Toxin-like neuropeptides in the sea anemoneNematostellaunravel recruitment from the nervous system to venom

Abstract

The sea anemone Nematostella vectensis (Anthozoa, Cnidaria) is a powerful model system for characterizing the evolution of genes functioning in venom and nervous systems. Despite being an example for evolutionary novelty, the evolutionary origin of most toxins remains unknown.Here we report the first bona fide case of protein recruitment from the cnidarian nervous to venom system. The ShK-like1 peptide has ShKT cysteine motif, is lethal for fish larvae and packaged into nematocysts, the cnidarian venom-producing stinging capsules. Thus, ShK-like1 is a toxic venom component. Its paralog, ShK-like2, is a neuropeptide localized to neurons and is involved in development. Interestingly, both peptides exhibit similarities in their functional activities: both of them provoke contraction in Nematostella polyps and are toxic to fish. Because ShK-like2 but not ShK-like1 is conserved throughout sea anemone phylogeny, we conclude that the two paralogs originated due to a Nematostella-specific duplication of a ShK-like2 ancestor, a neuropeptideencoding gene, followed by diversification and partial functional specialization. Strikingly, ShK-like2 is represented by two gene isoforms controlled by alternative promoters conferring regulatory flexibility throughout development. Additionally, we characterized the expression patterns of four other peptides with structural similarities to studied venom components, and revealed their unexpected neuronal localization. Thus, we employed genomics, transcriptomics and functional approaches to reveal one new venom component, five neuropeptides with two different cysteine motifs and an evolutionary pathway from nervous to venom system in Cnidaria.

Insights into how development and life-history dynamics shape the evolution of venom

“…Interestingly, the homologous bilaterian SoxB genes are involved in neurogenesis as well [ 56 ], indicating that this role is conserved for hundreds of millions of years. Further, the existence of a common progenitor cell of neurons and cnidocytes in multiple cnidarians as well as the recent finding that nematocyte neurotoxins can be recruited from neurons in N. vectensis and possibly other cnidarians [ 57 ] support the notion that cnidocytes might be highly derived neurons [ 58 , 59 ].…”

Production, composition, and mode of action of the painful defensive venom produced by a limacodid caterpillar, Doratifera vulnerans

“…A prerequisite for this theory is the conservation of multiple groups of toxin-like polypeptides in the endogenous proteomes of nonvenomous animals. Signaling molecules such as neuropeptides, which are used by an animal to induce a change in its own physiology, are one class of suitable peptides from which the limacodid ACP-, ITP/CHH-, and DH 31 -like venom toxins have been recruited, similar to the recruitment of neurohormones into venoms of wasps, arachnids, sea anemones, and cone snails (39,(69)(70)(71). Another class are immune system peptides, which provide defense against pathogens and parasites, and from this class limacodids have recruited cecropinlike venom toxins and probably also ICK-and Diedel-like toxins.…”

Editorial: The Evolution of Neuropeptides - a Stroll Through the Animal Kingdom: Updates From the Ottawa 2019 ICCPB Symposium and Beyond

“…The authors note that a subset of protostome tachykinins have been recruited for use in venom or salivary glands to affect prey. This interesting evolutionary path of neuropeptide recruitment for novel toxins is also recently revealed in Nematostella vectensis through discovery of an ShK-like venom component, which causes muscle contractions in Nematostella but is toxic to fish larvae (1).…”