The MHC-E locus is the most well conserved of all known primate class I histocompatibility genes.
The HLA-E locus is characterized by limited polymorphism and low levels of cell surface expression. However, the function of the products of this nonclassical MHC class I gene remains unknown. To evaluate the conservation of the MHC-E locus throughout anthropoid primate evolution, we identified the homologue of the HLA-E locus in six different New World monkey species. Full-length sequencing of MHC-EcDNAs in four unrelated cotton-top tamarins (Saguinus oedipus) revealed no evidence for polymorphism. Using the PCR, denaturing gradient gel electrophoresis, and direct sequencing, we also identified MHC-E alleles in five other New World monkey species, representing all extant platyrrhine families. In contrast to all other classical and nonclassical MHC class I genes in primates, the rate of synonymous nucleotide substitution is much greater than the rate of nonsynonymous nucleotide substitution within exons 2 and 3 encoding the peptide binding region (PBR) in MHC-E genes. The PBR of the MHC-E molecule, therefore, has evolved under purifying selective pressures, and the very unusual evolutionary history of this ancient gene provides further evidence that the products of the HLA-E locus serve a critical immunological function. Given the remarkable conservation of the PBR during primate evolution, this critical immunological function is probably related to the peptide binding ability of the MHC-E protein.
Knapp
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Wisconsin Regional Primate Research Center, University of Wisconsin, Madison 53715, USA.
Cadavid
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Watkins
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D000595:Amino Acid Sequence; D000818:Animals; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011323:Primates / Q000235:genetics* / Q000276:immunology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000097625:HLA-E Antigens
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens