Quantifying the impact of protein tertiary structure on molecular evolution

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Structural Biology

Background:

• Understanding the evolutionary trajectory of proteins is crucial for deciphering biological complexity.
• The influence of protein tertiary structure on evolutionary rates has been a subject of ongoing investigation.
• Previous models often simplified or omitted the direct impact of structural features on sequence evolution.

Purpose of the Study:

• To quantitatively assess the evolutionary impact of protein tertiary structure.
• To determine the relative contributions of solvent accessibility and amino acid interactions to evolutionary rates.
• To test the hypothesis that protein structure significantly influences protein evolution.

Main Methods:

• Collected experimentally determined tertiary structures and DNA sequences for 1,195 genes.
• Developed a computational model incorporating structural effects on evolutionary rates.
• Utilized Bayes factors to compare models with and without structural influence.
• Analyzed the roles of solvent accessibility and pairwise amino acid interactions.

Main Results:

• Bayes factors strongly supported the hypothesis that protein structure influences protein evolution across most genes.
• Both solvent accessibility and pairwise amino acid interactions were inferred as significant factors in protein evolution.
• A weak but real correlation was found between structural-evolutionary relationships and Gene Ontology annotations.
• The mean impacts of solvent accessibility and pairwise interactions on evolutionary rates were comparable.

Conclusions:

• Protein tertiary structure is a significant driver of protein evolution.
• Solvent accessibility and amino acid interactions are critical structural determinants of evolutionary rates.
• These findings provide a more nuanced understanding of the interplay between protein structure and evolution.