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Cryptic genetic variation promotes rapid evolutionary adaptation in an RNA enzyme


Cryptic variation is caused by the robustness of phenotypes to mutations1. Cryptic variation has no effect on phenotypes in a given genetic or environmental background, but it can have effects after mutations or environmental change2,3,4,5. Because evolutionary adaptation by natural selection requires phenotypic variation, phenotypically revealed cryptic genetic variation may facilitate evolutionary adaptation6,7,8. This is possible if the cryptic variation happens to be pre-adapted, or “exapted”9, to a new environment, and is thus advantageous once revealed. However, this facilitating role for cryptic variation has not been proven, partly because most pertinent work focuses on complex phenotypes of whole organisms whose genetic basis is incompletely understood. Here we show that populations of RNA enzymes with accumulated cryptic variation adapt more rapidly to a new substrate than a population without cryptic variation. A detailed analysis of our evolving RNA populations in genotype space shows that cryptic variation allows a population to explore new genotypes that become adaptive only in a new environment. Our observations show that cryptic variation contains new genotypes pre-adapted to a changed environment. Our results highlight the positive role that robustness and epistasis can have in adaptive evolution10,11.

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Figure 1: Evolution during selection for the native activity.
Figure 2: Evolution during selection for the new activity.
Figure 3: Evolution in genotype space.


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We thank R. Dhar and N. de la Chaux for bioinformatic support. We thank the Functional Genomics Center, Zurich, for collecting sequence data. We acknowledge support from Swiss National Science Foundation grants 315200-116814, 315200-119697 and 315230-129708, from the YeastX program of, and from the Research Priority Program in Systems Biology at the University of Zurich.

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Authors and Affiliations



E.J.H. and A.W. contributed to the design of the experiments; E.J.H. performed the experiments; E.J.H., E.F., and A.W. all contributed to analysis of the data and co-wrote the paper.

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Correspondence to Andreas Wagner.

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The authors declare no competing financial interests.

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Hayden, E., Ferrada, E. & Wagner, A. Cryptic genetic variation promotes rapid evolutionary adaptation in an RNA enzyme. Nature 474, 92–95 (2011).

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