Interactions between evolutionary processes at high mutation rates.

Area of Science:

• Evolutionary Biology
• Computational Biology
• Genetics

Background:

• High mutation rates present complex evolutionary dynamics.
• Several processes like mutation-selection balance, Muller's Ratchet, and clonal interference can impact evolution.
• Modeling these interactions analytically is challenging.

Purpose of the Study:

• To investigate evolutionary processes in finite, asexual populations under varying mutation rates.
• To develop criteria predicting the importance of different evolutionary mechanisms.
• To model genotype-phenotype-fitness relationships using RNA folding simulations.

Main Methods:

• Simulations of asexual populations with realistic genotype-phenotype-fitness maps.
• Modeling RNA folding to represent these maps.
• Varying mutation rates and analyzing population dynamics.

Main Results:

• Strong purifying selection relative to mutation led to mutation-selection balance and maintained maximal fitness.
• Weaker purifying selection resulted in the loss of optimal genotypes but ongoing compensatory evolution led to approximate fitness equilibration.
• Mean fitness was comparable across strong and weak purifying selection relative to the total genomic mutation rate.

Conclusions:

• Simple criteria can predict the dominance of specific evolutionary processes at high mutation rates.
• Mutation-selection balance and compensatory evolution play key roles in maintaining or equilibrating fitness.
• Further theoretical work is needed to fully interpret the complex interactions observed in simulations.