Snakebites are responsible for approximately 100,000 fatalities across the globe annually. Scientists at the Technical University of Munich (TUM) delved into the origins of snake venom, which emerged between 50 and 120 million years ago due to genetic modifications in a shared gene found in mammals and other reptiles. These findings hold promise for the development of improved snakebite treatments and offer insights into addressing conditions like type 2 diabetes and hypertension.
When venom enters a snakebite victim, it binds to receptors on nerve and muscle cells, disrupting their communication pathways. This initial effect leads to paralysis, and without an antidote, it can result in death within minutes or hours. A research team investigated the structural changes in snake venoms, specifically the three-finger toxins (3FTxs), over the course of evolution.
Emergence of three-finger toxins
Under the guidance of Professor Burkhard Rost in the field of bioinformatics, a team made a significant discovery regarding three-finger toxins. They traced the development of these toxins back to the Ly6 gene, a gene shared with mammals and other reptiles. Interestingly, the Ly6 gene serves multiple roles, including contributions to immune responses in cells and neural regulation. This groundbreaking research has been documented in the journal Nature Communications.
Dr. Ivan Koludarov, a researcher at the Chair for Bioinformatics and the study’s primary author, explains, “Previous research suggests that snakes diverged from other lizards approximately 120 million years ago. Modern venomous snakes and non-venomous snake species diverged about 50 million years ago, both already possessing functional 3FTx genes. This means that over the course of 50 to 120 million years, the Ly6 gene underwent such substantial changes that it now yields a potent toxic effect.”
Throughout the evolutionary process, the Ly6 gene, responsible for toxin production, underwent repeated duplications. As a result, venomous snakes now carry multiple copies of this gene, with various segments undergoing mutations. This radical transformation in the gene’s protein function led it to abandon its original purpose and instead become a potent toxin.
Various forms of the venom
Tobias Senoner, currently pursuing a doctoral degree at the Chair for Bioinformatics, adds his perspective, stating, “The gene has undergone diverse mutations in various snake species. These mutations have resulted in four distinct forms of the 3FTx toxin, each with unique structures and, consequently, different effects on the snake’s prey.”
Professor Burkhard Rost elaborates on their research approach, saying, “In our study, we compiled a comprehensive dataset from the UniProt database, encompassing protein information from all known living organisms and viruses. Additionally, we accessed biomedical and genetic data from the National Center for Biotechnology Information. This wealth of data was then subjected to thorough analysis employing artificial intelligence techniques.”
The findings from this study hold the potential to enhance the treatment of snakebite victims and advance drug development. Understanding these toxins may contribute to the development of novel treatment approaches for conditions like type 2 diabetes or hypertension, as well as more effective pain medications.
Source: Technical University Munich