From Neuropeptides to Toxins: Illuminating the Origins of Venom Complexity in Cone Snails
Thomas Lund Koch, Giada Ferrari, Sunita B Sumanam, Paula Flórez Salcedo, Maren Watkins, Kevin Chase, Ave Tooming-Klunderud, Arturo O Lluisma, Angel Yanagihara, Neil D Young, Baldomero M Olivera, Eivind A B Undheim, Helena Safavi-HemamiAbstract
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 ∼200 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.