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Published on: November 30, 2018
Nutrient-dependent growth defects and mutability of mutators in Escherichia coli
Yuuka Ishizawa1, Bei-Wen Ying, Saburo Tsuru
1Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Abstract:
So-called mutators emerge when mismatch repair and proofreading mechanisms are defective. Mutators not only accelerate the accumulation of mutations that are beneficial for adaptation but also cause a large number of deleterious mutations that are disadvantageous for cell growth. However, such growth defects may be compensated by nutrient availability. How the growth burden is associated with high mutability in relation to nutritional variation is an intriguing question. To address this question, we constructed a variety of Escherichia coli mutator strains through combinatorial deletions of mismatch repair and proofreading genes and quantitatively evaluated their growth and mutation rates under different nutritional conditions. Growth defects caused by high mutation rates were commonly observed in all mutators, and these defects were alleviated by nutrient supplementation in most mutators. In addition, the mutation rates of the mutators fluctuated greatly in response to nutritional conditions, in contrast to the nearly constant mutation rate of the wild-type strain under varying nutritional conditions. The results showed conditional growth defects and nutrition-sensitive mutability as general features of mutators. This study indicates the importance of modulating mutability in response to changing nutrient conditions to minimize the risk of extinction due to genetic load.
Insights
Mutator strains exhibit conditional growth defects and nutrition-sensitive mutation rates. Nutrient availability can alleviate growth burdens, highlighting the importance of modulating mutability for survival.
Area of Science:
- Microbiology
- Genetics
- Evolutionary Biology
Background:
- Mutators, arising from defects in DNA repair, accelerate mutation accumulation.
- While beneficial mutations aid adaptation, deleterious mutations can impair cell growth.
- Nutrient availability may offset growth defects associated with high mutation rates.
Purpose of the Study:
- To investigate the relationship between high mutability and growth burden under varying nutritional conditions.
- To determine if nutrient availability can compensate for growth defects in mutator strains.
- To assess the impact of nutritional variation on mutation rates in mutators.
Main Methods:
- Constructed Escherichia coli mutator strains via gene deletions in mismatch repair and proofreading pathways.
- Quantitatively assessed growth rates and mutation rates under diverse nutritional conditions.
- Compared mutator strains to wild-type strains across different nutrient availabilities.
Main Results:
- All mutator strains displayed growth defects, which were mitigated by nutrient supplementation in most cases.
- Mutator strains showed significant fluctuations in mutation rates with changing nutritional conditions.
- Wild-type strains maintained a relatively constant mutation rate irrespective of nutritional variation.
Conclusions:
- Conditional growth defects and nutrition-sensitive mutability are general characteristics of mutators.
- Mutability can be modulated in response to nutrient availability, crucial for minimizing extinction risk.
- This study underscores the adaptive significance of regulating mutation rates in dynamic environments.
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