Selection maintaining protein stability at equilibrium.

Area of Science:

• Protein Evolution
• Molecular Biology
• Biophysics

Background:

• Traditional views attribute protein evolution to neutral mutations and random drift.
• Recent studies suggest protein stability and misfolding costs significantly impact evolutionary rates.
• Understanding these factors is crucial for predicting protein evolution dynamics.

Purpose of the Study:

• To investigate protein evolution under selection pressures that maintain protein stability.
• To model the relationship between protein stability, fitness costs, and evolutionary rates.
• To analyze the influence of protein abundance, indispensability, and structural constraints on evolutionary dynamics.

Main Methods:

• Developed a model for protein fitness incorporating costs of misfolded proteins (s=κexp(ΔG/kT)(1-exp(ΔΔG/kT))).
• Approximated the distribution of stability changes (ΔΔG) as bi-Gaussian.
• Analyzed the equilibrium point (ΔGe) of protein stability and its relation to Ka/Ks ratios.

Main Results:

• Nearly neutral selection dominates only in low-abundance, non-essential proteins.
• Positive selection for stabilizing mutations is significant in other proteins to maintain stability.
• Protein abundance/indispensability and structural constraints modulate evolutionary rates differently based on protein type.
• Protein stability and Ka/Ks decrease with increasing growth temperature.

Conclusions:

• Protein stability is a significant driving force in protein evolution, alongside random drift.
• Selection for protein stability plays a key role, particularly in essential and abundant proteins.
• Environmental factors like temperature influence protein stability and evolutionary rates.