Evolution in colubrids

[Lisa]

This was just posted at http://www.**************/toxinology/downloads/BGF_Colubroidea_RCMS.pdf but for clicking sake i've reposted it @ http://www.geekgrrl.ca/bgf_colubroidea_rcms.pdf . It suggests that colubrids are evolved from venomous snakes which evolved from boids

[Dr. Bryan Fry]

Actually, it gets even cuter than that. We pulled the classic cobra-style toxin out of a bloody ratsnake. We showed that these, and other viper and elapid types, toxins are diverse in the various different 'colubrid' families. In a nutshell, venom evolved once, just before the viperidae lineage split off (one of the most basal events in the evolution of the advanced snakes (Colubroidea)). From an evolutionary perspective, this is extremely cool.

The ancientness of venom means that all the lineages we think of as 'colubrids' are technically venomous and that the toxins differ as much as they differ from each other (and some of the 'colubrids' are actually far far more closely related to cobras than to a corn snake).

Some of these snakes are pumping out huge amounts of venom. At the end of the day are the implications in two different arenas: from the pet store perspective its pretty straightforward
1. Are all the vast majority of these snakes now considered venomous (and the Duvernoy's gland concept being dead and buried as its now been shown that its the same bloody venom gland)? Yes
2. Are all dangerously venomous? Certainly not.
3. Are there highly dangerous species lurking in there? Yes
4. Has this happened before? Yes, most acutely with the Rhabdophis in the late 70s/early 80s. It was supposed to be a psychadelic Asian garter snake, turned out to be a garter snake on crack. Highly toxic and even lethal venoms. Some of the 'colubrids' we were working with I'd considered as dangerously venomous (particularly any Psammophiinae (e.g. Psammophis and Malpolon). Even scarier, none of the existing antivenoms touch any of the colubrid venoms.

What we're after is a process of education not prohibition. I think keeping venomous should be on about the same standard as getting a motorcycle license. A reasonable baseline.

Another implication is in the area of drug design & discovery: instead of the couple hundred usual suspects being available for biomedical research, there is now about 2700!

This all made our brains hurt for a while. Your turn to feel a bit of pain ;-)

Cheers
Bryan

[Simon R. Sansom]

Well, once the Canadian authorities get hold of that little gem we'll all be ble kiss most of our colubrids good-bye! It'll be the typical, knee-jerk, blanket legislation...

I hear the death-knell of Canadian herpetoculture.

Thanks for the ray of sunshine.

Simon

[Dr. Bryan Fry]

Hi Simon,

I don't think it'll be as bad as all that. Yes the situation is a bit more complex but not unworkable or un-understandable. I am trying to make very clear the difference between technically venomous (pretty much all of them now) and venomous from a practical perpective (some are still to be considered utterly harmless).

Cheers
B

[Andy_G]

I think Simon is right. Once they hear that snakes that were not percieved to be venomous before actually are, our stupid politcians will ban everything without thinking twice or even looking into the subject.

[BoidKeeper]

Well we'll just have to conduct a study of our own that discredits their findings I guess. lol
Cheers,
Trevor

[Lisa]

Actually I don't think the canadian government will notice or care. here in ontario hots are legal, and not all colubrids are dangerous.

[Simon R. Sansom]

Hi Lisa,
Here's the thing to worry about...
Yes, hots are legal in Ontario at the Provincial level, not the municipal level (I know of precious few cities or towns where hots are allowed).
So, any snakes that you may own which were previously considered harmless but now are technically "venomous" (although actually harmless) may become by-law violations seeing as MOST municipalities ban venomous snakes.

And once the animal rights freaks get hold of that information they will finally be able to do what they've been trying to do for years - Shut us down, once and for all. These nuts never used to bother me, but now they've got a smoking gun.

And, do you think that legislators will tackle the problem sensibly?...Of course not. Like I said, we'll be looking at blanket legislation and even your corn snake may become a controlled entity.

Dr. Fry, I hope that you're right and this doesn't get out of hand, but I just have a bad feeling about this.

Cheers!

Simon

[Simon R. Sansom]

By the way, "hello" Dr. Fry! I'd like to welcome you to the forum on behalf of all of us.

You mentioned making distinctions between dangerously venomous and essentially harmless "venomous"...While that may work in theory, it's a proven fact that when legislators hear "venomous" and "snake" in the same sentence, common sense flies out the window and madness reigns!

