Sequence variability, gene structure, and expression of full-length human endogenous retrovirus H
Sequence variability, gene structure, and expression of full-length human endogenous retrovirus H
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DOI：
10.1128/jvi.79.10.6325-6337.2005
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发表时间：
2005-05-01
影响因子：
5.4
通讯作者：
Blomberg, J
中科院分区：
文献类型：
--
作者：
Jern, P;Sperber, GO;Blomberg, J
最近，我们在人类基因组中鉴定并分类了926个人类内源性逆转录病毒H（HERV-H）样前病毒。在本文中，我们使用的信息，在硅片上，重建一个假定的祖先HERV-H。计算的共有序列在所有基因中几乎是开放的。经过一些手动调整，产生了推定的9-kb HERV-H前病毒，其在gag、pro、pol和env中具有开放阅读框（ORF）。长末端重复序列（LTR）相差1.1%，表明接近整合事件。gag ORF延伸到正常肉豆蔻基化起始位点的上游。有一个长的前导序列（包括一个"pre-gag" ORF）区域，位置类似于鼠白血病病毒（MLV）"glyco-Gag"的N末端，可能编码一个与MLV pp12远程相似的富含脯氨酸和丝氨酸的结构域。另一个ORE，在5'LTR内开始，与已知的蛋白质结构域没有明显的相似性。与迄今为止描述的其他γ逆转录病毒不同，重建的Gag具有两个锌指基序。使用dbEST数据证实了与HERV-H共有序列相关的可变剪接。env转录本在结肠肿瘤中最普遍，但也在正常睾丸中。我们在dbEST中没有发现全长env转录本的证据。HERV-H的核苷酸组成明显偏态，不利于鸟嘌呤，有利于胞苷。我们的结论是，HERV-H共有的基因排列与γ逆转录病毒共有，gag与pro-pol在同一阅读框中被终止密码子隔开，而env位于另一个阅读框中。还有选择性剪接。HERV-H共识在γ逆转录病毒进化中产生了新的见解，并将作为表达和功能研究的模型。
Recently, we identified and classified 926 human endogenous retrovirus H (HERV-H)-like proviruses in the human genome. In this paper, we used the information to, in silico, reconstruct a putative ancestral HERV-H. A calculated consensus sequence was nearly open in all genes. A few manual adjustments resulted in a putative 9-kb HERV-H provirus with open reading frames (ORFs) in gag, pro, pol, and env. Long terminal repeats (LTRs) differed by 1.1%, indicating proximity to an integration event. The gag ORF was extended upstream of the normal myristylation start site. There was a long leader (including a "pre-gag" ORF) region positioned like the N terminus of murine leukemia virus (MLV) "glyco-Gag," potentially encoding a proline- and serine-rich domain remotely similar to MLV pp12. Another ORE, starting inside the 5' LTR, had no obvious similarity to known protein domains. Unlike other hitherto described gammaretroviruses, the reconstructed Gag had two zinc finger motifs. Alternative splicing of sequences related to the HERV-H consensus was confirmed using dbEST data. env transcripts were most prevalent in colon tumors, but also in normal testis. We found no evidence for full length env transcripts in the dbEST. HERV-H had a markedly skewed nucleotide composition, disfavoring guanine and favoring cytidine. We conclude that the HERV-H consensus shared a gene arrangement common to gammaretroviruses with gag separated by stop codon from pro-pol in the same reading frame, while env resides in another reading frame. There was also alternative splicing. HERV-H consensus yielded new insights in gammaretroviral evolution and will be useful as a model in studies on expression and function.