title: High-throughput identification of novel conotoxins from the Chinese tubular cone snail (Conus betulinus) by multi-transcriptome sequencing.
abstract: BACKGROUND
  The venom of predatory marine cone snails mainly contains a diverse array of unique bioactive peptides commonly referred to as conopeptides or conotoxins. These peptides have proven to be valuable pharmacological probes and potential drugs because of their high specificity and affinity to important ion channels, receptors and transporters of the nervous system. Most previous studies have focused specifically on the conopeptides from piscivorous and molluscivorous cone snails, but little attention has been devoted to the dominant vermivorous species.
  
  
  RESULTS
  The vermivorous Chinese tubular cone snail, Conus betulinus, is the dominant Conus species inhabiting the South China Sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in the identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including nine new superfamilies. It appeared that most of the identified conopeptides were synthesized in the venom duct, while a handful of conopeptides were identified only in the venom bulb and at very low levels.
  
  
  CONCLUSIONS
  We identified 215 unique putative conopeptide transcripts from the combination of five transcriptomes and one EST sequencing dataset. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for the development of new pharmaceuticals, and a pathway for the discovery of new conotoxins.
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China.
authors.forename: Chao
authors.initials: C
authors.lastname: Peng
authors.affiliation: Research Institute of Pharmaceutical Chemistry, Beijing, 102205 China.
authors.forename: Ge
authors.initials: G
authors.lastname: Yao
authors.affiliation: School of Pharmaceutical Sciences, Hainan Medical University, Haikou, 571199 China.
authors.forename: Bing-Miao
authors.initials: BM
authors.lastname: Gao
authors.affiliation: Research Institute of Pharmaceutical Chemistry, Beijing, 102205 China.
authors.forename: Chong-Xu
authors.initials: CX
authors.lastname: Fan
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Marine Genomics, Guangdong Provincial Key Laboratory of Molecular Breeding in Marine Economic Animals, State Key Laboratory of Agricultural Genomics, Shenzhen, 518083 China.
authors.forename: Chao
authors.initials: C
authors.lastname: Bian
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China.
authors.forename: Jintu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Research Institute of Pharmaceutical Chemistry, Beijing, 102205 China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cao
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wen
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China.
authors.forename: Yabing
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Marine Genomics, Guangdong Provincial Key Laboratory of Molecular Breeding in Marine Economic Animals, State Key Laboratory of Agricultural Genomics, Shenzhen, 518083 China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: Micro Pharmatech Ltd, Wuhan, 430075 China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Marine Genomics, Guangdong Provincial Key Laboratory of Molecular Breeding in Marine Economic Animals, State Key Laboratory of Agricultural Genomics, Shenzhen, 518083 China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: You
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Marine Genomics, Guangdong Provincial Key Laboratory of Molecular Breeding in Marine Economic Animals, State Key Laboratory of Agricultural Genomics, Shenzhen, 518083 China.
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Marine Genomics, Guangdong Provincial Key Laboratory of Molecular Breeding in Marine Economic Animals, State Key Laboratory of Agricultural Genomics, Shenzhen, 518083 China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Zou
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Marine Genomics, Guangdong Provincial Key Laboratory of Molecular Breeding in Marine Economic Animals, State Key Laboratory of Agricultural Genomics, Shenzhen, 518083 China.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Marine Genomics, Guangdong Provincial Key Laboratory of Molecular Breeding in Marine Economic Animals, State Key Laboratory of Agricultural Genomics, Shenzhen, 518083 China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Marine Genomics, Guangdong Provincial Key Laboratory of Molecular Breeding in Marine Economic Animals, State Key Laboratory of Agricultural Genomics, Shenzhen, 518083 China.
authors.forename: Jieming
authors.initials: J
authors.lastname: Chen
authors.affiliation: Molecular Genomics Laboratory, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Coon
authors.affiliation: Micro Pharmatech Ltd, Wuhan, 430075 China.
authors.forename: Jiaan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Research Institute of Pharmaceutical Chemistry, Beijing, 102205 China.
authors.forename: Ji-Sheng
authors.initials: JS
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083 China ; Shenzhen Key Laboratory of Marine Genomics, Guangdong Provincial Key Laboratory of Molecular Breeding in Marine Economic Animals, State Key Laboratory of Agricultural Genomics, Shenzhen, 518083 China ; BGI-Zhenjiang Institute of Hydrobiology, Zhenjiang, 212000 China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002681:China; D020916:Conotoxins / Q000235:genetics*; D052078:Conus Snail / Q000145:classification / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D008969:Molecular Sequence Data; D009792:Oceans and Seas; D010455:Peptides / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA / Q000379:methods*; D013045:Species Specificity; D059467:Transcriptome
chemical_list: D020916:Conotoxins; D010455:Peptides
keywords: Cone snail; Conopeptide; Conotoxin; Conus betulinus; Transcriptome; Venom bulb; Venom duct