Biology Reference
In-Depth Information
(a)
(b)
(c)
(d)
Figure 10.1.
Proposed phylogenies for the vitamin K-dependent factors of coagulation. A:
Krawczak
et al.
(1996), B: Doolittle (1993); C: Doolittle and Feng (1987), D: Patthy
(1990).
EGF domains. Prothrombin's EGF domain(s) served as a site for the binding of
tissue factor which at this time possessed the ability to activate it to yield throm-
bin. After the emergence of fibrinogen, factor X appeared as a result of a pro-
thrombin gene duplication. The ability of factor X to activate prothrombin
released the latter from its dependence on tissue factor. Factor VII, duplicated
from factor X, was able to bind tissue factor and to activate factor X. Factor IX
emerged last, again duplicated from factor X. Prothrombin then acquired kringle
domains via exon shuffling (Rogers, 1985) allowing it to bind fibrin. The con-
comitant loss of prothrombin's EGF domains abolished its now redundant inter-
action with tissue factor. The plausibility of this scheme was tested by Krawczak
et al
. (1996) whose approach is described in subsequent sections.
10.2.2 Reconstruction of mammalian ancestral cDNAs
Krawczak
et al
. (1996) reconstructed the catalytic domains of the early mam-
malian ancestors of the vitamin K-dependent factors and the common ancestor of
all five proteins. The study of Krawczak
et al
. (1996) relied upon mammalian phy-
logenies from different sources (Nei, 1987; Novacek, 1992; Vogel and Motulsky,
