Snake venoms share similar ingredients

Susanta Pahari from National University of Singapore, Singapore (currently working at Sri Bhagawan Mahaveer Jain College, Bangalore, India) used venom glands from a rare rattlesnake that lives in arid and desert grasslands. Known as Desert Massasauga (Sistrurus catenatus edwardsii), this pitviper is a subspecies of the North American Massasauga Rattlesnake (Sistrurus catenatus).

Together with Stephen Mackessy from the University of Northern Colorado, USA and R. Manjunatha Kini from National University of Singapore, Singapore, Pahari constructed a cDNA library of the snake's venom gland and created 576 tagged sequences. A cocktail of recognized venom toxin sequences was detected in the library, but the venom also contained three-finger toxin-like transcripts, a family of poisons thought only to occur in another family of snakes (Elapidae). The team also spotted a novel toxin-like transcript generated by the fusion of two individual toxin genes, a mechanism not previously observed in toxin evolution. Toxin diversity is usually the result of gene duplication and subsequently neofunctionalization is achieved through several point mutations (called accelerated evolution) on the surface of the protein. Pahari says “In addition to gene duplication, exon shuffling or transcriptional splicing may also contribute to generating the diversity of toxins and toxin isoforms observed among snake venoms.”

Previously, researchers identified venom compounds using protein chemistry or individual gene cloning methods. However, less abundant toxins were often missed. The library method has now revealed new toxin genes and even new families of toxins. Taking low abundance toxins into consideration shows advanced snakes' venoms actually have a greater similarity than previously recognized.

Snake venoms are complex mixtures of pharmacologically active proteins and peptides. Treating snake venom victims can be complicated because of the variation between venoms even within snake families. Kini says “Such a diversity of toxins provides a gold mine of bioactive polypeptides, which could aid the development of novel therapeutic agents.”