Escherichia coli with a Tunable Point Mutation Rate for Evolution Experiments

Area of Science:

• Evolutionary biology
• Microbial genetics

Background:

• Mutation rates and their fitness effects are fundamental to evolutionary processes.
• Selection acts on mutation rates due to linkage with mutation effects, with direction dependent on the fitness landscape.
• Previous studies using mutator/antimutator strains had limitations in controlling mutation rate variation.

Purpose of the Study:

• To investigate the direct effect of a variable mutation rate on evolution within a single organism and environment.
• To develop a model system for smoothly controlling mutation rates over a significant range.

Main Methods:

• Genetically engineered *Escherichia coli* with inducible control over mismatch repair proteins (MutH and MutL) to vary point mutation rates.
• Conducted an approximately 350-generation evolution experiment with controlled, continuous variation of the mutation rate.
• Confirmed stability of the engineered construct and mutation rate throughout the experiment.

Main Results:

• Demonstrated a stable, inducible system for smoothly varying mutation rates over two orders of magnitude in *E. coli*.
• Observed a higher number of single nucleotide polymorphisms in strains evolved at higher mutation rates.
• These variations are likely attributable to beneficial mutations or linkage of mutations to beneficial alleles.

Conclusions:

• The study provides a novel tool to experimentally manipulate mutation rates and study their evolutionary consequences.
• Higher mutation rates can accelerate the accumulation of genetic variation, potentially driving adaptation.
• Findings highlight the interplay between mutation rate, fitness landscape, and evolutionary trajectories.