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1.
BMC Evol Biol ; 20(1): 119, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933484

RESUMO

BACKGROUND: Many species are threatened with extinction as their population sizes decrease with changing environments or face novel pathogenic threats. A reduction of genetic diversity at major histocompatibility complex (MHC) genes may have dramatic effects on populations' survival, as these genes play a key role in adaptive immunity. This might be the case for chimpanzees, the MHC genes of which reveal signatures of an ancient selective sweep likely due to a viral epidemic that reduced their population size a few million years ago. To better assess how this past event affected MHC variation in chimpanzees compared to humans, we analysed several indexes of genetic diversity and linkage disequilibrium across seven MHC genes on four cohorts of chimpanzees and we compared them to those estimated at orthologous HLA genes in a large set of human populations. RESULTS: Interestingly, the analyses uncovered similar patterns of both molecular diversity and linkage disequilibrium across the seven MHC genes in chimpanzees and humans. Indeed, in both species the greatest allelic richness and heterozygosity were found at loci A, B, C and DRB1, the greatest nucleotide diversity at loci DRB1, DQA1 and DQB1, and both significant global linkage disequilibrium and the greatest proportions of haplotypes in linkage disequilibrium were observed at pairs DQA1 ~ DQB1, DQA1 ~ DRB1, DQB1 ~ DRB1 and B ~ C. Our results also showed that, despite some differences among loci, the levels of genetic diversity and linkage disequilibrium observed in contemporary chimpanzees were globally similar to those estimated in small isolated human populations, in contrast to significant differences compared to large populations. CONCLUSIONS: We conclude, first, that highly conserved mechanisms shaped the diversity of orthologous MHC genes in chimpanzees and humans. Furthermore, our findings support the hypothesis that an ancient demographic decline affecting the chimpanzee populations - like that ascribed to a viral epidemic - exerted a substantial effect on the molecular diversity of their MHC genes, albeit not more pronounced than that experienced by HLA genes in human populations that underwent rapid genetic drift during humans' peopling history. We thus propose a model where chimpanzees' MHC genes regenerated molecular variation through recombination/gene conversion and/or balancing selection after the selective sweep.


Assuntos
Evolução Molecular , Variação Genética , Antígenos HLA-D/genética , Hominidae/genética , Desequilíbrio de Ligação , Pan troglodytes , Alelos , Animais , Frequência do Gene , Genética Populacional , Haplótipos , Humanos , Pan troglodytes/genética
2.
PLoS Biol ; 18(8): e3000838, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32804933

RESUMO

In humans, most germline mutations are inherited from the father. This observation has been widely interpreted as reflecting the replication errors that accrue during spermatogenesis. If so, the male bias in mutation should be substantially lower in a closely related species with similar rates of spermatogonial stem cell divisions but a shorter mean age of reproduction. To test this hypothesis, we resequenced two 3-4 generation nuclear families (totaling 29 individuals) of olive baboons (Papio anubis), who reproduce at approximately 10 years of age on average, and analyzed the data in parallel with three 3-generation human pedigrees (26 individuals). We estimated a mutation rate per generation in baboons of 0.57×10-8 per base pair, approximately half that of humans. Strikingly, however, the degree of male bias in germline mutations is approximately 4:1, similar to that of humans-indeed, a similar male bias is seen across mammals that reproduce months, years, or decades after birth. These results mirror the finding in humans that the male mutation bias is stable with parental ages and cast further doubt on the assumption that germline mutations track cell divisions. Our mutation rate estimates for baboons raise a further puzzle, suggesting a divergence time between apes and Old World monkeys of 65 million years, too old to be consistent with the fossil record; reconciling them now requires not only a slowdown of the mutation rate per generation in humans but also in baboons.


