Prof. Yi- Professor & Leader of proposed Shanghai Institutes for Bio-Medicine Director Shanghai Center for Bioinformation Technology Vice Director Key Laboratory of Systems Biology Shanghai Institutes for Biological Sciences

Topic： Protein phosphorylation plays essential role in the evolution of vertebrates

Abstract： Recent publications have revealed that the evolution of phosphosites are influenced by 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 modules according to the functional categories of KEGG, and we investigated their evolutionary conservation in several vertebrate genomes from mouse to zebrafish. We found that phosphosites in the basic functional modules (BFMs) such as metabolic and genetic processes, display a lower evolutionary conservation than those in the vertebrate-specific functional modules (VFMs) such as signaling processes and more complex organic systems. The phosphosites in the VFMs are also significantly more conserved than their flanking regions, but those in the BFMs are not. The above results hold for both serine/threonine and tyrosine residues, although the fraction of phosphorylated tyrosine is raised in the VFMs. Moreover, the difference in evolutionary conservation of the phosphosites cannot be explained by their difference in local protein structures, and there are also more phosphosites with known functions in the VFMs. Based on these results, we concluded that protein phosphorylation may play more dominant roles for the VFMs than the BFMs. As phosphorylation is a quite rapid biological reaction, the VFMs that quickly respond to outer stimuli and inner signals might more heavily depend on this regulatory mechanism. Our results imply that phosphorylation may have an essential role in the evolution of vertebrates.

Resume:

Yi-Xue Li was born in Xinjiang, China. Currently, is vice Director and a full research professor of Key Laboratory of Systems Biology at Shanghai

Institutes for Biological Sciences, Chinese Academy of Sciences， Director in

Shanghai Center for Bioinformation Technology， Dean of Department of

Bioinformatics and Biostatistics, Shanghai Jiaotong University. Dr. Li received his BSc. and Msc. degrees in theoretical physics from Xinjiang

University, China, in 1982 and 1987, respectively, and his Ph.D. degree in theoretical physics from Heidelberg University, Germany in 1996. After Dr. Li got his Ph.D. degree he worked as a bioinformatics research staff in European

Molecular Biology Laboratory (EMBL) from 1997-2000, and came back to

Shanghai, China in the middle of 2000.

Dr. Li has published more than 100 journal papers published in various international scientific journals, such as Science, Nature Genetics, Nature

Biotechnology, PNAS, Bioinformatics, NAR, Plos Computational Biology, Plos

One, Molecular Systems Biology, Molecular Biology and Evolution, Molecular

Cellular Proteomics, Oncogene, BMC Bioinformatics, Genome Biology, etc., and his research results have been cited by more than 1500 researchers

worldwide in books, theses, journal and conference papers. He has served as a

reviewer/panelist for many national research foundations/agencies such as the Chinese National Science Foundation, the National High-Tech

Program(863) and National Key Basic Research Program(973).

Selected publications:

1. Zhen , Guohui , Ludwig Geistlinger, Li Hong, , Rong *, Yoshio

Tateno*, Yixue Li*，2010，Evolution of protein phosphorylation for distinct

functional modules in vertebrate genomes，on Oct. 18 online published by

Molecular Biology and Evolution.

2. Shen , , Kaiyan Feng, Yudong *, Yixue Li*，Prediction of

tyrosine‐sulfation with mRMR feature selection and analysis，on Oct.16 onloine

published by Journal of Proteome Research.

3. Huang T，…, Yudong Cai, Yixue Li*: Prediction of Deleterious Non‐Synonymous

SNPs Based on Protein Interaction Network and Hybrid Properties. PLoS ONE 2010, 5(7):e11900. 4. Hong Li, Guohui Ding, , Yixue Li*, 2010, dbDEPC: a Database of Differentially Expressed Proteins in Human Cancer. Nucleic Acids Research.;38(Database issue):D658‐64. 5. Huang T, …, Yixue Li*, Yudong Cai*, 2010, Analysis and prediction of the metabolic stability of proteins based on their sequential features, subcellular locations and interaction networks. PLoS ONE, 5(6):e10972. 6. J, C, Tao L, D, Jiang Y, Tang K, R, H, Zhang W, He F, Li Y*,

