The Effect of Balancing Selection on Population Differentiation: A Study with HLA Genes.
The Effect of Balancing Selection on Population Differentiation: A Study with HLA Genes.
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DOI：
10.1534/g3.118.200367
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发表时间：
2018-07-31
期刊：
影响因子：
--
通讯作者：
Meyer D
中科院分区：
文献类型：
--
作者：
Brandt DYC;César J;Goudet J;Meyer D
平衡选择被定义为一类选择性机制，其保持多态性高于中立条件下的预期。理论预测，平衡选择会减少群体分化（如 F 所示）。然而，在不同群体中维持不同组等位基因的平衡选择机制可能会增加群体分化。为了解决平衡选择和群体分化之间的联系，我们研究了 HLA 基因的群体分化，这构成了人类平衡选择最引人注目的例子。我们发现 HLA 基因上的单核苷酸多态性 (SNP) 的群体分化平均低于其他基因组区域中的 SNP。我们表明，这些结果需要使用计算来解释 F 对等位基因频率的依赖性。然而，在密切相关的群体中，全基因组分化较低，HLA 的分化高于其他基因组区域。只要不同种群之间纯合子的适应性不同，最近分化的种群对的 HLA 基因的种群分化就会在过度显性选择的模拟中重现。这些结果让我们深入了解了人类 HLA 基因平衡选择本质上可能存在的“发散性过度优势”机制。
Balancing selection is defined as a class of selective regimes that maintain polymorphism above what is expected under neutrality. Theory predicts that balancing selection reduces population differentiation, as measured by F. However, balancing selection regimes in which different sets of alleles are maintained in different populations could increase population differentiation. To tackle the connection between balancing selection and population differentiation, we investigated population differentiation at the HLA genes, which constitute the most striking example of balancing selection in humans. We found that population differentiation of single nucleotide polymorphisms (SNPs) at the HLA genes is on average lower than that of SNPs in other genomic regions. We show that these results require using a computation that accounts for the dependence of F on allele frequencies. However, in pairs of closely related populations, where genome-wide differentiation is low, differentiation at HLA is higher than in other genomic regions. Such increased population differentiation at HLA genes for recently diverged population pairs was reproduced in simulations of overdominant selection, as long as the fitness of the homozygotes differs between the diverging populations. The results give insight into a possible “divergent overdominance” mechanism for the nature of balancing selection on HLA genes across human populations.
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