MHC genes are also the most polymorphic loci known for vertebrates. This allelic sequence diversification results because MHC allelic lineages are ancient, more ancient than recent speciation events. So, for example, any given human MHC allele is more related to some alleles from chimpanzees and gorillas than it is to most other human alleles. It can be demonstrated that to account for each of the above features some form of natural selection acting on the antigen binding site is required. Answering this question is a central focus of my laboratory and leads to at least four major levels of inquiry involving host-parasite interactions, inbreeding, sexual selection and kin recognition systems.
Current understanding suggests the following relationships.
This in turn favors the evolution of MHC-based disassortative mating preferences because such matings produce progeny that are high fitness because either they are MHC heterozygotes or they have an advantage in the molecular arms race with pathogens. Such mating preferences would further increase MHC genetic diversity, making these loci increasingly useful as a kin recognition marker. None of these hypothesized interactions enjoy definitive support and we are testing aspects of each. Pathogen variants that escape MHC-dependent immune recognition will be favored by natural selection. We are testing this prediction by conducting experimental evolution experiments involving serial passage of various pathogens through strains of mice that differ only at MHC genes.