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Protein structure and evolutionary history determine sequence space topology
Boris E Shakhnovich1, Eric Deeds, Charles Delisi
1Bioinformatics Program, Boston University, Boston, Massachusetts 02215, USA.
Genome Research
|March 3, 2005
Summary
Protein structure's contact density influences gene family size by determining sequence plasticity and fold stability. This relationship holds across various evolutionary divergences, impacting gene duplication and evolution.
Area of Science:
- Structural biology
- Evolutionary biology
- Bioinformatics
Background:
- Variability in gene homolog numbers is a significant challenge with implications for understanding gene duplication, pseudogene formation, and disease.
- The relationship between protein structure and sequence evolution remains incompletely understood.
Purpose of the Study:
- To define and elucidate causes for sequence variability in protein families.
- To investigate the influence of protein structure characteristics on sequence plasticity and functional diversity.
Main Methods:
- Analysis of quantifiable protein structure characteristics.
- Identification of 'contact density' as a measure of fold designability.
- Statistical correlation analysis between gene family size and structural features.
Main Results:
- Protein structure characteristics, specifically contact density, correlate strongly (R² > 0.9) with the average size of gene families.
- Contact density quantifies a protein's ability to accept mutations without losing thermodynamic stability or fold integrity.
- Gene family size is influenced by both structural designability and evolutionary history (gene family age).
Conclusions:
- Protein structure's contact density is a key determinant of sequence entropy and gene family size.
- The correlation between gene family size and contact density is robust across different levels of evolutionary divergence.
- Understanding these structural-sequence relationships offers insights into gene family evolution and diversity.