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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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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Francisco, Rodrigo dos Santos [1, 2, 3] ; Buhler, Stephane [3, 4, 5] ; Nunes, Jose Manuel [3, 6] ; Bitarello, Barbara Domingues [2] ; Franca, Gustavo Starvaggi [7, 8] ; Meyer, Diogo [2] ; Sanchez-Mazas, Alicia [3, 6]
Total Authors: 7
[1] Hosp Israelita Albert Einstein, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Genet & Evolutionary Biol, Sao Paulo - Brazil
[3] Univ Geneva, Anthropol Unit, Dept Genet & Evolut, Lab Anthropol Genet & Peopling Hist, Geneva - Switzerland
[4] Univ Hosp Geneva, Dept Genet & Lab Med, Transplantat Immunol Unit, Geneva - Switzerland
[5] Univ Hosp Geneva, Dept Genet & Lab Med, Natl Reference Lab Histocompatibil, Geneva - Switzerland
[6] Inst Genet & Genom Geneva IGE3, Geneva - Switzerland
[7] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil
[8] Sirio Libanes Hosp, Ctr Mol Oncol, Sao Paulo - Brazil
Total Affiliations: 8
Document type: Journal article
Source: IMMUNOGENETICS; v. 67, n. 11-12, p. 651-663, NOV 2015.
Web of Science Citations: 12

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. (AU)

FAPESP's process: 12/18010-0 - Balancing selection in the human genome: detection, causes and consequences
Grantee:Diogo Meyer
Support type: Regular Research Grants