Cao Z*. 2010，Reconstruction and Analysis of Human Liver‐Specific Metabolic

Network Based on CNHLPP Data. JOURNAL OF PROTEOME RESEARCH, 9( 4):1648‐1658. 7. Yi , Zili Zhang, Yixue Li*, Xinguang Zhu*, Liu*. 2010, Identifying cooperative transcriptional factors by combing ChIP‐chip data and knock‐out data. Accepted by Cell Research. 8. Peter Lorenz, Sabine Dietmann, Thomas Wilhelm, Dirk Koczan, Sandra Autran, Sophie Gad, Gaiping , Guohui Ding, Yixue Li, Marie‐Françoise

Rousseau‐Merck and Hans‐Juergen Thiesen，The ancient mammalian KRAB zinc

finger gene cluster on human chromosome 8q24.3 illustrates principles of C2H2 zinc finger evolution associated with unique expression profiles in human

tissues，BMC Genomics 2010, 11:206doi:10.1186/1471‐2164‐11‐206.

9. Zhen Wang, Dong, Guohui Ding,and Yixue Li*, Comparing the retention

mechanisms of tandem duplicates and retrogenes in human and mouse genomes, Genet Sel Evol. 2010; 42(1): 24. 10. Tao Huang, Weiren , Zhi‐ S. He, Lele , Liu, Tieqiao Wen, Yixue Li*, Yudong Cai*, 2009, Functional association between influenza A (H1N1) virus and human. Biochemical and biophysical research ommunications. Volume 390, Issue 4, Pages 1111‐1113. 11. Tao Huang , WeiRen Cui, LeLe Hu, KaiYan Feng, Yi‐Xue Li*, Yu‐Dong Cai, 2009, Prediction of Pharmacological and Xenobiotic Responses to Drugs Based on Time Course Gene Expression Profiles. Plos One, 2009, 4(12):e8126. 12. Hui Yu, ‐Dong Yu, ‐Qing Zhang, Shen, Yun‐ , ‐Yuan Li,* and Yi‐Xue Li*, DBH2H: vertebrate head‐to‐head gene pairs annotated at genomic and post‐genomic levels. Database , 2009, doi:10.1093/database/bap006.

13. Yu， , Siyuan , Yun Li, Guohui Ding, Jie Ping, and Yixue

Li*，GEOGLE: context mining tool for the correlation between gene expression

and the phenotypic distinction. BMC Bioinformatics 2009, 10:264 doi:10.1186/1471‐2105‐10‐264. 14. Tu, Kang; Yu, Hui; , Youjia; Li, Yuanyuan; Liu, Lei, Xie, Lu, Yixue Li*, Combinatorial network of primary and secondary microRNA‐driven regulatory

mechanisms, Nucleic Acids Research. 2009，37(18):5969‐80.

15. Jing , Di , Tianlei , Xiaojing Wang, Xiaolian Xu, Tao, Y. X. Li* and Z. W.

Cao*，SEPPA: a computational server for spatial epitope prediction of protein

antigens，Nucleic Acids Research. 2009，W612–W616.

16. Hong Li, Guohui Ding, Lu Xie* and Yixue Li*, PAnnBuilder: an R package for assembling proteomic annotation data, Bioinformatics , 2009, 25(8):1094‐1095. 17. Hong Li, Xiaobing , Guohui Din proteomic g, Lu Xie*, Rong Zeng*, Yixue Li*, SysPTM ‐ a systematic resource for research of post‐translational modifications, Molecular and Cellular Proteomics. 2009, 8(8):1839‐49. 18. Zhen Wang, Guohui Ding, Zhonghao Yu, Lei Liu*, Yixue Li *, CHSMiner: a GUI tool to identify chromosomal homologous segments. Algorithms Mol. Biol., 2009, 4(1):2.

19. Songling Li, Hong Li, Minfa Li, Lu Xie*, Yixue Li*. 2009，Improved prediction of

lysine acetylation by support vector machines. Accepted by Protein and Peptide Letters.

