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Adaptive tuning of mutation rates allows fast response to lethal stress in Escherichia coli
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DOI：10.7554/eLife.22939.png)
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Abstract
En 中文
While specific mutations allow organisms to adapt to stressful environments, most changes in an organism's DNA negatively impact fitness. The mutation rate is therefore strictly regulated and often considered a slowly-evolving parameter. In contrast, we demonstrate an unexpected flexibility in cellular mutation rates as a response to changes in selective pressure. We show that hypermutation independently evolves when different Escherichia coli cultures adapt to high ethanol stress. Furthermore, hypermutator states are transitory and repeatedly alternate with decreases in mutation rate. Specifically, population mutation rates rise when cells experience higher stress and decline again once cells are adapted. Interestingly, we identified cellular mortality as the major force driving the quick evolution of mutation rates. Together, these findings show how organisms balance robustness and evolvability and help explain the prevalence of hypermutation in various settings, ranging from emergence of antibiotic resistance in microbes to cancer relapses upon chemotherapy.
Keywords:
DNA-REPLICATION ERRORS
EXPERIMENTAL EVOLUTION
ETHANOL TOLERANCE
MISMATCH REPAIR
PSEUDOMONAS-AERUGINOSA
BACTERIAL-POPULATIONS
FLUCTUATION ANALYSIS
ENVIRONMENTAL-CHANGE
ASEXUAL POPULATIONS
CYSTIC-FIBROSIS
