Using Alu J elements as molecular clocks to trace the evolutionary relationships between duplicated HLA class I genomic segments

The class I region of the major histocompatibility complex contains two sub genomic blocks (250-350 kb each), known as the alpha and beta blocks. These blocks contain members of multicopy gene families including HLA class I, H ERV-16 (previously called P5 sequences), and PERB 11 (MIC). We have previou sly shown that each block consists of imperfect duplicated segments (duplic ons) containing linked members of different gene families, retroelements an d transposons that have coevolved as part of two separate evolutionary even ts. Another region provisionally designated here as the kappa block is loca ted between the alpha and the beta blocks and contains HLA-E, -30, and -92, HERV-16 (P5.3), and PERB11.3 (MICC) within about 250 kb of sequence. Using Alu elements to trace the evolutionary relationships between different cla ss I duplicons, we have found that (a) the kappa block contains paralogous (duplicated) Alu J sequences and other retroelement patterns more in common with the beta than the alpha block; (b) the retroelement pattern associate d with the HLA-E duplicon is different from all other HLA class I duplicons , indicating a more complex evolution; (c) the HLA-92 duplicon, although su bstantially shorter, is closely related in sequence to the HLA-B and -C dup licons; (d) two of the six paralogous Alu J elements within the HLA-B and - C duplicons are associated with the HLA-X duplicon, confirming their evolut ionary relationships within the beta block; and (e) the paralogous Alu J el ements within the alpha block are distinctly different from those identifie d within the beta and kappa blocks. The sequence conservation and location of duplicated (paralogous) Alu J elements in the MHC class I region show th at the beta and kappa blocks have evolved separately from the alpha block b eginning at a time before or during the evolution of Alu J elements in prim ates.