WAYNE POTTS

My research interests focus on the genetics of host-pathogen coevolution. Our current studies focus on the genes of the major histocompatibility complex (MHC), which play a central role in vertebrate immune recognition. MHC genes are also the most polymorphic loci known for vertebrates and many MHC alleles confer susceptibility to autoimmune and infectious diseases. What evolutionary mechanisms account for the extreme diversity of MHC genes? Why are these demonstrably "bad" alleles not eliminated by natural selection? These questions currently form the central focus of my laboratory and lead to at least four major levels of inquiry involving host-parasite interactions, inbreeding, sexual selection and kin recognition systems. Our current understanding suggests the following relationships. Parasite-driven selection favors MHC genetic diversity through both heterozygote advantage and relentless pathogen adaptation to common host genotypes, leading to rare MHC allele advantage. This in turn favors the evolution of MHC-based disassortative mating preferences because they preferentially produce high-fitness (disease-resistant) progeny. Such mating preferences would further increase MHC genetic diversity, making these loci increasingly useful as a kin recognition marker. Consequently, the avoidance of matings with kin (i.e. inbreeding) is an additional factor favoring MHC-based mating preferences. None of these hypothesized interactions enjoy definitive support and we are testing predictions from each. To test these hypotheses we use a varied set of approaches including laboratory experiments involving host-parasite interactions and sexual selection. Molecular genetic techniques are utilized extensively to characterize the genotypes of both hosts and parasites in these studies. We also use population and behavioral studies on natural and semi-natural populations of vertebrate species, primarily house mice. Recently we have begun a collaboration with Tracey Lamb attempting to understand the basis of asymptomatic malaria, which constitutes over 60% of human infections. Progress on this problem was hindered by the lack of an animal model; all laboratory rodents were susceptible. We discovered that our wild-derived mice have a full range of resistance/susceptibility profiles, much like humans. This discovery now allows animal experiments to test important hypotheses regarding asymptomatic malaria. The NSF and NIH proposals that are currently under review and each have a major specific aim with experiments using our wild-derived mice as the model system.