Identification of Coevolving Residues and Coevolution Potentials Emphasizing Structure, Bond Formation and Catalytic Coordination in Protein Evolution
2009

Identifying Coevolving Residues in Protein Evolution

Sample size: 1592 publication Evidence: high

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)

10.1371/journal.pone.0004762

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