Venomous cobras may not seem like snakes we should get up close and personal with, but an ancient Homininae ancestor of chimps, gorillas and humans evolved strong resistance to neurotoxins in snake venom – and passed it on to us.
But grandad Hominine (not to be confused with their hominin descendants, which excludes gorillas) didn’t end up with resistance due to happenstance – it was part of an ongoing evolutionary arms race between African apes and deadly venomous snakes.
Over 10 million years ago – well before chimps and gorillas diverged but after orangutans did – grandad Hominine and friends were learning the lay of the land after coming down from the trees. He was picking up rocks, wandering around in shrubs and waggling sticks. The problem was, these were also places frequented by venomous snakes, which could easily lead to a toxic bite or two.
And these neurotoxins are nasty.
“You can think particular type of neurotoxin sort of like a heroin overdose,” says study author Professor Bryan Fry of the University of Queensland, AKA Venom Doc.
“You die of flaccid paralysis, because the diaphragm, the muscle that moves your lungs, doesn’t move anymore.
“So, no movement of your lungs, no air. No air, no oxygen. No oxygen, no life.”
According to the study, published in BMC Biology, the threat of venomous snakes appeared to be a driving force towards developing resistance to neurotoxins – after all, a hominine that’s alive after a snake bite is far more likely to pass on their genes than one who’s dead.
“Our movement down from the trees [to walk] more commonly on land meant more interactions with venomous snakes, thus driving the evolutionary selection of this increased resistance,” says Fry.
“It is important to note that this resistance is not absolute – we are not immune to cobra venom, just much less likely to die than other primates.”
Interestingly, this resistance was still passed down to us today, meaning that we have proportionately 80% resistance – that’s around five times more resistance than lots of other primates who didn’t benefit from grandad Hominine’s good genes.
Thanks grandad.
Venomous snakes and primates in other places
The evolutionary war between animals and venomous snakes has many chapters. Three different types of spitting cobras evolved to shoot super-painful projectile venom from their fangs to deter predators, blue-tongue lizards got involved by evolving resistance to red-bellied black snakes, and snakes even bolstered themselves by evolving resistance to their own venom using a weird kind of magnetism.
These evolutionary processes were largely influenced by animals and snakes trying to one-up each other.
But how do we know that this hominine resistance arose specifically to counteract venomous snakes? Because other primates that didn’t have to deal with venomous snakes didn’t evolve the same resistance.
“Madagascan Lemurs and Central and South American monkeys, which live in regions that haven’t been colonised by or come in close contact with neurotoxic venomous snakes, did not evolve this kind of resistance to snake venoms,” says PhD candidate and lead author Richard Harris.
“It’s been long-theorised that snakes have strongly influenced primate evolution, with many examples just like this, but we now have additional biological evidence to support this theory.”
All about balance
Interestingly, some types of venom resistance can actually be bad for primates. This is because neurotoxins target receptors in the brain that are necessary for keeping organs running.
“They do that through a series of very complex interactions involving electrostatic and hydrophobic-hydrophilic interactions,” explains Fry, “It’s an exquisite kind of lock-and-key arrangement.”
Modifications to these receptors can disrupt this enough that the toxin can’t bind, but neither can important molecules like acetylcholine , which is responsible for memory and cellular communication.
“You can only modify these so much before you start having a fitness disadvantage,” says Fry.
So, it is all about striking a balance. Selective pressure (ie, lots of snake bites) drives evolution so animals must compromise the need for resistance with possible detriments to brain function. In fact, some types of African vipers that were once resistant to cobras later lost resistance as they moved into Europe, because they were no longer threatened by their toxic cousins.
“We have shown in other studies that resistance to snake venoms comes with a fitness disadvantage whereby the receptors don’t do their normal function as efficiently, so there is a fine balance to be struck where the gain has to outweigh the loss,” says Fry.
“In this (hominine’s) case, partial resistance was enough to gain the evolutionary advantage, without the fitness disadvantage being too taxing.
“We are increasingly recognising the importance snakes have played in the evolution of primates, including the way our brain is structured, aspects of language, and even tool use.
“This work reveals yet another piece in the puzzle of this complex arms race between snakes and primates.”
A tale of toxins – NOT tested on animals
Thanks to modern technology, the receptor-neurotoxin interaction could be tested in the lab – without relying on a 10-million-year-old hominine subject donating a bit of brain tissue.
The researchers built and analysed artificial nerves using a special machine called the Octet HTX, the only machine like it in the southern hemisphere.
These artificial nerves simulated the interactions between neurotoxins and receptors of African and Asian primates compared to American and Madagascan primates, who are extremely sensitive to venom.
“We were able to make any primate neurological receptor that we wanted of this particular receptor, which is the α1 nicotinic acetylcholine receptor,” explains Fry.
“So, we made the version from Gibbons through to mandrills, to chimps, to lemurs to capuchin monkeys, all of their native versions and then even some made hybrid versions.”
By switching and swapping amino acids around in, the researchers were able to test which versions were functionally resistant to toxins, and which ones weren’t.
“And it all it came down to two amino acids. Just those two were responsible for that radical increase in resistance. It shows the exquisite subtlety of this interaction between the toxin and the target.
“It was a lot of fun.”
Better yet, the Octet HTX means that absolutely no animals needed to be involved in the receptor research.
“At the end of the day, our approach was more ethical and allowed us to do things that would just be impossible to do from a technical perspective any other way,” says Fry.
Originally published by Cosmos as Venom showdown: ancient primates vs venomous snakes
Read science facts, not fiction...
There’s never been a more important time to explain the facts, cherish evidence-based knowledge and to showcase the latest scientific, technological and engineering breakthroughs. Cosmos is published by The Royal Institution of Australia, a charity dedicated to connecting people with the world of science. Financial contributions, however big or small, help us provide access to trusted science information at a time when the world needs it most. Please support us by making a donation or purchasing a subscription today.
