Mistranslation Reduces Mutation Load in Evolving Proteins through Negative Epistasis with DNA Mutations

Area of Science:

• Evolutionary Biology
• Molecular Biology
• Genetics

Background:

• Phenotypic mutations from translational errors are more frequent than DNA mutations.
• These phenotypic mutations can interact with DNA mutations, influencing adaptive evolution.

Purpose of the Study:

• To investigate how mistranslation affects the adaptive evolution of proteins.
• To understand the interaction between phenotypic and DNA mutations under varying mistranslation rates.

Main Methods:

• Evolving populations of green fluorescent protein (GFP) in Escherichia coli hosts with high and low mistranslation rates.
• Applying purifying selection for ancestral fluorescence and directional selection for a new fluorescence.
• Utilizing high-throughput sequencing to analyze DNA mutations and phenotypic changes.

Main Results:

• High-mistranslation populations showed modestly increased yellow fluorescence evolution.
• Elevated mistranslation reduced the accumulation of deleterious DNA mutations under both purifying and directional selection.
• Mistranslation amplified the fitness effects of deleterious DNA mutations via negative epistasis, but did not affect beneficial mutations.

Conclusions:

• Phenotypic mutations arising from mistranslation interact epistatically with DNA mutations.
• Mistranslation can reduce a population's mutation load, thereby influencing evolvability.
• This study highlights a novel mechanism by which translational accuracy impacts evolutionary trajectories.