A phylogenomic data-driven exploration of viral origins and evolution

Nasir, Arshan; Caetano-Anollés, Gustavo

Testing capsid/coat structure-based viral lineages Viruses infecting different organisms often use conserved 3D protein folds to produce capsids and show striking similarities in their virion architecture. These observations have led to the proposal of a structurebased viral taxonomy (47) . Now, four major viral lineages have been defined mainly for icosahedral viruses (the most commonly seen capsid symmetry): "picornavirus-like," "PRD1/adenovirus-like," "HK97-like," and "BTV-like" (47) . These lineages capture many viral families and attempt to simplify the overall diversity of the virosphere. Member viruses of the PRD1/adenovirus-like (characterized by the double jelly-roll fold) and HK97-like lineages infect species in the three superkingdoms, suggesting their ancient origin before the divergence of modern cells (47) . To test this classification and to determine how the signature FSFs of each lineage distributed in our data set, we identified 22 capsid/coatrelated FSFs using a keyword search of "capsid" and "coat" in SCOP 1.75 and in the literature (Table 3) . Member FSFs of each major lineage, along with their abundance in cellular proteomes, are listed in Table 3 . The HMM-based computational approach quickly reproduced the four major capsid-based viral lineages along with proposals for additions to some lineages (for example, negative-sense RNA viruses in picornaviruslike lineage) (table S6) . Only very few members were missing (table S6) , which could be a result of using a stringent criterion in assigning FSFs to viral proteins (E < 0.0001) that likely missed some hits but also protected from false-positive assignments. In short, FSFs identified in our study could be used as bait for quick assignment of viruses to major viral lineages defined by a common virion architecture and capsid/ coat similarities (47) .