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Optimization of lag phase shapes the evolution of a bacterial enzyme


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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Figure 1: Biophysical and intracellular properties of Adk.
Figure 2: Traits of population growth.
Figure 3: Binary growth competition.
Figure 4: Growth curves at various nutrient concentrations.
Figure 5: Tradeoffs between lag and exponential growth in binary competitions.


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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




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.

Corresponding author

Correspondence to Eugene I. Shakhnovich.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Methods; Supplementary Figures 1–12; Supplementary Tables 1–3 (PDF 2072 kb)

Supplementary Dataset 1

Growth curve data for Adk in E. coli. (XLS 207 kb)

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Adkar, B., Manhart, M., Bhattacharyya, S. et al. Optimization of lag phase shapes the evolution of a bacterial enzyme. Nat Ecol Evol 1, 0149 (2017).

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