Pharyngula

Evolving proteins in snakes

Blogging on Peer-Reviewed Research

We’ve heard the arguments about the relative importance of mutations in cis regulatory regions vs. coding sequences in evolution before — it’s the idea that major transitions in evolution were accomplished more by changes in the timing and pattern of gene expression than by significant changes in the genes themselves. We developmental biologists tend to side with the cis-sies, because timing and pattern are what we’re most interested in. But I have to admit that there are plenty of accounts of functional adaptation in populations that are well-founded in molecular evidence, and the cis regulatory element story is weaker in the practical sense that counts most in science (In large part, I think that’s an artifact of the tools — we have better techniques for examining expressed sequences, while regulatory elements are hidden away in unexpressed regions of the genome. Give it time, the cis proponents will catch up!)

This morning, I was sent a nice paper that describes a pattern of functional change in an important molecule — there is absolutely no development in it. It’s a classic example of an evolutionary arms race, though, so it’s good that I mention this important and dominant side of the discipline of evolutionary biology — I know I leave the impression that all the cool stuff is in evo-devo, but there’s even more exciting biology outside the scope of my tunnel vision. Also, this paper describes a situation and animals with which I am very familiar, and wondered about years ago.

i-0d89556d645c307d4d7d99b3f75dd2b0-taricha.jpg

When I was a graduate student in Oregon, I worked now and then with an emeritus faculty member named Jim Kezer — a great guy who was classically trained in natural history, and who would dazzle us benchies by taking us on field trips into the Oregon Cascades, where he could name every weed and insect we’d encounter, and he’d tell us all kinds of stories about these otherwise almost unnoticeable organisms. We made collecting trips up into a remote lake where we’d harvest rough-skinned newts, Taricha granulosa, for histology studies. This lake was swarming with newts — it was pretty much the only large animal you’d find there, and that was because they had a potent biochemical defense mechanism: they oozed a neurotoxin. These newts were not popular denizens of the lakes, because where they were found, the fish and frogs soon disappeared.

i-df0b0a4231a0de272649929ae3be911d-ttx.jpg

The toxin they secreted is called tetrodotoxin, or TTX. It’s the same nasty substance that the pufferfish, fugu, contains — it binds the sodium channels of the nerves, blocking all electrical transmission. It’s notoriously popular in sushi because at low doses it can cause a tingling sensation, similar to what you felt when the novocaine was wearing off after your visit to the dentist, and it also provides the titillating thrill of danger. Overdoses cause a flaccid paralysis, and can be lethal. More than a mild tingle, I suspect it’s that entirely psychological frisson that this food might just kill you that lends fugu its culinary notoriety.

The newt has no other defenses. They don’t have fangs or claws, they are as soft as noodles, and so these lakes are reduced to big bowls of squirmy delicate amphibian meat that is frustratingly untouchable by most predators because of the unfortunate fact that they are also using a nasty biotoxin in violation of all of the rules of the Geneva Convention. You might expect that if something…evolved…a countermeasure, this would be a situation ripe for exploitation.

And so it is. Some of the most successful predators of small amphibians are another herpetological marvel, the garter snakes, Thamnophis. Unfortunately, if you feed ordinary garter snakes a diet of rough-skinned newts, they tend to move more and more slowly as the innervation of their skeletal muscles undergoes a toxin blockade, and if they eat enough, they die. This is not a good thing from the snake’s perspective, although the newts do get revenge and their relatives benefit from the subsequent reluctance of snakes to eat them. It also presents an evolutionary opportunity, in that resistance to TTX in snakes can be a real advantage, since they won’t die and they’ll be able to feast on squishy purplish-brown and orange tubes of meat.

This is happening right now. Populations of garter snakes, T. sirtalis, in California, Oregon, and Idaho are showing different degrees of resistance to TTX, and these differences are being traced right down to specific changes in the amino acid sequence of the snake sodium channel. It’s happening repeatedly, too, with different populations independently acquiring different variations that confer differing degrees of resistance.

We know a lot about the structure and biophysics of the sodium channel — it’s one of those universal proteins we find all over the animal kingdom. It’s a protein that loops through the membrane multiple times, forming four cylindrical domains. These cylinders pack together, leaving a space at the center that is the pore proper; there are also regions of the protein that act as gates, opening to allow sodium to flow through and generate an electrical current, or closing to block it.

i-d59f60697e2867a1de9c1555bd6320c5-nachannel.jpg

We also know how TTX works. It binds especially strongly to an aromatic amino acid on the outside of the cell, in domain I. In that place, it effectively blocks the pore, making the channel permanently closed so no current flows.

Obviously, the animal that must most effectively resist the effects of TTX is the one that is producing the toxin. Species that make TTX, like fugu, typically replace that aromatic amino acid with one that doesn’t bind TTX. It’s a testimony to the hit-or-miss nature of mutations and evolutionary change that the snakes haven’t stumbled onto that same change—they’ve instead made other small changes to the protein to reduce binding of TTX. Instead, they’ve tweaked the pore helix and β-strand from domain IV, which also reduces the effectiveness of TTX binding.

Here’s a summary tree diagram of the differences found in these populations. We’re looking at 5 different populations of snakes, named after their collection sites; Benton and Warrenton are in Oregon, Willow Creek is in California, and Bear Lake is in Idaho. Illinois represents the ancestral phenotypic state, a population from a state without TTX-secreting newts, and which has no TTX resistance.

TTX resistance is measured in MAMUs, or mass-adjusted mouse units — low numbers mean they have no particular resistance, while large numbers indicate increasing resistance. The Bear Lake and Illinois populations are sensitive, while the others have varying degrees of resistance.

