Chabukswar Saili, Grandi Nicole, Tramontano Enzo
Laboratory of Molecular Virology, Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
Front Microbiol. 2022 Dec 1;13:1040792. doi: 10.3389/fmicb.2022.1040792. eCollection 2022.
Around 8% of the human genome comprises Human Endogenous Retroviruses (HERVs) acquired over primate evolution. Some are specific to primates such as HERV-K, consisting of 10 HML subtypes and including the most recently acquired elements. Particularly, HML2 is the youngest clade, having some human-specific integrations, and while it has been widely described in humans its presence and distribution in non-human primates remain poorly characterized. To investigate HML2 distribution in non-human primates, the present study focused on the characterization of HML2 integrations in and which are the most evolutionarily distant species related to humans in the parvorder. We identified overall 208 HML2 proviruses for (77) and (131). Among them, 46 proviruses are shared by the two species while the others are species specific. Only 12 proviruses were shared with humans, confirming that the major wave of HML2 diffusion in humans occurred after macaques' divergence. Phylogenetic analysis confirmed structural variations between HML2 macaques' species-specific proviruses, and the ones shared between macaques and humans. The HML2 loci were characterized in terms of structure, focusing on potential residual open reading frames (ORFs) for and genes for the latter being reported to be expressed in human pathological conditions. The analysis identified highly conserved and genes, while the genes had a very divergent nature. Of the 208 HML2 proviral sequences present in Macaca species, 81 sequences form a cluster having a MER11A, a characteristic HML8 LTR sequence, insertion in the env region indicating a recombination event that occurred between the HML2 gene and the HML8 LTR. This recombination event, which was shown to be present only in a subset of macaques' shared sequences and species-specific sequences, highlights a recent viral activity leading to the emergence of an variant specific to the Old World Monkeys (OWMs). We performed an exhaustive analysis of HML2 in two species of OWMs, in terms of its evolutionary history, structural features, and potential residual coding capacity highlighting recent activity of HML2 in macaques that occurred after its split from the parvorder, leading to the emergence of viral variants, hence providing a better understanding of the endogenization and diffusion of HML2 along primate evolution.
大约8%的人类基因组由在灵长类动物进化过程中获得的人类内源性逆转录病毒（HERV）组成。其中一些是灵长类动物特有的，如HERV-K，它由10个HML亚型组成，包括最近获得的元件。特别是，HML2是最年轻的进化枝，有一些人类特有的整合，虽然它在人类中已有广泛描述，但其在非人类灵长类动物中的存在和分布仍知之甚少。为了研究HML2在非人类灵长类动物中的分布，本研究重点对小猿亚目中与人类进化关系最远的 和 的HML2整合进行了特征分析。我们总共鉴定出了208个HML2前病毒，其中 有77个， 有131个。其中，46个前病毒为两个物种所共有，其他的则是物种特异性的。只有12个前病毒与人类共有，这证实了HML2在人类中的主要扩散浪潮发生在猕猴分化之后。系统发育分析证实了猕猴物种特异性前病毒与猕猴和人类共有的前病毒之间的结构差异。对HML2位点进行了结构特征分析，重点关注潜在的残留开放阅读框（ORF）以及 基因，后者据报道在人类病理状况下会表达。分析确定了高度保守的 和 基因，而 基因具有非常大的差异。在猕猴物种中存在的208个HML2前病毒序列中，81个序列形成一个簇，该簇在env区域有一个MER11A插入，MER11A是一种特征性的HML8 LTR序列，这表明在HML2 基因和HML8 LTR之间发生了重组事件。这一重组事件仅在猕猴共有序列和物种特异性序列的一个子集中出现，突出了最近导致旧世界猴（OWM）特异性 变体出现的病毒活动。我们对两种旧世界猴中的HML2进行了详尽分析，涉及其进化历史、结构特征和潜在的残留编码能力，突出了HML2在猕猴与小猿亚目分化后发生的近期活动，导致了病毒变体的出现，从而更好地理解了HML2在灵长类动物进化过程中的内源性和扩散情况。
