HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms

Article Article scientifique Article HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms eng 2015 author Dos Santos Francisco Rodrigo 794241 author Buhler Stéphane 0000-0001-6675-5287 502714 author Nunes Jose Manuel 122321 author Bitarello Bárbara Domingues author França Gustavo Starvaggi author Meyer Diogo 793556 author Sanchez-Mazas Alicia 22545 651-663 10.1007/s00251-015-0875-9 0093-7711 http://link.springer.com/10.1007/s00251-015-0875-9 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 (G ST) 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 G ST 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. HLA Supertypes Human populations Natural selection Pathogens Adaptation Dewey 590 44 Département de génétique et évolution 162 false 824 Groupe Sanchez-Mazas 1056 Unité d'anthropologie Immunogenetics 67 11-12 7e2d46fd-6f1e-4a8a-a0f3-6cc1721a0a66 Article (Published version) Public Francisco_et_al_2015.pdf 1340861 application/pdf openAccess Faculté des sciences / Section de biologie / Département de génétique et évolution

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HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms	Immunogenetics			2015	663	251

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Dos Santos Francisco, Rodrigo