Department of Anthropology, University of Michigan, Ann Arbor, Michigan.
Department of Biomedical Data Science, Stanford University, Stanford, California.
Genome Biol Evol. 2023 Mar 3;15(3). doi: 10.1093/gbe/evad015.
To characterize host risk factors for infectious disease in Mesoamerican populations, we interrogated 857,481 SNPs assayed using the Affymetrix 6.0 genotyping array for signatures of natural selection in immune response genes. We applied three statistical tests to identify signatures of natural selection: locus-specific branch length (LSBL), the cross-population extended haplotype homozygosity (XP-EHH), and the integrated haplotype score (iHS). Each of the haplotype tests (XP-EHH and iHS) were paired with LSBL and significance was determined at the 1% level. For the paired analyses, we identified 95 statistically significant windows for XP-EHH/LSBL and 63 statistically significant windows for iHS/LSBL. Among our top immune response loci, we found evidence of recent directional selection associated with the major histocompatibility complex (MHC) and the peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway. These findings illustrate that Mesoamerican populations' immunity has been shaped by exposure to infectious disease. As targets of selection, these variants are likely to encode phenotypes that manifest themselves physiologically and therefore may contribute to population-level variation in immune response. Our results shed light on past selective events influencing the host response to modern diseases, both pathogenic infection as well as autoimmune disorders.
为了描述中美洲人群中传染病的宿主风险因素，我们使用 Affymetrix 6.0 基因分型芯片检测了 857481 个单核苷酸多态性，以寻找免疫反应基因中自然选择的特征。我们应用了三种统计测试来识别自然选择的特征：局部分支长度（LSBL）、跨群体扩展单倍型纯合性（XP-EHH）和整合单倍型得分（iHS）。每个单倍型测试（XP-EHH 和 iHS）都与 LSBL 配对，并在 1%的水平上确定了显著性。对于配对分析，我们确定了 95 个具有统计学意义的 XP-EHH/LSBL 窗口和 63 个具有统计学意义的 iHS/LSBL 窗口。在我们的顶级免疫反应基因座中，我们发现了与主要组织相容性复合体（MHC）和过氧化物酶体增殖物激活受体γ（PPAR-γ）信号通路相关的近期定向选择的证据。这些发现表明，中美洲人群的免疫功能受到传染病暴露的影响。作为选择的目标，这些变体可能编码表型，这些表型在生理上表现出来，因此可能导致免疫反应的人群水平变异。我们的研究结果揭示了过去影响宿主对现代疾病（包括致病性感染和自身免疫性疾病）反应的选择事件。
