Genetic Ancestry and Natural Selection Drive Population Differences in Immune Responses to Pathogens
Genetic Ancestry and Natural Selection Drive Population Differences in Immune Responses to Pathogens
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DOI：
10.1016/j.cell.2016.09.025
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发表时间：
2016-10-20
期刊：
影响因子：
64.5
通讯作者：
Barreiro, Luis B.
中科院分区：
文献类型：
--
作者：
Nedelec, Yohann;Sanz, Joaquin;Barreiro, Luis B.
不同人群的个体对免疫相关疾病的易感性差异很大。为了了解遗传变异和自然选择如何导致这些差异，我们测试了非洲与欧洲血统对原代巨噬细胞对活细菌病原体的转录反应的影响。总共有9.3%的巨噬细胞表达的基因在对感染的基因调控反应中显示出与祖先相关的差异，非洲血统特别预测了更强的炎症反应和减少的细胞内细菌生长。这些差异中很大一部分受到遗传控制：对于804个基因，超过75%的血统对免疫反应的影响可以通过单个顺式或反式作用表达数量性状基因座（eQTL）来解释。最后，我们表明，遗传对免疫反应的影响是非常丰富的最近，人口特异性的适应签名。总之，我们的研究结果表明，历史选择事件如何继续塑造今天的人类表型多样性，包括控制感染的关键特征。
Individuals from different populations vary considerably in their susceptibility to immune-related diseases. To understand how genetic variation and natural selection contribute to these differences, we tested for the effects of African versus European ancestry on the transcriptional response of primary macrophages to live bacterial pathogens. A total of 9.3% of macrophage-expressed genes show ancestry-associated differences in the gene regulatory response to infection, and African ancestry specifically predicts a stronger inflammatory response and reduced intracellular bacterial growth. A large proportion of these differences are under genetic control: for 804 genes, more than 75% of ancestry effects on the immune response can be explained by a single cis- or trans-acting expression quantitative trait locus (eQTL). Finally, we show that genetic effects on the immune response are strongly enriched for recent, population-specific signatures of adaptation. Together, our results demonstrate how historical selective events continue to shape human phenotypic diversity today, including for traits that are key to controlling infection.