SEQUENCE VARIATION AT THE MAJOR HISTOCOMPATIBILITY COMPLEX DRB LOCI IN BELUGA (DELPHINAPTERUS-LEUCAS) AND NARWHAL (MONODON-MONOCEROS)

The variation at loci with similarity to DRB class II major histocompa tibility complex loci was assessed in 313 beluga collected from 13 sam pling locations across North America, and 11 narwhal collected in the Canadian high Arctic. Variation was assessed by amplification of exon 2, which codes for the peptide binding region, via the polymerase chai n reaction, followed by either cloning and DNA sequencing or single-st randed conformation polymorphism analysis. Two DRB loci were identifie d in beluga: DRB1, a polymorphic locus, and, DRB2, a monomorphic locus . Eight alleles representing five distinct lineages (based on sequence similarity) were found at the beluga DRB1 locus. Although the relativ e number of alleles is low when compared with terrestrial mammals, the amino acid variation found among the lineages is moderate. At the DRB 1 locus, the average number of nonsynonymous substitutions per site is greater than the average number of synonymous substitutions per site (0.0806 : 0.0207, respectively; P < 0.01). Most of the 31 amino acid s ubstitutions do not conserve the physiochemical properties of the resi due, and 21 of these are located at positions implicated as forming po ckets responsible for the selective binding of foreign peptide side ch ains. Only DRB1 variation was examined in 11 narwhal, revealing a low amount of variation. These data are consistent with an important role for the DRBI locus in the cellular immune response of beluga. In addit ion, the ratio of nonsynonymous to synonymous substitutions is similar to that among primate alleles, arguing against a reduction in the bal ancing selection pressure in the marine environment. Two hypotheses ma y explain the modest amount of Mhc variation when compared with terres trial mammals: small population sizes at speciation or a reduced neutr al substitution rate in cetaceans.