When Snakes Strike: SMRT Sequencing Reveals Hidden “Venom-ome”
Monday, January 27, 2020
Snake milking, horse blood harvesting and brewing — antivenom production is still more medieval art than modern science. But a new high-quality snake genome may finally pull it into the 21st century.
As recently reported in Nature Genetics, a team of scientists led by Somasekar Seshagiri, a former staff scientist at Genentech and now president of the nonprofit SciGenom Research Foundation (@SGRF_Science) in India, assembled the genome and transcriptome of the lethal Indian Cobra (Naja naja) using PacBio long-read sequencing and other genomic technologies.
They also created a “venom-ome,” a catalog of venom-gland-specific toxin genes they hope can be used for the development of synthetic antivenom of defined composition using recombinant technologies.
The new cobra genome is one of only a few snake genomes ever published. Previous assemblies were generated primarily using short-read sequencing, resulting in highly fragmented assemblies, “thus limiting their utility for creating a complete catalog of venom-relevant toxin genes,” the authors noted. Compared with the king cobra genome, the Indian cobra genome contains far fewer scaffolds (1,897 versus 296,399), and 929-fold better contiguity.
“This high-quality genome allowed us to study various aspects of snake venom biology, including venom gene genomic organization, genetic variability, evolution and expression of key venom genes,” the authors wrote.
A team of scientists from AgriGenome (@agrigenome), a PacBio certified service provider, was instrumental in generating long-read PacBio whole genome and venom gland Iso-seq data. Their bioinformatics team helped build a functional annotation pipeline that leveraged 101,761 Iso-seq transcript isoforms to identify and correctly annotate 139 toxin genes out of the 12,346 genes expressed in the venom gland, the ‘venom-ome’. Of the 139 toxin genes, 19 were expressed primarily in the venom gland.
Targeting these core toxins — which are responsible for a wide range of symptoms in humans, including heart-function problems, paralysis, nausea, blurred vision, internal bleeding and 100,000 deaths per year worldwide — could lead to the development of a safe and effective humanized antivenom, as well as drugs to treat hypertension, pain and other disorders, the authors suggest.
“The genome and the associated predicted proteome will also serve as a powerful platform for evolutionary studies of venomous organisms,” the authors wrote.
Learn more about the methods and workflow for PacBio whole genome sequencing.