Simon

[Dr. Bryan Fry]

Hi Simon

Fangs for the welcome ;-)

As for potential legislative problems, there's only one way to counteract this, and thats of course through education.

Take care
B

[BoidKeeper]

Yes Welcome Dr. Fry. It's so nice to have a professional among us. As for the education aspect, that's where I come in. I'm a public school teacher and I do educational shows for schools in my district. It's supposed to be for the students but I try to educate my fellow educators and administrators as well.
Cheers,
Trevor

[Simon R. Sansom]

Good for you, Trevor! I sometimes think it's more important to get through to the adults, because they're the ones who promote all the fear and prejudices.

Simon

[BoidKeeper]

You said it! I know the kids will love it no matter what. I think that most kids who fear snakes learn it from the adults in their life. Like most behaviours they pick up, they pick them up from the adults in their lives who model behaviours for them.
Cheers,
Trevor

[Lisa]

Originally posted by BoidKeeper
You said it! I know the kids will love it no matter what. I think that most kids who fear snakes learn it from the adults in their life. Like most behaviours they pick up, they pick them up from the adults in their lives who model behaviours for them.
Cheers,
Trevor


You hit the nail on the head right there
My cousin is a perfect example of this. She used to play with snakes in the backyard when she was a toddler, her mom would freak out. now she's terrified of snakes. she can't even look at pics of them.

[Joe]

thats very interesting! thanks for posting that!

[Ace]

My cousin is a perfect example of this. She used to play with snakes in the backyard when she was a toddler, her mom would freak out. now she's terrified of snakes.

This is how I actually started my collection. I had found a gartersnake In my yard and brought it in to show the kids to show them snakes aren't "nasty little critters" Once they figured out it was a real snake they cleared out of the room faster than if I would've yelled "FIRE!". So, I did research, found a species I liked (Kings) and picked one up at the next show. Now snakes are just second nature to them. My son's considered the reptile expert in his class :D. They're aware there are dangerous species and not to pick up wild ones.

Dr. Fry: First off welcome to Ssnakess!
Second: You state "As for potential legislative problems, there's only one way to counteract this, and thats of course through education." This may be easier said then done. Considering your research has just changed many of the things we "THOUGHT" we knew of many of the species we know. Your research basically sought to find out if there was or wasn't venom in these species. The problem is it didn't go to the point of figuring the potency of these venoms.(as I understand it anyway) Till that's done many legislatures will base their laws on just the "venomous or non-venomous" aspect of your research. Not whether they're dangerous or harmless venoms.

[Invictus]

I have a question for the good Dr.

Would it be fair to say that even if all snakes do possess venom, that certain colubrids (corns and kings, for example) lack a delivery system for this venom? Or have you discovered that even corns have the ability to inject venom?

[BoidKeeper]

I was think of asking the same question but couldn't get it worded right.
Thanks,
Trevor

[Dr. Bryan Fry]

Hi Ace

This paper is part of a series (two others are in press and should be out soon (in the next couple weeks), two more have just been sent in and a few more projects are being finished up in the lab).

We did test the venoms and they are just as toxic as the comparative range of elapids (and some are staggeringly toxic, approaching death adder level). The venoms are just as complex.

Some of the snakes (such as Psammophis and Telescopus) have massive venom yields coming from staggeringly big glands. So, we have a range funning from small yeilds (ie radiated rat snakes) to massive yields (Telescopus), pretty inefficient delivery (radiated rats again) to very efficient (Psammophis).

The American Elaphe-types (e.g. Pantherophis/Pituphis/Lampropeltis) have recently undergone a secondarly loss of the gland and reverted back to the more primative condition of constricting. This allowed them to switch from an amphibian/reptile diet to a rodent diet. The venom delivery wasn't up to scratch for this task. This is of course what drove the development of highly effective fangs on at least four separate occasions (the Elapidae, Dispholidus in the Colubrinae, the Atractaspidae and the Viperidae).

The toxins themselves include the archetypal cobra-style toxins (three-finger toxins and Type I phospholipase A2 toxins) as well as a myriad of other sorts (including the M12B metalloprotease type for example that is responsible for the devastating action upon the blood by Dispholidus, Rhabdophis and Thelatornis, is widespread in all the Colubroidea venoms (including vipers)).

