Quantifying the impact of changes in effective population size and expression level on the rate of coding sequence...

Area of Science:

• Evolutionary biology
• Molecular evolution
• Population genetics

Background:

• Molecular sequences evolve under selection and genetic drift, with effective population size (N_e) modulating selection strength.
• The ratio of selected to neutral substitution rates (ω) is expected to decrease with higher N_e due to stronger purifying selection.
• Existing models suggest ω might be independent of N_e, and empirical data show increased protein expression lowers ω.

Purpose of the Study:

• To theoretically approximate the response of ω to changes in N_e and protein expression level.
• To investigate the relationship between genotype, phenotype, fitness, and evolutionary rates.
• To evaluate if protein conformational stability adequately explains empirical variations in ω.

Main Methods:

• Derived a theoretical approximation for ω response using an explicit genotype-phenotype-fitness map.
• Applied the method to proteins under selection for conformational stability.
• Validated findings with simulations using more complex models.

Main Results:

• Predicted a weak and interchangeable response of ω to changes in N_e or expression level.
• The derived theoretical approximation is generally valid for additive traits and log-concave fitness functions.
• Conformational stability alone may not fully explain empirically observed ω variations across species.

Conclusions:

• Protein conformational stability is likely insufficient to explain all observed variations in ω.
• Other biophysical factors, such as protein-protein interactions, may be crucial.
• Future research should explore these additional factors to better understand molecular evolution dynamics.