THE-MHC-E LOCUS IN MACAQUES IS POLYMORPHIC AND IS CONSERVED BETWEEN MACAQUES AND HUMANS

Although the functions of the molecules encoded by the classical MHC c lass I loci are well defined, no function has been ascribed to the mol ecules encoded by the nan-classical MHC class I loci. To investigate t he evolution and conservation of the non-classical loci, we cloned and sequenced HLA-E homologues in macaques. We isolated four E locus alle les from five rhesus monkeys and two E locus alleles from one cynomolg us monkey, which indicated that the E locus in macaques is polymorphic . We also compared the rate of nucleotide substitution in the second i ntron of the macaque and human E locus alleles with that of exons two and three. The rate of nucleotide substitution was significantly highe r in the introns, which suggested that the E locus has evolved under s elective pressure. Additionally, comparison of the rates of synonymous and non-synonymous substitutions in the peptide binding region versus the remainder of the molecule suggested that the codons encoding the amino acids in the peptide binding region had been conserved in macaqu es and humans over the 36 million years since macaques and humans last shared a common ancestor.