The right side of the figure is the interesting bit: it shows the amino acid sequence of a small stretch of the protein in domain IV, and you can see the differences. All the resistant populations have a valine at position 1561, but notice that it is likely that these represent two independent origins. That valine alone only weakly improves resistance; the Benton population has an additional amino acid substitution that doubles the resistance. Willow Creek snakes have substantially greater resistance, and they also have 3 other different substitutions.

i-0919ac98e8ec4a9ae32a79ce4c7484af-ttx_resist_seq.jpg
Amino-acid sequence differences for four snake populations. a, Phylogeographic relationships based on mitochondrial DNA analysis of 19 North American populations of Thamnophis sirtalis indicate separate origins of elevated resistance to TTX in the Willow Creek population compared with populations from Benton and Warrenton. Bear Lake is from a third lineage and is not resistant to TTX. Whole-animal TTX resistance for each population is reported in mass-adjusted mouse units (MAMU); branch colours reflect statistically distinguishable levels of resistance. Whole-animal TTX resistance was measured as a mass-adjusted dose of TTX (MAMU) that produced an average of 50% decrease in snake sprint speed in each population. b, Amino-acid alignment of part of the domain IV S5-S6 linker that affects TTX binding from tsNaV1.4. Green, pore α-helix; purple, β-strand; asterisk, selectivity filter. Dots indicate identical amino acids and grey shading highlights sequence differences between populations. Despite independent evolutionary histories, all resistant snakes share the substitution of valine for isoleucine at position 1,561.

There are other details — the proteins have been isolated, chimeric proteins generated to isolate specific regions, and they’ve been expressed in Xenopus oocytes, all demonstrating that these small changes are actually responsible for conferring TTX resistance. The meat of the story, though, is that we have concrete measurements of specific molecular changes that are responses to an evolutionary arms race, and we’re seeing these differences emerge in different populations of a single species. This is evolution in action, and the observed appearance of new properties, traced right down to single changes in proteins.


Geffeney SL, Fujimoto E, Brodie ED III, Brodie ED Jr., Ruben PC (2005) Evolutionary diversification of TTX-resistant sodium channels in a predator-prey interaction, Nature 434:759-763.

Soong TW, Venkatesh B (2006) Adaptive evolution of tetrodotoxin resistance in animals. Trends Genet. 2006 Nov;22(11):621-6.

Comments

  1. #1 dogmeatib
    June 30, 2008

    *sigh*

    Had to be about snakes …

    I’m feeling bad because I killed a snake this morning. Turns out it was just a western blind snake, but it was in our family room and the cats were very curious … on top of that, in AZ, you see snake, you think *rattle rattle*, so to be honest I didn’t take a very close look before grabbing a shovel I was working with out on the patio and, well…

    Truly interesting paper though.

    *sigh*

  2. #2 yorktank
    June 30, 2008

    It’s okay dogmeatib. I’m sure that snake in your family room was actually the devil in disguise.

  3. #3 Glen Davidson
    June 30, 2008

    C’mon Behe, explain the intelligent design rationale behind such “irreducible complexity” in this mutual evolution.

    “Intelligent” actually means something, right?

    Glen D
    http://tinyurl.com/2kxyc7

  4. #4 Sili
    June 30, 2008

    I take it the newts (or ewts, if you prefer) are an invasive species. Why’ve they’ve been introduced?

    Shibby!

  5. #5 Nomadiq
    June 30, 2008

    There are a few species of Newt that are native to the Western USA. There are many rivers in the San Gabriel Mountains near Los Angeles that are full of one species (name escapes me now). From memory, the “rough skin” newt is native as well.

  6. #6 Shaggy Maniac
    June 30, 2008

    Are these the same newts and snakes that were highlighted in the PBS Evolution series? IIRC, they showed performance tests of snakes that had either ingested a newt or had been injected with the TTX. Cool stuff.

  7. #7 Draconiz
    June 30, 2008

    Doesn’t matter, they are still snakes!! If the snakes in the garden can talk and this one can’t it only shows that beneficial mutation never happens! never!!!!

    (Screaming into the sunset)

  8. #8 Steve F
    June 30, 2008

    “But it is only micro-evolution”, LOL. Very enlightening article. Being from Idaho, it must be the conservatives that are keeping our Newt’s MMU’s down.

  9. #9 amphiox
    June 30, 2008

    Is it a single aromatic amino acid substitution that the newts use to resist their own toxin? If so it actually surprises me a little that no garter snake population has stumbled onto that particular mutation (also, if an intelligent designer were making garter snakes with resistance to TTX, I’d imagine that this is what he’d do, not any of those others).

    Are there any known associated costs with the newt’s mutation? Could that be why no snake populations are using it (that we know of yet)?

  10. #10 Lord Zero
    June 30, 2008

    Great ^^, i feel sorry for the poor newts, but
    this its nature, this its evolution.
    Its something really great to watch in action,
    more when we can attack this phenomena from
    different views.
    Doing some in field analisis of their behaviour
    would be great too, im sure this resistance would
    trigger a switch on the natural behaviour of both
    the snakes and the newts.
    Anyway, thats more my field of interest anyway. ^^

    I try to check the original paper later.

  11. #11 AdamK
    June 30, 2008

    Ewts? Efts!

  12. #12 raven
    June 30, 2008

    There is a case of a college student in Oregon eating a rough skinned newt once. He only ate one because it promptly killed him.

    Not sure of the motivation but it was probably just some young people fooling around.

  13. #13 jj
    June 30, 2008

    WITCH! She turned me into a newt! I got better..

    Nice post, very interesting indeed!

  14. #14 Rey Fox
    June 30, 2008

    “MAMUs, or mass-adjusted mouse units”

    Does that name have to do with lab mice? And how much TTX it takes to kill one?

    Makes me wonder if there are other populations of newts & garter snakes on my side of Idaho. Bear Lake is way in the southeast corner of the state, so it makes sense to me that there would be less resistance to TTX there because it’s the furthest east of the study sites.

