scholarly journals Polygenic patterns of adaptive introgression in modern humans are mainly shaped by response to pathogens

2019 ◽  
Author(s):  
Alexandre Gouy ◽  
Laurent Excoffier
Keyword(s):  
Functional Enrichment ◽  
Modern Humans ◽  
Adaptive Introgression ◽  
Metabolic Functions ◽  
Gene Sets ◽  
Sequential Selection ◽  
Anatomically Modern Humans ◽  
Polygenic Adaptation ◽  
The Subject ◽  
Archaic Introgression

AbstractAnatomically modern humans carry many introgressed variants from other hominins in their genomes. Some of them affect their phenotype and can thus be negatively or positively selected. Several individual genes have been proposed to be the subject of adaptive introgression, but the possibility of polygenic adaptive introgression has not been extensively investigated yet. In this study, we analyze archaic introgression maps with refined functional enrichment methods to find signals of polygenic adaptation of introgressed variants. We first apply a method to detect sets of connected genes (sub-networks) within biological pathways that present higher-than-expected levels of archaic introgression. We then introduce and apply a new statistical test to distinguish between epistatic and independent selection in gene sets of present-day humans. We identify several known targets of adaptive introgression, and we show that they belong to larger networks of introgressed genes. After correction for genetic linkage, we find that signals of polygenic adaptation are mostly explained by independent and potentially sequential selection episodes. However, we also find some gene sets where introgressed variants present significant signals of epistatic selection. Our results confirm that archaic introgression has facilitated local adaptation, especially in immunity-related and metabolic functions and highlight its involvement in a coordinated response to pathogens out of Africa.

scholarly journals Polygenic Patterns of Adaptive Introgression in Modern Humans Are Mainly Shaped by Response to Pathogens

2020 ◽  
Vol 37 (5) ◽  
pp. 1420-1433 ◽  
Author(s):  
Alexandre Gouy ◽  
Laurent Excoffier
Keyword(s):  
Functional Enrichment ◽  
Modern Humans ◽  
Adaptive Introgression ◽  
Metabolic Functions ◽  
Gene Sets ◽  
Sequential Selection ◽  
Anatomically Modern Humans ◽  
Polygenic Adaptation ◽  
The Subject ◽  
Archaic Introgression

Abstract Anatomically modern humans carry many introgressed variants from other hominins in their genomes. Some of them affect their phenotype and can thus be negatively or positively selected. Several individual genes have been proposed to be the subject of adaptive introgression, but the possibility of polygenic adaptive introgression has not been extensively investigated yet. In this study, we analyze archaic introgression maps with refined functional enrichment methods to find signals of polygenic adaptation of introgressed variants. We first apply a method to detect sets of connected genes (subnetworks) within biological pathways that present higher-than-expected levels of archaic introgression. We then introduce and apply a new statistical test to distinguish between epistatic and independent selection in gene sets of present-day humans. We identify several known targets of adaptive introgression, and we show that they belong to larger networks of introgressed genes. After correction for genetic linkage, we find that signals of polygenic adaptation are mostly explained by independent and potentially sequential selection episodes. However, we also find some gene sets where introgressed variants present significant signals of epistatic selection. Our results confirm that archaic introgression has facilitated local adaptation, especially in immunity related and metabolic functions and highlight its involvement in a coordinated response to pathogens out of Africa.

scholarly journals Recovering signals of ghost archaic introgression in African populations

2020 ◽  
Vol 6 (7) ◽  
pp. eaax5097 ◽  
Author(s):  
Arun Durvasula ◽  
Sriram Sankararaman
Keyword(s):  
High Frequency ◽  
West African ◽  
Substantial Contribution ◽  
Modern Humans ◽  
Frequency Spectra ◽  
Adaptive Introgression ◽  
Genome Wide ◽  
African Populations ◽  
Archaic Introgression ◽  
Lines Of Evidence

While introgression from Neanderthals and Denisovans has been documented in modern humans outside Africa, the contribution of archaic hominins to the genetic variation of present-day Africans remains poorly understood. We provide complementary lines of evidence for archaic introgression into four West African populations. Our analyses of site frequency spectra indicate that these populations derive 2 to 19% of their genetic ancestry from an archaic population that diverged before the split of Neanderthals and modern humans. Using a method that can identify segments of archaic ancestry without the need for reference archaic genomes, we built genome-wide maps of archaic ancestry in the Yoruba and the Mende populations. Analyses of these maps reveal segments of archaic ancestry at high frequency in these populations that represent potential targets of adaptive introgression. Our results reveal the substantial contribution of archaic ancestry in shaping the gene pool of present-day West African populations.

