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Heloderma venom evolution
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by BGF on January 14, 2010
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Our study dragging Heloderma venom out of the dark ages has finally been published Smile
Despite a state of fame that extends far beyond the fields of herpetology and natural history, Heloderma suspectum ssp (Gila Monsters) and Heloderma horridum ssp Mexican (Beaded Lizards) have remained remarkably enigmatic animals. In particular, the evolution of their venom system has remained controversial, mainly due to their secretive ecology and persistent folkloristic misconceptions that strongly influenced earlier scientific reports. Misunderstandings persist even today. For example the therapeutically useful exendin peptide toxins (marketed under the diabetes drug name Byetta) have been erroneously referred to as originating from the ‘saliva’ when they have in fact only ever been isolated from venom and mRNA coding for these specific compounds only ever recovered from the venom gland.
The origin and evolution of venom proteins in helodermatid lizards was investigated by multidisciplinary techniques. Our analyses elucidated novel toxin types resultant from three unique domain-expression processes:
i) the first full-length sequences of Lethal Toxin isoforms (helofensins) revealed this toxin type to be constructed by an ancestral mono-domain, mono-product gene (beta-defensin) which underwent three tandem domain duplications to encode a tetra-domain, mono-product with a possible novel protein fold;
(ii) an ancestral mono-domain gene (encoding a natriuretic peptide) was medially extended to become a penta-domain, penta-product through the additional encoding of four tandemly repeated proline-rich peptides (helokinestatins), with the five discrete peptides liberated from each other by post-translational proteolysis;
iii) an ancestral multi-domain, multi-product gene belonging to the VIP/glucagon family being mutated to encode for a mono-domain, mono-product (exendins) followed by duplication and diversification into two variant classes (exendins 1&2 and exendins 3&4).
Bioactivity characterization of exendin and helokinestatin elucidated variable cardioactivity between isofroms within each class.
These results highlight the importance of utilising evolutionary-based search strategies for biodiscovery and the virtually unexplored potential of lizard venoms in drug design and discovery.
I have made the paper freely downloadable to anyone who wants to read it. The link to the PDF is below.
http://www.venomdoc.com/downloads/2010_Fry_Heloderma.pdf
http://www.venomdoc.com/venomdoc/Heloderma_files/shapeimage_2.png
Enjoy
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RE: Heloderma venom evolution
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by nietzsche on January 19, 2010
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I recently read this paper and it rocks! It is nice to have access to papers like this, without having to pay an arm and a leg to an online journal (there are a ton) in order to get accurate, current, info. Thank you Dr. Fry!
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RE: Heloderma venom evolution
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by snakeguy101 on January 25, 2010
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very cool research, thanks for sharing. is the venom similar to what you have found in varanids?
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RE: Heloderma venom evolution
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by pictigaster1 on January 25, 2010
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John M you are very young you at the rate you are going most likely be the next BF WW or alot of these people you wish to be you have a better start than Most of us ever did.You will have a head start in school as you are already well versed in venoms as well as venomous reptiles your time will come Of that I am sure.I love the fact we have these young people here that will kick the start of a new and brighter future for us all as herpetologists ,,,,,.....KUDOS BRO.....
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RE: Heloderma venom evolution
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by BGF on January 30, 2010
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As to the question of whether it is similar to varanids, by and large yes they are very similar to each other in that they contain abundant amounts of CRiSP, kallikrein and phospholipase A2 (type III) toxins. There are however a number of other toxin types in there, some, including five brand new toxin classes we just discovered (that paper is currently under review) :) Some are shared, others are currenly only known from restricted lineages. I'll post when the paper finally goes live later this year.
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RE: Heloderma venom evolution
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by Kokopelliman on January 30, 2010
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This saliva is composed of mainly neurotoxins right? Awesome info by the way! And Heloderms roll upside down to forcefully inject because of their glands on the bottom jaw?
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RE: Heloderma venom evolution
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by theemojohnm on January 30, 2010
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Well Thanks Archie.
Must have missed these last few posts here.
I'm happy with things as of late. Finally got my Nerodia stuff finished and published, and that is a load off my mind.
Now, just as I get some free time, spring is right around the corner again.. LOL.
Thanks again.
Take Care,
-John Mendrola.
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RE: Heloderma venom evolution
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by BGF on February 1, 2010
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There are a wide variety of toxins in there, that hit a myriad of different systems. Ranging from neurotoxic (CRiSP and helofensins) to cardioactive (exendin, helokinestatin, some kallikrein isoforms and natriuretic) to hemotoxic (PLA2 and some kallikrein isoforms).
The venom has been greatly underrated in its role in predation. Wild gilas often have extensive scarring from the local rodents and captive gilas are easily able to dispatch and eat mice and small rats.
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