A billion years arms-race between viruses, virophages, and eukaryotes.

Abstract

Bamfordviruses are arguably the most diverse group of viruses infecting eukaryotes. They include the Nucleocytoplasmic Large DNA viruses (NCLDVs), virophages, adenoviruses, <i>Mavericks</i> and Polinton-like viruses. Two main hypotheses for their origins have been proposed: the 'nuclear-escape' and 'virophage-first' hypotheses. The nuclear-escape hypothesis proposes an endogenous, <i>Maverick</i>-like ancestor which escaped from the nucleus and gave rise to adenoviruses and NCLDVs. In contrast, the virophage-first hypothesis proposes that NCLDVs coevolved with protovirophages; <i>Mavericks</i> then evolved from virophages that became endogenous, with adenoviruses escaping from the nucleus at a later stage. Here, we test the predictions made by both models and consider alternative evolutionary scenarios. We use a data set of the four core virion proteins sampled across the diversity of the lineage, together with Bayesian and maximum-likelihood hypothesis-testing methods, and estimate rooted phylogenies. We find strong evidence that adenoviruses and NCLDVs are not sister groups, and that <i>Mavericks</i> and Mavirus acquired the rve-integrase independently. We also found strong support for a monophyletic group of virophages (family <i>Lavidaviridae</i>) and a most likely root placed between virophages and the other lineages. Our observations support alternatives to the nuclear-escape scenario and a billion years evolutionary arms-race between virophages and NCLDVs.