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MHC ANTIGEN BINDING LOCUS DRB1 SHOWS STRONG SIGNAL OF SELECTION AND HIGH VARIABILITY IN FUNDULUS HETERCLITUS POPULATIONS
Citation:
Cohen, S. MHC ANTIGEN BINDING LOCUS DRB1 SHOWS STRONG SIGNAL OF SELECTION AND HIGH VARIABILITY IN FUNDULUS HETERCLITUS POPULATIONS. Presented at Society of Molecular Biology/Evolution and American Genetics Association, New Haven, CT, June 17-21, 2000.
Description:
The major histocompatibility system provides a unique complex of genetic loci in vertebrates to assess genetic diversity and to look for the effects of selection on the adaptive immune system. Studies using mammals and birds
have demonstrated relationships between MHC genotype and disease resistance or mating success. Aspects of adaptive immunity in lower vertebrates differ substantially from birds and mammals raising the question of how MHC may
operate in these organisms. Marine fish population studies using MHC thus far have focused largely on endangered populations and aquacultural stocks. I isolated MHC DRB1 loci from the common non-migratory estuarine fish,
Fundulus heteroclitus, and compared sequence variation within and between populations including one location where the fish are under severe chemical stress and also show unusual patterns of parasitism. Two hallmark features of MHC in higher vertebrates are also evident in wild fish populations. First, the antigen binding locus DRB1 is extraordinarily polymorphic within populations, showing 7-28% sequence divergence in the coding region within a population. Second, antigen-binding sites inferred from mammalian models are highly variable and show a strong signal of positive selection. In addition, between population comparisons showed that fish from a PCB-contaminated EPA superfund site have a 13% incidence of unusually divergent MHC alleles (~30% mean genetic distance from other alleles) that may be associated with unusual patterns of parasitism and may be indicative of unusually strong selective pressures at the superfund site. Additional sampling of polluted and unpolluted sites for MHC genotypes and rates of parasitism is underway to investigate the relationships between alleleic diversity and chemical and parasite stress in these fish. The high levels of allelic diversity and variation in inferred antigen-binding sites found thus far demonstrate that: 1.) MHC genetic variation is an important tool for examining selective pressures and response of the immune system in a lower vertebrate; and 2.) Fundulus heteroclitus is a useful species for making population-level comparisons of immunogenetic response to anthropogenic stress in coastal environments.