Natural selection of protein structural and functional properties: a single nucleotide polymorphism perspective
Jinfeng Liu1, Yan Zhang, Xingye Lei
1Department of Bioinformatics, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Genome Biology
|April 10, 2008
Summary
The SNP A/S ratio effectively measures selective constraints on proteins, correlating with evolutionary divergence. This analysis reveals how protein properties influence natural selection, offering insights into human-specific gene evolution.
Area of Science:
- Molecular Biology
- Evolutionary Genetics
- Bioinformatics
Background:
- Protein evolution rates are governed by functional and structural constraints.
- The Ka/Ks ratio traditionally measures selective constraints using interspecies data.
- Single nucleotide polymorphism (SNP) data allows for the calculation of SNP A/S ratios, reflecting intraspecies constraints.
Purpose of the Study:
- To conduct the first large-scale survey of SNP A/S ratios across diverse protein properties.
- To validate the SNP A/S ratio as a robust indicator of selective constraints.
- To explore the relationship between SNP A/S ratios and various protein structural and functional characteristics.
Main Methods:
- Utilized the dbSNP database for large-scale SNP data analysis.
- Calculated SNP A/S ratios for numerous proteins and their properties.
- Correlated SNP A/S ratios with protein expression levels, paralogy, evolutionary age, structural features (disordered regions, solvent exposure, loops), cellular localization, and disease association.
Main Results:
- Confirmed a strong correlation between SNP A/S ratios and Ka/Ks ratios for evolutionary divergence.
- Identified stronger selective constraints in proteins with high/broad mRNA expression, no paralogs, earlier evolutionary origin, disordered regions, cytoplasmic/nuclear localization, and disease relevance.
- Found increased residue variation in solvent-exposed, loop, disordered, low-complexity regions, and signal peptides.
- Highlighted histones and protein kinases as highly constrained, while olfactory and taste receptors are highly variable.
Conclusions:
- The SNP A/S ratio is a reliable measure for assessing selective constraints.
- Correlations provide insights into natural selection acting on protein properties, especially for human genes.
- This study enhances understanding of evolutionary pressures shaping protein diversity within the human lineage.
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