Department of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London, United Kingdom.
Human Evolutionary Genetics Unit, Institut Pasteur, UMR2000, CNRS, Paris, France.
Mol Biol Evol. 2022 Apr 11;39(4). doi: 10.1093/molbev/msac076.
Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.
在人类进化历史上,大规模的迁徙导致了先前分离的人类群体之间的混合(即混合)。尽管经典和最近的研究表明,研究混合可以产生新的历史见解,但这一过程对适应的贡献程度仍未得到充分探索。在这里,我们引入了一种新的统计模型,专门针对混合人群,该模型在确定选择是否可能发生在混合之后或在一个祖先源群体中混合之前,识别受选择影响的基因座。通过广泛的模拟,我们表明,即使在最近形成的混合人群中,这种方法也能够检测到选择,并能够准确地区分选择是在祖先群体还是混合群体中发生的。我们将这种方法应用于来自巴西、智利、哥伦比亚、墨西哥和秘鲁的五个拉丁美洲混合人群中约 4000 个人的全基因组 SNP 数据。我们的方法复制了先前在人类白细胞抗原区域发现的选择报告,这些报告与混合后的选择一致。我们还报告了在跨越 47 个基因的基因组区域中选择的新信号,用另一种常用的局部祖先推断方法强化了其中的许多信号。这些信号包括几个参与免疫的基因,这可能反映了对美洲地方病原体和欧洲接触带来的传染病挑战的反应。此外,在现代拉丁美洲人的美洲原住民群体中推断出的一些最强的选择信号与涉及能量代谢表型的基因重叠,这可能反映了对美洲新出现的饮食来源的适应。