Venom evolution in lizards & snakes

Python bites can produce false positives when
using venom detection kits. JCM

In 2005 it became apparent that venom  first evolved in the ancestor of the the Iguiana Lizards, Anguingmoprh lizards and the snakes. These three clades form a larger clade now known as Toxicofera. In a forthcoming paper Fry et al. (2013)  examine the oral glands in both the upper and lower jaws of the toxicoferans and find they are all involved in making the various molecules found in venom. Even the poorly known rictal glands of snakes make a variety of molecules that are venom components.  Rictal glands were investigated in two studies about 100 years ago. The secretions were shown to be highly toxic to birds but  no  investigations followed up on these glands, until now. Fry and colleagues show the rictal glands are in fact derived from the well-studied venom glands.Suggesting that the secretion of venom by snakes is much more complex than previously thought.

Several other interesting pieces of evidence regarding the evolution of venom were found during this study. Pythons have a novel, low-molecular weight disulphide bridged peptide class. This is the first evidence that pythons are still carrying at least some of the genetic material to make venom, and transcribing those genes. Iguanian lizards maybe using their venom molecules to control microbes. And,  proteins with hemotoxic or neurotoxic activity at low levels occur in iguanian and anguimorph lizards and caenophidian snakes. Even the ‘basal’ snakes (like Cylindrophis) surprisingly were found to express the 3-finger toxin and lectin toxins as the dominant transcripts. Also, in the constricting pythonid and boid snakes, where the glands are predominantly mucous-secreting, low-levels of toxin transcripts can be detected. Venom  appears to play a minimal role in the feeding behavior of most iguanian lizards and constricting snakes, and the low levels of expression argue against a defensive role.

Doctors in Australia rely on the venom detection kit to aid in diagnosis of snake bite. False-positives could lead to patients getting very expensive antivenom they don’t need and  possibly triggering life-threatening allergies and reducing the supply for patients who actually need it. This paper shows a surprising potential source of false-positives: pythons. A previous study showed that pythons cross-react in the Snake Venom Detection Kit (sVDK) but this curious result was dismissed as an anomaly. Fry et al. show that even though python oral glands overwhelmingly secrete mucus to lubricate prey for swallowing, there is still a trace of venom in their oral secretions. The venom is not enough to harm a human or  kill  prey, but enough to confuse an extremely sensitive diagnostic tool like the sVDK. While this poses a problem for doctors and snakebite victims it also provides an opportunity. The low level of ancient venom still secreted in these glands contained novel compounds that were quite different than those from the  well-studied front-fanged snakes like rattlesnakes and  mambas. These novel molecules therefore represent an untapped resource for biodiscovery.

Bryan G. Fry, Eivind A.B. Undheim, Syed A. Ali1, Jordan Debono, Holger Scheib, Tim Ruder, Timothy N. W. Jackson, David Morgenstern, Luke Cadwallader, Darryl Whitehead, Rob Nabuurs, Louise van der Weerd, Nicolas Vidal, Kim Roelants, Iwan Hendrikx, Sandy Pineda Gonzalez, Alun Jones, Glenn F. King, Agostinho Antunes, Kartik Sunagar. 2013. Squeezers and leaf-cutters: differential diversification and degeneration of the venom system in toxicoferan reptiles. Molecular & Cellular Proteomics In press. M112.023143

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