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Robust signals of coevolution of interacting residues in mammalian proteomes identified by phylogeny-aided structural analysis

Nature Genetics 37, 1367–1371 (2005) | Download Citation

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Abstract

The structure of a protein depends critically on the complex interactions among its amino acid residues. It has long been hypothesized that interacting residues might tend to coevolve, but it is not known whether such coevolution is a general phenomenon across the proteome. Here, we describe a novel methodology called phylogeny-aided structural analysis, which uncovers robust signals of interacting-residue coevolution in mammalian proteomes. Furthermore, this new method allows the magnitude of coevolution to be quantified. Finally, it facilitates a comprehensive evaluation of various factors that affect interacting-residue coevolution, such as the physicochemical properties of the interactions between residues, solvent accessibility of the residues and their secondary structure context.

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Acknowledgements

We thank C.M. Malcom, P.A. Rice, T.R. Sosnick, E.J. Vallender, G.J. Wyckoff and X. Yang for technical help, discussions and comments on the manuscript.

Author information

    • Sun Shim Choi
    •  & Weimin Li

    These authors contributed equally to this work.

Affiliations

  1. Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.

    • Sun Shim Choi
    • , Weimin Li
    •  & Bruce T Lahn

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Bruce T Lahn.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Declining signal of coevolution as the sequence identity between the modeled protein and the template declines.

  2. 2.

    Supplementary Table 1

    Proteins in the rat-human-dog data set.

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DOI

https://doi.org/10.1038/ng1685

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