20. Pei Hao, Siyuan Zheng, Jie Ping, Kang Tu, Christian Gieger, Rui

Wang-Sattler, Yang *, Yixue Li*，Human gene expression sensitivity

according to large scale meta-analysis，BMC Bioinformatics. 2009,

10(Suppl 1):S56.

21. Hong Sun, Geir Skogerbo, Xiaohui Zheng, Wei Liu* and Yixue Li*, Genomic regions with distinct genomic distance conservation in vertebrate genomes, BMC Genomics, 2009, 10:133.

22. Hong Xi, ⋯, Yixue Li*, SysPIMP: the web-based systematical platform for

identifying human disease-related mutated sequences from mass

spectrometry, Nucleic Acids Research. 2009 37:D913-D920.

23. Sujun Li, Hong Li, Yixue Li*, Rong Zeng, Sys-BodyFluid: a Systematical

Database for Human Body Fluid Proteome Research, Nucleic Acids

Research. 2009 Jan;37:D907-12.

24. Guohui Ding, ⋯, Yixue Li*, H.J. Thiesen*, SysZNF: the C2H2 Zinc Finger

Gene database, Nucleic Acids Research. 2009 37:D267-D273.

25. Zhen Wang, Guohui Ding, Zhonghao Yu, Lei Liu*, Yixue Li*, Modeling the

age distribution of gene duplications in vertebrate genome using mixture

density. Genomics. 2009;93(2):146-51. 26. Ruo-Yu Luo, Hai-Bin Wei, Lin , Kankan Wang, Lei Liu,Yuan-Yuan Li,

Yi-Xue Li* and Yang Zhong*,Photosynthetic metabolism of C3 plants

shows highly cooperative regulation to maintain function under changing

environmental conditions: a systems biological analysis of robustness,

PNAS.2009, vol. 106 no. 3 847-852.

27. Hong Sun,⋯, Wei, Liu*, Yixue Li*, Structural Relationships between Highly

Conserved Elements and Genes in Vertebrate Genomes, Plos One. 2008,

Vol. 3, No. 11, e3727.

28. Guohui Ding, ⋯, Yixue Li*, Tree of Life Based on Genome Context

Networks, Plos One. 2008, Vol.3, No.10,e3357.

29. Yun Li, Pei Hao, Siyuan Zgeng, Kang Tu, Lei Liu*, Yixue Li*, 2008, Gene

Expression Module based Chemical Function Similarity Search, Nucleic

Acids Research，2008, Vol. 36, No. 20 e137.

30. Guangyong Zheng, Kang Tu, ⋯, Yixue Li*,ITFP: an integrated platform of

mammalian transcription factors, Bioinformatics， 2008，Vol.24(No.20)

31. W Li, L Xie, X He, J Li, K Tu, L Wei, J Wu, Y Guo, Wenxi Li, Lu Xie,

Xianghuo He, Jinjun Li, Kang Tu,⋯,Yixue Li*, Jianren *, 2008,

Diagnostic and prognostic implications of microRNAs in human

hepatocellular carcinoma, Int. J. Cancer, 123, 1616–1622.

32. Siyuan Zheng, ⋯, Pei Hao*, Lei Liu*, Yixue Li*, 2008, MPSQ: A web tool for

protein state searching, Bioinformatics. 2008 24(20):2412-2413. 33. Tao Huang, Kang Tu, Yu Shyr, Chao-Chun Wei, Lu Xie* and Yi-Xue Li*, The

prediction of interferon treatment effects based on time series microarray

gene expression profiles, Journal of Translational Medicine, 2008 Aug

9;6(1):44.

34. Guangyong Zheng, Ziliang , Qing Yang, Chaochun Wei,Lu Xie,

Yangyong Zhu* and Yixue Li*, 2008, The combination approach of SVM

and ECOC for powerful identification and classification of transcription

factor, BMC Bioinformatics, 9:282.

35. Hua YJ, Tu K., Tang ZY, Li YX*, Xiao HS*, 2008, Comparison of

normalization methods with microRNA microarray. Genomics,

doi:10.1016/j.ygeno.2008.04.002.

