The molecular descent of the major histocompatibility complex

In the last few years, more than 500 primate major histocompatibility complex (Mhc) genes or parts thereof have been sequenced. The extraordinary sequence information is used here to draw conclusions about the manner of Mhc evolution. The Mhc genes are found to evolve at a relatively slow rate with the regularity of a clock. It takes from 1 to 6 million years for a new mutation to be incorporated into an Mhc allele, and the mutation rate is comparable to that of most other primate genes. The nonsynonymous sites coding for the peptide-binding region (PBR) are under relatively weak positive selection pressure (selection coefficient of a few percent only); the nonsynonymous non-PBR sites are under moderate negative selection pressure. The positive pressure is probably provided by parasites and is responsible for the trans-species persistence of allelic lineages at functional Mhc loci for more than 40 million years.