Cone Snail Broad-Transcriptomics Elucidate the Evolutionary Diversification and Anti-Microbial Potential of Conopeptides

Conus venoms are both highly powerful and complex, exhibiting a remarkably intriguing molecular variability. The biologic reasons behind such astonishing molecular diversity are yet to be fully understood. We hypothesized that the current knowledge has been hampered by a lack of studies targeting the whole Conus genus backed by a feeding habit analysis, as opposed to the abundant studies focused on single species or at the individual level. We aim to enlighten the understanding of the remarkable venom variability in cone snails while pushing to deliver novel peptides for biomedical applications through a broad transcriptomics approach. Here, we assessed 76 publicly available venom-related and unrelated transcriptomes from a total of 20 different Conus species. The shared transcriptomic repertoire revealed several gene variations in accordance with predatory diets (e.g., gene loss in piscivorous species), indicating that feeding habit largely influences venom evolution. Furthermore, evidences of ubiquitous symbiotic relationships within the venom organs were depicted, as biological processes alien to Conus species (e.g., Sorocarp morphogenesis) were found in all analyzed transcriptomes. Moreover, 88 potential anti-microbial peptides were bioinformatically detected, including one showing similarity with the human ACE2 receptor. Our study highlights the importance of in-depth comparative transcriptomic analyses, fostering cross-field synergic assessments by relying on informatic, biologic, and pharmacologic resources.