Zeroing in on the genes that snakes use to produce venom

Only about ten percent of the world’s roughly 4,000 snake species have venom strong enough to seriously hurt a human, but that’s enough for snake bites to be an important public health concern. To help better understand how snakes make their venom and how venoms differ from one species to another, researchers developed a new way to zero in on the genes that snakes use in venom production. Their work was published in the journal Molecular Ecology Resources.

“We’ve developed a tool that can tell us which venom-producing genes are present across an entire snake family in one fell swoop,” says Sara Ruane, the Assistant Curator of Herpetology in the Field Museum’s Negaunee Integrative Research Center and the study’s senior author. 

All living things contain DNA, a molecule that provides chemical instructions for building and operating an organism’s body. These instructions are called a genome, and smaller sections of the genome are called genes. The human genome, for instance, is made up of about 20,000 genes, which contain instructions for everything from cell growth to eye color. 

In snakes, there are thousands of genes involved with producing venom, and different species of venomous snakes use different combinations and versions of those genes to produce their toxins. 

“It’s important to know what’s in a snake’s venom, because different kinds of venom do different things-- some venoms affect the nervous system, some affect the circulatory system, some affect cell function,” says Ruane. “Knowing what’s in a certain kind of venom can help in the development of antivenom for treating that kind of snakebite.” 

What’s more, there are compounds in snake venoms that are actually used in pharmaceutical development and human medicine-- for instance, the first ACE-inhibitor drug for treating high blood pressure was created from a compound found in the venom of a Brazilian pit viper. “You can harness the power of death in a controlled way,” says Ruane.

Since there are thousands of genes that produce venom and each snake’s genome contains tens of thousands of genes, it can be difficult to zero in on the ones present for venom production in a given species. To solve this problem, Ruane and her colleagues, led by the study’s first author, Scott Travers, developed a technique called VenomCap.

VenomCap is a set of exon-capturing probes, which are groups of molecules designed to interact with a specific group of genes. VenomCap was designed to bind with any of the several thousands of genes that previous studies have shown are involved with venom production in snakes. Rather than having to sequence a snake’s entire genome (a lengthy and expensive process) and combing through it for 2,000+ possible venom-making genes, VenomCap could provide a quicker, easier means for scientists to see which of these genes a snake possesses. 

To test VenomCap’s ability to bind with venom-producing genes, the researchers took tissue samples from 24 kinds of snakes across the medically important family Elapidae, which includes cobras, mambas, and coral snakes. Previous genomic studies have already shown many of the venom-producing genes these snakes have, and VenomCap was able to match those results, on average, with 76% accuracy. VenomCap can be used with previously collected tissues from anywhere in a snake’s body, rather than needing to come from the venom glands directly, which is another frequently used technique for determining venom genes in snakes.

Since VenomCap can be used to analyze venom genes from individual species across the whole elapid family (about 400 species), it may make it easier for scientists to study the relationships between these snakes’ lifestyles and the venoms they produce. “Let’s say you’re interested in some closely-related species of snakes that look different from each other, live in different environments, and eat different things. VenomCap could help scientists compare the venoms that these snakes produce, and that could help answer bigger-picture questions of whether venoms evolve to match the snakes’ lifestyles, or if their lifestyles evolve to match the venom they produce,” says Ruane.

In addition to shining a light on snake evolution, a tool like VenomCap could make a difference for scientists trying to treat dangerous snake bites. “Snake bite is considered a neglected disease on the global-scale. In the United States, we don’t come into contact with venomous snakes that often, and when we do, we have extremely good medical treatment-- if you expeditiously go to the hospital with a snakebite, you are almost certainly not going to die,” says Ruane. “But in other parts of the world, a hospital might be too far away to reach in time, or they might not have the right kind of antivenom on hand, because antivenom is in very short supply. So any kind of work that looks at snake venom and helps us identify the venoms present in different species can be extremely important to provide baseline data for developing effective treatments.”

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