Nature Genetics 37, 1367 - 1371 (2005)
Published online: 13 November 2005; | doi:10.1038/ng1685
Robust signals of coevolution of interacting residues in mammalian proteomes identified by phylogeny-aided structural analysisSun Shim Choi1, 2, Weimin Li1, 2
& Bruce T Lahn11
Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA. 2
These authors contributed equally to this work.
Correspondence should be addressed to Bruce T Lahn blahn@bsd.uchicago.edu 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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