Identifying Coevolving Residues in Protein Evolution
Author Information
Author(s): Little Daniel Y., Chen Lu
Primary Institution: University of California, Berkeley
Hypothesis
The selective pressures associated with a mutation at one site depend on the amino acid identity of interacting sites.
Conclusion
The study demonstrates that coevolving residue pairs tend to be in close physical proximity and that pairs of catalytic residues are more likely to be identified as coevolving.
Supporting Evidence
- Coevolving residue pairs are significantly closer together than all tested residue pairs.
- Pairs of catalytic residues have a significantly increased likelihood to be identified as coevolving.
- The algorithm shows high correlation with protein structure.
Takeaway
This study looks at how certain parts of proteins change together over time, showing that parts that are close to each other in the protein structure often influence each other's evolution.
Methodology
The study refines mutual information as a measure of coevolution, removing biases and accounting for variability, and analyzes a large database of protein alignments.
Potential Biases
Potential biases from phylogenetic relationships and site-specific conservation may affect results.
Limitations
The true coevolutionary history of a protein cannot be experimentally determined, complicating validation.
Statistical Information
P-Value
p<1×10−16
Statistical Significance
p<1×10−16
Digital Object Identifier (DOI)
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