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Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7527-32. Epub 2003 Jun 13.

The evolution of vertebrate blood coagulation as viewed from a comparison of puffer fish and sea squirt genomes.

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Center for Molecular Genetics, University of California at San Diego, La Jolla, CA 92093-0634, USA.


The blood coagulation scheme for the puffer fish, Fugu rubripes, has been reconstructed on the basis of orthologs of genes for mammalian blood clotting factors being present in its genome. As expected, clotting follows the same fundamental pattern as has been observed in other vertebrates, even though genes for some clotting factors found in mammals are absent and some others are present in more than one gene copy. All told, 26 different proteins involved in clotting or fibrinolysis were searched against the puffer fish genome. Of these, orthologs were found for 21. Genes for the "contact system" factors (factor XI, factor XII, and prekallikrein) could not be identified. On the other hand, two genes were found for factor IX and four for factor VII. It was evident that not all four factor VII genes are functional, essential active-site residues having been replaced in two of them. A search of the genome of a urochordate, the sea squirt, Ciona intestinalis, did not turn up any genuine orthologs for these 26 factors, although paralogs and/or constituent domains were evident for virtually all of them.

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