Summary
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.
Supplementary information to this article available at both http://europium.csc.mrc.ac.uk and www.thrombosis-online.com
Keywords
Evolution - serine proteases - blood coagulation - cofactors