Among extant reptiles only two lineages are known to have evolved venom delivery systems, the advanced snakes and helodermatid lizards (Gila Monster and Beaded Lizard). Evolution of the venom system is thought to underlie the impressive radiation of the advanced snakes (2,500 of 3,000 snake species). In contrast, the lizard venom system is thought to be restricted to just two species and to have evolved independently from the snake venom system. Here we report the presence of venom toxins in two additional lizard lineages (Monitor Lizards and Iguania) and show that all lineages possessing toxin-secreting oral glands form a clade, demonstrating a single early origin of the venom system in lizards and snakes. Construction of gland complementary-DNA libraries and phylogenetic analysis of transcripts revealed that nine toxin types are shared between lizards and snakes. Toxinological analyses of venom components from the Lace Monitor Varanus varius showed potent effects on blood pressure and clotting ability, bioactivities associated with a rapid loss of consciousness and extensive bleeding in prey. The iguanian lizard Pogona barbata retains characteristics of the ancestral venom system, namely serial, lobular non-compound venom-secreting glands on both the upper and lower jaws, whereas the advanced snakes and anguimorph lizards (including Monitor Lizards, Gila Monster and Beaded Lizard) have more derived venom systems characterized by the loss of the mandibular (lower) or maxillary (upper) glands. Demonstration that the snakes, iguanians and anguimorphs form a single clade provides overwhelming support for a single, early origin of the venom system in lizards and snakes. These results provide new insights into the evolution of the venom system in squamate reptiles and open new avenues for biomedical research and drug design using hitherto unexplored venom proteins.

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The predatory ecology of Varanus komodoensis (Komodo Dragon) has been a subject of long-standing interest and considerable conjecture. Here, we investigate the roles and potential interplay between cranial mechanics, toxic bacteria, and venom. Our analyses point to the presence of a sophisticated combined-arsenal killing apparatus. We find that the lightweight skull is relatively poorly adapted to generate high bite forces but better adapted to resist high pulling loads. We reject the popular notion regarding toxic bacteria utilization. Instead, we demonstrate that the effects of deep wounds inflicted are potentiated through venom with toxic activities including anticoagulation and shock induction. Anatomical comparisons of V. komodoensis with V. (Megalania) priscus fossils suggest that the closely related extinct giant was the largest venomous animal to have ever lived. evolution ͉ phylogeny ͉ squamate ͉ protein ͉ toxin P redation by Varanus komodoensis, the world's largest extant lizard, has been an area of great controversy (cf. ref. 1). Three-dimensional finite element (FE) modeling has suggested that the skull and bite force of V. komodoensis are weak (2). However, the relevance of bite force and cranial mechanics to interpretations of feeding behavior cannot be fully evaluated in the absence of comparative data. Moreover, this previous analysis did not account for gape angle, which can significantly influence results (3). Irrespective of evidence for or against a powerful bite, V. komodoensis is clearly capable of opening wounds that can lead to death through blood loss (4). Controversially, the proposition that utilization of pathogenic bacteria facilitates the prey capture (4, 5) has been widely accepted despite a conspicuous lack of supporting evidence for a role in predation. In contrast, recent evidence has revealed that venom is a basal characteristic of the Toxicofera reptile clade (6), which includes the varanid lizards (7), suggesting a potential role of venom in prey capture by V. komodoensis that has remained unexplored. This is consistent with prey animals reported as being unusually quiet after being bitten and rapidly going into shock (4) and the anecdotal reports of persistent bleeding in human victims after bites (including B.G.F.'s personal observations). Shock-inducing and prolonged bleeding pathophysiological effects are also characteristic of helodermatid lizard envenomations (cf. ref . 8), consistent with the similarity between helodermatid and varanid venoms (6).Here, we examine the feeding ecology of V. komodoensis in detail. We compare the skull architecture and dentition with the related extinct giant V. priscus (Megalania). In this 3D finite element modeling of reptilian cranial mechanics that applies a comparative approach, we also compare the bite force and skull stress performance with that of Crocodylus porosus (Australian Saltwater Crocodile), including the identification of optimal gape angle (an aspect not considered in previous nonreptilian comparative FE analyses). We als...

α-Neurotoxins have been isolated from hydrophid, elapid and, more recently, colubrid snake venoms. Also referred to as postsynaptic neurotoxins or 'curare mimetic' neurotoxins, they play an important role in the capture and/or killing of prey by binding to the nicotinic acetylcholine receptor on the skeletal muscle disrupting neurotransmission. They are also thought to cause respiratory paralysis in envenomed humans. This review will discuss the historical background into the discovery, isolation, structure and mechanism of action of the α-neurotoxins, including targets and cellular outcomes, and then will examine the potential uses of α-neurotoxins as pharmacological tools and/or as drug leads.

The evolution of venom in advanced snakes has been a focus of long-standing interest. Here we provide the first complete amino acid sequence of a colubrid toxin, which we have called alpha-colubritoxin, isolated from the Asian ratsnake Coelognathus radiatus (formerly known as Elaphe radiata), an archetypal nonvenomous snake as sold in pet stores. This potent postsynaptic neurotoxin displays readily reversible, competitive antagonism at the nicotinic receptor. The toxin is homologous with, and phylogenetically rooted within, the three-finger toxins, previously thought unique to elapids, suggesting that this toxin family was recruited into the chemical arsenal of advanced snakes early in their evolutionary history. LC-MS analysis of venoms from most other advanced snake lineages revealed the widespread presence of components of the same molecular weight class, suggesting the ubiquity of three-finger toxins across advanced snakes, with the exclusion of Viperidae. These results support the role of venom as a key evolutionary innovation in the early diversification of advanced snakes and provide evidence that forces a fundamental rethink of the very concept of nonvenomous snake.