Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 236
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
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
5.
Evol Anthropol ; 28(4): 189-209, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31222847

RESUMO

During the late Pleistocene, isolated lineages of hominins exchanged genes thus influencing genomic variation in humans in both the past and present. However, the dynamics of this genetic exchange and associated phenotypic consequences through time remain poorly understood. Gene exchange across divergent lineages can result in myriad outcomes arising from these dynamics and the environmental conditions under which it occurs. Here we draw from our collective research across various organisms, illustrating some of the ways in which gene exchange can structure genomic/phenotypic diversity within/among species. We present a range of examples relevant to questions about the evolution of hominins. These examples are not meant to be exhaustive, but rather illustrative of the diverse evolutionary causes/consequences of hybridization, highlighting potential drivers of human evolution in the context of hybridization including: influences on adaptive evolution, climate change, developmental systems, sex-differences in behavior, Haldane's rule and the large X-effect, and transgressive phenotypic variation.


Assuntos
Evolução Biológica , Hominidae , Hibridização Genética/genética , Animais , Antropologia Física , Feminino , Genoma Humano/genética , Hominidae/anatomia & histologia , Hominidae/genética , Humanos , Masculino , Camundongos , Homem de Neandertal/anatomia & histologia , Homem de Neandertal/genética , Fenótipo , Crânio/anatomia & histologia
6.
Ann Hum Biol ; 46(2): 99-108, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31113254

RESUMO

Background: Simonti et al. reported variation in the frequency of Neanderthal alleles found in modern humans and argued that they may have provided an evolutionary advantage. One such allele is SNP rs3917862, associated with hypercoagulability. rs3917862 can be deleterious, but can also help prevent blood loss. Aim: To investigate two possible selective pressure hypotheses for rs3917862 surviving to higher frequencies: deaths from interpersonal violent trauma and childbirth. Subjects and methods: Mortality data from modern hunter-gatherers models the living conditions and causes of death of humans and Neanderthals at the point of admixture. Results: National census data indicates a positive correlation between the presence of rs3917862 and decreased maternal mortality ratios. When the maternal mortality ratio is modelled using GDP, births attended by skilled assistants and the presence of rs3917862, women are 0.1% more likely to die in childbirth in populations lacking rs3917862. Deaths due to violence show no correlation with rs3917862. Conclusion: These findings challenge the idea that Neanderthal admixture has negatively impacted the overall health of modern humans. Maternal survival may have acted as a selective pressure for the persistence of hypercoagulability alleles in modern Europeans. Understanding the role of hypercoagulability in childbirth, and the role of rs3917862, could help to reduce maternal mortality ratios.


Assuntos
Longevidade/genética , Mães/estatística & dados numéricos , Selectina-P/genética , Abuso Físico/estatística & dados numéricos , Polimorfismo de Nucleotídeo Único/genética , Seleção Genética , Alelos , Animais , Europa (Continente) , Grupo com Ancestrais do Continente Europeu , Frequência do Gene , Humanos , Homem de Neandertal/genética , Selectina-P/metabolismo , Tanzânia , Trombofilia/genética
7.
PLoS One ; 14(5): e0216742, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31141515

RESUMO

The causes of disappearance of the Neanderthals, the only human population living in Europe before the arrival of Homo sapiens, have been debated for decades by the scientific community. Different hypotheses have been advanced to explain this demise, such as cognitive, adaptive and cultural inferiority of Neanderthals. Here, we investigate the disappearance of Neanderthals by examining the extent of demographic changes needed over a period of 10,000 years (yrs) to lead to their extinction. In regard to such fossil populations, we inferred demographic parameters from present day and past hunter-gatherer populations, and from bio-anthropological rules. We used demographic modeling and simulations to identify the set of plausible demographic parameters of the Neanderthal population compatible with the observed dynamics, and to explore the circumstances under which they might have led to the disappearance of Neanderthals. A slight (<4%) but continuous decrease in the fertility rate of younger Neanderthal women could have had a significant impact on these dynamics, and could have precipitated their demise. Our results open the way to non-catastrophic events as plausible explanations for Neanderthal extinction.


