The history of venoms is a wonderful example of an evolutionary process. We're all familiar with the idea of venomous snakes, but the cool thing is that when we examine exactly what it is they're injecting into their prey, it's a collection of proteins that show a nested hierarchy of descent. Ancient reptiles had a small and nasty set of poisons they would use, and to improve their efficacy, more and more have been added to the cocktail; so some lizards produce venomous proteins, while the really dangerous members of the Serpentes produce those same proteins, plus a large array of others.

So something like CRISP (Cystein RIch Secretory Protein) is common to all, but only the most refined predators add PLA2 (Phosopholipase A2) to the mix.
Now lethally poisonous snakes are nice and cute and all, but we all know where the interesting action really is: cephalopods. Let's leave the vertebrates altogether and look at a venomous protostome clade to see what they do.

Relative glandular arrangements of a cuttlefish and b octopus. Posterior gland is shown in green; anterior, in blue. Orange structure is the beak.
Brian Fry, who did all that excellent work characterizing and cataloging the pharmacy of venoms secreted by poisonous snakes, has also turned his hand to the cephalopods. He examined the products of the venom glands of octopus, squid, and cuttlefish, and found a range of proteins, some unique, and others familiar: CAP (a CRISP protein), chitinase, peptidase S1, PLA2 and others. There are a couple of interesting lessons in that list.
First, evolution doesn't just invent something brand new on the spot to fill a function — what we find instead is that existing proteins are repurposed to do a job. This is how evolution generally operates, taking what already exists and tinkering and reshaping it to better fulfill a useful function. Phospholipase A2, for instance, is a perfectly harmless and extremely useful non-venomous protein in many organisms — we non-toxic humans also make it. We use it as a regulatory signal to control the inflammation response to infection and injury — in moderation, it's a good thing. What venomous animals can do, though, is inject us with an overdose of this regulator to send our local repair and recovery systems berserk, producing swelling that can incapacitate a tissue. Similarly, a peptidase is a useful enzyme for breaking down proteins in the digestive system…but a poisonous snake or cephalopod biting your hand can squirt it into the tissues, and now it's being used to digest your muscles and connective tissue. Some effective venoms are simply common proteins used inappropriately (from the perspective of the target).
Another interesting observation is that cephalopods and vertebrates have independently converged in using some of the same venoms. In part, this is a consequence of historical availability — all animals have phospholipases,, since they are important general signalling molecules, so it's part of the collection of widgets in the metazoan toolbox from which evolution can draw. It's also part of an inflammation pathway that can be exploited by predators, in the same way that we have shared proteins used in the operation of the nervous system that can be targeted by neurotoxins. So there is independent convergence on a specific use of these proteins as toxins, but one of the things that facilitates the convergence is a shared ancestry.
In fact, some very diverse groups seem to consistently settle on the same likely suspects in their venoms.

But finally, there must also be physical and chemical proteins of these particular proteins that must also predispose them to use as toxins. After all, animals aren't coopting just any protein for venoms — they aren't injecting large quantities of tubulin or heat shock proteins into their prey. There must be something about each of the standard suspects in venoms that make them particularly dangerous. What the comparative evolutionary approach allows us to do is identify the common molecular properties that make for a good venom. As Fry explains it,
Typically the proteins chosen are from widely dispersed multigene secretory protein families with extensive cysteine cross-linking. These proteins are collectively much more numerous than globular enzymes, transmembrane proteins, or intracellular protein. Although the relative abundance of these protein types in animal venoms may reflect stochastic recruitment processes, there has not been a single reported case of a signal peptide added onto a transmembrane or intracellular protein or a hybrid protein expressed in a venom gland. A strong bias is also evident for all of the protein-scaffold types, whether from peptides or enzymes. Although the protein scaffolds present in venoms represent functionally and structurally versatile kinds, they share an underlying biochemistry that would produce toxic effects when delivered as an "overdose". Toxic effects include taking advantage of a universally present substrate to cause physical damage or causing changes in physiological chemistry though agonistic or antagonistic targeting. This allows the new venom gland protein to have an immediate effect based on overexpression of the original bioactivity. Furthermore, the features of widely dispersed body proteins, particularly the presence of a molecular scaffold amenable to functional diversification, are features that make a protein suitable for accelerated gene duplication and diversification in the venom gland.
To simplify, killing something with a secreted poison typically involves reusing an extant protein, but not just any protein — only a subset of the proteins in an animal's proteome has just the right properties to make for a good venom. Therefore, we see the same small set of proteins get independently coopted into the venom glands of various creatures.
