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Pathogen-driven selection and worldwide HLA class I diversity

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journal contribution
posted on 2005-06-07, 00:00 authored by F Prugnolle, A Manica, M Charpentier, J F Guégan, Vanina Guernier, F Balloux
The human leukocyte antigen (HLA; known as MHC in other vertebrates) plays a central role in the recognition and presentation of antigens to the immune system and represents the most polymorphic gene cluster in the human genome [1]. Pathogen-driven balancing selection (PDBS) has been previously hypothesized to explain the remarkable polymorphism in the HLA complex, but there is, as yet, no direct support for this hypothesis [2, 3]. A straightforward prediction coming out of the PDBS hypothesis is that populations from areas with high pathogen diversity should have increased HLA diversity in relation to their average genomic diversity. We tested this prediction by using HLA class I genetic diversity from 61 human populations. Our results show that human colonization history explains a substantial proportion of HLA genetic diversity worldwide. However, between-population variation at the HLA class I genes is also positively correlated with local pathogen richness (notably for the HLA B gene), thus providing support for the PDBS hypothesis. The proportion of variations explained by pathogen richness is higher for the HLA B gene than for the HLA A and HLA C genes. This is in good agreement with both previous immunological and genetic data suggesting that HLA B could be under a higher selective pressure from pathogens. ©2005 Elsevier Ltd All rights reserved.

History

Journal

Current biology

Volume

15

Issue

11

Pagination

1022 - 1027

Publisher

Elsevier

Location

Amsterdam, The Netherlands

ISSN

0960-9822

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2005, Elsevier Ltd