scholarly journals Recovering signals of ghost archaic introgression in African populations

2018 ◽  
Author(s):  
Arun Durvasula ◽  
Sriram Sankararaman
Keyword(s):  
High Frequency ◽  
Substantial Contribution ◽  
Genome Sequences ◽  
Modern Humans ◽  
Frequency Spectra ◽  
Adaptive Introgression ◽  
Genome Wide ◽  
African Populations ◽  
Archaic Introgression ◽  
Sub Saharan

AbstractWhile introgression from Neanderthals and Denisovans has been well-documented in modern humans outside Africa, the contribution of archaic hominins to the genetic variation of present-day Africans remains poorly understood. Using 405 whole-genome sequences from four sub-Saharan African populations, we provide complementary lines of evidence for archaic introgression into these populations. Our analyses of site frequency spectra indicate that these populations derive 2-19% of their genetic ancestry from an archaic population that diverged prior to the split of Neanderthals and modern humans. Using a method that can identify segments of archaic ancestry without the need for reference archaic genomes, we built genome-wide maps of archaic ancestry in the Yoruba and the Mende populations that recover about 482 and 502 megabases of archaic sequence, respectively. Analyses of these maps reveal segments of archaic ancestry at high frequency in these populations that represent potential targets of adaptive introgression. Our results reveal the substantial contribution of archaic ancestry in shaping the gene pool of present-day African populations.One sentence summaryMultiple present-day African populations inherited genes from an unknown archaic population that diverged before modern humans and Neanderthals split.

scholarly journals Cold-induction of afadin in brown fat supports its thermogenic capacity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morten Lundh ◽  
Ali Altıntaş ◽  
Marco Tozzi ◽  
Odile Fabre ◽  
Tao Ma ◽  
...  
Keyword(s):  
Cold Exposure ◽  
Functional Enrichment ◽  
Activation Process ◽  
Target Tissue ◽  
Cold Stimulation ◽  
Brown Adipocytes ◽  
Protein Levels ◽  
Mrna Induction ◽  
Metabolic Functions ◽  
Brown Adipose

AbstractThe profound energy-expending nature of brown adipose tissue (BAT) thermogenesis makes it an attractive target tissue to combat obesity-associated metabolic disorders. While cold exposure is the strongest inducer of BAT activity, the temporal mechanisms tuning BAT adaptation during this activation process are incompletely understood. Here we show that the scaffold protein Afadin is dynamically regulated by cold in BAT, and participates in cold acclimation. Cold exposure acutely increases Afadin protein levels and its phosphorylation in BAT. Knockdown of Afadin in brown pre-adipocytes does not alter adipogenesis but restricts β3-adrenegic induction of thermogenic genes expression and HSL phosphorylation in mature brown adipocytes. Consistent with a defect in thermogenesis, an impaired cold tolerance was observed in fat-specific Afadin knockout mice. However, while Afadin depletion led to reduced Ucp1 mRNA induction by cold, stimulation of Ucp1 protein was conserved. Transcriptomic analysis revealed that fat-specific ablation of Afadin led to decreased functional enrichment of gene sets controlling essential metabolic functions at thermoneutrality in BAT, whereas it led to an altered reprogramming in response to cold, with enhanced enrichment of different pathways related to metabolism and remodeling. Collectively, we demonstrate a role for Afadin in supporting the adrenergic response in brown adipocytes and BAT function.

scholarly journals Stochastic models support rapid peopling of Late Pleistocene Sahul

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Corey J. A. Bradshaw ◽  
Kasih Norman ◽  
Sean Ulm ◽  
Alan N. Williams ◽  
Chris Clarkson ◽  
...  
Keyword(s):  
Stochastic Models ◽  
Ecological Model ◽  
New Guinea ◽  
Emergent Properties ◽  
Modern Humans ◽  
Global Migration ◽  
Early Settlement ◽  
Anatomically Modern Humans ◽  
Settlement Event ◽  
Initial Entry

