title: Early evolution of the venom system in lizards and snakes.
abstract: 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.
authors.affiliation: Australian Venom Research Unit, Level 8, School of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia. bgf@unimelb.edu.au
authors.forename: Bryan G
authors.initials: BG
authors.lastname: Fry
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vidal
authors.forename: Janette A
authors.initials: JA
authors.lastname: Norman
authors.forename: Freek J
authors.initials: FJ
authors.lastname: Vonk
authors.forename: Holger
authors.initials: H
authors.lastname: Scheib
authors.forename: S F Ryan
authors.initials: SF
authors.lastname: Ramjan
authors.forename: Sanjaya
authors.initials: S
authors.lastname: Kuruppu
authors.forename: Kim
authors.initials: K
authors.lastname: Fung
authors.forename: S Blair
authors.initials: SB
authors.lastname: Hedges
authors.forename: Michael K
authors.initials: MK
authors.lastname: Richardson
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Hodgson
authors.forename: Vera
authors.initials: V
authors.lastname: Ignjatovic
authors.forename: Robyn
authors.initials: R
authors.lastname: Summerhayes
authors.forename: Elazar
authors.initials: E
authors.lastname: Kochva
mesh_terms: D000818:Animals; D005075:Biological Evolution; D019143:Evolution, Molecular; D008116:Lizards / Q000033:anatomy & histology / Q000502:physiology*; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D010974:Platelet Aggregation / Q000187:drug effects; D011487:Protein Conformation; D051381:Rats; D012910:Snake Venoms / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D012911:Snakes / Q000033:anatomy & histology / Q000502:physiology*; D014688:Venoms / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D012910:Snake Venoms; D014688:Venoms