UNIVERSITY OF MELBOURNE (Australia) 01 March 05 Nature’s best bioweapon evolved from bits of body parts
Nature’s most sophisticated biological weapon, snake venom, largely evolved from bits of body parts a Melbourne researcher has found.
In the first comprehensive analysis of the origin and evolution of snake venom, Dr Bryan Fry from the University of Melbourne’s Australian Venom Research Unit says the findings may help to explain why snake venom is so effective.
“These findings help to explain the amazing diversity of ways that venomous snakes can kill their prey and why they have so much potential use in medial research,” he says.
In his research, Dr Fry found that rather that being derived from saliva, 21 of the 24 known snake venom toxins were found to have originally derived from proteins normally expressed in other body tissues, including brain, eye, lung, heart, liver, muscle, mammary gland, ovary and testis.
Only two were derived from proteins presumably expressed in reptile saliva and one did not have any similarity to any known proteins.
The findings will be published in the March edition of Genome Research.
Dr Fry says, “By recruiting and tweaking proteins from other body tissues, snakes developed a clever mechanism for creating more specific and highly potent toxins, ones that would cause their victims’ bodies to turn against themselves upon injection.”
Over time, these newly derived toxins became a normal part of the saliva protein repertoire, he says.
Dr Fry believes that his findings will further research efforts focussed on the use of snake toxins for therapy and treatment of diseases, including cancer, arthritis and heart disease.
“There is something peculiarly fascinating in the use of a deadly toxin as a life-saving medicine,” he says. “The natural pharmacology that exists within animal venoms is a tremendous resource waiting to be tapped.”
http://uninews.unimelb.edu.au/articleid_2110.html

EUREKALERT (Washington, DC) 28 February 05 'Venom doc' tracks down snake bioweapons - Evolutionary analysis of snake venom reveals that toxin proteins arose from multiple body tissues (Contact: Maria A. Smit, smit@cshl.edu, 1-516-422-4013 Cold Spring Harbor Laboratory)
Melbourne, Australia: Bryan Grieg Fry, Ph.D., a scientist from the University of Melbourne, Australia, has conducted the first comprehensive analysis of the origin and evolution of one of nature's most sophisticated bioweapons: snake venom. His results are reported in the March issue of the journal Genome Research.
Venomous snakes, all of which belong to the superfamily Colubroidea, evolved glands for the storage and dispersal of their saliva approximately 60-80 million years ago. Since that time, various prey-immobilizing toxins have evolved from innocuous proteins that were normally produced in other body tissues.
Scientists believe that snakes, rather than simply tweaking proteins already expressed in their saliva, recruited and altered proteins for their chemical arsenal from other body tissues. This enabled snakes to develop more specific, highly potent toxins, ones that would cause their victims' bodies to turn against themselves upon injection. Over time, these newly derived toxins became a normal part of the saliva protein repertoire. To date, 24 different snake venom toxins have been characterized by scientists, but the evolutionary history – or tissue origin – of these proteins has not been documented.
In his March 2005 Genome Research article, Fry, the Deputy Director of the Australian Venom Research Unit, identified the origin of the 24 known snake toxin types. Surprisingly, rather than being saliva-modified proteins, 21 of the toxins were shown to have been originally derived from proteins normally expressed in other body tissues, including brain, eye, lung, heart, liver, muscle, mammary gland, ovary, and testis.
Only two of the toxins were derived from proteins presumably expressed in ancient reptile saliva. Both of these toxin types, CRISP and kallikrein, are closely related to toxins called helothermine and gilatoxin, which are produced by the Beaded Lizard and the Gila Monster, respectively.
One of the toxins in this study (called the waglerin peptide) did not exhibit any similarity to known proteins. Fry believes that it may be a reptile-specific protein.
"The wide-ranging origins of snake venom toxin - body counterparts explain the amazing diversity of ways that venomous snakes can kill their prey and why they have so much potential use in medical research," Fry explains.
Fry hopes that his findings will further research efforts focused on the use of snake toxins for therapy and treatment of diseases, including cancer, arthritis, and heart disease. "There is something peculiarly fascinating in the use of a deadly toxin as a life-saving medicine," Fry says. "The natural pharmacology that exists within animal venoms is a tremendous resource waiting to be tapped."
By comparing the amino acid sequence of each toxin to the amino acid sequences of multiple proteins from non-venomous tissues, Fry was able to reconstruct the phylogenetic history of each snake venom constituent. He determined which protein family each toxin type belonged to, and based the normal expression pattern of that protein family, he predicted from which tissue type each toxin protein had been derived.
Despite the differences in tissue origin, Fry observed that all toxins were derived from protein families with secretory function. This means that the proteins were produced in a specific tissue type and later transported out of that tissue, a necessary biochemical characteristic for saliva production in the snake venom glands.
Fry also observed that the proteins most frequently recruited and modified into toxins where those with a very stable molecular structure – those that are rich in the amino acid cysteine, which enables proteins to form intramolecular disulfide linkages. "These structures provided an excellent framework for the 60-80 million years of 'evolutionary tinkering' that have turned these proteins into potent, highly specific snake venom toxins," Fry concluded.
http://www.eurekalert.org/pub_releases/2005-02/cshl-dt022305.php

HEALTH DAY NEWS (Sunnyvale, California) 28 February 05 Study Shows Snake Venom's Hisstory
Snake venom is one of nature's most sophisticated bioweapons, containing toxins that cause their victims' bodies to turn against themselves.
Now scientists have found the reason why these poisons are so potent: They're made of altered proteins from body tissues located throughout the snake's body.
The findings might even help researchers someday turn deadly venoms into lifesaving medicines.
The new study, published in the March issue of Genome Research, provides the first comprehensive analysis of the origin and evolution of snake venoms.
Research conducted by Bryan Grieg Fry, of the University of Melbourne, Australia, has identified the origin of all 24 known types of snake toxin.
Although snake venom is transferred through bites, scientists have doubted the venoms are saliva-based. Instead, the theory was that snakes recruit and alter proteins for their chemical arsenal from other body tissues.
Fry's research has proven that point, demonstrating that 21 of the 24 known venoms are derived from proteins normally expressed in other body tissues. The identified origin tissues are found in the brain, eye, lung, heart, liver, muscle, mammary gland, ovary and testis of snakes.
Of the three remaining venoms, two toxin types are derived from proteins presumably expressed in ancient reptile saliva, while the third did not exhibit any similarity to known proteins.
"The wide-ranging origins of snake venom toxin from body counterparts explains the amazing diversity of ways that venomous snakes can kill their prey and why they have so much potential use in medical research," Fry said.
Fry hopes his findings will aid research focused on the use of snake toxins for therapy and treatment of diseases, including cancer, arthritis and heart disease.
"The natural pharmacology that exists within animal venoms is a tremendous resource waiting to be tapped," he said.
Venom-based research may already be bearing fruit. In August, scientists at Wake Forest University used a protein in snake venom to help elucidate why heart medications called integrin antagonists can sometimes cause patients more harm than good.
http://news.yahoo.com/news?tmpl=story&u=/hsn/20050301/hl_hsn/studyshowssnakevenomshisstory