Brandt Débora Y C, César Jônatas, Goudet Jérôme, Meyer Diogo
Departamento de Genética e Biologia Evolutiva, Universidade de São Paulo, São Paulo, SP, Brazil.
Department of Ecology and Evolution, University of Lausanne, Lausanne, Switzerland
G3 (Bethesda). 2018 Jul 31;8(8):2805-2815. doi: 10.1534/g3.118.200367.
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 FST. 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 FST 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.
平衡选择被定义为一类选择性机制，它维持的多态性高于中性条件下预期的水平。理论预测，平衡选择会降低种群分化，如通过FST所衡量的那样。然而，在不同种群中维持不同等位基因组合的平衡选择机制可能会增加种群分化。为了探讨平衡选择与种群分化之间的联系，我们研究了HLA基因的种群分化情况，HLA基因是人类平衡选择最显著的例子。我们发现，HLA基因上单核苷酸多态性（SNP）的种群分化平均低于其他基因组区域的SNP。我们表明，这些结果需要使用一种考虑FST对等位基因频率依赖性的计算方法。然而，在亲缘关系密切的种群对中，在全基因组分化较低的情况下，HLA的分化高于其他基因组区域。只要杂合子的适应性在分化的种群之间存在差异，在超显性选择的模拟中就会重现这种最近分化的种群对中HLA基因种群分化增加的情况。这些结果为跨人类种群的HLA基因平衡选择性质的一种可能的“分歧超显性”机制提供了见解。
