikingly, the strongest introgressed effects on chronotype increase morningness, consistent with adaptations to high latitude in other species. Finally, we identified several circadian loci with evidence of adaptive introgression or latitudinal clines in allele frequency. These findings identify differences in circadian gene regulation between modern humans and archaic hominins and support the contribution of introgression via coordinated effects on variation in human chronotype.

RevDate: 2023-12-11

Wragg Sykes R (2023)

Were Neanderthals soulful inventors or strange cannibals?.

Nature, 624(7991):247-248.

RevDate: 2023-12-11

Yilmaz F, Karageorgiou C, Kim K, et al (2023)

Ancient AMY1 gene duplications primed the amylase locus for adaptive evolution upon the onset of agriculture.

bioRxiv : the preprint server for biology pii:2023.11.27.568916.

Starch digestion is a cornerstone of human nutrition. The amylase enzyme, which digests starch, plays a key role in starch metabolism. Indeed, the copy number of the human amylase gene has been associated with metabolic diseases and adaptation to agricultural diets. Previous studies suggested that duplications of the salivary amylase gene are of recent origin. In the course of characterizing 51 distinct amylase haplotypes across 98 individuals employing long-read DNA sequencing and optical mapping methods, we detected four 31mers linked to duplication of the amylase locus. Analyses with these 31mers suggest that the first duplication of the amylase locus occurred more than 700,000 years ago before the split between modern humans and Neanderthals. After the original duplication events, amplification of the AMY1 genes likely occurred via nonallelic homologous recombination in a manner that consistently results in an odd number of copies per chromosome. These findings suggest that amylase haplotypes may have been primed for bursts of natural-selection associated duplications that coincided with the incorporation of starch into human diets.

RevDate: 2023-12-05

Wroblewski TH, Witt KE, Lee SB, et al (2023)

Pharmacogenetic variation in Neanderthals and Denisovans and implications for human health and response to medications.

Genome biology and evolution pii:7459155 [Epub ahead of print].

Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals. The impact of archaic DNA may be particularly evident in pharmacogenes - genes responsible for the processing of exogenous substances such as food, pollutants, and medications - as these can relate to changing environmental effects, and beneficial variants may have been retained as modern humans encountered new environments. However, the health implications and contribution of archaic ancestry in pharmacogenes of modern humans remain understudied. Here, we explore eleven key cytochrome P450 genes (CYP450) involved in 75% of all drug metabolizing reactions in three Neanderthal and one Denisovan individuals and examine archaic introgression in modern human populations. We infer the metabolizing efficiency of these eleven CYP450 genes in archaic individuals and find important predicted phenotypic differences relative to modern human variants. We identify several single nucleotide variants shared between archaic and modern humans in each gene, including some potentially function-altering mutations in archaic CYP450 genes, which may result in altered metabolism in living people carrying these variants. We also identified several variants in the archaic CYP450 genes that are novel and unique to archaic humans as well as one gene, CYP2B6, that shows evidence for a gene duplication found only in Neanderthals and modern Africans. Finally, we highlight CYP2A6, CYP2C9, and CYP2J2, genes which show evidence for archaic introgression into modern humans and posit evolutionary hypotheses that explain their allele frequencies in modern populations.

RevDate: 2023-12-04

Gaudzinski-Windheuser S, Kindler L, W Roebroeks (2023)

Widespread evidence for elephant exploitation by Last Interglacial Neanderthals on the North European plain.

Proceedings of the National Academy of Sciences of the United States of America, 120(50):e2309427120.

Neanderthals hunted and butchered straight-tusked elephants, the largest terrestrial mammals of the Pleistocene, in a lake landscape on the North European plain, 125,000 years ago, as recently shown by a study of the Last Interglacial elephant assemblage from Neumark-Nord (Germany). With evidence for a remarkable focus on adult males and on their extended utilization, the data from this location are thus far without parallel in the archaeological record. Given their relevance for our knowledge of the Neanderthal niche, we investigated whether the Neumark-Nord subsistence practices were more than a local phenomenon, possibly determined by local characteristics. Analyzing elephant remains from two other Last Interglacial archaeological sites on the North European plain, Gröbern and Taubach, we identified in both assemblages similar butchering patterns as at Neumark-Nord, demonstrating that extended elephant exploitation was a widespread Neanderthal practice during the (early part of the) Last Interglacial. The substantial efforts needed to process these animals, weighing up to 13 metric tons, and the large amounts of food generated suggest that Neanderthals either had ways of storing vast amounts of meat and fat and/or temporarily aggregated in larger groups than commonly acknowledged. The data do not allow us to rule out one of the two explanations, and furthermore both factors, short-term larger group sizes as well as some form of food preservation, may have played a role. What the data do show is that exploitation of large straight-tusked elephants was a widespread and recurring phenomenon amongst Last Interglacial Neanderthals on the North European plain.

RevDate: 2023-12-03

Abrams G, Devièse T, Pirson S, et al (2023)

Investigating the co-occurrence of Neanderthals and modern humans in Belgium through direct radiocarbon dating of bone implements.

Journal of human evolution, 186:103471 pii:S0047-2484(23)00150-1 [Epub ahead of print].

RevDate: 2023-11-29

Agata A, Ohtsuka S, Noji R, et al (2023)

A Neanderthal/Denisovan GLI3 variant contributes to anatomical variations in mice.

Frontiers in cell and developmental biology, 11:1247361 pii:1247361.

Changes in genomic structures underlie phenotypic diversification in organisms. Amino acid-changing mutations affect pleiotropic functions of proteins, although little is known about how mutated proteins are adapted in existing developmental programs. Here we investigate the biological effects of a variant of the GLI3 transcription factor (GLI3[R1537C]) carried in Neanderthals and Denisovans, which are extinct hominins close to modern humans. R1537C does not compromise protein stability or GLI3 activator-dependent transcriptional activities. In contrast, R1537C affects the regulation of downstream target genes associated with developmental processes. Furthermore, genome-edited mice carrying the Neanderthal/Denisovan GLI3 mutation exhibited various alterations in skeletal morphology. Our data suggest that an extinct hominin-type GLI3 contributes to species-specific anatomical variations, which were tolerated by relaxed constraint in developmental programs during human evolution.

RevDate: 2023-11-28

Lee OY, Wu HHT, Besra GS, et al (2023)

Sensitive lipid biomarker detection for tuberculosis in late Neanderthal skeletons from Subalyuk Cave, Hungary.

Tuberculosis (Edinburgh, Scotland), 143S:102420.

Skeletal remains of two Neanderthal individuals, a 25-35 year-old woman and a 3-4 year-old child, were discovered in a Subalyuk Cave in North-Eastern Hungary. Radiocarbon dating of the female and child remains revealed an age of 39,732-39,076 and 36,117-35,387 cal BP, respectively. Paleopathological studies of these Neanderthal remains revealed probable evidence of skeletal mycobacterial infection, including in the sacrum of the adult specimen and the endocranial surface of the child's skull. Application of PCR amplification to the juvenile cranium and a vertebra gave a positive result (IS6110) for tuberculosis, backed up by spoligotyping. Lipid biomarker analyses of the same two specimens revealed definitive signals for C32 mycoserosates, a very characteristic component of the Mycobacterium tuberculosis complex (MTBC). A vertebra from the adult provided weak evidence for mycocerosate biomarkers. The correlation of probable skeletal lesions with characteristic amplified DNA fragments and a proven lipid biomarker points to the presence of tuberculosis in these Neanderthals. In particular, the closely similar biomarker profiles, for two distinct juvenile cranial and vertebral bones, strengthen this diagnosis.

RevDate: 2023-11-28

Pálfi G, Molnár E, Bereczki Z, et al (2023)

Re-examination of the Subalyuk Neanderthal remains uncovers signs of probable TB infection (Subalyuk Cave, Hungary).

Tuberculosis (Edinburgh, Scotland), 143S:102419.

In 1932, skeletal remains of two Neanderthal individuals, a young adult female and a 3-4-year-old child, were discovered in Subalyuk Cave in Northern Hungary [1,2]. Results of the anthropological examination were published some years after this important discovery. Methodological progress encouraged re-examination of the material during the last few years. Radiocarbon dating revealed a chronological age of 39,732-39,076 cal. BP for the adult female and 36,117-35,387 cal. BP for the child [3]. Morphological paleopathological studies of these Neanderthal remains uncovered distinct evidence of skeletal infections. Alterations of the adult individual's sacrum suggest probable early-stage sacroiliitis, while several vertebral bodies indicate superficial osseous remodelling of infectious origin. Traces of pathological lesions were observed on the endocranial surface of the child's skull, reflecting a reaction of meningeal tissues, a consequence of a probable TB-related meningeal infectious process. Results of recent paleomicrobiological examinations - lipid biomarker and aDNA studies - support the morphological diagnosis of probable TB infections [4].

RevDate: 2023-11-27
CmpDate: 2023-11-27

López-Rey JM, García-Martínez D, Martelli S, et al (2023)

Estimation of the upper diaphragm in KNM-WT 15000 (Homo erectus s.l.) and Kebara 2 (Homo neanderthalensis) using a Homo sapiens model.

Journal of human evolution, 185:103442.

RevDate: 2023-11-22

Di Santo LN, Quilodran CS, M Currat (2023)

Temporal variation in introgressed segments' length statistics computed from a limited number of ancient genomes sheds light on past admixture pulses.

Molecular biology and evolution pii:7441957 [Epub ahead of print].

Hybridization is recognized as an important evolutionary force, but identifying and timing admixture events between divergent lineages remains a major aim of evolutionary biology. While this has traditionally been done using inferential tools on contemporary genomes, the latest advances in paleogenomics have provided a growing wealth of temporally distributed genomic data. Here, we used individual-based simulations to generate chromosome-level genomic data for a two-population system and described temporal neutral introgression patterns under a single- and two-pulse admixture model. We computed six summary statistics aiming to inform the timing and number of admixture pulses between interbreeding entities: lengths of introgressed sequences and their variance within-genomes, as well as genome-wide introgression proportions and related measures. The first two statistics could confidently be used to infer inter-lineage hybridization history, peaking at the beginning and shortly after an admixture pulse. Temporal variation in introgression proportions and related statistics provided more limited insights, particularly when considering their application to ancient genomes still scant in number. Lastly, we computed these statistics on Homo sapiens paleogenomes and successfully inferred the hybridization pulse from Neanderthal that occurred approximately 40 to 60 kya. The scarce number of genomes dating from this period prevented more precise inferences, but the accumulation of paleogenomic data opens promising perspectives as our approach only requires a limited number of ancient genomes.

RevDate: 2023-11-21

Ragsdale AP (2023)

Human evolution: Neanderthal footprints in African genomes.

Current biology : CB, 33(22):R1197-R1200.

