Mapping gene flow between ancient hominins through demography-aware inference of the ancestral recombination graph
Mapping gene flow between ancient hominins through demography-aware inference of the ancestral recombination graph
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DOI：
10.1371/journal.pgen.1008895
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发表时间：
2020-08-01
期刊：
影响因子：
4.5
通讯作者：
Siepel, Adam
中科院分区：
文献类型：
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作者：
Hubisz, Melissa J.;Williams, Amy L.;Siepel, Adam
尼安德特人和丹尼索瓦人的基因组测序为灭绝的原始人和现代人的祖先之间的杂交事件提供了许多新的见解。虽然人们对尼安德特人和丹尼索瓦人最近从尼安德特人和丹尼索瓦人进入现代人的基因流动给予了很大关注，但其他导入的例子留下了更微妙的基因组证据，受到的关注较少。在这里，我们提出了ARGweaver算法的一个主要扩展，称为ARGweaver-D，它可以在用户定义的人口模型下推断局部遗传关系，该模型包括人口分裂和迁移事件。这种贝叶斯算法对祖先重组图(ARG)进行概率抽样，这些ARG不仅指定了基因组上的树状拓扑和分支长度，而且还指示了迁徙谱系。因此，可以对采样的ARG进行解析，以产生沿基因组的渗入概率。我们表明，即使只有很少的样本，这种方法也能很好地检测到古代人向现代人的迁移。然后，我们表明，该方法还可以检测来自较老的迁移事件或来自未抽样人口的导入区域。我们将其应用于人类、尼安德特人和丹尼索瓦人的基因组，寻找更早提出的迁徙事件的签名，包括古人类进入尼安德特人，以及未知的古人类进入丹尼索瓦人。我们确定了3%的尼安德特人基因组被认为是从古人类中导入的，并估计基因流发生在200-300kya之间。我们没有找到令人信服的证据表明，负选择对这些区域起了不利作用。最后，我们预测丹尼索瓦人1%的基因组是从一个未测序但高度分化的古人类祖先中导入的。其中约15%的超古老区域-至少包含约4Mb-反过来被引入现代人并继续存在于今天活着的人的基因组中。作者摘要我们提出了ARGweaver-D，它是ARGweaver算法的扩展，可以在用户定义的人口模型下应用，包括人口分裂和迁移事件。给出来自多个密切相关的种群或亚种的个体集合的基因组序列数据，ARGweaver-D可以根据人口统计模型推断描述基因组沿线每个位置的这些个体之间的遗传关系的树。与ARGweaver一样，ARGweaver-D是一种贝叶斯方法，从后验分布中对树进行采样，以考虑不确定性。通过仿真，我们证明了ARGweaver-D可以成功地识别从尼安德特人和丹尼索瓦人导入现代人的区域。它还能很好地检测来自较老的基因流动事件的导入区域。我们将ARGweaver-D应用于两名尼安德特人、一名丹尼索瓦人和两名非洲人的基因组。我们确定了3%的尼安德特人基因组，这可能来自古人类的基因流。我们还鉴定了约1%的丹尼索瓦人基因组，这些基因组可能追溯到未测序的古人类；这些区域中的15%随后传递给了现代人。我们没有找到令人信服的证据表明，选择对这些导入区域中的任何一个起作用。
The sequencing of Neanderthal and Denisovan genomes has yielded many new insights about interbreeding events between extinct hominins and the ancestors of modern humans. While much attention has been paid to the relatively recent gene flow from Neanderthals and Denisovans into modern humans, other instances of introgression leave more subtle genomic evidence and have received less attention. Here, we present a major extension of the ARGweaver algorithm, called ARGweaver-D, which can infer local genetic relationships under a user-defined demographic model that includes population splits and migration events. This Bayesian algorithm probabilistically samples ancestral recombination graphs (ARGs) that specify not only tree topologies and branch lengths along the genome, but also indicate migrant lineages. The sampled ARGs can therefore be parsed to produce probabilities of introgression along the genome. We show that this method is well powered to detect the archaic migration into modern humans, even with only a few samples. We then show that the method can also detect introgressed regions stemming from older migration events, or from unsampled populations. We apply it to human, Neanderthal, and Denisovan genomes, looking for signatures of older proposed migration events, including ancient humans into Neanderthal, and unknown archaic hominins into Denisovans. We identify 3% of the Neanderthal genome that is putatively introgressed from ancient humans, and estimate that the gene flow occurred between 200-300kya. We find no convincing evidence that negative selection acted against these regions. Finally, we predict that 1% of the Denisovan genome was introgressed from an unsequenced, but highly diverged, archaic hominin ancestor. About 15% of these "super-archaic" regions-comprising at least about 4Mb-were, in turn, introgressed into modern humans and continue to exist in the genomes of people alive today.Author summary We present ARGweaver-D, an extension of the ARGweaver algorithm which can be applied under a user-defined demographic model including population splits and migration events. Given genome sequence data from a collection of individuals across multiple closely related populations or subspecies, ARGweaver-D can infer trees describing the genetic relationships among these individuals at every location along the genome, conditional on the demographic model. Like ARGweaver, ARGweaver-D is a Bayesian method, sampling trees from the posterior distribution in order to account for uncertainty. Using simulations, we show that ARGweaver-D can successfully identify regions introgressed from Neanderthals and Denisovans into modern humans. It is also well-powered to detect introgressed regions stemming from older gene-flow events. We apply ARGweaver-D to the genomes of two Neanderthals, a Denisovan, and two African humans. We identify 3% of the Neanderthal genome which is likely derived from gene flow from ancient humans. We also identify about 1% of the Denisovan genome that may be traced to an unsequenced archaic hominin; 15% of these regions were subsequently passed to modern humans. We find no convincing evidence that selection acted against any of these introgressed regions.