Kulski J K, Gaudieri S, Inoko H, Dawkins R L
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.
J Mol Evol. 1999 Jun;48(6):675-83. doi: 10.1007/pl00006511.
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.
在从主要组织相容性复合体（MHC）I类区域的α和β块获得的656 kb基因组序列中检测到16个人类内源性逆转录病毒（HERV）序列。通过使用CENSOR或Repeat Masker进行序列比较、BLAST搜索和点阵图，将这些HERV鉴定并表征为HERV - 16（11个拷贝）、HERV - L（1个拷贝）、HERV - I（2个拷贝）、HERV - K91（1个拷贝）和HARLEQUIN（1个拷贝）的家族成员。HERV - 16的11个拷贝是包含HLA I类（HLAcI）和PERB11（MIC）基因等的基因组片段重复的产物，而其他五个HERV可能是由于单个插入事件或易位导致重复后出现的。HERV - L和HERV - I分别位于重复基因PERB11.2（MICB）和PERB11.1（MICA）之间，以及HLA - B和HLA - C之间，而HERV - K91和HARLEQUIN位于HLA - C的端粒。在PERB11.4的端粒也发现了一个高度片段化的HERV - I拷贝。开放阅读框（ORF）的结构分析表明，除了HERV - K91在假定的蛋白酶和pol基因区域内有两个大的ORF外，所有HERV的假定gag、pol和env基因区域内均不存在完整的编码序列。此外，HERV - L的5'-LTR包含一个2.5 kb的元件，该元件富含AT，并且有大的ORF，其假定的氨基酸序列富含酪氨酸和异亮氨酸。HERV - I、HARLEQUIN和至少四个HERV - 16拷贝似乎是包括Alu元件以及L1和THE1片段在内的其他逆转录转座子插入的受体。侧翼序列的检查表明，HERV - I和HERV - L是通过插入到古老的L1片段中而出现的。这项研究表明，MHC内的α和β块区域富含HERV序列，其出现比例（10比1）远高于人类基因组中通常观察到的比例。因此，这些HERV序列将加强对疾病关联、人类单倍型与灵长类动物之间差异以及它们在MHC I类基因进化中的作用的进一步研究。