Fry BG, Roelants K, Norman JA (2009) Tentacles of venom: toxic protein convergence in the Kingdom Animalia. J Mol Evol Mar 18. [Epub ahead of print].

77 Comments
mrg · 2 April 2009
Very interesting, PZM -- animal venoms are a very intriguing subject on which not so much is written.
debaser · 2 April 2009
Very Cool. I remember Fry's snake venom paper from a previous venom-posting on pharyngula (Fry showed up in the comments and gave a link, which was great). I hadn't thought about the selection of venom proteins before - why choose one protein over another. It is a good example of organisms exploiting common descent. By acting on the universal substrate -- modified versions of proteins shared by most every living animal -- the venom will work on everything it tries to eat to some degree.
Vince · 2 April 2009
Great stuff (invert's are, of course, WAY COOLER than vert's anyway). A quick Q, however: Table 1 in the post denotes eleven animals/animal groups - what is the context for including "proboscis" and "Stinger" - are these body parts or critters I'm not familiar with? Not being critical here, just wishing for a more detailed "Legend" for the figure. (Note: I am, of course, being both lazy and cheap in asking, as the article is not presently available free without a subscription...).
Anton Mates · 2 April 2009
I think "proboscis" and "stinger" both fall under insects, along with "bristle"--presumably each of those has evolved independently to be a venom-delivery system.
mrg · 2 April 2009
[blockquote]
To simplify, killing something with a secreted poison typically involves reusing an extant protein, but not just any protein — only a subset of the proteins in an animal's proteome has just the right properties to make for a good venom. Therefore, we see the same small set of proteins get independently coopted into the venom glands of various creatures.
[/blockquote]
I was thinking of an analogy -- we don't normally use anything in the kitchen drawer as a weapon, but if we have to improvise we always go for the butcher knife before we go to the basting spoon.
Oh, also thanks for remembering that us layfolk don't always follow the verbiage in a science journal paper all that easily. Some folks with advanced degrees can be a bit inconsiderate in that respect.
Stanton · 2 April 2009
Vince · 2 April 2009
Stanton · 2 April 2009
As for stingers (hit submit button too soon), well, any venom-delivering organ that isn't directly related to the mouth (i.e., proboscis or fangs) is termed a "stinger," i.e, the fin-spines of scorpion-fishes, the spines of fireworms, the telson of scorpions, the business ends of bees and wasps...
As far as I know, though, there are two exceptions to this convention, one being that the "stingers" of the male platypus are simply termed "spurs," and the venomous chelae or claws of pseudoscorpions are referred to as venomous chelae or venomous claws.
Stanton · 2 April 2009
JimmyJ · 2 April 2009
I loved this article. really interesting.
So the vemons are literally too much of a good thing...
Makes me wonder about spiders, particularly the brown recluse. Has a nasty necrotizing venom, I wonder what its other uses are...
Y · 2 April 2009
Wow. What a great article. That's really interesting that cephalopods and vertebrates independently converged on using the same venoms.
A · 2 April 2009
Anton Mates · 3 April 2009
The above was me...
who is your creator · 3 April 2009
In regard to PZ's comments:
"So something like CRISP (Cystein RIch Secretory Protein) is common to all, but only the most refined predators add PLA2 (Phosopholipase A2) to the mix."
and
"First, evolution doesn't just invent something brand new on the spot to fill a function — what we find instead is that existing proteins are repurposed to do a job. This is how evolution generally operates, taking what already exists and tinkering and reshaping it to better fulfill a useful function."
Yes, this is the big dilema for your failed theory. Where did the existing and/or added proteins come from?
For PZ's (and Dawkin's) problematic explanation for the origin of an eye, go to Example #2 & #3:
http://www.whoisyourcreator.com/how_does_evolution_occur.html
"Professing themselves to be wise, they became fools ..."
- Romans 1:22
mrg · 3 April 2009
Y'know, the PT posting system leaves a lot to be desired in a technical sense. The lack of a killfile mechanism is a particular failing.
eric · 3 April 2009
Stanton · 3 April 2009
Stanton · 3 April 2009
eric · 3 April 2009
mrg · 3 April 2009
who is your creator · 3 April 2009
mrg · 3 April 2009
Maxwell Smart: "It's the old YOU HAVE TO PROVE EVERYTHING AND WE DON'T HAVE TO PROVE ANYTHING trick again!"
Stanton · 3 April 2009
John Kwok · 3 April 2009
Seward · 3 April 2009
John Kwok,
FWIW, while I'm an atheist, I find the study of the exegesis, provenance, etc. of the Bible (and other religious texts) to be of great interest. It is basically too influential a text to simply ignore.
