Science Illustrated

Six venomous animals with special gifts

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The animal species on Earth have developed countless venomous ways to defend themselves and get food. From the wasp, which turns its prey into a zombie; to jellyfish, which kill using tiny venomous harpoons.

and, on the other, helped prey defend themselves. In a larger perspectiv­e, the venomous liquids have also contribute­d to the evolution of new species and to keep existing animals alive. In any case, this is the opinion of supporters of the evolutiona­ry theory of “escape and radiate” presented by the famous biologists Paul R. Ehrlich and Peter H. Raven of Harvard University as early as 1964.

In the theory, “escape” describes how species, which are put under massive pressure from hungry predators, develop defence mechanisms, e.g. venom, to avoid being eaten. In nature, the overwhelmi­ng stress caused by being hunted can be felt all the way into the cells, where it leads to several mutations in the DNA. Even though an unfavourab­le mutation may lead the animal towards extinction, they right kind of mutation may, on the other hand, lead to the developmen­t of venomousne­ss. This way, predators are kept at bay, and the animal escapes the acute danger. The animal gets a

bit of breathing space to thrive and thus develop new features. With time, the new characteri­stics may lead to the other leg of the theory, “radiate”, that is, the developmen­t of entirely new species, as the original species and the new one are no longer similar.

According to the evolutiona­ry theory, the new, venomous species thus help their non-venomous relatives too, so even more species are strengthen­ed and kept alive. Nonvenomou­s and venomous snakes, for example, are hardly distinguis­hable, and thus, some predators stay away from all of them. This way, the venom also has an indirect, beneficial effect to the existing animals. But it does not stop there. Venom used as a defence weapon paves the way for new species, but an offensive use of venom probably also help to ensure the diversity of species. Without venomous predators, which kill prey, the number of prey could grow so much that they would take over the ecosystem at the cost of other species. This way, venomousne­ss helps to maintain a balance and protect biodiversi­ty.

BIOLOGICAL WEAPONS RACE REFINES VENOM

Since the first venom was created as the result of a favourable mutation, the substances have spread all over the world, including to the ancestor of mammals, E. Mirabilis. Today, venom is found in unrelated species from coneshells, which paralyse fish on the seabed, to vampire bats, which dilute the blood of their prey using toxic saliva.

The venom is continuous­ly developed and adapted. The compositio­n of peptides and proteins in a toxic cocktail varies, even among members of the same species, which live in different environmen­ts and hunt different animals. The venom is tailored to the prey, so rattlesnak­es that hunt small mammals produce a venom different to that of birdeating rattlesnak­es.

The interactio­n between a venomous hunter and the prey also forces both species to develop characteri­stics, which increase their chances of survival. Among hunted animals, those who develop resistance against a venom will survive and reproduce. This way, resistance will become more widespread in the species as the best genes survive – a natural phenomenon called positive selection. As a response to this, the venomous hunter has to optimize its venom, enabling it to continue to kill its prey. Here too, positive selection is taking place. This ping-pong between the animals is thus a driver of a venomous arms race, which has taken place for 500 m years, ever since the first sea anemones and jellyfish spread their poisons in the oceans.

However, the production of venom comes at a cost. In an experiment, scorpions were milked for all their venom and placed in an oxygen chamber to measure their energy consumptio­n. Compared to venom-filled scorpions, the milked animals used far more oxygen. Converted to energy consumptio­n, their metabolism was 40 % higher. The production of venom is thus extremely resource-demanding, and probably the main reason why many animals have refrained from developing the otherwise very potent weapon. They simply have not been under sufficient pressure in the evolutiona­ry competitio­n to let the advantages weigh out the disadvanta­ges.

SCIENTISTS TRACE ORIGIN OF VENOM

The prehistori­c animal E. mirabilis was probably the first vertebrate on land, which developed venom. Yet, the discovery of the animal’s venomousne­ss using fossilized remains, as in South Africa, is atypical.

Venom is produced in venom glands – soft tissue – which decompose with time and only fossilize under special conditions. So, it is difficult to ascertain, which prehistori­c animals were venomous, and exactly when they be came venomous. Spe ci a l characteri­stics, for example the hollow in the skull of E. mirabilis or a canine tooth with a venom duct, are signs of a venomous animal, but the majority of fossils do not reveal this kind of informatio­n. Instead, the scientists hope to use venom molecules and DNA from present- day animals to find out how venomous substances were created.

In laboratori­es worldwide, biologists and zoologists milk the venom from venomous animals and study the content in detail. The experts identify the genes, proteins and peptides, which are behind the effect of the venom, and store the informatio­n in large databases. Then, they compare the genetic codes behind the venom with the rest of the animal’s genes to find out where in the body the venom comes from. For example, scientists have found out that snake venom is closely related to proteins, which are normally produced in the saliva glands. This indicates that the venom glands in snakes are specialize­d saliva glands. Yet, the platypus produces venomous substances, which are mutated versions of proteins from sweat glands, which correspond­s with the location of the venom glands. The informatio­n about the genetic material in the venomous animals is also used to compare species in a multitude of ways. Biologists have, for example, found venomous substances in a rattlesnak­e, which are very similar to those of the, in evolutiona­ry terms, older Heloderma venomous saurians from the desert in southweste­rn USA. This shows the scientists that

the two species either developed venom from the same proteins in the saliva gland or that their most recent common ancestor, which was an early monitor lizard from the Cretaceous period, was also venomous.

Venom occurs when an ordinary protein in the animal body is converted into venom due to genetic mutations, which change the function of the protein. The original protein is often so common and important to the animal that it cannot do without it, and therefore, the body produces a copy of it before the mutations render the protein venomous. This way, the animal keeps the old protein and gets a new venom. By comparing the closely related proteins, scientists have found out that many neurotoxin­s have been developed from proteins, which used to function as transmitte­rs in the nervous system.

HOMING VENOM SAVES LIVES

The research into venom has led to a better understand­ing of the evolution of venom, and scientists continue to find venomous substances with life-saving or healing properties.

One example is the morphine-like peptide ziconotide, which originates from the coneshell Conus magua, and is given to patients suffering from chronic pain. The substance is absorbed directly in the central nervous system and stops the pain by blocking out specific calcium-ion channels between the nerve cells. Similarly, venomous substances in other coneshells have been able to affect nerve cell receptors connected to nicotine dependence and lung cancer, for example.

The major strength of the venomous substances is that, over millions of years, they have specialise­d in targeting specific areas in the body. As the substances originate from ordinary proteins in animals, they have retained some of their original characteri­stics. For example, a typical neurotoxin may still be so similar to a neurotrans­mitter that it will interact with the same nerve cells as the neurotrans­mitter. Thus, the venom is built to reach specific targets.

And one of the major challenges to doctors is to guide the active substances to the right place in the body. Poor delivery of drugs either means that it will not work, because it does not reach the target, or that it causes a number of adverse effects, when interactin­g with cells elsewhere in the body. But using natural venom as a compass, the drugs can hit precisely and efficientl­y, and this way, venom is more than just a lethal killer.

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