Polygenic Patterns of Adaptive Introgression in Modern Humans Are Mainly Shaped by Response to Pathogens
Polygenic Patterns of Adaptive Introgression in Modern Humans Are Mainly Shaped by Response to Pathogens
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DOI：
10.1093/molbev/msz306
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发表时间：
2020-05-01
影响因子：
10.7
通讯作者：
Excoffier, Laurent
中科院分区：
文献类型：
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作者：
Gouy, Alexandre;Excoffier, Laurent
从解剖学上讲，现代人的基因组中携带着许多来自其他古人类的基因渗入变体。它们中的一些影响它们的表型，因此可以被负选择或正选择。一些个体基因被认为是适应性渐渗的主体，但多基因适应性渐渗的可能性尚未得到广泛研究。在这项研究中，我们分析了古老的渐渗图与完善的功能富集方法，以找到信号的多基因适应渐渗变异。我们首先应用一种方法来检测生物通路内的连接基因（子网络），这些基因呈现出高于预期的古老基因渗入水平。然后，我们引入并应用一种新的统计检验来区分当今人类基因组中的上位选择和独立选择。我们确定了几个已知的适应性基因渗入的目标，我们表明，他们属于更大的网络基因渗入。校正遗传连锁后，我们发现多基因适应的信号主要是由独立的和潜在的顺序选择事件解释。然而，我们也发现了一些基因集，其中渗入的变体呈现上位选择的显著信号。我们的研究结果证实，古老的基因渗入促进了当地的适应，特别是在免疫相关和代谢功能，并强调其参与协调响应非洲的病原体。
Anatomically modern humans carry many introgressed variants from other hominins in their genomes. Some of them affect their phenotype and can thus be negatively or positively selected. Several individual genes have been proposed to be the subject of adaptive introgression, but the possibility of polygenic adaptive introgression has not been extensively investigated yet. In this study, we analyze archaic introgression maps with refined functional enrichment methods to find signals of polygenic adaptation of introgressed variants. We first apply a method to detect sets of connected genes (subnetworks) within biological pathways that present higher-than-expected levels of archaic introgression. We then introduce and apply a new statistical test to distinguish between epistatic and independent selection in gene sets of present-day humans. We identify several known targets of adaptive introgression, and we show that they belong to larger networks of introgressed genes. After correction for genetic linkage, we find that signals of polygenic adaptation are mostly explained by independent and potentially sequential selection episodes. However, we also find some gene sets where introgressed variants present significant signals of epistatic selection. Our results confirm that archaic introgression has facilitated local adaptation, especially in immunity related and metabolic functions and highlight its involvement in a coordinated response to pathogens out of Africa.