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

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.

How many single-copy orthologous genes from whole genomes reveal deep gastropod relationships?

“…In our case, the inclusion of C. consors led to a significant decrease in the number of shared SOGs and influenced the following phylogenetic inference. This might be caused by the fragmentation and incomplete assembly of C. consors (scaffold N50 = 1,128 bp) ( Andreson et al, 2019 ), which in future studies can be replaced with the newly published chromosome level genome of cone snails, such as Conus betulinus Linnaeus, 1758 ( Peng et al, 2021 ) and Lautoconus ventricosus Gmelin, 1791 ( Pardos-Blas et al, 2021 ).…”

Discovery of 194 Unreported Conopeptides and Identification of a New Protein Disulfide Isomerase in Conus caracteristicus Using Integrated Transcriptomic and Proteomic Analysis

“…In order to compare 3,289 differentially expressed transcripts with the genome annotation data of C. betulinus, we downloaded the EST data (ID: PRJNA290540) associated with the article (Peng et al, 2021) and compared it through BLASTN. The threshold value is set to 1e-5.…”

“…To the best of our knowledge, an in-depth comparison of conopeptides among individual Conus caracteristicus, a vermivorous species, has yet to be performed. Furthermore, it is interesting that previous studies have identified hundreds of unique toxins or conopeptides from a single Conus specimen using genomic or proteomic methods (Biass et al, 2009;Davis et al, 2009;Kaas et al, 2010;Lavergne et al, 2015;Peng et al, 2021). Besides the diversity on gene or protein sequence level, the high toxin diversity is attributed to the oxidative folding of proteases in the venom (Buczek et al, 2005;Bulaj and Olivera, 2008).…”

High-Throughput Identification of Antihypertensive Peptides (AHTPs) and Characterization of AHTP-Derived Genes in the Lined Seahorse (Hippocampus erectus)

“…Advanced omics along with bioinformatic tools are efficient approaches for high-throughput prediction of bioactive peptides such as AHTPs, toxins (Gao et al, 2018;Peng et al, 2021), antimicrobial peptides (Chen et al, 2020) and anticancer peptides (Zhong et al, 2020). In this study, we predicted some ATHP-rich proteins in the lined seahorse, especially those with high expression by integration of genome, transcriptome, and proteome data.…”