Assuntos
Mutação em Linhagem Germinativa , Hominidae/genética , Taxa de Mutação , Papio/genética , Reprodução/genética , Espermatozoides/metabolismo , Fatores Etários , Animais , Evolução Biológica , Divisão Celular , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Modelos Genéticos , Linhagem , Fatores Sexuais , Especificidade da Espécie , Espermatogênese/genética , Espermatozoides/citologia
3.
Nat Genet ; 52(8): 849-858, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32541924

RESUMO

Inversions play an important role in disease and evolution but are difficult to characterize because their breakpoints map to large repeats. We increased by sixfold the number (n = 1,069) of previously reported great ape inversions by using single-cell DNA template strand and long-read sequencing. We find that the X chromosome is most enriched (2.5-fold) for inversions, on the basis of its size and duplication content. There is an excess of differentially expressed primate genes near the breakpoints of large (>100 kilobases (kb)) inversions but not smaller events. We show that when great ape lineage-specific duplications emerge, they preferentially (approximately 75%) occur in an inverted orientation compared to that at their ancestral locus. We construct megabase-pair scale haplotypes for individual chromosomes and identify 23 genomic regions that have recurrently toggled between a direct and an inverted state over 15 million years. The direct orientation is most frequently the derived state for human polymorphisms that predispose to recurrent copy number variants associated with neurodevelopmental disease.


Assuntos
Inversão Cromossômica/genética , Genoma/genética , Hominidae/genética , Animais , Cromossomos/genética , Variações do Número de Cópias de DNA/genética , Evolução Molecular , Feminino , Haplótipos/genética , Humanos , Masculino
4.
Med Sci (Paris) ; 36(4): 421-423, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32356723

RESUMO

Sophisticated analyses of current human populations compared to a high-coverage Neandertal genome sequence indicate that, contrary to the previous consensus, African genomes carry a small but significant amount of Neandertal-specific DNA. This indicates back-migration into Africa of modern humans (carrying some Neandertal sequences) and underlines the complexity of ancient human migrations.


Assuntos
DNA/genética , Hominidae/genética , Homem de Neandertal/genética , África , Animais , DNA/análise , Evolução Molecular , Genética Populacional , Genoma , História do Século XXI , História Antiga , Hominidae/classificação , Humanos , Hibridização Genética , Homem de Neandertal/classificação , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
5.
Science ; 367(6484)2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32193295

RESUMO

Genome sequences from diverse human groups are needed to understand the structure of genetic variation in our species and the history of, and relationships between, different populations. We present 929 high-coverage genome sequences from 54 diverse human populations, 26 of which are physically phased using linked-read sequencing. Analyses of these genomes reveal an excess of previously undocumented common genetic variation private to southern Africa, central Africa, Oceania, and the Americas, but an absence of such variants fixed between major geographical regions. We also find deep and gradual population separations within Africa, contrasting population size histories between hunter-gatherer and agriculturalist groups in the past 10,000 years, and a contrast between single Neanderthal but multiple Denisovan source populations contributing to present-day human populations.


Assuntos
Variação Genética , Genética Populacional , Genoma Humano , Sequenciamento Completo do Genoma , África , América , Animais , Ásia , Grupos de Populações Continentais/genética , Variações do Número de Cópias de DNA , Haplótipos , Hominidae/genética , Humanos , Mutação INDEL , Homem de Neandertal/genética , Oceania , Filogenia , Polimorfismo de Nucleotídeo Único , Densidade Demográfica
6.
Sci Adv ; 6(8): eaay5483, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32128408

RESUMO

Previous research has shown that modern Eurasians interbred with their Neanderthal and Denisovan predecessors. We show here that hundreds of thousands of years earlier, the ancestors of Neanderthals and Denisovans interbred with their own Eurasian predecessors-members of a "superarchaic" population that separated from other humans about 2 million years ago. The superarchaic population was large, with an effective size between 20 and 50 thousand individuals. We confirm previous findings that (i) Denisovans also interbred with superarchaics, (ii) Neanderthals and Denisovans separated early in the middle Pleistocene, (iii) their ancestors endured a bottleneck of population size, and (iv) the Neanderthal population was large at first but then declined in size. We provide qualified support for the view that (v) Neanderthals interbred with the ancestors of modern humans.


Assuntos
Consanguinidade , Hominidae/genética , Homem de Neandertal/genética , Animais , Intervalos de Confiança , Fluxo Gênico , Genética Populacional , Modelos Genéticos , Filogenia
8.
Nat Commun ; 11(1): 301, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949148

RESUMO

Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains perferentially affect oligodendrocyte function postnatally and are preferentially affected in the brains of autism patients. This preference is also observed for human-specific GREs suggesting this system is under continued selective pressure. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease.