Human and Neanderthal populations met and mixed on multiple occasions over evolutionary time, resulting in the exchange of genetic material. New genomic analyses of diverse African populations reveal a history of bidirectional gene flow and selection acting on introgressed alleles.

RevDate: 2023-11-17

Urnikyte A, Masiulyte A, Pranckeniene L, et al (2023)

Disentangling archaic introgression and genomic signatures of selection at human immunity genes.

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases pii:S1567-1348(23)00126-0 [Epub ahead of print].

Pathogens and infectious diseases have imposed exceptionally strong selective pressure on ancient and modern human genomes and contributed to the current variation in many genes. There is evidence that modern humans acquired immune variants through interbreeding with ancient hominins, but the impact of such variants on human traits is not fully understood. The main objectives of this research were to infer the genetic signatures of positive selection that may be involved in adaptation to infectious diseases and to investigate the function of Neanderthal alleles identified within a set of 50 Lithuanian genomes. Introgressed regions were identified using the machine learning tool ArchIE. Recent positive selection signatures were analysed using iHS. We detected high-scoring signals of positive selection at innate immunity genes (EMB, PARP8, HLAC, and CDSN) and evaluated their interactions with the structural proteins of pathogens. Interactions with human immunodeficiency virus (HIV) 1 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified. Overall, genomic regions introgressed from Neanderthals were shown to be enriched in genes related to immunity, keratinocyte differentiation, and sensory perception.

RevDate: 2023-11-05

Raja A, JJW Kuiper (2023)

Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2).

Genes and immunity [Epub ahead of print].

Endoplasmic reticulum aminopeptidase 2 (ERAP2) is a proteolytic enzyme involved in adaptive immunity. The ERAP2 gene is highly polymorphic and encodes haplotypes that confer resistance against lethal infectious diseases, but also increase the risk for autoimmune disorders. Identifying how ERAP2 influences susceptibility to these traits requires an understanding of the selective pressures that shaped and maintained allelic variation throughout human evolution. Our review discusses the genetic regulation of haplotypes and diversity in naturally occurring ERAP2 allotypes in the global population. We outline how these ERAP2 haplotypes evolved during human history and highlight the presence of Neanderthal DNA sequences in ERAP2 of modern humans. Recent evidence suggests that human adaptation during the last ~10,000 years and historic pandemics left a significant mark on the ERAP2 gene that determines susceptibility to infectious and inflammatory diseases today.

RevDate: 2023-10-18

Quilodrán CS, Rio J, Tsoupas A, et al (2023)

Past human expansions shaped the spatial pattern of Neanderthal ancestry.

Science advances, 9(42):eadg9817.

The worldwide expansion of modern humans (Homo sapiens) started before the extinction of Neanderthals (Homo neanderthalensis). Both species coexisted and interbred, leading to slightly higher introgression in East Asians than in Europeans. This distinct ancestry level has been argued to result from selection, but range expansions of modern humans could provide an alternative explanation. This hypothesis would lead to spatial introgression gradients, increasing with distance from the expansion source. We investigate the presence of Neanderthal introgression gradients after past human expansions by analyzing Eurasian paleogenomes. We show that the out-of-Africa expansion resulted in spatial gradients of Neanderthal ancestry that persisted through time. While keeping the same gradient orientation, the expansion of early Neolithic farmers contributed decisively to reducing the Neanderthal introgression in European populations compared to Asian populations. This is because Neolithic farmers carried less Neanderthal DNA than preceding Paleolithic hunter-gatherers. This study shows that inferences about past human population dynamics can be made from the spatiotemporal variation in archaic introgression.

RevDate: 2023-10-17

Chen Y, Yu XY, Xu SJ, et al (2023)

An indel introduced by Neanderthal introgression, rs3835124:ATTTATT > ATT, might contribute to prostate cancer risk by regulating PDK1 expression.

Annals of human genetics [Epub ahead of print].

INTRODUCTION: Prostate cancer is one of the most common cancer types in males and rs12621278:A > G has been suggested to be associated with this disease by previous genome-wide association studies. One thousand genomes project data analysis indicated that rs12621278:A > G is within two long-core haplotypes. However, the origin, causal variant(s), and molecular function of these haplotypes were remaining unclear.

MATERIALS AND METHODS: Population genetics analysis and functional genomics work was performed for this locus.

RESULTS: Phylogeny analysis verified that the rare haplotype is derived from Neanderthal introgression. Genome annotation suggested that three genetic variants in the core haplotypes, rs116108611:G > A, rs139972066:AAAAAAAA > AAAAAAAAA, and rs3835124:ATTTATT > ATT, are located in functional regions. Luciferase assay indicated that rs139972066:AAAAAAAA > AAAAAAAAA and rs116108611:G > A are not able to alter ITGA6 (integrin alpha 6) and ITGA6 antisense RNA 1 expression, respectively. In contrast, rs3835124:ATTTATT > ATT can significantly influence PDK1 (pyruvate dehydrogenase kinase 1) expression, which was verified by expression quantitative trait locus analysis. This genetic variant can alter transcription factor cut like homeobox 1 interaction efficiency. The introgressed haplotype was observed to be subject to positive selection in East Asian populations. The molecular function of the haplotype suggested that Neanderthal should be with lower PDK1 expression and further different energy homeostasis from modern human.

CONCLUSION: This study provided new insight into the contribution of Neanderthal introgression to human phenotypes.

RevDate: 2023-10-14

Harris DN, Platt A, Hansen MEB, et al (2023)

Diverse African genomes reveal selection on ancient modern human introgressions in Neanderthals.

Current biology : CB pii:S0960-9822(23)01315-5 [Epub ahead of print].

Comparisons of Neanderthal genomes to anatomically modern human (AMH) genomes show a history of Neanderthal-to-AMH introgression stemming from interbreeding after the migration of AMHs from Africa to Eurasia. All non-sub-Saharan African AMHs have genomic regions genetically similar to Neanderthals that descend from this introgression. Regions of the genome with Neanderthal similarities have also been identified in sub-Saharan African populations, but their origins have been unclear. To better understand how these regions are distributed across sub-Saharan Africa, the source of their origin, and what their distribution within the genome tells us about early AMH and Neanderthal evolution, we analyzed a dataset of high-coverage, whole-genome sequences from 180 individuals from 12 diverse sub-Saharan African populations. In sub-Saharan African populations with non-sub-Saharan African ancestry, as much as 1% of their genomes can be attributed to Neanderthal sequence introduced by recent migration, and subsequent admixture, of AMH populations originating from the Levant and North Africa. However, most Neanderthal homologous regions in sub-Saharan African populations originate from migration of AMH populations from Africa to Eurasia ∼250 kya, and subsequent admixture with Neanderthals, resulting in ∼6% AMH ancestry in Neanderthals. These results indicate that there have been multiple migration events of AMHs out of Africa and that Neanderthal and AMH gene flow has been bi-directional. Observing that genomic regions where AMHs show a depletion of Neanderthal introgression are also regions where Neanderthal genomes show a depletion of AMH introgression points to deleterious interactions between introgressed variants and background genomes in both groups-a hallmark of incipient speciation.

RevDate: 2023-10-12

Russo G, Milks A, Leder D, et al (2023)

First direct evidence of lion hunting and the early use of a lion pelt by Neanderthals.

Scientific reports, 13(1):16405.

During the Upper Paleolithic, lions become an important theme in Paleolithic art and are more frequent in anthropogenic faunal assemblages. However, the relationship between hominins and lions in earlier periods is poorly known and primarily interpreted as interspecies competition. Here we present new evidence for Neanderthal-cave lion interactions during the Middle Paleolithic. We report new evidence of hunting lesions on the 48,000 old cave lion skeleton found at Siegsdorf (Germany) that attest to the earliest direct instance of a large predator kill in human history. A comparative analysis of a partial puncture to a rib suggests that the fatal stab was delivered with a wooden thrusting spear. We also present the discovery of distal lion phalanges at least 190,000 old from Einhornhöhle (Germany), representing the earliest example of the use of cave lion skin by Neanderthals in Central Europe. Our study provides novel evidence on a new dimension of Neanderthal behavioral complexity.

RevDate: 2023-10-11

Angelucci DE, Nabais M, J Zilhão (2023)

Formation processes, fire use, and patterns of human occupation across the Middle Palaeolithic (MIS 5a-5b) of Gruta da Oliveira (Almonda karst system, Torres Novas, Portugal).

PloS one, 18(10):e0292075 pii:PONE-D-23-05775.

Gruta da Oliveira features a c. 13 m-thick infilling that includes a c. 6.5 m-thick archaeological deposit (the "Middle Palaeolithic sequence" complex), which Bayesian modelling of available dating results places in MIS 5a (layers 7-14) and MIS 5b (layers 15-25), c. 71,000-93,000 years ago. The accumulation primarily consists of sediment washed in from the slope through gravitational processes and surface dynamics. The coarse fraction derives from weathering of the cave's limestone bedrock. Tectonic activity and structural instability caused the erosional retreat of the scarp face, explaining the large, roof-collapsed rock masses found through the stratification. The changes in deposition and diagenesis observed across the archaeological sequence are minor and primarily controlled by local factors and the impact of humans and other biological agents. Pulses of stadial accumulation-reflected in the composition of the assemblages of hunted ungulates, mostly open-country and rocky terrain taxa (rhino, horse, ibex)-alternate with interstadial hiatuses-during which carbonate crusts and flowstone formed. Humans were active at the cave throughout, but occupation was intermittent, which allowed for limited usage by carnivores when people visited less frequently. During the accumulation of layers 15-25 (c. 85,000-93,000 years ago), the carnivore guild was dominated by wolf and lion, while brown bear and lynx predominate in layers 7-14 (c. 71,000-78,000 years ago). In the excavated areas, conditions for residential use were optimal during the accumulation of layers 20-22 (c. 90,000-92,000 years ago) and 14 (c. 76,000-78,000 years ago), which yielded dense, hearth-focused scatters of stone tools and burnt bones. The latter are ubiquitous, adding to the growing body of evidence that Middle Palaeolithic Neandertals used fire in regular, consistent manner. The patterns of site usage revealed at Gruta da Oliveira are no different from those observed 50,000 years later in comparable early Upper Palaeolithic and Solutrean cave sites of central Portugal.

RevDate: 2023-10-10

Faux P, Ding L, Ramirez-Aristeguieta LM, et al (2023)

Neanderthal introgression in SCN9A impacts mechanical pain sensitivity.

Communications biology, 6(1):958.

The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of ~123 kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function.

RevDate: 2023-10-09

Villanea FA, Peede D, Kaufman EJ, et al (2023)

The MUC19 gene in Denisovans, Neanderthals, and Modern Humans: An Evolutionary History of Recurrent Introgression and Natural Selection.

bioRxiv : the preprint server for biology pii:2023.09.25.559202.

