Mustela nivalis, the smallest member of the family Mustelidae, is widely distributed in the Holarctic region and shows high geographical variation. To further understand the molecular evolution of major histocompatibility complex (MHC), we sequenced part of MHC class II DRB gene exon 2, including codons encoding the antigen binding site (ABS), from 35 individuals from Finland, Bulgaria, Russia, and Japan. We detected 27 species-specific alleles (Muni-DRBs), some of which were broadly distributed and others geographically restricted. The ratio of nonsynonymous to synonymous substitution rates for predicted ABS codons exceeded 1, though not statistically significant. In addition, the single break point recombination (SBP) and mixed-effects model evolution (MEME) analyses demonstrated a recombination site and positive selection sites that could be committed to maintain the diversity of Muni-DRBs. In a Bayesian phylogenetic tree, all Muni-DRBs grouped within a Mustelidae clade. The Muni-DRBs showed transspecies polymorphism in related Mustela species that could have appeared to be evolved under long-lasting balancing selection. However, the sister-group patterns suggested that Mustela itatsi and Mustela sibirica alleles are much more closely related to one another than either are to M. nivalis alleles. This result correlates with the large genetic distance separating M. nivalis from M. itatsi or M. sibirica, data for which we have previously reported.
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