title: A novel method to detect proteins evolving at correlated rates: identifying new functional relationships between coevolving proteins.
abstract: Interacting proteins evolve at correlated rates, possibly as the result of evolutionary pressures shared by functional groups and/or coevolution between interacting proteins. This evolutionary signature can be exploited to learn more about protein networks and to infer functional relationships between proteins on a genome-wide scale. Multiple methods have been introduced that detect correlated evolution using amino acid distances. One assumption made by these methods is that the neutral rate of nucleotide substitution is uniform over time; however, this is unlikely and such rate heterogeneity would adversely affect amino acid distance methods. We explored alternative methods that detect correlated rates using protein-coding nucleotide sequences in order to better estimate the rate of nonsynonymous substitution at each branch (d(N)) normalized by the underlying synonymous substitution rate (d(S)). Our novel likelihood method, which was robust to realistic simulation parameters, was tested on Drosophila nuclear pore proteins, which form a complex with well-documented physical interactions. The method revealed significantly correlated evolution between nuclear pore proteins, where members of a stable subcomplex showed stronger correlations compared with those proteins that interact transiently. Furthermore, our likelihood approach was better able to detect correlated evolution among closely related species than previous methods. Hence, these sequence-based methods are a complementary approach for detecting correlated evolution and could be applied genome-wide to provide candidate protein-protein interactions and functional group assignments using just coding sequences.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, USA. nlc47@cornell.edu
authors.forename: Nathaniel L
authors.initials: NL
authors.lastname: Clark
authors.forename: Charles F
authors.initials: CF
authors.lastname: Aquadro
mesh_terms: D000818:Animals; D003198:Computer Simulation; D030562:Databases, Protein; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D016013:Likelihood Functions; D008957:Models, Genetic; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D020539:Sequence Analysis, Protein / Q000379:methods*
chemical_list: D029721:Drosophila Proteins; D028861:Nuclear Pore Complex Proteins