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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

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, whil...

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Autores principales: dos Santos Francisco, Rodrigo, Buhler, Stéphane, Nunes, José Manuel, Bitarello, Bárbara Domingues, França, Gustavo Starvaggi, Meyer, Diogo, Sanchez-Mazas, Alicia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636516/
https://www.ncbi.nlm.nih.gov/pubmed/26459025
http://dx.doi.org/10.1007/s00251-015-0875-9
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author dos Santos Francisco, Rodrigo
Buhler, Stéphane
Nunes, José Manuel
Bitarello, Bárbara Domingues
França, Gustavo Starvaggi
Meyer, Diogo
Sanchez-Mazas, Alicia
author_facet dos Santos Francisco, Rodrigo
Buhler, Stéphane
Nunes, José Manuel
Bitarello, Bárbara Domingues
França, Gustavo Starvaggi
Meyer, Diogo
Sanchez-Mazas, Alicia
author_sort dos Santos Francisco, Rodrigo
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00251-015-0875-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-46365162015-11-10 HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms dos Santos Francisco, Rodrigo Buhler, Stéphane Nunes, José Manuel Bitarello, Bárbara Domingues França, Gustavo Starvaggi Meyer, Diogo Sanchez-Mazas, Alicia Immunogenetics Original Paper 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00251-015-0875-9) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2015-10-12 2015 /pmc/articles/PMC4636516/ /pubmed/26459025 http://dx.doi.org/10.1007/s00251-015-0875-9 Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Paper
dos Santos Francisco, Rodrigo
Buhler, Stéphane
Nunes, José Manuel
Bitarello, Bárbara Domingues
França, Gustavo Starvaggi
Meyer, Diogo
Sanchez-Mazas, Alicia
HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms
title HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms
title_full HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms
title_fullStr HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms
title_full_unstemmed HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms
title_short HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms
title_sort hla supertype variation across populations: new insights into the role of natural selection in the evolution of hla-a and hla-b polymorphisms
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636516/
https://www.ncbi.nlm.nih.gov/pubmed/26459025
http://dx.doi.org/10.1007/s00251-015-0875-9
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