All humans carry a small fraction of archaic ancestry across the genome, the legacy of gene flow from Neanderthals, Denisovans, and other hominids into the ancestors of modern humans. While the effects of Neanderthal ancestry on human fitness and health have been explored more thoroughly, there are fewer examples of adaptive introgression of Denisovan variants. Here, we study the gene MUC19 , for which some modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions, from lubrication to immunity. We find the diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals among global population, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that some Neanderthals--Vindija and Chagyrskaya--carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression. Finally, we find that the Denisovan-like MUC19 haplotype carries a higher copy number of a 30 base-pair variable number tandem repeat relative to the Human-like haplotype, and that copy numbers of this repeat are exceedingly high in American populations. Our results suggest that the Denisovan-like MUC19 haplotype served as the raw genetic material for positive selection as American populations adapted to novel environments during their movement from Beringia into North and then South America.

RevDate: 2023-10-05

Carretero JM, Rodríguez L, García-González R, et al (2023)

Main morphological characteristics and sexual dimorphism of hominin adult femora from the Sima de los Huesos Middle Pleistocene site (Sierra de Atapuerca, Spain).

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

The excellent fossil record from Sima de los Huesos (SH) includes three well-known complete adult femora and several partial specimens that have not yet been published in detail. This fossil record provides an opportunity to analyze the morphology of European pre-Neandertal adult femur and its variation with different evolution patterns. Currently, there are a minimum of five adult individuals (males or females). In this study, we compiled previously published basic anatomical and biometric characteristics of SH adult femora, emphasizing the most relevant features compared to other recent and fossil hominins. The SH femora exhibited a primitive morphological pattern common to all non-Homo sapiens femora, as well as most of the Neandertal traits. Therefore, the complete Upper Pleistocene Neandertal pattern was well-established in Middle Pleistocene ancestors long before the proper Neandertals appeared. Additionally, we highlight that the SH and Neandertal femora share some morphological traits and proportions with modern humans that hold sexual significance in our species, regardless of size. Keeping this in mind, we discussed the sex determination of the complete SH specimens and re-evaluated sex allocation in two of them.

RevDate: 2023-10-04

Rodríguez L, García-González R, Arsuaga JL, et al (2023)

Exploring the morphology of adult tibia and fibula from Sima de los Huesos site in sierra de Atapuerca, Burgos, Spain.

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

The analysis of the locomotor anatomy of Late Pleistocene Homo has largely focused on changes in proximal femur and pelvic morphologies, with much attention centered on the emergence of modern humans. Although much of the focus has been on changes in the proximal femur, some research has also been conducted on tibiae and, to a lesser extent, fibulae. With this in mind, we present one of the largest samples of the same population of human tibiae and fibulae from the Middle Pleistocene to determine their main characteristic traits and establish similarities and differences, primarily with those of Neanderthals and modern humans, but also with other Middle Pleistocene specimens in the fossil record. Through this study, we established that the Middle Pleistocene population from the Sima de los Huesos (Atapuerca, Burgos, Spain) had lower leg long bones similar to those of Neanderthals, although there were some important differences, such as bone length, which this fossil individuals resembled those of modern humans and not to Neanderthals. This fact is related to the crural index and leg length, even though we do not have any true association between femora and tibiae yet, it has implications for establishing locomotor efficiency and climate adaptation.

RevDate: 2023-10-04

Giacomini K, Yee SW, Ferrández-Peral L, et al (2023)

Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates.

Research square pii:rs.3.rs-3263845.

SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17β-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates.

RevDate: 2023-10-02

Zhang Y, Z Li (2023)

Investigating the internal structure of the suprainiac fossa in Xuchang 2.

Journal of human evolution, 184:103440 pii:S0047-2484(23)00119-7 [Epub ahead of print].

RevDate: 2023-09-25

Hui J, A Balzeau (2023)

The diploic venous system in Homo neanderthalensis and fossil Homo sapiens: A study using high-resolution computed tomography.

American journal of biological anthropology [Epub ahead of print].

OBJECTIVES: The diploic venous system has been hypothesized to be related to human brain evolution, though its evolutionary trajectory and physiological functions remain largely unclear. This study examines the characteristics of the diploic venous channels (DCs) in a selection of well-preserved Homo neanderthalensis and Upper Paleolithic Homo sapiens crania, searching for the differences between the two taxa and exploring the associations between brain anatomy and DCs.

MATERIALS AND METHODS: Five H. neanderthalensis and four H. sapiens fossil specimens from Western Europe were analyzed. Based on Micro-CT scanning and 3D reconstruction, the distribution pattern and draining orifices of the DCs were inspected qualitatively. The size of the DCs was quantified by volume calculation, and the degree of complexity was quantified by fractal analyses.

RESULTS: High-resolution data show the details of the DC structures not documented in previous studies. H. neanderthalensis and H. sapiens specimens share substantial similarities in the DCs. The noticeable differences between the two samples manifest in the connecting points surrounding the frontal sinuses, parietal foramina, and asterional area.

DISCUSSION: This study provides a better understanding of the anatomy of the DCs in H. neanderthalensis and H. sapiens. The connection patterns of the DCs have potential utility in distinguishing between the two taxa and in the phylogenetic and taxonomic discussion of the Neandertal-like specimens with controversial taxonomic status.

RevDate: 2023-09-22

Vidal-Cordasco M, Terlato G, Ocio D, et al (2023)

Neanderthal coexistence with Homo sapiens in Europe was affected by herbivore carrying capacity.

Science advances, 9(38):eadi4099.

It has been proposed that climate change and the arrival of modern humans in Europe affected the disappearance of Neanderthals due to their impact on trophic resources; however, it has remained challenging to quantify the effect of these factors. By using Bayesian age models to derive the chronology of the European Middle to Upper Paleolithic transition, followed by a dynamic vegetation model that provides the Net Primary Productivity, and a macroecological model to compute herbivore abundance, we show that in continental regions where the ecosystem productivity was low or unstable, Neanderthals disappeared before or just after the arrival of Homo sapiens. In contrast, regions with high and stable productivity witnessed a prolonged coexistence between both species. The temporal overlap between Neanderthals and H. sapiens is significantly correlated with the carrying capacity of small- and medium-sized herbivores. These results suggest that herbivore abundance released the trophic pressure of the secondary consumers guild, which affected the coexistence likelihood between both human species.

RevDate: 2023-09-22

Fajardo S, Kozowyk PRB, GHJ Langejans (2023)

Measuring ancient technological complexity and its cognitive implications using Petri nets.

Scientific reports, 13(1):14961.

We implement a method from computer sciences to address a challenge in Paleolithic archaeology: how to infer cognition differences from material culture. Archaeological material culture is linked to cognition, and more complex ancient technologies are assumed to have required complex cognition. We present an application of Petri net analysis to compare Neanderthal tar production technologies and tie the results to cognitive requirements. We applied three complexity metrics, each relying on their own unique definitions of complexity, to the modeled production processes. Based on the results, we propose that Neanderthal technical cognition may have been analogous to that of contemporary modern humans. This method also enables us to distinguish the high-order cognitive functions combining traits like planning, inhibitory control, and learning that were likely required by different ancient technological processes. The Petri net approach can contribute to our understanding of technology and cognitive evolution as it can be used on different materials and technologies, across time and species.

RevDate: 2023-09-21

Breno M, Noris M, Rubis N, et al (2023)

A GWAS in the pandemic epicenter highlights the severe COVID-19 risk locus introgressed by Neanderthals.

iScience, 26(10):107629.

Large GWAS indicated that genetic factors influence the response to SARS-CoV-2. However, sex, age, concomitant diseases, differences in ancestry, and uneven exposure to the virus impacted the interpretation of data. We aimed to perform a GWAS of COVID-19 outcome in a homogeneous population who experienced a high exposure to the virus and with a known infection status. We recruited inhabitants of Bergamo province-that in spring 2020 was the epicenter of the SARS-Cov-2 pandemic in Europe-via an online questionnaire followed by personal interviews. Cases and controls were matched by age, sex and risk factors. We genotyped 1195 individuals and replicated the association at the 3p21.31 locus with severity, but with a stronger effect size that further increased in gravely ill patients. Transcriptome-wide association study highlighted eQTLs for LZTFL1 and CCR9. We also identified 17 loci not previously reported, suggestive for an association with either COVID-19 severity or susceptibility.

RevDate: 2023-09-15

Ge X, Lu Y, Chen S, et al (2023)

Genetic origins and adaptive evolution of the Deng people on the Tibetan Plateau.

Molecular biology and evolution pii:7275013 [Epub ahead of print].

The Tibetan Plateau is populated by diverse ethnic groups, but most of them are under-represented in genomics studies compared with the Tibetans. Here, to gain further insight into the genetic diversity and evolutionary history of the people living in the Tibetan Plateau, we sequenced 54 whole genomes of the Deng people with high coverage (30-60×) and analyzed the data together with that of Tibetans and Sherpas, as well as 968 ancient Asian genomes and available archaic and modern human data. We identified 17.74 million novel single-nucleotide variants from the newly sequenced genomes, although the Deng people showed reduced genomic diversity and a relatively small effective population size. Compared with the other Tibetan highlander groups which are highly admixed, the Deng people are dominated by a sole ancestry that could be traced to some ancient northern East Asian populations. The divergence between Deng and Tibetan people (∼4,700-7,200 years) was more recent than that between highlanders and the Han Chinese (HAN) (Deng-HAN: ∼9,000-14,000 years, TIB-HAN: 7,200-10,000 years). Adaptive genetic variants (AGVs) identified in the Deng are only partially shared with those previously reported in the Tibetans like HLA-DQB1; while others like KLHL12, were not reported in Tibetans. In contrast, the top candidate genes harboring AGVs as previously identified in Tibetans, like EPAS1 and EGLN1, do not show strong positive selection signals in Deng. Interestingly, Deng also showed a different archaic introgression scenario from that observed in the Tibetans. Our results suggest that convergent adaptation might be prevalent on the Tibetan Plateau.

RevDate: 2023-09-07

Kozowyk PRB, Baron LI, GHJ Langejans (2023)

Identifying Palaeolithic birch tar production techniques: challenges from an experimental biomolecular approach.

Scientific reports, 13(1):14727.

The intentional production of birch bark tar by European Neanderthals as early as 190,000 years ago plays an important role in discussions about the technological and behavioural complexity of Pleistocene hominins. However, research is hampered because it is currently unknown how Neanderthals were producing birch tar. There are several different techniques that could have been employed, but these differ in their apparent production complexity, time and resource efficiency. Identifying production processes in the archaeological record is therefore paramount for furthering research on the technical behavioural repertoire. Organic biomarkers, identified with Gas Chromatograph-Mass Spectrometry (GC-MS), have been used to identify possible production processes during the Neolithic. Here we test whether these biomarkers can also distinguish Palaeolithic (aceramic) tar production methods. We produced tar using five different methods and analysed their biomolecular composition with GC-MS. Our results show that the biomarkers used to distinguish Neolithic tar production strategies using ceramic technology cannot be reliably used to identify tar production processes using aceramic Palaeolithic techniques. More experimentation is required to produce a larger reference library of different tars for future comparisons. To achieve this, complete GC-MS datasets must also be made publicly available, as we have done with our data.