  15. #15 raven
    June 30, 2008

    Neuroscience for kids newsletter:

    With a little library detective work, I discovered descriptions of three people who ate toxic newts. In two cases, men swallowed Oregon rough-skinned newts on dares. Soon after eating the newts, these men became weak, vomited and felt tingling in their lips or hands. One man died and the other recovered 24 hours later. The third case involved a two-year-old girl who bit off the tail of the family pet: an Oregon rough-skinned newt! The girl started to cry immediately after biting the newt’s tail and the girl’s mother was able to brush the tail out of the girl’s mouth. Both the girl and the newt survived.

  16. #16 Lord Zero
    June 30, 2008

    My country its blessed without any (Almost)poisonous
    animals nor plants. Just a tiny spider easily
    identifiable [Loxosceles laeta] and wandering
    jellyfish like most country with marine coast, but
    they are extremately rare cases anyway.

  17. #17 Morgan
    June 30, 2008

    TTX resistance is measured in MAMUs, or mass-adjusted mouse units…

    …is this for the reason I suspect?

  18. #18 mattmc
    June 30, 2008

    Nice article PZ,

    I actually did some research on this topic while in college a few years back. My vert. bio professor worked with the Brodies on some of the earlier research with T. sirtalis and Taricha sp.. I may have even caught some of the specimens from the non-resistant control group. Neat. I have always found these types of “arms races” to be among the most fascinating evolutionary phenomena there are.

  19. #19 Mark (Monty) Montague
    June 30, 2008

    You blew it, PZ, you missed a perfect chance for a cephalopod tie-in: the blue ringed octopuses (Hapalochlaena) also use TTX in their venom, and unlike wussy animals like puffers and newts, they actively inject it for hunting! Also, all of the animals that use TTX have developed ways to cultivate symbiotic bacteria to make the TTX for them, rather than producing it directly (in octos it’s vibrio, and I think also in the puffers and newts… interestingly, a different vibrio species is cultured to glow in the light organs of bobtailed squids.

    Blue rings, like the puffers and newts, have modified sodium channels that resist TTX blocking as well. Since this is clearly convergent evolution for symbiosis with TTX-producing bacteria, it would be very interesting to find out how the TTX-resistant sodium channel conformations and the genes that encode them are different in the octopuses as in the snakes and puffers, since octos are the only non-vertebrate in the story, yet Hodgkin and Huxley demonstrated that voltage-gated channels in axons pre-date the cephalopod/vertebrate split.

  20. #20 Le
    June 30, 2008

    Wow that’s really cool, I took an elective cellular neurobiology course that went in-depth with all sorts of neurotoxins like TTX, alpha-bungarotoxin, curare, etc; who would have thought garner snakes would develop (or I should say EVOLVE) a slightly-structurally different Na channel? Could chaperone-mediated protein folding be involved in these different structures as well?…

  21. #21 Anon
    June 30, 2008

    I know this isn’t really contributing anything, so I shouldn’t really post it (but then again, plenty do also): but I really did love reading this (And the comment about the octopus).

    Maybe I’ll go pick up biology as my third study, I always did want to study it as primary, but things just never got around to do it.

  22. #22 Torbjörn Larsson, OM
    June 30, 2008

    There is a case of a college student in Oregon eating a rough skinned newt once.

    The Arizona Poison and Drug Information Center agrees, and claims a post-mortem examination.

    On July 9. 1979 a 29 year-old male college student Oregon suddenly collapsed and died at a party. Only alcohol was consumed and on post-mortem toxicology the blood alcohol level was < 30mg% (.03); stomach contents recovered did yield undigested remnants of Taricha granulosa. What is the cause of death?

    The victim on a “dare” had swollowed a rough-skinned newt (salamander) just prior to his collapse. Certain species of newts native to the Oregon and California coasts secrete tetrodotoxin, a potent neurotoxin, that causes muscle weakening and respiratory collapse rapidly after ingestion.

    Well, if it isn’t too much to “swollow”…

    @ Lord Zero:

    Here too, the poisonous animals are mostly dangerous for small children or allergics. The one venomous snake is IIRC primarily using it for defense, so it’s not more bothering than a few wasp stings. One rare large and poisonous spider in swamps is arguably dangerous, but there isn’t any modern cases I know of.

    It’s the plants and mushrooms that will kill you. And we do like mushrooms…

  23. #23 Torbjörn Larsson, OM
    June 30, 2008

    Aargh! The mindless parser resubstituted the & lt; sign explicitly:

    There is a case of a college student in Oregon eating a rough skinned newt once.

    The Arizona Poison and Drug Information Center agrees, so it must be true then. ;-)

    On July 9. 1979 a 29 year-old male college student Oregon suddenly collapsed and died at a party. Only alcohol was consumed and on post-mortem toxicology the blood alcohol level was < 30mg% (.03); stomach contents recovered did yield undigested remnants of Taricha granulosa. What is the cause of death?

    The victim on a “dare” had swollowed a rough-skinned newt (salamander) just prior to his collapse. Certain species of newts native to the Oregon and California coasts secrete tetrodotoxin, a potent neurotoxin, that causes muscle weakening and respiratory collapse rapidly after ingestion.

    Well, if it isn’t too much to “swollow”…

    @ Lord Zero:

    Here too, the poisonous animals are mostly dangerous for small children or allergics. The one venomous snake is IIRC primarily using it for defense, so it’s not more bothering than a few wasp stings. One rare large and poisonous spider in swamps is arguably dangerous, but there isn’t any modern cases I know of.

    It’s the plants and mushrooms that will kill you. And we do like mushrooms…

  24. #24 Mrs Tilton
    June 30, 2008

    Raven @15,

    Both the girl and the newt survived

    And so here we have a rare example of two interacting species learning evolutionarily valuable lessons without either paying the standard fee demanded by natural selection. Proof, were more proof needed, that evolution is guided by a just and beneficent deity! (As for all those other instances where one or the other animal has to die horribly, that’s, emm, different. Somehow.)

