Molecular evolution caught in action: gene duplication and evolution of molecular isoforms of prothrombin activators in Pseudonaja textilis (brown snake).
BACKGROUND
The evolution of structurally and functionally similar proteins with highly diverse physiological roles within a single organism is of great interest. Australian elapid snakes offer an excellent opportunity to study the molecular evolution of prothrombin activators. Venom from Pseudonaja textilis contains pseutarin C, a group C prothrombin activator. Its enzymatic subunit is structurally and functionally similar to mammalian factor (F) Xa, whereas its non-enzymatic subunit is similar to FVa. As vertebrates, the snakes also contain a system to activate prothrombin in their own blood during injury. These hemostatic factors are produced in the liver.


RESULTS
Here we describe the presence of two molecular forms of FX expressed in the liver of P. textilis. Both isoforms have molecular signatures and domain architecture of FX. However, one isoform shows approximately 94% sequence identity with the snake FX from Tropidechis carinatus, whereas the other is much closer (90% identity) to the catalytic subunit of pseutarin C (PCCS). Real-time polymerase chain reaction reveals that the latter isoform is expressed approximately 56 000 times lower in the liver of P. textilis. However, the isoforms are not expressed in the venom gland.


CONCLUSIONS
A detailed analysis of deletions and insertions along with the sequence indicates that the second isoform is an intermediate caught in the evolution of venom prothrombin activator from the blood coagulation FX. Thus, this isoform represents a 'molecular fossil' and reveals the likely evolutionary path of recruitment of FX in the venom gland.
Reza
M A
MA
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.
Minh Le
T N
TN
Swarup
S
S
Manjunatha Kini
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004546:Elapid Venoms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017815:Elapidae / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D019143:Evolution, Molecular; D005088:Exocrine Glands / Q000378:metabolism; D005170:Factor X / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020440:Gene Duplication; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism*; D012333:RNA, Messenger; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D004546:Elapid Venoms; D020033:Protein Isoforms; C475049:Pseutarin C; D012333:RNA, Messenger; D011516:Prothrombin; D005170:Factor X