RevDate: 2023-09-07

Kozowyk PRB, Fajardo S, GHJ Langejans (2023)

Scaling Palaeolithic tar production processes exponentially increases behavioural complexity.

Scientific reports, 13(1):14709.

Technological processes, reconstructed from the archaeological record, are used to study the evolution of behaviour and cognition of Neanderthals and early modern humans. In comparisons, technologies that are more complex infer more complex behaviour and cognition. The manufacture of birch bark tar adhesives is regarded as particularly telling and often features in debates about Neanderthal cognition. One method of tar production, the 'condensation technique', demonstrates a pathway for Neanderthals to have discovered birch bark tar. However, to improve on the relatively low yield, and to turn tar into a perennial innovation, this method likely needed to be scaled up. Yet, it is currently unknown how scaling Palaeolithic technological processes influences their complexity. We used Petri net models and the Extended Cyclomatic Metric to measure system complexity of birch tar production with a single and three concurrent condensation assemblies. Our results show that changing the number of concurrent tar production assemblies substantially increases the measured complexity. This has potential implications on the behavioural and cognitive capacities required by Neanderthals, such as an increase in cooperation or inhibition control.

RevDate: 2023-09-07

Flegontov P, Işıldak U, Maier R, et al (2023)

Modeling of African population history using f-statistics is biased when applying all previously proposed SNP ascertainment schemes.

PLoS genetics, 19(9):e1010931 pii:PGENETICS-D-23-00086 [Epub ahead of print].

f-statistics have emerged as a first line of analysis for making inferences about demographic history from genome-wide data. Not only are they guaranteed to allow robust tests of the fits of proposed models of population history to data when analyzing full genome sequencing data-that is, all single nucleotide polymorphisms (SNPs) in the individuals being analyzed-but they are also guaranteed to allow robust tests of models for SNPs ascertained as polymorphic in a population that is an outgroup in a phylogenetic sense to all groups being analyzed. True "outgroup ascertainment" is in practice impossible in humans because our species has arisen from a substructured ancestral population that does not descend from a homogeneous ancestral population going back many hundreds of thousands of years into the past. However, initial studies suggested that non-outgroup-ascertainment schemes might produce robust enough results using f-statistics, and that motivated widespread fitting of models to data using non-outgroup-ascertained SNP panels such as the "Affymetrix Human Origins array" which has been genotyped on thousands of modern individuals from hundreds of populations, or the "1240k" in-solution enrichment reagent which has been the source of about 70% of published genome-wide data for ancient humans. In this study, we show that while analyses of population history using such panels work well for studies of relationships among non-African populations and one African outgroup, when co-modeling more than one sub-Saharan African and/or archaic human groups (Neanderthals and Denisovans), fitting of f-statistics to such SNP sets is expected to frequently lead to false rejection of true demographic histories, and failure to reject incorrect models. Analyzing panels of SNPs polymorphic in archaic humans, which has been suggested as a solution for the ascertainment problem, has limited statistical power and retains important biases. However, by carrying out simulations of diverse demographic histories, we show that bias in inferences based on f-statistics can be minimized by ascertaining on variants common in a union of diverse African groups; such ascertainment retains high statistical power while allowing co-analysis of archaic and modern groups.

RevDate: 2023-09-07

Mester Z, Coqueugniot H, Tillier AM, et al (2023)

First direct dating of the Late Neanderthal remains from Subalyuk Cave in Northern Hungary.

Anthropologischer Anzeiger; Bericht uber die biologisch-anthropologische Literatur [Epub ahead of print].

The Subalyuk hominin remains were uncovered in 1932 in a cave of the same name in the Bükk Mountains, near the village of Cserépfalu in Borsod-Abaúj-Zemplén County, Northern Hungary. The remains represent two individuals, an adult and a young child who have been described in a few publications since their discovery, providing substantial anthropological data and general assessments of their Neanderthal affiliation. They were associated with Late Mousterian industry. Thus, the Bükk Mountains gain importance in the discussion concerning the contribution of East Central European sites to the debate on the peopling history of Europe during the Late Middle to Early Upper Palaeolithic transition. In this paper, we summarize the archaeological and chronological context of the two individuals, and publish the first direct dating results that place them among the Last Neanderthals of Central Europe.

RevDate: 2023-09-02

Glunčić M, Vlahović I, Rosandić M, et al (2023)

Tandem NBPF 3mer HORs (Olduvai triplets) in Neanderthal and two novel HOR tandem arrays in human chromosome 1 T2T-CHM13 assembly.

Scientific reports, 13(1):14420.

It is known that the ~ 1.6 kb Neuroblastoma BreakPoint Family (NBPF) repeats are human specific and contributing to cognitive capabilities, with increasing frequency in higher order repeat 3mer HORs (Olduvai triplets). From chimpanzee to modern human there is a discontinuous jump from 0 to ~ 50 tandemly organized 3mer HORs. Here we investigate the structure of NBPF 3mer HORs in the Neanderthal genome assembly of Pääbo et al., comparing it to the results obtained for human hg38.p14 chromosome 1. Our findings reveal corresponding NBPF 3mer HOR arrays in Neanderthals with slightly different monomer structures and numbers of HOR copies compared to humans. Additionally, we compute the NBPF 3mer HOR pattern for the complete telomere-to-telomere human genome assembly (T2T-CHM13) by Miga et al., identifying two novel tandem arrays of NBPF 3mer HOR repeats with 5 and 9 NBPF 3mer HOR copies. We hypothesize that these arrays correspond to novel NBPF genes (here referred to as NBPFA1 and NBPFA2). Further improving the quality of the Neanderthal genome using T2T-CHM13 as a reference would be of great interest in determining the presence of such distant novel NBPF genes in the Neanderthal genome and enhancing our understanding of human evolution.

RevDate: 2023-09-02

Fiorenza L, Habashi W, Moggi-Cecchi J, et al (2023)

Relationship between interproximal and occlusal wear in Australopithecus africanus and Neanderthal molars.

Journal of human evolution, 183:103423 pii:S0047-2484(23)00102-1 [Epub ahead of print].

RevDate: 2023-08-28
CmpDate: 2023-08-28

Chevy ET, Huerta-Sánchez E, S Ramachandran (2023)

Integrating sex-bias into studies of archaic introgression on chromosome X.

PLoS genetics, 19(8):e1010399.

Evidence of interbreeding between archaic hominins and humans comes from methods that infer the locations of segments of archaic haplotypes, or 'archaic coverage' using the genomes of people living today. As more estimates of archaic coverage have emerged, it has become clear that most of this coverage is found on the autosomes- very little is retained on chromosome X. Here, we summarize published estimates of archaic coverage on autosomes and chromosome X from extant human samples. We find on average 7 times more archaic coverage on autosomes than chromosome X, and identify broad continental patterns in this ratio: greatest in European samples, and least in South Asian samples. We also perform extensive simulation studies to investigate how the amount of archaic coverage, lengths of coverage, and rates of purging of archaic coverage are affected by sex-bias caused by an unequal sex ratio within the archaic introgressors. Our results generally confirm that, with increasing male sex-bias, less archaic coverage is retained on chromosome X. Ours is the first study to explicitly model such sex-bias and its potential role in creating the dearth of archaic coverage on chromosome X.

RevDate: 2023-08-23

Yee SW, Ferrández-Peral L, Alentorn P, et al (2023)

Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates.

bioRxiv : the preprint server for biology pii:2023.08.08.552553.

SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17β-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates.

RevDate: 2023-08-17

Sánchez Goñi MF (2020)

Regional impacts of climate change and its relevance to human evolution.

Evolutionary human sciences, 2:e55.

The traditional concept of long and gradual, glacial-interglacial climate changes during the Quaternary has been challenged since the 1980s. High temporal resolution analysis of marine, terrestrial and ice geological archives has identified rapid, millennial- to centennial-scale, and large-amplitude climatic cycles throughout the last few million years. These changes were global but have had contrasting regional impacts on the terrestrial and marine ecosystems, with in some cases strong changes in the high latitudes of both hemispheres but muted changes elsewhere. Such a regionalization has produced environmental barriers and corridors that have probably triggered niche contractions/expansions of hominin populations living in Eurasia and Africa. This article reviews the long- and short-timescale ecosystem changes that have punctuated the last few million years, paying particular attention to the environments of the last 650,000 years, which have witnessed key events in the evolution of our lineage in Africa and Eurasia. This review highlights, for the first time, a contemporaneity between the split between Denisovan and Neanderthals, at ~650-400 ka, and the strong Eurasian ice-sheet expansion down to the Black Sea. This ice expansion could form an ice barrier between Europe and Asia that may have triggered the genetic drift between these two populations.

RevDate: 2023-08-13

Piccardi M, Gentiluomo M, Bertoncini S, et al (2023)

Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians.

Biological research, 56(1):46.

BACKGROUND: The genomes of present-day non-Africans are composed of 1-3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50-60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations.

RESULTS: The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19-1.54, P = 3.59 × 10[-6]), with a P-value close to a threshold that takes into account multiple testing.

CONCLUSIONS: Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

RevDate: 2023-08-10

Ruan J, Timmermann A, Raia P, et al (2023)

Climate shifts orchestrated hominin interbreeding events across Eurasia.

Science (New York, N.Y.), 381(6658):699-704.

When, where, and how often hominin interbreeding happened is largely unknown. We study the potential for Neanderthal-Denisovan admixture using species distribution models that integrate extensive fossil, archaeological, and genetic data with transient coupled general circulation model simulations of global climate and biomes. Our Pleistocene hindcast of past hominins' habitat suitability reveals pronounced climate-driven zonal shifts in the main overlap region of Denisovans and Neanderthals in central Eurasia. These shifts, which influenced the timing and intensity of potential interbreeding events, can be attributed to the response of climate and vegetation to past variations in atmospheric carbon dioxide and Northern Hemisphere ice-sheet volume. Therefore, glacial-interglacial climate swings likely played an important role in favoring gene flow between archaic humans.

RevDate: 2023-08-10

Garralda MD, Le Cabec A, Maíllo Fernández JM, et al (2023)

Mousterian human fossils from El Castillo cave (Puente Viesgo, Cantabria, Spain).

Journal of anthropological sciences = Rivista di antropologia : JASS, 100: [Epub ahead of print].

