Evolution of Mutational Robustness in an RNA Virus

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.

Mutations Leading to Loss of Sporulation Ability in Bacillus subtilis Are Sufficiently Frequent to Favor Genetic Canalization

“…RNA viruses are known to have high values for both m and N, and in agreement with this, genetic canalization has been observed for RNA viruses (Montville et al 2005). Genetic canalization has also been inferred from microRNA sequences in a range of eukaryotes with smaller effective population sizes (Borenstein and Ruppin 2006).…”

Predicting Virus Evolution: The Relationship between Genetic Robustness and Evolvability of Thermotolerance

“…Our studies with phage φ6 provided a unique collection of virus genotypes that were shown to differ in their evolved genetic robustness (Montville et al 2005). With this known difference in hand, we were able to capitalize on the collection of viruses to test whether a positive relationship exists between robustness and evolvability, as suggested by theory but rarely examined experimentally ).…”

“…In our experiments with the RNA virus φ6, we examined a different selection pressure where evolved changes in robustness were expected (Montville et al 2005; see also Turner and Chao 1998). We used a single genotype of the lytic RNA bacteriophage (phage) φ6 to found six populations.…”

“…By this logic, conditions fostering complementation (and hence, coinfection) may weaken selection for phage φ6 genomes to maintain their individual-level robustness, because coinfection provides mutational buffering. We therefore predicted that the degree of coinfection-high multiplicity versus low multiplicity-should influence evolution of robustness in phage φ6 populations (Montville et al 2005). More specifically, we hypothesized that selection for robustness should be greatly relaxed in the phage φ6 populations that evolved for 300 generations under high levels of coinfection.…”

“…From the collection of 60 virus clones that were isolated from populations which experienced 300 generations of viral evolution under high versus low moi (Montville et al 2005), we chose a subset of 24 clones to study the relationship between robustness and evolvability. These 24 clones (12 robust, 12 brittle) were first examined for their survival under 45°C heat shock.…”