Origins and Evolution of the Global RNA Virome

Abstract

Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (ϩ) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (Ϫ) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from ϩRNA viruses on at least two independent occasions, whereas ϪRNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of ϩRNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy. IMPORTANCE The majority of the diverse viruses infecting eukaryotes have RNA genomes, including numerous human, animal, and plant pathogens. Recent advances of metagenomics have led to the discovery of many new groups of RNA viruses in a wide range of hosts. These findings enable a far more complete reconstruction of the evolution of RNA viruses than was attainable previously. This reconstruction reveals the relationships between different Baltimore classes of viruses and indicates extensive transfer of viruses between distantly related hosts, such as plants and animals. These results call for a major revision of the existing taxonomy of RNA viruses.

Metatranscriptomic reconstruction reveals RNA viruses with the potential to shape carbon cycling in soil

“…We searched the assembled sequences for the RNA-dependent RNA polymerase (RdRp), a conserved gene in all RNA viruses that lack a DNA stage (generally referred to as Baltimore type III-V RNA viruses). Although recent work tracing the deep evolutionary history of RNA viruses has merged viral families into supergroups (21)(22)(23), our focus was not on resolving deep phylogenetic viral branches. Rather, our objectives were to investigate fine scale diversity of RNA viruses, their putative hosts, and possible functional importance in soil.…”

Evidence for Internal Initiation of RNA Synthesis by the Hepatitis C Virus RNA-Dependent RNA Polymerase NS5B In Cellulo

“…We furthermore forced this process by introduction of a second copy of the UTR within the HCV genome, which naturally does not occur. We therefore do not claim that the principle observation of internal initiation by the HCV polymerase has any direct relevance in the regular replication cycle but rather that this process (55). Taxa in italics were formally approved by the ICTV (74; https://talk.ictvonline.org/taxonomy/).…”

“…From an evolutionary standpoint, it is intriguing that even though the replication cycle of HCV likely relies exclusively on terminal de novo initiation, the capability of the polymerase for alternative modes of initiation is maintained, likely because the overall structure and functional motifs of RdRps are conserved among positive-strand RNA viruses and might have evolved from an ancestral reverse transcriptase (55). If the RdRp is inherently able to initiate internally, simple in-frame insertions creating a suitable platform for the replicase at a junction within the polyprotein could enable a novel regulatory step in the viral RNA life cycle resulting in the evolution of multipartite virus genomes.…”

“…10). Groups within branch 3 generating subgenomic RNAs by premature termination of negative strand synthesis (Nodaviridae and Tombusviridae) or by de novo initiation from a negative-strand promoter (most well-characterized members of the "alphavirus supergroup," Bromoviridae, Togaviridae, and Hepeviridae [55]) are comparably distant from the "flavivirus supergroup." Therefore, the evolutionary view also does not allow a clear judgement on the mechanism of the HCV RdRp in generating subgenomic transcripts, unless new viruses are found that might bridge those gaps in the future.…”

The genome of the blind soil-dwelling and ancestrally wingless dipluranCampodea augens, a key reference hexapod for studying the emergence of insect innovations

“…All quaranjavirus-like insertions found in C. augens encode the PB1 protein (polymerase basic protein 1) ( Supplementary Table 12), a subunit of the RNA-dependent RNA polymerase (RdRp), which in Orthomyxoviridae is typically a heterotrimeric complex (formed by the PA, PB1, and PB2 proteins) (Stubbs & te Velthuis 2014), contrary to RdRps from other RNA viruses (e.g. double-stranded and positive-stranded RNA viruses) which are typically monomeric (Wolf et al 2018). The corresponding open reading frames of PB1 proteins are incomplete, though, and contain stop codons and/or frameshift mutations (Supplementary Fasta), suggesting that these elements are not functional.…”