El Castillo cave is a well-known site because of its Paleolithic archaeology and parietal rock art. This paper is focused on the human remains found by V. Cabrera in the Mousterian Unit XX assigned to MIS 4 and early MIS 3. The fossils consist of one upper left second premolar (ULP4), one incomplete proximal hand phalanx, and one partial femoral head. The tooth and the phalanx were assigned to adults, whereas the femoral head belonged to an immature individual due to the absence of fusion traces to the metaphyseal surface. The external morphology and metrical characterization of the Castillo-1466 (ULP4) tooth crown was quantified and compared to the variability of other Neanderthal dental remains and a sample of modern human populations. We also quantified its 3D enamel thickness distribution, its roots morphology, as well as the presence of chipping, and their possible relation to masticatory or paramasticatory activities. Castillo-1466 shows crown dimensions compatible with middle-sized Neanderthal teeth, but with a remarkably thicker enamel than other Neanderthal premolars, such as Marillac 13. The femoral head and the hand phalanx fragment are compared to published values for Neanderthals, although both partial fossils lack diagnostic features precluding any clear taxonomic diagnostic. Therefore, their attribution to Neanderthals is assumed based on the dating of the layers in which they were discovered. El Castillo cave Mousterian fossils represent another contribution to the knowledge of the Middle Paleolithic populations of Northern Spain, where different sites along the Cantabrian mountains yielded several human remains assigned to MIS 4 and early MIS 3.

RevDate: 2023-08-09

Aquino Y, Bisiaux A, Li Z, et al (2023)

Dissecting human population variation in single-cell responses to SARS-CoV-2.

Nature [Epub ahead of print].

Humans display substantial interindividual clinical variability after SARS-CoV-2 infection[1-3], the genetic and immunological basis of which has begun to be deciphered[4]. However, the extent and drivers of population differences in immune responses to SARS-CoV-2 remain unclear. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells-from 222 healthy donors of diverse ancestries-that were stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces weaker, but more heterogeneous, interferon-stimulated gene activity compared with influenza A virus, and a unique pro-inflammatory signature in myeloid cells. Transcriptional responses to viruses display marked population differences, primarily driven by changes in cell abundance including increased lymphoid differentiation associated with latent cytomegalovirus infection. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell composition on population disparities in immune responses, with genetic variants exerting a strong effect on specific loci. Furthermore, we show that natural selection has increased population differences in immune responses, particularly for variants associated with SARS-CoV-2 response in East Asians, and document the cellular and molecular mechanisms by which Neanderthal introgression has altered immune functions, such as the response of myeloid cells to viruses. Finally, colocalization and transcriptome-wide association analyses reveal an overlap between the genetic basis of immune responses to SARS-CoV-2 and COVID-19 severity, providing insights into the factors contributing to current disparities in COVID-19 risk.

RevDate: 2023-08-06

Augoyard M, Zanolli C, Santos F, et al (2023)

Evaluation of age, sex, and ancestry-related variation in cortical bone and dentine volumes in modern humans, and a preliminary assessment of cortical bone-dentine covariation in later Homo.

Journal of anthropological sciences = Rivista di antropologia : JASS, 100: [Epub ahead of print].

Cortical bone and dentine share similarities in their embryological origin, development, and genetic background. Few analyses have combined the study of cortical bone and dentine to quantify their covariation relative to endogenous and exogenous factors. However, knowing how these tissues relate in individuals is of great importance to decipher the factors acting on their evolution, and ultimately to understand the mechanisms responsible for the different patterns of tissue proportions shown in hominins. The aims of this study are to examine age-, sex-, and ancestry-related variation in cortical bone and dentine volumes, and to preliminary assess the possible covariation between these tissues in modern humans and in five composite Neandertals. The modern analytical sample includes 12 immature individuals from France and 49 adults from France and South Africa. Three-dimensional tissue proportions were assessed from microtomographic records of radii and permanent maxillary canines. Results suggest ontogenic differences and a strong sexual dimorphism in cortical bone and dentine developments. The developmental pattern of dentine also seems to vary according to individual's ancestry. We measure a stronger covariation signal between cortical bone and dentine volumes than with any other dental tissue. A more complex covariation pattern is shown when splitting the modern sample by age, sex, and ancestry, as no signal is found in some subsamples while others show a covariation between cortical bone and either crown or radicular dentine. Finally, no difference in cortical bone volume is noticed between the modern young adults and the five young adult composite Neandertals from Marine Isotopic Stages (MIS) 5 and 3. Greater dentine Cortical bone and dentine (co)variation volumes are measured in the MIS 5 chimeric Neandertals whereas a strong interpopulation variation in dentine thickness is noticed in the MIS 3 chimeric Neandertals. Further research on the cortical bonedentine covariation will increase understanding of the impact of endogenous and exogenous factors on the development of the mineralized tissues.

RevDate: 2023-08-07
CmpDate: 2023-08-07

Gicqueau A, Schuh A, Henrion J, et al (2023)

Anatomically modern human in the Châtelperronian hominin collection from the Grotte du Renne (Arcy-sur-Cure, Northeast France).

Scientific reports, 13(1):12682.

Around 42,000 years ago, anatomically modern humans appeared in Western Europe to the detriment of indigenous Neanderthal groups. It is during this period that new techno-cultural complexes appear, such as the Châtelperronian that extends from northern Spain to the Paris Basin. The Grotte du Renne (Arcy-sur-Cure) is a key site for discussing the biological identity of its makers. This deposit has yielded several Neanderthal human remains in its Châtelperronian levels. However, the last inventory of the paleoanthropological collection attributed to this techno-complex allowed the identification of an ilium belonging to a neonate (AR-63) whose morphology required a thorough analysis to assess its taxonomic attribution. Using geometric morphometrics, we quantified its morphology and compared it to that of 2 Neanderthals and 32 recent individuals deceased during the perinatal period to explore their morphological variation. Our results indicate a morphological distinction between the ilia of Neanderthals and anatomically modern neonates. Although AR-63 is slightly outside recent variability, it clearly differs from the Neanderthals. We propose that this is due to its belonging to an early modern human lineage whose morphology differs slightly from present-day humans. We also explore different hypotheses about the presence of this anatomically modern neonate ilium among Neanderthal remains.

RevDate: 2023-08-04
CmpDate: 2023-08-03

Badino F, Pini R, Ravazzi C, et al (2023)

High-resolution ecosystem changes pacing the millennial climate variability at the Middle to Upper Palaeolithic transition in NE-Italy.

Scientific reports, 13(1):12478.

Observation of high-resolution terrestrial palaeoecological series can decipher relationships between past climatic transitions, their effects on ecosystems and wildfire cyclicity. Here we present a new radiocarbon dated record from Lake Fimon (NE-Italy) covering the 60-27 ka interval. Palynological, charcoal fragments and sediment lithology analysis were carried out at centennial to sub-centennial resolutions. Identification of the best modern analogues for MIS 3 ecosystems further enabled to thoroughly reconstruct structural changes in the vegetation through time. This series also represents an "off-site" reference record for chronologically well-constrained Palaeolithic sites documenting Neanderthal and Homo sapiens occupations within the same region. Neanderthals lived in a mosaic of grasslands and woodlands, composed of a mixture of boreal and broad-leaved temperate trees analogous to those of the modern Central-Eastern Europe, the Southern Urals and central-southern Siberia. Dry and other grassland types expanded steadily from 44 to 43 ka and peaked between 42 and 39 ka, i.e., about the same time when Sapiens reached this region. This vegetation, which finds very few reliable modern analogues in the adopted Eurasian calibration set, led to the expansion of ecosystems able to sustain large herds of herbivores. During 39-27 ka, the landscape was covered by steppe, desert-steppe and open dry boreal forests similar to those of the modern Altai-Sayan region. Both Neanderthal and Sapiens lived in contexts of expanded fire-prone ecosystems modulated by the high-frequency climatic cycles of MIS 3.

RevDate: 2023-07-29

Maasch JRMA, Torres MDT, Melo MCR, et al (2023)

Molecular de-extinction of ancient antimicrobial peptides enabled by machine learning.

Cell host & microbe pii:S1931-3128(23)00296-2 [Epub ahead of print].

Molecular de-extinction could offer avenues for drug discovery by reintroducing bioactive molecules that are no longer encoded by extant organisms. To prospect for antimicrobial peptides encrypted within extinct and extant human proteins, we introduce the panCleave random forest model for proteome-wide cleavage site prediction. Our model outperformed multiple protease-specific cleavage site classifiers for three modern human caspases, despite its pan-protease design. Antimicrobial activity was observed in vitro for modern and archaic protein fragments identified with panCleave. Lead peptides showed resistance to proteolysis and exhibited variable membrane permeabilization. Additionally, representative modern and archaic protein fragments showed anti-infective efficacy against A. baumannii in both a skin abscess infection model and a preclinical murine thigh infection model. These results suggest that machine-learning-based encrypted peptide prospection can identify stable, nontoxic peptide antibiotics. Moreover, we establish molecular de-extinction through paleoproteome mining as a framework for antibacterial drug discovery.

RevDate: 2023-08-03

Sidik S (2023)

AI search of Neanderthal proteins resurrects 'extinct' antibiotics.

RevDate: 2023-07-27

Pawar H, Rymbekova A, Cuadros-Espinoza S, et al (2023)

Ghost admixture in eastern gorillas.

Nature ecology & evolution [Epub ahead of print].

Archaic admixture has had a substantial impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. In great apes, archaic admixture has been identified in chimpanzees and bonobos but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole-genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using approximate Bayesian computation with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic 'ghost' lineage into the common ancestor of eastern gorillas but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, probably more than 40 thousand years ago and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.

RevDate: 2023-07-27

Muotri AR (2023)

Brain Model Technology and Its Implications.

Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees pii:S096318012300018X [Epub ahead of print].

The complexity of the human brain creates a spectrum of sophisticated behavioral repertoires, such as language, tool use, self-awareness, symbolic thought, cultural learning, and consciousness. Understanding how the human brain achieves that has been a longstanding challenge for neuroscientists and may bring insights into the evolution of human cognition and disease states. Human pluripotent stem cells could differentiate into specialized cell types and tissues in vitro. From this pluripotent state, it is possible to generate models of the human brain, such as brain organoids. The recent observation that brain organoids can spontaneously develop complex neural network activity in a dish can help one understand how neural network oscillations evolve and vary between normal and disease states. Moreover, this finding can be leveraged to other applications outside medicine, including engineering and artificial intelligence. However, as the brain model technology becomes more complex, it raises a series of ethical and moral dilemmas. This article discusses the status of this technology, some of its current limitations, and a vision of the future.

RevDate: 2023-07-26

Bird EE, Kivell TL, Dunmore CJ, et al (2023)

Trabecular bone structure of the proximal capitate in extant hominids and fossil hominins with implications for midcarpal joint loading and the dart-thrower's motion.

American journal of biological anthropology [Epub ahead of print].

OBJECTIVES: This research examines whether the distribution of trabecular bone in the proximal capitates of extant hominids, as well as several fossil hominin taxa, is associated with the oblique path of the midcarpal joint known as the dart-thrower's motion (DTM).

