title: Correlated evolution between CK1δ Protein and the Serine-rich Motif Contributes to Regulating the Mammalian Circadian Clock.
abstract: Understanding the mechanism underlying the physiological divergence of species is a long-standing issue in evolutionary biology. The circadian clock is a highly conserved system existing in almost all organisms that regulates a wide range of physiological and behavioral events to adapt to the day-night cycle. Here, the interactions between hCK1ϵ/δ/DBT (Drosophila ortholog of CK1δ/ϵ) and serine-rich (SR) motifs from hPER2 (ortholog of Drosophila per) were reconstructed in a Drosophila circadian system. The results indicated that in Drosophila, the SR mutant form hPER2S662Gdoes not recapitulate the mouse or human mutant phenotype. However, introducing hCK1δ (but not DBT) shortened the circadian period and restored the SR motif function. We found that hCK1δ is catalytically more efficient than DBT in phosphorylating the SR motif, which demonstrates that the evolution of CK1δ activity is required for SR motif modulation. Moreover, an abundance of phosphorylatable SR motifs and the striking emergence of putative SR motifs in vertebrate proteins were observed, which provides further evidence that the correlated evolution between kinase activity and its substrates set the stage for functional diversity in vertebrates. It is possible that such correlated evolution may serve as a biomarker associated with the adaptive benefits of diverse organisms. These results also provide a concrete example of how functional synthesis can be achieved through introducing evolutionary partners in vivo.
authors.affiliation: From the Cambridge-Suda Genomic Resource Center, Soochow University, 199 Renai Road, Suzhou 215123 and.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Xing
authors.affiliation: the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Pukou District, Nanjing 210061, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: An
authors.affiliation: From the Cambridge-Suda Genomic Resource Center, Soochow University, 199 Renai Road, Suzhou 215123 and.
authors.forename: Guangsen
authors.initials: G
authors.lastname: Shi
authors.affiliation: From the Cambridge-Suda Genomic Resource Center, Soochow University, 199 Renai Road, Suzhou 215123 and.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Pukou District, Nanjing 210061, China.
authors.forename: Pancheng
authors.initials: P
authors.lastname: Xie
authors.affiliation: the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Pukou District, Nanjing 210061, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Qu
authors.affiliation: the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Pukou District, Nanjing 210061, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: From the Cambridge-Suda Genomic Resource Center, Soochow University, 199 Renai Road, Suzhou 215123 and.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: From the Cambridge-Suda Genomic Resource Center, Soochow University, 199 Renai Road, Suzhou 215123 and pandejing@suda.edu.cn.
authors.forename: Dejing
authors.initials: D
authors.lastname: Pan
authors.affiliation: From the Cambridge-Suda Genomic Resource Center, Soochow University, 199 Renai Road, Suzhou 215123 and yingxu@suda.edu.cn.|the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Pukou District, Nanjing 210061, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D056926:CLOCK Proteins / Q000378:metabolism*; D048149:Casein Kinase 1 epsilon / Q000378:metabolism*; D057906:Circadian Clocks / Q000502:physiology*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D010641:Phenotype; D010766:Phosphorylation; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism*
chemical_list: D012694:Serine; D056926:CLOCK Proteins; D048149:Casein Kinase 1 epsilon
keywords: Drosophila; circadian clock; correlated evolution; invertebrate; kinase; mammal; mouse; orthologs; phosphorylation; substrates