10月18日，Molecular Biology and Evolution杂志在线发表了中科院系统生物学重点实验室李亦学研究组与曾嵘研究组、日本国立遗传研究所Yoshio Tateno教授以及德国国家环境生物学研究中心流行病研究所在中科院系统生物学重点实验室的进修生Ludwig Geistlinger等共同合作取得的研究成果。该项研究报道了蛋白质磷酸化修饰的进化与功能的相关性在脊椎动物和无脊椎动物之间存在显着的差异。该项工作主要由博士研究生王振在李亦学研究员和曾嵘研究员的指导下完成。

蛋白质的翻译后修饰对细胞内众多的生物学过程具有重要的调控作用。研究在漫长的进化的过程中蛋白质的翻译后修饰位点的变异与蛋白质功能的关系有助于对蛋白质的翻译后修饰的重要性进行分类，发现蛋白质的翻译后修饰调控的精细机制。

通过建立的分析方法，作者研究发现，蛋白质磷酸化修饰的进化及其与功能的相关性在脊椎动物和无脊椎动物之间存在显着的差异。该项研究纠正了2009年Tan发表在Science上的文章中的模糊结论（Science , 2009， Vol. 325, pp-1686），指出tyrosine磷酸化位点的丢失对于脊椎动物来说仅仅存在于一些与细胞基本的生化过程相关的蛋白质中，而脊椎动物特有的细胞生化过程相关的蛋白质中tyrosine磷酸化位点整体上不仅没有丢失，而且存在非常显着的增加。这个现象可能预示脊椎动物和无脊椎动物应对环境压力，在蛋白质磷酸化修饰调控机制的进化方面采取了一种截然不同的方式，其背后的驱动力值得进一步研究。

该研究工作得到国家973项目、国家自然科学基金委、中科院知识创新工程、科技部863项的经费资助。

英文摘要：

Mol Biol Evol doi: 10.1093/molbev/msq268

Evolution of protein phosphorylation for distinct functional modules in vertebrate genomes
Zhen Wang1,2,?, Guohui Ding1,3,?, Ludwig Geistlinger4, Li Hong1,2, Lei Liu1,3, Rong Zeng1,*, Yoshio Tateno5,* and Yixue Li1,3,*

1Key Lab of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, P.R.China
2Graduate School of the Chinese Academy of Sciences, 19 Yuquan Road, Beijing, P.R.China
3Shanghai Center for Bioinformation Technology, 100 Qinzhou Road, Shanghai, P.R.China
4Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
5Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima, Shizuoka, Japan

Recent publications have revealed that the evolution of phosphosites is influenced by the local protein structures and whether the phosphosites have characterized functions or not. With knowledge of the wide functional range of phosphorylation, we attempted to clarify whether the evolutionary conservation of phosphosites is different among distinct functional modules. We grouped the phosphosites in the human genome into the modules according to the functional categories of KEGG, and investigated their evolutionary conservation in vertebrate genomes from mouse to zebrafish. We have found that the phosphosites in the vertebrate-specific functional modules (VFMs) such as cellular signaling processes and responses to stimuli are evolutionarily more conserved than those in the basic functional modules (BFMs) such as metabolic and genetic processes. The phosphosites in the VFMs are also significantly more conserved than their flanking regions, whereas those in the BFMs are not. These results hold for both serine/threonine and tyrosine residues, although the fraction of phosphorylated tyrosine residues is increased in the VFMs. Moreover, the difference in the evolutionary conservation of the phosphosites between the VFMs and BFMs could not be explained by the difference in the local protein structures. There is also a higher fraction of phosphosites with known functions in the VFMs than BFMs. Based on these findings, we have concluded that protein phosphorylation may play more dominant roles for the VFMs than BFMs during the vertebrate evolution. As phosphorylation is a quite rapid biological reaction, the VFMs that quickly respond to outer stimuli and inner signals might heavily depend on this regulatory mechanism. Our results imply that phosphorylation may have an essential role in the evolution of vertebrates.