Population Heterogeneity in Mutation Rate Increases the Frequency of Higher-Order Mutants and Reduces Long-Term...

Area of Science:

• Evolutionary Biology
• Population Genetics

Background:

• Mutation rate is traditionally assumed constant in population genetics.
• Evidence suggests mutation rates vary among individuals due to genetic and environmental factors.

Purpose of the Study:

• To investigate the evolutionary consequences of mutation rate heterogeneity within populations.
• To extend population genetic models to incorporate variable mutation rates.

Main Methods:

• Reviewing existing evidence for mutation rate variation.
• Developing new population genetic models allowing for arbitrary mutation rate distributions.
• Analyzing effects across different evolutionary timescales and with/without inheritance.

Main Results:

• Mutation rate heterogeneity increases the probability of extreme mutation outcomes per generation.
• It accelerates the evolution of multi-point mutants (deleterious and beneficial) under selection.
• Population mean fitness is consistently enhanced by mutation rate variation.

Conclusions:

• Mutation rate heterogeneity significantly impacts evolutionary trajectories.
• Assuming a constant mutation rate may underestimate adaptive potential, particularly in medically relevant contexts (e.g., cancer, pathogens).
• Further empirical quantification of mutation rate distributions is needed.