Molecular Evolution and Diversity of Conus Peptide Toxins, as Revealed by Gene Structure and Intron Sequence Analyses

Yun Wu,Shaonan Luo,Anlong Xu,Yuwen You,Yuanyuan Qiang,Zhenghua Ren,Lei Wang,Mengying Qin,Xiaoyan Zhu,Maojun Zhou,Yi Xing

doi:10.1371/journal.pone.0082495

Abstract

Cone snails, which are predatory marine gastropods, produce a cocktail of venoms used for predation, defense and competition. The major venom component, conotoxin, has received significant attention because it is useful in neuroscience research, drug development and molecular diversity studies. In this study, we report the genomic characterization of nine conotoxin gene superfamilies from 18 Conus species and investigate the relationships among conotoxin gene structure, molecular evolution and diversity. The I1, I2, M, O2, O3, P, S, and T superfamily precursors all contain three exons and two introns, while A superfamily members contain two exons and one intron. The introns are conserved within a certain gene superfamily, and also conserved across different Conus species, but divergent among different superfamilies. The intronic sequences contain many simple repeat sequences and regulatory elements that may influence conotoxin gene expression. Furthermore, due to the unique gene structure of conotoxins, the base substitution rates and the number of positively selected sites vary greatly among exons. Many more point mutations and trinucleotide indels were observed in the mature peptide exon than in the other exons. In addition, the first example of alternative splicing in conotoxin genes was found. These results suggest that the diversity of conotoxin genes has been shaped by point mutations and indels, as well as rare gene recombination or alternative splicing events, and that the unique gene structures could have made a contribution to the evolution of conotoxin genes.

Highlights

The genus Conus, which contains .500 species, is one of the largest genera of marine invertebrates [1]
The dominant components of cone snail venoms are small peptide toxins typically comprising 12,50 residues and 1–5 disulfide bridges, which have become known as conotoxins or conopeptides [1]
Conotoxin gene structures are correlated to the gene superfamily only As mentioned above, three classification schemes have been used to define conotoxins: the ‘‘gene superfamily’’, the ‘‘cysteine framework’’ and the ‘‘pharmacological family’’

Summary

Introduction

The genus Conus, which contains .500 species, is one of the largest genera of marine invertebrates [1]. Most cone snails are specialist predators, feeding predominantly on worms (vermivorous), fish (piscivorous), or other marine gastropods (molluscivorous) [2]. There are approximately 100,1000 different conotoxins per Conus species, and it has been estimated that .100,000 different pharmacologically active components are present in the venoms of all living cone snails [4,5]. Other classification schemes have been used to describe different aspects of conotoxins, such as the ‘‘gene superfamily’’, the ‘‘cysteine framework’’ and the ‘‘pharmacological family’’ classification schemes [6]. The ‘‘gene superfamily’’ classification scheme maybe the most popular, and it can be applied to most conotoxins [6]

Methods

Results

Conclusion