COHEN, C.S.*; TIRINDELLI, J.; GOMEZ-CHIARRI, M.; GAUGER, E.; NACCI, D.; San Francisco State University, Harvard University: Major Histocompatibility Complex (MHC) variation at the population level: making the most of functional and structural models, with an example using estuarine fish
Structural models of the MHC antigen-binding cleft offer the opportunity to test for functional differences in substitution patterns at the population level. The mammalian crystal model for the antigen-binding receptor has been used successfully across vertebrates to infer binding areas and test hypotheses of positive selection at broad taxonomic levels. More recently, MHC researchers have found additional ways to test for shorter term, local effects of selection on the MHC. Some species with relatively low genetic diversity or under strong directional pathogen selection have revealed fascinating cases of MHC allelic disease linkage. But, more generally in genetically diverse species, these linkages may be hard to find. We are taking an alternative approach using the structural model to produce a population composite of antigen-binding region variation by mapping population-specific substitutions onto functional regions of the molecule. This population level approach is related to the strong differences in parasite load observed in highly disturbed, chemically contaminated estuaries, in comparison to reference sites. This approach will be illustrated with examples from EPA Superfund sites such as the one in New Bedford Harbor where resident killifish, Fundulus heteroclitus, show evolved resistance to chemical contaminants and have highly unusual parasite loads in comparison to fish from reference populations. Laboratory Vibrio challenges confirm functional aspects of the immune system in Superfund site fish. Population-specific patterns of antigen-binding region variation are a new tool for inferring functional changes in MHC. Funding for this included grants from the NRC, US EPA, Hudson River Foundation, NSF, Harvard University, and San Francisco State.
