A comparative genomics study of neuropeptide genes in the cnidarian subclasses Hexacorallia and Ceriantharia

Abstract

Background Nervous systems originated before the split of Proto- and Deuterostomia, more than 600 million years ago. Four animal phyla (Cnidaria, Placozoa, Ctenophora, Porifera) diverged before this split and studying these phyla could give us important information on the evolution of the nervous system. Here, we have annotated the neuropeptide preprohormone genes of twenty species belonging to the subclass Hexacorallia or Ceriantharia (Anthozoa: Cnidaria), using thirty-seven publicly accessible genome or transcriptome databases. Studying hexacorals is important, because they are versatile laboratory models for development (e.g., Nematostella vectensis) and symbiosis (e.g., Exaiptasia diaphana) and also are prominent reef-builders. Results We found that each hexacoral or ceriantharian species contains five to ten neuropeptide preprohormone genes. Many of these preprohormones contain multiple copies of immature neuropeptides, which can be up to 50 copies of identical or similar neuropeptide sequences. We also discovered preprohormones that only contained one neuropeptide sequence positioned directly after the signal sequence. Examples of them are neuropeptides that terminate with the sequence RWamide (the Antho-RWamides). Most neuropeptide sequences are N-terminally protected by pyroglutamyl (pQ) or one or more prolyl residues, while they are C-terminally protected by an amide group. Previously, we isolated and sequenced small neuropeptides from hexacorals that were N-terminally protected by an unusual L-3-phenyllactyl group. In our current analysis, we found that these N-phenyllactyl-peptides are derived from N-phenylalanyl-peptides located directly after the signal sequence of the preprohormone. The N-phenyllactyl- peptides appear to be confined to the hexacorallian order Actiniaria and do not occur in other cnidarians. On the other hand, (1) the neuropeptide Antho-RFamide (pQGRFamide); (2) peptides with the C-terminal sequence GLWamide; and (3) tetrapeptides with the X1PRX2amide consensus sequence (most frequently GPRGamide) are ubiquitous in Hexacorallia. Conclusions We found GRFamide, GLWamide, and X1PRX2amide peptides in all tested Hexacorallia. Previously, we discovered these three neuropeptide classes also in Cubozoa, Scyphozoa, and Staurozoa, indicating that these neuropeptides originated in the common cnidarian ancestor and are evolutionarily ancient. In addition to these ubiquitous neuropeptides, other neuropeptides appear to be confined to specific cnidarian orders or subclasses.

Leucokinins: Multifunctional Neuropeptides and Hormones in Insects and Other Invertebrates

“…It can be noted that an LK-like peptide sequence (Nlp43: KQFYAWAamide) has been identified in nematodes such as C. elegans [ 70 ] (see Figure 1 ), but it is not derived from a canonical LK precursor and no LKR could be found [ 3 , 15 ]. Furthermore, LK signaling components are not found in cnidarians (see [ 71 , 72 ]) or flatworms (Platyhelminthes) [ 73 ]. In lower bilaterians, such as species of Xenoturbella and Nemertodermatid worms (both phylum Xenacoelomorpha), orthologs of LK-type receptors were detected by bioinformatics, but no LK peptides [ 74 ].…”

The unique neuronal structure and neuropeptide repertoire in the ctenophore Mnemiopsis leidyi shed light on the evolution of animal nervous systems

“…We also predicted the processing of neuropeptide precursors at positively charged cleavage sites (mostly dibasic). However, it is possible that cleavage occurs at other sites too as reported in cnidarians 48 .…”

Nemertean, brachiopod and phoronid neuropeptidomics reveals ancestral spiralian signalling systems

“…As most protostome receptors in this expanded group are activated by peptides with C-terminal amidated aromatic amino acids and also the human GPR139 is activated by peptides, amino acids and other antagonists with aromatic rings, it is likely that the ancestral bilaterian GPCR was activated by peptides with C-terminal aromatic amino acids. RFamides and Wamide peptides are also present outside Bilateria, in Cnidaria and Placozoa (Walker, Papaioannou and Holden-Dye, 2009;Nikitin, 2015;Hayakawa et al ., 2019; Koch and Grimmelikhuijzen, 2019,2020; Williams, 2020). Such non-bilaterian RFamide/Wamide peptides may be orthologous to the whole protostome expansion, rather than to specific bilaterian peptides.…”