PNAS：早期人类扩张的遗传效应

近日，在PNAS上科研人员报告了早期人类走出非洲的扩张的遗传影响。每一个人类基因组携带了数以百计的可能有害的突变，但是尚不清楚各人群的有害突变数量如何变化。

Brenna Henn及其同事使用来自人类基因组多样性组的纳米比亚人群、刚果人群、阿尔及利亚人群、巴基斯坦人群、柬埔寨人群、西伯利亚人群和墨西哥人群的基因组数据，描述了各人类人群的有害突变分布的特征。

这组作者在个体中间观察到了预测为有害的等位基因数量随着与撒哈拉以南非洲距离的增加而增加。对于预测具有大的但不是极端的有害效应的等位基因，这种相关性最强，而对于最严重的突变，这个数字在各人群中的差异不是非常显著。

在人群层次上，非非洲人群比非洲人群的有害突变更常见，尽管某些突变可能实际上对于新环境是有益的。这组作者描述了隐性突变如何对计算人类基因组突变的有害负担具有重要作用。这些结果提示，非洲人群比非非洲人群的反对强有害突变的选择更强烈。

在非非洲人群中，许多温和的有害突变进化了出来，仿佛它们是中性的。这组作者说，这些结果符合人类走出非洲的扩张期间的一系列创始人效应。

.原文链接：Distance from sub-Saharan Africa predicts mutational load in diverse human genomes

原文摘要：The Out-of-Africa (OOA) dispersal ∼50,000 y ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from seven geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia, and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were neutral during the expansion out of Africa. Under a model where selection is inversely related to dominance, we show that OOA populations are likely to have a higher mutation load due to increased allele frequencies of nearly neutral variants that are recessive or partially recessive.

DOI: 10.1073/PNAS.1510805112

作者：阳光森林