The bite of a rattlesnake can, within minutes, cause paralysis and extensive internal bleeding. If untreated it can kill. It might also hold the key to treating high blood pressure, heart diseases and stroke. In 1998 two drugs to prevent heart attacks, derived from rattlesnake and viper venoms, were approved. Since then a number of other venom components have proved effective against some varieties of cancer and brain disorders like Alzheimer’s or Parkinson’s, but gaining regulatory approval has proved tricky. Part of the reason is that it is difficult to tweak toxins such that they preserve their medicinal effects but lose their nefarious ones, like stanching blood flow or numbing the nervous system.
Now, though, Wolfgang Wüster, of Bangor University, in Britain, and his colleagues have stumbled on an evolutionary mechanism that might make such modifications easier in future. Dr Wüster was investigating venomous snakes and lizards to understand what they had in common. They differ in many respects—most venomous lizards, for instance, have fangs in the lower jaw, whereas snakes have them in the upper jaw. But in 2005 Bryan Fry of Sydney University found that snakes and lizards in fact share venom-making genes, suggesting that both share a venomous reptilian ancestor.
Whereas Dr Fry looked only at selected venom-making genes, Dr Wüster had the luxury of complete genetic data for different snake and lizard species. This allowed him to check if venom-spitting reptiles possess other shared genetic traits, too. As he and his team report in Nature Communications, they do.
These include genes to produce enzymes that perform some basic physiological functions. Intriguingly, some of these housekeeping genes were sitting among venom-producing ones. Venom genes are known to have evolved from more innocuous sorts, but it was thought that all the genes in a particular stretch of DNA assumed the venom-producing function. To find some that did not, therefore, posed a quandary. Were the innocuous genes among the insidious ones simply evolutionary relics? Were they evolved versions of the original innocuous genes that, unlike their venom-producing neighbours, remained innocuous? Or did they in fact evolve from venom genes that had lost their venom-producing prowess?
To help decide the matter, Dr Wüster ran a computer model to trace the genes’ evolutionary histories. This revealed that the third scenario was the most likely. Moreover, it seems that certain housekeeping genes turned into venom-producing ones and back again several times in reptiles’ genetic past. This means that the venom-producing genes and the housekeeping variety nested among them are genetically similar. As such, they produce proteins which are themselves alike in many respects, but not necessarily in their ability to do harm.
Practical applications of this knowledge are not an immediate prospect. But by understanding what makes a venom protein venomous researchers may get a better idea of how to remove the unwanted sting. That is one trick drugmakers would love to be able to pull of.
First published on economist.com.
Image credit: The Economist