The venom of spitting cobras evolved to inflict pain | Science

By Mitch LeslieJan. 21, 2021 at 2:00 p.m.

Spitting cobras protect themselves by throwing jets of venom into the eyes of their attackers. A new study suggests that over millions of years, all three groups of spitters independently adapted the chemistry of their toxins in similar ways to cause pain in a potential predator. The work provides a new example of convergent evolution that “deepens our understanding of this unique system” for delivering venom, says Timothy Jackson, an evolutionary toxinologist at the University of Melbourne.

Like other cobras, spitting cobras will bite attackers in self-defense. Spitting is their signature move, however, and snakes are crack shots. They can direct a jet of venom into the face of an attacker from over 2 meters away, aiming at the eyes. The behavior is such a formidable defense that it has evolved independently three times: in Asian cobras, African cobras, and a cousin cobra called the rinkhals (Hemachatus haemachatus) who lives in southern Africa.

Scientists have already discovered that the venom of some other snakes has evolved to better control their prey. By analyzing the venoms of 17 spitting, stingless species – and measuring their effects – venom biologist Nicholas Casewell of the Liverpool School of Tropical Medicine and his colleagues tested whether the composition of spitting cobra venom had also changed over time to become a more effective defense.

The most common compounds in cobra venom are the so-called three-finger toxins – proteins named for their 3D chemical form, not the number of digits you can expect to lose if a snake bites your hand. Three-fingered toxins are also abundant in the venom of spitters and non-spitters, Casewell and colleagues found, making up about 60% of toxic molecules. However, the venom of the spitting species contained higher levels of another group of proteins known as phospholipase A.₂ toxins, which non-spitters produce only in small amounts, or not at all.

To probe the effects of additional phospholipase A₂ proteins, scientists have buffered different combinations of toxins from snakes onto nerves isolated from pain-sensitive mice. The more neurons a toxin stimulates, the more pain will result. The researchers determined that the three-finger toxins caused more pain when combined with phospholipase A₂ toxins that alone. For example, when researchers applied the two types of toxins from rinkhal venom to the nerves of mice, the mixture stimulated about twice as many nerve cells as the three-finger toxins from rinkhals alone, they report today in Science.

The work suggests that natural selection has refined the makeup of snake venom to make it a better defense, Casewell says. That all three groups of spitters independently derived the same solution – increased abundance of phospholipase A₂ toxins – is an example of convergent evolution, in which species that are not closely related but face similar survival challenges acquire similar adaptations. “Evolution can be highly reproducible,” says Casewell.

The study’s evolutionary logic makes sense, says toxinologist Stephen Mackessy of the University of Northern Colorado at Greeley, who was unrelated to the research. Increasing the agony-inducing power of the venom would help snakes keep predators away because “one of the best learning tools is pain production,” he says. But Joe Alcock, an evolutionary medicine researcher at the University of New Mexico, Albuquerque, says it’s possible that damaging an attacker’s eyes was the driving force to evolve a unique chemistry. “If you can blind a predator, it would prevent an independent pain attack,” he says.

Why some cobras have started vaporizing venom rather than just delivering it by bite remains unclear. Some researchers claim that the behavior prevents snakes from being trampled by hoofed mammals. But the side eyes of buffaloes, zebras and other heavy-footed mammals would be difficult to reach with a single jet of venom, notes Casewell. Instead, he and his colleagues postulate that early humans motivated the origin of the sputum behavior. Our ancestors would have been a threat to snakes, and they conveniently had forward looking eyes that would make good targets for a flood of noxious venom.