Calibrating Evolutionary Rates at Major Histocompatibility Complex Loci
Unlike alleles at many other loci, major histocompatibility complex (Mhc) locus alleles often differ by nucleotide substitutions at more than one site, often as many as 88 sites. The substitutions accumulate gradually during evolution by the same process that leads to the divergence of genes in two biological species. The difference between the inter- and intraspecific variation is that in the former, substitutions become fixed in the population (reach a frequency of 1.0), whereas in the latter, they reach polymorphic frequencies (≥ 0.01, < 1.0). Since accumulation of interspecific differences is believed by many geneticists to proceed with a clock-like regularity within certain taxonomic groups, there is no a priori reason why the same should not be true for the accumulation of polymorphic differences. Here we demonstrate the validity of this assumption by comparing alleles at the Mhc-DRB and Mhc-DQB loci of different primate species. We then estimate the evolutionary rates at the DRB and DQB loci; the overall rates of these loci are 0.97 ± 0.17 and 1.2 ± 0.39 (site/billion years), respectively. However, the rate of the sites (both synonymous and nonsynonymous) encoding the peptide (antigen)-binding region (PBR) is 4 to 7 times higher than in the rest of the gene. As previously suggested, the enhanced nonsynonymous rate at the PBR is most likely due to balancing selection, but the PBR as a whole may be a hot spot of nucleotide substitutions.
KeywordsCodon Mane Canis
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