title: Comprehensive analysis of blood coagulation pathways in teleostei: evolution of coagulation factor genes and identification of zebrafish factor VIIi.
abstract: It is not clear how the complex mammalian coagulation pathways evolved from an entirely dissimilar invertebrate coagulation cascade. Comprehensive analysis of pro-coagulant factors and their regulators is lacking in early vertebrates to discern the mechanism of evolution of these genes from the invertebrates. To elucidate the coagulation pathways found in early vertebrates, zebrafish cDNAs/gene orthologues for major coagulant, anticoagulant, and fibrinolytic proteins were identified and characterized by homology to mammalian sequences. We found that zebrafish carry all hemostatic genes present in mammals, providing evidence that the coagulation system of teleosts is nearly identical to mammals. Zebrafish factor VII and X genes were identified and analyzed to reveal a novel factor VII-like gene flanked by the factor VII and factor X genes. This gene encodes a protein homologous to factor VII, but lacks critical residues for factor VII activity. Expression of the factor VII-like protein (named factor VIIi) demonstrated that it functions as an inhibitor of blood coagulation in biochemical assays using zebrafish or human plasmas. Analysis of intergenic DNA between the zebrafish VII/VIIi/X gene cluster and a Drosophila trypsin gene cluster revealed significant homology, and based upon these data, we propose a model for a rapid evolution of coagulation factors from the invertebrates.
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Hanumanthaiah
authors.forename: Kenneth
authors.initials: K
authors.lastname: Day
authors.forename: Pudur
authors.initials: P
authors.lastname: Jagadeeswaran
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000990:Antithrombin III / Q000235:genetics; D001777:Blood Coagulation / Q000235:genetics*; D019774:Blood Coagulation Factor Inhibitors / Q000235:genetics*; D001779:Blood Coagulation Factors / Q000235:genetics*; D021901:DNA, Intergenic; D019143:Evolution, Molecular; D005164:Factor IX / Q000235:genetics; D005165:Factor V / Q000235:genetics; D005167:Factor VII / Q000235:genetics*; D005170:Factor X / Q000235:genetics; D015844:Heparin Cofactor II / Q000235:genetics; D008074:Lipoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D010958:Plasminogen / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000097:blood / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D021901:DNA, Intergenic; D008074:Lipoproteins; D029961:Zebrafish Proteins; C476080:coagulation factor VIIi, zebrafish; C051928:lipoprotein-associated coagulation inhibitor; D015844:Heparin Cofactor II; D000990:Antithrombin III; D005165:Factor V; D005167:Factor VII; D005164:Factor IX; D005170:Factor X; D010958:Plasminogen