New York Genome Center, New York, New York 10013
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350, Denmark.
Genetics. 2018 Apr;208(4):1565-1584. doi: 10.1534/genetics.117.300489. Epub 2018 Jan 18.
An open question in human evolution is the importance of polygenic adaptation: adaptive changes in the mean of a multifactorial trait due to shifts in allele frequencies across many loci. In recent years, several methods have been developed to detect polygenic adaptation using loci identified in genome-wide association studies (GWAS). Though powerful, these methods suffer from limited interpretability: they can detect which sets of populations have evidence for polygenic adaptation, but are unable to reveal where in the history of multiple populations these processes occurred. To address this, we created a method to detect polygenic adaptation in an admixture graph, which is a representation of the historical divergences and admixture events relating different populations through time. We developed a Markov chain Monte Carlo (MCMC) algorithm to infer branch-specific parameters reflecting the strength of selection in each branch of a graph. Additionally, we developed a set of summary statistics that are fast to compute and can indicate which branches are most likely to have experienced polygenic adaptation. We show via simulations that this method-which we call PolyGraph-has good power to detect polygenic adaptation, and applied it to human population genomic data from around the world. We also provide evidence that variants associated with several traits, including height, educational attainment, and self-reported unibrow, have been influenced by polygenic adaptation in different populations during human evolution.
由于许多基因座上的等位基因频率发生变化,多因素性状的平均值发生适应性变化。近年来,已经开发了几种使用全基因组关联研究 (GWAS) 中鉴定的基因座来检测多基因适应的方法。虽然这些方法很强大,但它们的解释能力有限:它们可以检测哪些群体有证据表明存在多基因适应,但无法揭示这些过程在多个群体的历史中何时发生。为了解决这个问题,我们创建了一种在混合图中检测多基因适应的方法,混合图是通过时间关联不同群体的历史分歧和混合事件的表示。我们开发了一种马尔可夫链蒙特卡罗 (MCMC) 算法来推断反映图中每个分支选择强度的分支特定参数。此外,我们开发了一组快速计算的汇总统计数据,可以指示哪些分支最有可能经历多基因适应。我们通过模拟表明,这种方法(我们称之为 PolyGraph)具有很好的检测多基因适应的能力,并将其应用于来自世界各地的人类群体基因组数据。我们还提供了证据表明,与身高、教育程度和自我报告的单眉等几个特征相关的变异在人类进化过程中受到了不同群体的多基因适应的影响。