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Study of Protein Dynamics via Neutron Spin Echo Spectroscopy
Published on: April 13, 2022
Protein biophysics explains why highly abundant proteins evolve slowly
Adrian W R Serohijos1, Zilvinas Rimas, Eugene I Shakhnovich
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Cell Reports
|September 4, 2012
Summary
Cellular abundance and protein folding stability (ΔG) are key factors influencing protein evolutionary rates. Biophysical principles explain how these factors, along with selection against misfolded proteins, shape molecular evolution across all life.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Biophysics
Background:
- Highly abundant proteins consistently evolve slowly across all life, suggesting cellular abundance is a primary determinant of protein evolutionary rate.
- However, the broad distribution of evolutionary rates indicates other factors also influence this process.
Purpose of the Study:
- To investigate the role of protein folding stability (ΔG) as a determinant of protein evolutionary rate, alongside cellular abundance.
- To elucidate the biophysical mechanisms underlying the relationship between protein abundance, stability, and evolutionary rate.
Main Methods:
- Theoretical analysis and multiscale simulations were employed to model protein evolution.
- Empirical data from bacteria were used to validate predictions regarding abundance-evolutionary rate correlations.
Main Results:
- Protein folding stability (ΔG) is identified as a causal variable in protein evolutionary rate, acting in concert with abundance under selection against misfolded proteins.
- A biophysically driven anticorrelation between premutation folding stability (ΔG) and the effect of mutations (ΔΔG) is essential for the observed covariation between abundance and evolutionary rate.
- The strength of the abundance-evolutionary rate correlation is shown to be dependent on the divergence time between genomes.
Conclusions:
- Protein biophysics, specifically folding stability and its interplay with abundance, plays an intrinsic role in shaping universal patterns of molecular evolution.
- The findings provide a deeper understanding of the evolutionary constraints and mechanisms governing protein sequence evolution.
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