36. Qingwei Xu, Yixiang Shi, Qiang Lu, Guoqing Zhang, Qingming Luo* and

Yixue Li*，2008，GORouter: an RDF model for providing semantic query

and inference services for Gene Ontology and its associations，BMC

Bioinformatics, 9(Suppl 1):S6.

37. C Bin, Kang, Lie Liu*, Yixue Li*, 2008, Modeling Effects of Cell Cycle

M-phase Transcriptional Inhibition on Circadian Oscillator, Plos

computational Biology, V. 4, Issue 3.

38. Peilin , Ziliang Qian, Kaiyan Feng, Wencong Lu, Yixue Li*, Yudong Cai*,

2008, Prediction of membrane protein types in a hybrid space, J Proteome

Research, 7 (3), 1131–1137. 39. Changzhen Dong, ⋯, Yixue Li*, Gene-centric Characteristics of

Genome-wide Association Studies, Plos One, 2007; 2(12): e1262.

40. Jing Li, Zijing Liu, Yuchun , Qi Liu, Xing Fu, Nigel G.F. Cooper, Yixue Li*,

Mengsheng Qiu* and Tieliu Shi*, Regulatory Module Network of bHLH

Transcription Factors in Mouse Brain, Genome Biology 2007, 8:R244.

41. Guohui Ding, Sun, Hong Li, Zhen Wang, Haiwei Fan, Chuan Wang, Dan

Yang and Yixue Li*, 2007, EPGD: a comprehensive web resource for

integrating and displaying eukaryotic paralog/paralogon information.

Nucleic Acids Research, v.36(Database issue): D255–D262.

42. Cui, Li, Guang Li, Feng Xu, Chen Zhao, Yuhua Li, Zhongnan Yang,

Guang Wang, Qingbo Yu, Yixue Li* and Tieliu Shi*, AtPID: Arabidopsis

thaliana protein interactome database—an integrative platform for plant

systems biology, 2007, Nucleic Acids Research, 36: D999-D1008.

43. Juwen Shen, JianZhang, Xiaomin Luo, Weiliang Zhu, Kunqian Yu, Kaixian

Chen, Yixue Li, Hualiang Jiang*. Predicting protein-protein interactions

only based on sequences information. Proceedings of the National

Academy of Sciences U.S.A., 104 (2007), 4337-4341.

44. Peilin Jia, Ziliang Qian，Zhen Bin Zeng, Yudong Cai*, and Yixue Li*,

Prediction of subcellular protein localization based on functional domain

composition, Biochemical and Biophysical Research Communications，

Volume 357, Issue 2, 1 June 2007, Pages 366-370. 45. Ziliang Qian, Lingyi Lu, XiaoJun Liu, Yu-Dong Cai*, and Yixue Li*，2007,

An Approach to Predict Transcription Factor DNA Binding Site Specificity

Based upon Gene and Transcription Factor Functional Categorization,

Bioinformatics, 23(18):2449-2454.

46. Boshu Liu,Sujun Li, Yinglin Wang, Lin Lu, Yixue Li* and Yudong Cai*，

Predicting the protein SUMO modification sites based on Properties

Sequential Forward Selection (PSFS)，Biochemical and Biophysical Research

Communications，2007， Volume 358, Issue 1, 22 June 2007, Pages

136-139.

47. L Lu, Z Qian, YD Cai*, Y Li*，Software note: ECS: An automatic enzyme

classifier based on functional domain composition，2007，Computational

Biology and Chemistry, Volume 31， 226-232.

48. Jing Zhao, Guo-Hui Ding, Lin Tao, Hong Yu, Zhong-Hao Yu, Jian-Hua Luo,

Zhi-Wei Cao* and Yi-Xue Li*，2007，Modular co-evolution of metabolic

networks，BMC Bioinformatics, 8:311, doi:10.1186/1471-2105-8-311.

49. Hui Yu, Feng Wang, Kang Tu, Lu Xie, Yuan-Yuan Li* and Yi-Xue Li*，

2007，Transcript-level annotation of Affymetrix probesets improves the

interpretation of gene expression data，BMC Bioinformatics, 8:194,

doi:10.1186/1471-2105-8-194.

