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.

中文翻译：

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现代人类适应性渗入的多基因模式主要是由对病原体的反应所决定。

解剖学上现代的人类在其基因组中携带许多其他人源蛋白的渗入变体。其中一些影响其表型，因此可以被否定或肯定地选择。已经提出了几种个体基因作为适应性渗入的对象，但是尚未广泛研究多基因适应性渗入的可能性。在这项研究中，我们用完善的功能富集方法分析了古老的基因渗入图，以发现基因渗入变体的多基因适应信号。我们首先应用一种方法来检测呈现出高于预期水平的古老基因渗入的生物途径内的连接基因（子网）集。然后，我们介绍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性选择和独立选择。我们确定了自适应基因渗入的几个已知目标，我们表明它们属于基因渗入的较大网络。校正基因连锁后，我们发现多基因适应的信号主要由独立的和潜在的顺序选择事件解释。但是，我们还发现了一些基因组，其中渗入的变体呈现出上位选择的重要信号。我们的结果证实，古老的基因渗入促进了局部适应，特别是在免疫相关和代谢功能方面，并突显了其参与对非洲以外病原体的协调反应。我们发现多基因适应的信号主要由独立的和潜在的顺序选择事件解释。但是，我们还发现了一些基因组，其中渗入的变体呈现出上位选择的重要信号。我们的结果证实，古老的基因渗入促进了局部适应，特别是在免疫相关和代谢功能方面，并突显了其参与对非洲以外病原体的协调反应。我们发现多基因适应的信号主要由独立的和潜在的顺序选择事件解释。但是，我们还发现了一些基因组，其中渗入的变体呈现出上位选择的重要信号。我们的结果证实，古老的基因渗入促进了局部适应，特别是在免疫相关和代谢功能方面，并突显了其参与对非洲以外病原体的协调反应。