MATERIALS AND METHODS: We analyzed proximal capitates from extant (Pongo n = 12; Gorilla n = 11; Pan n = 10; fossil and recent Homo sapiens n = 29) and extinct (Australopithecus sediba n = 2; Homo naledi n = 1; Homo floresiensis n = 2; Neandertals n = 3) hominids using a new canonical holistic morphometric analysis, which quantifies and visualizes the distribution of trabecular bone using relative bone volume as a fraction of total volume (rBV/TV).

RESULTS: Homo sapiens and Neandertals had a continuous band of high rBV/TV that extended across the scaphoid, lunate, and hamate subarticular regions, but other fossil hominins and extant great apes did not. A. sediba expressed a distinct combination of human-like and Pan-like rBV/TV distribution. Both H. floresiensis and H. naledi had high rBV/TV on the ulnar-side of the capitate but low rBV/TV on the radial-side.

CONCLUSION: The proximal capitates of H. sapiens and Neandertals share a distinctive distribution of trabecular bone that suggests that these two species of Homo regularly load(ed) their midcarpal joints along the full extent of the oblique path of the DTM. The observed pattern in A. sediba suggests that human-like stress at the capito-scaphoid articular surface was combined with Pan-like wrist postures, whereas the patterns in H. floresiensis and H. naledi suggest their midcarpal joints were loaded differently from that of H. sapiens and Neandertals.

RevDate: 2023-07-14

Yang C, Zhou Y, Song Y, et al (2023)

The complete and fully-phased diploid genome of a male Han Chinese.

Cell research [Epub ahead of print].

Since the release of the complete human genome, the priority of human genomic study has now been shifting towards closing gaps in ethnic diversity. Here, we present a fully phased and well-annotated diploid human genome from a Han Chinese male individual (CN1), in which the assemblies of both haploids achieve the telomere-to-telomere (T2T) level. Comparison of this diploid genome with the CHM13 haploid T2T genome revealed significant variations in the centromere. Outside the centromere, we discovered 11,413 structural variations, including numerous novel ones. We also detected thousands of CN1 alleles that have accumulated high substitution rates and a few that have been under positive selection in the East Asian population. Further, we found that CN1 outperforms CHM13 as a reference genome in mapping and variant calling for the East Asian population owing to the distinct structural variants of the two references. Comparison of SNP calling for a large cohort of 8869 Chinese genomes using CN1 and CHM13 as reference respectively showed that the reference bias profoundly impacts rare SNP calling, with nearly 2 million rare SNPs miss-called with different reference genomes. Finally, applying the CN1 as a reference, we discovered 5.80 Mb and 4.21 Mb putative introgression sequences from Neanderthal and Denisovan, respectively, including many East Asian specific ones undetected using CHM13 as the reference. Our analyses reveal the advances of using CN1 as a reference for population genomic studies and paleo-genomic studies. This complete genome will serve as an alternative reference for future genomic studies on the East Asian population.

RevDate: 2023-07-20
CmpDate: 2023-07-07

Smith TM, Arora M, Bharatiya M, et al (2023)

Brief Communication: Elemental Models of Primate Nursing and Weaning Revisited.

American journal of biological anthropology, 180(1):216-223.

OBJECTIVES: Intra-tooth patterns of trace elements barium (Ba) and strontium (Sr) have been used to infer human and nonhuman primate nursing histories, including australopithecine and Neanderthal juveniles. Here we contrast the two elemental models in first molars (M1s) of four wild baboons and explore the assumptions that underlie each.

MATERIALS AND METHODS: Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was employed to create comprehensive calcium-normalized barium and strontium (Ba/Ca, Sr/Ca) maps of M1 enamel and dentine at 35 micron resolution.

RESULTS: Postnatal Ba/Ca values were typically high, peaking ~0.5 years of age and then decreasing throughout M1 crown formation; all four individuals showed minimal Ba/Ca values between ~1.2-1.8 years, consistent with field reports of the cessation of suckling. Enamel Sr/Ca did not support patterns of previous LA-ICP-MS spot sampling as the enamel rarely showed discrete Sr/Ca secretory zonation. Increases in Sr/Ca appeared in coronal dentine beginning ~0.3 years, with varied peak value ages (~0.7-2.7 years) and no evidence of a predicted postweaning decline.

DISCUSSION: Inferences of baboon weaning ages from initial Ba/Ca minima are more congruent with behavioral observations than Sr/Ca maxima; this is consistent with studies of captive macaques of known weaning ages. Elemental variation is more apparent in the coronal dentine than the enamel of these baboons, which may relate to its more rapid mineralization and protection from the oral environment. Inferences of nursing histories from enamel Sr/Ca patterns alone should be reconsidered, and elevated values of Ba/Ca and Sr/Ca in teeth formed after weaning require further study.

RevDate: 2023-08-02
CmpDate: 2023-07-31

Henrion J, Hublin JJ, B Maureille (2023)

New Neanderthal remains from the Châtelperronian-attributed layer X of the Grotte du Renne (Arcy-sur-Cure, France).

Journal of human evolution, 181:103402.

RevDate: 2023-07-01

Tozzi A (2023)

Non-ultrametric phylogenetic trees shed new light on Neanderthal introgression.

Organisms, diversity & evolution [Epub ahead of print].

Ultrametric spaces are widely used to depict evolutionary times in phylogenetic trees since they assume that every population/species is located at the tips of bifurcating branches of the same length. The discrete branching of ultrametric trees permits the measurement of distances between pairs of individuals that are proportional to their divergence time. Here the traditional ultrametric concept of bifurcating and divergent phylogenetic tree is overturned and a new type of non-ultrametric diagram is introduced. The objective of this study is the description of gene flows in branching species/populations in terms of converging trees instead of bifurcating trees. To provide an operational example, the paleoanthropological issue of the date of Neanderthal genome's introgression in non-African humans is examined. Neanderthals and ancient humans are not anymore two species that exchange chunks of DNA, rather become a single, novel cluster of extant hominins that must be considered by itself. The novel converging, non-ultrametric phylogenetic trees permit the calibration of molecular clocks with a twofold benefit. When the date of the branching of two population/species from a common ancestor is known, the novel approach allows to calculate the time of subsequent introgressions. On the contrary, when the date of the introgression between two population/species is known, the novel approach allows to detect the time of their previous branching from a common ancestor.

RevDate: 2023-06-24

Condemi S, Panuel M, Chaumoitre K, et al (2023)

A pathological Neandertal thumb phalanx from Moula-Guercy (France).

International journal of paleopathology, 42:14-17 pii:S1879-9817(23)00035-9 [Epub ahead of print].

OBJECTIVE: To discuss a Neandertal pathological adult first pollical proximal phalanx (I2-104) from the Baume de Moula-Guercy (Ardèche, France) and evaluate the possible causes of this pathology.

METHODS: Macroscopic analyses of external features, as well as CT imaging, were used in the analysis RESULTS: The presence of asymmetric eburnation on the distal epiphysis associated with an osteophyte on the palmar surface, as well as the absence of periosteal bone reaction visible on CT images, is consistent with osteoarthritis.

CONCLUSION: Osteoarthritis (OA) can have different origins and the cause is difficult to identify. The pathology of the Moula-Guercy I2-104 phalanx may be due to a genetic predisposition for OA known in Neandertals and associated with short limb bones. The OA could have been aggravated by the age of this individual and by an inflammatory reaction caused by repeated movements and intense vibrations provoked by high-frequency knapping or by other use of the hands SIGNIFICANCE: The I2-104 phalanx is the first Neandertal pollical phalanx known to display OA, although joints of this bone are frequently affected by this pathology in modern humans. Thus, greater insight into the presence and consequences of Neandertal behaviors is offered LIMITATION: It is impossible to give a definitive conclusion on the cause(s) of the OA in this case.

More data is needed concerning OA within Neandertals and its relationship with behavior and genetics.

RevDate: 2023-06-22

Rodríguez L, García-González R, Arsuaga JL, et al (2023)

Uncovering the adult morphology of the forearm bones from the Sima de los Huesos Site in Atapuerca (Spain), with comments on biomechanical features.

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

The forearm skeleton is composed of two bones: the radius and the ulna. This is closely related to manipulative movements. The ulna is part of the elbow joint, whereas the radius and ulna together with the scaphoid and lunate bones, form the wrist joints. Thus, morphofunctional analysis of the adult Sima de los Huesos (SH) forearm bones, provides clues about manipulative activities in one Pleistocene population. From 1976 to the present, over 7000 human fossils have been recovered from the SH site. The radial sample comprised 98 labeled fragments, of which 49 belonged to adult individuals, representing at least 7 individuals. The ulnar sample included 31 labeled adult fossils representing at least nine individuals. In this study, we describe the SH radii and ulnae and analyze their functional implications for manipulative and forearm movements. We confirmed that the SH radii are long and curved, with variations in robusticity and radial tuberosity orientation. The SH ulnae are characterized by an anteriorly oriented trochlear notch, a massive olecranon process, an obliquely oriented radial notch, a blunt and short supinator crest, a gracile and curved diaphysis, and a round and anteriorly oriented pronator crests. In general, they exhibit Neanderthal morphology. The SH collection provides a unique opportunity to conduct morphological analyses of these bones in the Middle Pleistocene population.

RevDate: 2023-07-01
CmpDate: 2023-06-23

Marquet JC, Freiesleben TH, Thomsen KJ, et al (2023)

The earliest unambiguous Neanderthal engravings on cave walls: La Roche-Cotard, Loire Valley, France.

PloS one, 18(6):e0286568.

Here we report on Neanderthal engravings on a cave wall at La Roche-Cotard (LRC) in central France, made more than 57±3 thousand years ago. Following human occupation, the cave was completely sealed by cold-period sediments, which prevented access until its discovery in the 19th century and first excavation in the early 20th century. The timing of the closure of the cave is based on 50 optically stimulated luminescence ages derived from sediment collected inside and from around the cave. The anthropogenic origin of the spatially-structured, non-figurative marks found within the cave is confirmed using taphonomic, traceological and experimental evidence. Cave closure occurred significantly before the regional arrival of H. sapiens, and all artefacts from within the cave are typical Mousterian lithics; in Western Europe these are uniquely attributed to H. neanderthalensis. We conclude that the LRC engravings are unambiguous examples of Neanderthal abstract design.

RevDate: 2023-07-01
CmpDate: 2023-06-23

Mocci S, Littera R, Chessa L, et al (2023)

A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G.

Frontiers in immunology, 14:1138559.

INTRODUCTION: A large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including HLA-G gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection.

MATERIALS AND METHODS: We compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy).

