A phylogenomic data-driven exploration of viral origins and evolution

Nasir, Arshan; Caetano-Anollés, Gustavo

If the host of the fusion event was an archaeon or if eukaryotes branched off from some archaeal phyla, one should expect eukaryoviruses to resemble archaeoviruses at the molecular and/or phenotypic (that is, virion architecture) levels and to recognize archaeal membranes for infectivity. This is clearly not the case. Only two FSFs were shared by archaeoviruses and eukaryoviruses involved in DNA replication/repair (a.60.6) and metabolism (c.76.1), both apparently unrelated to viral pathogenicity. Similarly, we recently compared the virion morphotype distribution in viruses and discovered that two morphotypes (rod-shaped and bacilliform) were unique to archaeoviruses and eukaryoviruses (44) . However, close examination of the 3D folds of coat proteins of "rodshaped" viruses does not suggest a common origin (68, 115) , and the same is probably also true for the "baciliform" morphotype (44) . Moreover, member viruses of the two morphotypes did not cluster together in our ToP (Fig. 7A) , suggesting that the observed phenotypic resemblance is more likely a result of convergence than divergence. The distribution and abundance of RNA viruses in eukaryotes are in disagreement with the aforementioned scenarios because of the paucity of RNA viruses in prokaryotes. Although RNA viruses are abundant in the superkingdom Eukarya (for example, dsRNA in Fungi, RNA in Plants, and retrotranscribing viruses in Plants and Metazoa), no RNA viruses are now known in Archaea (and are rare in Bacteria). Although Bolduc et al. (116) isolated putative RNA viruses from a metagenomic sample rich in archaeal organisms, their host tropism could not be established with confidence and they considered contamination as an alternative but unlikely explanation. These observations greatly reduce confidence in the emergence of eukaryotic RNA viruses from viruses of a prokaryotic ancestor and point toward an alternative scenario for the origin of modern cells that is linked to differential selection of the virosphere [see also (43, 44, 46) ]. Because several archaeal members are characterized by thermophilic habitats and RNA is unstable at high temperatures, the apparent bias in the distribution of viruses in cellular superkingdoms (that is, DNA viruses in prokaryotes and RNA in eukaryotes; Fig. 3A ) is better explained by early loss of RNA viruses in Archaea when they migrated to harsh temperatures. Perhaps it was a driving force behind this transition (46) . Archaeal viruses, plasmids, insertion sequences, and antiviral defense (clustered regularly interspaced short palindromic repeats) closely resemble the mobilome and defense system in Bacteria. In turn, plasmids are rare in eukaryotes, and more sophisticated defense systems (mediated by small interfering RNA) are used against invading viruses (46) . Even the archaeal member viruses of the PRD1/ adenovirus-like and HK97-like lineages are more similar to bacterioviruses than to eukaryoviruses (117) . This suggests that both Archaea and Bacteria have experienced similar selection pressure to get rid of RNA viruses early in evolution (46) . Although Archaea migrated to warm temperatures to escape RNA viruses, the development of a thick peptidoglycan-containing cell wall in Bacteria likely blocked the entry of many viral families (34, 118) . In turn, Eukarya likely benefited from the interaction with RNA and retroviruses (triggering genomic rearrangements) and evolved toward complexity, as recently discussed by Forterre (46)