Departamento de Genética e Biologia Evolutiva, Universidade de São Paulo, São Paulo, Brazil.
Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil.
Hum Immunol. 2021 Jul;82(7):523-531. doi: 10.1016/j.humimm.2021.03.005. Epub 2021 Mar 31.
The Human Leukocyte Antigen (HLA) loci are extremely well documented targets of balancing selection, yet few studies have explored how selection affects population differentiation at these loci. In the present study we investigate genetic differentiation at HLA genes by comparing differentiation at microsatellites distributed genomewide to those in the MHC region. Our study uses a sample of 494 individuals from 30 human populations, 28 of which are Native Americans, all of whom were typed for genomewide and MHC region microsatellites. We find greater differentiation in the MHC than in the remainder of the genome (F = 0.130 and F = 0.087), and use a permutation approach to show that this difference is statistically significant, and not accounted for by confounding factors. This finding lies in the opposite direction to the expectation that balancing selection reduces population differentiation. We interpret our findings as evidence that selection favors different sets of alleles in distinct localities, leading to increased differentiation. Thus, balancing selection at HLA genes simultaneously increases intra-population polymorphism and inter-population differentiation in Native Americans.
人类白细胞抗原（HLA）基因座是平衡选择的极好目标，但很少有研究探讨选择如何影响这些基因座的群体分化。在本研究中，我们通过比较分布在整个基因组的微卫星与 MHC 区域的微卫星在 HLA 基因上的遗传分化来研究。我们的研究使用了来自 30 个人群的 494 个人的样本，其中 28 个是美洲原住民，他们都被进行了全基因组和 MHC 区域微卫星的分型。我们发现 MHC 区的分化比基因组其他部分更大（F 值为 0.130 和 F 值为 0.087），并使用随机置换方法表明这种差异具有统计学意义，且不能用混杂因素来解释。这一发现与平衡选择降低群体分化的预期相反。我们将这一发现解释为选择有利于不同局部地区的不同等位基因的证据，导致分化增加。因此，HLA 基因座上的平衡选择同时增加了美洲原住民的群体内多态性和群体间分化。
