Abstract

Envenomation resulted from sea snake bite is a highly lethal health hazard in Southeast Asia. Although commonly caused by sea snakes of Hydrophiinae, each species is evolutionarily distinct and thus, unveiling the toxin gene diversity within individual species is important. Applying next-generation sequencing, this study investigated the venom-gland transcriptome of Hydrophis curtus (spine-bellied sea snake) from Penang, West Malaysia. The transcriptome was de novo assembled, followed by gene annotation and sequence analyses. Transcripts with toxin annotation were only 96 in number but highly expressed, constituting 48.18% of total FPKM in the overall transcriptome. Of the 21 toxin families, three-finger toxins (3FTX) were the most abundantly expressed and functionally diverse, followed by phospholipases A2. Lh_FTX001 (short neurotoxin) and Lh_FTX013 (long neurotoxin) were the most dominant 3FTXs expressed, consistent with the pathophysiology of envenomation. Lh_FTX001 and Lh_FTX013 were variable in amino acid compositions and predicted epitopes, while Lh_FTX001 showed high sequence similarity with the short neurotoxin from Hydrophis schistosus, supporting cross-neutralization effect of Sea Snake Antivenom. Other toxins of low gene expression, for example, snake venom metalloproteinases and L-amino acid oxidases not commonly studied in sea snake venom were also identified, enriching the knowledgebase of sea snake toxins for future study.

Highlights

  • The majority of studies on sea snake envenomation and pathophysiology were reported since early 1950s for the beaked sea snake (Hydrophis schistosus or Enhydrina schistosa prior to taxonomic revision [11]) in the western coast of Peninsular Malaya, ostensibly due to its common occurrence and frequent bites in the waters

  • We investigated the venom gene profile of H. curtus, a medically and commercially important sea snake species in Southeast Asia through de novo venom-gland transcriptomics, applying next-generation sequencing technique

  • De novo assembly of the reads resulted in 126,790 contigs (N50 = 921), which were further clustered and streamlined into 82,209 unigenes (N50 = 2073)

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Summary

Introduction

Snakebite envenomation is a World Health Organisation (WHO)-classified neglected tropical disease that heavily affects many impoverished populations in the tropics and subtropics [1]. Each year, it causes 81,000 to 138,000 deaths across the world and approximately three times as many permanent disabilities and psychological trauma in those who survive [2,3]. The majority of studies on sea snake envenomation and pathophysiology were reported since early 1950s for the beaked sea snake (Hydrophis schistosus or Enhydrina schistosa prior to taxonomic revision [11]) in the western coast of Peninsular Malaya, ostensibly due to its common occurrence and frequent bites in the waters. Unlike Aipysurus which has a relatively stable taxonomic history and is mainly restricted in the Australo-Papuan region, the Hydrophis complex is a far more diverse monophyletic clade that consists of close to 50 species distributed in the waters of Indo-Malayan Archipelago, Indonesia, Australia and South China

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