Assuntos
Transtorno Autístico/metabolismo , Encéfalo/metabolismo , Hominidae/metabolismo , Oligodendroglia/metabolismo , Sequências Reguladoras de Ácido Nucleico/fisiologia , Animais , Transtorno Autístico/genética , Callithrix , Cromatina , Imunoprecipitação da Cromatina , Cromossomos/química , Suscetibilidade a Doenças , Evolução Molecular , Feminino , Regulação da Expressão Gênica , Genômica , Hominidae/genética , Humanos , Macaca mulatta , Pan troglodytes
9.
Immunogenetics ; 72(1-2): 25-36, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31624862

RESUMO

The major histocompatibility complex (MHC) is central to the innate and adaptive immune responses of jawed vertebrates. Characteristic of the MHC are high gene density, gene copy number variation, and allelic polymorphism. Because apes and monkeys are the closest living relatives of humans, the MHCs of these non-human primates (NHP) are studied in depth in the context of evolution, biomedicine, and conservation biology. The Immuno Polymorphism Database (IPD)-MHC NHP Database (IPD-MHC NHP), which curates MHC data of great and small apes, as well as Old and New World monkeys, has been upgraded. The curators of the database are responsible for providing official designations for newly discovered alleles. This nomenclature report updates the 2012 report, and summarizes important nomenclature issues and relevant novel features of the IPD-MHC NHP Database.


Assuntos
Bases de Dados Genéticas , Complexo Principal de Histocompatibilidade/genética , Primatas/genética , Primatas/imunologia , Alelos , Animais , Cercopithecidae/genética , Hominidae/genética , Complexo Principal de Histocompatibilidade/fisiologia , Filogenia , Platirrinos/genética , Polimorfismo Genético , Terminologia como Assunto
10.
BMC Evol Biol ; 19(1): 218, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791241

RESUMO

BACKGROUND: Lymphotoxin-α (LTα), located in the Major Histocompatibility Complex (MHC) class III region on chromosome 6, encodes a cytotoxic protein that mediates a variety of antiviral responses among other biological functions. Furthermore, several genotypes at this gene have been implicated in the onset of a number of complex diseases, including myocardial infarction, autoimmunity, and various types of cancer. However, little is known about levels of nucleotide variation and linkage disequilibrium (LD) in and near LTα, which could also influence phenotypic variance. To address this gap in knowledge, we examined sequence variation across ~ 10 kilobases (kbs), encompassing LTα and the upstream region, in 2039 individuals from the 1000 Genomes Project originating from 21 global populations. RESULTS: Here, we observed striking patterns of diversity, including an excess of intermediate-frequency alleles, the maintenance of multiple common haplotypes and a deep coalescence time for variation (dating > 1.0 million years ago), in global populations. While these results are generally consistent with a model of balancing selection, we also uncovered a signature of positive selection in the form of long-range LD on chromosomes with derived alleles primarily in Eurasian populations. To reconcile these findings, which appear to support different models of selection, we argue that selective sweeps (particularly, soft sweeps) of multiple derived alleles in and/or near LTα occurred in non-Africans after their ancestors left Africa. Furthermore, these targets of selection were predicted to alter transcription factor binding site affinity and protein stability, suggesting they play a role in gene function. Additionally, our data also showed that a subset of these functional adaptive variants are present in archaic hominin genomes. CONCLUSIONS: Overall, this study identified candidate functional alleles in a biologically-relevant genomic region, and offers new insights into the evolutionary origins of these loci in modern human populations.


Assuntos
Linfotoxina-alfa/genética , Complexo Principal de Histocompatibilidade , África , Animais , Evolução Biológica , Cromossomos Humanos Par 6 , Evolução Molecular , Frequência do Gene , Genética Populacional , Haplótipos , Hominidae/genética , Projeto Genoma Humano , Humanos , Desequilíbrio de Ligação , Linfotoxina-alfa/imunologia , Polimorfismo de Nucleotídeo Único
11.
Am J Hum Genet ; 105(6): 1254-1261, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31809748

