Grandi Nicole, Pisano Maria Paola, Pessiu Eleonora, Scognamiglio Sante, Tramontano Enzo
Laboratory of Molecular Virology, Department of Life and Environmental Sciences, University of Cagliari, 09042 Monserrato, Cagliari, Italy.
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), 09042 Monserrato, Cagliari, Italy.
Biology (Basel). 2021 May 14;10(5):439. doi: 10.3390/biology10050439.
Endogenous Retroviruses (ERVs) are ancient relics of infections that affected the primate germ line and constitute about 8% of our genome. Growing evidence indicates that ERVs had a major role in vertebrate evolution, being occasionally domesticated by the host physiology. In addition, human ERV (HERV) expression is highly investigated for a possible pathological role, even if no clear associations have been reported yet. In fact, on the one side, the study of HERV expression in high-throughput data is a powerful and promising tool to assess their actual dysregulation in diseased conditions; but, on the other side, the poor knowledge about the various HERV group genomic diversity and individual members somehow prevented the association between specific HERV loci and a given molecular mechanism of pathogenesis. The present study is focused on the HERV-K(HML7) group that-differently from the other HERV-K members-still remains poorly characterized. Starting from an initial identification performed with the software RetroTector, we collected 23 HML7 proviral insertions and about 160 HML7 solitary LTRs that were analyzed in terms of genomic distribution, revealing a significant enrichment in chromosome X and the frequent localization within human gene introns as well as in pericentromeric and centromeric regions. Phylogenetic analyses showed that HML7 members form a monophyletic group, which based on age estimation and comparative localization in non-human primates had its major diffusion between 20 and 30 million years ago. Structural characterization revealed that besides 3 complete HML7 proviruses, the other group members shared a highly defective structure that, however, still presents recognizable functional domains, making it worth further investigation in the human population to assess the presence of residual coding potential.
内源性逆转录病毒（ERVs）是影响灵长类种系的感染的古老遗迹，约占我们基因组的8%。越来越多的证据表明，ERVs在脊椎动物进化中发挥了重要作用，偶尔会被宿主生理机制驯化。此外，即使尚未报道明确的关联，但人类内源性逆转录病毒（HERV）的表达因其可能的病理作用而受到高度研究。事实上，一方面，在高通量数据中研究HERV表达是评估其在疾病状态下实际失调的有力且有前景的工具；但另一方面，对各种HERV基因组多样性和个体成员的了解不足，在某种程度上阻碍了特定HERV位点与特定发病机制分子机制之间的关联。本研究聚焦于HERV-K（HML7）组，与其他HERV-K成员不同，该组的特征仍不清楚。从使用RetroTector软件进行的初步鉴定开始，我们收集了23个HML7前病毒插入序列和约160个HML7孤立长末端重复序列（LTRs），并对其基因组分布进行了分析，结果显示在X染色体上有显著富集，且频繁定位于人类基因内含子以及着丝粒周围和着丝粒区域。系统发育分析表明，HML7成员形成一个单系群，根据年龄估计和在非人类灵长类动物中的比较定位，其主要扩散发生在2000万至3000万年前。结构特征表明，除了3个完整的HML7前病毒外，其他组成员共享高度缺陷的结构，然而，该结构仍呈现出可识别的功能域，这使得有必要在人类群体中进一步研究，以评估残留编码潜力的存在情况。