50. Changzheng Dong，Xun Chu，Ying Wang，Yi Wang，Li ，Tieliu Shi，

Wei Huang*，Yixue Li*，2007, Exploration of Gene-Gene Interaction Effects Using Entropy-Based Methods，European Journal of Human Genetics,

16(2):229-35.

51. Wu Wei, ⋯, Yixue Li, Lars Steinmetz*, 2007, "Genome sequencing and

comparative analysis of Saccharomyces, PNAS, vol. 104, no. 31,

12825-12830.

52. Sujun Li, ⋯, Yixue Li*, 2007, Prediction Protein N-glycosylation by

Combining Functional Doman and Secretion Information, J. Biomolecular

Structure & Dynamics, Vol. 25, 49-54.

53. Quanhu , ⋯, Yixue Li, Rong Zeng*, Jiarui Wu*, 2006, Comparison of

Proteomic Approach to Microarray-based Approach for Detecting Exons of

Mouse Genome. Nature Genetics, 38, 1223 – 1224.

54. Guohui Ding, Jiuhong Kang, Qi Liu, Tieliu Shi, Gang Pei, and Yixue Li*,

2006, Insights into the coupling of duplication events and macroevolution

from an age distribution of animal transmembrane gene families, Plos

Computational Biology, Vol. 2, issue 8, e102.

55. Jing Zhao, Hong Yu, Jian-Hua Luo, Zhi-Wei Cao,Yi-Xue Li*，2006,

Hierarchical modularity of nested bow-ties in metabolic networks，BMC

Bioinformatics, 7:386.

56. Ziliang Qian, Yudong Cai, Yixue Li*, 2006, Automatic Transcription Factor

Classifier based on Functional Domain Composition, Biochemical and

Biophysical Research Communications， 18;347(1):141-4. 57. PL Jia, TL Shi*, YD Cai*.and YX Li*, 2006, Demonstration of two novel

methods for predicting functional siRNA efficiency, BMC Bioinformatics,

7:271, doi: 10.1186/ 471-2105-7-271.

58. Pei Hao, ⋯, Yixue Li*, 2006, “ Bioinformatics Research on the SARS

Coronavirus in China” , Curr. Pharm. Design. Vol. 12, Nr. 35.

59. Ziliang Qian，Yanbin Yin，Yong Zhang, Lingyi Lu,Yixue Li and Ying Jiang*，

2006, Genomic characterization of ribitol teichoic acid synthesis in

Staphylococcus aureus: genes, genomic organization and gene duplication,

BMC Genomics, 7: 74.

60. Wu Wei, Ziwei Cao, ⋯,Yixue Li*，2006, The path from commensalism to

pathogenicity: comparative phylogenetic profiles of Staphylococcus

epidermidis RP62A and ATCC12228, BMC Genomics, 7:112，

doi:10.1186/1471-2164-7-112.

61. Xiaojing Yu, ⋯, Yixue Li*, 2006, Classification of protein quaternary

structure by functional domain composition, BMC Bioinformatics, 7:187.

62. Yuanyuan Li, ⋯, Yixue Li*, 2006, "In silico discovery of human natural

antisense transcripts", BMC Bioinformatics. 13;7:18.

63. Sujun Li, ⋯, Yixue Li*, 2006, Predicting O-glycosylation sites in

mammalian proteins by using SVMs, Comput Biol Chem. 30(3): 203-208.

64. Kang Tu, ⋯, Yixue Li*, 2006, Combining Gene Expression Profiles and

Protein-Protein Interaction data to infer Gene Functions Bioinformatics: microarray analysis & PPI network analysis, Journal of Biotechnology,

124,475-485.

65. Yu X, Cao J, Cai Y, Shi T, Yixue Li*. 2006, Predicting rRNA-, RNA-, and

DNA-binding proteins from primary structure with support vector

machines. J Theor. Biol. 21;240(2):175-84.

66. Wang, -Guang Zhu, ⋯, Yuanyuan Li, Yixue Li*, Lei Liu*, 2006,

Exploring photosynthesis evolution by comparative analysis of metabolic

networks between chloroplasts and photosynthetic bacteria, BMC

Genomics., 7:100, doi: 10.1186/1471-2164-7-100.

