Cousins Trevor, Scally Aylwyn, Durbin Richard
Department of Genetics, University of Cambridge, Cambridge, UK.
Nat Genet. 2025 Apr;57(4):856-864. doi: 10.1038/s41588-025-02117-1. Epub 2025 Mar 18.
Understanding the history of admixture events and population size changes leading to modern humans is central to human evolutionary genetics. Here we introduce a coalescence-based hidden Markov model, cobraa, that explicitly represents an ancestral population split and rejoin, and demonstrate its application on simulated and real data across multiple species. Using cobraa, we present evidence for an extended period of structure in the history of all modern humans, in which two ancestral populations that diverged ~1.5 million years ago came together in an admixture event ~300 thousand years ago, in a ratio of ~80:20%. Immediately after their divergence, we detect a strong bottleneck in the major ancestral population. We inferred regions of the present-day genome derived from each ancestral population, finding that material from the minority correlates strongly with distance to coding sequence, suggesting it was deleterious against the majority background. Moreover, we found a strong correlation between regions of majority ancestry and human-Neanderthal or human-Denisovan divergence, suggesting the majority population was also ancestral to those archaic humans.
了解导致现代人类的混合事件历史和种群大小变化是人类进化遗传学的核心。在此，我们引入了一种基于合并的隐马尔可夫模型cobraa，该模型明确表示了一个祖先种群的分裂和重新合并，并展示了其在多个物种的模拟数据和真实数据上的应用。使用cobraa，我们提供了证据，表明所有现代人类历史上存在一段长期的种群结构，其中大约150万年前分化的两个祖先种群在大约30万年前的一次混合事件中重新聚合，比例约为80:20%。在它们刚分化后，我们在主要祖先种群中检测到一个强烈的瓶颈。我们推断了当今基因组中来自每个祖先种群的区域，发现来自少数群体的物质与到编码序列的距离密切相关，这表明它在多数群体背景下是有害的。此外，我们发现多数祖先区域与人类 - 尼安德特人或人类 - 丹尼索瓦人的分化之间存在强烈相关性，这表明多数群体也是那些古人类的祖先。
