Specificity in protein interactions and its relationship with sequence diversity and coevolution

Hakes, L., Lovell, S. C., Oliver, S. G. and Robertson, D. L. (2007) Specificity in protein interactions and its relationship with sequence diversity and coevolution. Proceedings of the National Academy of Sciences of the United States of America, 104(19), pp. 7999-8004. (doi:10.1073/pnas.0609962104) (PMID:17468399) (PMCID:PMC1876561)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robertson, Professor David
Authors: Hakes, L., Lovell, S. C., Oliver, S. G., and Robertson, D. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490

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