The Enigmatic Venoms of Heloderma – Trophic Adaptation or Optimized for Defense?

Mackessy, Stephen P.

School of Biological Sciences

University of Northern Colorado

Greeley, Colorado USA

stephen.mackessy@unco.edu

The Gila Monster (Heloderma suspectum) and Beaded Lizard (H. horridum) are the only non-snake squamate reptiles known to produce venoms, and the protein compositional complexity of these venoms is comparable to that observed in many viperid species. Like rattlesnake venoms, Heloderma venoms contain representatives of more than 12 protein families, including potent hemorrhagic metalloproteinases, and the lethal toxicity (~1-2 µg/g) is likewise similar. However, unlike all venomous snakes, which produce venoms in temporal venom gland, venoms are produced in a non-homologous submandibular gland and delivered under low pressure via grooved mandibular teeth. The primary role of venoms in snakes as a trophic adaptation is well accepted, but a similar role for Heloderma venoms, which feed largely on defenseless prey, seems unlikely. An anti-predator role has long been suggested, and human envenomations by Heloderma are quite painful (i.e., strong negative stimulus), but the complexity of the venom has argued against this as a primary role, as a much simpler venom should suffice. However, recent observations suggest that secretion of venom from the submandibular glands is stimulated by agitation of the animal, and greatly decreased in a quiescent animal, again suggesting a role in defense. Heloderma venoms lack several canonical venom proteins, including L-amino acid oxidase and phosphodiesterase, and contain several novel peptides, including exendins, which possess interesting pharmacologies but lack any significant toxicity, strongly indicating that these are not venom toxins in the traditional sense. The actual biological role remains uncertain but likely extends beyond these typical functions. Unraveling the function(s) of submandibular “venoms” in helodermatid lizards will require a novel approach to determining exactly how these secretions are used by the lizards and what biological roles they fulfill.