John Kwok · 3 April 2009
KP · 3 April 2009
PZ Myers · 3 April 2009
Whining might incur my wrath, that is true. So stop whining.
Stanton · 3 April 2009
Seward · 3 April 2009
What incurs my wrath is the overuse (as well as poor use) of the term wrath. ;)
harold · 3 April 2009
who is your creator -
You make a common error. The theory of evolution explains the evolution of cellular and post-cellular life.
Hypotheses that deal with the origin of cellular life, or of major biochemical molecules, are generally said to deal with "abiogenesis".
Although clearly, a strong understanding of the origin of cellular life would be complementary to and related to the theory of evolution, the current theory of evolution deals with what happens after cellular life already exists.
Now, we all know that you'll waste a vast amount of your own time repeating your incorrect point. You could just listen to me and learn something, but based on past experience, I strongly predict that you won't. Nevertheless, I've given you the benefit of the doubt and corrected your misunderstanding.
harold · 3 April 2009
On the topic of cephalopods -
What's astonishing to me is the parallel evolution of what we call intelligence (flexible behavior, learning, high level information processing) in this class of invertebrates.
Although I recently learned that some invertebrates have myelin, cephalopods apparently don't. Also, most so-called intelligent animals are long-lived and social; neither of these tends to be true of octopi.
If I were independently wealthy, I'd be strongly tempted to try to go to graduate school to study cephalopod intelligence.
http://www.pbrc.hawaii.edu/~danh/InvertebrateMyelin/
http://www.pbrc.hawaii.edu/~danh/InvertebrateMyelin/invertebrate_myelin.html
http://en.wikipedia.org/wiki/Myelin
gregwrld · 3 April 2009
So, "Who's your creator": why don't you tell us what the actual origin of proteins is? And no, "goddidit" will not suffice.
Henry J · 3 April 2009
So, has anybody used this as evidence for "common design" yet?
Henry
Felix · 3 April 2009
Stanton,
I think PZ was talking about John Kwok (not a creationist in the relevant sense). John was recently banned from PZ's blog comment sections. No I'm not explaining why,because I don't care about any of it.
eric · 3 April 2009
Seward · 3 April 2009
gregwrld,
I'm not a creationist, but I would say that many would see a very pragmatic benefit for taking on such an idea; namely the salvation of the soul issue. Questioning the Bible for some means questioning all other manner of things about religious belief.
fnxtr · 3 April 2009
Anyrandomfool · 3 April 2009
Paul Burnett · 3 April 2009
KP · 3 April 2009
GuyeFaux · 3 April 2009
Just Bob · 3 April 2009
Dale Husband · 4 April 2009
who is your creator:
...would be better named "who is your imaginary friend".
If he's the one who runs the website http://www.whoisyourcreator.com/ , he has IDIOT written all over it! Or maybe LIAR would be a bit more accurate.
mrg · 4 April 2009
Frank J · 4 April 2009
Frank J · 4 April 2009
mrg · 4 April 2009
"Dots? We don't have to connect no steeking dots!"
MrG http://www.vectorsite.net
who is your creator · 4 April 2009
Mike Elzinga · 4 April 2009
mrg · 4 April 2009
gregwrld · 4 April 2009
gregwrld · 4 April 2009
gregwrld · 4 April 2009
gregwrld · 4 April 2009
fnxtr · 4 April 2009
robert van bakel · 4 April 2009
To 'Who is your...etc...',
reading is wonderful, not only ONE BOOK mind you, but reading generally. Recently while, reading, I stumbled, as you do while reading, upon this:
"The Copernican Revolution: Planetary Astronomy in the Development of Western Thought", Thomas S.Kuhn, Harvard University Press, 1957.
I'd like to read to you a little, 'Who is your....wateva', lend me your evolved audio function.
P.191, "Citation of Scripture against Copernicus began even before the publication of the 'De Revolutionibus'. In one of his 'Table Talks' held in 1539, Martin Luther is quoted as saying: 'People gave ear to an upstart astrologer who strove to show that the earth revolves, not the heavens or the firmament, the sun and the moon.....This fool wishes to reverse the entire SCIENCE of astronomy; but sacred scripture tells us [Joshua 10:13] that Joshua commanded the sun to stand still, and not the earth.'"
Sound like anyone you know you blockhead?
Rob.
Vince · 5 April 2009
Stanton · 5 April 2009
Just Bob · 5 April 2009
Still waitin'. How is evolution a "failed theory"?
