EVOLUTION OF MHC POLYMORPHISM - EXTENSIVE SHARING OF POLYMORPHIC SEQUENCE MOTIFS BETWEEN HUMAN AND BOVINE DRB ALLELES

The evolution of MHC polymorphism has been studied by comparing the amino acid and nucleotide sequences of 14 bovine and 32 human DRB alleles. The comparison revealed an extensive sharing of polymorphic sequence motifs in the two species. Almost identical sets of residues were found at several highly polymorphic amino acid positions in the putative antigen recognition site. Consequently, certain bovine alleles than to other bovine alleles. In contrast, the frequencies of silent nucleotide substitutions were found to be much higher in comparisons between species than within species implying that none of the human or bovine DRB alleles originated before the divergence of these distantly related species. The results suggest that the observed similarity in DRB polymorphism is due to convergent evolution and possibly the sharing of short ancestral sequence motifs. However, the relative role of the latter mechanism is difficult to assess due to the biased base composition in the first domain exon of polymorphic class II beta-genes. The frequency of silent substitutions between DRB alleles was markedly lower in cattle than in man suggesting that the DRB diversity has evolved more rapidly in the former species.