Viruses and mobile genetic elements are molecular parasites or symbionts that coevolve with nearly all forms of cellular life. The route of virus replication and protein expression is determined by the viral genome type. Comparison of these routes led to the classification of viruses into seven “Baltimore classes” (BCs) that define the major features of virus reproduction. However, recent phylogenomic studies identified multiple evolutionary connections among viruses within each of the BCs as well as between different classes.

Background: The Nucleo-Cytoplasmic Large DNA Viruses (NCLDV) comprise an apparently monophyletic class of viruses that infect a broad variety of eukaryotic hosts. Recent progress in isolation of new viruses and genome sequencing resulted in a substantial expansion of the NCLDV diversity, resulting in additional opportunities for comparative genomic analysis, and a demand for a comprehensive classification of viral genes. Results: A comprehensive comparison of the protein sequences encoded in the genomes of 45 NCLDV belonging to 6 families was performed in order to delineate cluster of orthologous viral genes. Using previously developed computational methods for orthology identification, 1445 Nucleo-Cytoplasmic Virus Orthologous Groups (NCVOGs) were identified of which 177 are represented in more than one NCLDV family. The NCVOGs were manually curated and annotated and can be used as a computational platform for functional annotation and evolutionary analysis of new NCLDV genomes. A maximum-likelihood reconstruction of the NCLDV evolution yielded a set of 47 conserved genes that were probably present in the genome of the common ancestor of this class of eukaryotic viruses. This reconstructed ancestral gene set is robust to the parameters of the reconstruction procedure and so is likely to accurately reflect the gene core of the ancestral NCLDV, indicating that this virus encoded a complex machinery of replication, expression and morphogenesis that made it relatively independent from host cell functions. Conclusions: The NCVOGs are a flexible and expandable platform for genome analysis and functional annotation of newly characterized NCLDV. Evolutionary reconstructions employing NCVOGs point to complex ancestral viruses.

Viral evolution is revealed by giant viruses encoding multiple components of the protein translation machinery.

Background: Phagocytosis, that is, engulfment of large particles by eukaryotic cells, is found in diverse organisms and is often thought to be central to the very origin of the eukaryotic cell, in particular, for the acquisition of bacterial endosymbionts including the ancestor of the mitochondrion. Results: Comparisons of the sets of proteins implicated in phagocytosis in different eukaryotes reveal extreme diversity, with very few highly conserved components that typically do not possess readily identifiable prokaryotic homologs. Nevertheless, phylogenetic analysis of those proteins for which such homologs do exist yields clues to the possible origin of phagocytosis. The central finding is that a subset of archaea encode actins that are not only monophyletic with eukaryotic actins but also share unique structural features with actin-related proteins (Arp) 2 and 3. All phagocytic processes are strictly dependent on remodeling of the actin cytoskeleton and the formation of branched filaments for which Arp2/3 are responsible. The presence of common structural features in Arp2/3 and the archaeal actins suggests that the common ancestors of the archaeal and eukaryotic actins were capable of forming branched filaments, like modern Arp2/3. The Rho family GTPases that are ubiquitous regulators of phagocytosis in eukaryotes appear to be of bacterial origin, so assuming that the host of the mitochondrial endosymbiont was an archaeon, the genes for these GTPases come via horizontal gene transfer from the endosymbiont or in an earlier event. Conclusion: The present findings suggest a hypothetical scenario of eukaryogenesis under which the archaeal ancestor of eukaryotes had no cell wall (like modern Thermoplasma) but had an actin-based cytoskeleton including branched actin filaments that allowed this organism to produce actin-supported membrane protrusions. These protrusions would facilitate accidental, occasional engulfment of bacteria, one of which eventually became the mitochondrion. The acquisition of the endosymbiont triggered eukaryogenesis, in particular, the emergence of the endomembrane system that eventually led to the evolution of modern-type phagocytosis, independently in several eukaryotic lineages. Reviewers: This article was reviewed by Simonetta Gribaldo, Gaspar Jekely, and Pierre Pontarotti. For the full reviews, please go to the Reviewers' Reports section.

Eukaryotic single-stranded DNA (ssDNA) viruses are classified into 10 families (Table 1), but many remain unclassified (1, 2). Viruses from seven families (Bacilladnaviridae, Circoviridae, Geminiviridae, Genomoviridae, Nanoviridae, Redondoviridae, and Smacoviridae) have small circular genomes, with some encompassing only two genes, encoding the replication initiation protein (Rep) and the capsid protein (3–5). The genomes are replicated by the rolling-circle mechanism initiated by the virus-encoded Rep proteins of the HUH endonuclease superfamily (6–10). In eukaryotic ssDNA viruses, the HUH endonuclease domain is followed by a superfamily 3 helicase (S3H) domain, which is not found in prokaryotic ssDNA virus Reps, although homologous two-domain Reps are encoded by several groups of bacterial plasmids (5). Informally, this assemblage of ssDNA viruses has been referred to as “circular, Rep-encoding single-stranded (CRESS) DNA viruses” (4, 8). Viruses from the seven families infect hosts across the eukaryotic domain, including animals (Circoviridae), diatoms (Bacilladnaviridae), fungi (Genomoviridae), and plants (Nanoviridae and Geminiviridae), whereas members of the Smacoviridae and the newly created Redondoviridae have been discovered by metagenomics and are suspected to infect animals (3, 11), although an association of smacovirids with methanogenic archaea has also been suggested (12).