College of Science

Genetic research on highly venomous Tiger Rattlesnakes breaks new ground


CLEMSON, South Carolina – While the Tiger Rattlesnake has the most toxic venom of any rattlesnake species, it also has the simplest.

A team of Clemson researchers used next-generation sequencing techniques more commonly implemented in research on fruit flies, mice and humans to sequence and characterize the genome of the Tiger Rattlesnake to determine whether the rattlesnake’s venom was the product of a simple or complex genotype. They were the first to use PacBio long-read sequencing in snakes. 

They found that the number of venom genes greatly exceeds the number of venom proteins, suggesting genetic regulatory mechanisms – and not gene number or sequence – are  responsible for the snake’s deadly venom.

The research was led by Christopher Parkinson, a professor in the College of Science’s Department of Biological Sciences, and former Clemson postdoctoral researcher Mark Margres, now an assistant professor at the University of South Florida. The journal Proceedings of the National Academy of Sciences published the findings in a paper titled “The Tiger Rattlesnake genome reveals a complex genotype underlying a simple venom phenotype.”

Parkinson, who has a dual appointment in the College of Agriculture, Forestry and Life Science’s Department of Forestry and Environmental Conservation, said the research is part of biologists’ quest to understand the evolution of venomous snakes and their venom.

Chris Parkinson in the field.
Clemson University professor Christopher Parkinson and his team of researchers were the first to use PacBio long-read sequencing in snakes. Image credit: College of Science

The Tiger Rattlesnake lives in desert areas in southern Arizona and northern Mexico and preys on lizards and small mammals. Its neurotoxic venom’s enzymes and peptides disrupt the nervous system, shutting down breathing and dropping blood pressure. The Tiger Rattlesnake’s highly neurotoxic venom kills its prey quickly, lessening the chance of it escaping into the desert’s rocky terrain.

Some rattlesnake species have complex venoms that result from lots of toxin-producing genes. But the Tiger Rattlesnake’s venom is simple. As few as 15 of its 51 toxin-producing genes are actively expressed.

“Simple genotypes can produce complex traits,” Margres said. “Here, we have shown the opposite is also true – a complex genotype can produce simple traits.”

Parkinson said scientists don’t know what exactly is driving the turning off and turning on of the genes.

“This paper addresses the how and sets up the why,” Margres added.

Margres said the research has broader implications than a better understanding of one species of rattlesnake. It could lead to scientists understanding the genotype-phenotype relationship in other organisms as well. He said that understanding the relationship at a detailed level could lead to better treatments for diseases and other benefits for society, such as an increase in crop yields.

Parkinson said the research, funded in part by Clemson University, required additional collaboration from a team at Florida State University.

Rattlesnake in desert
Tiger Rattlesnakes have small heads and large rattles. Rattlesnake images courtesy of Wolfgang Wuster.

“It truly is a collaboration on a multi-dimensional scale to investigate the evolution of this venom,” Parkinson said. “We couldn’t have done it without all the different types of scientists involved in this project.”

Other authors of the paper were Clemson researchers Rhett Rautsaw, Jason Strickland, Andrew Mason, Tristan Schramer, Erich Hofmann and Erin Stiers, and Florida State researchers Schyler Ellsworth, Gunnar Nystrom, Michael Hogan, Daniel Bartlett, Timothy Colston, David Gilbert and Darin Rokyta.

Research reported in this publication was supported by National Science Foundation Grants DEB 1638879 and DEB 1822417 and National Institute of General Medicine Sciences Institutional Development Award P20GM109094. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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