Assuntos
Extinção Biológica , Homem de Neandertal , Animais , Simulação por Computador , Demografia/estatística & dados numéricos , Europa (Continente) , Feminino , Fósseis , História Antiga , Humanos , Masculino , Modelos Biológicos , Homem de Neandertal/classificação , Homem de Neandertal/genética , Dinâmica Populacional/história , Processos Estocásticos
8.
PLoS Genet ; 15(5): e1008175, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31136573

RESUMO

Statistical analyses of genomic data from diverse human populations have demonstrated that archaic hominins, such as Neanderthals and Denisovans, interbred or admixed with the ancestors of present-day humans. Central to these analyses are methods for inferring archaic ancestry along the genomes of present-day individuals (archaic local ancestry). Methods for archaic local ancestry inference rely on the availability of reference genomes from the ancestral archaic populations for accurate inference. However, several instances of archaic admixture lack reference archaic genomes, making it difficult to characterize these events. We present a statistical method that combines diverse population genetic summary statistics to infer archaic local ancestry without access to an archaic reference genome. We validate the accuracy and robustness of our method in simulations. When applied to genomes of European individuals, our method recovers segments that are substantially enriched for Neanderthal ancestry, even though our method did not have access to any Neanderthal reference genomes.


Assuntos
Genética Populacional/métodos , Genômica/métodos , Hominidae/genética , Animais , Genoma Humano/genética , Humanos , Modelos Estatísticos , Homem de Neandertal/genética
9.
PLoS One ; 14(4): e0216155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31034533

RESUMO

The purpose of this study was to determine the estimated mutation age and conservation of single-nucleotide polymorphisms (SNPs) associated with physical activity (PA) in humans. All human SNPs found to be significantly associated with PA levels in the literature were cross-referenced with the National Heart, Lung, and Blood Institute's Grand Opportunity Exome Sequencing Project to find estimated African-American (AA) and European-American (EA) mutation age. As a secondary measure of mutation age, SNPs were searched for in Hawk's mutation age prediction database which utilizes linkage equilibrium. To determine conservation among hominids, all SNPs were searched in the University of California, Santa Cruz Genome Browser, which contains Neanderthal and chimpanzee reference genomes. Six of the 104 SNPs associated with PA regulation were exon-located missense variants found in IFNAR2, PPARGC1A, PML, CTBP2, IL5RA, and APOE genes. The remaining 98 SNPs were located in non-protein coding regions. Average AA and EA estimated mutation age of the exon-located SNPs were 478.4 ± 327.5 kya and 542.1 ± 369.4 kya, respectively. There were four selective sweeps (suggestive of strong positive selection) of SNPs in humans when compared to Neanderthal or chimpanzee genomes. Exon-located PA candidate SNPs are older than the hypothesized emergence of anatomically modern humans. However, 95% of PA associated SNPs are found in intron and intergenic location. Across all SNPs, there seems to be a high level of conservation of alleles between humans, Neanderthals, and chimpanzees. However, the presence of four selective sweeps suggests there were selection pressures or drift unique to Homo sapiens that influenced the development of mutations associated with PA regulation.


Assuntos
Alelos , Exercício/fisiologia , Grupo com Ancestrais do Continente Africano/genética , Animais , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Frequência do Gene , Genética Populacional , Humanos , Mutação/genética , Homem de Neandertal/genética , Pan troglodytes/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Tempo
10.
Nat Commun ; 10(1): 1671, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975994

RESUMO

Host and environmental factors contribute to variation in human immune responses, yet the genetic and evolutionary drivers of alternative splicing in response to infection remain largely uncharacterised. Leveraging 970 RNA-sequencing profiles of resting and stimulated monocytes from 200 individuals of African- and European-descent, we show that immune activation elicits a marked remodelling of the isoform repertoire, while increasing the levels of erroneous splicing. We identify 1,464 loci associated with variation in isoform usage (sQTLs), 9% of them being stimulation-specific, which are enriched in disease-related loci. Furthermore, we detect a longstanding increased plasticity of immune gene splicing, and show that positive selection and Neanderthal introgression have both contributed to diversify the splicing landscape of human populations. Together, these findings suggest that differential isoform usage has been an important substrate of innovation in the long-term evolution of immune responses and a more recent vehicle of population local adaptation.


