The sea anemone Nematostella vectensis (Anthozoa, Cnidaria) is a powerful model for characterizing the evolution of genes functioning in venom and nervous systems. Although venom has evolved independently numerous times in animals, the evolutionary origin of many toxins remains unknown. In this work, we pinpoint an ancestral gene giving rise to a new toxin and functionally characterize both genes in the same species. Thus, we report a case of protein recruitment from the cnidarian nervous to venom system. The ShK-like1 peptide has a 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. Both peptides exhibit similarities in their functional activities: They 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 neuropeptide-encoding gene, followed by diversification and partial functional specialization. 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 venom component, five neuropeptides with two different cysteine motifs, and an evolutionary pathway from nervous to venom system in Cnidaria.

海葵Nematostella vectensis（Anthozoa，Cnidaria）是一个强大的模型，可表征在毒液和神经系统中起作用的基因的进化。尽管毒液已在动物中独立进化了许多次，但许多毒素的进化起源仍然未知。在这项工作中，我们查明了一个产生新毒素的祖先基因，并在功能上表征了同一物种中的两个基因。因此，我们报道了一例从中枢神经到毒液系统的蛋白质募集的案例。ShK-like1肽具有ShKT半胱氨酸基序，对鱼幼虫具有致死性，并被包装成线虫囊，即产生刺鼻毒液的刺痛胶囊。因此，ShK-like1是有毒的毒液成分。它的旁系同源蛋白ShK-like2是一种定位于神经元的神经肽，参与发育。两种肽在其功能活性上都表现出相似性：线虫的息肉对鱼类有毒。因为在整个海葵系统发育过程中，ShK-like2而不是ShK-like1是保守的，所以我们得出结论，这两个旁系同源物是由线虫产生的ShK样2祖先（一种神经肽编码基因）的基因特异复制，然后进行多样化和部分功能特化。ShK样2代表由两个基因的同工型，由替代启动子控制，在整个开发过程中赋予调节灵活性。此外，我们表征了与研究毒液成分具有结构相似性的其他四种肽的表达模式，并揭示了其意外的神经元定位。因此，我们采用基因组学，转录组学和功能方法来揭示一种毒液成分，五种具有两个不同半胱氨酸基序的神经肽以及一条从刺ni神经到毒液系统的进化途径。