Structural comparison of the genes of two HLA-DR supertypic groups: The loci encoding DRw52 and DRw53 are not truly allelic

Abstract

The organization and sequence of the HLA-DR _β chain genes are compared in the two supertypic groups, DRw52 and DRw53, which together account for more than 80% of HLA-DR alleles. From the structural data, we conclude that these two groups represent distinct lineages which have followed different patterns of evolution. The fine structure of the β chain locus encoding the DRw53 specificity corresponds most closely to the DR _βII pseudogene in the DRw52 haplotypes. Concomitantly, the DR _βI locus in DRw53 haplotypes is more closely related to both of the two expressed DR _β loci of theDRw5 haplotypes (DR _βI and DR _β III). These two loci are the result of a recent duplication. This leads to the proposal that both expressed DR _β chain genes in the DRw52 haplotypes (DR _βI and DR _βIII) are derived from a single precursor locus, while the two loci expressed in the DRw53 haplotypes are derived from distinct ancestral loci. The genes encoding DRw52 and DRw53 are therefore not true alleles of the same original locus. A scheme is proposed that accounts for the evolution of DR specificities within the DRw52 and DRw53 groups of haplotypes. It is evident that the differentHLA-DR alleles are not structurally equidistant and that one must take into consideration different degrees of heterozygosity or mismatch among the DR alleles.