Mutations that improve efficiency of a weak-link enzyme are rare compared to adaptive mutations elsewhere in the genome
- University of Colorado, Boulder, United States
- 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.
Article and author information
Author details
Andrew B Morgenthaler
Christopher C Ebmeier
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.
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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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
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