RESUMO

Recent work has demonstrated that two archaic human groups (Neanderthals and Denisovans) interbred with modern humans and contributed to the contemporary human gene pool. These findings relied on the availability of high-coverage genomes from both Neanderthals and Denisovans. Here we search for evidence of archaic admixture from a worldwide panel of 1,667 individuals using an approach that does not require the presence of an archaic human reference genome. We find no evidence for archaic admixture in the Andaman Islands, as previously claimed, or on the island of Flores, where Homo floresiensis fossils have been found. However, we do find evidence for at least one archaic admixture event in sub-Saharan Africa, with the strongest signal in Khoesan and Pygmy individuals from Southern and Central Africa. The locations of these putative archaic admixture tracts are weighted against functional regions of the genome, consistent with the long-term effects of purifying selection against introgressed genetic material.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Fósseis , Genética Populacional , Genoma Humano , Hominidae/genética , Homem de Neandertal/genética , Animais , Pool Gênico , Humanos
12.
BMC Genomics ; 20(1): 1017, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31878873

RESUMO

BACKGROUND: Traces of interbreeding of Neanderthals and Denisovans with modern humans in the form of archaic DNA have been detected in the genomes of present-day human populations outside sub-Saharan Africa. Up to now, only nuclear archaic DNA has been detected in modern humans; we therefore attempted to identify archaic mitochondrial DNA (mtDNA) residing in modern human nuclear genomes as nuclear inserts of mitochondrial DNA (NUMTs). RESULTS: We analysed 221 high-coverage genomes from Oceania and Indonesia using an approach which identifies reads that map both to the nuclear and mitochondrial DNA. We then classified reads according to the source of the mtDNA, and found one NUMT of Denisovan mtDNA origin, present in 15 analysed genomes; analysis of the flanking region suggests that this insertion is more likely to have happened in a Denisovan individual and introgressed into modern humans with the Denisovan nuclear DNA, rather than in a descendant of a Denisovan female and a modern human male. CONCLUSIONS: Here we present our pipeline for detecting introgressed NUMTs in next generation sequencing data that can be used on genomes sequenced in the future. Further discovery of such archaic NUMTs in modern humans can be used to detect interbreeding between archaic and modern humans and can reveal new insights into the nature of such interbreeding events.


Assuntos
Núcleo Celular/genética , DNA Mitocondrial/genética , Genômica/métodos , Animais , Evolução Molecular , Hominidae/genética , Homem de Neandertal/genética , Filogenia
13.
Cells ; 9(1)2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878147

RESUMO

High coverage sequences of archaic humans enabled the reconstruction of their DNA methylation patterns. This allowed comparing gene regulation between human groups, and linking such regulatory changes to phenotypic differences. In a previous work, a detailed comparison of DNA methylation in modern humans, archaic humans, and chimpanzees revealed 873 modern human-derived differentially methylated regions (DMRs). To understand the regulatory implications of these DMRs, we defined differentially methylated genes (DMGs) as genes that harbor DMRs in their promoter or gene body. While most of the modern human-derived DMRs could be linked to DMGs, many others remained unassigned. Here, we used information on 3D genome organization to link ~70 out of the remaining 288 unassigned DMRs to genes. Combined with the previously identified DMGs, we reinforce the enrichment of these genes with vocal and facial anatomy, and additionally find significant enrichment with the spinal column, chin, hair, and scalp. These results reveal the importance of 3D genomic organization in understanding gene regulation by DNA methylation.


Assuntos
Cabeça/anatomia & histologia , Hominidae/genética , Medula Espinal/anatomia & histologia , Animais , Metilação de DNA/genética , DNA Antigo/análise , Bases de Dados Genéticas , Epigênese Genética/genética , Genoma/genética , Genômica/métodos , Humanos , Homem de Neandertal/genética , Regiões Promotoras Genéticas/genética
14.
Elife ; 82019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729316

