Evolution of the Large Nucleocytoplasmic DNA Viruses of Eukaryotes and Convergent Origins of Viral Gigantism

Abstract

The Nucleocytoplasmic Large DNA Viruses (NCLDV) of eukaryotes (proposed order “Megavirales”) comprise an expansive group of eukaryotic viruses that consists of the families Poxviridae, Asfarviridae, Iridoviridae, Ascoviridae, Phycodnaviridae, Marseilleviridae, Pithoviridae, and Mimiviridae, as well as Pandoraviruses, Molliviruses, and Faustoviruses that so far remain unaccounted by the official virus taxonomy. All these viruses have double-stranded DNA genomes that range in size from about 100 kilobases (kb) to more than 2.5 megabases. The viruses with genomes larger than 500 kb are informally considered “giant,” and the largest giant viruses surpass numerous bacteria and archaea in both particle and genome size. The discovery of giant viruses has been highly unexpected and has changed the perception of viral size and complexity, and even, arguably, the entire concept of a virus. Given that giant viruses encode multiple proteins that are universal among cellular life forms and are components of the translation system, the quintessential cellular molecular machinery, attempts have been made to incorporate these viruses in the evolutionary tree of cellular life. Moreover, evolutionary scenarios of the origin of giant viruses from a fourth, supposedly extinct domain of cellular life have been proposed. However, despite all the differences in the genome size and gene repertoire, the NCLDV can be confidently defined as monophyletic group, on the strength of the presence of about 40 genes that can be traced back to their last common ancestor. Using several most strongly conserved genes from this ancestral set, a well-resolved phylogenetic tree of the NCLDV was built and employed as the scaffold to reconstruct the history of gene gain and loss throughout the course of the evolution of this group of viruses. This reconstruction reveals extremely dynamic evolution that involved extensive gene gain and loss in many groups of viruses and indicates that giant viruses emerged independently in several clades of the NCLDV. Thus, these giants of the virus world evolved repeatedly from smaller and simpler viruses, rather than from a fourth domain of cellular life, and captured numerous genes, including those for translation system components, from eukaryotes, along with some bacterial genes. Even deeper evolutionary reconstructions reveal apparent links between the NCLDV and smaller viruses of eukaryotes, such as adenoviruses, and ultimately, derive all these viruses from tailless bacteriophages.