HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms.
HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms.
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DOI：
10.1007/s00251-015-0875-9
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发表时间：
2015-11
期刊：
影响因子：
3.2
通讯作者：
Sanchez-Mazas A
中科院分区：
文献类型：
--
作者：
Dos Santos Francisco R;Buhler S;Nunes JM;Bitarello BD;França GS;Meyer D;Sanchez-Mazas A
超型是一组人类白细胞抗原（HLA）等位基因，由于在肽结合区（PBR）的锚位置（B和F口袋）共享特定残基，它们结合重叠的肽组。同一超型内的HLA等位基因预期在功能上相似，而来自不同超型的HLA等位基因预期在功能上不同，呈现不同的肽组。在这项研究中，我们应用超型分类的HLA-A和HLA-B数据的55个世界各地的人口，以调查自然选择的超型，而不是在这些位点的等位基因变异的影响。我们比较了核苷酸多样性的B和F口袋与其他PBR地区，通过一个resternation程序，并比较了模式的种群内杂合性（He）和种群间分化（GST）时，观察到的超型定义时，估计使用随机组的等位基因。在HLA-A中，在B和F囊袋中观察到低水平的变异，并且随机化He和GST与观察到的数据没有差异。相比之下，HLA-B集中了超型之间的大部分差异，B口袋显示出特别高的变异水平。此外，在HLA-B中，等位基因重新分配到随机组中并不能再现超型所观察到的群体分化模式。因此，我们得出结论，不同的HLA-A，其中超型和等位基因变异表现出类似的模式的核苷酸多样性内和人群之间，HLA-B可能是通过其B口袋的特定适应当地病原体的演变。本文的在线版本（doi：10.1007/s 00251 -015-0875-9）包含补充材料，可供授权用户使用。
Supertypes are groups of human leukocyte antigen (HLA) alleles which bind overlapping sets of peptides due to sharing specific residues at the anchor positions—the B and F pockets—of the peptide-binding region (PBR). HLA alleles within the same supertype are expected to be functionally similar, while those from different supertypes are expected to be functionally distinct, presenting different sets of peptides. In this study, we applied the supertype classification to the HLA-A and HLA-B data of 55 worldwide populations in order to investigate the effect of natural selection on supertype rather than allelic variation at these loci. We compared the nucleotide diversity of the B and F pockets with that of the other PBR regions through a resampling procedure and compared the patterns of within-population heterozygosity (He) and between-population differentiation (GST) observed when using the supertype definition to those estimated when using randomized groups of alleles. At HLA-A, low levels of variation are observed at B and F pockets and randomized He and GST do not differ from the observed data. By contrast, HLA-B concentrates most of the differences between supertypes, the B pocket showing a particularly high level of variation. Moreover, at HLA-B, the reassignment of alleles into random groups does not reproduce the patterns of population differentiation observed with supertypes. We thus conclude that differently from HLA-A, for which supertype and allelic variation show similar patterns of nucleotide diversity within and between populations, HLA-B has likely evolved through specific adaptations of its B pocket to local pathogens. The online version of this article (doi:10.1007/s00251-015-0875-9) contains supplementary material, which is available to authorized users.