67. Ruoyu Luo, Sha , Guanyang Tao, Yuanyuan Li, Yixue Li*, Qingming

Luo*. 2006, Dynamic analysis of optimality in myocardial metabolic

network under normal and ischemic conditions, Molecular Systems Biology,

2:2006.0031.

68. Yuan-Yuan Li, Hui Yu, Zong-Ming Guo, Ting-Qing Guo, Kang Tu, Wei Lin,

Yi-Xue Li*, 2006, Systematic analysis of head-to-head gene organization:

evolutionary conservation and potential biological relevance, Plos

Computational Biology, Vol. 2, issue 7, e74.

69. Guo-qing Zhang, Zhi-wei Cao, Qing-ming Luoa, Yu-Dong Cai, Yixue Li*，

2006, Operon prediction based on SVM，Comput Biol Chem, 30, 233-240.

70. Lili Wang, Zhong Yang, ⋯, Yixue Li*, Wei Hu*, 2006, Reconstruction and

in silico analysis of MAPK signalling pathways in the human blood fluke,

Schistosoma japonicum, FEBS Letters 580, 3677-3686. 71. Zhuo Fang, Jiong Yang, Yixue Li, Qingming Luo and Lei Liu*, Knowledge

guided analysis of microarray data, 2006, J Biomed Inform, Volume 39,

Issue 4, p:401-411.

72. Jing Li, Qi Liu, Mengsheng Qiu, Yuchun Pan,Yixue Li and Tieliu Shi, 2006,

Identification and analysis of the mouse basic/Helix-Loop-Helix

transcription factor family, Biochemical and Biophysical Research

Communications, Volume 350, Issue 3, 24 November 2006, Pages

648-656.

73. Lu Q, Hao P, Curcin V, He W, Li YY, Luo QM, Guo YK, Li YX. 2005, KDE

Bioscience: Platform for bioinformatics analysis workflows. J Biomed

Inform, Volume 39, Issue 4, August 2006, Pages 440-450.

74. Pei Hao, ⋯, Yixue Li*，Guoping Zhao*, 2005, Cross-host evolution of SARS

coronavirus in palm civet and human, PNAS. 102(7)，2430–2435.

75. Jingchun Sun, ⋯, Yixue Li*, 2005, Refined phylogenetic profiles method

for predicting protein-protein interactions, Bioinformatics,

15;21(16):3409-15.

76. Pei Hao, ⋯, Yixue Li* & Yang Zhong*, 2005, “ MPSS: an integrated

database system for surveying a set of proteins ” ，Bioinformatics. Vol. 21

no. 9, 2142–2143.

77. Lu W, Wu XD, ⋯, Li YX, ⋯, Pei G, Wu JR, Sun B, et al., 2005, Synthetic

peptides derived from SARS coronavirus S protein with diagnostic and

therapeutic potential. FEBS Lett. 11;579(10):2130-6. 78. Pei Hao, ⋯⋯, Yixue Li, ⋯⋯, Guoping Zhao, et.al., 2004, ‘Molecular

evolution of the SARS-coronavirus during the course of the SARS epidemic

in China’, Science, 12 March, 303: 1666-1669.

79. Henning Hermjakob，⋯⋯, Yixue Li, ⋯⋯, Chris Hogue & Rolf Apweiler,

2004, The HUPO PSI's Molecular Interaction format—a community

standard for the representation of protein interaction data, Nature

Biotechnology,22，pp177–183.

80. Lijian Hui,⋯⋯,Yixue Li*，et al., 2004, “ Identification of Alternatively

Spliced mRNA Variants Related to Cancers by Genome-wide ESTs

Alignment.” , Oncogene， 1-11.

81. Luo, ⋯⋯, Yixue Li, Xu She, and Hualiang Jiang, 2004, Nucleocapsid

protein of SARS coronavirus tightly binds to human cyclophilin A, Biochem

Biophys Res Commun. Aug 27;321(3):557-65.

82. X, Qiu L, Yixue L*, 2004, Scoring hidden Markov models to

discriminate beta-barrel membrane proteins. Comput Biol Chem,

Jul;28(3):189-94.