Beltrao Pedro, Trinidad Jonathan C, Fiedler Dorothea, Roguev Assen, Lim Wendell A, Shokat Kevan M, Burlingame Alma L, Krogan Nevan J
Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, United States of America.
PLoS Biol. 2009 Jun 16;7(6):e1000134. doi: 10.1371/journal.pbio.1000134. Epub 2009 Jun 23.
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.
不同细胞成分产生表型多样性的程度，是进化生物学中一个仍在进行的争论话题，尚未通过定量比较研究得到解决。我们对三种酵母物种（酿酒酵母、白色念珠菌和粟酒裂殖酵母）的磷酸化蛋白质组进行了体内质谱研究，以量化磷酸化的进化变化速率。我们估计，激酶 - 底物相互作用的变化速度，至多比转录因子（TF）- 启动子相互作用慢两个数量级。我们将激酶与推定底物联系起来的计算分析概括了已知的磷酸化调控事件，并为11种酵母物种中蛋白质复合物的激酶调控提供了推定的进化历史。为了验证这些趋势，我们使用E-MAP方法分析了酿酒酵母和粟酒裂殖酵母中超过2000种定量遗传相互作用，结果表明蛋白激酶，以及在更大程度上的转录因子，显示出低于平均水平的遗传相互作用保守性。因此，我们提出蛋白激酶是表型多样性的一个重要来源。