This of course means that the entire conept of Duvernoy's gland is toast. Same venom, same gland.

Check out the scary size of these glands. Bloody huge!

Psammophis mossambicus
http://www.venomdoc.com/ryan/Snakes/Glands01.jpg
http://www.venomdoc.com/ryan/Snakes/Glands02.jpg

Telescopus dhara
http://www.venomdoc.com/ryan/Snakes/Glands03.jpg

Where this all gets very cute is that none of the existing antivenoms do touch them. So while they are less likely to get you, if they do you are screwed.

Certainly not what we expected when we started this all.

Cheers
BGF

[Dr. Bryan Fry]

Hi Invictus

They do have a delivery mechanism and some of them can deliver it quite well. However fangs are of course a vast improvement and this is of course what drove the development of fangs. Just like the ability to make noise in the primate far preceeded our voice box but this advanced piece of architecture was a tremendous modification. Fangs evolved separately on four separate occasions but came much later than the potent venom. There could be no strong selection pressure for the development of fangs unless there was already a potent, complex venom worth delivering.

Cheers
B

[BoidKeeper]

Links did not work for me. So were venom glands found in colubrids that we deem as harmless?
Thanks,
Trevor

[Ace]

The American Elaphe-types (e.g. Pantherophis/Pituphis/Lampropeltis) have recently undergone a secondarly loss of the gland and reverted back to the more primative condition of constricting. .

I thought this meant they were the few that didn't have venom because they no longer had Duvenroy (or now venom) glands?

How do you test the degree of toxicity of the venoms? As I understand it (I'm by no means a scientist) these snakes only carried parts of the venom proteins that previously more dangerous snakes have. How do you conclude the venoms just as deadly? Do certain venom proteins carry certain levels of toxicity? Are some more toxic at lower levels than others?
Sorry for all the ???'s, just trying to make sense of your study, and I'm not well versed in the venomous side of snakes :D.

[reverendsterlin]

I think part of the confusion may be the use of the term venom and real differences between what is venom, what is toxic saliva, and is there a real difference between the two. The other confusion will be the definition of venomous used, whether glands, delivery system, use for prey aquisition, defense, and other questions defining the parameters of venom, poison, venomous, and poisonous. Welcome to the site Dr. Fry

[Dr. Bryan Fry]

Hi mate

Thie ancestor of this clade of American (but not the Asian) 'Elaphe-types) lost the venom gland as it evolved (devolved?) to become a more efficient feeder on rodents. This lineage is one of the very few that doesn't have it. Trimorphodon (lyre snakes) share a common ancestor with these snakes and do have the gland.

As for how we tested the venom, our initial tests have been on the neurotoxicity, using the same assays we've used in the past for death adders, sea snakes, etc. Some of the venoms are very very toxic. Effects upon the blood will be the next major pharmacological area to be investigated. In the meantime I'm sequencing as wide of a diversity of toxins as possible in order to study how they evolved.

The various 'colubrids' share at leasat six toxin types with the elapids and have no doubt evolved new ones of their own just as the elapids have developed new ones as well. Some toxin types are more toxic than others, and the 'colubrids' contain at least three of the most toxic (three-finger toxins, phospholipase A2 and M12B metalloproteases (this last group is the toxin type widespread in viper and elapid venoms that the boomslang uses to exert its devastating effect upon the blood chemistry and toast the ability to clot).

Cheers
B

[Dr. Bryan Fry]

Hi Reverendsterlin,

These venoms are true venoms. The concept 'toxic saliva' was used when 'colubrids' were thought to have evolved toxic secretions independently. However what we've shown is that venom originated only once and that some toxin types (4-6) are shared amongst all the lineages, including the vipers. The 'colubrids' share these six with vipers and elapids and further share at least an additional two with the elapids. It is the same venom gland.

Venom was a key evolutionary step for prey capture. The next step was a refinement of the gland and delivery mechanism. This was through the development of a musclar compressor set to create a high pressure delivery system terminating in long fangs (typically hypodermic-needle like). This has happened independently at least four occasions.

Cheers
B

[Simon R. Sansom]

Dr. Fry,
Are you able to observe the developement/evolution of the venom-delivery system in the fossil record?

