Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals.
Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals.
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DOI：
10.1371/journal.pgen.1010243
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发表时间：
2022-06
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
创始人活动在塑造一个群体的遗传多样性、健康状况和疾病风险方面发挥着关键作用。然而，我们对创始人事件在人类和其他物种中的流行和分布的了解仍然不完整，因为大多数现有方法需要大量样本或分阶段基因组。因此，我们开发了Ascend，它测量整个基因组中成对个体之间的等位基因共享的相关性，以推断创始人事件的年龄和强度。我们表明，在一系列人口统计情景下，Ascend可以可靠地估计创始人事件的参数。然后，我们将Ascend应用于两个进化历史截然不同的物种：全球约460个人类种群和约40个现代犬种。在人类中，我们发现超过一半的被分析人群有最近创始人事件的证据，这些事件与地理隔离、生存模式或内婚制等文化习俗有关。值得注意的是，岛上居民的人口规模低于大陆群体，大多数狩猎-采集、游牧和土著群体都有最近创始人事件的证据。当今的许多群体--包括美洲原住民、大洋洲人和南亚人--经历过比德系犹太人更极端的创始人事件，后者由于已知的创始人事件历史而有很高的隐性疾病发生率。利用古代基因组，我们发现创始人事件的强度因地理区域和时间的不同而显著不同--与美洲人相关的三个主要创始人事件，以及在新石器时代过渡和草原迁移之后欧洲创始人事件强度下降的趋势。在狗方面，我们估计大多数品种的极端创始人事件发生在过去25代，这与维多利亚时代许多狗品种的确立一致。我们的分析突出了创始人事件在人类和狗中的广泛历史，并阐明了与这些事件相关的一些人口统计学和文化习俗。当少数祖先的个体产生了很大一部分人口时，就会发生创始人事件。创始人事件减少了遗传变异，增加了隐性疾病的风险。尽管它们在进化和疾病研究中很重要，但我们对它们在人类和其他物种中的流行和特性仍然只有有限的理解，因为大多数现有的方法需要大量的样本或分阶段的基因组。这里，我们提出了一种灵活的方法Ascend来推断创始人事件的时间和强度，该方法适用于样本较少或覆盖范围有限的稀疏数据集。Ascend在广泛的人口统计场景中提供可靠的估计。通过将其应用于两个物种(人类和狗)的数据，我们记录了这两个物种最近创始人事件的广泛历史，并提供了与这些事件相关的人口统计过程的见解。我们的分析有助于确定具有强大创始人事件的群体，这些群体应该在未来的研究中优先考虑，因为他们提供了一个独特的机会，可以通过绘制隐性致病基因和途径图来进行生物学发现和减少疾病负担，就像之前对德系犹太人和芬兰人的研究所显示的那样。
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. A founder event occurs when small numbers of ancestral individuals give rise to a large fraction of the population. Founder events reduce genetic variation and increase the risk of recessive diseases. Despite their importance in evolutionary and disease studies, we still only have a limited comprehension of their prevalence and properties in humans and other species, as most existing methods require large sample sizes or phased genomes. Here, we present a flexible method, ASCEND, to infer the timing and the strength of founder events that is suitable for sparse datasets with few samples or limited coverage. ASCEND provides reliable estimates across a wide range of demographic scenarios. By applying it to data from two species (humans and dogs), we document a widespread history of recent founder events in both species and provide insights about the demographic processes related to these events. Our analysis helps to identify groups with strong founder events that should be prioritized for future studies as they offer a unique opportunity for biological discovery and reducing disease burden through mapping of recessive disease-causing genes and pathways, as previously shown in studies of Ashkenazi Jews and Finns.
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