Imagine being able to kill your enemies with a single, venomous bite. It might sound a little farfetched, but new research shows that humans do have the potential to become venomous, as the genes that regulate our salivary glands are the same that allow snakes to produce oral toxins.
According to a new study in the Proceedings of the National Academy of Sciences (PNAS), the genetic building blocks behind the production of oral venom in snakes are shared by mammals and reptiles. Therefore, while we may not currently possess a death-inducing bite, the prospect of one day evolving such a weapon is not out of the question.
The study authors began with a curiosity for the roots of oral venom, which has developed independently in a wide range of animals, from snakes to spiders. Previous research has tended to focus on the genes behind the specific toxins contained within the venoms of different species but has failed to provide any concrete answers as to how the oral venom system first developed.
In search of a solution, the authors of this latest study chose not to examine the genes associated with toxin production and focused instead on the so-called ‘housekeeping genes’ that support and regulate the oral venom system. Examining the genome of a type of viper known as the Taiwan habu snake, the researchers identified around 3,000 such genes, which they have collectively labeled the “metavenom network”.
The genes within this network are primarily concerned with the regulation of protein folding – an essential step in the production of venom, which is made up of an array of proteins that must all be correctly regulated. More specifically, the genes within the metavenom network generally fell into two distinct pathways: the unfolding protein response (UPR), which “anticipates, detects, and correctly folds misfolded proteins”, and the endoplasmic reticulum-associated protein degradation (ERAD), which “ensures that misfolded proteins are degraded so as to prevent cellular toxicity.”
When the researchers then examined the genomes of various reptiles and mammals – including humans – they discovered that they all contained the same types of genes. The only difference is that instead of supporting the production of venom proteins, this network ensures the correct folding of saliva proteins in non-venomous species.
Therefore, while the venom glands of snakes and the salivary glands of mammals may ultimately serve different functions, they share a common suite of regulatory genes that have persisted ever since the two lineages diverged in the distant past.
“Many scientists have intuitively believed this is true, but this is the first real solid evidence for the theory that venom glands evolved from early salivary glands,” explained study author Agneesh Barua in a statement. “And while snakes then went crazy, incorporating many different toxins into their venom and increasing the number of genes involved in producing venom, mammals like shrews produce simpler venom that has a high similarity to saliva.”
What’s more, this discovery illuminates a clear evolutionary pathway by which certain mammals could one day develop oral venom.
“There were experiments in the 1980s that showed that male mice produce compounds in their saliva that are highly toxic when injected into rats,” said Barua. “If under certain ecological conditions, mice that produce more toxic proteins in their saliva have better reproductive success, then in a few thousand years, we might encounter venomous mice.”
Similarly, human saliva contains a protein called kallikrein, which is also present in a number of venomous secretions. In other words, we already have the basic components for the development of a deadly bite.