Molecular evolution of the vertebrate blood coagulation network (2003)

Author(s): Hirt RP; Davidson CJ; Lal K; Snell P; Elgar G; Tuddenham EG; McVey JH

  • : Molecular evolution of the vertebrate blood coagulation network

Abstract: In mammalian blood coagulation 5 proteases, factor VII (FVII), factor IX (FIX), factor X (FX), protein C (PC) and prothrombin act with two cofactors factor V and factor VIII to control the generation of fibrin. Biochemical evidence and molecular cloning data have previously indicated that blood coagulation involving tissue factor, prothrombin and fibrinogen is present in all vertebrates. Using degenerate RT-PCR we have isolated and characterized novel cDNAs with sequence identity to the blood coagulation serine proteases and cofactors from chicken and the puffer fish (Fugu rubripes). Sequence alignments, phylogenetic and comparative sequence analysis all support the existence of the Gla-EGF1-EGF2-SP domain serine proteases FVII, FIX, FX, PC and the A1-A2-B-A3-C1-C2 domain protein cofactors FV and FVIII in these species. These results strongly suggest that the blood coagulation network is present in all jawed vertebrates and evolved before the divergence of tetrapods and teleosts over 430 million years ago; and that vertebrate blood coagulation may have benefited from two rounds of gene or whole genome duplication. Sequences identified in Fugu coding for additional FVII-like, FIX-like and PC-like sequences support the possibility of further tandem and large-scale duplications in teleosts. Comparative sequence analyses of amino acid residues in the active site region suggest these additional sequences have evolved new and as yet unknown functions.

Notes: 0340-6245 Journal Article

  • Short Title: Molecular evolution of the vertebrate blood coagulation network
  • Date: 01-03-2003
  • Journal: Thrombosis and Haemostasis
  • Volume: 89
  • Issue: 3
  • Pages: 420-428
  • Publisher: Schattauer GmbH
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Amino Acid Sequence Animals Base Sequence Blood Coagulation Factors/chemistry/*genetics Chickens/blood/genetics Comparative Study DNA, Complementary/genetics/isolation & purification *Evolution, Molecular Factor IX/genetics Factor VIII/genetics Humans Molecular Sequence Data Phylogeny Protein C/genetics Protein Structure, Tertiary Research Support, Non-U.S. Gov't Sequence Homology, Amino Acid Serine Endopeptidases/genetics Takifugu/blood/genetics Vertebrates/*blood/*genetics


Professor Robert Hirt
Professor of Evolutionary Parasitology