Prugnolle Franck, Manica A., Charpentier M., Guégan Jean-François, Guernier Vanina, Balloux F. (2005). Pathogen-driven selection and worldwide HLA class I diversity. Current Biology, 15 (11), p. 1022-1027. ISSN 0960-9822.
Titre du document
Pathogen-driven selection and worldwide HLA class I diversity
Prugnolle Franck, Manica A., Charpentier M., Guégan Jean-François, Guernier Vanina, Balloux F.
Source
Current Biology, 2005,
15 (11), p. 1022-1027 ISSN 0960-9822
The human leukocyte antigen (HILA; 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 HILA diversity in relation to their average genomic diversity. We tested this prediction by using HILA class I genetic diversity from 61 human populations. Our results show that human colonization history explains a substantial proportion of HILA genetic diversity worldwide. However, between-population variation at the HILA class I genes is also positively correlated with local pathogen richness (notably for the HILA 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 HILA A and HILA C genes. This is in good agreement with both previous immunological and genetic data suggesting that HILA B could be under a higher selective pressure from pathogens.
