We conduct high coverage (>30×) whole-genome sequencing of 180 individuals from 12 indigenous African populations. We identify millions of unreported variants, many predicted to be functionally important. We observe that the ancestors of southern African San and central African rainforest hunter-gatherers (RHG) diverged from other populations >200 kya and maintained a large effective population size. We observe evidence for ancient population structure in Africa and for multiple introgression events from “ghost” populations with highly diverged genetic lineages. Although currently geographically isolated, we observe evidence for gene flow between eastern and southern Khoesan-speaking hunter-gatherer populations lasting until ∼12 kya. We identify signatures of local adaptation for traits related to skin color, immune response, height, and metabolic processes. We identify a positively selected variant in the lightly pigmented San that influences pigmentation in vitro by regulating the enhancer activity and gene expression of PDPK1.

我们对来自 12 个非洲土著群体的 180 名个体进行了高覆盖率 (>30×) 全基因组测序。我们发现了数百万个未报告的变体，其中许多预计具有重要的功能。我们观察到，南部非洲桑人和中非雨林狩猎采集者 (RHG) 的祖先与其他种群的分化超过 200 kya，并保持着较大的有效种群规模。我们观察到非洲古代种群结构的证据，以及来自具有高度分化遗传谱系的“幽灵”种群的多次渗入事件的证据。尽管目前在地理上是孤立的，但我们观察到东部和南部科桑语狩猎采集人群之间的基因流动持续到约 12 kya 的证据。我们确定了与肤色、免疫反应、身高和代谢过程相关的特征的局部适应特征。我们在浅色素 San 中鉴定出一个积极选择的变体，它通过调节PDPK1的增强子活性和基因表达来影响体外色素沉着。