Evolution of Mutational Robustness in an RNA Virus

TLDR

Mutational robustness, the maintenance of phenotype despite genomic mutations, is essential for evolution but its adaptive evolution in biological populations remains controversial, especially given RNA viruses’ high mutation rates and the potential buffering effect of co‑infection. The authors hypothesized that increasing co‑infection frequency weakens selection for genetic robustness in viruses. They experimentally evolved ϕ6 phage populations under low and high co‑infection, then subjected lineages to mutation‑accumulation bottlenecks to assess robustness. Viruses evolved with high co‑infection exhibited larger and more variable fitness effects from random mutations, supporting the hypothesis that co‑infection weakens robustness selection, and these robust viruses also displayed higher mutation rates, suggesting a trade‑off between robustness and replication fidelity.

Abstract

Mutational (genetic) robustness is phenotypic constancy in the face of mutational changes to the genome. Robustness is critical to the understanding of evolution because phenotypically expressed genetic variation is the fuel of natural selection. Nonetheless, the evidence for adaptive evolution of mutational robustness in biological populations is controversial. Robustness should be selectively favored when mutation rates are high, a common feature of RNA viruses. However, selection for robustness may be relaxed under virus co-infection because complementation between virus genotypes can buffer mutational effects. We therefore hypothesized that selection for genetic robustness in viruses will be weakened with increasing frequency of co-infection. To test this idea, we used populations of RNA phage ϕ6 that were experimentally evolved at low and high levels of co-infection and subjected lineages of these viruses to mutation accumulation through population bottlenecking. The data demonstrate that viruses evolved under high co-infection show relatively greater mean magnitude and variance in the fitness changes generated by addition of random mutations, confirming our hypothesis that they experience weakened selection for robustness. Our study further suggests that co-infection of host cells may be advantageous to RNA viruses only in the short term. In addition, we observed higher mutation frequencies in the more robust viruses, indicating that evolution of robustness might foster less-accurate genome replication in RNA viruses.