Functional and structural diversification of the Anguimorpha lizard venom system

Bryan G Fry, Kelly Lee Winter, Jeanette A Norman, Kim Roelants, Rob JA Nabuurs, Matthias JP van Osch, Wouter M Teeuwisse, Louise van der Weerd, Judith E McNaughton, Hang Fai Kwok, Holger Scheib, Laura Greisman, Elazar Kochva, Laurence J Miller, Fan Gao, John Karas, Denis Scanlon, Feng Lin, Don M Sanjaya Kuruppu, Chris ShawLily Wong, Wayne Clarence Hodgson

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Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this a??130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A(2) toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and....
Original languageEnglish
Pages (from-to)2369 - 2390
Number of pages22
JournalMolecular & Cellular Proteomics
Issue number11
Publication statusPublished - 2010

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