On the Pattern of Polymorphisms at Major Histocompatibility Complex Loci

The pattern of polymorphisms at major histocompatibility complex loci was studied by computer simulations and by DNA sequence analysis. Two types of selection, overdominance plus short-term selection and maternal–fetal incompatibility, were simulated for a gene family with intra- and interlocus gene conversion. Both types of selection were found to be consistent with the observed patterns of polymorphisms. It was also found that the more interlocus conversion occurs, the higher the divergence becomes at both nonsynonymous and synonymous sites. The ratio of nonsynonymous-to-synonymous divergence among alleles decreases as the interlocus conversion rate increases. These results agree with the interpretation that the rate of interlocus conversion is lower in human genes than in genes of other nonprimate mammals. This is because, in the latter, synonymous divergence at the ARS (antigen recognition site) is often higher than that at the non-ARS, whereas in the former, this is not so. Also, the ratio of nonsynonymous to synonymous substitutions at the ARS tends to be higher in human genes than in other mammalian genes. The main difference between overdominance plus short-term selection and maternal–fetal interaction is that the number of alleles and heterozygosity per locus are higher in the latter than in the former under the presumed selection intensities. However, the average divergence among alleles tends to be lower in the latter than in the former under similar conditions.