title: Functional constraints on adaptive evolution of protein ubiquitination sites.
abstract: It is still unclear whether there exist functional constraints on the evolution of protein ubiquitination sites, because most previous studies regarded all protein ubiquitination sites as a whole or only focused on limited structural properties. We tried to clarify the relation between functional constraints and ubiquitination sites evolution. We investigated the evolutionary conservation of human ubiquitination sites in a broad evolutionary scale from G. gorilla to S. pombe, and we found that in organisms originated after the divergence of vertebrate, ubiquitination sites are more conserved than their flanking regions, while the opposite tendency is observed before this divergence time. By grouping the ubiquitination proteins into different functional categories, we confirm that many functional constraints like certain molecular functions, protein tissue expression specificity and protein connectivity in protein-protein interaction network enhance the evolutionary conservation of ubiquitination sites. Furthermore, by analyzing the gains of ubiquitination sites at different divergence time and their functional characters, we validate that the emergences of ubiquitination sites at different evolutionary time were also affected by the uncovered functional constraints. The above results suggest that functional constraints on the adaptive evolution of ubiquitination sites increase the opportunity for ubiquitination to synthetically regulate various cellular and developmental processes during evolution.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.|National Center for Protein Sciences Beijing, 38 Life Science Park Road, Beijing 102206, China.|State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, 26 Beiqing Road, Beijing 100094, China.|Space Institute of Southern China, 3 Pingdi Industrial Road, Shenzhen 518117, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.|National Center for Protein Sciences Beijing, 38 Life Science Park Road, Beijing 102206, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.|National Center for Protein Sciences Beijing, 38 Life Science Park Road, Beijing 102206, China.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, 26 Beiqing Road, Beijing 100094, China.|Space Institute of Southern China, 3 Pingdi Industrial Road, Shenzhen 518117, China.
authors.forename: Fengji
authors.initials: F
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.|National Center for Protein Sciences Beijing, 38 Life Science Park Road, Beijing 102206, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.|National Center for Protein Sciences Beijing, 38 Life Science Park Road, Beijing 102206, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.|National Center for Protein Sciences Beijing, 38 Life Science Park Road, Beijing 102206, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.|National Center for Protein Sciences Beijing, 38 Life Science Park Road, Beijing 102206, China.
authors.forename: Yangzhige
authors.initials: Y
authors.lastname: He
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, 26 Beiqing Road, Beijing 100094, China.|Space Institute of Southern China, 3 Pingdi Industrial Road, Shenzhen 518117, China.
authors.forename: Jianghui
authors.initials: J
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.|National Center for Protein Sciences Beijing, 38 Life Science Park Road, Beijing 102206, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.|National Center for Protein Sciences Beijing, 38 Life Science Park Road, Beijing 102206, China.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005658:Fungi; D006801:Humans; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D057149:Ubiquitinated Proteins / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D011506:Proteins; D057149:Ubiquitinated Proteins