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Evolution of gene knockout strains of E. coli reveal regulatory architectures governed by metabolism

Author

Listed:
  • Douglas McCloskey

    (University of California–San Diego
    Technical University of Denmark)

  • Sibei Xu

    (University of California–San Diego)

  • Troy E. Sandberg

    (University of California–San Diego)

  • Elizabeth Brunk

    (University of California–San Diego)

  • Ying Hefner

    (University of California–San Diego)

  • Richard Szubin

    (University of California–San Diego)

  • Adam M. Feist

    (University of California–San Diego
    Technical University of Denmark)

  • Bernhard O. Palsson

    (University of California–San Diego
    Technical University of Denmark)

Abstract

Biological regulatory network architectures are multi-scale in their function and can adaptively acquire new functions. Gene knockout (KO) experiments provide an established experimental approach not just for studying gene function, but also for unraveling regulatory networks in which a gene and its gene product are involved. Here we study the regulatory architecture of Escherichia coli K-12 MG1655 by applying adaptive laboratory evolution (ALE) to metabolic gene KO strains. Multi-omic analysis reveal a common overall schema describing the process of adaptation whereby perturbations in metabolite concentrations lead regulatory networks to produce suboptimal states, whose function is subsequently altered and re-optimized through acquisition of mutations during ALE. These results indicate that metabolite levels, through metabolite-transcription factor interactions, have a dominant role in determining the function of a multi-scale regulatory architecture that has been molded by evolution.

Suggested Citation

  • Douglas McCloskey & Sibei Xu & Troy E. Sandberg & Elizabeth Brunk & Ying Hefner & Richard Szubin & Adam M. Feist & Bernhard O. Palsson, 2018. "Evolution of gene knockout strains of E. coli reveal regulatory architectures governed by metabolism," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06219-9
    DOI: 10.1038/s41467-018-06219-9
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