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2017 SMRT Grant Finalist

Genomics And Venomics Of The Sexually Dimorphic Temple Pitviper

Principal Investigators:
Dr. Mrinalini, Research Fellow, South East Asian Biodiversity Genomics, Department of Biological Sciences, National University of Singapore
Dr. Ryan McCleary, Postdoctoral Fellow, Department of Biology, Utah State University
Professor Manjunatha Kini, Protein Science Laboratory, South East Asian Biodiversity Genomics, Department of Biological Sciences, National University of Singapore

About This Project

Snakes! More often than not, they evoke strong reactions in humans – usually fear, fascination, awe, and even reverence. But, a few of us think they are great animals to study! Snakes are often venomous, and their venom is a cocktail of toxic proteins that can kill. However, snake venom toxins have been developed into several lifesaving drugs and provide a rich resource for finding novel cures. Research on snakes also contributes to antivenom design and a better understanding of venom evolution, body plan, and development. With our expertise in venom biology, herpetology, and toxinology, we aim to sequence the genome of an unusual snake – Tropidolaemus wagleri. Famously found in the Snake Temple of Penang, Malaysia, this species is also called ‘The Temple Pitviper’.

Why is this the most interesting genome in the world?
The Temple Pitviper is a highly venomous snake common to South East Asia. This non-model species is fascinating to study for multiple reasons. Firstly, it secretes potent venom containing unique toxins not found in other snake species. A prime example of this is a class of novel toxins called Waglerins that are highly selective neuromuscular inhibitors. Secondly, while in most snake species males and females are virtually indistinguishable, the Temple Pitviper displays extreme sexual dimorphism. Males are small and green whereas females grow up to ten times their size and are brilliantly colored. Interestingly, all neonates display a male phenotype. The developmental switch producing this dramatic sex-specific phenotype remains a mystery. It is also unknown whether sex-based differences exist in venom, habitat, behavior, and/or diet.

 

What are the goals of this project?
Our goal is to sequence the genome of the Temple Pitviper and to explore venom functional genomics and venom evolution in this species. Snake venom evolves rapidly via gene duplication and accelerated evolution of exons in toxin gene families, and this complicates the resolution of toxin gene sequences. We will use the latest technology from PacBio, the Sequel System, to perform high-coverage genome sequencing, and we will assemble and annotate the genome. Using PacBio long reads and the genome assembly, we aim to characterize full-length sequences of toxin genes in the Temple Pitviper. We will trace the evolution of toxin gene families, including unusual toxins like Waglerins. We will also investigate the sexual dimorphism aspect of this remarkable species with implications to venom and development.

 

What is the global impact of your research?
Snakebite related deaths are estimated at about 100,000 a year the world over. In contrast, the drugs developed from snake venom toxins, such as the cardiovascular and neurological agents captopril, eptifibatide, and tirofiban, save the lives of millions of humans every year. The venom of the Temple Pitviper is not only potent, but also unique in that it contains novel toxins such as Waglerins. Our investigation of the toxin genes in the Temple Pitviper therefore has dual potential, i.e., to contribute to the discovery of medically important drugs as well as to antivenom research. The PacBio genome assembly and the toxin gene sequences resulting from this project will also provide a tremendously useful resource for furthering the study of snake venom genes and their evolution.

 

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