Genomic Evidence for Local Adaptation of Hunter-Gatherers to the African Rainforest

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. •A strong selective sweep at TRPS1 occurred in African rainforest hunter-gatherers•Pleiotropic height genes lead to polygenic selection signals for reproductive age•Pathogen-driven selection, mostly viral, has been pervasive among hunter-gatherers•Post-admixture selection has maintained adaptive variation in hunter-gatherers Lopez et al. search for genomic evidence of local adaptation of hunter-gatherers to the African rainforest. They find signals of classic sweeps, polygenic adaptation, and post-admixture selection at height, development, and immune response genes. They show that pleiotropy of height genes leads to polygenic selection signals for lif