RESULTS: HLA-G locus analysis showed that the extended haplotype HLA-G*01:01:01:01/UTR-1 was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% vs 15.7%, OR = 0.634 (95% CI 0.440 - 0.913); P = 0.016]. Furthermore, the most significant HLA-G 3'UTR polymorphism (rs371194629) shows that the HLA-G 3'UTR Del/Del genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X[2 ]= 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X[2 ]= 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as β-thalassemia trait (rs11549407C>T in the HBB gene), KIR2DS2/HLA-C C1+ group combination and the HLA-B*58:01, C*07:01, DRB1*03:01 haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal LZTFL1 gene variant (rs35044562A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, HLA-G 3'UTR Del/Del genotype was independent from the other significant variables [ORM = 0.4 (95% CI 0.2 - 0.7), PM = 6.5 x 10[-4]].

CONCLUSION: Our results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients.

RevDate: 2023-06-21

Groh J, G Coop (2023)

The temporal and genomic scale of selection following hybridization.

bioRxiv : the preprint server for biology.

Genomic evidence supports an important role for selection in shaping patterns of introgression along the genome, but frameworks for understanding the dynamics underlying these patterns within hybrid populations have been lacking. Here, we develop methods based on the Wavelet Transform to understand the spatial genomic scale of local ancestry variation and its association with recombination rates. We present theory and use simulations to show how wavelet-based decompositions of ancestry variance along the genome and the correlation between ancestry and recombination reflect the joint effects of recombination, genetic drift, and genome-wide selection against introgressed alleles. Due to the clock-like effect of recombination in hybrids breaking up parental haplotypes, drift and selection produce predictable patterns of local ancestry variation at varying spatial genomic scales through time. Using wavelet approaches to identify the genomic scale of variance in ancestry and its correlates, we show that these methods can detect temporally localized effects of drift and selection. We apply these methods to previously published datasets from hybrid populations of swordtail fish (Xiphophorus) and baboons (Papio), and to inferred Neanderthal introgression in modern humans. Across systems, we find that upwards of 20% of the variation in local ancestry at the broadest genomic scales can be attributed to systematic selection against introgressed alleles, consistent with strong selection acting on early-generation hybrids. We also see signals of selection at fine genomic scales and much longer time scales. However, we show that our ability to confidently infer selection at fine scales is likely limited by inherent biases in current methods for estimating local ancestry from genomic similarity. Wavelet approaches will become widely applicable as genomic data from systems with introgression become increasingly available, and can help shed light on generalities of the genomic consequences of interspecific hybridization.

RevDate: 2023-08-03

Baquedano E, Arsuaga JL, Pérez-González A, et al (2023)

Author Correction: A symbolic Neanderthal accumulation of large herbivore crania.

Nature human behaviour, 7(7):1228.

RevDate: 2023-06-19
CmpDate: 2023-06-16

Ågren R, Patil S, Zhou X, et al (2023)

Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals.

Molecular biology and evolution, 40(6):.

Dupuytren's disease is characterized by fingers becoming permanently bent in a flexed position. Whereas people of African ancestry are rarely afflicted by Dupuytren's disease, up to ∼30% of men over 60 years suffer from this condition in northern Europe. Here, we meta-analyze 3 biobanks comprising 7,871 cases and 645,880 controls and find 61 genome-wide significant variants associated with Dupuytren's disease. We show that 3 of the 61 loci harbor alleles of Neandertal origin, including the second and third most strongly associated ones (P = 6.4 × 10-132 and P = 9.2 × 10-69, respectively). For the most strongly associated Neandertal variant, we identify EPDR1 as the causal gene. Dupuytren's disease is an example of how admixture with Neandertals has shaped regional differences in disease prevalence.

RevDate: 2023-06-18
CmpDate: 2023-06-16

Baumann M, Plisson H, Maury S, et al (2023)

On the Quina side: A Neanderthal bone industry at Chez-Pinaud site, France.

PloS one, 18(6):e0284081.

Did Neanderthal produce a bone industry? The recent discovery of a large bone tool assemblage at the Neanderthal site of Chagyrskaya (Altai, Siberia, Russia) and the increasing discoveries of isolated finds of bone tools in various Mousterian sites across Eurasia stimulate the debate. Assuming that the isolate finds may be the tip of the iceberg and that the Siberian occurrence did not result from a local adaptation of easternmost Neanderthals, we looked for evidence of a similar industry in the Western side of their spread area. We assessed the bone tool potential of the Quina bone-bed level currently under excavation at chez Pinaud site (Jonzac, Charente-Maritime, France) and found as many bone tools as flint ones: not only the well-known retouchers but also beveled tools, retouched artifacts and a smooth-ended rib. Their diversity opens a window on a range of activities not expected in a butchering site and not documented by the flint tools, all involved in the carcass processing. The re-use of 20% of the bone blanks, which are mainly from large ungulates among faunal remains largely dominated by reindeer, raises the question of blank procurement and management. From the Altai to the Atlantic shore, through a multitude of sites where only a few objects have been reported so far, evidence of a Neanderthal bone industry is emerging which provides new insights on Middle Paleolithic subsistence strategies.

RevDate: 2023-06-12

Curtis D, W Amos (2023)

The human genome harbours widespread exclusive yin yang haplotypes.

European journal of human genetics : EJHG [Epub ahead of print].

There have been reports of examples of exclusive yin yang haplotypes, differing at every locus, but there has been no systematic search for them. Unphased whole genome sequence data for 2504 unrelated 1000 Genomes subjects was searched for chains of SNPs having global minor allele frequency (MAF) > =0.1 made up of at least 20 SNPs in complete linkage disequilibrium with each other and with no pair being separated by more than 9 other SNPs. The global distribution of these haplotypes was investigated, along with their ancestral origins and associations with genes and phenotypes. A number of previously unrecognised repeats were noted, flagged by all or most subjects being called as heterozygotes, and these were discarded. There were 5114 exclusive yin yang haplotypes each consisting of on average 34.8 SNPs, each spanning on average 15.7 kb and cumulatively covering 80 Mb. Although for some haplotypes the MAF varied markedly between populations the average global fixation index was similar to that for SNPs elsewhere in the genome and there was no evidence of enrichment for genes or gene ontologies. For all but 92 haplotypes there were partial forms present in the chimpanzee and/or Neanderthal genome, indicating that they had been formed in a gradual process but that intermediate haplotypes were now absent from modern humans. Exclusive yin yang haplotypes cover over 2% of the human genome. The mechanisms accounting for their formation and preservation are unclear. They may serve as useful markers of the dispersal of chromosomal regions through human history.

RevDate: 2023-06-13

Kou SH, Li J, Tam B, et al (2023)

TP53 germline pathogenic variants in modern humans were likely originated during recent human history.

NAR cancer, 5(3):zcad025.

TP53 is crucial for maintaining genome stability and preventing oncogenesis. Germline pathogenic variation in TP53 damages its function, causing genome instability and increased cancer risk. Despite extensive study in TP53, the evolutionary origin of the human TP53 germline pathogenic variants remains largely unclear. In this study, we applied phylogenetic and archaeological approaches to identify the evolutionary origin of TP53 germline pathogenic variants in modern humans. In the phylogenic analysis, we searched 406 human TP53 germline pathogenic variants in 99 vertebrates distributed in eight clades of Primate, Euarchontoglires, Laurasiatheria, Afrotheria, Mammal, Aves, Sarcopterygii and Fish, but we observed no direct evidence for the cross-species conservation as the origin; in the archaeological analysis, we searched the variants in 5031 ancient human genomes dated between 45045 and 100 years before present, and identified 45 pathogenic variants in 62 ancient humans dated mostly within the last 8000 years; we also identified 6 pathogenic variants in 3 Neanderthals dated 44000 to 38515 years before present and 1 Denisovan dated 158 550 years before present. Our study reveals that TP53 germline pathogenic variants in modern humans were likely originated in recent human history and partially inherited from the extinct Neanderthals and Denisovans.

RevDate: 2023-06-03

Garcia-Heras J (2023)

The 2022 Nobel Prize in Physiology or Medicine.

Journal of the Association of Genetic Technologists, 49(2):56-67.

The Nobel Assembly at the Karolinska Institute awarded the 2022 Nobel Prize in Physiology or Medicine to Svante Pääbo (Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany). This award acknowledged his discoveries about the genomes of extinct hominins (Neandertal man and the Denisovans), the molecular genetic insights of human origin and evolutionary history, and the understanding of phylogenetic relationships between archaic hominins and modern humans. The scientific advances included detection of Neandertal and Denisovan DNA carried by modern humans due to past admixture events, which in turn stimulated active research about the functional and phenotypic significance of such archaic ancestry on non-disease and disease phenotypic features in modern populations. In addition, comparative genomic studies started to delineate the genes and genetic regulation mechanisms that distinguish modern-day humans from the archaic hominins and our immediate ancestors, the anatomically modern humans. These breakthroughs allowed a more thorough understanding of ancestral and modern human population genetics, and propelled the take-off of human paleogenomics as a new scientific discipline in its own right.

RevDate: 2023-05-31

Demidenko YE, P Škrdla (2023)

Lincombian-Ranisian-Jerzmanowician Industry and South Moravian Sites: a Homo sapiens Late Initial Upper Paleolithic with Bohunician Industrial Generic Roots in Europe.

Journal of paleolithic archaeology, 6(1):17.

This article re-examines the Lincombian-Ranisian-Jerzmanowician (LRJ) industry, a well-known Early Upper Paleolithic complex in northern Europe. It is widely thought that the LRJ was produced by late Neanderthals and that its industrial roots are in late Middle Paleolithic industries with bifacial leaf points in north-western Europe. On the basis of evidence from four recently excavated open-air sites in southern Moravia (Czech Republic) (Líšeň/Podolí I, Želešice III/Želešice-Hoynerhügel, Líšeň I/Líšeň-Čtvrtě, and Tvarožná X/Tvarožná, "Za školou"), combined with findings from two cave sites in Bohemia (Nad Kačákem Cave) and southern Moravia (Pekárna Cave) and critical re-examination of the LRJ sites and materials from other areas, we propose that the LRJ should actually be considered a late Initial Upper Paleolithic industry. Its initial dates are just before Heinrich Event 4 (HE-4) and the Campanian Ignimbrite (CI) super-eruption, c. 42-40 ka cal BP. We further propose that LRJ assemblages were produced by Homo sapiens, and that its roots are in the Bohunician industry. The LRJ originated as a result of a gradual technological transition, centering on the development of Levallois points into Jerzmanowice-type blade-points. It is also suggested that the LRJ industry first appeared in Moravia, in central Europe, and spread along with its makers (Homo sapiens) across the northern latitudes of central and western Europe. Accordingly, the IUP "Bohunician package" did not disappear in Europe but gave rise to another IUP industry successfully adapted for the then steppe-tundra belts in northern Europe.

RevDate: 2023-06-19
CmpDate: 2023-06-02

Petersen J, Englmaier L, Artemov AV, et al (2023)

A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology.

Nature communications, 14(1):3092.

In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.

