MHC class II haplotypes and linkage disequilibrium in primates

Abstract

The loci encoding the major histocompatibility class II cell surface antigens DR, DQ, and DP exhibit a remarkable degree of allelic polymorphism. Strong linkage disequilibrium is also found between these loci in the human population. To study the evolutionary conservation of this disequilibrium the DQA1, DQB1, and DRB1-6 loci were analyzed in chimpanzee and gorilla by sequencing or/and oligonucleotide hybridization of PCR-amplified DNA. This analysis revealed several new DRB sequences. The distribution of DRB loci differs between human and nonhuman primate haplotypes, and the strong disequilibrium found on human haplotypes between alleles at DQA1 and DQB1 as well as between the DQ loci and the DRB1 locus was not detected in the nonhuman hominoids. Extensive recombination within and between the DR and DQ region appears to have occurred during the 3–7 million years since the divergence of the three species, resulting in little similarity of haplotypes between species. The strong disequilibrium found in the human species between these loci may either reflect haplotype-specific barriers to recombination, recent founder effects in the evolution of humans, or selection for specific haplotypes.