Assuntos
Processamento Alternativo/imunologia , Imunidade/genética , Seleção Genética/imunologia , Transcriptoma/imunologia , Grupo com Ancestrais do Continente Africano/genética , Animais , Evolução Biológica , Grupo com Ancestrais do Continente Europeu/genética , Variação Genética/imunologia , Voluntários Saudáveis , Humanos , Masculino , Homem de Neandertal/genética , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Locos de Características Quantitativas/imunologia , Análise de Sequência de RNA , Sequenciamento Completo do Exoma
12.
Curr Biol ; 29(3): R95-R97, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30721683

RESUMO

Human populations that migrated out of Africa interbred with Neandertals. A new study assesses the effects of Neandertal gene variants on brain shape in modern humans, providing insights into the genomic basis of the uniquely globular human brain.


Assuntos
Hominidae , Homem de Neandertal/genética , África , Animais , Encéfalo , Genoma , Humanos
13.
Hum Immunol ; 80(2): 112-119, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30773169

RESUMO

HLA-F is one of the most conserved loci among the HLA gene family. The exact function of HLA-F is still under investigation. HLA-F might present tolerogenic features, participate in the stabilization of HLA molecules in open conformation, and also participate in the recycling of HLA molecules. Here we evaluate the variability and haplotype structure of the HLA-F distal promoter segment (from -1893 to -943) and how this segment is correlated with the coding region. Variability at the promoter segment was surveyed in 196 Brazilian samples using second-generation sequencing. The HLA-F promoter region presents two major haplotype lineages. Most of the variable sites are in perfect linkage and associated with a single promoter haplotype, here named F∗distal-C. This haplotype is associated with F∗01:01:02 alleles, while alleles from the F∗01:01:01 or F∗01:03 groups present closely related promoter sequences. F∗distal-C is quite frequent in Brazil and in worldwide populations, with frequencies ranging from 8.41% at the Iberian Population in Spain to 34.34% in Vietnam. F∗distal-C is also present in Neanderthal and Denisovan samples. In silico analyses demonstrated that F∗distal-C presents a different transcription factor binding profile compared with other HLA-F promoters. Moreover, individuals carrying this haplotype present higher HLA-F mRNA expression levels. Functional studies are required to define the exact mechanism underlying this higher HLA-F mRNA expression level associated with F∗distal-C and F∗01:01:02 alleles.


Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , Animais , Brasil , Regulação da Expressão Gênica , Frequência do Gene , Genética Populacional , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Desequilíbrio de Ligação , Homem de Neandertal/genética , Polimorfismo Genético
14.
Nature ; 565(7741): 640-644, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30700871

RESUMO

Denisova Cave in the Siberian Altai (Russia) is a key site for understanding the complex relationships between hominin groups that inhabited Eurasia in the Middle and Late Pleistocene epoch. DNA sequenced from human remains found at this site has revealed the presence of a hitherto unknown hominin group, the Denisovans1,2, and high-coverage genomes from both Neanderthal and Denisovan fossils provide evidence for admixture between these two populations3. Determining the age of these fossils is important if we are to understand the nature of hominin interaction, and aspects of their cultural and subsistence adaptations. Here we present 50 radiocarbon determinations from the late Middle and Upper Palaeolithic layers of the site. We also report three direct dates for hominin fragments and obtain a mitochondrial DNA sequence for one of them. We apply a Bayesian age modelling approach that combines chronometric (radiocarbon, uranium series and optical ages), stratigraphic and genetic data to calculate probabilistically the age of the human fossils at the site. Our modelled estimate for the age of the oldest Denisovan fossil suggests that this group was present at the site as early as 195,000 years ago (at 95.4% probability). All Neanderthal fossils-as well as Denisova 11, the daughter of a Neanderthal and a Denisovan4-date to between 80,000 and 140,000 years ago. The youngest Denisovan dates to 52,000-76,000 years ago. Direct radiocarbon dating of Upper Palaeolithic tooth pendants and bone points yielded the earliest evidence for the production of these artefacts in northern Eurasia, between 43,000 and 49,000 calibrated years before present (taken as AD 1950). On the basis of current archaeological evidence, it may be assumed that these artefacts are associated with the Denisovan population. It is not currently possible to determine whether anatomically modern humans were involved in their production, as modern-human fossil and genetic evidence of such antiquity has not yet been identified in the Altai region.


