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Evolution of gene network activity by tuning the strength of negative-feedback regulation

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  • Weilin Peng

    (Yale University
    Systems Biology Institute, Yale University)

  • Ping Liu

    (Yale University
    Systems Biology Institute, Yale University)

  • Yuan Xue

    (Yale University
    Systems Biology Institute, Yale University)

  • Murat Acar

    (Yale University
    Systems Biology Institute, Yale University
    Yale University)

Abstract

Despite the examples of protein evolution via mutations in coding sequences, we have very limited understanding on gene network evolution via changes in cis-regulatory elements. Using the galactose network as a model, here we show how the regulatory promoters of the network contribute to the evolved network activity between two yeast species. In Saccharomyces cerevisiae, we combinatorially replace all regulatory network promoters by their counterparts from Saccharomyces paradoxus, measure the resulting network inducibility profiles, and model the results. Lowering relative strength of GAL80-mediated negative feedback by replacing GAL80 promoter is necessary and sufficient to have high network inducibility levels as in S. paradoxus. This is achieved by increasing OFF-to-ON phenotypic switching rates. Competitions performed among strains with or without the GAL80 promoter replacement show strong relationships between network inducibility and fitness. Our results support the hypothesis that gene network activity can evolve by optimizing the strength of negative-feedback regulation.

Suggested Citation

  • Weilin Peng & Ping Liu & Yuan Xue & Murat Acar, 2015. "Evolution of gene network activity by tuning the strength of negative-feedback regulation," Nature Communications, Nature, vol. 6(1), pages 1-9, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7226
    DOI: 10.1038/ncomms7226
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