    Your Lordship @16,

    goodness, where are you from? At “lack of poisonous things” I immediately thought NZ, but then NZ does have Latrodectus if nothing else. But Loxosceles laeta a “tiny” spider? Like all spiders, even the largest mygalomorphs, it’s not big. But it’s hardly tiny. (I’ve collected its cousin L. rufescens, which is a good bit smaller but still not tiny; “tiny” I’d reserve for Oonops, the Erigonine Linyphiidae etc.)

  25. #25 Mrs Tilton
    June 30, 2008

    Torbjörn @22-23,

    One rare large and poisonous spider in swamps is arguably dangerous

    You have me all excited now. Is it Argyroneta aquatica? Do you really have them up your way? (For the rest of you, this is the water spider, the one you’ve all seen television carrying its air-bubble on its abdomen.) They can administer a very painful and somewhat toxic but not life-threatening bite, but the circumstances under which they might do so are extremely rare (in part, sadly, because this magnificent animal is itself becoming rare). The only other even arguably (and then only mildly) dangerous spiders I know of in northern European climes are the larger Cheiracanthium spp., and I think of them more as denizens of the meadow than of the wetlands.

  26. #26 windy
    June 30, 2008

    Here too, the poisonous animals are mostly dangerous for small children or allergics. The one venomous snake is IIRC primarily using it for defense, so it’s not more bothering than a few wasp stings. One rare large and poisonous spider in swamps is arguably dangerous, but there isn’t any modern cases I know of.

    If you are talking about the “kärrspindel” or raft spider (Dolomedes fimbriatus), they aren’t rare or particularly poisonous. They’re one of the few spiders up north with a bite that can penetrate human skin, but adder bites are definitely more dangerous.

  27. #27 Cuttlefish, OM
    June 30, 2008

    Mercy me! For goodness’ sakes!
    Evolving proteins in some snakes
    Are letting them make meals of newts
    (No, not the kind in business suits,
    But Gingrich is a special case,
    And this is not the time nor place)
    Without the nasty tummy-ache
    That signals curtains for the snake–
    The newts, you see, have TTX
    (Tetrodotoxin) which effects
    The channeling of sodium
    Through nervous membranes, which for some
    Makes Fugu into “Tasty Fish”
    But would not be a snake’s first wish;
    There are three groups of which we speak,
    From Warrenton, and Willow Creek,
    And Benton. Populations vary
    In mutations that they carry,
    Also in resistance found,
    Compared to other snakes around.
    Mutations in the protein chains
    Have been confirmed, and this explains
    The difference in immunity–
    It’s quite what you’d expect to see
    If such things worked by miss and hit
    And not by some Creation shit.

  28. #28 Lord Zero
    June 30, 2008

    Im from Chile in the farend of south america,
    this country its very secluded biologicaly,
    since we have in the north the driest desert in
    the world [Atacama Desert], so not even spores
    reach us, and in the east there is the Andes
    mountains, no animals can cross them in most of
    the extension of it.
    Im quite lucky of being a biologist there,
    since we have a fair share of endemism too.

    Regarding the spider, well, we have many
    Teraphosidae, like my personal favourite,
    the Grammostola rosea, endemic of my country.

    I used to have one as a pet when i was a child.

  29. #29 Tony W
    June 30, 2008

    #6: Yes, these are the same newts and snakes from the PBS series. We show that particular video (The Evolutionary Arms Race) in our Intro Bio class, and the students love it. Now I’m thinking it would be a good opportunity to bring in some primary literature as well, if the papers are at a level the students could grasp.

    A PLoS Biology article earlier this year reported that, in many populations, the snakes are so far “ahead” in the arms race that they’re no longer experiencing significant selection for increased resistance. They didn’t find any corresponding cases where the newts were winning. VERY cool stuff.

  30. #30 Helioprogenus
    June 30, 2008

    In theory then, you can introduce these amino acid substitutions in altered mice and observe the reduced efficacy of the TTX Neurotoxin? These mutational changes within the various domains (whether I, IV, or for that matter others as well) should be present in various other creatures resistant to neurotoxins that bind to the sodium channel. There must be predators of puffer fish, snakes (such as mongoose, badgers, birds of prey?), as well as newts (besides garter snakes) that must develop genomic changes which can be accounted for in a similar manner. Quite the interesting field of research.

  31. #31 windy
    June 30, 2008

    Cuttlefish:

    It’s quite what you’d expect to see
    If such things worked by miss and hit
    And not by some Creation shit.

    Tee hee! Are you back from your European tour already, Cuttlefish?

    Mrs Tilton:

    You have me all excited now. Is it Argyroneta aquatica? Do you really have them up your way?

    We have lots of them so I assume that the Swedes have some too… here are some nice pics from a Finnish guy and a youtube video (scroll down for link). I had no idea they were endangered in some parts. Do you know what’s the cause? Destruction of habitat?

  32. #32 Marlowe
    June 30, 2008

    I suppose now that the snakes are immune it is only a matter of time until they start using TTX as well. Where will it end?

  33. #33 Mrs Tilton
    June 30, 2008

    Lord Zero @28,

    Chile? Then L. laeta makes sense. (Still: “tiny”? Maybe next to a theraposid.) I know that S. America has some of the nastier Ctenidae (Phoneutria spp.) as well as some of the stupendously venomous Sicariidae more often found in SW Africa, but I suppose the Andes and Atacama keep you free of them.

