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Quantifying the evolutionary divergence of protein structures: the role of function change and function conservation
Alberto Pascual-García1, David Abia, Raúl Méndez
1Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, Spain.
Proteins
|October 16, 2009
Summary
Protein evolution shows that structure and sequence divergence are linked. Functional constraints impact divergence rates, with differing functions accelerating changes and promoting diversity.
Area of Science:
- Molecular Evolution
- Structural Bioinformatics
- Protein Science
Background:
- The molecular clock hypothesis posits a constant rate of protein sequence divergence.
- Previous work established a link between protein structure and sequence divergence.
- The influence of protein function on these divergence rates remains less understood.
Purpose of the Study:
- To investigate how protein function affects the relationship between sequence and structure divergence.
- To introduce a new measure, contact divergence, for analyzing structural changes.
- To test the molecular clock hypothesis across different protein superfamilies.
Main Methods:
- Analysis of four large protein superfamilies (globins, aldolases, P-loop, NADP-binding).
- Introduction and application of 'contact divergence' as a structure divergence measure.
- Examination of structure similarity networks and clustering coefficients.
Main Results:
- Small structure and sequence divergences are proportional, supporting the molecular clock.
- Proteins with the same function exhibit limited structure divergence due to functional constraints.
- Proteins with different functions show accelerated structure divergence, potentially driven by positive selection.
- Low sequence identity correlates with a significant increase in structural diversity, suggesting functional diversification.
- Large insertions/deletions (indels) are strongly associated with functional changes.
Conclusions:
- Protein function significantly modulates the rates of sequence and structure divergence.
- Functional constraints can stabilize protein structure, while the pursuit of new functions drives divergence.
- Structural diversity explosion at low sequence identity likely reflects functional diversification.
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