Portal de Periódicos da CAPES

Pathogen-Driven Selection and Worldwide HLA Class I Diversity

2005; Elsevier BV; Volume: 15; Issue: 11 Linguagem: Inglês

10.1016/j.cub.2005.04.050

1879-0445

Franck Prugnolle, Andrea Manica, Marie J. E. Charpentier, Jean‐François Guégan, Vanina Guernier, François Balloux,

Zoonotic diseases and public health

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 [1Hughes A.L. Yeager M. Natural selection at major histocompatibility complex loci of vertebrates.Annu. Rev. Genet. 1998; 32: 415-435Crossref PubMed Scopus (471) Google Scholar]. 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 [2Apanius V. Penn D. Slev P.R. Ruff L.R. Potts W.K. The nature of selection on the major histocompatibility complex.Crit. Rev. Immunol. 1997; 17: 179-224Crossref PubMed Google Scholar, 3Jeffery K.J.M. Bangham C.R.M. Do infectious diseases drive MHC diversity?.Microbes Infect. 2000; 2: 1335-1341Crossref PubMed Scopus (132) Google Scholar]. 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.