ABSTRACT
Endogenous retroviruses (ERVs) are integrated into host DNA as the result of ancient germ line infections, primarily by extinct exogenous retroviruses. Thus, vertebrates' genomes contain thousands of ERV copies, providing a "fossil" record for ancestral retroviral diversity and its evolution within the host genome. Like other retroviruses, the ERV proviral sequence consists of gag, pro, pol, and env genes flanked by long terminal repeats (LTRs). Particularly, the env gene encodes for the envelope proteins that initiate the infection process by binding to the host cellular receptor(s), causing membrane fusion. For this reason, a major element in understanding ERVs' evolutionary trajectory is the characterization of env changes over time. Most of the studies dedicated to ERVs' env have been aimed at finding an "actual" physiological or pathological function, while few of them have focused on how these genes were once acquired and modified within the host. Once acquired into the organism, genome ERVs undergo common cellular events, including recombination. Indeed, genome recombination plays a role in ERV evolutionary dynamics. Retroviral recombination events that might have been involved in env divergence include the acquisition of env genes from distantly related retroviruses, env swapping facilitating multiple cross-species transmission over millions of years, ectopic recombination between the homologous sequences present in different positions in the chromosomes, and template switching during transcriptional events. The occurrence of these recombinational events might have aided in shaping retroviral diversification and evolution until the present day. Hence, this review describes and discusses in detail the reported recombination events involving ERV env to provide the basis for further studies in the field.
ABSTRACT
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 Macaca fascicularis and Macaca mulatta which are the most evolutionarily distant species related to humans in the Catarrhini parvorder. We identified overall 208 HML2 proviruses for M. fascicularis (77) and M. mulatta (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 gag, pol, and env genes for the latter being reported to be expressed in human pathological conditions. The analysis identified highly conserved gag and pol genes, while the env 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 env 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 env 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 Catarrhini parvorder, leading to the emergence of viral variants, hence providing a better understanding of the endogenization and diffusion of HML2 along primate evolution.
