Because of the central role of major histocompatibility complex (MHC) genes in immune recognition1-3, it is often assumed that parasite-driven selection maintains the unprecendented genetic diversity of these genes4-7. But associations between MHC genotype and specific infectious diseases have been difficult to identify8,9 with a few exceptions such as Marek's disease10 and malaria11. Alternatively, MHC-related reproductive mechanisms such as selective abortion12-15 and mating preferences16,17 could be responsible for the diversity. To determine both the nature and strength of selection operating on MHC genes by we have studied components of selection in seminatural populations of mice (Mils musculus domesticus). Here we assess MHC-related patterns of reproduction and early (preweaning) mortality by analysing 1,139 progeny born in nine populations, and 662 progeny from laboratory matings. Reproductive mechanisms, primarily mating preferences, result in 27% fewer MHC-homozygous offspring than expected from random mating. MHC genotype had no detectable influence on neonatal (preweaning) mortality. These mating preferences are strong enough to account for most of the MHC genetic diversity found in natural populations of Mus.
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