Evolution of phosphoregulation: Comparison of phosphorylation patterns across yeast species

Pedro Beltrao, Jonathan C. Trinidad, Dorothea Fiedler, Assen Roguev, Wendell A. Lim, Kevan M. Shokat, Alma L. Burlingame, Nevan J. Krogan

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

The extent by which different cellular components generate phenotypic diversity is an ongoing debate in evolutionary biology that is yet to be addressed by quantitative comparative studies. We conducted an in vivo mass-spectrometry study of the phosphoproteomes of three yeast species (Saccharomyces cerevisiae, Candida albicans, and Schizosaccharomyces pombe) in order to quantify the evolutionary rate of change of phosphorylation. We estimate that kinase-substrate interactions change, at most, two orders of magnitude more slowly than transcription factor (TF)-promoter interactions. Our computational analysis linking kinases to putative substrates recapitulates known phosphoregulation events and provides putative evolutionary histories for the kinase regulation of protein complexes across 11 yeast species. To validate these trends, we used the E-MAP approach to analyze over 2,000 quantitative genetic interactions in S. cerevisiae and Sc. pombe, which demonstrated that protein kinases, and to a greater extent TFs, show lower than average conservation of genetic interactions. We propose therefore that protein kinases are an important source of phenotypic diversity.

Original languageEnglish
Article numbere1000134
JournalPLoS Biology
Volume7
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

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