Exploring the Diversity and Novelty of Toxin Genes in Naja sumatrana, the Equatorial Spitting Cobra from Malaysia through De Novo Venom-Gland Transcriptomics.

Ho Phin Chong,Choo Hock Tan,Kae Yi Tan,Nget Hong Tan

doi:10.3390/toxins11020104

Abstract

The equatorial spitting cobra, Naja sumatrana, is a distinct species of medically important venomous snakes, listed as WHO Category 1 in Southeast Asia. The diversity of its venom genes has not been comprehensively examined, although a few toxin sequences annotated to Naja sputatrix were reported previously through cloning studies. To investigate this species venom genes’ diversity, de novo venom-gland transcriptomics of N. sumatrana from West Malaysia was conducted using next-generation sequencing technology. Genes encoding toxins represented only 60 of the 55,396 transcripts, but were highly expressed, contributing to 79.22% of total gene expression (by total FPKM) in the venom-glands. The toxin transcripts belong to 21 families, and 29 transcripts were further identified as full-length. Three-finger toxins (3FTx) composed of long, short, and non-conventional groups, constituted the majority of toxin transcripts (91.11% of total toxin FPKM), followed by phospholipase A2 (PLA2, 7.42%)—which are putatively pro-inflammatory and cytotoxic. The remaining transcripts in the 19 families were expressed at extremely low levels. Presumably, these toxins were associated with ancillary functions. Our findings unveil the diverse toxin genes unique to N. sumatrana, and provide insights into the pathophysiology of N. sumatrana envenoming.

Highlights

Venom is a sophisticated and versatile weapon harnessed by venomous snakes for prey capture, and defense [1,2]
Sequencing of the cDNA libraries yielded a total of 46,878,172 clean reads for the Malaysian
Following BLASTx alignment, the Unigenes— referred as transcripts—were assigned to three categories: (a) “unidentified”; (b) “non-toxin”; and (c) “toxin”

Summary

Introduction

Venom is a sophisticated and versatile weapon harnessed by venomous snakes for prey capture, and defense [1,2]. As the fundamental purpose of snake venom is predation, venom gene adaption is strongly driven by diet [3,4]. Variations in snake venom composition has ramifications on snakebite management, as it may lead to unexpected clinical manifestations of envenomation. Variation in venom protein antigenicity can result in suboptimal antivenom efficacy or even treatment failure [10,11,12]. This is relevant to snakes that are widely distributed such as cobras in Asia. Cobra venom compositions have been shown to vary widely

Methods

Results

Conclusion