Evolutionary relationship between human major histocompatibility complex HLA-DR haplotypes

HLA-DR haplotypes of the human major histocompatibility complex are organized in five different groups. They can be identified based on the serological specificity expressed by the polymorphicDRB1 locus and by the presence of a characteristic set ofDRB genes. The nucleotide sequences of introns 4 and 5 of the twoDRB genes (DRB1 *01 andDRB6 *01) from aDR1 haplotype and the threeDRB genes (DRB1 *15, DRB6*15, andDRB5 *15), from aDR51 haplotype were determined. This study identified endogenous retrovial long terminal repeat elements (ERV9 LTR) located at identical positions in intron 5 of theDRB1 genes in both theDR1 andDR51 haplotypes. Phylogenetic analyses revealed a close evolutionary relationship between these two haplotypes. TheDRB5 gene, unique for theDR51 haplotype, may have been lost by a recent gene deletion event creating theDR1 haplotype. A model for the evolution of the humanDR haplotypes involving separate duplication and contraction events is presented.