title: Evolutionary analysis for functional divergence of Jak protein kinase domains and tissue-specific genes.
abstract: Jak (Janus kinase) is a nonreceptor tyrosine kinase, which plays important roles in signal transduction pathways. The unique feature of Jak is that, in addition to a fully functional tyrosine kinase domain (JH1), Jak possesses a pseudokinase domain (JH2). Although JH2 lost its catalytic function, experimental evidence has shown that this domain may have acquired some new but unknown functions. This apparent functional divergence after the (internal) domain duplication may result in dramatic changes of selective constraints at some sites. We conducted a data analysis to test this hypothesis. Our result shows that shifted selective constraints (or shifted evolutionary rates) between the JH1 and the JH2 domains are statistically significant. Predicted amino acid sites by posterior analysis can be classified into two groups: very conserved in JH1 but highly variable in JH2, and vice versa. Moreover, we have studied the evolutionary pattern of four tissue-specific genes, Jak1, Jak2, Jak3, and Tyk2, which were generated in the early stages of vertebrates. We found that after the (first) gene duplication, site-specific rate shifts between Jak2/Jak3 and Jak1/Tyk are significant, presumably as a consequence of functional divergence among these genes. The implication of our study for functional genomics is discussed.
authors.affiliation: Department of Zoology and Genetics, Iowa State University, Ames, IA 50011, USA.
authors.forename: Jianying
authors.initials: J
authors.lastname: Gu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Gu
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D016415:Sequence Alignment; D053634:TYK2 Kinase
chemical_list: D000596:Amino Acids; D007527:Isoenzymes; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D053634:TYK2 Kinase; C070139:TYK2 protein, human