Interdependent MHC-DRB exon-plus-intron evolution in artiodactyls

Exon 2 sequences of an expressed MHC-DRB locus from sheep were examined forpolymorphisms in both the antigen-binding regions and the adjacent intronicmixed simple tandem repeat. Twenty-one novel exon 2 Ovar-DRB alleles wereidentified. Short nucleotide motifs are extensively shared between certainexon 2 regions of Ovar-DRB alleles. The simple repeat variations, thenumber of different amino acids at usually polymorphic sites, and thenumber of silent substitutions were reduced in the intraspecies analyses ofsheep DRB sequences, compared with those of cattle and goats. It wasparadoxical that the abundance of different sheep alleles was similar tothat of cattle and goats. This paradox may be explained by postulating arelatively small number of "ancient" alleles, with the present-day Ovar-DRBalleles being generated by reciprocal exchange of nucleotide motifs. At theantigen-binding sites, new combinations of amino acids were maintained inOvar-DRB alleles by strong positive selection. In sheep--and lesspronounced in goats and cattle--the DRB alleles can be divided into twogroups. In one group, silent substitutions are increased when compared withthe other. This suggests separate evolutionary pathways for certain groupsof DRB alleles within a species. The simple repetitive sequences are alsodiscussed with respect to the evolution of DRB alleles.