Ancient Host-Virus Gene Transfer Hints at a Diverse Pre-LECA Virosphere

Abstract

The details surrounding the early evolution of eukaryotes and their viruses are largely unknown. Several key enzymes involved in DNA synthesis and transcription are shared between eukaryotes and large DNA viruses in the phylum Nucleocytoviricota, but the evolutionary relationships between these genes remain unclear. In particular, previous studies of eukaryotic DNA and RNA polymerases often show deep-branching clades of eukaryotes and viruses indicative of ancient gene exchange. Here, we performed updated phylogenetic analysis of eukaryotic and viral family B DNA polymerases, multimeric RNA polymerases, and mRNA-capping enzymes to explore their evolutionary relationships. Our results show that viral enzymes form clades that are typically adjacent to eukaryotes, suggesting that they originate prior to the emergence of the Last Eukaryotic Common Ancestor (LECA). The machinery for viral DNA replication, transcription, and mRNA capping are all key processes needed for the maintenance of virus factories, which are complex structures formed by many nucleocytoviruses during infection, indicating that viruses capable of making these structures are ancient. These findings hint at a diverse and complex pre-LECA virosphere and indicate that large DNA viruses may encode proteins that are relics of extinct proto-eukaryotic lineages.

Keywords: Early eukaryotes; Giant viruses; Mirusviruses; Nucleocytoviricota; Virus factory.

Fig. 1

Phylogenetic tree of DNA polymerase family B demonstrating nested placement of Polδ in a viral clade and Polε with Asgard archaea (957 total sequences, 1417 sites). a Maximum-likelihood analysis was performed using IQ-TREE using the complex model LG+C60+F+G. Ultrafast bootstrap support values for select deep-branching nodes are shown (black dot > = 95%, blue dot 90–94%). For clarity, support values are only provided for select internal nodes. b Rectangular representation of the region of the polB phylogenetic tree highlighting the evolutionary relationships between viral groups and eukaryotic Polδ. Values at nodes represent their ultrafast bootstrap support. Polζ = PolZeta; Polα = PolAlpha; Polδ = PolDelta and Polε = PolEpsilon in the figure (Color figure online)

Fig. 2

Phylogenetic tree for RNA Polymerase (RNAP). The alignment is based on a concatenated set of Beta and Beta prime subunits from 1017 sequences (resulting in a total alignment length of 3812 sites). Maximum-likelihood analysis was performed using IQ-TREE under a complex model (LG+C60+F+G). The dots on the branches represent ultrafast bootstrap support values (black dot > = 99%). For clarity, support values are only provided for selected internal nodes. Full trees are available in the supplemental material. The tree is rooted between the bacteria and all other taxa (Color figure online)

Fig. 3

Phylogenetic tree for mRNA-capping enzyme (upper clade) along with ATP-dependent DNA ligase (lower clade, labeled). Trees were made using different trimming strategies. Sites with 90% gaps removed (left) resulting in total alignment of 856 sites. Sites with 50% gaps removed, resulting in total alignment of 326 sites (right). Maximum-likelihood analysis was performed using IQ-TREE using LG+F+R10 model

Fig. 4

Schematic of possible evolutionary scenarios that would lead to the nested placement of core eukaryotic genes within broader clades of viruses. In scenario 1 (S1), viruses acquire core machinery from proto-eukaryotic lineages that subsequently go extinct, In scenario 2 (S2), virus-to-eukaryotic gene transfer takes place prior to the emergence of LECA