Nature 439, 584-588 (2 February 2006) | doi:10.1038/nature04328

Early evolution of the venom system in lizards and snakes

Bryan G. Fry1,2, Nicolas Vidal3,4, Janette A. Norman2, Freek J. Vonk5, Holger Scheib6,7, S. F. Ryan Ramjan1, Sanjaya Kuruppu8, Kim Fung9, S. Blair Hedges3, Michael K. Richardson5, Wayne. C. Hodgson8, Vera Ignjatovic10,11, Robyn Summerhayes10,11 and Elazar Kochva12

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)1. Evolution of the venom system is thought to underlie the impressive radiation of the advanced snakes (2,500 of 3,000 snake species)2, 3, 4, 5. In contrast, the lizard venom system is thought to be restricted to just two species and to have evolved independently from the snake venom system1. 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.

  1. Australian Venom Research Unit, Level 8, School of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia
  2. Population and Evolutionary Genetics Unit, Museum Victoria, GPO Box 666E, Melbourne, Victoria 3001, Australia
  3. Department of Biology and Astrobiology Research Center, 208 Mueller Lab, Pennsylvania State University, University Park, Pennsylvania 16802-5301, USA
  4. UMS 602, Taxonomie et collections, Reptiles-Amphibiens, Département Systématique et Évolution, Muséum National d'Histoire Naturelle, 25 Rue Cuvier, Paris 75005, France
  5. Institute of Biology, Leiden University, Kaiserstraat 63, PO Box 9516, 2300 RA, Leiden, The Netherlands
  6. Department of Structural Biology and Bioinformatics, University of Geneva and Swiss Institute of Bioinformatics, Centre Médical Universitaire, 1 Rue Michel-Servet, 1211 Geneva 4, Switzerland
  7. SBC Lab AG, Seebüelstrasse 26, 8185 Winkel, Switzerland
  8. Monash Venom Group, Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia
  9. Molecular and Health Technologies, CSIRO, 343 Royal Parade, Parkville, Victoria 3010, Australia
  10. Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia
  11. Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia
  12. Department of Zoology, Tel Aviv University, Tel Aviv 69978, Israel

Correspondence to: Bryan G. Fry1,2 Correspondence and requests for materials should be addressed to B.G.F. (Email: bgf@unimelb.edu.au). The sequences of the cDNA clones have been deposited in GenBank (accession numbers DQ139877–DQ139931 and DQ184481), as have the nuclear gene sequences (DQ119594–DQ119641).

Received 13 July 2005; Accepted 17 October 2005


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