Simon

[Dr. Bryan Fry]

Hi Simon

Not the venom glands they are soft tissue. We can however physically watch the emergence of different dentition types in the fossil record. Also, by mapping the presense of certain toxin types over the genetic tree of the animals themselves we can map the evolution of these toxin types. Further to this phylogenetic analysis of a toxins present in more than one lineage can also provide evidence for a single recruitment event.

Cheers
B

[Jeff_Favelle]

Holy crap, I just saw Brian on TV!! Way cool. Talking about Taipans or something. Great stuff man!

[Simon R. Sansom]

Jeff, I was just sitting here thinking about how amazing it is that we can have a group dialogue with the top man in the field when he's on the other side of the world!

Great Stuff!

Simon

[Jeff_Favelle]

I would have to say amazing as well Simon. For all the bad that technology does, its still pretty cool sometimes eh?

[Dr. Bryan Fry]

I have to agree, anyone who knows me will agree that in addition to being smitten by snakes, I'm also a complete computer geek ;-) My addiction to the internet drives my wife to distraction, I've even managed to track down an internet connection while on remote islands in Asia ;-p Lasted three days before I cracked and went searching!

Cheers
B

[Dr. Bryan Fry]

PS

I'm writing this while at the very tip of Cape York in Queensland Australia, we've been here for a week and a half now catching sea snakes. Always too much fun ;-)

Cheers
B

[HetForHuman]

that sounds like fun, i wish i could join you.

[Jeff_Favelle]

Cape York? Go get me some new maculosa bloood man!! And then head south and pick up some Womas!

Cheque is in the mail.............

[Lisa]

Three thoughts.
Dr Fry, I would have expected you to have a portable sat hook up or something :) I hear you on the addiction thing. katey considers my laptop be be the "other woman"

Where else but herping do you get to do stuff like rock climbing, scuba diving, get a tan, etc.

I'm looking forward to seeing the rest of the papers. What's next for colubrids? A delivery system?

I'm not too concerned about this causing the banning of snakes. As Dr Fry said, there are some colubrids with out any venom glands and the ones that do carry venom are technicaly already banned where venomous snakes are already banned, which here in ontario depends on your location (it seems if you want to live in a big city here you have to give up your venomous snakes). There's still lots of snakes to play with. Learn the laws of your area. Do you want a cobra in your collection? How about a colubrid that's as leathal as a cobra? Would you let just anyone have access to same said cobra? Then why is it so important to keep a snake that is as potentialy leathal (if not more due to the lack of antivenom)? Remember not all Colubrid snakes are venomous, just some of them. And this doesn't affect boids either (though they seem to have a bad rap in parts of Canada, maybe because we don't have any native to the country). I don't have a problem with people keeping venomous snakes, as long as they're properly housed and not against the law.

[Scales Zoo]

Hello Dr. Fry.

Nice to see you on ssnakess.com - I hope you stay!

Midwest rocks, we've been pushing it here in Western Canada for over a year.

I am very interested in the developements of the venoms associated with colubrids. We live in an area where there are 3 types of garter snakes. Their bites really itch for a long time, or so I have heard.

We also keep quite a few different asian elaphe, and other non typical ratsnakes.

We do many educational shows, and I am suprised how many times I am asked about garter and hognose "venom". I always like to have a very informative answer.

Have you studied these species?

Regardless, you have an open invitation to visit the zoo, our home collection, the rattlesnake hibernacula 12 kms from our back dore (Northern most rattlesnakes in the world), and have the chance to find many garters and a few hoggies possibly.

Keep up the good work Dr.

Ryan and Sheila

[Simon R. Sansom]

Dr. Fry;

Have you looked at any boids in your study?
The reason that I ask is because I seem to be fairly sensitive to snake "saliva".
When I get bitten I USUALLY get the swelling, itching, welts, etc. My most annoying bite was actually from a friend's Candoia carinata (Roy, if you're reading this, remember the "Flying carinata" incident? LOL!). The itching and swelling lasted for five days. It was actually worse than a Thamnophis bite, which I suffered just a couple of weeks prior. The Candoia bite was just a VERY quick, defensive nip, whereas the Thamnophis hung on and chewed for a good five minutes, yet the symptoms from the Garter bite went away after about twenty minutes as is usual. The Candoia bite left my knuckle swollen, red, itchy and with white, puffy marks around each tooth-hole.

