title: δ-Conotoxin SuVIA suggests an evolutionary link between ancestral predator defence and the origin of fish-hunting behaviour in carnivorous cone snails.
abstract: Some venomous cone snails feed on small fishes using an immobilizing combination of synergistic venom peptides that target Kv and Nav channels. As part of this envenomation strategy, δ-conotoxins are potent ichtyotoxins that enhance Nav channel function. δ-Conotoxins belong to an ancient and widely distributed gene superfamily, but any evolutionary link from ancestral worm-eating cone snails to modern piscivorous species has not been elucidated. Here, we report the discovery of SuVIA, a potent vertebrate-active δ-conotoxin characterized from a vermivorous cone snail (Conus suturatus). SuVIA is equipotent at hNaV1.3, hNaV1.4 and hNaV1.6 with EC50s in the low nanomolar range. SuVIA also increased peak hNaV1.7 current by approximately 75% and shifted the voltage-dependence of activation to more hyperpolarized potentials from -15 mV to -25 mV, with little effect on the voltage-dependence of inactivation. Interestingly, the proximal venom gland expression and pain-inducing effect of SuVIA in mammals suggest that δ-conotoxins in vermivorous cone snails play a defensive role against higher order vertebrates. We propose that δ-conotoxins originally evolved in ancestral vermivorous cones to defend against larger predators including fishes have been repurposed to facilitate a shift to piscivorous behaviour, suggesting an unexpected underlying mechanism for this remarkable evolutionary transition.
authors.affiliation: The Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Jin
authors.affiliation: The Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: Mathilde R
authors.initials: MR
authors.lastname: Israel
authors.affiliation: The Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia The School of Pharmacy, The University of Queensland, Woolloongabba, Queensland 4102, Australia.
authors.forename: Marco C
authors.initials: MC
authors.lastname: Inserra
authors.affiliation: The Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Smith
authors.affiliation: The Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lewis
authors.affiliation: The Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
authors.affiliation: The Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia The School of Pharmacy, The University of Queensland, Woolloongabba, Queensland 4102, Australia i.vetter@uq.edu.au.
authors.forename: Irina
authors.initials: I
authors.lastname: Vetter
authors.affiliation: The Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia Institut des Biomolécules Max Mousseron, UMR 5247, Université Montpellier - CNRS, Place Eugène Bataillon, Montpellier Cedex 5 34095, France sebastien.dutertre@univ-montp2.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dutertre
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D020916:Conotoxins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D052078:Conus Snail / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice / Q000502:physiology*; D008810:Mice, Inbred C57BL; D010146:Pain; D011235:Predatory Behavior; D016415:Sequence Alignment
chemical_list: D020916:Conotoxins
keywords: conotoxin; defence; molecular evolution; predation; venom