Allelic diversity is generated by intraexon sequence exchange at the DRB1 locus of primates.
The loci encoding the class II cell surface antigens HLA-DR, -DQ, and -DP exhibit a remarkable degree of allelic polymorphism. Most of the class II allelic diversity is localized to the second exon, which encodes a beta-pleated sheet followed by an alpha-helical domain. Here, phylogenetic analysis of 39 human DRB1 alleles and 21 DRB1 alleles obtained by polymerase chain reaction (PCR) amplification from a set of closely related primates reveals that sequences encoding the beta-pleated sheet and those encoding the alpha-helix of the second domain have different evolutionary histories. The polymorphisms in the beta-pleated sheet have been conserved between species and appear to reflect the ancestral relationships among haplotypes, whereas polymorphic segments encoding the alpha-helical domain appear to have been inserted by interallelic sequence exchange into the framework of different ancestral DRB1 sequences. Allelic polymorphism at the DRB1 locus may thus have been generated in part by combining different variants of the two structural domains.
Gyllensten
U B
UB
Department of Medical Genetics, University of Uppsala, Sweden.
Sundvall
M
M
Erlich
H A
HA
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005091:Exons; D006071:Gorilla gorilla / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics / Q000276:immunology; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011323:Primates / Q000235:genetics* / Q000382:microbiology; D011487:Protein Conformation; D011995:Recombination, Genetic
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II