Evolution can occur with surprising predictability when organisms face similar ecological challenges. For most traits, it is difficult to determine whether this is due to limitations imposed by the number of possible phenotypic solutions or to parallel reactions imposed by a common genetic and regulatory architecture. As an exception, oral poisons are a controllable model of trait development. This is because it is mainly made up of proteinaceous toxins that evolved in many tetrapods, from reptiles to mammals.
Snakes, lizards, and even some mammals can have a venomous bite. Although these lineages split more than 300 million years ago, their poisons evolved from the same ancestral salivary protein, scientists reported in BMC Biology today.
Researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) in Japan and the Australian National University focused on toxins found in most snake venom and all other reptile and mammalian venom called the mammalian kallikrein serine proteases. They also traced their origins back to a gene found in a common ancestor.
“Poisons are cocktails made from toxic proteins that have evolved throughout the animal kingdom, typically as a method of killing or immobilizing prey.” explained Agneesh Barua, co-first author and Ph.D. Student at the OIST. “The oral poison systems found in snakes are particularly complex and the origin of their poisons is still unclear.”
In previous work, Barua and colleagues found that the mammalian salivary gland and snake venom gland share a similar pattern of activity in a group of regulatory genes, suggesting that the basis for venom development is present in both snakes and mammals.
“In this work we hypothesized that the ancestors of snakes and mammals shared a common set of genes that had toxic potential.” said Barua. “Snakes and mammals then took different evolutionary paths, with serpentine lines developing diverse and increasingly poisonous brews, while mammals developing poisons, albeit to a much lesser extent. But what we wanted to know is whether the toxins in mammalian and snake venom developed from a common ancestral gene. “
Kallikrein serine proteases are a protein-breaking enzyme that plays a key role in regulating blood pressure.
The saliva of mammals contains small amounts of these proteins, but their function is still unclear. But in poisonous snakes and mammals such as shrews and solenodons, these proteins have developed toxicity. When injected in large quantities, they drastically reduce Blood pressurepossibly resulting in unconsciousness and even death.
Early on, researchers noticed biochemical similarities between kallikrein serine proteases in snake venom and those in mammalian saliva, but until now scientists did not know whether they were actually related. “There are so many different serine proteases that show a high degree of similarity that it has been too difficult to isolate the right genes that are needed to elucidate the history of evolution.” said Barua.
With recent advances in genomic methods, the research group was able to identify all kallikrein genes in reptiles, amphibians, fishes, and mammals to create an evolutionary tree.
Excitingly, they discovered that snake venom kallikrein serine proteases and mammalian salivary kallikrein evolved from the same ancestral gene.
“This is really strong evidence for our hypothesis that the venom evolved from a common set of genes in an ancestor that had toxic potential.” said Barua. “But the most surprising thing was that non-toxic salivary kallikreins, such as those found in humans and mice, developed from the same ancestral gene.”
“Most exaptations have bifunctional intermediate stages in which both the old and the new functions are retained. This bifunctional nature is likely to allow a gradual transition from one phenotypic state to another. For example, after the gene duplication, one or both gene copies can fulfill their original function; or a copy can accidentally acquire a new function in the course of the accumulation of neutral mutations. This is the standard model of snake toxin evolution, which requires a gene duplication before acquiring a new function (toxicity). Study quotes.
The researchers found that the non-toxic kallikreins in mammalian saliva were more closely related to the toxic toxins in snakes than to other kallikreins found in mammals.
Taken together, this evidence suggests that salivary kallikrein proteins also have evolutionary potential to become toxic in mammals, including humans.
But, Barua quickly added, there is one caveat. “Just because we have the building blocks to create poison doesn’t mean this will happen. The production of poison is energetically very expensive, so there had to be strong ecological pressure that humans and most mammals do not have. “
But what this tells us, he said, is that the line between venomous and non-venomous mammals is more blurred than previously thought.
- Barua, A., Koludarov, I. & Mikheyev, AS The co-option of the same ancestral family of genes resulted in toxins from mammals and reptiles. BMC Biol 19, 268 (2021). DOI: 10.1186/s12915-021-01191-1