A new research reveals that humans do have the tool kit to produce venom - in fact, all reptiles and mammals do.
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This collection of flexible genes, particularly associated with the salivary glands in humans, explains how venom has evolved independently from nonvenomous ancestors more than 100 times in the animal kingdom.
"Essentially, we have all the building blocks in place," said study co-author Agneesh Barua, a doctoral student in evolutionary genetics at the Okinawa Institute of Science and Technology in Japan. "Now it's up to evolution to take us there."
Oral venom is common across the animal kingdom, present in creatures as diverse as spiders, snakes and slow lorises, the only known venomous species of primate. Biologists knew that oral venom glands are modified salivary glands, but the new research reveals the molecular mechanics behind the change.
"It's going to be a real landmark in the field," said Bryan Fry, a biochemist and venom expert at The University of Queensland in Australia who was not involved in the research. "They've done an absolutely sensational job of some extraordinarily complex studies."
Venom is the ultimate example of nature's flexibility. Many of the toxins in venom are common across very different animals; some components of centipede venom, for example, are also found in snake venom, said Ronald Jenner, a venom researcher at the Natural History Museum in London who was not involved in the research.
The new study doesn't focus on toxins themselves, as those evolve quickly and are a complex mix of compounds, Barua told Live Science.
Instead, Barua and study co-author Alexander Mikheyev, an evolutionary biologist at Australian National University who focuses on "housekeeping" genes, the genes that are associated with venom but aren't responsible for creating the toxins themselves. These regulatory genes form the basis of the whole venom system.
The researchers started with the genome of the Taiwan habu (Trimeresurus mucrosquamatus), a brown pit viper that is well studied, in part because it's an invasive species in Okinawa.
"Since we know the function of all the genes that were present in the animal, we could just see what genes the venom genes are associated with," Barua said.
The team found a constellation of genes that are common in multiple body tissues across all amniotes. (Amniotes are animals that fertilize their eggs internally or lay eggs on land; they include reptiles, birds and some mammals.)
Many of these genes are involved in folding proteins, Barua said, which makes sense, because venomous animals must manufacture a large quantity of toxins, which are made of proteins.
"A tissue like this really has to make sure that the protein it is producing is of high quality," he said.
Unsurprisingly, the same sorts of regulatory housekeeping genes are found in abundance in the human salivary gland, which also produces an important stew of proteins - found in saliva - in large quantities. This genetic foundation is what enables the wide array of independently evolved venoms across the animal kingdom.
In other words, every mammal or reptile has the genetic scaffolding upon which an oral venom system is built. And humans (along with mice) also already produce a key protein used in many venom systems. Kallikreins, which are proteins that digest other proteins, are secreted in saliva; they're also a key part of many venoms.
That's because kallikreins are very stable proteins, Fry said, and they don't simply stop working when subjected to mutation. Thus, it's easy to get beneficial mutations of kallikreins that make venom more painful, and more deadly (one effect of kallikreins is a precipitous drop in blood pressure). ■