Suppressors of RNAi from plant viruses are subject to episodic positive selection

Gemma G. R. Murray,Darren J. Obbard,Sergei L. Kosakovsky Pond

doi:10.1098/rspb.2013.0965

Abstract

Viral suppressors of RNAi (VSRs) are proteins that actively inhibit the antiviral RNA interference (RNAi) immune response, providing an immune evasion route for viruses. It has been hypothesized that VSRs are engaged in a molecular ‘arms race’ with RNAi pathway genes. Two lines of evidence support this. First, VSRs from plant viruses display high sequence diversity, and are frequently gained and lost over evolutionary time scales. Second, Drosophila antiviral RNAi genes show high rates of adaptive evolution. Here, we investigate whether VSRs diversify faster than other genes and, if so, whether this is a result of positive selection, as might be expected in an arms race. By analysis of 12 plant RNA viruses, we show that the relative rate of protein evolution is higher for VSRs than for other genes, but that this is not attributable to pervasive positive selection. We argue that, because evolutionary time scales are extremely different for viruses and eukaryotes, it is improbable that viral adaptation (as measured by the ratio of non-synonymous to synonymous change) will be dominated by one-to-one coevolution with eukaryotes. Instead, for plant virus VSRs, we find strong evidence of episodic selection—diversifying selection that acts on a subset of lineages—which might be attributable to frequent shifts between different host genotypes or species.

Highlights

The interests of viruses and hosts often conflict: for a virus, host infection is necessary for replication, whereas for a host, infection can cause disease
We find that some Viral suppressors of RNA interference (RNAi) (VSRs) show evidence of persistent positive selection, but that others do not, and this may be a true reflection of the evolutionary process
VSRs are predicted to be a focus of antagonistic host –virus interaction [5,6], we found little evidence for ubiquitous positive selection acting on the VSRs of plant viruses

Summary

Introduction

The interests of viruses and hosts often conflict: for a virus, host infection is necessary for replication, whereas for a host, infection can cause disease. If the genes mediating antiviral RNAi pathways were engaged in a classical one-to-one arms race with VSRs, both host and virus genes might be expected to undergo rapid diversifying evolution under the force of strong positive selection. Consistent with this scenario, three key proteins in the antiviral RNAi pathway of Drosophila (Dcr-2, Ago-2 and R2D2) are among the most rapidly evolving genes in the Drosophila genome, and population-genetic analysis suggests that this is due to positive selection rather than relaxed constraint [33,34]. The significance of VSR clustering in the evolutionary fingerprint analysis was tested using a permutation test, allowing the comparison of the null distribution of ESDs between VSRs (estimated by permuting distances to calculate a null distribution) and the observed average ESD between VSRs to be compared

Results

Discussion

Conclusions

Findings

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