Complex Origin of the HLA-DR10 Haplotype

The region of the HLA complex occupied by the DRB genes has undergone many rearrangements in the course of primate evolution. The rearrangements have produced a number of haplotypes differing from one another in the number and composition of the DRB genes. Some of the rearrangements also affected the DRB genes themselves. Selective intron sequencing has revealed the DR10 haplotype to be composed of at least three segments, each of different origin. The haplotype carries three DRB genes (gene fragments): DRB1*10, DRB6, and DRB9. The 5′ end of the DRB1*10 gene, from the promoter region to a site in intron 1 approximately 500 bp from the beginning of exon 2, is derived from a DRB1*03-like gene. The segment of the DR10 haplotype encompassing the rest of the DRB1*10 gene and extending to the region between the DRB1 and DRB6 genes is of independent origin; it diverged from other DRBgenes (DRB1*01 and DRB1*03) approximately 30 million years ago. Finally, the third segment encompassing the remainder of the DR10 haplotype is derived from a DR1-like haplotype. Since the functional part of the DR10 haplotype is of independent origin, there is little justification for the currently common practice of placing the haplotype together with DR1 in the group of DR1 haplotypes. The rearrangements in the DR haplotypes may constitute one of several mechanisms for increasing diversity at the DRB loci. The region of high instability seems to be flanked by conservatively evolving regions.