But does the coagulation system even meet the definition of irreducible complexity? The answer is no. The clotting cascade consists of sequential activation of a series of proenzymes or inactive precursor proteins (zymogens) to active enzymes. There are two arms to the clotting cascade: intrinsic and extrinsic. Both converge on the common pathway, which ultimately promotes thrombin generation and fibrin formation.
Humans who are deficient in one or another zymogen often have bleeding diatheses, but many can live a normal life and reproduce.
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By examining the genomes of various classes of extant vertebrates, it is possible to infer the evolutionary history of the coagulation system. We learn that the clotting cascade first arose in an ancestral vertebrate some 600 million years ago. Moreover, the clotting cascade, as we recognize it in humans, did not evolve all at once. The extrinsic system appeared first (in jawless fish), followed by FIX (in jawed fish) and then the contact system (in amphibians) (see Figure below). This sequence of events is backed by strong biological plausibility: clotting is always initiated by the FVII of the extrinsic cascade, is amplified by FIX of the intrinsic pathway and is further accelerated by FXI, which lies downstream of the contact pathway.