Molecular fossils illuminate the evolution of retroviruses following a macroevolutionary transition from land to water

Abstract

The ancestor of cetaceans underwent a macroevolutionary transition from land to water early in the Eocene Period >50 million years ago. However, little is known about how diverse retroviruses evolved during this shift from terrestrial to aquatic environments. Did retroviruses transition into water accompanying their hosts? Did retroviruses infect cetaceans through cross-species transmission after cetaceans invaded the aquatic environments? Endogenous retroviruses (ERVs) provide important molecular fossils for tracing the evolution of retroviruses during this macroevolutionary transition. Here, we use a phylogenomic approach to study the origin and evolution of ERVs in cetaceans. We identify a total of 8,724 ERVs within the genomes of 25 cetaceans, and phylogenetic analyses suggest these ERVs cluster into 315 independent lineages, each of which represents one or more independent endogenization events. We find that cetacean ERVs originated through two possible routes. 298 ERV lineages may derive from retrovirus endogenization that occurred before or during the transition from land to water of cetaceans, and most of these cetacean ERVs were reaching evolutionary dead-ends. 17 ERV lineages are likely to arise from independent retrovirus endogenization events that occurred after the split of mysticetes and odontocetes, indicating that diverse retroviruses infected cetaceans through cross-species transmission from non-cetacean mammals after the transition to aquatic life of cetaceans. Both integration time and synteny analyses support the recent or ongoing activity of multiple retroviral lineages in cetaceans, some of which proliferated into hundreds of copies within the host genomes. Although ERVs only recorded a proportion of past retroviral infections, our findings illuminate the complex evolution of retroviruses during one of the most marked macroevolutionary transitions in vertebrate history.

The diversity and evolution of retroviruses: Perspectives from viral “fossils”

“…α , β , γ , δ , ε , Lenti -, and Spuma -represent A lpharetrovirus , Betaretrovirus , Gammaretrovirus , Deltaretrovirus , Epsilonretrovirus , Lentivirus , and Spumaretrovirinae , respectively. The dark blue and orange circles indicate the presence of corresponding exogenous retroviruses and ERVs based on literature ( Xu et al., 2018 ; Zheng et al., 2021 ; Hayward et al., 2015 ; Han and Worobey, 2012a , 2012b , 2012c , 2014 , 2015 ; Chen et al. 2019 , 2021a , 2021b ; Wang and Han, 2021a ).…”

“…Large-scale phylogenomic analyses show that ERVs are present in all the genomes of jawed vertebrates studied to date ( Hayward et al. 2013 , 2015 ; Xu et al., 2018 ; Zheng et al., 2021 ). Within jawless vertebrates, ERVs (later classified to endogenous lokiretroviruses) were also identified in sea lamprey ( Petromyzon marinus ) and Arctic lamprey ( Lethenteron camtschaticum ) ( Hayward et al., 2015 ; Xu et al., 2018 ; Wang and Han, 2021a ).…”

“…4 B). Clade Jin retroviruses (including gamma-related retroviruses) infect mammals, reptiles, and birds ( Xu et al., 2018 ; Zheng et al., 2021 ). Clade Mu retroviruses (including epsilon-related retroviruses) infect almost all jawed vertebrates ( Xu et al., 2018 ).…”

“…2016 , 2018 ; Farkašová et al., 2017 ; Xu et al., 2018 ; Chen et al. 2021a , 2021b ; Zheng et al., 2021 ). Clade Huo retroviruses (ERV-L and snakehead retrovirus related) infect all the major lineages of vertebrates ( Xu et al., 2018 ).…”

“…These endogenous lentiviruses invaded host genomes from 1.9 to 3.8 million years ago (Mya) (in Malagasy lemurs) to 21–40 Mya (in Colugo) ( Han and Worobey, 2012b , 2015 ; Cui and Holmes, 2012 ; Hron et al., 2016 ). Endogenous delta-retroviruses have been identified in bats, carnivores, cetaceans, and insectivores ( Farkašová et al., 2017 ; Hron et al., 2018 ; Zheng et al., 2021 ). A delta-retrovirus was estimated to integrate into carnivore genomes >24.6 Mya ( Hron et al., 2018 ).…”