title: Specificity in protein interactions and its relationship with sequence diversity and coevolution.
abstract: Studies of interacting proteins have found correlated evolution of the sequences of binding partners, apparently as a result of compensating mutations to maintain specificity (i.e., molecular coevolution). Here, we analyze the coevolution of interacting proteins in yeast and demonstrate correlated evolution of binding partners in eukaryotes. Detailed investigation of this apparent coevolution, focusing on the proteins' surface and binding interface, surprisingly leads to no improvement in the correlation. We conclude that true coevolution, as characterized by compensatory mutations between binding partners, is unlikely to be chiefly responsible for the apparent correlated evolution. We postulate that the correlation between sequence alignments is simply due to interacting proteins being subject to similar constraints on their evolutionary rate. Because gene expression has a strong influence on evolutionary rate, and interacting proteins will tend to have similar levels of expression, we investigated this particular constraint. We found that the absolute expression level outperformed correlated evolution for predicting interacting protein partners. A correlation between sequence alignments could also be identified not only between pairs of proteins that physically interact but also between those that are merely functionally related (i.e., within the same protein complex). This indicates that the observed correlated evolution of interacting proteins is due to similar constraints on evolutionary rate and not coevolution.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, United Kingdom.
authors.forename: Luke
authors.initials: L
authors.lastname: Hakes
authors.forename: Simon C
authors.initials: SC
authors.lastname: Lovell
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Oliver
authors.forename: David L
authors.initials: DL
authors.lastname: Robertson
mesh_terms: D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D015870:Gene Expression; D011506:Proteins / Q000737:chemistry*; D012372:ROC Curve; D016415:Sequence Alignment
chemical_list: D011506:Proteins