Snake venoms are the undisputed masterpieces of evolution

\ Killing colors of neurotoxins, bright tones of hemolytic proteins ... these cocktails have been perfected for many millions of years and have become real works of chemical art that can strike a gape on the spot.

It seems to us who is stronger - the one and the main. Predators hone their reactions, grow sharp teeth, train powerful jaws; herbivores oppose them with a mighty mass and fast legs. But poison is nature's firearm, the "great equalizer." With his appearance, the weak can overcome the strong, the slow will catch up with the fast. It is not without reason that completely different animals, from jellyfish to mammals (for example, some shrews are poisonous), from spiders and insects to, of course, snakes, independently "thought of" the use of toxins.

There are poisonous animals in every class of animals (with the exception of birds), but each of them moved towards this in its own way. Jellyfish have developed specialized stinging cells containing a complex organelle cnidocil with a sharp thorn. In bees and wasps, the accessory glands of the reproductive system are adapted for the production of poison. Snake venom is saliva, a thick aqueous solution containing a complex and deadly mixture of toxic proteins. It is so flawless that it already includes a certain amount of proteolytic enzymes that soften tissues and begin to digest the victim: it will still not go anywhere.

Common Poisonous Ancestor

Before the advent of methods of analysis and comparison of DNA, biologists had to rely on the not very reliable soil of comparative anatomy, embryology and related disciplines. This traditional approach said that the common ancestor of all venomous snakes could have lived about 100 million years ago, when they had long since parted with their scaly lizard cousins. Indeed, venomous lizards are extremely rare, while at least a quarter of snake species have venom. The severe consequences of the bites of many lizards have been associated with bacteria, including numerous pathogens that inhabit their oral cavity.

However, not so long ago, in experiments with cell cultures, it was found that the saliva of many lizards has real toxicity and is able to suppress blood clotting, cause paralysis and other unpleasant effects. Individual protein components of snake venom have been found in 1, 500 species of lizards, including the famous Komodo dragons. Adding to this the data of chemical and DNA analysis, scientists put forward a hypothesis about a much more ancient evolutionary origin of poisons, attributing this significant moment to the common ancestor of snakes, iguanas and some other lizards, which lived about 170 million years ago and made special rearrangements of its genome.

Genes encoding proteins important for the functioning of various cells and tissues were duplicated and began to act in the salivary glands. Such duplications are not uncommon in nature - for example, the short-leggedness of beagles, dachshunds and related dog breeds is the result of a duplication of the gene for the signaling factor FGF4, which is involved in the regulation of limb growth. However, in the "poisonous ancestor", random mutations and selection changed the functions of the original molecule - and the protein, which peacefully served as some kind of regulator of blood clotting, could turn into a lethal toxin causing its uncontrolled coagulation. For example, phospholipase A2, a small and generally harmless enzyme involved in lipid digestion, has turned into a real killer that indiscriminately destroys living cells by dissolving their membranes. And there can be dozens of such killers in snake venom: proteins account for up to 90% of its dry mass and almost 100% of its lethal effects.

Slaughter Recipes

Snake venoms are the most complex of all natural poisons, and comparing them to chemical weapons would be to underestimate their excellence. Chlorine or mustard gas are simple molecules that work roughly and erratically; Cobra or black mamba toxins work with deadly precision and efficiency. Each of them individually - and the general recipe for their mixture - have been honed over millions of years of evolution and attack very specific targets in the victim's body. The key ones are the cells of the blood, nervous and cardiovascular systems.

Dendrotoxin 1, which is part of the venom of mambas, is capable of blocking a large group of voltage-sensitive potassium channels, disrupting the transmission of nerve impulses through neurons. A variety of α-neurotoxins, found in cobras and many other snakes, bind to acetylcholine receptors, completely blocking the work of synapses - primarily those that transmit the command from nerve cells to muscle cells - which results in paralysis and death from asphyxia. Fasciculins in the venom of rattlesnakes deactivate acetylcholinesterase, which removes excess neurotransmitter from the synaptic space - and an excess of it causes uncontrolled spasms and convulsions.

