Functional implications of Neandertal introgression in modern humans.
Functional implications of Neandertal introgression in modern humans.
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DOI：
10.1186/s13059-017-1181-7
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发表时间：
2017-04-03
期刊：
影响因子：
12.3
通讯作者：
Kelso J
中科院分区：
文献类型：
--
作者：
Dannemann M;Prüfer K;Kelso J
大约5万至6万年前，早期现代人和尼安德特人的混合导致了今天非非洲人基因组中1.5%至4%的尼安德特人祖先。越来越多的证据表明，这些古老的等位基因中的一些对现代人类有利，而另一些则是有害的;然而，这些古老等位基因的主要作用机制尚未得到充分研究。在这里，我们评估的贡献渗入的非同义和调节变异现代人类蛋白质和基因表达的变化。我们表明，基因表达变化往往与尼安德特人的祖先比预期的，和渗入的非同义变体往往有较少的预测功能的影响，对现代人类蛋白质比突变，出现在人类谱系。相反，渐渗等位基因比非渐渗等位基因对表达变异的贡献成比例地更大。我们的研究结果表明，尼安德特人渗入等位基因的主要影响是通过他们对基因调控的影响。本文的在线版本（doi：10.1186/s13059-017-1181-7）包含补充材料，可供授权用户使用。
Admixture between early modern humans and Neandertals approximately 50,000–60,000 years ago has resulted in 1.5–4% Neandertal ancestry in the genomes of present-day non-Africans. Evidence is accumulating that some of these archaic alleles are advantageous for modern humans, while others are deleterious; however, the major mechanism by which these archaic alleles act has not been fully explored. Here we assess the contributions of introgressed non-synonymous and regulatory variants to modern human protein and gene expression variation. We show that gene expression changes are more often associated with Neandertal ancestry than expected, and that the introgressed non-synonymous variants tend to have less predicted functional effect on modern human proteins than mutations that arose on the human lineage. Conversely, introgressed alleles contribute proportionally more to expression variation than non-introgressed alleles. Our results suggest that the major influence of Neandertal introgressed alleles is through their effects on gene regulation. The online version of this article (doi:10.1186/s13059-017-1181-7) contains supplementary material, which is available to authorized users.