10月18日,，Molecular Biology and Evolution雜志在線發(fā)表了中科院系統(tǒng)生物學(xué)重點(diǎn)實(shí)驗(yàn)室李亦學(xué)研究組與曾嶸研究組,、日本國立遺傳研究所Yoshio Tateno教授以及德國國家環(huán)境生物學(xué)研究中心流行病研究所在中科院系統(tǒng)生物學(xué)重點(diǎn)實(shí)驗(yàn)室的進(jìn)修生Ludwig Geistlinger等共同合作取得的研究成果。該項(xiàng)研究報(bào)道了蛋白質(zhì)磷酸化修飾的進(jìn)化與功能的相關(guān)性在脊椎動物和無脊椎動物之間存在顯著的差異,。該項(xiàng)工作主要由博士研究生王振在李亦學(xué)研究員和曾嶸研究員的指導(dǎo)下完成,。
蛋白質(zhì)的翻譯后修飾對細(xì)胞內(nèi)眾多的生物學(xué)過程具有重要的調(diào)控作用。研究在漫長的進(jìn)化的過程中蛋白質(zhì)的翻譯后修飾位點(diǎn)的變異與蛋白質(zhì)功能的關(guān)系有助于對蛋白質(zhì)的翻譯后修飾的重要性進(jìn)行分類,，發(fā)現(xiàn)蛋白質(zhì)的翻譯后修飾調(diào)控的精細(xì)機(jī)制,。
通過建立的分析方法，作者研究發(fā)現(xiàn),，蛋白質(zhì)磷酸化修飾的進(jìn)化及其與功能的相關(guān)性在脊椎動物和無脊椎動物之間存在顯著的差異。該項(xiàng)研究糾正了2009年Tan發(fā)表在Science上的文章中的模糊結(jié)論（Science , 2009,， Vol. 325, pp-1686）,，指出tyrosine磷酸化位點(diǎn)的丟失對于脊椎動物來說僅僅存在于一些與細(xì)胞基本的生化過程相關(guān)的蛋白質(zhì)中，而脊椎動物特有的細(xì)胞生化過程相關(guān)的蛋白質(zhì)中tyrosine磷酸化位點(diǎn)整體上不僅沒有丟失,，而且存在非常顯著的增加,。這個現(xiàn)象可能預(yù)示脊椎動物和無脊椎動物應(yīng)對環(huán)境壓力，在蛋白質(zhì)磷酸化修飾調(diào)控機(jī)制的進(jìn)化方面采取了一種截然不同的方式,，其背后的驅(qū)動力值得進(jìn)一步研究,。
該研究工作得到國家973項(xiàng)目、國家自然科學(xué)基金委,、中科院知識創(chuàng)新工程,、科技部863項(xiàng)的經(jīng)費(fèi)資助。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
