Structure of two genes encoding parallel prothrombin activators in Tropidechis carinatus snake: Gene duplication and recruitment of factor X gene to the venom gland

Abstract

Background: Proteins with new function originate through gene duplication followed by divergence. In nature, occurrence of structurally and functionally similar proteins performing highly diverse physiological roles within an organism is rare. Several Australian elapid snakes have two parallel prothrombin activating systems with distinct physiological roles. For example, in Tropidechis carinatus, trocarin D exists in the venom and acts as toxin, whereas coagulation factor (F) X exists in plasma and plays a role in hemostasis. Results: Here, we show that FX and the trocarin D genes are expressed in a highly tissue-specific manner in T. carinatus. To understand their origin, recruitment and evolution, we determined the complete structure of their genes. Both genes have eight exons with identical exon-intron boundaries. All the introns are 92-99% identical with the exception of intron 1, indicating a recent gene duplication event. The first intron of the trocarin D gene is also nearly identical to that of the FX gene, except for two deletions (255 and 1406 bp) and three insertions (214, 1975, and 2174 bp). The third insertion has a potential scaffold/matrix attached region. The putative promoter of the snake FX gene shares similar cis-elements compared with those of human and murine FX genes. Interestingly, the trocarin D promoter has a 264-bp insertion with core promoter sequences and cis-elements that are known to induce high-level expression. This insertion might be responsible for switching from constitutive expression of the FX gene to inducible expression of trocarin D. Thus, we named this segment as VERSE (Venom Recruitment/Switch Element). Conclusion: To our knowledge, this is the first molecular evidence for the recruitment of a duplicated gene for expression in venom glands by a simple insertion. © 2007 International Society on Thrombosis and Haemostasis.