The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system

Abstract

Significance Snake venoms are toxic protein cocktails used for prey capture. To investigate the evolution of these complex biological weapon systems, we sequenced the genome of a venomous snake, the king cobra, and assessed the composition of venom gland expressed genes, small RNAs, and secreted venom proteins. We show that regulatory components of the venom secretory system may have evolved from a pancreatic origin and that venom toxin genes were co-opted by distinct genomic mechanisms. After co-option, toxin genes important for prey capture have massively expanded by gene duplication and evolved under positive selection, resulting in protein neofunctionalization. This diverse and dramatic venom-related genomic response seemingly occurs in response to a coevolutionary arms race between venomous snakes and their prey.

Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms

“…S15). These results are perhaps unsurprising, but they further reflect the apparent distinction between pathogenically important toxin families (e.g., SVMP and SP) and so-called "ancillary" toxin families (e.g., LAAO and CRISP) described (15). Here, we demonstrate that this dichotomy appears to extend from the mode and tempo of gene family evolution noted (15) to the mechanisms governing toxin transcription and translation.…”

“…Typically, toxins are encoded by relatively few (approximately 5-10) multilocus gene families, with each family capable of producing related isoforms generated by gene duplication events occurring over evolutionary time (1,14,15). The birth and death model of gene evolution (16) is frequently invoked as the mechanism giving rise to venom gene paralogs, with evidence that natural selection acting on surface exposed residues of the resulting gene duplicates facilitates subfunctionalization/neofunctionalization of the encoded proteins (15,(17)(18)(19). The result of these processes is a complex suite of toxins that act synergistically to cause rapid prey death.…”

Endocytotic Routes of Cobra Cardiotoxins Depend on Spatial Distribution of Positively Charged and Hydrophobic Domains to Target Distinct Types of Sulfated Glycoconjugates on Cell Surface

“…Recent proteomic and genomic investigations of snake venom toxins have indicated that toxin genes are important for capturing prey and have been massively expanded by variable levels of gene duplication, resulting in protein neofunctionalization with directional selection (14). However, the exact molecular interactions involved in these fast evolving toxin homologues at the cellular level have not been addressed.…”

“…Recent genomic investigation of the King cobra has indicated that dynamic gene evolution and adaptation actually is in operation in the snake venom system (14). For the fast evolving biological weapon systems such as snake toxins, a comparative structural and functional study of naturally abundant CTX homologues should shed light on how venom proteins evolve at the molecular and cellular levels.…”

Crystal Structure of Snake Venom Acetylcholinesterase in Complex with Inhibitory Antibody Fragment Fab410 Bound at the Peripheral Site

“…However, it could be a vestige of the pancreatic origin of the venom gland (30). These snake venom AChEs are inhibited by small, organic PAS ligands such as propidium, albeit at a lower affinity compared with the other species found in neuronal or neuromuscular tissues, but they differ widely in their sensitivity to larger, peptidic PAS ligands such as Fas2 or mAb Elec410 (see below) (27,31,32).…”