Different evolutionary histories in two subgenomic regions of the major histocompatibility complex

Two subgenomic regions within the major histocompatibility complex, the alp ha and beta blocks, contain members of the multicopy gene families HLA clas s I, human endogenous retroviral sequence (HERV-16; previously known as P5 and PERB3), hemochromatosis candidate genes (HCG) (II, IV, VIII, IX), 3.8-1 , and MIC (PERB11). In this study we show that the two blocks consist of im perfect duplicated segments, which contain linked members of the different gene families. The duplication and truncation sites of the segments are ass ociated with retroelements. The retroelement sites appear to generate the i mperfect duplications, insertions/deletions, and rearrangements, most likel y via homologous recombination. Although the two blocks share several chara cteristics, they differ in the number and orientation of the duplicated seg ments. On the 62.1 haplotype, the alpha block consists of at least 10 dupli cated segments that predominantly contain pseudogenes and gene fragments of the HLA class I and MIC (PERB11) gene families. In contrast, the beta bloc k has two major duplications containing the genes HLA-B and HLA-C, and MICA (PERB11.1) and MICE (PERB11.2). Given the common origin between the blocks , we reconstructed the duplication history of the segments to understand th e processes involved in producing the different organization in the two blo cks. We then found that the beta block contains four distinct duplications from two separate events, whereas the alpha block is characterized by multi segment duplications. We will discuss these results in relation to the gene tic content of the two blocks.