Can you shed any light on this for me? I assume that I'm just sensitive to certain components of the saliva??

Thank you.

Simon

[Dr. Bryan Fry]

Hi mate

Have you had a chance to check out the article? I've uploaded it and you can download it at
http://www.venomdoc.com/downloads/BGF_Colubroidea_RCMS.pdf

Basically it means that venom evolved only once, over a hundred million years ago. This was before any of the lineages of the Colubroidea (advanced snakes) we even thinkl of (elapids, vipers, atractaspids, colubrines, natricines, etc.) even existed. The vipers were the first to split off but the venom gland already existed and already contained a potent venom. This was before any fangs showed up. It makes sense. Evolution does one thing at a time.

First a potent, complex venom that is delivered through sharp, evenly sized teeth. Then comes a more refined delivery mechanism. Can't do both at the same time and a complex delivery mechanism certainly evolve if there was nothing to deliver. So, efficient fangs came after the venom. One thing drives another. Just as the ability to make noise in the primates drove the development of our voice box.

These ancestral half a dozen toxin types we worked out, made for quite a complex mitures with potent activities. The snakes have been refining them ever sense. Some toxin types have appeared at different point in the evolutionary tree. We discovered that all the 'colubrid' lineages contain in their venom the same sorts of toxins as a cobra or mamba. We isolated from the venom of the radiated ratsnake (the archetypal 'non-venomous' snake) a 3FTx (three-finger toxin), the typical cobra-style toxin. As is the common actiivity of 3FTx, this toxin was a potent neurotoxin. Thus, these very potent neurotoxins were evolved after the vipers split off from the main evolutionary tree but before any of the various 'colubrid' lineages. These toxins however are just as potent as the homologous toxins found in death adder or krait venoms. Some of the crude venoms are scarily toxic (some Boigas are as toxic as any elapid). Some of the snakes have huge venom glands as well (the ones in Telescopus and Psammophis are truly scary. As big as any elapid and more so than many.)

So, the venom predated the different 'colubrids' and all the 'colubrids' contain actual venom. The idea of the Duvernoy's gland is toast. Same venom, same gland.

However, one lineage has recently lost the gland and reverted back to the more primative, adept constricters. The American 'Elaphe-type' i.e. Pantherophis, Pituouphis, Lampropeltis, share a common ancestor. This snake was venomous but with small yields and not exactly the world's most brilliant delivery system. This snake didn't really constrict that much but instead bit the hell out of the prey ala the Asian Elaphe. This lineage also fed on amphibians and reptiles.

The American 'Elaphe-types' made the switch from amphibians/reptiles to feeding on rodents. The venom system wasn't up to scratch for rodents but constricting did the job quite nicely. The Lyre snakes (Trimorphodon) are a good example of an American split that stayed venomous. The Central American lineages stayed nicely venomous and several lethal ones are in there (i.e. Philodryas).

Even Coluber have been known to deliver a nasty bite, I consulted on a pet store bite to an employee who was nicely paralysed by the bite from an Egyptian Coluber.

So, are the vast majority of the colubrids venomous? Yes.
Are all dangerous? Yes.
Have dangerous ones previously been sold as harmless? Yes (e.g. Rhabdophis in the late 70s and early 80s or Psammophis in pet shops now).
Are all the known lethal ones related or scattered liberally across the taxonomical tree? The lethal species have been seemingly by random, all the seven 'colubrid' families have had at least one genera shown to be capable of severe envenonomations.
Are there lethal species yet to be known? Definately.

The truly scary part is that non of the existing antivenoms are likely to touch any of the colubrid venoms. So while they may be less likely to get you, if they do you are screwed.

I'd love to come up, I haven't been to North America much for the last ten years. Certainly never have been to Canada. However, no idea when I'll be up that way. I am going to try for the next years Daytona show. I went a couple years ago and had a blast.

Cheers
B

[Dr. Bryan Fry]

Hi Simon,

We did look at the saliva of the reticulated python. No proteins in there at all. The saliva is full of mucous and this stuff could of course be irritating as hell. The worst of course is when those long brittle teeth break off in your flesh. Always truly sucks.