    Windy @31,

    at least here in Germany, habitat loss is the major if not sole cause of their rarity. They are redlisted in deepest crimson. I might turn a blind eye at somebody snaffling a specimen from the odd redlisted species, perhaps Atypus (we are supposed to have them in bucketloads here to the east of the city, but I have never seen their pursewebs); but I think I would physically attack somebody to prevent them collecting A. aquatica. Irrational, I know; their vanishing is hardly down to the two or three arachnologists per year that might bother them. It’s just so frustrating and saddening to witness a spectacular adaptation disappear.

  34. #34 Mokele
    June 30, 2008

    There’s an ever cooler part to this that you missed, PZ:

    The snakes gain a benefit from eating poison newts – because it takes so long for them to break down TTX (which is stored in their liver in the interim), they effectively become toxic to their predators.

    Even cooler – the snakes closer to this newt population have brighter red markings those further away, with the most resistant population being the brightest.

    So they’re not just evolving resistance, they’re also harnessing the toxin for their own use and evolving aposematic coloration.

  35. #35 stanley
    June 30, 2008

    “it’s the idea that major transitions in evolution were accomplished more by changes in the timing and pattern of gene expression than by significant changes in the genes themselves”

    So, PZ, how does it feel to shoot ToE in the foot? (How do you explain the emergence of the genetic code without selection sorting through random mutations, which supposedly build selectable bodies??)

    And what is your evidence that the aforementioned genetic expressions happen randomly, for no reason? Do you admit that the environment (internal or external) may cue the organism to re-express itself? Do you deny that the mind/beliefs/emotions can re-express genes in as little as 3 seconds? How do you fit the purposeful re-expression of genes in with a theory that says variation arises randomly?

  36. #36 stan
    June 30, 2008

    PZ: “it’s the idea that major transitions in evolution were accomplished more by changes in the timing and pattern of gene expression than by significant changes in the genes themselves”
    ———–

    uh….that’s not what these guys say:

    http://evolution.berkeley.edu/evosite/evo101/IIIBMechanismsofchange.shtml

    I see no mention of the “timing of gene expression” in there. maybe you can point it out. If not, it’s pretty safe to say that your beliefs are in direct contradiction to what the textbooks are teaching — er, brainwashing — the masses. Why do you think that is?

  37. #37 Kseniya
    June 30, 2008

    Stan,

    How does it feel to be the glean of an oil slick on a road-side puddle?

    Did you even read past the first sentence? I doubt it. You thought you had a “gotcha” moment, and went with it.

    LOL?

    Not all variation is due to random mutation, and the ToE does’t claim otherwise.

    Try again.

  38. #38 windy
    June 30, 2008

    I might turn a blind eye at somebody snaffling a specimen from the odd redlisted species, perhaps Atypus (we are supposed to have them in bucketloads here to the east of the city, but I have never seen their pursewebs); but I think I would physically attack somebody to prevent them collecting A. aquatica.

    Whoops, then you might not want to know what that Finnish page says :P

    But at least these spideys are getting some good PR in the process.

  39. #39 Helioprogenus
    June 30, 2008

    So being such an expert in the field of genetics Stan, tell us what you think leads to the diversity in the species that we see today? You actually believe that some half-rate intelligent created all the creatures in the world with all the observable flaws that we see today? Go shove that holy book of yours up your ass, because you know you have no evidence to support your assertions. You’re an empty bag of shit, and the fact that you keep going is extremely sad. Here’s some free advice, get checked out for schizophrenia. Previously, someone had called you a lamarckian troll, but that’s unfair to Lamarck, as he didn’t have the theory of natural selection and the subsequent century plus to dwell on. You are worse then that, you’re just a fucking liar and absolute lame motherfucker. Perhaps we should label you as a trollerina. Fluttering from thread to thread, attempting to disrupt serious conversation, and ultimately crashing and burning. So, STAN THE TROLLERINA, go flutter about with your delusional idiots.

  40. #40 windy
    June 30, 2008

    Kseniya:

    Did you even read past the first sentence?

    He didn’t even read the first sentence very well, since it started like this:

    We’ve heard the arguments about the relative importance of MUTATIONS in cis regulatory regions vs. coding sequences in evolution before…

    Not all variation is due to random mutation, and the ToE does’t claim otherwise.

    You’re right, but mutations in cis-regulatory regions are still mutations.

  41. #41 Owlmirror
    June 30, 2008

    stan, you fallen-over pigscum loser!

    When are you going to jump in the ocean and sprout gills for us?
    When are you going to walk naked and proud in the Antarctic winter?

    When are you going to stop contradicting yourself?

  42. #42 raven
    June 30, 2008

    Stan is a schizophrenic. Thanks for babbling enough for a diagnosis. Incoherent, delusional thought patterns are the norm.

    The snakes and salamanders were interesting but stan is not.

  43. #43 Ichthyic
    June 30, 2008

    Stan’s yet to be tossed?

    *sigh*

    why does it always have to end up like Kenny?

  44. #44 Wowbagger
    June 30, 2008

    Stan!

    How have you escaped the Evil Evolutionist Conspiracy™ hit squad? Man, that tinfoil hat of yours must be good.

  45. #45 clinteas
    June 30, 2008

    Guys,
    cant we just ignore the lil deranged thread derailer,its really not worth the effort..

    As to thread topic,what amazes me so often in here is that PZ can post some however esoteric research on the most obscure topic,and there will always be a few people in here who have either contributed in one way or another to the original research,or know a heck of a lot more obscure(and I mean that in a good way) details about the whole thing,its truly amazing !
    I dont have enough knowledge to comment on the cis or whatever-the-not-cis-people-call-themselves thing,but this (change in expression and timing rather then in the gene itself,which was there all along)sounds a bit similar to what happened to Lenski’s E Coli populations,right?

  46. #46 Paper Hand
    June 30, 2008

    Question: What has kept these newts restricted to a few locations? With such a powerful defense mechanism, what prevents them from taking over all ponds and lakes with suitable food?

