Coevolution of PERB11 (MIC) and HLA class I genes with HERV-16 and retroelements by extended genomic duplication

The recent availability of genomic sequence information for the class I reg ion of the MHC has provided an opportunity to examine the genomic organizat ion of HLA class I (HLAcI) and PERB11/MIC genes with a view to explaining t heir evolution from the perspective. of extended genomic duplications rathe r than by simple gene duplications and/or gene conversion events. Analysis of genomic sequence from two regions of the MHC (the alpha- and beta-blocks ) revealed that at least 6 PERB11 and 14 HLAcI genes, pseudogenes, and gene fragments are contained within extended duplicated segments. Each segment was searched for the presence of shared (paralogous) retroelements by Repea tMasker in order to use them as markers of evolution, genetic rearrangement s, and evidence of segmental duplications. Shared Alu elements and other re troelements allowed the duplicated segments to be classified into five dist inct groups (A to E) that could be further distilled down to an ancient pre duplication segment containing a HLA and PERB11 gene, an endogenous retrovi rus (HERV-16), and distinctive retroelements. The breakpoints within and be tween the different HLAcI segments were found mainly within the PERB11 and HLA genes, HERV-16, and other retroelements, suggesting that the latter hav e played a major role in duplication and indel events leading to the presen t organization of PERB11 and HLAcI genes. On the basis of the features cont ained within the segments, a coevolutionary model premised on tandem duplic ation of single and multipartite genomic segments is proposed. The model is used to explain the origins and genomic organization of retroelements, HER V-16, DNA transposons, PERB11, and HLAcI genes as distinct segmental combin ations within the alpha- and beta-blocks of the human MHC.