Salcedo, P. F. | bioRxiv Science

bioRxiv2025

From Neuropeptides to Toxins: Illuminating the Origins of Venom Complexity in Cone Snails

New genes and gene functions are key drivers of evolutionary innovation. Venomous animals, such as cone snails, provide striking examples of gene innovation, yet the mechanisms by which toxins arise remain poorly understood. Using the Conus textile genome, we uncover how neuropeptide genes were recruited into the venom and neofunctionalized as doppelganger toxins. We identify over 20 independent recruitment events that evolved dynamically across the Conus lineage. Rather than arising from ohnologs of a whole-genome duplication event [~]100 mya, these toxins evolved through diverse mechanisms, including exon shuffling, alternative splicing, and ectopic recombination, often facilitated by lineage-specific transposable elements. Our findings reveal a dynamic interplay between genome architecture and molecular innovation, offering broad insight into the evolution of complex gene repertoires in venoms and beyond. One-Sentence SummaryDoppelganger toxins reveal how modular gene architecture, including 5UTR reuse and TE-driven recombination, fuels gene innovation in cone snails.

evolutionary biology↗

bioRxiv2022

Discovery of Novel Bilaterian Signaling Peptides Using Cone Snail Toxins

Peptide hormones and neuropeptides form a diverse class of signaling molecules that control essential processes in animals. Despite several breakthroughs in peptide discovery, many signaling peptides remain undiscovered. Recently, we demonstrated the use of somatostatin-like toxins from cone snail venom to identify homologous signaling peptides in prey. Here, we demonstrate that this toxin-based approach can be systematically applied to the discovery of other unknown bilaterian signaling peptides. Using large sequencing datasets, we searched for homologies between cone snail toxins and putative peptides from several important model organisms representing the snails prey. We identified five toxin families that share strong similarities with previously unknown signaling peptides from mollusks and annelids. One of the peptides was also identified in rotifers, brachiopods, platyhelminths, and arthropods, and another was found to be structurally related to crustacean hyperglycemic hormone, a peptide not previously known to exist in Spiralia. Based on several lines of evidence we propose that these signaling peptides not only exist but serve important physiological functions. Finally, we propose that the discovery pipeline developed here can be more broadly applied to other systems in which one organism has evolved molecules to manipulate the physiology of another.

evolutionary biology↗