A highly unexpected strong correlation between fixation probability of nonsynonymous mutations and mutation rate

Area of Science:

• Evolutionary biology
• Molecular evolution
• Genomics

Background:

• The nonsynonymous-to-synonymous substitution ratio (K(a)/K(s)) is a key metric in molecular evolution.
• It is widely used to infer the strength of natural selection acting on protein-coding genes.
• Current theories posit a direct correlation between K(a)/K(s) and selective pressure.

Purpose of the Study:

• To investigate the relationship between K(a)/K(s) and mutation rate.
• To challenge existing paradigms in coding-sequence evolution.
• To reassess the utility of K(a)/K(s) as a sole indicator of selection strength.

Main Methods:

• Analysis of substitution rates in coding sequences.
• Quantification of nonsynonymous (K(a)) and synonymous (K(s)) substitution rates.
• Statistical correlation analysis between K(a)/K(s) and K(s).

Main Results:

• A strong correlation was observed between K(a)/K(s) and the mutation rate (K(s)).
• This correlation's magnitude is comparable to that between K(a)/K(s) and selection strength.
• The findings are inconsistent with prevailing theories of molecular evolution.

Conclusions:

• The mutation rate significantly influences K(a)/K(s), independent of selection.
• Current models of coding-sequence evolution require re-evaluation.
• The application of K(a)/K(s) as a measure of selection strength needs critical reassessment.