  47. #47 djlactin
    June 30, 2008

    For shame, PZ:

    they’ve instead made other small changes to the protein to reduce binding of TTX. Instead, they’ve tweaked the pore helix and ?-strand from domain IV, which also reduces the eff…

    Is it any wonder that many people misunderstand evolution to be a conscious process?!

  48. #48 Chris G
    June 30, 2008

    using the info you gathered with the snakes. do you think you can come up with a vaccine for TTX?
    *BTW im a noobie to this Site* ^_^
    i always like snakes over newts! oh no i might be the DEVIL AHHAHAHA

  49. #49 Ichthyic
    June 30, 2008

    Question: What has kept these newts restricted to a few locations? With such a powerful defense mechanism, what prevents them from taking over all ponds and lakes with suitable food?

    Isn’t that one of the reasons proposed for the rise of the Cane Toad in OZ?

    as far as the newts are concerned, I’d be thinking issues of mobility.

    newts don’t move very fast typically. Might be too far between breeding ponds for them to “leapfrog” (pardon the pun) like the toads do.

  50. #50 Ichthyic
    June 30, 2008

    using the info you gathered with the snakes. do you think you can come up with a vaccine for TTX?

    not a vaccine, but an anti-toxin, maybe.

    OTOH, I’ve never heard of an anti-toxin developed for amphibian-based toxins, even though there are certain species that have developed the ability to detoxify even poison dart frogs and eat them.

  51. #51 Meee
    June 30, 2008

    I can trump all of you claiming you have only a few dangerous creatures: I live in the UK. There’s pretty much nothing dangerous here, except dogs owned by other people.
    Once every few years we have an earthquake that knocks a tin off a shelf somewhere, but that’s it.

    But onto the article:

    I agree with djlactin. The wording of the article implies some kind of conscious force in action here. Pretty much everyone here understands it’s just a bit of wordplay, but others might not. Can you imagine finding your own wording working against you if someone used it to defend some strain of ID?

  52. #52 Torbjörn Larsson, OM
    June 30, 2008

    You have me all excited now. Is it Argyroneta aquatica? Do you really have them up your way?

    We still have have Argoryneta as windy suspects, and it is mentioned on Lund University zoo physiological department Q&A page for ‘poison and unpleasant animals’ [swedish], among other spiders.

    It wasn’t the one I was thinking of however, it was Dolomedes plantarius (and its smaller relative Dolomedes fimbriatus) that can be up to 7 cm large over the legs and fit in your hand. It can float on water and fish for insects but also fish fry.

    But the earlier link claims that the risks are folk tales. This surprises me, since I was warned of at an university course in ecology where we covered some wet ground; but I guess I have over time mixed the folk tale with some warning against a painful bite.

    But it’s good to get such mistakes eliminated.

    PS. You can note from the first link, if you can get it through some Babel machine, that we are getting the hobo spider Tegenaria agrestis from the continent as the AGW progresses. I believe UK have the same problem.

    Oh, and your Cheiracanthium, Cheiracanthium punctorium, has been spotted on Öland. Dunno why, because it is a (bridged) island albeit with meadows. But they have many tourists which might explain why.

    No reported bites so far, though.

  53. #53 Paper Hand
    June 30, 2008

    Ichthyic @ #49:
    Thank you. I should’ve thought of that myself. :-)

  54. #54 Kelly O'Quin
    June 30, 2008

    What about trans acting elements, PZ? I think the fewer examples of this relative to cis acting factors is probably due to acertainment bias–cis elements are a little easier to identify.
    Also, I’m not sure how tran-sy sounds. Cis-y, Trans-y. I don’t know.

  55. #55 Ichthyic
    June 30, 2008

    it is mentioned on Lund University zoo physiological department Q&A page

    I’m curious why that species of parasitic mite is mentioned in the first picture on that page?

  56. #56 Ichthyic
    June 30, 2008

    I’m curious why that species of parasitic mite is mentioned in the first picture on that page?

    ah, nevermind, figured it out.

  57. #57 Rick T
    July 1, 2008

    This has been reported on Oregon Field Guide (if I remember correctly). The garter snake has not yet developed full immunity because after eating the salamander it goes into a lethargic state and is quite vulnerable for a time while it processes the toxin. Maybe this would explain the brighter, bolder red markings. They would be a warning sign for those who would consider taking advantage of an easy meal.
    Just a thought.
    I wonder if this was the species of salamander that I used to collect and play around with as a child. Good thing I didn’t forget to wash my hands before eating after handling them.

  58. #58 Kseniya
    July 1, 2008

    The Sodium Channel – is that part of the basic cable package?

    Ah, the Cane Toad. It is an introduced species… few natural enemies other than the 4×4. It seems the garter snakes in California are evolving right along with the newts – a chemical arms race – and may have been doing so for quite some time. (No?) Perhaps those snakes are keeping the newts confined (to a degree) in their local ponds. However, it may be a while before anything in Oz catches up with the Cane Toad. Of course, Ichthyic’s idea makes a lot of sense, too – those toads are a lot more mobile and robust than any newt.

    While we’re on the subject, I must recommend the film Cane Toads: An Unnatural History. It is informative, and rather droll.

  59. #59 Ichthyic
    July 1, 2008

    Ichthyic’s idea makes a lot of sense, too – those toads are a lot more mobile and robust than any newt.

    interestingly, they appear to be evolving to be even MORE mobile:

    http://news.nationalgeographic.com/news/2006/02/0215_060215_cane_toads.html

    IIRC, there was discussion about this paper either here or on the Thumb when the paper came out.