Assuntos
Cavernas , Fósseis , Hominidae , Datação Radiométrica , Animais , Teorema de Bayes , DNA Mitocondrial/genética , Cervos , Fêmur/química , Sedimentos Geológicos/química , História Antiga , Hominidae/genética , Humanos , Homem de Neandertal/genética , Isótopos de Oxigênio , Sibéria , Fatores de Tempo , Dente/química
15.
Med Sci (Paris) ; 35(1): 39-45, 2019 Jan.
Artigo em Francês | MEDLINE | ID: mdl-30672457

RESUMO

Usually, paleoanthropology studies remains and artefacts. However, more recently, genetics offer new avenues. Information on humanisation mechanisms has been obtained from comparison with primate or archaic Homo DNA sequences. Likewise, the 1 000 Genomes Project has characterized the geographic spectrum of human genetic variation offering a basis for a genomic study of Homo sapiens phylogeny. From these studies, a model, Out of Africa, was derived. His origin is Africa, where he lived 200 000 years ago. A small fraction of the population left Africa between 50 and 100 000 years ago that have populated the rest of the world, to Europe, coastal Asia to Australia and mainland Asia to Behring Land Bridge and America. The model is supported by the decrease of genetic diversity with the distance to Eastern Africa (serial founder effect). In Europe and Asia, Homo sapiens met archaic Homo neanderthalis and H denisova. The presence of 1-3% neanderthalis sequences in modern Homo ADN indicates admixtures between these groups. Some archaic sequences are on positive selection pressure, thus suggesting that the extinct hominins might have facilitated the adaptation of H sapiens to new environments.


Assuntos
Evolução Molecular , Genoma Humano , Hominidae/genética , África , Animais , Ásia , Evolução Biológica , DNA/análise , DNA/química , Europa (Continente) , Projeto Genoma Humano , Humanos , Homem de Neandertal/genética , Filogenia , Polimorfismo de Nucleotídeo Único , Seleção Genética , Homologia de Sequência
16.
Proc Natl Acad Sci U S A ; 116(5): 1639-1644, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30647110

RESUMO

Several studies have suggested that introgressed Neandertal DNA was subjected to negative selection in modern humans. A striking observation in support of this is an apparent monotonic decline in Neandertal ancestry observed in modern humans in Europe over the past 45,000 years. Here, we show that this decline is an artifact likely caused by gene flow between modern human populations, which is not taken into account by statistics previously used to estimate Neandertal ancestry. When we apply a statistic that avoids assumptions about modern human demography by taking advantage of two high-coverage Neandertal genomes, we find no evidence for a change in Neandertal ancestry in Europe over the past 45,000 years. We use whole-genome simulations of selection and introgression to investigate a wide range of model parameters and find that negative selection is not expected to cause a significant long-term decline in genome-wide Neandertal ancestry. Nevertheless, these models recapitulate previously observed signals of selection against Neandertal alleles, in particular the depletion of Neandertal ancestry in conserved genomic regions. Surprisingly, we find that this depletion is strongest in regulatory and conserved noncoding regions and in the most conserved portion of protein-coding sequences.


Assuntos
Homem de Neandertal/genética , Seleção Genética/genética , Alelos , Animais , Sequência Conservada/genética , DNA/genética , Europa (Continente) , Grupo com Ancestrais do Continente Europeu/genética , Evolução Molecular , Fluxo Gênico/genética , Humanos , RNA não Traduzido/genética
18.
Nat Ecol Evol ; 3(1): 39-44, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30478305

