Human Evolutionary Genetics Unit, Institut Pasteur, UMR 2000, CNRS, Paris 75015, France.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Genetics. 2021 Dec 10;219(4). doi: 10.1093/genetics/iyab161.
During their dispersals over the last 100,000 years, modern humans have been exposed to a large variety of environments, resulting in genetic adaptation. While genome-wide scans for the footprints of positive Darwinian selection have increased knowledge of genes and functions potentially involved in human local adaptation, they have globally produced evidence of a limited contribution of selective sweeps in humans. Conversely, studies based on machine learning algorithms suggest that recent sweeps from standing variation are widespread in humans, an observation that has been recently questioned. Here, we sought to formally quantify the number of recent selective sweeps in humans, by leveraging approximate Bayesian computation and whole-genome sequence data. Our computer simulations revealed suitable ABC estimations, regardless of the frequency of the selected alleles at the onset of selection and the completion of sweeps. Under a model of recent selection from standing variation, we inferred that an average of 68 (from 56 to 79) and 140 (from 94 to 198) sweeps occurred over the last 100,000 years of human history, in African and Eurasian populations, respectively. The former estimation is compatible with human adaptation rates estimated since divergence with chimps, and reveals numbers of sweeps per generation per site in the range of values estimated in Drosophila. Our results confirm the rarity of selective sweeps in humans and show a low contribution of sweeps from standing variation to recent human adaptation.
在过去的 10 万年中,现代人类在迁徙过程中暴露于各种环境中,从而产生了遗传适应。虽然全基因组扫描寻找正向达尔文选择的足迹增加了人类局部适应中潜在涉及的基因和功能的知识,但它们在全球范围内仅提供了选择压力在人类中有限贡献的证据。相反,基于机器学习算法的研究表明,人类中近期从固定变异中发生的选择压力广泛存在,这一观察结果最近受到了质疑。在这里,我们通过近似贝叶斯计算和全基因组序列数据,试图正式量化人类中近期选择压力的数量。我们的计算机模拟显示,无论选择开始时选定等位基因的频率以及选择压力的完成情况如何,近似贝叶斯计算都可以进行合适的估计。在近期来自固定变异的选择模型下,我们推断在过去 10 万年的人类历史中,非洲和欧亚人群分别发生了平均 68(56 到 79)和 140(94 到 198)次选择压力。前者的估计与自与黑猩猩分化以来估计的人类适应率相兼容,并揭示了每个世代每个位点的选择压力数量在果蝇中估计的值域内。我们的研究结果证实了人类中选择压力的罕见性,并表明来自固定变异的选择压力对人类近期适应的贡献较低。