Integrative and Comparative Biology Advance Access originally published online on October 11, 2006
Integrative and Comparative Biology 2006 46(6):1016-1029; doi:10.1093/icb/icl044
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Functional implications of Major Histocompatibility (MH) variation using estuarine fish populations
* Romberg Tiburon Center, Department of Biology, San Francisco State University 3152 Paradise Dr., Tiburon, CA 94920-1205, USA
Department of Fisheries, Animal and Veterinary Science, University of Rhode Island Kingston, RI 02881, USA
US Environmental Protection Agency, Office of Research and Development, Atlantic Ecology Division Narragansett, RI 02882, USA
Correspondence: 1E-mail: sarahcoh{at}sfsu.edu
Recently, there has been a dramatic expansion of studies of major histocompatibility complex (MHC) variation aimed at discovering functional differences in immunity across wild populations of diverse vertebrate species. Some species with relatively low genetic diversity or under strong directional selection by pathogens have revealed fascinating cases of MHC allelic disease linkage. More generally in genetically diverse species, however, these linkages may be hard to find. In this paper, we review approaches for assessing functional variation in MHC and discuss their potential use for discovering smaller-scale intraspecific spatial and temporal patterns of MHC variation. Then, we describe and illustrate an approach using the structural model to produce a population composite of variation in antigen-binding regions by mapping population-specific substitutions onto functional regions of the molecule. We are producing models of variation in major histocompatibility (MH) loci for populations of non-migratory fish (killifish, Fundulus heteroclitus) resident at sites that vary dramatically in environmental quality. We discuss the goal of relating MH population variation to functional differences in disease susceptibility such as those inferred by observations of parasitic infection and direct measurement of bacterial challenges in the laboratory. Our study has focused on relatively well-studied killifish populations, including those resident in a highly disturbed, chemically contaminated estuary and nearby less contaminated sites. Population-specific genetic changes at MHC antigen-binding loci are described, and evidence relevant to functional implications of these changes is reviewed. Population-specific patterns of variation in antigen-binding regions in combination with a range of assessments of immune function will provide a powerful new approach to reveal functional changes in MHC.