Neuropeptides are diverse signalling molecules in animals commonly acting through G-protein coupled receptors (GPCRs). Neuropeptides and their receptors underwent extensive diversification in bilaterians and the relationships of many peptide-receptor systems have been clarified. However, we lack a detailed picture of neuropeptide evolution in lophotrochozoans as in-depth studies only exist for molluscs and annelids. Here we analyse peptidergic systems in Nemertea, Brachiopoda and Phoronida. We screened transcriptomes from thirteen nemertean, six brachiopod and four phoronid species for proneuropeptides and neuropeptide GPCRs. With mass spectrometry from the nemertean Lineus longissimus, we validated several predicted peptides and identified novel ones. Molecular phylogeny combined with peptide-sequence and gene-structure comparisons allowed us to comprehensively map spiralian neuropeptide evolution. We found most mollusc and annelid peptidergic systems also in nemerteans, brachiopods and phoronids. We uncovered previously hidden relationships including the orthologies of spiralian CCWamides to arthropod agatoxin-like peptides and of mollusc APGWamides to RGWamides from annelids, with orthologues systems in nemerteans, brachiopods and phoronids. We found that pleurin neuropeptides previously only found in molluscs are also present in nemerteans and brachiopods. We also identified cases of gene family duplications and losses. These include a protostome-specific expansion of RFamide/Wamide signalling, a spiralian expansion of GnRH-related peptides, and duplications of vasopressin/oxytocin before the divergence of brachiopods, phoronids and nemerteans. This analysis expands our knowledge of peptidergic signalling in spiralians and protostomes. Our annotated dataset of nearly 1,300 proneuropeptide sequences and 600 GPCRs presents a useful resource for further studies of neuropeptide signalling in protostomes.

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Nemertean，腕足动物和类鱼体神经肽组学揭示了祖先的螺旋信号系统

神经肽是动物中的多种信号分子，通常通过G蛋白偶联受体（GPCR）发挥作用。神经肽及其受体在双语者中经历了广泛的多样化，并且许多肽-受体系统之间的关系已经阐明。但是，由于缺乏深入的研究，仅针对软体动物和肢体动物，我们缺乏在光子虫中神经肽进化的详细图片。在这里，我们分析了Nemertea，Brachiopoda和Phoronida中的肽能系统。我们从前十个nemertean，六个腕足动物和四个线虫种类的转录组中筛选了proneuropepteptes和neuropeptide GPCRs。通过对立长线虫的质谱进行质谱分析，我们验证了几种预测的肽并鉴定了新的肽。分子系统发育结合肽序列和基因结构比较使我们能够全面绘制螺旋神经肽的进化图。我们在nemerteans，腕足动物和披着类动物中也发现了大多数软体动物和类环肽的肽能系统。我们发现了以前隐藏的关系，包括螺旋形CCWamides与节肢动物类毒素毒素肽和软体动物APGWamides与拟南芥从拟南芥，腕足动物和线虫类的直系同源物的直系同源。我们发现以前仅在软体动物中发现的胸膜神经肽也存在于nemerteans和腕足动物中。我们还确定了基因家族重复和丢失的情况。这些措施包括RF酰胺/ Wamide信号转导的原蛋白质组特异性扩展，GnRH相关肽的螺旋扩展，和加压素/催产素的复制，然后再将腕足动物，类软骨动物和nemerteans分开。这项分析扩展了我们对螺旋虫和原虫中肽能信号传导的认识。我们带有注释的近1300个前神经肽序列和600个GPCR数据集为进一步研究原型记忆中的神经肽信号提供了有用的资源。