Stanton · 5 April 2009
imbeciliccredulous enough to trust the aforementioned some people with their hearts, souls, and pitiful remnants of their minds.Frank J · 5 April 2009
Frank J · 5 April 2009
Dr. Bryan Grieg Fry · 5 April 2009
If anyone would like a copy of the article, feel free to email me for it.
The journal changed the box view and I didn't catch it in the proofs. Insects were supposed to be divided into three layers in the one box: bristle, probiscis and stinger. These each represent independent evolution of venom within the insects. And the use of the probiscis to deliver venom is something that almost certainly has been convergently utilised on several occasions but it was beyond the scope of this article to go into that. We do, however, have a very lengthy article coming out soon(ish) in Annual Review of Genomics and Human Genetics in which we explore this in greater detail. The abstract for the ARGHG article is as follows:
Convergently recruited proteins were compared from the venoms of centipedes, cephalopods, cone snails, fish, insects (e.g. ants, bees, Lonomia caterpillars, wasps), platypus, scorpions, shrew, spiders, toxicoferan reptiles (lizards and snakes) and sea anemones. Proteins types that have been convergently recruited into disparate venoms are AVIT/Colipase/Prokineticin, CAP, Chitinase, Cystatin, Defensins, Hyaluronidase, Kunitz, Lectin, Lipocalin, Natriuretic, Peptidase S1, Phospholipase A2, Sphingomyelinase D and SPRY. Many of these same venom protein types have also been convergently recruited for use in the hematophagous gland secretions of bloodmeal-feeding invertebrates (e.g. fleas, leeches, kissing bugs, mosquitos, ticks) and vertebrates (Vampire Bats). We discuss a number of overarching structural, functional and evolutionary generalities of these protein families from which toxins have been frequently recruited and propose a revised and expanded working-definition for venom. Given the large number of striking similarites between the protein compositions of conventional venoms and hematophagous secretions, we argue that the latter should also fall under the same definition.
Cheers
Bryam
Dr. Bryan Grieg Fry · 5 April 2009
email address is bgf AT unimelb.edu.au
phantomreader42 · 6 April 2009
Stanton · 6 April 2009
Dr. J Lewis · 7 April 2009
Are we to imply that just because lizards have venom and snakes have venom that one came from the other?
When DNA information demonstrates a loss of functions and never a gain of functions how do we explain this gentlemen?
Dr. J Lewis · 7 April 2009
fnxtr · 8 April 2009
Dave Luckett · 8 April 2009
Dave Luckett · 8 April 2009
Oh, and I should have added: after we have established that you are not fraudulently claiming qualifications you do not have, we can discuss what your findings are, and what evidence you can cite. That should be very interesting. You do know, don't you, that if you've actually found any evidence for separate creation of the species, you're up for a Nobel?
mrg · 8 April 2009
Stanton · 8 April 2009
eric · 8 April 2009
phantomreader42 · 10 April 2009
BRM · 17 April 2009
Anyone like to look for antibodies specific to venom in my blood after years of working with exotics?
"...envenomation I did experience:
- lots of different bees and wasps - the worst are on the island of Utila, Honduras - they feel like you are hit hard by a 2x4
- Central American tarantulas are not too bad - unless they hit bone, it takes longer for the soreness to go away
- several species of scorpion have stung me, the smaller types always seem to pack a bigger wallop, especially in the mountains of Mexico
- rear-fang snakes - none have done more then leave me with an itchy bite;
- poisonous frogs and toads - the only mistake I've made there is rubbing my eyes after handling them, it is like rubbing your eyes after eating Jalapeno peppers!
- Atlantic Stonefish - I grabbed a small one (2-3 inches) in my collectors net, thinking it was a little grouper, and was rewarded for my effort with immediate excruciating pain that felt like a red hot poker slowly traveling up my arm, finally stopping at the shoulder
- Walking Catfish - I stepped on a big one and the poisonous dorsal spine went deep into my instep, took me two days to get the swelling down and be able to walk again;
- Saltwater Catfish of the South Pacific - the dorsal & pectoral fins all have venomous spines with a very painful sting, they travel in swarms and act like the Army Ants of the reef
- Micronesian Lionfish - a couple have hit me while handling them in holding tanks, like a bee sting;
- Pacific Crown-Of-Thorns Starfish - very painful stings that only diminish after soaking the wound in hot water to kill the enzymes
- Fire Coral - short term 'burning' sensation
- Fire Ants - long term 'itch'
- Portugese-Man-O-War , where the tentacles wrapped around your body it feels like some one traced the lines with a blow torch - extreme pain;
- plants - Poisonwood, nettles, Dumb Cane, Pencil Cactus, Poison Sumac, experiences with them come to mind, but their poisonous experiences with me have been minor."