Thermodynamics of neutral protein evolution

Area of Science:

• Protein evolution
• Molecular evolution
• Biophysics

Background:

• Proteins accumulate mutations during neutral evolution, maintaining stable structures.
• This neutral evolution is key to the molecular clock, a measure of evolutionary change.
• Understanding the relationship between protein stability and mutation is crucial for evolutionary studies.

Purpose of the Study:

• To develop a mathematical theory predicting evolutionary outcomes based on mutation effects.
• To quantitatively describe how neutral evolution impacts protein stability and the molecular clock.
• To investigate the role of protein biophysics in shaping evolutionary processes.

Main Methods:

• Formulating a mathematical theory based on single-mutation stability effects (delta deltaG values).
• Analyzing the number of accumulated mutations, index of dispersion, and stability distribution.
• Considering different population sizes and mutation rates (small and large products).
• Validating theoretical predictions using lattice protein simulations.

Main Results:

• The theory quantitatively predicts marginally stable proteins resulting from neutral evolution.
• Formulas are provided to calculate how stability fluctuations affect the molecular clock.
• Structural influences on evolutionary rates can be derived from single-mutation delta deltaG values.
• High population size and mutation rates lead to increased mutational robustness, stability, and evolutionary rates.

Conclusions:

• Protein biophysics fundamentally shapes neutral evolution and sequence divergence.
• The developed mathematical framework provides a foundation for understanding protein evolution.
• The findings offer insights into molecular clock variations and evolutionary rate determinants.