Endogenous retroviruses of non-avian/mammalian vertebrates illuminate diversity and deep history of retroviruses

Abstract

The deep history and early diversification of retroviruses remains elusive, largely because few retroviruses have been characterized in vertebrates other than mammals and birds. Endogenous retroviruses (ERVs) documented past retroviral infections and thus provide ‘molecular fossils’ for studying the deep history of retroviruses. Here we perform a comprehensive phylogenomic analysis of ERVs within the genomes of 92 non-avian/mammalian vertebrates, including 72 fishes, 4 amphibians, and 16 reptiles. We find that ERVs are present in all the genomes of jawed vertebrates, revealing the ubiquitous presence of ERVs in jawed vertebrates. We identify a total of >8,000 ERVs and reconstruct ~450 complete or partial ERV genomes, which dramatically expands the phylogenetic diversity of retroviruses and suggests that the diversity of exogenous retroviruses might be much underestimated in non-avian/mammalian vertebrates. Phylogenetic analyses show that retroviruses cluster into five major groups with different host distributions, providing important insights into the classification and diversification of retroviruses. Moreover, we find retroviruses mainly underwent frequent host switches in non-avian/mammalian vertebrates, with exception of spumavirus-related viruses that codiverged with their ray-finned fish hosts. Interestingly, ray-finned fishes and turtles appear to serve as unappreciated hubs for the transmission of retroviruses. Finally, we find retroviruses underwent many independent water-land transmissions, indicating the water-land interface is not a strict barrier for retrovirus transmission. Our analyses provide unprecedented insights into and valuable resources for studying the diversification, key evolutionary transitions, and macroevolution of retroviruses.

Nomenclature for endogenous retrovirus (ERV) loci

“…Software tools have also been developed specifically to assist in the identification and characterization of ERVs (for instance, see [ 56 – 58 ]), and these, more focused systems can be used to map ERVs to a fine scale of detail, demarcating genes, protein domains, and functional RNA sequences [ 6 , 59 ]. Unfortunately, however, there is currently no straightforward way to link the ERV annotations generated by distinct systems with one another, or with the taxonomic groupings of ERVs that have been defined in broad-based phylogenetic studies [ 27 , 28 , 45 , 60 – 62 ].…”

Six new reference-quality bat genomes illuminate the molecular basis and evolution of bat adaptations

“…Additionally, we detected ERV sequences with hits for alpha- and lenti-retroviruses in reciprocal BLAST searches. Until now, alpharetroviruses were considered as exclusively endogenous avian viruses 92 . Thus, our discovery of endogenous alpharetroviral-like elements in bats is the first record of these sequences in mammalian genomes, widening the known biodiversity of potential hosts for retrovirus transmission.…”

A Reptilian Endogenous Foamy Virus Sheds Light on the Early Evolution of Retroviruses

“…Retroviruses (family Retroviridae ) are viruses of major medical significance as some are associated with severe infectious disease or are oncogenic (Hayward, et al 2015; Aiewsakun and Katzourakis 2017; Xu, et al 2018). Retroviruses are also of note because of their ability to integrate into the host germ-line, generating endogenous retroviruses (ERVs) that then exhibit Mendelian inheritance (Stoye 2012; Johnson 2015).…”

“…Retroviruses are also of note because of their ability to integrate into the host germ-line, generating endogenous retroviruses (ERVs) that then exhibit Mendelian inheritance (Stoye 2012; Johnson 2015). ERVs are widely distributed in vertebrates (Hayward, et al 2013; Cui, et al 2014; Hayward, et al 2015; Xu, et al 2018) and constitute important molecular “fossils” for the study of retrovirus evolution. ERVs related to all seven major retroviral genera have been described, although some of the more complex retroviruses, such as lenti-, delta- and foamy viruses, rarely appear as endogenous copies.…”

“…The discovery of a EFV in the coelacanth genome indicated that foamy viruses could have an ancient evolutionary history (Han and Worobey 2012a), likely co-diverging with their vertebrate hosts over time-scales of hundreds of million years (Aiewsakun and Katzourakis 2017). Although EFVs or foamy-like elements have been reported in fish, amphibians and mammals, they have currently not been reported in genomes of two other major classes of vertebrates - reptiles and birds (Tristem, et al 1995; Hayward, et al 2015; Xu, et al 2018).…”