    50 Ways to kill a cane toad

    The problem is all inside your head
    She said to me
    The answer is easy if you
    Take it logically
    I’d like to help you in your struggle
    To be free
    There must be fifty ways
    To kill a cane toad

    She said it’s really not my habit
    To intrude
    Furthermore, I hope my meaning
    Won’t be lost or misconstrued
    But I’ll repeat myself
    At the risk of being crude
    There must be fifty ways
    To kill a cane toad
    Fifty ways to kill a cane toad

    CHORUS:
    Just jump on its back, Jack
    Fry it in the pan, Stan
    You don’t need to be coy, Roy
    Just get yourself free
    Run over it with a bus, Gus
    You don’t need to discuss much
    Just put it in the fridge, Midge
    And get yourself free

    Club this frog to death, Jeff,
    impale it on a spike, Mike
    shoot it in the head, Fred,
    stuff it with a firecracker
    And blow it to smithereens

    She said it grieves me so
    To see you in such pain
    I wish there was something I could do
    To make this frog smile again
    I said I appreciate that
    And would you please explain
    About the fifty ways
    She said why don’t we both
    Just sleep on it tonight
    And I believe in the morning
    You’ll begin to see the light
    And then she kissed me
    And I realized she probably was right
    There must be fifty ways
    To kill a cane toad
    Fifty ways to kill a cane toad

  60. #60 chris G
    July 1, 2008

    UK has many dangerous things:
    their uglywomen!
    bad teeth!
    Pop Music!
    beer!
    Gas Prices!
    little cars!(which now adays might be a good thing)
    (too tired to finish joke add more to the list)

  61. #61 chris G
    July 1, 2008

    JK Lol ^_^

  62. #62 Mrs Tilton
    July 1, 2008

    Torbjörn @52,

    the funny thing is, SFAIK there have been no reports of medically significant T. agrestis bites in Europe. The present-day, online-only version of the key I use merely mentions the reported bites in America as an aside; the previous dead-tree versions didn’t mention bites at all. Maybe bites are a problem in America because the spiders have become synanthropes there (on their home turf one finds them, as the name implies, out in fields). Or maybe the ones imported into the American NW are homesick and it’s making them irritable.

    As for why C. punctorium is now found up your way: I’m sure climate change has nothing to do with it!

  63. #63 DLC
    July 1, 2008

    UR AL WRONG!! !111! iT’S OBBVIOS That teh snakes r DESIGNED!!!11 TO include this!

    On a more serious note, I wonder how many generations it’s taken the garter snakes to develop this level of protection from the TTX poison ? By extension, how many generations of snakes to go before the immunity is complete ? And what if the species of newt should happen to die off ? will the immunity continue to be passed down as a vestigial ability?
    ::shrug:: blame me for staying awake through physics and sleeping through biology.

  64. #64 Peter Ashby
    July 1, 2008

    With Cane toads (Bufo marinus if memory serves) the toxin is ouabain which blocks the Na/K co-transporter protein which shuttles sodium out and potassium into cells. The physiology dept where I did my degrees used them extensively for teaching (skin: osmosis; nerves: nerve transduction; nerve&muscle: neuromuscular physiol; heart: cardiac physiol) but also research patch clamping the urinary bladder as a model system for the distal convoluted tubule (we used bladders in 3rd year labs too).

    I have also used TTX to paralyse developing mouse embryos in utero using slow release glass capsules. I can tell you that TTX crosses the placenta, one capsule in one embryo was ok, two led to maternal death. So no eating Fugu if you are pregnant…

  65. #65 Iain Walker
    July 1, 2008

    stanley (Comment #35):

    And what is your evidence that the aforementioned genetic expressions happen randomly, for no reason?

    Firstly, the changes giving rise to TTX resistance are not changes in expression, as PZ makes clear, but substitution mutations in the relevant genes.

    Secondly, “random” in this context does not mean “for no reason”. There is a reason for mutations – i.e., the fact that genetic copying mechanisms are error-prone. Mutations are random in the sense that they tend to be independent of the organism’s needs vis a vis their environment.

    Do you admit that the environment (internal or external) may cue the organism to re-express itself?

    Nobody denies that changes in the way an organism interacts with its environment can give rise to changes in gene expression. However, such changes are rarely inheritable, and to the extent that they are, there is little evidence that this plays anything more than a minor role in evolution.

    Do you deny that the mind/beliefs/emotions can re-express genes in as little as 3 seconds?

    It’s entirely believable that someone might misunderstand epigenetic inheritance as somehow vindicating Lamarckism, but now we’re into the realms of the wackiest of woo.

    How do you fit the purposeful re-expression of genes in with a theory that says variation arises randomly?

    Nothing purposeful about phenotypic plasticity and epigenetic inheritance, Stanley, as I pointed out to you in the other thread. Not unless you want to ascribe intentions and purpose to plants.

  66. #66 caynazzo
    July 1, 2008

    This reminds me of a recent talk as part of seminar on medicine and evolution at the NIH I attended by Mohamed Noor at Duke. It was titled, “Evolution and the concept of species.

    Some of the points I jotted down:

    1. All biodiversity depends on the process of speciation: truism

    2. Concept of species grows fuzzy as we learn the genetics of speciation.

    3. Evolution: change through time, specifically heritable change through time.

    4. Multiple traits help maintain the distinction of species.

    4. “Kirk Cameron is an idiot.” Direct quote.

    5. Cladogenesis has to be made permanent in some way. Darwin did not rigorously address this–considered species and genera to be extensions of varieties.

    Then he went on to describe his research with wild populations of drosophila pseudoobscura and d. persimilis as a way to investigate how natural selection can favor and strengthen the evolution of mate discrimination; hence, natural selection plays a direct role in cladogenesis.

  67. #67 David vun Kannon, FCD
    July 1, 2008

    Great article. It makes me wonder if growing resistance to TTX in snakes is triggering higher levels of TTX in newts, and how recently these newts acquired the TTX defense. If it really is an arms race, I would expect populations of newts that are close to resistant snakes would be more toxic than populations further away. Also, if the newts have wiped out their predator species and we are seeing snakes only beginning to react, I would expect this to be a relatively recent change.

