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Evolvability of an RNA virus is determined by its mutational neighbourhood

Abstract

The ubiquity of mechanisms that generate genetic variation has spurred arguments that evolvability, the ability to generate adaptive variation, has itself evolved in response to natural selection1,2. The high mutation rate of RNA viruses is postulated to be an adaptation for evolvability3,4, but the paradox is that whereas some RNA viruses evolve at high rates4,5, others are highly stable5,6. Here we show that evolvability in the RNA bacteriophage φ6 is also determined by the accessibility of advantageous genotypes within the mutational neighbourhood (the set of mutants one or a few mutational steps away). We found that two φ6 populations that were derived from a single ancestral phage repeatedly evolved at different rates and toward different fitness maxima. Fitness measurements of individual phages showed that the fitness distribution of mutants differed between the two populations. Whereas population A, which evolved toward a higher maximum, had a distribution that contained many advantageous mutants, population B, which evolved toward a lower maximum, had a distribution that contained only deleterious mutants. We interpret these distributions to measure the fitness effects of genotypes that are mutationally available to the two populations. Thus, the /evolvability of φ6 is constrained by the distribution of its mutational neighbours, despite the fact that this phage has the characteristic high mutation rate of RNA viruses.

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Figure 1: Fitness trajectories of populations A (open circles) and B (filled circles) successively propagated using a bottleneck of 1,000 phage.
Figure 2: Fitness trajectories of five replicate populations founded by clone A (a) and clone B (b).
Figure 3: Plaque-size distribution over time for one clone A replicate and one clone B replicate (both from Fig. 2).
Figure 4: An interpretative representation of the evolution of clones A and B on a two-peaked adaptive landscape.

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Acknowledgements

We thank our laboratory group for feedback, D. Metzgar for comments on manuscript and L. Mindich for discussion and stocks. Support was provided to C.L.B. by a predoctoral fellowship from the Howard Hughes Medical Institute and a Dissertation Improvement Grant from the National Science Foundation. Support was provided to L.C. by the University of California San Diego and the National Institutes of Health (NIGMS).

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Correspondence to Christina L. Burch.

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Burch, C., Chao, L. Evolvability of an RNA virus is determined by its mutational neighbourhood . Nature 406, 625–628 (2000). https://doi.org/10.1038/35020564

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