The decline of human endogenous retroviruses: extinction and survival

Abstract

BackgroundEndogenous Retroviruses (ERVs) are retroviruses that over the course of evolution have integrated into germline cells and eventually become part of the host genome. They proliferate within the germline of their host, making up ~5% of the human and mouse genome sequences. Several lines of evidence have suggested a decline in the rate of ERV integration into the human genome in recent evolutionary history but this has not been investigated quantitatively or possible causes explored.ResultsBy dating the integration of ERV loci in 40 mammal species, we show that the human genome and that of other hominoids (great apes and gibbons) have experienced an approximately four-fold decline in the ERV integration rate over the last 10 million years. A major cause is the recent extinction of one very large ERV lineage (HERV-H), which is responsible for most of the integrations over the last 30 million years. The decline however affects most other ERV lineages. Only about 10% of the decline might be attributed to an accompanying increase in body mass (a trait we have shown recently to be negatively correlated with ERV integration rate). Humans are unusual compared to related species – Old World monkeys, great apes and gibbons – in (a) having not acquired any new ERV lineages during the last 30 million years and (b) the possession of an old ERV lineage that has continued to replicate up until at least the last few hundred thousand years – the potentially medically significant HERVK(HML2).ConclusionsThe human genome shares with the genome of other great apes and gibbons a recent decline in ERV integration that is not typical of other primates and mammals. The human genome differs from that of related species both in maintaining up until at least recently a replicating old ERV lineage and in not having acquired any new lineages. We speculate that the decline in ERV integration in the human genome has been exacerbated by a relatively low burden of horizontally-transmitted retroviruses and subsequent reduced risk of endogenization.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-015-0136-x) contains supplementary material, which is available to authorized users.

Cross-species transmission and differential fate of an endogenous retrovirus in three mammal lineages

“…Such ‘empty’ site can be corroborated by the presence of a single copy of the host target sequence duplicated upon proviral integration (typically 4-bp target site duplication for gammaretroviruses). This cross-species presence/absence approach has been widely applied to date a variety of mobile element insertions, including ERVs [14,41,58,59].…”

Intact piRNA pathway prevents L1 mobilization in male meiosis

“…SINEs are nonautonomous elements and rely on L1's proteins for propagation in the genome (4). LTR retrotransposons are autonomous but appear to be inactivated in the human genome (5). Retrotransposition endangers the integrity of both somatic and germline genomes through insertional mutagenesis.…”

On the classification and evolution of endogenous retrovirus: human endogenous retroviruses may not be ‘human’ after all

“…Further evidence supporting the diversification and expansion of HERVs in catarrhines has been proven by microarray screening for the HERV polymerase gene ( pol ) within the primate lineage showing that platyrrhines appear to either lack or have only low copy numbers of the human‐primate shared HERV sequences (with a pol gene) . In terms of infection dynamics, it is of interest that the human genome displays a recent decline in ERV integration rate compared to other primates (hominoids and Old World Monkeys) and mammals .…”