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Updated: Aug 28, 2025

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
Simple mechanisms for the evolution of protein complexity.
Arvind S Pillai1,2, Georg K A Hochberg3,4, Joseph W Thornton1,5
1Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, USA.
Protein evolution is faster than previously thought. Just a few genetic mutations can unlock complex protein functions, revealing that chance plays a significant role alongside natural selection in molecular complexity.
Area of Science:
- Biochemistry
- Molecular Biology
- Evolutionary Biology
Background:
- Proteins exhibit complex structures and functions, including folding, complex assembly, and allostery.
- Traditionally, protein evolution was believed to occur through gradual changes driven by natural selection over long periods.
Purpose of the Study:
- To investigate the mechanisms underlying the evolution of protein complexity.
- To challenge the classical view of gradual evolutionary trajectories for protein features.
Main Methods:
- Review of evidence from biochemistry, protein engineering, and molecular evolution studies.
- Analysis of the genetic and physical underpinnings of protein multimerization, allostery, and novel folds.
Main Results:
- Naturally occurring proteins often possess latent complex properties, accessible via few mutations.
- Underlying physical properties for complex features can be fortuitous by-products of simpler protein architectures.
- Vast sequence spaces encode complex protein features, allowing access from numerous evolutionary starting points.
Conclusions:
- Protein complexity can evolve rapidly through sudden transitions, not just gradual change.
- Both random chance and natural selection are critical drivers of protein molecular evolution.
- The evolution of complex protein functions is facilitated by short and numerous mutational pathways.
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