Bioinformatics, Department of Biology, Faculty of Science, Utrecht University, Padualaan, The Netherlands.
Genome Biol. 2008 Oct 1;9(10):R144. doi: 10.1186/gb-2008-9-10-r144.
Reversible phosphorylation of proteins is involved in a wide range of processes, ranging from signaling cascades to regulation of protein complex assembly. Little is known about the structure and evolution of phosphorylation networks. Recent high-throughput phosphoproteomics studies have resulted in the rapid accumulation of phosphopeptide datasets for many model organisms. Here, we exploit these novel data for the comparative analysis of phosphorylation events between different species of eukaryotes.
Comparison of phosphoproteomics datasets of six eukaryotes yields an overlap ranging from approximately 700 sites for human and mouse (two large datasets of closely related species) to a single site for fish and yeast (distantly related as well as two of the smallest datasets). Some conserved events appear surprisingly old; those shared by plant and animals suggest conservation over the time scale of a billion years. In spite of the hypothesized incomprehensive nature of phosphoproteomics datasets and differences in experimental procedures, we show that the overlap between phosphoproteomes is greater than expected by chance and indicates increased functional relevance. Despite the dynamic nature of the evolution of phosphorylation, the relative overlap between the different datasets is identical to the phylogeny of the species studied.
This analysis provides a framework for the generation of biological insights by comparative analysis of high-throughput phosphoproteomics datasets. We expect the rapidly growing body of data from high-throughput mass spectrometry analysis to make comparative phosphoproteomics a powerful tool for elucidating the evolutionary and functional dynamics of reversible phosphorylation.
蛋白质的可逆磷酸化参与了广泛的过程，从信号级联到蛋白质复合物组装的调控。关于磷酸化网络的结构和进化知之甚少。最近高通量磷酸蛋白质组学研究导致了许多模式生物的磷酸肽数据集的快速积累。在这里，我们利用这些新的数据来比较不同真核生物物种之间的磷酸化事件。
比较六种真核生物的磷酸蛋白质组学数据集，发现人类和小鼠（两个密切相关物种的大型数据集）之间的重叠约为 700 个位点，而鱼类和酵母（远缘关系以及两个最小数据集）之间只有一个位点。一些保守的事件似乎非常古老；那些在植物和动物中共享的事件表明，在十亿年的时间尺度上是保守的。尽管磷酸蛋白质组学数据集被假设为不完整，实验程序也存在差异，但我们表明，磷酸蛋白质组之间的重叠大于偶然发生的重叠，表明功能相关性增加。尽管磷酸化的进化具有动态性质，但不同数据集之间的相对重叠与所研究物种的系统发育相同。
通过比较高通量磷酸蛋白质组学数据集的分析，这项分析为通过比较分析产生生物学见解提供了一个框架。我们期望高通量质谱分析产生的大量数据能够使比较磷酸蛋白质组学成为阐明可逆磷酸化的进化和功能动态的有力工具。
