期刊
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
卷 367, 期 1590, 页码 830-839出版社
ROYAL SOC
DOI: 10.1098/rstb.2011.0312
关键词
human leucocyte antigen; immunogenetics; pathogen-driven-balancing selection; pathogen richness; human migrations; genetic drift
类别
资金
- Swiss National Science Foundation (SNF, Switzerland) [3100A0-112651, 31003A-127465]
- ESF (Europe) COST [BM0803]
Human leucocyte antigen (HLA) loci have a complex evolution where both stochastic (e. g. genetic drift) and deterministic (natural selection) forces are involved. Owing to their extraordinary level of polymorphism, HLA genes are useful markers for reconstructing human settlement history. However, HLA variation often deviates significantly from neutral expectations towards an excess of genetic diversity. Because HLA molecules play a crucial role in immunity, this observation is generally explained by pathogen-driven-balancing selection (PDBS). In this study, we investigate the PDBS model by analysing HLA allelic diversity on a large database of 535 populations in relation to pathogen richness. Our results confirm that geographical distances are excellent predictors of HLA genetic differentiation worldwide. We also find a significant positive correlation between genetic diversity and pathogen richness at two HLA class I loci (HLA-A and -B), as predicted by PDBS, and a significant negative correlation at one HLA class II locus (HLA-DQB1). Although these effects are weak, as shown by a loss of significance when populations submitted to rapid genetic drift are removed from the analysis, the inverse relationship between genetic diversity and pathogen richness at different loci indicates that HLA genes have adopted distinct evolutionary strategies to provide immune protection in pathogen-rich environments.
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