The hypothesis that pathogens drive MHC genetic diversity predicts that 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. We know pathogens adapt during such passages as reflected in increased virulence. These experiments will determine if some of the increased virulence is MHC-dependent. We have also begun testing the heterozygote advantage hypothesis and have recently demonstrated that MHC heterozygotes have an advantage when coinfected with Salmonella and Theiler s virus.
Heterozygotes have no advantage when infected individually with either pathogen.
This is the first experimental confirmation that MHC heterozygote advantage may emerge because heterozygotes have greater overall resistance during coinfections. We are also testing predictions from the pathogen hypothesis by determining if MHC genotype effects fitness in seminatural populations of house mice containing both normal parasite loads and experimental parasite infections. We are investigating the adaptive significance and mechanisms of MHC-based mating preferences. We are using olfaction assays and cross-fostering experiments designed to reveal the development of perceived odor profiles that individuals subsequently avoid during mate choice. We are evaluating the importance of inbreeding avoidance in the evolution of MHC-based mating preferences by measuring the fitness consequences of inbreeding in house mice.