RESUMO

Immune regulation is a finely balanced process of positive and negative signals. PD-L1 and its receptor PD-1 are critical regulators of autoimmune, antiviral and antitumoural T cell responses. Although the function of its predominant membrane-bound form is well established, the source and biological activity of soluble PD-L1 (sPD-L1) remain incompletely understood. Here, we show that sPD-L1 in human healthy tissues and tumours is produced by exaptation of an intronic LINE-2A (L2A) endogenous retroelement in the CD274 gene, encoding PD-L1, which causes omission of the transmembrane domain and the regulatory sequence in the canonical 3' untranslated region. The alternatively spliced CD274-L2A transcript forms the major source of sPD-L1 and is highly conserved in hominids, but lost in mice and a few related species. Importantly, CD274-L2A-encoded sPD-L1 lacks measurable T cell inhibitory activity. Instead, it functions as a receptor antagonist, blocking the inhibitory activity of PD-L1 bound on cellular or exosomal membranes.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Retroelementos/genética , Processamento Alternativo/genética , Animais , Antígeno B7-H1/química , Antígeno B7-H1/genética , Proliferação de Células , Sequência Conservada/genética , Evolução Molecular , Éxons/genética , Células HEK293 , Hominidae/genética , Humanos , Imunossupressão , Camundongos Endogâmicos C57BL , Domínios Proteicos , Solubilidade
15.
Nature ; 576(7786): 262-265, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31723270

RESUMO

Gigantopithecus blacki was a giant hominid that inhabited densely forested environments of Southeast Asia during the Pleistocene epoch1. Its evolutionary relationships to other great ape species, and the divergence of these species during the Middle and Late Miocene epoch (16-5.3 million years ago), remain unclear2,3. Hypotheses regarding the relationships between Gigantopithecus and extinct and extant hominids are wide ranging but difficult to substantiate because of its highly derived dentognathic morphology, the absence of cranial and post-cranial remains1,3-6, and the lack of independent molecular validation. We retrieved dental enamel proteome sequences from a 1.9-million-year-old G. blacki molar found in Chuifeng Cave, China7,8. The thermal age of these protein sequences is approximately five times greater than that of any previously published mammalian proteome or genome. We demonstrate that Gigantopithecus is a sister clade to orangutans (genus Pongo) with a common ancestor about 12-10 million years ago, implying that the divergence of Gigantopithecus from Pongo forms part of the Miocene radiation of great apes. In addition, we hypothesize that the expression of alpha-2-HS-glycoprotein, which has not been previously observed in enamel proteomes, had a role in the biomineralization of the thick enamel crowns that characterize the large molars in Gigantopithecus9,10. The survival of an Early Pleistocene dental enamel proteome in the subtropics further expands the scope of palaeoproteomic analysis into geographical areas and time periods previously considered incompatible with the preservation of substantial amounts of genetic information.


Assuntos
Hominidae/genética , Proteoma , Sequência de Aminoácidos , Animais , Teorema de Bayes , Humanos , Filogenia , Fatores de Tempo
16.
PLoS Genet ; 15(11): e1008449, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31725722

RESUMO

Understanding the causes and consequences of recombination landscape evolution is a fundamental goal in genetics that requires recombination maps from across the tree of life. Such maps can be obtained from population genomic datasets, but require large sample sizes. Alternative methods are therefore necessary to research organisms where such datasets cannot be generated easily, such as non-model or ancient species. Here we extend the sequentially Markovian coalescent model to jointly infer demography and the spatial variation in recombination rate. Using extensive simulations and sequence data from humans, fruit-flies and a fungal pathogen, we demonstrate that iSMC accurately infers recombination maps under a wide range of scenarios-remarkably, even from a single pair of unphased genomes. We exploit this possibility and reconstruct the recombination maps of ancient hominins. We report that the ancient and modern maps are correlated in a manner that reflects the established phylogeny of Neanderthals, Denisovans, and modern human populations.


Assuntos
Genoma Humano/genética , Hominidae/genética , Metagenômica , Recombinação Genética/genética , Animais , Mapeamento Cromossômico , Variação Genética/genética , Humanos , Cadeias de Markov , Homem de Neandertal/genética , Paleontologia/tendências , Filogenia
17.
BMC Genomics ; 20(1): 842, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718558

