Evidence for a billion-years arms race between viruses, virophages and eukaryotes

Abstract

AbstractThe PRD1-adenovirus lineage is one of the oldest and most diverse lineages of viruses. In eukaryotes, they have diversified to an unprecedented extent giving rise to adenoviruses, virophages, Mavericks, Polinton-like viruses and Nucleocytoplasmic Large DNA viruses (NCLDVs) which include the poxviruses, asfarviruses and iridoviruses, among others. Two major hypotheses for their origins have been proposed: the ‘virophage first’ and ‘nuclear escape’ hypotheses, but their plausibility until now has remained unexplored. Here, we use maximum-likelihood and Bayesian hypothesis-testing to compare the two scenarios based on the shared proteins forming the virus particle and a comprehensive genomic character matrix. We also compare the phylogenetic origin of the transcriptional proteins shared by NCLDVs and cytoplasmic linear plasmids. Our analyses overwhelmingly favour the virophage first model. These findings shed light on one of the earliest diversifications seen in the virosphere, supporting a billion-years arms race between viruses, virophages and eukaryotes.