Paleogenomic Record of the Extinction of Human Endogenous Retrovirus ERV9

Abstract

An outstanding question of genome evolution is what stops the invasion of a host genome by transposable elements (TEs). The human genome, harboring the remnants of many extinct TE families, offers an extraordinary opportunity to investigate this problem. ERV9 is an endogenous retrovirus repeatedly mobilized during primate evolution, 15 to 6 million years ago (MYA), which left a trace of over a hundred provirus-like copies and at least 4,000 solitary long terminal repeats (LTRs) in the human genome. Then, its proliferation ceased for unknown reasons, and the family went extinct. We have made a detailed reconstruction of its last active subfamily, ERV9_XII, by examining 115 solitary LTRs from it. These insertions were grouped into 11 sets according to shared nucleotide variants, which could be placed in a sequential order of 10 to 6 MYA. At least 75% of the subfamily was produced 8 to 6 MYA, during a stage of intense proliferation. With new analytical tools, we show that the youngest and most prolific sets may have been produced by effectively instantaneous expansions of corresponding single-sequence variants. The extinction of this family apparently was not a consequence of its slow gradual degeneration, but the outcome of the fixation of specific restrictive alleles in the human-chimpanzee ancestral population. Three species-specific insertions (two in humans and one in chimpanzees) were identified, further supporting that extinction took place when these two species were beginning to diverge. These are the only fixed differences of this kind so far observed between humans and chimpanzees, apart from those belonging to the human endogenous retrovirus K family.

Endogenous retrovirus drives hitherto unknown proapoptotic p63 isoforms in the male germ line of humans and great apes

“…This theory is supported by previous paleogenomic analysis indicating that ERV9 underwent repeated mobilization when great apes (hominids) branched off from other primate lineages (18). The GTAp63-associated LTR is most closely related to subfamily IX of ERV9 sequences, which emerged 18 to 19 million years ago (19) (Fig.…”

Comprehensive identification of genes driven by ERV9-LTRs reveals TNFRSF10B as a re-activatable mediator of testicular cancer cell death

“…Consistently, there were 'outbreaks' of ERV9 mobilization during recent primate evolution. 6,27,53 Nonetheless, we propose that at least a subset of ERV9 insertions were beneficial for the host, allowing enhanced germline protection in the face of prolonged lifetime and fertility of male individuals, as compared with more ancient primates. The work presented here suggests that this ERV9-LTR-driven cell death U Beyer et al association of ERV9 with such surveillance genes has occurred more than once, perhaps representing a prerequisite for human evolution.…”

“…The spread of ERV9 through the genome occurred fairly recently, in a period when higher primates were arising. 27 In the case of GTAp63, we had previously raised the hypothesis that LTR insertion occurred concomitantly with the development of hominids, perhaps facilitating the maintenance of their genome in the male germline. 3 Here, we tested at which evolutionary stage the insertion of the LTR upstream of TNFRSF10B occurred.…”

Expression Profiles of Endogenous Retroviruses in Old World Monkeys

“…Members of the HERV-K family have been identified as potentially transpositionally active and polymorphic in human populations (2,8,36). Thus, at the DNA level, HERV evolution involves both vertical transmission and de novo integration of elements by retrotransposition or reinfection, whether looking within or among species (3,4,26). However, the majority of elements integrated before the OWM and great ape lineages diverged and thus have a similar genomic distribution pattern among catarrhines (16,10,27).…”