Cited by 241Bacterial Genetics and BiotechnologyEvolution and Genetic DynamicsMicrobial Metabolic Engineering and Bioproduction

RNA polymerase mutants found through adaptive evolution reprogram Escherichia coli for optimal growth in minimal media

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Conrad, Tom M., Frazier, Michael, Joyce, Andrew R., Cho, Byung-Kwan, Knight, Eric M., Lewis, Nathan E., Landick, Robert, Palsson, Bernhard Ø.·2010·Proceedings of the National Academy of Sciences

Abstract

Specific small deletions within the rpoC gene encoding the β′-subunit of RNA polymerase (RNAP) are found repeatedly after adaptation of Escherichia coli K-12 MG1655 to growth in minimal media. Here we present a multiscale analysis of these mutations. At the physiological level, the mutants grow 60% faster than the parent strain and convert the carbon source 15–35% more efficiently to biomass, but grow about 30% slower than the parent strain in rich medium. At the molecular level, the kinetic parameters of the mutated RNAP were found to be altered, resulting in a 4- to 30-fold decrease in open complex longevity at an rRNA promoter and a ∼10-fold decrease in transcriptional pausing, with consequent increase in transcript elongation rate. At a genome-scale, systems biology level, gene expression changes between the parent strain and adapted RNAP mutants reveal large-scale systematic transcriptional changes that influence specific cellular processes, including strong down-regulation of motility, acid resistance, fimbria, and curlin genes. RNAP genome-binding maps reveal redistribution of RNAP that may facilitate relief of a metabolic bottleneck to growth. These findings suggest that reprogramming the kinetic parameters of RNAP through specific mutations allows regulatory adaptation for optimal growth in new environments.

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  • During ALE, clonal interference, bet hedging, genetic hitchhiking and fluctuating growth environments can lead to significant population heterogeneity.

    “Stable phenotypes will accumulate rapidly, although clonal interference [42], bet hedging [43,60], genetic hitchhiking [61] and fluctuating growth environments can lead to significant population heterogeneity [22,62,63].”

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Authors
Conrad, T. M., Frazier, M., Joyce, A. R., Cho, B.-K., Knight, E. M., Lewis, N. E., Landick, R., & Palsson, B. Ø.
Affiliations
  • University of California San Diego (US)
  • University of Wisconsin System (US)
  • Bioinformatics Program, and
Venue
Proceedings of the National Academy of Sciences
Published
2010-11-05
Volume
107
Issue
47
Pages
20500-20505
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2072862994
Cited by
241
References
45
Citations by year
2026: 12 · 2025: 13 · 2024: 22 · 2023: 22 · 2022: 16 · 2021: 21 · 2020: 18 · 2019: 20 · 2018: 19 · 2017: 10 · 2016: 6 · 2015: 13 · 2014: 14 · 2013: 10 · 2012: 15
FWCI
6.30
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (R01GM062791, R01GM057089, R37 GM38660, R37GM038660)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
Keywords
RNA polymerase, rpoC, adaptive evolution, Escherichia coli MG1655, minimal medium, transcription kinetics, transcriptional pausing, genome-wide gene expression, metabolic bottlenecks, growth rate optimization, carbon source utilization
MeSH terms
Adaptation, Physiological, Base Sequence, Culture Media, Escherichia coli, Kinetics, Molecular Sequence Data, DNA-Directed RNA Polymerases, Transcription, Genetic, Mutagenesis, Site-Directed, Sequence Deletion, Sequence Analysis, DNA, DNA Primers, Evolution, Molecular, Gene Expression Profiling, Escherichia coli Proteins, Protein Array Analysis, Chromatin Immunoprecipitation, Gene Knockout Techniques

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