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利用个体间等位基因共享的全基因组模式重建奠基者事件的历史。

Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals.

机构信息

Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.

Center for Computational Biology, University of California, Berkeley, California, United States of America.

出版信息

PLoS Genet. 2022 Jun 23;18(6):e1010243. doi: 10.1371/journal.pgen.1010243. eCollection 2022 Jun.

Abstract

Founder events play a critical role in shaping genetic diversity, fitness and disease risk in a population. Yet our understanding of the prevalence and distribution of founder events in humans and other species remains incomplete, as most existing methods require large sample sizes or phased genomes. Thus, we developed ASCEND that measures the correlation in allele sharing between pairs of individuals across the genome to infer the age and strength of founder events. We show that ASCEND can reliably estimate the parameters of founder events under a range of demographic scenarios. We then apply ASCEND to two species with contrasting evolutionary histories: ~460 worldwide human populations and ~40 modern dog breeds. In humans, we find that over half of the analyzed populations have evidence for recent founder events, associated with geographic isolation, modes of sustenance, or cultural practices such as endogamy. Notably, island populations have lower population sizes than continental groups and most hunter-gatherer, nomadic and indigenous groups have evidence of recent founder events. Many present-day groups--including Native Americans, Oceanians and South Asians--have experienced more extreme founder events than Ashkenazi Jews who have high rates of recessive diseases due their known history of founder events. Using ancient genomes, we show that the strength of founder events differs markedly across geographic regions and time--with three major founder events related to the peopling of Americas and a trend in decreasing strength of founder events in Europe following the Neolithic transition and steppe migrations. In dogs, we estimate extreme founder events in most breeds that occurred in the last 25 generations, concordant with the establishment of many dog breeds during the Victorian times. Our analysis highlights a widespread history of founder events in humans and dogs and elucidates some of the demographic and cultural practices related to these events.

摘要

奠基者事件在塑造群体的遗传多样性、适应性和疾病风险方面起着关键作用。然而,由于大多数现有方法需要大样本量或相分离基因组,我们对人类和其他物种中奠基者事件的普遍性和分布的理解仍然不完整。因此,我们开发了 ASCEND,它通过测量个体之间基因组上等位基因共享的相关性来推断奠基者事件的年龄和强度。我们表明,ASCEND 可以在一系列人口统计场景下可靠地估计奠基者事件的参数。然后,我们将 ASCEND 应用于两种具有不同进化历史的物种:来自全球的 460 个人类群体和 40 个现代犬种。在人类中,我们发现超过一半的分析群体有最近奠基者事件的证据,这些事件与地理隔离、维持方式或文化习俗(如近亲繁殖)有关。值得注意的是,岛屿群体的人口规模小于大陆群体,大多数狩猎采集者、游牧民族和原住民群体都有最近的奠基者事件的证据。许多当今的群体——包括美洲原住民、大洋洲人和南亚人——经历了比由于其已知的奠基者事件历史而导致隐性疾病发病率高的阿什肯纳兹犹太人更为极端的奠基者事件。利用古代基因组,我们表明奠基者事件的强度在地理区域和时间上有明显的差异——与美洲人口有关的三个主要奠基者事件,以及新石器时代过渡和草原迁徙后欧洲奠基者事件强度的下降趋势。在犬类中,我们估计大多数品种都发生了最近 25 代的极端奠基者事件,这与维多利亚时代许多犬种的建立是一致的。我们的分析强调了人类和犬类中广泛存在的奠基者事件历史,并阐明了一些与这些事件相关的人口和文化习俗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f350/9223333/29d992fa2c7e/pgen.1010243.g001.jpg

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