ERV Project Background
The Lentivirus-GLUE-ERV project is an extension to Lentivirus-GLUE that incorporates data from endogenous retroviruses (ERVs).
ERVs are retrovirus-derived DNA sequences that occur in the germline genomes of host species. ERVs arise when retroviruses infect germline cells (i.e. spermatozoa, eggs, or early embryonic cells) so that integrated retrovirus DNA is vertically inherited as a novel host allele.
This project layer extends Lentivirus-GLUE through the incorporation of endogenous retrovirus (ERV) sequence data.
For many years, the scientific consensus was that lentiviruses---the retroviral genus that includes HIV---did not leave a fossil record in the genomes of their hosts. Endogenous retroviruses (ERVs) derived from other retroviral genera, such as Gammaretrovirus and Betaretrovirus, are widespread and well-documented, but no evidence of lentiviral ERVs had been found. This absence, combined with the extraordinary evolutionary speed observed in HIV during the HIV/AIDS pandemic, led many researchers to infer that lentiviruses were a relatively recent addition to the retroviral family, and might possibly have emerged within a timescale of thousands, rather than millions of years.
This view began to shift in 2007 with the publication of the European rabbit genome, which revealed the presence of rabbit endogenous lentivirus K (RELIK). RELIK was not an isolated curiosity; its presence in multiple leporid species demonstrated that this lentivirus had integrated into the genome of an ancient common ancestor at least 12 million years ago. This discovery provided definitive proof that lentiviruses have existed for far longer than previously assumed, upending the idea that they were a recent evolutionary phenomenon.
Since the discovery of RELIK, additional endogenous lentiviruses have been identified in a variety of mammals, including lemurs, mustelids, colugos, and springhares. These findings have painted a more nuanced picture of lentiviral evolution. While endogenous lentiviruses remain rare compared to those of other retroviral genera, their existence shows that lentiviruses have been infecting mammals for millions of years, occasionally leaving behind genomic fossils that offer invaluable insights into their ancient diversity and host-virus interactions.
The rarity of endogenous lentiviruses raises intriguing questions about their biology and evolutionary history. Perhaps their genomic integration is less frequent or less likely to be preserved than that of other retroviruses. Alternatively, their sequences may degrade more rapidly due to evolutionary pressures, or their presence may be underrepresented in the genomes that have been studied to date. Regardless, the identification of these rare remnants has fundamentally reshaped our understanding of the lentivirus genus, pushing its origins back into deep evolutionary time.
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Phylogenetic relationships within the Lentivirus genus. Maximum likelihood phylogeny showing reconstructed evolutionary relationships between all known lentivirus species, including the extinct species represented by endogenous lentiviruses. Brackets to the left indicate proposed subgroupings within genus Lentivirus. Coloured circles adjacent virus taxa labels indicate the ecological characteristics of the associated host species (grassland-dwelling or arboreal) as shown in the key top right. The scale bar shows evolutionary distance in substitutions per site. Asterisks indicate nodes with bootstrap support > 70% (1000 replicates). Arrows indicate genome evolution events as follows (1) acquisition of tat, rev and vif genes (putatively); (2) loss of dUTPase; (3) partial loss of dUTPase. Abbreviations: FIV = Feline immunodeficiency virus; SRLV = small ruminant lentivirus; BIV = Bovine immunodeficiency virus; RELIK = Rabbit endogenous lentivirus type K; EIAV = equine infectious anaemia virus; MELV = Mustelidae endogenous lentivirus; SIV = Simian immunodeficiency virus; PSIV = Prosimian immunodeficiency virus; DELV = Dermopteran endogenous lentivirus; SpELV = springhare endogenous lentivirus
ERVs provide a unique source of retrospective information about the long-term history and retroviruses and their hosts. ERVs derived from lentiviruses are very rare, and for decades they were assumed not to occur. However, whole genome sequencing of vertebrates in the 2000s led to the discovery of lentivirus-derived ERV insertions derived in a variety of species genomes.
Progress in characterising ERVs has been hampered by the challenges encountered attempting to analyse their fragmentary and degenerated sequences. This greatly complicates comparative genomic analysis. Lentivirus-GLUE aims to address these issues for lentiviral ERVs. it applies a set of programmatic principles for systematically organising and refining the ERV 'fossil record'.