AbstractThe peopling of Sahul (the combined continent of Australia and New Guinea) represents the earliest continental migration and settlement event of solely anatomically modern humans, but its patterns and ecological drivers remain largely conceptual in the current literature. We present an advanced stochastic-ecological model to test the relative support for scenarios describing where and when the first humans entered Sahul, and their most probable routes of early settlement. The model supports a dominant entry via the northwest Sahul Shelf first, potentially followed by a second entry through New Guinea, with initial entry most consistent with 50,000 or 75,000 years ago based on comparison with bias-corrected archaeological map layers. The model’s emergent properties predict that peopling of the entire continent occurred rapidly across all ecological environments within 156–208 human generations (4368–5599 years) and at a plausible rate of 0.71–0.92 km year−1. More broadly, our methods and approaches can readily inform other global migration debates, with results supporting an exit of anatomically modern humans from Africa 63,000–90,000 years ago, and the peopling of Eurasia in as little as 12,000–15,000 years via inland routes.

Review Feature: A review of The Mind in the Cave: Consciousness and the Origins of Art by David Lewis-Williams. London: Thames & Hudson, 2002. ISBN 0-500-05117-8 hardback £18.95 & US$29.95; 320 pp., 66 figs., 29 colour plates

2003 ◽  
Vol 13 (2) ◽  
pp. 263-279 ◽  
Author(s):  
David Lewis-Williams ◽  
E. Thomas Lawson ◽  
Knut Helskog ◽  
David S. Whitley ◽  
Paul Mellars
Keyword(s):  
Rock Art ◽  
David Lewis ◽  
Modern Human ◽  
Hominid Evolution ◽  
Modern Humans ◽  
Radiocarbon Dates ◽  
Anatomically Modern Humans ◽  
The Mind ◽  
Cave Art ◽  
West European

David Lewis-Williams is well-known in rock-art circles as the author of a series of articles drawing on ethnographic material and shamanism (notably connected with the San rock art of southern Africa) to gain new insights into the Palaeolithic cave art of western Europe. Some 15 years ago, with Thomas Dowson, he proposed that Palaeolithic art owed its inspiration at least in part to trance experiences (altered states of consciousness) associated with shamanistic practices. Since that article appeared, the shamanistic hypothesis has both been widely adopted and developed in the study of different rock-art traditions, and has become the subject of lively and sometimes heated controversy. In the present volume, Lewis-Williams takes the argument further, and combines the shamanistic hypothesis with an interpretation of the development of human consciousness. He thus enters another contentious area of archaeological debate, seeking to understand west European cave art in the context of (and as a marker of) the new intellectual capacities of anatomically modern humans. Radiocarbon dates for the earliest west European cave art now place it contemporary with the demise of the Neanderthals around 30,000 years ago, and cave art, along with carved or decorated portable items, appears to announce the arrival and denote the success of modern humans in this region. Lewis-Williams argues that such cave art would have been beyond the capabilities of Neanderthals, and that this kind of artistic ability is unique to anatomically modern humans. Furthermore, he concludes that the development of the new ability cannot have been the product of hundreds of thousands of years of gradual hominid evolution, but must have arisen much more abruptly, within the novel neurological structure of anatomically modern humans. The Mind in the Cave is thus the product of two hypotheses, both of them contentious — the shamanistic interpretation of west European Upper Palaeolithic cave art, and the cognitive separation of modern humans and Neanderthals. But is it as simple as that? Was cave art the hallmark of a new cognitive ability and social consciousness that were beyond the reach of previous hominids? And is shamanism an outgrowth of the hard-wired structure of the modern human brain? We begin this Review Feature with a brief summary by David Lewis-Williams of the book's principal arguments. There follows a series of comments addressing both the meaning of the west European cave art, and its wider relevance for the understanding of the Neanderthal/modern human transition.

scholarly journals The Use of Ochre and Painting During the Upper Paleolithic of the Swabian Jura in the Context of the Development of Ochre Use in Africa and Europe

2018 ◽  
Vol 4 (1) ◽  
pp. 185-205 ◽  
Author(s):  
Sibylle Wolf ◽  
Nicholas J. Conard ◽  
Harald Floss ◽  
Rimtautas Dapschauskas ◽  
Elizabeth Velliky ◽  
...  
Keyword(s):  
Central Europe ◽  
Upper Paleolithic ◽  
Archaeological Sites ◽  
Modern Humans ◽  
Anatomically Modern Humans

