Abstract

Mutations provide the variation that drives evolution, yet their effects on fitness remain poorly understood. Here we explore how mutations in the essential enzyme adenylate kinase (Adk) of Escherichia coli affect multiple phases of population growth. We introduce a biophysical fitness landscape for these phases, showing how they depend on molecular and cellular properties of Adk. We find that Adk catalytic capacity in the cell (the product of activity and abundance) is the major determinant of mutational fitness effects. We show that bacterial lag times are at a well-defined optimum with respect to Adk’s catalytic capacity, while exponential growth rates are only weakly affected by variation in Adk. Direct pairwise competitions between strains show how environmental conditions modulate the outcome of a competition where growth rates and lag times have a tradeoff, shedding light on the multidimensional nature of fitness and its importance in the evolutionary optimization of enzymes.

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Acknowledgements

This work was supported by NIH award R01 GM068670 to E.I.S. M.Ma. was supported by NIH award F32 GM116217. We thank S. Bershtein and A. Serohijos for helpful discussions.

Author information

Affiliations

  1. Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.

    • Bharat V. Adkar
    • , Michael Manhart
    • , Sanchari Bhattacharyya
    • , Jian Tian
    • , Michael Musharbash
    •  & Eugene I. Shakhnovich
  2. Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, 12 Zhongguancun South Street, Beijing, 100081, China.

    • Jian Tian

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Contributions

B.V.A. and E.I.S. designed the research; B.V.A., S.B., J.T. and M.Mu. performed experiments; B.V.A., M.Ma., S.B. and E.I.S. analysed the data; B.V.A., M.Ma., S.B. and E.I.S. wrote the paper. All authors edited and approved the final version.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Eugene I. Shakhnovich.

Supplementary information

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    Supplementary Information

    Supplementary Methods; Supplementary Figures 1–12; Supplementary Tables 1–3

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    Supplementary Dataset 1

    Growth curve data for Adk in E. coli.

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DOI

https://doi.org/10.1038/s41559-017-0149

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