Sign of selection on mutation rate modifiers depends on population size.

Area of Science:

• Evolutionary biology
• Population genetics
• Molecular evolution

Background:

• Natural selection's influence on fitness alleles is well-established.
• Genetic drift can overwhelm selection as population size (N) declines.
• Indirect selection affects offspring fitness distribution, not individual fitness directly.

Purpose of the Study:

• To investigate the effect of population size (N) on indirect selection acting on mutation rate-increasing alleles (mutators).
• To understand how mutators are affected by genomic associations with beneficial and deleterious mutations they generate.

Main Methods:

• Analytical calculations
• Computer simulations
• Experimental evolution using Saccharomyces cerevisiae populations

Main Results:

• Indirect selection favoring mutators in large populations is overcome by genetic drift as N declines.
• Deleterious mutation load is not neutralized by drift before beneficial mutation selection is lost.
• Mutators shift from being favored to disfavored by indirect selection as population size decreases.

Conclusions:

• Indirect selection on mutators shows a strong, qualitatively distinct dependence on population size (N).
• A sign inversion in the selective effect of mutators occurs as population size changes.
• This N-dependent sign inversion highlights the complex interplay between drift, selection, and mutation rate variation.