Cheers
B

[Simon R. Sansom]

Thanks, Doc! Very interesting.
Yes, I once had a Carpet Python tooth in one of my hands for over a year before it worked it's way out!

Simon

[Janiman]

Dr Fry,

I'm very curious about the potential for delivering these toxins. Where do the toxins vent into the mouth (saliva glands or another route?), and does it take a conscious effort by the snake to excrete it or is it present in the mouth/saliva at all times?

Thanks for such a fascinating thread,
F

[Dr. Bryan Fry]

Hi Jaiman,

In some species there is a well developed opening in the back of the mounth and a few enlarged teeth poking out (ie Leiheterodon). In others its much less developed (ie. radiated ratsnakes). Some alternate arrangements seem to be in development (ie Psammophis seems to be dumping venom forward as well as back). Some have muscles attached to the venom gland (e.g. Mehelya) which is the next refinement level up.


The distinctions 'aglyphous' and 'opistoglyphous' are totally artificial distinctions and are dropped. Similarily abandoned is the very concept of the 'duvernoy's gland. Also 'colubrid' is not longer the taxonomical dumping ground for anything that is not obviously a viper or elapid, when in fact there are seven very distinct families in the 'colubrids', some of which are vastly more closely related to a cobra than to a cornsnake.

Cheers
B

[BWSmith]

I have not even begun to read this thread yet, just got back in town a couple hours ago. I just have to say:

Princess White Devil is Everywhere I turn!!!!!! ;)

How goes it mate?

[Simon R. Sansom]

Dr.Fry, which snakes are considered to be the most advanced/modern?.

Simon

[Dr. Bryan Fry]

BW!!!! Are you just back from your wedding? If so, congrats mate ;-) And yes, I've been spending a bit of time online lately ;-p

Simon, as for which snakes are considered the most modern, thats a good Q and depends on what you define as modern. While the Viperidae are the most ancient of splits in the advanced snakes (Colubroidea), they haven't just been killing time since then. The fang architecture and the Crotalidae clade's heat seeking pits certainly make them tremendously advanced.

On the venom side of things, the Australian elapids have been the busiest in recent times, with the recent development of many new toxin lineages (as well as the remarkable streamlining of the sea snakes venoms). So, based upon recent high level of evolution and novelty of groups, I'd say that the Australian elapids have the most advanced venom. However, while the mambas have been quite stingy in the development of new toxin groups, they have taken the 3FTx (three-finger toxins) into a truly different arena.

At the end of the day, I'd break it down this way:

Most advanced fang architecture - vipers although the Atractaspis fangs are pretty trippy and just as advanced. On the elapid side, the death adders have the most highly evolved fangs of any elapid, actually being semi-mobile in a viper-like way. Of the 'colubrids' the boomslang certainly takes the prize.
Most advanced venom glands - Either the Atractaspis venom glands or the Calliophis bivirgata venom glands (both have evolved new glands that connect behind the normal gland and run up to 1/3 the length of their body).
Most highly refined venom (taking old toxin types and turning them into an art form) - Dendroaspis (Mambas)
Most novel venom (evolving potent new toxin types) - The Australian terrestrial elapids, they have quite a few new toxin types, including new ways to completely screw up your blood.
Most advanced genetically - this is still being worked out.

All the best
B

[Simon R. Sansom]

Dr. Fry,

I've heard that Atractaspis venom is fairly potent. In addition to the relatively potent venom, why have they developed such huge venom glands? Why does a fossorial snake need that huge quantity of venom?

Cheers!

Simon

[Dr. Bryan Fry]

Hi Simon

Yeah, the Atractaspis genus (Stilleto snakes) are weird little bast*rds. Why they have the side opening fangs may be from the burrowing (they don't even need to open their mouths to pop the fangs out).

They don't actually put out that much venom relatively speaking, the long gland is quite thin. and doesn't secrete really that much more. It is quite potent though and contains a unique toxin class called sarafotoxins. These guys have a devastating effect upon the blood pressure, jacking it up very very quickly and violently.

They also have a couple big enzymes, the M12B class of metalloproteinases, this class is one of the 'ancestral toxins' that were in the venom of the very first venomous snake.

The Atractaspids are therefore a good example of how venom has evolved, it still has as one of its major venom components one of the original toxins but it also has a unique toxin type (sarafotoxins) that is found only in these venoms.

Cheers
B