Rampant purifying selection conserves positions with posttranslational modifications in human proteins
1Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University.
Molecular Biology and Evolution
|January 29, 2011
Summary
Posttranslational modifications (PTMs) are crucial for protein function. Evolutionary analysis reveals significant purifying selection at PTM sites, indicating their long-term importance in human proteins.
Area of Science:
- Evolutionary biology
- Molecular biology
- Biochemistry
Background:
- Posttranslational modifications (PTMs) are vital chemical alterations affecting protein structure and function.
- Previous evolutionary analyses yielded unclear results regarding selective pressures on PTMs.
- PTMs are implicated in numerous human diseases.
Purpose of the Study:
- To investigate evolutionary selective pressures at posttranslational modification sites in human proteins.
- To determine if PTMs are under significant purifying selection.
- To enhance understanding of PTMs' historical function and aid in predicting PTM sites.
Main Methods:
- Large-scale analysis of 16,836 PTM positions across 4,484 human proteins.
- Comparative analysis of evolutionary selection at PTM residues versus unmodified amino acids.
- Focus on phosphorylated and N-linked glycosylated proteins.
Main Results:
- Higher purifying selection observed at PTM sites in 70% of analyzed phosphorylated and N-linked glycosylated proteins.
- Purifying selection was up to 42% more intense at PTM residues compared to unmodified sites.
- Evidence of extensive, long-term selective pressures on human protein positions with PTMs.
Conclusions:
- PTMs are subject to significant evolutionary purifying selection, challenging previous assumptions.
- These findings highlight the conserved functional importance of PTMs throughout evolutionary history.
- Evolutionary comparisons can improve the prediction of functional PTM sites.
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