Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, United States of America.
Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.
PLoS Genet. 2020 Aug 6;16(8):e1008895. doi: 10.1371/journal.pgen.1008895. eCollection 2020 Aug.
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.
尼安德特人和丹尼索瓦人基因组的测序为研究已灭绝人类与现代人类祖先之间的杂交事件提供了许多新的见解。虽然人们对来自尼安德特人和丹尼索瓦人的相对较近的基因流进入现代人类的情况给予了很多关注，但其他类型的基因渗入则留下了更微妙的基因组证据，因此受到的关注较少。在这里，我们提出了一种 ARGweaver 算法的主要扩展，称为 ARGweaver-D，它可以根据包括人口分裂和迁移事件在内的用户定义的人口模型推断局部遗传关系。这种贝叶斯算法可以概率抽样祖先重组图（ARG），这些图不仅指定了基因组上的树拓扑和分支长度，还指示了移徙谱系。因此，抽样的 ARG 可以被解析以产生基因组上基因渗入的概率。我们表明，即使只有少数样本，这种方法也可以很好地检测到古代人类向现代人类的迁移。然后，我们表明该方法还可以检测到源自较旧迁移事件或未采样种群的渗入区域。我们将其应用于人类、尼安德特人和丹尼索瓦人的基因组，寻找旧的提议迁移事件的特征，包括远古人类进入尼安德特人，以及未知的古代人类进入丹尼索瓦人。我们确定了 3%的尼安德特人基因组可能是从远古人类中渗入的，并估计基因流发生在 20 万至 30 万年前。我们没有发现令人信服的证据表明这些区域受到了负选择的影响。最后，我们预测 1%的丹尼索瓦人基因组是从一个未测序但高度分化的古代人类祖先中渗入的。这些“超级古老”区域中的 15%（至少包含约 4Mb）又被渗入现代人类中，并继续存在于今天活着的人的基因组中。
