RNA polymerase mutants found through adaptive evolution reprogram Escherichia coli for optimal growth in minimal media
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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].”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [61]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.
Datsenko, K., & Wanner, B. (2000) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.120163297 · Cited by 15,902 · see citing works
Gene Expression Omnibus: NCBI gene expression and hybridization array data repository
Edgar, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.207 · Cited by 13,288 · see citing works
Statistical significance for genomewide studies
Storey, J. D., & Tibshirani, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530509100 · Cited by 9,692 · see citing works
Escherichia coli and Salmonella.
Neidhart, F. C. (1996) · Cited by 1,584 · see citing works
Mead, P. S., & Griffin, P. M. (1998) · The Lancet · doi:10.1016/s0140-6736(98)01267-7 · Cited by 1,031 · see citing works
Xiao, H., Kálmán, M., Ikehara, K., Zemel, S., Glaser, G., & Cashel, M. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)67694-5 · Cited by 721 · see citing works
Jin, D. J., & Gross, C. A. (1988) · Journal of Molecular Biology · doi:10.1016/0022-2836(88)90517-7 · Cited by 678 · see citing works
ppGpp: a global regulator in Escherichia coli
Magnusson, L. U., Farewell, A., & Nyström, T. (2005) · Trends in Microbiology · doi:10.1016/j.tim.2005.03.008 · Cited by 644 · see citing works
The global, ppGpp‐mediated stringent response to amino acid starvation in Escherichia coli
Traxler, M. F., Summers, S. M., Nguyen, H., Zacharia, V. M., Hightower, G. A., Smith, J. T., & Conway, T. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06229.x · Cited by 519 · see citing works
Jensen, K. F. (1993) · Journal of Bacteriology · doi:10.1128/jb.175.11.3401-3407.1993 · Cited by 509 · see citing works
Paul, B. J., Berkmen, M. B., Ross, W., Schneider, D. A., Webb, C., Foster, J. W., & Gourse, R. L. (2004) · Cell · doi:10.1016/j.cell.2004.07.009 · Cited by 479 · see citing works
Cooper, T. F., Rozen, D. E., & Lenski, R. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0334340100 · Cited by 440 · see citing works
Herring, C. D., Raghunathan, A., Honisch, C., Patel, T., Applebee, M. K., Joyce, A. R., Albert, T. J., Blattner, F. R., van den Boom, D., Cantor, C. R., et al. (2006) · Nature Genetics · doi:10.1038/ng1906 · Cited by 381 · see citing works
Self-citationTranscription Profiling of the Stringent Response in Escherichia coli
Durfee, T., Hansen, A., Zhi, H., Blattner, F. R., & Jin, D. J. (2007) · Journal of Bacteriology · doi:10.1128/jb.01092-07 · Cited by 374 · see citing works
Preprocessing of oligonucleotide array data
Wu, Z. J., & Irizarry, R. A. (2004) · Nature Biotechnology · doi:10.1038/nbt0604-656b · Cited by 364 · see citing works
Ubiquitous Transcriptional Pausing Is Independent of RNA Polymerase Backtracking
Neuman, K. C., Abbondanzieri, E. A., Landick, R. C., Gelles, J., & Block, S. M. (2003) · Cell · doi:10.1016/s0092-8674(03)00845-6 · Cited by 327 · see citing works
Self-citationAdvances in bacterial promoter recognition and its control by factors that do not bind DNA
Haugen, S. P., Ross, W., & Gourse, R. L. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1912 · Cited by 320 · see citing works
Fong, S. S., Joyce, A. R., & Palsson, B. Ø. (2005) · Genome Research · doi:10.1101/gr.3832305 · Cited by 265 · cited 1× · see citing works
“Loss of motility in MG1655 adapted to growth in GMM has previously been observed (21).”
BackgroundSelf-citationThe regulatory roles and mechanism of transcriptional pausing
Landick, R. C. (2006) · Biochemical Society Transactions · doi:10.1042/bst0341062 · Cited by 251 · see citing works
Self-citationHaugen, S. P., Berkmen, M. B., Ross, W., Gaál, T., Ward, C. S., & Gourse, R. L. (2006) · Cell · doi:10.1016/j.cell.2006.04.034 · Cited by 218 · see citing works
Zhou, Y. N., & Jin, D. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.2908 · Cited by 218 · see citing works
Toulokhonov, I., Zhang, J., Palangat, M., & Landick, R. C. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.06.008 · Cited by 201 · see citing works
Self-citationEl-Mansi, E. M. T., & HOLMS, W. H. (1989) · Microbiology · doi:10.1099/00221287-135-11-2875 · Cited by 201 · see citing works
Conrad, T. M., Joyce, A. R., Applebee, M. K., Barrett, C. L., Xie, B., Gao, Y., & Palsson, B. Ø. (2009) · Genome biology · doi:10.1186/gb-2009-10-10-r118 · Cited by 196 · see citing works
Self-citationGene replacement without selection: regulated suppression of amber mutations in Escherichia coli
Herring, C. D., Glasner, J. D., & Blattner, F. R. (2003) · Gene · doi:10.1016/s0378-1119(03)00585-7 · Cited by 177 · see citing works
Jin, D. J., & Gross, C. A. (1989) · Journal of Bacteriology · doi:10.1128/jb.171.9.5229-5231.1989 · Cited by 165 · see citing works
Regulatory and metabolic rewiring during laboratory evolution of ethanol tolerance in E. coli
Goodarzi, H., Bennett, B. D., Amini, S., Reaves, M. L., Hottes, A. K., Rabinowitz, J. D., & Tavazoie, S. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.33 · Cited by 155 · see citing works
Kingston, R. E., Nierman, W. C., & Chamberlin, M. J. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69683-3 · Cited by 150 · see citing works
Evolution of global regulatory networks during a long‐term experiment with<i>Escherichia coli</i>
Philippe, N., Crozat, E., Lenski, R. E., & Schneider, D. (2007) · BioEssays · doi:10.1002/bies.20629 · Cited by 145 · see citing works
Klumpp, S., & Terence Hwa, B. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806084105 · Cited by 143 · see citing works
Artsimovitch, I., Svetlov, V. V., Murakami, K. S., & Landick, R. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211214200 · Cited by 139 · see citing works
Self-citationDksA and ppGpp directly regulate transcription of the Escherichia coli flagellar cascade
Lemke, J. J., Durfee, T., & Gourse, R. L. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06939.x · Cited by 98 · see citing works
Ederth, J., Artsimovitch, I., Isaksson, L. A., & Landick, R. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207038200 · Cited by 94 · see citing works
Self-citationLeatham, M. P., Stevenson, S. J., Gauger, E. J., Krogfelt, K. A., Lins, J. J., Haddock, T. L., Autieri, S. M., Conway, T., & Cohen, P. S. (2005) · Infection and Immunity · doi:10.1128/iai.73.12.8039-8049.2005 · Cited by 93 · see citing works
Mutagenesis of the Bacterial RNA Polymerase Alpha Subunit for Improvement of Complex Phenotypes
Klein‐Marcuschamer, D., Santos, C. N. S., Yu, H., & Stephanopoulos, G. N. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.01888-08 · Cited by 84 · see citing works
Jin, D., & Gross, C. A. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98711-9 · Cited by 83 · see citing works
Isolation of RNA Polymerase Suppressors of a (p)ppGpp Deficiency
Murphy, H., & Cashel, M. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)71044-1 · Cited by 81 · see citing works
Vogel, U. B., & Jensen, K. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.31.18335 · Cited by 73 · see citing works
High Concentrations of ppGpp Decrease the RNA Chain Growth Rate
Sørensen, M. A., Jensen, K. F., & Pedersen, S. B. (1994) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.1156 · Cited by 72 · see citing works
Structural Perspective on Mutations Affecting the Function of Multisubunit RNA Polymerases
Trinh, V. Q., Langelier, M.-F., Archambault, J., & Coulombe, B. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.70.1.12-36.2006 · Cited by 70 · see citing works
Fisher, R. F., & Yanofsky, C. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)82040-7 · Cited by 66 · see citing works
Applebee, M. K., Herrgård, M. J., & Palsson, B. Ø. (2008) · Journal of Bacteriology · doi:10.1128/jb.01976-07 · Cited by 51 · see citing works
Self-citationKyzer, S., Ha, K. S., Landick, R. C., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701483200 · Cited by 47 · see citing works
Self-citationPfeiffer, T., & Hartmann, R. K. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0744 · Cited by 22 · see citing works
Joyce, A. R. (2007) · eScholarship (California Digital Library) · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Adaptive laboratory evolution—Principles and applications for biotechnology
Dragosits, M., & Mattanovich, D. (2013) · Microbial Cell Factories · doi:10.1186/1475-2859-12-64 · Cited by 827 · see citing works
The Molecular Diversity of Adaptive Convergence
Tenaillon, O., Rodríguez-Verdugo, A., Gaut, R. L., McDonald, P., Bennett, A. F., Long, A. D., & Gaut, B. S. (2012) · Science · doi:10.1126/science.1212986 · Cited by 815 · see citing works
Adaptive laboratory evolution — harnessing the power of biology for metabolic engineering
Portnoy, V. A., Bezdan, D., & Zengler, K. (2011) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2011.03.007 · Cited by 309 · see citing works
Evolutionary insight from whole‐genome sequencing of experimentally evolved microbes
DETTMAN, J. R., RODRIGUE, N., MELNYK, A. H., WONG, A., BAILEY, S. F., & KASSEN, R. (2012) · Molecular Ecology · doi:10.1111/j.1365-294x.2012.05484.x · Cited by 160 · see citing works
Yeast metabolic innovations emerged via expanded metabolic network and gene positive selection
Lu, H., Li, F., Yuan, L., Domenzain, I., Yu, R., Wang, H., Li, G., Chen, Y., Ji, B., Kerkhoven, E. J., et al. (2021) · Molecular Systems Biology · doi:10.15252/msb.202110427 · Cited by 44 · see citing works
Summers, Z. M., Ueki, T., Ismail, W., Haveman, S. A., & Lovley, D. R. (2012) · The ISME Journal · doi:10.1038/ismej.2011.166 · Cited by 39 · see citing works
The role of cellular objectives and selective pressures in metabolic pathway evolution
Nam, H., Conrad, T. M., & Lewis, N. E. (2011) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2011.03.006 · Cited by 32 · see citing works
Self-citationIsenring, J., Geirnaert, A., Hall, A. R., Jans, C., Lacroix, C., & Stevens, M. J. A. (2021) · mSystems · doi:10.1128/msystems.01085-20 · Cited by 17 · see citing works
- 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
- Publisher
- National Academy of Sciences
- Published
- 2010-11-05
- Volume
- 107
- Issue
- 47
- Pages
- 20500-20505
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2996682
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review