A phylogenomic data-driven exploration of viral origins and evolution

Nasir, Arshan; Caetano-Anollés, Gustavo

It has been argued that viruses frequently pickpocket genes from cells and that this phenomenon explains their primary mode of evolution (76) . However, our data and previous genomic analyses (97) (98) (99) (100) strongly refute this idea and have revealed the abundance of unique genes (that is, class I proteins in Fig. 1B ) in viral proteomes lacking cellular homologs. A large number of these proteins are likely very ancient and thus are no longer detectable either by BLAST or HMMbased searches, whereas the remaining proteins probably originated rather recently in viral lineages (for example, VSFs in Fig. 5A ). In fact, genes are continuously created by viral lineages in infected cells during viral replication cycles, when viruses have full access to the cellular machinery to produce genes (34) . This phenomenon has been greatly underestimated in the past but is now being acknowledged [for example, (5, 90, 97, (100) (101) (102) ]. Discovery of viruses from atypical habitats and hosts is expected to improve the Protein Data Bank (PDB) representation of viral structures and will no doubt increase our knowledge about class I proteins. In turn, alternative explanations, such as the rapid evolution of class I proteins in viruses after uptake from cells or acquisition from yetto-be-discovered cellular species, are less satisfactory and account for only a minor fraction of class I proteins. For example, the former scenario is inconsistent with the presence of class II proteins that, surprisingly, remained robust to fast evolution in the same viral proteomes (42) . Moreover, synonymous-to-nonsynonymous substitution rates for "unique" genes in giant DNA viruses did not vary significantly from the substitution rates of vertebrate proteins (97) . In turn, the latter scenario posits a decrease in the number of VSFs with the sampling of more cellular genomes, which has not been observed [for example, comparison of (19) and the present study; also discussed in (49) ]. Together, the major fraction of viral proteomes includes proteins with no detectable cellular homologs. This subset is likely indicative of the genecreation abilities of viruses during the virocell life cycles.