Abstract While the earliest evidence for ochre use is very sparse, the habitual use of ochre by hominins appeared about 140,000 years ago and accompanied them ever since. Here, we present an overview of archaeological sites in southwestern Germany, which yielded remains of ochre. We focus on the artifacts belonging exclusively to anatomically modern humans who were the inhabitants of the cave sites in the Swabian Jura during the Upper Paleolithic. The painted limestones from the Magdalenian layers of Hohle Fels Cave are a particular focus. We present these artifacts in detail and argue that they represent the beginning of a tradition of painting in Central Europe.

scholarly journals Recessive deleterious variation has a limited impact on signals of adaptive introgression in human populations

2020 ◽  
Author(s):  
Xinjun Zhang ◽  
Bernard Kim ◽  
Kirk E. Lohmueller ◽  
Emilia Huerta-Sánchez
Keyword(s):  
False Positive ◽  
False Positive Rate ◽  
Genomic Variation ◽  
Human Populations ◽  
Deleterious Mutations ◽  
Modern Humans ◽  
Recombination Rates ◽  
Limited Impact ◽  
Adaptive Mutations ◽  
Adaptive Introgression

AbstractAdmixture with archaic hominins has altered the landscape of genomic variation in modern human populations. Several gene regions have been previously identified as candidates of adaptive introgression (AI) that facilitated human adaptation to specific environments. However, simulation-based studies have suggested that population genetics processes other than adaptive mutations, such as heterosis from recessive deleterious variants private to populations before admixture, can also lead to patterns in genomic data that resemble adaptive introgression. The extent to which the presence of deleterious variants affect the false-positive rate and the power of current methods to detect AI has not been fully assessed. Here, we used extensive simulations to show that recessive deleterious mutations can increase the false positive rates of tests for AI compared to models without deleterious variants. We further examined candidates of AI in modern humans identified from previous studies and show that, although deleterious variants may hinder the performance of AI detection in modern humans, most signals remained robust when deleterious variants are included in the null model. While deleterious variants may have a limited impact on detecting signals of adaptive introgression in humans, we found that at least two AI candidate genes, HYAL2 and HLA, are particularly susceptible to high false positive rates due to the recessive deleterious mutations. By quantifying parameters that affect heterosis, we show that the high false positives are largely attributed to the high exon densities together with low recombination rates in the genomic regions, which can further be exaggerated by the population growth in recent human evolution. Although the combination of such parameters is rare in the human genome, caution is still warranted in other species with different genomic composition and demographic histories.

scholarly journals Revisiting the Out of Africa event with a novel Deep Learning approach

2020 ◽  
Author(s):  
Francesco Montinaro ◽  
Vasili Pankratov ◽  
Burak Yelmen ◽  
Luca Pagani ◽  
Mayukh Mondal
Keyword(s):  
Deep Learning ◽  
Sequential Monte Carlo ◽  
Whole Genome Sequence ◽  
Learning Approach ◽  
Whole Genome ◽  
Modern Humans ◽  
Anatomically Modern Humans ◽  
Out Of Africa ◽  
Approximate Bayesian ◽  
Back To Africa

AbstractAnatomically modern humans evolved around 300 thousand years ago in Africa1. Modern humans started to appear in the fossil record outside of Africa about 100 thousand years ago though other hominins existed throughout Eurasia much earlier2–4. Recently, several researchers argued in favour of a single out of Africa event for modern humans based on whole-genome sequences analyses5–7. However, the single out of Africa model is in contrast with some of the findings from fossil records, which supports two out of Africa8,9, and uniparental data, which proposes back to Africa movement10,11. Here, we used a novel deep learning approach coupled with Approximate Bayesian Computation and Sequential Monte Carlo to revisit these hypotheses from the whole genome sequence perspective. Our results support the back to Africa model over other alternatives. We estimated that there are two successive splits between Africa and out of African populations happening around 60-80 thousand years ago and separated by 12-13 thousand years. One of the populations resulting from the more recent split has to a large extent replaced the older West African population while the other one has founded the out of Africa populations.

Sign in / Sign up

Export Citation Format

Share Document