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RE: Heloderma venom evolution

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Posted by: BGF at Thu Jan 14 20:12:42 2010  [ Report Abuse ] [ Email Message ] [ Show All Posts by BGF ]  
   

Noticed an oops in the post. I cut and pasted some of the material from the abstract of the paper but accidently grabbed an earlier version. This paper is a stripped down version of what was a much longer document originally. All of the animal genetics got moved out as did some of the toxin material. Here is the abstract from the final version of the paper (the published version that is now downloadable). Other material will be coming out in seperate papers.

The origin and evolution of venom proteins in helodermatid lizards were investigated by multidisciplinary techniques. Our analyses elucidated novel toxin types resultant from three unique domain-expression processes: 1) The first full-length sequences of lethal toxin isoforms (helofensins) revealed this toxin type to be constructed by an ancestral monodomain, monoproduct gene (beta-defensin) that underwent three tandem domain duplications to encode a tetradomain, monoproduct with a possible novel protein fold; 2) an ancestral monodomain gene (encoding a natriuretic peptide) was medially extended to become a pentadomain, pentaproduct through the additional encoding of four tandemly repeated proline-rich peptides (helokinestatins), with the five discrete peptides liberated from each other by posttranslational proteolysis; and 3) an ancestral multidomain, multiproduct gene belonging to the vasoactive intestinal peptide (VIP)/ glucagon family being mutated to encode for a monodomain, monoproduct (exendins) followed by duplication and diversification into two variant classes (exendins 1 and 2 and exendins 3 and 4). Bioactivity characterization of exendin and helokinestatin elucidated variable cardioactivity between isoforms within each class. These results highlight the importance of utilizing evolutionary-based search strategies for biodiscovery and the virtually unexplored potential of lizard venoms in drug design and discovery.
Heloderma paper download link


-----
Dr. Bryan Grieg Fry
~~~~~~~~~~~~~~~~~~~~~~
Venomics Research Laboratory,
Department of Biochemistry,
Bio21 Institute,
University of Melbourne
~~~~~~~~~~~~~~~~~~~~~~
http://www.venomdoc.com


   

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