The lower bound to the evolution of mutation rates

Area of Science:

• Evolutionary biology
• Molecular biology
• Genetics

Background:

• The evolutionary drivers of mutation rate variation within and between species are not fully understood.
• A common hypothesis suggests mutation rates are limited by physiological trade-offs between fidelity and reproductive output, but evidence is lacking for cellular organisms.

Purpose of the Study:

• To propose an alternative hypothesis for the lower barrier to mutation rate evolution.
• To investigate the role of random genetic drift in limiting the reduction of mutation rates.

Main Methods:

• Theoretical modeling of mutation rate evolution.
• Analysis of existing empirical data on mutation rates, genome size, and effective population size.

Main Results:

• The study suggests that random genetic drift, rather than molecular limitations, defines the lower boundary for mutation rate evolution.
• A critical point exists where the benefits of further mutation rate reduction are overcome by drift.
• This hypothesis aligns with observed inverse relationships between mutation rate and genome size in microbes, and negative scaling with effective population size in eukaryotes.

Conclusions:

• Random genetic drift is a key factor in shaping mutation rates, particularly at low levels.
• The physiological limit hypothesis for mutation rate evolution lacks empirical support in cellular organisms.
• Elevated error rates in less utilized polymerases and repair pathways may also be influenced by drift.