A phylogenomic data-driven exploration of viral origins and evolution

Nasir, Arshan; Caetano-Anollés, Gustavo

Our comparative and phylogenomic data refute the "virus-first" hypothesis or the precellular scenario for the origin of viruses [see (80) for a new version]. This proposal suggests an early origin of self-replicating viral replicons predating the origin of cells. However, the hypothesis is unsatisfactory because viruses are tightly associated with proteins (capsids) and must replicate in an intracellular environment to produce viral progeny. Fossil evidence also shows that cells appeared early in evolution (88, 89) . The large size of the ABEV group, which includes many FSFs of ancient origin and membrane proteins, is also incompatible with the virus-first scenario and suggests an ancient cellular origin of viruses (Figs. 1A and 5). Thus, our data can be better reconciled with either the "escape" hypothesis or the "reductive" hypothesis [see (31, 41, 90) for details], both of which associate viral origins with cells. Under the escape hypothesis, replicons in proto-virocells became autonomous and acquired virions to infect other ancient cells. In turn, the reduction hypothesis suggests loss of the primordial ribosomal machinery in proto-virocells and subsequent reduction into viruses. Although both hypotheses explain the origin of viruses in ancient cells, reduction seems to be more parsimonious with our data given the strong lifestyle resemblance of viruses to cellular parasites (that also evolve similarly) (37), the early loss of FSFs suggested by evolutionary timelines (Fig. 5A) , and the discovery of giant viruses that overlap cellular parasites in genomic and physical features (Fig. 1 , C and D) (69, 70, 91, 92) . Although reduction of modern cells into virions (enclosing few proteins) may seem far-fetched, this would be relatively more straightforward in ancient cells where ribosomal machinery and other cellular features were yet to fully materialize.