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The genetic toolkit for evolving a venomous bite

April 2021

The venom systems of solenodons and snakes evolved separately, but from the same evolutionary building blocks. Solenodon image courtesy of snl.no. Venomous blue viper courtesy of Wikimedia

If you scrolled past the non-stop coronavirus reporting in science news last month, you might have been hooked by some obvious clickbait "Humans will probably evolve to be venomous." Uh…they will? Well, of course not. We needn't worry about (or eagerly anticipate) becoming a lineage of fanged mutants. However, a look at the new research that inspired that extreme headline does provide a fascinating glimpse into how (and how easily) venom evolves in some situations.

Where's the evolution?

Animals across the Tree of Life have evolved to be venomous, meaning they can inject toxins into enemies or prey with a bite or sting. There are venomous fishes, lizards, mammals, mollusks, and a wide variety of venomous insects, arachnids, jellyfish, and snakes. This trait has evolved over and over again — and it's no wonder: a toxic bite or sting is both powerful protection and an easy way to get a meal. Of course, we'd expect natural selection to favor this trait in many different situations, if it were to arise. But how does a lineage come by venom in the first place? A new study from researchers in Japan and Australia tackled this question in animals with an amniotic sac (i.e., mammals, birds, lizards, snakes, turtles, and crocodiles).

In amniotes, oral venom (which is delivered through the mouth) has evolved multiple times, in snakes, of course, but also in venomous mammal lineages (e.g., solenodons and shrews) and in venomous lizard lineages (e.g., monitors and Gila monsters). In each case, it seems that salivary glands have been adapted to produce and deliver the toxic mix of molecules that go into venom. However, studying the origins of venom through the venom itself has been tricky because venom evolves so quickly. After all, it's harder to retrace the path of a car that zipped back and forth all over town than one that slowly chugged down a straight street.

Rather than focus on the evolution of a specific venom molecule or the mix of molecules in a particular venom, the researchers took a big-picture view, looking at the entire molecular system needed to produce venom. They studied the set of genes that are turned off and on at the same time in venom glands. This network of interacting genes includes all the genes that code for the venom toxins themselves, as well as many others that are involved with venom production.

Interestingly, the researchers found this same network of genes in other amniotes, even those that aren't venomous. The patterns of the genes' expression in venom glands matched those same patterns in the salivary glands of non-venomous amniotes. Whether we are looking at the salivary glands of a human or the venom glands of a cobra, the same set of genes is turned off and on in the same patterns. This means that this genetic system must be ancient. It must have existed in the common ancestor of humans and snakes (four-legged creatures that roamed the earth around 300 million years ago) and was then passed down to humans, snakes, and all other amniotes living today. This network seems to be the genetic toolkit that evolution has repeatedly co-opted to produce venom.

In evolutionary terms, we would say that this gene network is homologous — inherited from a shared ancestor — among amniotes. In contrast, oral venom is homoplasious — not inherited from a shared ancestor — among amniotes. Instead, this trait arose multiple times through convergent evolution, but interestingly, in the same way each time: from the salivary system.

This helps explain why venom has evolved so many times in amniotes. The basic architecture for venom production was there the whole time in the salivary system — not just the anatomy of glands and ducts, but also the genetic factory that can be tweaked to make venom. The same logic inspired that clickbait headline. Since we humans have a salivary system, we too have the infrastructure to evolve venom. Of course, what's left out of the headline is that even if a lineage has the raw material to evolve venom, that will only happen in a situation where venom offers a selective advantage. So…yeah…the next time you find yourself chasing down and immobilizing a sandwich with your teeth alone, you'll know where our species is headed.

Read more about it

Primary literature:

  • Barua, A., and A. S. Mikheyev. (2021). An ancient, conserved gene regulatory network led to the rise of oral venom systems. Proceedings of the National Academy of Sciences USA. 118:e2021311118. read it
News articles:

Understanding Evolution resources:

Discussion and extension questions

  1. Describe the selective advantages that having a venomous bite (as opposed to a nonvenomous one) might have in a population of snakes or small predatory mammals.
  2. In your own words, explain what a homology is.
  3. Do some research to find an example of a homology not mentioned in the article above and describe that example.
  4. In your own words, explain what convergent evolution is.
  5. Do some research to find an example of convergent evolution not mentioned in the article above and describe that example.
  6. Based on the new research, would you expect the genes that control the production of venom in a mammal (e.g., in a shrew) and in a cobra to be homologous to one another? Explain your reasoning.
  7. Based on the new research, would you expect the toxic components of mammalian venom (e.g., from a shrew) and cobra venom to be homologous to one another? Explain your reasoning
Related lessons and teaching resources

  • Teach about homology: This case study for high school and college students models the scientific process and examines the concept of homology in mammals, using scientific debate over classification of the platypus as an example.
  • Teach about classification and convergent evolution: This research profile for grades 9-12 follows scientist Chelsea Specht as she pieces together the evolutionary history of tropical plants and their pollinators — and in the process, tries to figure out how to conserve endangered species.
  • Teach about homology and evolutionary trees: In a flexible multisession laboratory, college students learn about phylogenetic analysis at both the molecular and the morphological level. Students finish by conducting their own analysis on collections skeletons using the Mesquite software.


  • Barua, A., and A. S. Mikheyev. (2021). An ancient, conserved gene regulatory network led to the rise of oral venom systems. Proceedings of the National Academy of Sciences USA. 118:e2021311118. https://www.kctv5.com/could-humans-evolve-to-be-venomous-researchers-say-theres-potential/article_ba691271-1c14-5ded-9157-d6e168f33d2a.html

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