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

Abstract 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 doppelgänger 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 Summary Doppelgänger toxins reveal how modular gene architecture, including 5’UTR reuse and TE-driven recombination, fuels gene innovation in cone snails. Competing Interest Statement The authors have declared no competing interest.