Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802.
Department of Biology, Pennsylvania State University, University Park, PA 16802.
Genome Biol Evol. 2020 Apr 1;12(4):358-369. doi: 10.1093/gbe/evaa021.
Much of the enormous phenotypic variation observed across human populations is thought to have arisen from events experienced as our ancestors peopled different regions of the world. However, little is known about the genes involved in these population-specific adaptations. Here, we explore this problem by simultaneously examining population-specific genetic and expression differentiation in four human populations. In particular, we derive a branch-based estimator of population-specific differentiation in four populations, and apply this statistic to single-nucleotide polymorphism and RNA-seq data from Italian, British, Finish, and Yoruban populations. As expected, genome-wide estimates of genetic and expression differentiation each independently recapitulate the known relationships among these four human populations, highlighting the utility of our statistic for identifying putative targets of population-specific adaptations. Moreover, genes with large copy number variations display elevated levels of population-specific genetic and expression differentiation, consistent with the hypothesis that gene duplication and deletion events are key reservoirs of adaptive variation. Further, many top-scoring genes are well-known targets of adaptation in Europeans, including those involved in lactase persistence and vitamin D absorption, and a handful of novel candidates represent promising avenues for future research. Together, these analyses reveal that our statistic can aid in uncovering genes involved in population-specific genetic and expression differentiation, and that such genes often play important roles in a diversity of adaptive and disease-related phenotypes in humans.
在人类群体中观察到的大量巨大表型变异被认为是由于我们的祖先在不同地区定居而产生的。然而，关于这些特定于群体的适应性相关的基因知之甚少。在这里，我们通过同时检查四个人类群体中特定于群体的遗传和表达分化来探索这个问题。具体来说，我们在四个群体中推导出了一种基于分支的群体特异性分化估计量，并将该统计量应用于来自意大利、英国、芬兰和约鲁巴人的单核苷酸多态性和 RNA-seq 数据。正如预期的那样，遗传和表达分化的全基因组估计值各自独立地再现了这四个人类群体之间的已知关系，突出了我们的统计量用于识别特定于群体的适应性的潜在目标的实用性。此外，具有大量拷贝数变异的基因表现出高水平的特定于群体的遗传和表达分化，这与基因重复和缺失事件是适应性变异的关键库的假说一致。此外，许多得分最高的基因是欧洲人适应的已知靶点，包括那些与乳糖耐受和维生素 D 吸收有关的基因，少数新的候选基因代表了未来研究的有前途的途径。总的来说，这些分析表明，我们的统计量可以帮助揭示参与特定于群体的遗传和表达分化的基因，并且这些基因通常在人类中许多适应性和与疾病相关的表型中起着重要作用。
