Diminishing returns epistasis among beneficial mutations decelerates adaptation

Area of Science:

• Evolutionary biology
• Genetics
• Microbiology

Background:

• Epistasis significantly influences evolutionary trajectories and the rate of adaptation.
• Understanding genetic interactions is crucial for predicting evolutionary outcomes.
• Bacterial adaptation provides a model system to study the effects of beneficial mutations.

Purpose of the Study:

• To investigate the impact of epistasis on adaptation by combining beneficial mutations.
• To determine how genetic backgrounds affect the selective benefits of mutations.
• To explore the relationship between epistasis and decelerating fitness gains during adaptation.

Main Methods:

• Generated combinations of beneficial mutations in a bacterium adapting to a new metabolic pathway.
• Assessed the proportional selective benefit of alleles on increasingly fit genetic backgrounds.
• Developed a theoretical model to predict allele interactions based on benefits and costs.

Main Results:

• Three of four beneficial alleles showed decreased selective benefits on more fit backgrounds, indicating diminishing returns epistasis.
• These alleles mitigated morphological defects associated with expressing a foreign metabolic pathway.
• A theoretical model accurately predicted the interactions between these beneficial alleles.

Conclusions:

• Epistasis patterns can differ between within-gene and between-gene interactions during adaptation.
• Diminishing returns epistasis is a key factor contributing to the observed deceleration of fitness gains during adaptation.
• This study provides novel insights into the genetic mechanisms underlying evolutionary adaptation.