title: Evolution of phosphoregulation: comparison of phosphorylation patterns across yeast species.
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.
authors: Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, United States of America. pedro.beltrao@ucsf.edu
authors: Pedro
authors: P
authors: Beltrao
authors: Jonathan C
authors: JC
authors: Trinidad
authors: Dorothea
authors: D
authors: Fiedler
authors: Assen
authors: A
authors: Roguev
authors: Wendell A
authors: WA
authors: Lim
authors: Kevan M
authors: KM
authors: Shokat
authors: Alma L
authors: AL
authors: Burlingame
authors: Nevan J
authors: NJ
authors: Krogan
mesh_terms: D002176:Candida albicans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity; D053719:Tandem Mass Spectrometry; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D009097:Multienzyme Complexes; D020543:Proteome; D014157:Transcription Factors; D010770:Phosphotransferases