RESUMO

Neanderthals and anatomically modern humans overlapped geographically for a period of over 30,000 years following human migration out of Africa. During this period, Neanderthals and humans interbred, as evidenced by Neanderthal portions of the genome carried by non-African individuals today. A key observation is that the proportion of Neanderthal ancestry is ~12-20% higher in East Asian individuals relative to European individuals. Here, we explore various demographic models that could explain this observation. These include distinguishing between a single admixture event and multiple Neanderthal contributions to either population, and the hypothesis that reduced Neanderthal ancestry in modern Europeans resulted from more recent admixture with a ghost population that lacked a Neanderthal ancestry component (the 'dilution' hypothesis). To summarize the asymmetric pattern of Neanderthal allele frequencies, we compiled the joint fragment frequency spectrum of European and East Asian Neanderthal fragments and compared it with both analytical theory and data simulated under various models of admixture. Using maximum-likelihood and machine learning, we found that a simple model of a single admixture did not fit the empirical data, and instead favour a model of multiple episodes of gene flow into both European and East Asian populations. These findings indicate a longer-term, more complex interaction between humans and Neanderthals than was previously appreciated.


Assuntos
Hibridização Genética , Homem de Neandertal/genética , Animais , Fluxo Gênico , Genoma Humano , Humanos , Modelos Teóricos
19.
Genome Biol Evol ; 11(1): 232-241, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30566634

RESUMO

Genome-wide analyses of two Neandertals and a Denisovan have shown that these archaic humans had lower genetic heterozygosity than present-day people. A similar reduction in genetic diversity of protein-coding genes (gene diversity) was found in exome sequences of three Neandertals. Reduced gene diversity, particularly in genes involved in immunity, may have important functional consequences. In fact, it has been suggested that reduced diversity in immune genes may have contributed to Neandertal extinction. We therefore explored gene diversity in different human groups, and at different time points on the Neandertal lineage, with a particular focus on the diversity of genes involved in innate immunity and genes of the Major Histocompatibility Complex (MHC).We find that the two Neandertals and a Denisovan have similar gene diversity, all significantly lower than any present-day human. This is true across gene categories, with no gene set showing an excess decrease in diversity compared with the genome-wide average. Innate immune-related genes show a similar reduction in diversity to other genes, both in present-day and archaic humans. There is also no observable decrease in gene diversity over time in Neandertals, suggesting that there may have been no ongoing reduction in gene diversity in later Neandertals, although this needs confirmation with a larger sample size. In both archaic and present-day humans, genes with the highest levels of diversity are enriched for MHC-related functions. In fact, in archaic humans the MHC genes show evidence of having retained more diversity than genes involved only in the innate immune system.


Assuntos
Imunidade Inata/genética , Complexo Principal de Histocompatibilidade , Homem de Neandertal/genética , Animais , Variação Genética , Humanos , Homem de Neandertal/imunologia
20.
Sci Rep ; 8(1): 18008, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30573755

RESUMO

The availability of genomic data from extinct homini such as Neanderthals has caused a revolution in palaeontology allowing the identification of modern human-specific protein substitutions. Currently, little is known as to how these substitutions alter the proteins on a molecular level. Here, we investigate adenylosuccinate lyase, a conserved enzyme involved in purine metabolism for which several substitutions in the modern human protein (hADSL) have been described to affect intelligence and behaviour. During evolution, modern humans acquired a specific substitution (Ala429Val) in ADSL distinguishing it from the ancestral variant present in Neanderthals (nADSL). We show here that despite this conservative substitution being solvent exposed and located distant from the active site, there is a difference in thermal stability, but not enzymology or ligand binding between nADSL and hADSL. Substitutions near residue 429 which do not profoundly affect enzymology were previously reported to cause neurological symptoms in humans. This study also reveals that ADSL undergoes conformational changes during catalysis which, together with the crystal structure of a hitherto undetermined product bound conformation, explains the molecular origin of disease for several modern human ADSL mutants.


Assuntos
Adenilossuccinato Liase/química , Adenilossuccinato Liase/genética , Evolução Molecular , Homem de Neandertal/genética , Sequência de Aminoácidos , Animais , Catálise , Domínio Catalítico , Cristalização , Estabilidade Enzimática , Humanos , Modelos Moleculares , Mutação de Sentido Incorreto , Conformação Proteica , Mudança Social , Temperatura Ambiente
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA