Zsíros J, Jebbink M F, Lukashov V V, Voûte P A, Berkhout B
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
J Mol Evol. 1999 Jan;48(1):102-11. doi: 10.1007/pl00006437.
The human genome contains a large number of sequences that belong to the HERV-K family of human endogenous retroviruses. Most of these elements are likely remnants of ancient infections by ancestral exogenous retroviruses. To obtain further insight into the evolutionary history and molecular mechanisms responsible for the diversity of the human HERV-K elements, we analyzed several aspects of their genome structure. The nucleotide composition of the HERV-K genome was found to be highly biased and asymmetric, with an abundance of the A nucleotide in the viral (+) strand. A similar trend has been reported for the genomes of several exogenous retroviruses, with different nucleotides as the preferred building block. Other genome characteristics that were reported previously for actively replicating retroviruses are also apparent for the endogenous HERV-K virus. In particular, we observed suppression of the dinucleotide CpG, which represents potential methylation sites, and a strong preference for synonymous substitutions within the open reading frame of the reverse transcriptase (RT) enzyme. Furthermore, the mutational spectrum of the HERV-K RT enzyme was evaluated by nucleotide sequence comparison of 34 available elements. Interestingly, this analysis revealed a striking similarity with the mutational pattern of the HIV-1 RT enzyme, with a preference for G-to-A and C-to-T transitions. It is proposed that the mutational bias of the HERV-K RT enzyme played a role in the shaping of this retroviral genome, which was actively replicating more than 30 million years ago. This effect can still be observed in the contemporary endogenous HERV-K elements.
人类基因组包含大量属于人类内源性逆转录病毒HERV-K家族的序列。这些元件中的大多数可能是祖先外源性逆转录病毒古代感染的残余物。为了进一步深入了解人类HERV-K元件多样性的进化历史和分子机制，我们分析了它们基因组结构的几个方面。发现HERV-K基因组的核苷酸组成高度偏向且不对称，病毒（+）链中A核苷酸丰富。对于几种外源性逆转录病毒的基因组也报道了类似的趋势，以不同的核苷酸作为首选构建块。先前报道的活跃复制逆转录病毒的其他基因组特征在内源性HERV-K病毒中也很明显。特别是，我们观察到代表潜在甲基化位点的二核苷酸CpG受到抑制，并且在逆转录酶（RT）酶的开放阅读框内对同义替换有强烈偏好。此外，通过对34个可用元件的核苷酸序列比较评估了HERV-K RT酶的突变谱。有趣的是，该分析揭示了与HIV-1 RT酶的突变模式有惊人的相似性，偏好G到A和C到T的转换。有人提出，HERV-K RT酶的突变偏向在这种逆转录病毒基因组的形成中起作用，这种逆转录病毒在3000多万年前活跃复制。这种效应在当代内源性HERV-K元件中仍然可以观察到。
