Venomous Evolution

Garter snake

A garter snake, which is one of the types used in the study

• Snake venom is mostly made up of many different proteins; some of these proteins are toxins while others are nontoxic proteins with pharmacological properties.

• Toxin proteins are large multi-gene families and arose from genes of proteins that do not code for toxins, followed by evolutionary modification. The evolution of toxin proteins occurs through a process known as gene duplication, where a duplicated gene is free from selection pressure to functionally diverge, creating ‘families’ of structurally related proteins that have slightly different functions.

• Snake venom acts by targeting natural biological processes in their prey, such as neuronal signalling or blood clotting. So it comes as no surprise that we can often use these venom molecules to our advantage in the treatment of diseases. For example, the hypertension drug captopril was developed from a peptide in the venom of a lancehead viper, Bothrops jararaca, which acts by dangerously lowing the blood pressure in its prey. However the chemical structure had to be modified first, and this drug was one of the earliest success stories of structure-based drug design.

• But what if you didn’t have to change the structure of the molecule, to make the drug safe for use while retaining potency? Researchers analyzed gene sequences from the Garter snake and the Burmese python, and then compared these sequences with those from venom glands in a wide variety of other snakes and lizards to construct an ‘evolutionary tree’ to work out how these venom sequences might be related to each other. They found out that the toxins that make snake venom deadly can evolve back into completely harmless molecules, raising the possibility that they could be developed into drugs. What does this mean? These ‘ex-venom’ proteins could be important because they’re made up of bioactive proteins;they already target metabolic processes, which is precisely what drugs need to do. So instead of developing synthetic compounds into drugs, it would be possible to screen these ex-venom proteins against whatever metabolic processes that need to be targeted.

• It is thought that the evolution of venom into ‘ex-venom’ proteins is due to the selective advantage afforded by having a dynamic repertoire of venom molecules. The snake’s prey tend to evolve resistance to venom, so it’s an arms race, with venom having to continually evolve to remain effective at killing prey. Indeed, snake venom toxins are some of the most rapidly-evolving proteins ever identified.

• I found these findings fascinating because it shows how seemingly harmful venom proteins that are literally perfected by millions of years of evolution to kill us can actually be useful in helping treat and cure other diseases. These findings also highlight the dynamic, ‘arms race’ nature of the evolutionary process, which is also beautiful in its own right 🙂

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Reference: Unfortunately this research is not Open Access, but if you do have access to Nature Communications it is well worth a read

Image: Steve Jurvetson

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