The first Conus genome assembly reveals a primary genetic central dogma of conopeptides in C. betulinus

Chao Peng,Xinhui Zhang,Bingmiao Gao,Xinxin You,Ge Yao,Jie Liu,Jieming Chen,Jia Li,Zhilong Lin,Zhiqiang Ruan,Kai Zhang,Xin Lin ,Jiaan Yang ,Yuexin He ,Chun‐An Fan ,Jisheng Chen ,Junmin Xu,Hui Jiang,Chao Bian,Ruobo Gu,Yunyun Lv,Yanping Li,Yu Huang,Yunhai Yi,Qiong Shi

doi:10.1038/s41421-021-00244-7

Abstract

Although there are various Conus species with publicly available transcriptome and proteome data, no genome assembly has been reported yet. Here, using Chinese tubular cone snail (C. betulinus) as a representative, we sequenced and assembled the first Conus genome with original identification of 133 genome-widely distributed conopeptide genes. After integration of our genomics, transcriptomics, and peptidomics data in the same species, we established a primary genetic central dogma of diverse conopeptides, assuming a rough number ratio of ~1:1:1:10s for the total genes: transcripts: proteins: post-translationally modified peptides. This ratio may be special for this worm-hunting Conus species, due to the high diversity of various Conus genomes and the big number ranges of conopeptide genes, transcripts, and peptides in previous reports of diverse Conus species. Only a fraction (45.9%) of the identified conotopeptide genes from our achieved genome assembly are transcribed with transcriptomic evidence, and few genes individually correspond to multiple transcripts possibly due to intraspecies or mutation-based variances. Variable peptide processing at the proteomic level, generating a big diversity of venom conopeptides with alternative cleavage sites, post-translational modifications, and N-/C-terminal truncations, may explain how the 133 genes and ~123 transcripts can generate thousands of conopeptides in the venom of individual C. betulinus. We also predicted many conopeptides with high stereostructural similarities to the putative analgesic ω-MVIIA, addiction therapy AuIB and insecticide ImI, suggesting that our current genome assembly for C. betulinus is a valuable genetic resource for high-throughput prediction and development of potential pharmaceuticals.

Highlights

Cone snails (Conus spp.) are a large genus of gastropods that feed on a variety of prey, including worms, snails, and fishes[1,2]
Given that there are ~700 Conus species around the world and each possesses over 100 various conopeptides[1,2,3,4], it has been estimated that there are over 80,000 natural conopeptides[1,5], of which some have been approved as valuable pharmacological probes and clinical drugs such as the well-known ω-MVIIA (Ziconotide) for
Generation of the first Conus genome assembly Specimens of wild middle body-sized[4] (8.5 ± 0.5 cm in length) C. betulinus were collected in the offshore areas of

Summary

Introduction

Cone snails (Conus spp.) are a large genus of gastropods that feed on a variety of prey, including worms, snails, and fishes[1,2]. Hundreds of conopeptide genes or conopeptide coding sequences (CDS) have been identified by PCR amplification or purified from crude venom of cone snails using mass chromatography (MS). Employing advanced MS systems, several research teams[9,11,12] have reported the presence of over 1000 different peptides in a single venom, which is a remarkable increase from the early popular estimates of 50–200 conopetides per species. Great difficulty in extraction of high-quality genomic DNAs has hindered whole-genome sequencing of cone snails[1], which should have become a valuable resource for comparative examinations of detailed transcription and translation of conopetide genes in single or different Conus species

Methods

Results

Conclusion