How plesiosaurs swam underwater

Breakthrough study examines the development of genes for snake venom

A new study from biologists at the University of Texas at Arlington and an international team of partners provides the first comprehensive explanation of how snake venom regulatory systems evolved – an important example illustrating the development of new complex properties.

Todd Castoe, UTA professor of biology, is the corresponding author of the article, entitled “Gene Expression of Snake Poison Coordinated by New Regulatory Architecture and the Integration of Multiple Adjunct Spinal Pathways.” It was published online on June 1 Genome research.

“We have relatively few detailed examples of how new regulatory systems are being developed to drive new complex properties,” Castoe said. “This study provides a valuable example that illustrates a surprising number of distinct ‘strategies’ for how evolution can switch regulatory networks, giving key expectations on how such switching can occur in other species, including humans.”

Ever since Darwin introduced the theory of evolution through natural selection in the 19th century, biologists have struggled to understand how new, complex properties evolve.

Snake venom and venom systems are an example of such complex properties. Little is known about their molecular mechanisms or the genomic and evolutionary origins of this regulatory system, Castoe said.

“This work gives us a better understanding of how snake venom evolved and how toxin production works at the genomic level,” said Blair Perry, a UTA alumnus and postdoctoral fellow at the School of Biological Sciences at Washington State University. He is the lead author of the new magazine.

“In addition to studying specific toxin genes, we can now examine parts of the genome that are involved in the regulation of these genes as well,” said Perry, who received his doctorate. from UTA 2021 with Castoe as his faculty advisor. “This opens up new opportunities to understand how variation in snake venom, both within and between snake species, corresponds to variation in the genome.”

In 2019, the World Health Organization declared snake bites a neglected tropical disease. The primary challenge in treating snake bites is the extreme variation in toxin composition between populations and species of snakes.

“Our work provides the first description of the regulatory architecture that drives the expression of snake venom, providing a critical context for understanding the molecular interactions that govern venom variation,” Castoe said.

The development of snake venom required that snakes develop a highly specialized venom gland to produce and store a versatile and lethal protein cocktail for delivery to their victims. Poison glands are thought to have evolved from ancestral salivary glands, but Perry and colleagues show that this also required the development of new regulatory sequences and the relocation of existing regulatory systems to control the exact expression of these dangerous genes.

“Think of the challenges of understanding the origin and maintenance of this complex chemical weapon system,” said Stephen Mackessy, a professor of biology at the University of Northern Colorado and co-author of the study. “Toxins consist largely of reused regulatory proteins and peptides, overexpressed and stored in a specialized gland just millimeters from the snake’s brain. These toxins must be stabilized, but still ready to be used at a moment’s notice, and they can be stored for long periods.

“Our previous work has shown that there are several mechanisms that promote this long-term storage, but the processes leading to the regulation, development and diversification of these systems have largely remained unknown. This study shows that in addition to the toxin genes, regulatory pathways that were common for vertebrate animals to control this system. “

Nicholas Casewell, professor and head of the Center for Snakebite Research & Interventions at the Liverpool School of Tropical Medicine in the UK, is an expert in the field who was not involved in the work. He said that snake venom is a valuable system for understanding the links between genotype and phenotype in animals, and these biochemically active secretions also have major consequences for humans, as snake bites cause over 100,000 deaths per year. Despite its importance, he noted, the regulation of venom by snakes is still almost poorly understood by scientists.

“In this study, the authors use a variety of groundbreaking approaches to investigate this topic, and their subsequent collection of regulatory sequence, transcription factor, signaling cascade and chromatin availability data, and associated analyzes provide completely unparalleled insight into the Casmatic regulatory system.” “Their results represent a major step forward in helping us better understand how genes associated with internal physiological processes can be reused for external use in the form of toxins.”

Giulia Pasquesi, a postdoctoral fellow at the University of Colorado at Boulder who took her Ph.D. from UTA 2020 with Castoe as his faculty advisor, is a co-author of the magazine. She investigated the role of transposable elements (TE) – DNA sequences that move from one place on the genome to another – in the evolution of snake venom.

“Whether snake-specific TEs contributed to the development of snake-specific traits, which have occurred in mammals for key traits such as placentation, remained a fascinating open question until now,” Pasquesi said. “One of the results of this study shows that the emergence of biological innovations follows recurring patterns, in particular that TEs can introduce new regulatory sequences that ultimately facilitate the development of new complex properties.”

Perry said the study also shows the value of considering many layers of biological complexity when trying to understand how a trait works and develops.

“By combining several types of genomic data, we were able to gain a more complete understanding of the various factors that play a role in the regulation and development of toxin genes,” Perry said. “Just in general, this work provides a valuable example of the peculiarities of evolution. It can be expected that all toxin genes followed the same evolutionary” strategies “to become involved in venom. Our findings suggest instead that remarkably different genomic and evolutionary processes played crucial roles in evolution. of specific toxin genes. “

#Breakthrough #study #examines #development #genes #snake #venom

Leave a Comment

Your email address will not be published.