    Is it confimed that these newts harbor a TTX producing bacterium?

  68. #68 Longtime Lurker
    July 1, 2008

    “they’ll be able to feast on squishy purplish-brown and orange tubes of meat”

    Am I the only one seething with jealousy at this point?

    And here’s Stein again, preaching his Lordly Lysenkoism:

    “Do you deny that the mind/beliefs/emotions can re-express genes in as little as 3 seconds? ”

    Yeah, and the average man has a fifteen inch dong!

    Sorry to feed the troll, although I think I’d love to feed him a newt newton. Remember in a previous thread when Stein wrote:

    “For example, snakes can alter the size of their jaw in response to eating bigger prey”

    Dumbest troll EVER!

  69. #69 NP
    July 1, 2008

    Interesting study…something else that has me wondering is the fact that TTX is present in several different organisms from various lineages.

    At first, my guess was that this might be an interesting case of convergent evolution. So I did a bit of reading on it, and the evidence seems to indicate that the pufferfish itself does not have the genes for proteins involving in TTX synthesis. It seems that is instead a fascinating case of symbiosis, where the TTX is synthesized by tetrodotoxin-producing bacteria!

  70. #70 NP
    July 1, 2008

    Interesting study…something else that has me wondering is the fact that TTX is present in several different organisms from various lineages.

    At first, my guess was that this might be an interesting case of convergent evolution. So I did a bit of reading on it, and the evidence seems to indicate that the pufferfish itself does not have the genes for proteins involving in TTX synthesis. It seems that is instead a fascinating case of symbiosis, where the TTX is synthesized by tetrodotoxin-producing bacteria!

  71. #71 NP
    July 1, 2008

    Interesting study…something else that has me wondering is the fact that TTX is present in several different organisms from various lineages.

    At first, my guess was that this might be an interesting case of convergent evolution. So I did a bit of reading on it, and the evidence seems to indicate that the pufferfish itself does not have the genes for proteins involving in TTX synthesis. It seems that is instead a fascinating case of symbiosis, where the TTX is synthesized by tetrodotoxin-producing bacteria!

  72. #72 Alethea
    July 1, 2008

    This is a little off topic, although related to snakes. I am sure that you will enjoy this paper if you haven’t read it already. I am looking forward to your clear explanation of the clock and wavefront model for somite generation – it’s just plain cool.

  73. #73 Chris G
    July 1, 2008

    “::shrug:: blame me for staying awake through physics and sleeping through biology.”
    DLC how can u SLEEP through Biology? Biology in HS was one of the greatest classes I had! Although I am an artist and not a biology major

    On another note. I believe that the resistance would happen quite quickly maybe 100 or so generation. Of course that was purely a guess! I did read a really cool artical saying that your DNA changes throughout your life time. I ASSume that it works the same way with other animals?

    ::shrug:: sleeping through Math and English was my problem! Thank you,California Public School System!!!!! LOL

  74. #74 karl
    July 1, 2008

    How’s the scenario: 10,000 years from now we’ll have a snake that only eats salamanders. Not only has it evolved the ability to tolerate the toxin but it might well be the snake’s only food source. It’s come to rely on some amino acid in the salamander and the snake no longer produces the amino acid itself.

    And 10,000 years from now a creationist will hold the garter snake up to be evolution’s worst nightmare. Since the garter snake can only eat salamanders and since it had to wait until it could evolve the ability to withstand the toxin, did the garter snake just starve to death waiting until it evolved the ability to eat salamander poison? I mean garter snakes in 12,008 can only eat salamanders. So they must have always only ate salamanders. So what came first? Huh? Is that what PZ Meyers XXIII is telling us? Huh?”

  75. #75 Chris G
    July 2, 2008

    looks at Karl
    thats a small snake ur holding there….. im sorry
    10,000 years from now natual selection will get rid of the ID and any other god loving people

    All Hail Queen queen spider!

  76. #76 Peter Ashby
    July 2, 2008

    Alethea the coolest thing is that the clock and wavefront model for somitogenesis predates things like wholemount in situ hybridisation etc. I have lost track of the number of pre molecular revolution of dev biol models that have bitten the dust. Just in limb development we had the French Flag model, the Polar Coordinate model, and of course the simple diffusible morphogen model. They all fitted the observable facts to at least some extent, and all have fallen to the complexity of molecular genetic reality.

    Clock and wavefront stands alone as the one based entirely on fiddling with tissues that reflected the underlying molecular reality, with added Notch of course. Cycling RNAs, that first paper from Olivier was seriously cool stuff.

  77. #77 Torbjörn Larsson, OM
    July 2, 2008

    As for why C. punctorium is now found up your way: I’m sure climate change has nothing to do with it!

    Yes, that is another claim I can’t back up now. Must have heard it on the telly. Pity too, since the climate has been mentioned as a factor behind the relatively few pests.

    Considering how the other species migrates, it’s more reasonable they have hitchhiked.

  78. #78 web design
    July 9, 2008

    Oh rly. How interesting; what was your name again?

  79. #79 Dennis
    July 25, 2008

    I have long been fascinated with garter snakes (Thamnophis) using bufotoxins as a weapon by incorporating the toxins into their Duvernoy’s glands. More and more people are beginning to believe Thamnophis should be regarded as a venomous species. Wandering garters (T. terrestris) are able to subdue mice with their bite and produce a reaction in humans during a feeding response.

    Heterdon (hognose snakes) also seems to be able to employ bufo secretions in their Duvernoy’s against other amphibians.

    I used to phtograph Taricha in Oregon while going to school and used to love watching their mating rituals in Crater lake.

    Thanks for the interesting post!

    DD