Mutations that improve efficiency of a weak-link enzyme are rare compared to adaptive mutations elsewhere in the genome

  1. Andrew B Morgenthaler
  2. Wallis R Kinney
  3. Christopher C Ebmeier
  4. Corinne M Walsh
  5. Daniel J Snyder
  6. Vaughn S Cooper
  7. William M Old
  8. Shelley D Copley  Is a corresponding author
  1. University of Colorado, Boulder, United States
  2. University of Pittsburgh, United States

Abstract

New enzymes often evolve by gene amplification and divergence. Previous experimental studies have followed the evolutionary trajectory of an amplified gene, but have not considered mutations elsewhere in the genome when fitness is limited by an evolving gene. We have evolved a strain of Escherichia coli in which a secondary promiscuous activity has been recruited to serve an essential function. The gene encoding the 'weak-link' enzyme amplified in all eight populations, but mutations improving the newly needed activity occurred in only one. Most adaptive mutations occurred elsewhere in the genome. Some mutations increase expression of the enzyme upstream of the weak-link enzyme, pushing material through the dysfunctional metabolic pathway. Others enhance production of a co-substrate for a downstream enzyme, thereby pulling material through the pathway. Most of these latter mutations are detrimental in wild-type E. coli, and thus would require reversion or compensation once a sufficient new activity has evolved.

Data availability

The genome sequence of E. coli strain AM187 used in this study has been deposited to NCBI GenBank under accession number CP037857.All other data generated or analyzed during this study are included in the manuscript and supporting files. Source code files have been provided for Figures 3 and 4 and Tables 2 and 3.

The following data sets were generated

Article and author information

Author details

  1. Andrew B Morgenthaler

    Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3822-0212
  2. Wallis R Kinney

    Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Christopher C Ebmeier

    Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7940-6190
  4. Corinne M Walsh

    Cooperative Institute for Research in Environmental Sciences, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Daniel J Snyder

    Center for Evolutionary Biology and Medicine, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Vaughn S Cooper

    Center for Evolutionary Biology and Medicine, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7726-0765
  7. William M Old

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Shelley D Copley

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Boulder, United States
    For correspondence
    Shelley.Copley@Colorado.EDU
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9727-7919

Funding

National Aeronautics and Space Administration (NNA15BB04A)

  • Shelley D Copley

National Aeronautics and Space Administration (NNA15BB04A)

  • Vaughn S Cooper

Department of Defense /Defense Advanced Research Projects Agency (13-34-RTA-FP-007)

  • William M Old

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Paul B Rainey, Max Planck Institute for Evolutionary Biology, Germany

Version history

  1. Received: November 12, 2019
  2. Accepted: December 2, 2019
  3. Accepted Manuscript published: December 9, 2019 (version 1)
  4. Version of Record published: January 3, 2020 (version 2)

Copyright

© 2019, Morgenthaler et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Andrew B Morgenthaler
  2. Wallis R Kinney
  3. Christopher C Ebmeier
  4. Corinne M Walsh
  5. Daniel J Snyder
  6. Vaughn S Cooper
  7. William M Old
  8. Shelley D Copley
(2019)
Mutations that improve efficiency of a weak-link enzyme are rare compared to adaptive mutations elsewhere in the genome
eLife 8:e53535.
https://doi.org/10.7554/eLife.53535

Share this article

https://doi.org/10.7554/eLife.53535

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