Functional and Structural Diversification of the Anguimorpha Lizard Venom System

Abstract

Because of significant differences in anatomy of the venom delivery system and distant phylogenetic relatedness, it had been long assumed that the venom systems of snakes and helodermatid lizards were independently evolved (1-3). However, both lineages were recently revealed to be members of a clade (Toxicofera) that also included several lineages of other lizards recently shown to be venomous (4, 5). In contrast to the hypothesis of independent origins, this new perspective revealed that lizard and snake venom systems are homologous but highly differentiated descendants of an early evolved venom system in squamates. The basal condition was incipient glands on both the mandibular and maxillary regions with snakes favoring the maxillary venom glands and secondarily losing the mandibular venom glands. However, the anguimorph lizards (anguids, helodermatids, and varanids) did the reverse, resulting in the modern condition seen today.The lizard venom delivery system is less sophisticated than the high pressure injection mechanism of the front fanged advanced snakes, and the vast majority of the species pose trivial direct medical risks to human (with the exception of helodermatids and large varanids such as Varanus komodoensis). However, the effects of envenomation from mediFrom the

Dynamic evolution of venom proteins in squamate reptiles

“…Both databases were interrogated using representative venom sequences utilised by Fry et al [10][11][12]29 . Sequence searches were undertaken for 12 toxin families identified as basal to the Toxicofera (AVIT, cystatin, cysteine-rich secretory protein, CVF, crotamine, hyaluronidase, kallikrein, lectin, natriuretic peptides, NGF, veficolin and vespryn) [10][11][12] . Contigs exhibiting a BLAST e-value cut-off of 1e − 05 were retained.…”

“…Contig hits were incorporated into DNA data sets of toxin (derived from members of the Toxicofera) and non-toxin (sampled from outside groups -that is, non-reptilian species) sequences used in the analyses of Fry et al [10][11][12]29 . All sequences were obtained from GenBank -GI accession numbers are displayed in the resulting gene trees (Figs 2-5; Supplementary Figs S2-S6).…”

“…In the absence of available genomic sequences, non-toxin homologues of the venom toxins in these studies were derived from a variety of other vertebrate taxa, most commonly mammals or birds 7,[9][10][11][12] . This is potentially problematic, because failure to sample non-toxin homologues from the focal clade can lead to gene trees that falsely depict the toxin genes as monophyletic, leading to the erroneous conclusion that they are the result of a single recruitment event (Fig.…”

Squeezers and Leaf-cutters: Differential Diversification and Degeneration of the Venom System in Toxicoferan Reptiles

“…The apparent lack of specialization of the venom system within the Iguania is likely because of the fact that most species are insectivorous or vegetarian; however, we have shown that toxin genes continue to be expressed by the oral glands of these lizards (18). In the snakes and Anguimorpha lizards, by contrast, the venom system has been extensively diversified (18,20,22,24,29). In the anguimorph lizards, specialization of the mandibular gland was favored, whereas in snakes it was the maxillary gland that became most specialized; in both lineages highly derived forms exist, including encapsulated glands.…”

“…(Fig. 1A) (2,7,(17)(18)(19)(20)(21)(22)(23)(24). Although Toxicofera, which consists of three lineages (Anguimorpha lizards, Iguania lizards, and Serpentes) is well established as a monophyletic clade within the squamate reptiles (18,25); phylogenetic studies based on nuclear genes have thus far failed to resolve the relative relationships of the snake/iguanian/anguimorph trichotomy [cf (2,25,26).…”