This is just a small fraction of snake venom toxins and their targets: others can cause kidney damage and cardiac muscle paralysis, destruction of the endothelium lining blood vessels and massive tissue necrosis. Vipers and many cobras have turned common blood clotting factors into killers. Of the whole cascade of coordinatedly acting proteins, which triggers the mechanism of thrombus formation in the event of injury, one or the other can “go over to the dark side” and cause general thrombus formation right in the vessels. The sight is terrible: the victim's body is no longer filled with thick blood, almost all of it turns into coagulated clots and watery plasma, which, due to the increase in pressure, makes the body swell like a balloon, and oozes literally from all the holes - including tiny traces left by poisonous teeth.

Delivery vehicles

The venom of the common ancestor of snakes and some lizards, which are sometimes combined into the Toxicofera group, apparently did not differ in such complexity and combined a rather limited number of mutated proteins. He did not have any special devices for the effective injection of toxic saliva into the victim's body. Therefore, different groups of these scaly ones went different ways, developing their own means and delivery mechanisms. By and large, this process encompassed all systems of the snake organism, although its epicenter, of course, fell on the salivary glands, which became real factories for the synthesis of toxins. And on the teeth, which turned into sharp, poison-filled syringes.

It is believed that representatives of the vast and ubiquitous family of vipers can boast of the most advanced poisonous apparatus. Their large venom glands are surrounded by powerful masseter and temporal muscles that can instantly squeeze out venom. Through the channels, it enters the large poisonous teeth, which in many species have become hollow and sharp, like needles. Immersed in a thick mucous base, these teeth automatically "unfold", as soon as the snake opens its mouth wide - and with the effort of the muscles that close it, the poison is squeezed out under the victim's skin.

Some cobras act even more vile - they spit poison at 1–2 m, while aiming in the eyes. But this skill is a rather late acquisition, and ordinary poisonous teeth with new side holes are adapted for spitting. In addition, the poison that got on the cornea is not fatal and only causes severe irritation, allowing the snake to inflict a bite, the ability of which these species have not lost at all. The blinded victim is doomed unless he can counter the poison with some kind of antidote.

Antidote Race

Many snakes have to be very careful not to bite their tail and die from their own venom. In the fights between them, death from poisoning is a common thing, especially if reptiles of different species have entered into conflict. But others have become insensitive to the action of their own toxins - like the Indian cobra, spectacle snake, whose acetylcholine receptors are insensitive to the action of the main component of its poison, α-neurotoxin. Random mutations endowed mongooses with such resistance, as well as hedgehogs, pigs and honey badgers - relatives of martens that hunt poisonous snakes much more actively than the beloved Rikki-Tikki-Tavi.

But the most striking resistance to snake venom is demonstrated by possums, which are almost immune even to the action of botulinum toxin and ricin. Their main secret lies in the amazing molecule LTNF - a protein factor in the blood that neutralizes lethal toxins. Isolated and injected intraperitoneally into mice, it helped them survive in experiments with lethal doses of venoms from all four major families of venomous snakes - and even some other toxins, including scorpion venom. The LTNF factor has been discovered recently, and its mechanism of action is still unclear, but it is being actively studied - after all, theoretically, the blood of possums can provide us with an antidote that is unique in its effectiveness.

In the meantime, the antidote for each case has to be obtained separately, injecting non-lethal doses to animals - usually cows or horses - and extracting ready-made antibodies from their blood as a result of the immune response. With some patience and great courage, such antibodies can be "brought up" in your own body: the legendary explorer, founder of the Miami serpentarium, Bill Haast, injected himself with microdoses of poisons throughout his life. He not only safely survived 172 bites, but also donated a unique blood that saved dozens of lives of people bitten by snakes, for which no antidote is produced.

Dear Displeasure

Toxins are incredibly effective, but not omnipotent. No wonder the overwhelming majority of animals still adhere to other methods of defense and attack, which are not so expensive for the body. Indeed, a study of rattlesnakes before and after taking venom from them showed that the synthesis of proteins necessary to replenish the supply of lethal doses makes the whole body tense and work in an enhanced mode for three days, increasing the metabolic rate by 11%. The same measurements were carried out for viper-like deadly snakes, extremely dangerous inhabitants of Australia: they have to increase their metabolism by almost 70% to recover.

Synthesis of poison is not for weaklings; it requires effort comparable to that of a marathon runner. But an even greater contribution is required by the evolution and growth of complex delivery systems. In fact, this is a separate direction of development, to which poisonous species sacrifice a lot of resources. In a way, it can be called an alternative to a complex and large brain: along with this voracious organ, chemical weapons are one of the most expensive and most effective finds in nature.