Domain Evolution of Vertebrate Blood Coagulation Cascade Proteins

Abstract

Vertebrate blood coagulation is controlled by a cascade containing more than 20 proteins. The cascade proteins are found in the blood in their zymogen forms and when the cascade is triggered by tissue damage, zymogens are activated and in turn activate their downstream proteins by serine protease activity. In this study, we examined proteomes of 21 chordates, of which 18 are vertebrates, to reveal the modular evolution of the blood coagulation cascade. Additionally, two Arthropoda species were used to compare domain arrangements of the proteins belonging to the hemolymph clotting and the blood coagulation cascades. Within the vertebrate coagulation protein set, almost half of the studied proteins are shared with jawless vertebrates. Domain similarity analyses revealed that there are multiple possible evolutionary trajectories for each coagulation protein. During the evolution of higher vertebrate clades, gene and genome duplications led to the formation of other coagulation cascade proteins.

Keywords: Blood coagulation; Hemolymph clotting; Modular evolution; Protein domains.

Fig. 1

Appearance and disappearance of the studied coagulation proteins on the vertebrate phylogeny. The proteins marked in red show the updated and/or improved resolution compared to the literature. This figure is a modified version of a previous study by Doolittle (2009)

Fig. 2

Phylogenetic tree with bootstrap values of zebrafish, human and mouse FXIIA, transglutaminases and arthropod transglutaminases. FXIIAs are depicted in red

Fig. 3

Phylogenetic tree with bootstrap values of proteins containing VWD, TIL and C8 domains in zebrafish, mouse, human, fruitfly, and horseshoe crab. vWFs are depicted in red

Fig. 4

Proposed evolutionary trajectories of blood coagulation cascade proteins. (K: Kringle, P: PAN1, G: Gla, E: EGF, F: FXa_inhibition, L: Ldl_recept_b, F2: fn2, C2: Cupper oxidase 2, C3: Cupper oxidase 3, F5_F8: F5_F8 type C, PKinase: PKinase_Tyr)

Fig. 5

Phylogenetic tree with bootstrap values of FV, FVIII, Ceruloplasmin and Hephaestin from zebrafish, mouse and human together with putative orthologs of FV in jawless vertebrates. Some branches (Groups 1–5) containing only jawless vertebrate proteins were collapsed to increase readability. For full tree, see supplementary Figure S4