RevDate: 2023-05-29

Boneta Jiménez I, Cardoso JL, A Pérez-García (2023)

The turtles from the middle Paleolithic site of Gruta Nova da Columbeira (Bombarral, Portugal): Update through an archaeozoological perspective.

Anatomical record (Hoboken, N.J. : 2007) [Epub ahead of print].

Twenty-five years after the preliminary systematic study of the turtle remains (Agrionemys [=Testudo] hermanni and Emys or Mauremys) recovered from Gruta Nova da Columbeira site (Bombarral, Portugal), the results of its review from systematic and archaeozoological perspectives are presented here. Tortoise remains studies from pre-Upper Paleolithic sites worldwide have provided relevant data confirming its role as a dietary supply for hominid populations and informing about their ability to adapt to local environmental resources. The Iberian Peninsula record in general, and specifically, that from Portugal, have yielded substantial evidence to this highly debated topic. In this sense, turtle remains recovered in Gruta Nova da Columbeira site, discovered in the 1960s and the main ensemble chronologically ascribed to the MIS-5 (87.1 ± 6.3 ka BP), offer new information to this debate. Its detailed restudy, has allowed us the identification, justification, and figuration of remains attributed to two Iberian turtle taxa, Chersine hermanni and Emys orbicularis. Therefore, this update on the data concerning the turtle record from Gruta Nova da Columbeira provides new justified taxonomic evidence regarding the Iberian turtle taxa distribution during the Upper Pleistocene. The previously suggested hypothesis about the tortoise human consumption on the site is here evaluated through the development of an archaeozoological and taphonomical analysis, as well as considering the potential documentation of anthropic alterations (e.g., burning, cutmarks, percussion marks). In this sense, this hypothesis is confirmed. In addition, the presence of carnivore activity evidence indicates the engagement of other agents in the deposit formation.

RevDate: 2023-05-28

Schmidt P, Koch TJ, Blessing MA, et al (2023)

Production method of the Königsaue birch tar documents cumulative culture in Neanderthals.

Archaeological and anthropological sciences, 15(6):84.

UNLABELLED: Birch tar is the oldest synthetic substance made by early humans. The earliest such artefacts are associated with Neanderthals. According to traditional interpretations, their study allows understanding Neanderthal tool behaviours, skills and cultural evolution. However, recent work has found that birch tar can also be produced with simple processes, or even result from fortuitous accidents. Even though these findings suggest that birch tar per se is not a proxy for cognition, they do not shed light on the process by which Neanderthals produced it, and, therefore, cannot evaluate the implications of that behaviour. Here, we address the question of how tar was made by Neanderthals. Through a comparative chemical analysis of the two exceptional birch tar pieces from Königsaue (Germany) and a large reference birch tar collection made with Stone Age techniques, we found that Neanderthals did not use the simplest method to make tar. Rather, they distilled tar in an intentionally created underground environment that restricted oxygen flow and remained invisible during the process. This degree of complexity is unlikely to have been invented spontaneously. Our results suggest that Neanderthals invented or developed this process based on previous simpler methods and constitute one of the clearest indicators of cumulative cultural evolution in the European Middle Palaeolithic.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12520-023-01789-2.

RevDate: 2023-06-05
CmpDate: 2023-05-25

Tobler R, Souilmi Y, Huber CD, et al (2023)

The role of genetic selection and climatic factors in the dispersal of anatomically modern humans out of Africa.

Proceedings of the National Academy of Sciences of the United States of America, 120(22):e2213061120.

The evolutionarily recent dispersal of anatomically modern humans (AMH) out of Africa (OoA) and across Eurasia provides a unique opportunity to examine the impacts of genetic selection as humans adapted to multiple new environments. Analysis of ancient Eurasian genomic datasets (~1,000 to 45,000 y old) reveals signatures of strong selection, including at least 57 hard sweeps after the initial AMH movement OoA, which have been obscured in modern populations by extensive admixture during the Holocene. The spatiotemporal patterns of these hard sweeps provide a means to reconstruct early AMH population dispersals OoA. We identify a previously unsuspected extended period of genetic adaptation lasting ~30,000 y, potentially in the Arabian Peninsula area, prior to a major Neandertal genetic introgression and subsequent rapid dispersal across Eurasia as far as Australia. Consistent functional targets of selection initiated during this period, which we term the Arabian Standstill, include loci involved in the regulation of fat storage, neural development, skin physiology, and cilia function. Similar adaptive signatures are also evident in introgressed archaic hominin loci and modern Arctic human groups, and we suggest that this signal represents selection for cold adaptation. Surprisingly, many of the candidate selected loci across these groups appear to directly interact and coordinately regulate biological processes, with a number associated with major modern diseases including the ciliopathies, metabolic syndrome, and neurodegenerative disorders. This expands the potential for ancestral human adaptation to directly impact modern diseases, providing a platform for evolutionary medicine.

RevDate: 2023-06-19
CmpDate: 2023-06-19

Klein K, Weniger GC, Ludwig P, et al (2023)

Assessing climatic impact on transition from Neanderthal to anatomically modern human population on Iberian Peninsula: a macroscopic perspective.

Science bulletin, 68(11):1176-1186.

The Iberian Peninsula is of particular interest for the research on the Neanderthal (NEA) to anatomically modern human (AMH) population transition. The AMHs arrived in Iberia last from Eastern Europe and thus any possible contacts between the two populations occurred here later than elsewhere. The transition process took place in the earlier part of the Marine Isotope Stage 3 (∼60-27 cal ka BP) as repeated and profound climate changes challenged the population stability. To investigate how climate change and population interactions influenced the transition, we combine climate data with archaeological-site data to reconstruct the Human Existence Potential, a measure of the probability of human existence, for both the NEA and AMH populations in the Greenland Interstadial 11-10 (GI11-10) and Stadial 10-9/Heinrich event 4 (GS10-9/HE4) times. It is found that during GS10-9/HE4, large parts of the peninsula became unsuitable for NEA human existence and the NEA settlement areas contracted to isolated coastal hot spots. As a consequence, the NEA networks became highly unstable, triggering the final collapse of the population. The AMHs arrived in Iberia in GI10 but were confined to patches in the northern most strip of the peninsula. They were soon facing the much colder climate of GS10-9/HE4, which prevented their further expansion or even caused a contraction of their settlement areas. Thus, due to the constellation of climate change and the dispersal of the two populations into different regions of the peninsula, it is unlikely that the NEAs and AMHs coexisted in extensive areas and the AMHs had a significant influence on the demography of the NEAs.

RevDate: 2023-05-17

Cobat A, Zhang Q, Covid Human Genetic Effort , et al (2023)

Human Genomics of COVID-19 Pneumonia: Contributions of Rare and Common Variants.

Annual review of biomedical data science [Epub ahead of print].

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is silent or benign in most infected individuals, but causes hypoxemic COVID-19 pneumonia in about 10% of cases. We review studies of the human genetics of life-threatening COVID-19 pneumonia, focusing on both rare and common variants. Large-scale genome-wide association studies have identified more than 20 common loci robustly associated with COVID-19 pneumonia with modest effect sizes, some implicating genes expressed in the lungs or leukocytes. The most robust association, on chromosome 3, concerns a haplotype inherited from Neanderthals. Sequencing studies focusing on rare variants with a strong effect have been particularly successful, identifying inborn errors of type I interferon (IFN) immunity in 1-5% of unvaccinated patients with critical pneumonia, and their autoimmune phenocopy, autoantibodies against type I IFN, in another 15-20% of cases. Our growing understanding of the impact of human genetic variation on immunity to SARS-CoV-2 is enabling health systems to improve protection for individuals and populations. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 6 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

RevDate: 2023-05-29
CmpDate: 2023-05-18

Rong S, Neil CR, Welch A, et al (2023)

Large-scale functional screen identifies genetic variants with splicing effects in modern and archaic humans.

Proceedings of the National Academy of Sciences of the United States of America, 120(21):e2218308120.

Humans coexisted and interbred with other hominins which later became extinct. These archaic hominins are known to us only through fossil records and for two cases, genome sequences. Here, we engineer Neanderthal and Denisovan sequences into thousands of artificial genes to reconstruct the pre-mRNA processing patterns of these extinct populations. Of the 5,169 alleles tested in this massively parallel splicing reporter assay (MaPSy), we report 962 exonic splicing mutations that correspond to differences in exon recognition between extant and extinct hominins. Using MaPSy splicing variants, predicted splicing variants, and splicing quantitative trait loci, we show that splice-disrupting variants experienced greater purifying selection in anatomically modern humans than that in Neanderthals. Adaptively introgressed variants were enriched for moderate-effect splicing variants, consistent with positive selection for alternative spliced alleles following introgression. As particularly compelling examples, we characterized a unique tissue-specific alternative splicing variant at the adaptively introgressed innate immunity gene TLR1, as well as a unique Neanderthal introgressed alternative splicing variant in the gene HSPG2 that encodes perlecan. We further identified potentially pathogenic splicing variants found only in Neanderthals and Denisovans in genes related to sperm maturation and immunity. Finally, we found splicing variants that may contribute to variation among modern humans in total bilirubin, balding, hemoglobin levels, and lung capacity. Our findings provide unique insights into natural selection acting on splicing in human evolution and demonstrate how functional assays can be used to identify candidate causal variants underlying differences in gene regulation and phenotype.

RevDate: 2023-05-15
CmpDate: 2023-05-10

Li Q, Chen J, Faux P, et al (2023)

Automatic landmarking identifies new loci associated with face morphology and implicates Neanderthal introgression in human nasal shape.

Communications biology, 6(1):481.

We report a genome-wide association study of facial features in >6000 Latin Americans based on automatic landmarking of 2D portraits and testing for association with inter-landmark distances. We detected significant associations (P-value <5 × 10[-8]) at 42 genome regions, nine of which have been previously reported. In follow-up analyses, 26 of the 33 novel regions replicate in East Asians, Europeans, or Africans, and one mouse homologous region influences craniofacial morphology in mice. The novel region in 1q32.3 shows introgression from Neanderthals and we find that the introgressed tract increases nasal height (consistent with the differentiation between Neanderthals and modern humans). Novel regions include candidate genes and genome regulatory elements previously implicated in craniofacial development, and show preferential transcription in cranial neural crest cells. The automated approach used here should simplify the collection of large study samples from across the world, facilitating a cosmopolitan characterization of the genetics of facial features.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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The first fossil recognized to be an ancestral human was found in the Neander Valley (thal in German) in 1856. William King suggested Homo neanderthalensis (human from the Neander Valley) as the scientific name for the specimen — hence Neanderthal became the common name by which this early human became known. Now Neanderthal genomes have been sequenced, more is known about their path to extinction, and the existence of Neanderthal culture, including music, has been established. To understand the evolutionary path of the hominid line, one must be familiar with Homo neanderthalensis. These books are highly recommended. R. Robbins

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E-mail: RJR8222@gmail.com

Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )