Regulation of mutY and Nature of Mutator Mutations in Escherichia coli Populations under Nutrient Limitation
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Previous analysis of aerobic, glucose-limited continuous cultures of Escherichia coli revealed that G:C-to-T:A (G:C→T:A) transversions were the most commonly occurring type of spontaneous mutation. One possible explanation for the preponderance of these mutations was that nutrient limitation repressed MutY-dependent DNA repair, resulting in increased proportions of G:C→T:A transversions. The regulation of the mutY -dependent DNA repair system was therefore studied with a transcriptional mutY-lacZ fusion recombined into the chromosome. Expression from the mutY promoter was fourfold higher under aerobic conditions than under anaerobic conditions. But mutY expression was higher in glucose- or ammonia-limited chemostats than in nutrient-excess batch culture, so mutY was not downregulated by nutrient limitation. An alternative explanation for the frequency of G:C→T:A transversions was the common appearance of mutY mutator mutations in the chemostat populations. Of 11 chemostat populations screened in detail, six contained mutators, and the mutator mutation in four cultures was located in the region of mutY at 66 min on the chromosome. The spectrum of mutations and rate of mutation in these isolates were fully consistent with a mutY -deficiency in each strain. Based on PCR analysis of the region within and around mutY , isolates from three individual populations contained deletions extending at least 2 kb upstream of mutY and more than 5 kb downstream. In the fourth population, the deletion was even longer, extending at least 5 kb upstream and 5 kb downstream of mutY . The isolation of mutY mutator strains from four independent populations with extensive chromosomal rearrangements suggests that mutY inactivation by deletion is a means of increasing mutation rates under nutrient limitation and explains the observed frequency of G:C→T:A mutations in glucose-limited chemostats.
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In certain cases ALE can lead to an even higher increase of up to 1000% as shown for the iron reduction rate of Geobacter sulfurreducens, although this increase was only achieved after 24 months of selection.
“In certain cases ALE can lead to an even higher increase of up to 1000% as recently shown for the iron reduction rate of Geobacter sulfurreducens[123], although this increase was only achieved after 24 months of selection”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [123]
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- Authors
- Notley-McRobb, L., Pinto, R., Seeto, S., & Ferenci, T.
- Affiliations
- Department of Microbiology G08, University of Sydney, New South Wales 2006, Australia
- The University of Sydney (AU)
- Corresponding author
- Ferenci, Thomas
- ORCID
- Ferenci, Thomas
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2002-02
- Volume
- 184
- Issue
- 3
- Pages
- 739-745
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC139514
- OpenAlex
- W2163879725
- Cited by
- 31
- References
- 39
- Citations by year
- 2025: 2 · 2021: 3 · 2017: 3 · 2015: 1 · 2014: 4 · 2013: 4
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Bacteriology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › DNA Repair Mechanisms
- Keywords
- MutY, DNA mismatch repair, nutrient limitation, glucose-limited chemostat, G:C to T:A transversions, spontaneous mutation, chromosomal rearrangements, Escherichia coli, aerobic and anaerobic conditions, mutation rate
- MeSH terms
- DNA Repair, Escherichia coli, Glucose, N-Glycosyl Hydrolases, Gene Expression Regulation, Bacterial, Mutagenesis, Point Mutation, DNA Glycosylases
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