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. 2022 Aug 8;6(10):1438–1448. doi: 10.1038/s41559-022-01835-7

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, Phylogenic relationships of animals related to this study and known peptidergic systems are shown at the top. Total ion chromatograms of endogenous peptide fractions of basal metazoans N. vectensis (Cnidaria), E. fluviatilis (Porifera) and B. mikado (Ctenophora) are shown below. b, Data processing workflow of mass spectrometry-based neuropeptide identification. c, Schematic representation of the primary structure of the B. mikado VWYamide peptide. The positions of fragmentations observed in the fragment spectrum are indicated. d, Fragment spectra of endogenous and synthetic VWYamide. e, Schematic representation of neuropeptide precursors of FGLa, VWYa (B. mikado), PRPa and VRHa (N. vectensis). Grey, red, green and yellow boxes indicate signal peptide, cleavage site, mature neuropeptide and glycine as amide donor, respectively. Triangles denote the putative cleavage sites of neprilysin endopeptidase. No neuropeptide was detected from E. fluviatilis. f, Sequence logo map of N-terminal and C-terminal flanking regions and AA compositions of the cleavage sites (boxed) of neuropeptides in Metazoa. Basic (K and R) and acidic (D and E) AAs are shown in blue and red, respectively. Illustrations of fly, sea anemone and sponge are from phylopic.org.