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Evolutionary capacitance as a general feature of complex gene networks

Abstract

An evolutionary capacitor buffers genotypic variation under normal conditions, thereby promoting the accumulation of hidden polymorphism. But it occasionally fails, thereby revealing this variation phenotypically1. The principal example of an evolutionary capacitor is Hsp90, a molecular chaperone that targets an important set of signal transduction proteins. Experiments in Drosophila and Arabidopsis have demonstrated three key properties of Hsp90: (1) it suppresses phenotypic variation under normal conditions and releases this variation when functionally compromised; (2) its function is overwhelmed by environmental stress; and (3) it exerts pleiotropic effects on key developmental processes1,2. But whether these properties necessarily make Hsp90 a significant and unique facilitator of adaptation1,2,3,4,5,6,7,8,9,10 is unclear. Here we use numerical simulations of complex gene networks, as well as genome-scale expression data from yeast single-gene deletion strains, to present a mechanism that extends the scope of evolutionary capacitance beyond the action of Hsp90 alone. We illustrate that most, and perhaps all, genes reveal phenotypic variation when functionally compromised, and that the availability of loss-of-function mutations accelerates adaptation to a new optimum phenotype. However, this effect does not require the mutations to be conditional on the environment. Thus, there might exist a large class of evolutionary capacitors whose effects on phenotypic variation complement the systemic, environment-induced effects of Hsp90.

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Figure 1: Representation of a gene network.
Figure 2: Greater phenotypic variation in single-gene knockouts than in the wild-type networks from which they derive.

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Acknowledgements

We thank B. Baker, D. Hartl, J. Hermisson, D. Kennedy, J. Masel, C. Meiklejohn, D. Petrov, G. Wagner, C. Yanofsky and E. Zuckerkandl for helpful discussions. This study was supported by the Center for Computational Genetics and Biological Modeling, Stanford University. M.L.S. was supported by a National Institutes of Health National Research Service Award Individual Postdoctoral Fellowship, and thanks B. Baker for his support. A.B. thanks the Paul G. Allen Charitable Foundation for its continual support.

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Correspondence to Mark L. Siegal.

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Bergman, A., Siegal, M. Evolutionary capacitance as a general feature of complex gene networks. Nature 424, 549–552 (2003). https://doi.org/10.1038/nature01765

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