Paleogenomic Record of the Extinction of Human Endogenous Retrovirus ERV9

Abstract

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.