Experimental evolution of diverse Escherichia coli metabolic mutants identifies genetic loci for convergent adaptation of growth rate

Thomas P. Wytock, Aretha Fiebig, Jonathan W. Willett, Julien Herrou, Aleksandra Fergin, Adilson E. Motter*, Sean Crosson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Cell growth is determined by substrate availability and the cell’s metabolic capacity to assimilate substrates into building blocks. Metabolic genes that determine growth rate may interact synergistically or antagonistically, and can accelerate or slow growth, depending on genetic background and environmental conditions. We evolved a diverse set of Escherichia coli single-gene deletion mutants with a spectrum of growth rates and identified mutations that generally increase growth rate. Despite the metabolic differences between parent strains, mutations that enhanced growth largely mapped to core transcription machinery, including the β and β’ subunits of RNA polymerase (RNAP) and the transcription elongation factor, NusA. The structural segments of RNAP that determine enhanced growth have been previously implicated in antibiotic resistance and in the control of transcription elongation and pausing. We further developed a computational framework to characterize how the transcriptional changes that occur upon acquisition of these mutations affect growth rate across strains. Our experimental and computational results provide evidence for cases in which RNAP mutations shift the competitive balance between active transcription and gene silencing. This study demonstrates that mutations in specific regions of RNAP are a convergent adaptive solution that can enhance the growth rate of cells from distinct metabolic states.

Original languageEnglish (US)
Article numbere1007284
JournalPLoS genetics
Volume14
Issue number3
DOIs
StatePublished - Mar 2018

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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