title: Comparison between two human endogenous retrovirus (HERV)-rich regions within the major histocompatibility complex.
abstract: Sixteen human endogenous retrovirus (HERV) sequences were detected within 656 kb of genomic sequence obtained from the alpha- and beta-block of the class I region of the major histocompatibility complex (MHC). The HERVs were identified and characterized as family members of HERV-16 (11 copies), HERV-L (1 copy), HERV-I (2 copies), HERV-K91 (1 copy), and HARLEQUIN (1 copy) by sequence comparison using CENSOR or Repeat Masker, BLAST searches, and dot plots. The 11 copies of HERV-16 arose as products of duplication of genomic segments containing HLA class I (HLAcI) and PERB11 (MIC) genes inter alia, whereas the other five HERVs arose after duplication probably as a consequence of single insertion events or translocations. HERV-L and HERV-I are located between the duplicated genes PERB11.2 (MICB) and PERB11.1 (MICA), and HLA-B and HLA-C, respectively, whereas HERV-K91 and HARLEQUIN are located telomeric of HLA-C. A highly fragmented copy of HERV-I was also found telomeric of PERB11. 4. Structural analysis of open reading frames (ORFs) revealed the absence of intact coding sequence within the putative gag, pol, and env gene regions of all the HERVs with the exception of HERV-K91, which had two large ORFs within the region of the putative protease and pol genes. In addition, the 5'-LTR of HERV-L contained a 2.5-kb element that was AT-rich and large ORFs with putative amino acid sequences rich in tyrosines and isoleucines. HERV-I, HARLEQUIN, and at least four copies of HERV-16 appear to have been receptors for the insertion of other retrotransposons including Alu elements and fragments of L1 and THE1. Examination of flanking sequences suggests that HERV-I and HERV-L had occurred by insertion into ancient L1 fragments. This study has revealed that the alpha- and beta-block region within the MHC is rich in HERV sequences occurring at a much higher ratio (10 to 1) than normally observed in the human genome. These HERV sequences will therefore enhance further studies on disease associations and differences between human haplotypes and primates and their role in the evolution of class I genes in the MHC.
authors.affiliation: Centre for Molecular Immunology and Instrumentation, University of Western Australia, Faculty of Medicine and Dentistry, P.O. Box 5100, Canning Vale, 6155, Western Australia, Australia. jkulski@cyllene.uwa.
authors.forename: J K
authors.initials: JK
authors.lastname: Kulski
authors.forename: S
authors.initials: S
authors.lastname: Gaudieri
authors.forename: H
authors.initials: H
authors.lastname: Inoko
authors.forename: R L
authors.initials: RL
authors.lastname: Dawkins
mesh_terms: D000595:Amino Acid Sequence; D020077:Endogenous Retroviruses / Q000235:genetics*; D018628:Gene Dosage; D015236:HLA-C Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D016366:Open Reading Frames; D011506:Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D018626:Retroelements; D012984:Software
chemical_list: C089801:HCG9 non-protein coding RNA, human; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D018626:Retroelements