Venomous Fables and Phenotypic Variations at the Molecular Level

Remembered for both his lucid writing ability and his tedious nature, the Greek historian Herodotus has often been criticized for the habit of adding unnecessary embellishment to his otherwise candid historical accounts. Focused primarily on the Greco-Persian Wars and personal travels around the Mediterranean, Herodotus’ works also included – on occasion – particulars that many of his 5th Century B.C. contemporaries considered questionable.

One such questionable account from Herodotus centered on the life of a certain Phrygian slave with a knack for composing short prose. Not quite Shakespearian in character, the prose rendered by this slave usually involved references to anthropomorphized wildlife and included a take-home moral message. Now typically, writing prose or verse is a rather benign enterprise, particularly when writing stories about personified animals. Moralizing on the other hand… Moralizing can sometimes get you in trouble, and regrettably for the Phrygian slave, trouble was precisely the result of his high-minded allegories - he was reportedly thrown from a precipice in Delphi for being ugly and “offensive.”

Modern historians raise doubt as to the veracity of Herodotus’ accounts of the Phrygian slave. In fact, many current scholars suspect that the slave never really existed, and further, that the voluminous writings credited to the fictional Phrygian are actually plagiarized collections of Indian folklore. Despite the questionable origins of the parables, the Phrygian slave’s name remains nearly synonymous with “allegory” to this day, and as far as I’m concerned some lessons can still be gleaned from Aesop’s Fables.

One fable in particular came to mind last Wednesday as I was traversing an ecotone between a cypress swamp and a small area of pine flatwoods near Goethe State Forest in central Florida. My eyes being drawn to the rank-and-file procession of hydrophytic plants marching from the wetlands, my ears neglected to notice the slight hum of a rattling creature underfoot. Well, the creature wasn’t quite underfoot; it was in reality about a foot’s distance from being underfoot, but none-the-less the range was sufficiently narrow to take me by surprise. After a couple of second’s pause to regain my bearings, I realized that the insect-like hum that I had heard was in actuality the warning emitted from the shaking tail of the beast – a pygmy rattlesnake!

Pygmy rattlesnakes (Sistrurus miliarius) are members of the Subfamily Crotalinae - the pitviper group - and like their larger Crotalus cousins (true rattlesnakes) the venom of the pygmy contains a toxic cocktail of tissue degrading molecules. Not exactly the kind of critter you want to accidently step on. The potency of the pygmy’s venom is uncontested and is comparable to that produced by other pit-vipers; however the quantity produced by S. miliarius is unlikely to cause death in a human – at least not the death of an adult human. As opposed to human prey, snakes belonging to the Genus Sistrurus have undergone adaptation to capture lizards, small mammals, insects and other snakes as foodstuffs, therefore striking a heavy-footed ecologist would be biting-off more than the snake could chew.

Don’t be misled however, even though the venom of the pygmy is unlikely to cause death, it would certainly pack enough punch to ruin your day; proteins “designed” to enzymaticaly induce hemorrhaging couldn’t be a good thing to have pulsing through your veins… I put the word “designed” in quotes in the previous sentence to emphasize that the protein concoction injected by Sistrurus is very much a product of adaptation - it’s a functional trait shaped by the process of natural selection. But before getting into that story, which will be forthcoming, let me first show you a snapshot of the snake encountered last week and share the Aesop fable that was alluded to above.

The Crow and the Snake
A hungry Crow spied a Snake lying asleep in a sunny spot, and, picking it up in his claws, he was carrying it off to a place where he could make a meal of it without being disturbed, when the Snake reared its head and bit him. It was a poisonous Snake, and the bite was fatal, and the dying Crow said, "What a cruel fate is mine! I thought I had made a lucky find, and it has cost me my life!" (Aesop’s Fables A New Translation by V. S. Vernon Jones, 1912 edition)


The pygmy is still considered a lucky find, though it would have been nice if the picture would have turned out a little better. I could have gotten a bit closer, but ‘as the crow teaches us’ using caution is important and un-scrupulous actions can turn a good scenario into a bad one very quickly… OK, enough with the corny fable, on with the science - before readers encouraged me to follow Aesop over the precipice!

The “designed” venom of Sistrurus… As stated above, the word “designed” refers to a natural process in which variations in phenotype have contributed to differential reproductive success between the individual organisms exhibiting the traits. Specific to this case, the proteins that make-up the hemorrhagic venom are coded for by genes contained within the snake’s genome. Variations in the venom’s genotype from individual to individual cause the overall “potency” of venom to also vary from individual to individual. So, reductively stated, variations in genes coding for venom lead to variations in the “strength” of that venom. The strength of the venom in turn affects the number and quality of prey killed by the snake.

Risking redundancy and stated a third time slightly differently, molecular alterations within the modified saliva of a snake change how those molecules fold and biosynthesize to form the constituent proteins of venom. These phenotypic variations at the molecular level translate to a modified functional trait in the snake’s predator-prey dynamic. Better venom chemistry equals more food, increased survivability and increased fecundity for the snake. Extending the gene’s reach even further, it is conceivable that the molecularly induced change in such a functional trait could even allow the snake to specialize on a certain type of prey, thereby changing its ecology all together.

Interestingly enough, earlier this year H. Lisle Gibbs of Ohio State University, and Stephen P. Mackessy from University of Northern Colorado published work in the journal Toxicon discussing the venom of several Sistrurus species. Their work centered on prey specific effects, and they hypothesized that a “high level of variation in venom at the inter- or intraspecific level allows snakes to specialize on different prey.” They tested the effects of venom on mice, lizards and frogs (typical prey items for Sistrurus) and determined that “toxicity to mammals [was] a major axis along which venom evolution has occurred among Sistrurus rattlesnakes, with little evidence for evolutionary changes in toxicity towards the other prey tested.”

So, the research published in Toxicon demonstrated that not only is the phenotypic functionality of Sistrurus’ venom significant, but also that the response to that venom by prey species may open the door to an evolutionary arms race between predator and prey - an epic battle between toxicity and immunity. Changes in venom chemistry could allow new prey items to be added to the snake’s menu, or conversely, the changes could, in time, ultimately remove current prey species from the carte du jour. Such shifts in dietary preference could easily serve as focal points for selective pressures.

I don’t know if the epic battle between snake venom and prey immunity would stir Herodotus’ interest in war writings, but the story behind the evolutionary dynamic is adequately fascinating to not require very much embellishment. As for me, I’ll take Aesop’s lesson about haste to heart and give greater attention to what’s underfoot.


Gibbs, H., & Mackessy, S. (2009). Functional basis of a molecular adaptation: Prey-specific toxic effects of venom from Sistrurus rattlesnakes Toxicon, 53 (6), 672-679 DOI: 10.1016/j.toxicon.2009.01.034