Institut Pasteur, Université de Paris, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris 75015, France; Sorbonne Université, Collège Doctoral, Paris 75005, France.
Institut Pasteur, Université de Paris, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris 75015, France.
Am J Hum Genet. 2022 Apr 7;109(4):710-726. doi: 10.1016/j.ajhg.2022.02.011. Epub 2022 Mar 7.
Admixture has been a pervasive phenomenon in human history, extensively shaping the patterns of population genetic diversity. There is increasing evidence to suggest that admixture can also facilitate genetic adaptation to local environments, i.e., admixed populations acquire beneficial mutations from source populations, a process that we refer to as "adaptive admixture." However, the role of adaptive admixture in human evolution and the power to detect it remain poorly characterized. Here, we use extensive computer simulations to evaluate the power of several neutrality statistics to detect natural selection in the admixed population, assuming multiple admixture scenarios. We show that statistics based on admixture proportions, F and LAD, show high power to detect mutations that are beneficial in the admixed population, whereas other statistics, including iHS and F, falsely detect neutral mutations that have been selected in the source populations only. By combining F and LAD into a single, powerful statistic, we scanned the genomes of 15 worldwide, admixed populations for signatures of adaptive admixture. We confirm that lactase persistence and resistance to malaria have been under adaptive admixture in West Africans and in Malagasy, North Africans, and South Asians, respectively. Our approach also uncovers other cases of adaptive admixture, including APOL1 in Fulani nomads and PKN2 in East Indonesians, involved in resistance to infection and metabolism, respectively. Collectively, our study provides evidence that adaptive admixture has occurred in human populations whose genetic history is characterized by periods of isolation and spatial expansions resulting in increased gene flow.
混合是人类历史上普遍存在的现象，广泛影响了人口遗传多样性的模式。越来越多的证据表明，混合也可以促进对当地环境的遗传适应，即混合人群从源人群中获得有益的突变，我们称之为“适应性混合”。然而，适应性混合在人类进化中的作用及其可检测性仍未得到充分描述。在这里，我们使用广泛的计算机模拟来评估几种中性统计数据在混合人群中检测自然选择的能力，假设了多种混合场景。我们表明，基于混合比例、F 和 LAD 的统计数据具有很高的能力来检测在混合人群中有益的突变，而其他统计数据，包括 iHS 和 F，错误地检测到仅在源人群中选择的中性突变。通过将 F 和 LAD 合并为一个单一的、强大的统计数据，我们扫描了全球 15 个混合人群的基因组，寻找适应性混合的特征。我们证实，乳糖耐受和对疟疾的抗性分别在西非人和马达加斯加人、北非人和南亚人中经历了适应性混合。我们的方法还揭示了其他适应性混合的情况，包括 Fulani 游牧民族中的 APOL1 和 East 印度尼西亚人的 PKN2，分别涉及感染和代谢的抗性。总的来说，我们的研究提供了证据表明，适应性混合发生在遗传史中具有隔离和空间扩张期的人类群体中，这些时期导致了基因流的增加。
