The evolution of allelic diversity at the primate major histocompatibility complex class II loci.
The evolutionary history of polymorphism at the DQ alpha, DQ beta, and DR beta loci appears to be quite distinct and reflects different genetic mechanisms and selection pressures for the different loci. Phylogenetic analysis of sequences from a variety of species allows the tentative reconstruction of the order of gene duplication and of allelic diversification. Some of the major allelic types or lineages appear to be very old (greater than 20 myr) and selection has acted to maintain these ancient allelic types as well as, in the case of the DR beta loci, to favor new variants generated by recombining beta-sheet and alpha-helix domains. Phylogenetic analysis can also reveal balancing selection at individual residues of the class II beta chains. The highest number of phylogenetically inferred changes attributed to balancing selection was found at beta-chain residues located in the ABS and at those residues implicated in disease susceptibility. For some residues, the number of different amino acids observed at individual polymorphic positions is highly restricted and the few tolerated residues are common to all primate species studied. This observation supports the view that these positions are subject to some form of balancing selection.
Erlich
H A
HA
Department of Human Genetics, Cetus Corporation, Emeryville, California 94608.
Gyllensten
U B
UB
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D003062:Codon; D005802:Genes, MHC Class II; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011323:Primates / Q000235:genetics*
D003062:Codon; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens