The definition of venom has nothing to do with human effects, whether the venom of a goanna, snake, cone snail etc. Any effect upon us is merely a pleasent side-effect as far as the animal is concerned. The evolution of venom in pretty much every lineage occured on a vast evolutionary timescale long before humans showed up on the scene. For example, the funnel web spider venoms are unusually toxic to humans. However, this is an evolutionary fluke as the spiders evolved tens of millions of years before humans evolved and in fact there weren't even any primates in Australia at the time of the evolution of funnel web venoms.



We have shown that venoms evolve via a process by which a gene encoding for a normal body protein, typically one involved in key regulatory processes or bioactivity, is duplicated and the copy selectively expressed in the venom gland. The newly created toxin type evolves via the birth-and-death model of protein evolution, in which a toxin multigene gene family is created by further gene duplication events followed by the deletion of some copies and conversion of others to non-functional copies or pseudogenes. As a result paralogous groups of genes are generated across taxonomic lineages where the gene duplication event occurred prior to their divergence. These evolutionary patterns are similar to those observed for multigene families involved in the adaptive immune response such as immunoglobins and major histocompatibility complex genes, a process which is thought to contribute to an organism’s ability to react to a wide range of foreign antigens. In an analogous manner, animal venom toxins must react with diverse compounds in their prey. The birth-and-death model of protein evolution generates suites of toxins that allow the predators to adapt to a variety of different prey species.



In our study, we identified expressed proteins from the venom glands of two families of lizards (Varanidae and Agamidae), which are homologous to toxins in venom gland secretions found in the venomous helodermatid lizards and many venomous advanced snakes. Toxic effects were demonstrated for both the crude protein and purified type III PLA2 isolated from the venom of a representative varanid. Consistent with the conserved functional residues, the activity of the varanid PLA2 toxin was identical to that of well-characterised forms from Heloderma venoms.



The relative abundance of toxin types sequenced and dominant effects of the crude venom were also congruent with the venom liquid chromatography – mass spectrometry fingerprinting of the venom, a technique previously used by us in the course of investigating snake venom evolution.



We simultaneously showed that all squamate lineages possessing homologous toxin-secreting oral glands form a strongly supported clade and interpreted these data to indicate an early evolution of the venom system in squamate reptiles



Our findings also highlight that venom delivery systems, like any other complex biological structure, exhibit a range of forms. The newly characterised venomous lizards possess relatively simple venom delivery systems. The varanid glands, for example, are characterised by possessing a compound mandibular gland with venom storage lumen and venom ducts (very similar to the venom system of Heloderma lizards), but lacking the highly specialized dentition (e.g. hollow fangs) and highly kinetic skulls and muscle attachments of some advanced snakes (e.g. atractaspidids, elapids, viperids). Thus, the venom systems of the front-fanged advanced snakes are highly specialized derived states, and not the only “true venom systems”.



The early appearance of the specialized, protein-secreting dental glands made possible the organization of the incipient toxin-producing organs. These glands are found in both the upper and lower jaw of the iguanians, have a multi-duct system connected with the teeth and produce several toxins in common with venomous snakes. These and other toxins may have evolved “locally” or may have been “recruited” from other organ systems and then continued along two lines – towards the mandibular venom glands of the anguimorphs and the complex maxillary venom glands of snakes. This does not preclude the possibility of additional toxins being developed or recruited at later stages in the different groups.



New insights into the evolution of venom systems and the medical importance of the associated toxins cannot be advanced without recognition of the true biochemical, ecological, morphological and pharmacological diversity of venoms and associated venom systems.



Cheers

Bryan
Nature paper


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Dr. Bryan Grieg Fry

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Australian Venom Research Unit,

University of Melbourne

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Population and Evolutionary Genetics Unit,

Museum Victoria

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http://www.venomdoc.com

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