Robustness promotes evolvability of thermotolerance in an RNA virus

Abstract

BackgroundThe ability for an evolving population to adapt to a novel environment is achieved through a balance of robustness and evolvability. Robustness is the invariance of phenotype in the face of perturbation and evolvability is the capacity to adapt in response to selection. Genetic robustness has been posited, depending on the underlying mechanism, to either decrease the efficacy of selection, or increase the possibility of future adaptation. However, the true effect of genetic robustness on evolvability in biological systems remains uncertain.ResultsHere we demonstrate that genetic robustness increases evolvability of thermotolerance in laboratory populations of the RNA virus φ6. We observed that populations founded by robust clones evolved greater resistance to heat shock, relative to populations founded by brittle (less-robust) clones. Thus, we provide empirical evidence for the idea that robustness can promote evolvability in this environment, and further suggest that evolvability can arise indirectly via selection for robustness, rather than through direct selective action.ConclusionOur data imply that greater tolerance of mutational change is associated with virus adaptability in a new niche, a finding generally relevant to evolutionary biology, and informative for elucidating how viruses might evolve to emerge in new habitats and/or overcome novel therapies.

On the possible role of robustness in the evolution of infectious diseases

“…14 One alternative explanation for the observations would be a higher mutation rate in the viruses evolved at high MOI, causing them to experience a greater number of fixed mutations ͑and hence, greater fitness loss͒ during the mutation accumulation; however, no evidence suggests that these viruses mutate at rates higher than their counterparts evolved at low MOI. 14,15 Thus, the study provided the first evidence that genetic robustness could evolve to change in biological populations.…”

“…11 That is, despite equivalent sensitivity to 45°C heat shock in the robust and brittle founding strains, the robust viruses may have proteins that tend to be capable of undergoing mutations while maintaining their proper folding when 45°C constitutes a selective environment. 15 Whether this exact relationship extends to other novel environments has yet to be explored. But the fact that a positive relationship exists at all is essential for tests of existing theory, 8 and begs the question of whether the observed relationship between genetic robustness and evolvability extends to evolution of human pathogens, as implicated in recent claims of evolved increases in genetic robustness in HIV.…”

“…While both involve the ability to withstand the influence of perturbations, robustness describes a more generalized response that affects performance in multiple environments 1,2 and evolvability. 15,16 …”

“…15 Phage 6 is typically cultured at 25°C, and exposure to 45°C heat shock for as little as 5 min leads to ϳ20% survival ͑%S͒ in populations of the virus. Robust and brittle clones of the virus from the aforementioned MOI experiment 14 were used to found lineages passaged for 50 generations of experimental evolution with periodic ͑every fifth generation͒ exposure to 45°C heat shock.…”

“…14 Below we review some of the evidence from these studies, and present new findings from an increasingly popular model system for examining evolution of robustness: the segmented RNA bacteriophage 6. [14][15][16] In reviewing these results, we hope to highlight the importance of empirical work in RNA viruses for testing theory pertaining to robustness, as well as for better understanding the evolutionary biology and evolvability of infectious organisms in general.…”