RESUMO

BACKGROUND: Recent advances in genomic technologies have facilitated genome-wide investigation of human genetic variations. However, most efforts have focused on the major populations, yet trio genomes of indigenous populations from Southeast Asia have been under-investigated. RESULTS: We analyzed the whole-genome deep sequencing data (~ 30×) of five native trios from Peninsular Malaysia and North Borneo, and characterized the genomic variants, including single nucleotide variants (SNVs), small insertions and deletions (indels) and copy number variants (CNVs). We discovered approximately 6.9 million SNVs, 1.2 million indels, and 9000 CNVs in the 15 samples, of which 2.7% SNVs, 2.3% indels and 22% CNVs were novel, implying the insufficient coverage of population diversity in existing databases. We identified a higher proportion of novel variants in the Orang Asli (OA) samples, i.e., the indigenous people from Peninsular Malaysia, than that of the North Bornean (NB) samples, likely due to more complex demographic history and long-time isolation of the OA groups. We used the pedigree information to identify de novo variants and estimated the autosomal mutation rates to be 0.81 × 10- 8 - 1.33 × 10- 8, 1.0 × 10- 9 - 2.9 × 10- 9, and ~ 0.001 per site per generation for SNVs, indels, and CNVs, respectively. The trio-genomes also allowed for haplotype phasing with high accuracy, which serves as references to the future genomic studies of OA and NB populations. In addition, high-frequency inherited CNVs specific to OA or NB were identified. One example is a 50-kb duplication in DEFA1B detected only in the Negrito trios, implying plausible effects on host defense against the exposure of diverse microbial in tropical rainforest environment of these hunter-gatherers. The CNVs shared between OA and NB groups were much fewer than those specific to each group. Nevertheless, we identified a 142-kb duplication in AMY1A in all the 15 samples, and this gene is associated with the high-starch diet. Moreover, novel insertions shared with archaic hominids were identified in our samples. CONCLUSION: Our study presents a full catalogue of the genome variants of the native Malaysian populations, which is a complement of the genome diversity in Southeast Asians. It implies specific population history of the native inhabitants, and demonstrated the necessity of more genome sequencing efforts on the multi-ethnic native groups of Malaysia and Southeast Asia.


Assuntos
Variação Genética , Genoma Humano , Animais , Bornéu/etnologia , Variações do Número de Cópias de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Hominidae/genética , Humanos , Mutação INDEL , Malásia/etnologia , Taxa de Mutação
18.
Nat Commun ; 10(1): 5003, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676766

RESUMO

Neanderthals and modern humans both occupied the Levant for tens of thousands of years prior to the spread of modern humans into the rest of Eurasia and their replacement of the Neanderthals. That the inter-species boundary remained geographically localized for so long is a puzzle, particularly in light of the rapidity of its subsequent movement. Here, we propose that infectious-disease dynamics can explain the localization and persistence of the inter-species boundary. We further propose, and support with dynamical-systems models, that introgression-based transmission of alleles related to the immune system would have gradually diminished this barrier to pervasive inter-species interaction, leading to the eventual release of the inter-species boundary from its geographic localization. Asymmetries between the species in the characteristics of their associated 'pathogen packages' could have generated feedback that allowed modern humans to overcome disease burden earlier than Neanderthals, giving them an advantage in their subsequent spread into Eurasia.


Assuntos
Doenças Transmissíveis/genética , Hominidae/genética , Homem de Neandertal/genética , Algoritmos , Animais , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/transmissão , Fósseis , Geografia , Hominidae/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Modelos Genéticos , Homem de Neandertal/imunologia , Dinâmica Populacional
20.
Science ; 366(6463)2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31624180

RESUMO

Copy number variants (CNVs) are subject to stronger selective pressure than single-nucleotide variants, but their roles in archaic introgression and adaptation have not been systematically investigated. We show that stratified CNVs are significantly associated with signatures of positive selection in Melanesians and provide evidence for adaptive introgression of large CNVs at chromosomes 16p11.2 and 8p21.3 from Denisovans and Neanderthals, respectively. Using long-read sequence data, we reconstruct the structure and complex evolutionary history of these polymorphisms and show that both encode positively selected genes absent from most human populations. Our results collectively suggest that large CNVs originating in archaic hominins and introgressed into modern humans have played an important role in local population adaptation and represent an insufficiently studied source of large-scale genetic variation.


Assuntos
Introgressão Genética , Animais , Duplicação Cromossômica , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 8/genética , Variações do Número de Cópias de DNA , Evolução Molecular , Genoma Humano , Haplótipos , Hominidae/genética , Humanos , Melanesia , Modelos Genéticos , Homem de Neandertal/genética , Polimorfismo Genético , Seleção Genética , Sequenciamento Completo do Genoma
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