The major histocompatibility complex (MHC) is one of the most variable gene families in vertebrates. MHC molecules can recognize antigens from pathogens and signal immune cells to invoke an adaptive immune response. Pathogen-mediated selection is believed to be the main force maintaining diversity at MHC genes and three main hypothesis have been proposed including heterozygote advantage, negative frequency-dependent selection and fluctuating selection. However, it has proven hard to demonstrate

more »

... the exact selection regime that maintains variation in natural populations. An effective method to examine contemporary selection on MHC genes is to test for association between MHC genetic variation and fitness. However, many previous studies suffer from poor genetic tools, low sample size, short time scale and inappropriate statistical approaches. Also, a critical question, which is rarely studied, is whether the associations between MHC variation and fitness are consistent with associations between MHC variation and phenotypic traits that predict fitness. Besides the paradigm of pathogen-mediated selection, sexual selection may also contribute to the maintenance of MHC diversity. MHC-dependent sexual selection could also occur via three mechanisms including selection for specific alleles or haplotypes, selection for heterozygosity and selection for compatibility. However, at present there is no consensus as to which of these mechanisms are involved and their importance. Previous studies have often suffered from limited genetic and behavioural data and small sample size, and were rarely able to examine all the mechanisms together, determine whether signatures of MHC-based non-random mating are independent of genomic effects or distinguish whether MHC-dependent sexual selection takes place at the pre- or post-copulatory stage. For more than three decades, Soay sheep living in the island of Hirta, St Kilda archipelago have been followed from birth, through all breeding attempts, to death. With a genetically-inferred multig [...]