Human Evolutionary Genetics Unit, Institut Pasteur, UMR2000, CNRS, Paris 75015, France; Sorbonne Universités, Ecole Doctorale Complexité du Vivant, 75005 Paris, France.
Human Evolutionary Genetics Unit, Institut Pasteur, UMR2000, CNRS, Paris 75015, France.
Curr Biol. 2019 Sep 9;29(17):2926-2935.e4. doi: 10.1016/j.cub.2019.07.013. Epub 2019 Aug 8.
African rainforests support exceptionally high biodiversity and host the world's largest number of active hunter-gatherers [1-3]. The genetic history of African rainforest hunter-gatherers and neighboring farmers is characterized by an ancient divergence more than 100,000 years ago, together with recent population collapses and expansions, respectively [4-12]. While the demographic past of rainforest hunter-gatherers has been deeply characterized, important aspects of their history of genetic adaptation remain unclear. Here, we investigated how these groups have adapted-through classic selective sweeps, polygenic adaptation, and selection since admixture-to the challenging rainforest environments. To do so, we analyzed a combined dataset of 566 high-coverage exomes, including 266 newly generated exomes, from 14 populations of rainforest hunter-gatherers and farmers, together with 40 newly generated, low-coverage genomes. We find evidence for a strong, shared selective sweep among all hunter-gatherer groups in the regulatory region of TRPS1-primarily involved in morphological traits. We detect strong signals of polygenic adaptation for height and life history traits such as reproductive age; however, the latter appear to result from pervasive pleiotropy of height-associated genes. Furthermore, polygenic adaptation signals for functions related to responses of mast cells to allergens and microbes, the IL-2 signaling pathway, and host interactions with viruses support a history of pathogen-driven selection in the rainforest. Finally, we find that genes involved in heart and bone development and immune responses are enriched in both selection signals and local hunter-gatherer ancestry in admixed populations, suggesting that selection has maintained adaptive variation in the face of recent gene flow from farmers.
非洲雨林拥有极高的生物多样性，是世界上数量最多的活跃狩猎采集者的家园[1-3]。非洲雨林狩猎采集者和邻近农民的遗传历史以 10 万多年前的古老分歧为特征，同时分别经历了近期的人口减少和扩张[4-12]。虽然已经深入描述了雨林狩猎采集者的人口历史，但他们在遗传适应方面的重要方面仍不清楚。在这里，我们研究了这些群体如何通过经典的选择清扫、多基因适应和混合后的选择来适应具有挑战性的雨林环境。为此，我们分析了包括 266 个新生成外显子组在内的 566 个高覆盖率外显子组的综合数据集，这些外显子组来自 14 个雨林狩猎采集者和农民群体，其中包括 40 个新生成的低覆盖率基因组。我们发现，在 TRPS1 的调控区域中，所有狩猎采集者群体都存在强烈的、共同的选择清扫，该区域主要与形态特征有关。我们检测到与身高和生殖年龄等生命史特征相关的多基因适应的强烈信号；然而，后者似乎是由与身高相关的基因普遍的多效性造成的。此外，与肥大细胞对过敏原和微生物的反应、IL-2 信号通路以及宿主与病毒的相互作用相关的功能的多基因适应信号支持了雨林中病原体驱动选择的历史。最后，我们发现，涉及心脏和骨骼发育以及免疫反应的基因在选择信号和混合人群中的本地狩猎采集者遗传背景中都有富集，这表明选择在面对来自农民的近期基因流时，维持了适应性变异。
