Living Systems Institute, University of Exeter, Exeter, United Kingdom.
Sars International Centre for Marine Molecular Biology, University of Bergen, Bergen, Norway.
Mol Biol Evol. 2021 Oct 27;38(11):4847-4866. doi: 10.1093/molbev/msab211.
Neuropeptides are diverse signaling 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 mollusks and annelids. Here, we analyze peptidergic systems in Nemertea, Brachiopoda, and Phoronida. We screened transcriptomes from 13 nemertean, 6 brachiopod, and 4 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 mollusk 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 mollusk APGWamides to RGWamides from annelids, with ortholog systems in nemerteans, brachiopods, and phoronids. We found that pleurin neuropeptides previously only found in mollusks 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 signaling, 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 signaling in spiralians and other protostomes. Our annotated data set of nearly 1,300 proneuropeptide sequences and 600 GPCRs presents a useful resource for further studies of neuropeptide signaling.
神经肽是动物中多样化的信号分子，通常通过 G 蛋白偶联受体 (GPCR) 发挥作用。神经肽及其受体在两侧对称动物中经历了广泛的多样化，许多肽-受体系统的关系已经得到阐明。然而，我们缺乏关于担轮动物神经肽进化的详细情况，因为只有深入研究软体动物和环节动物。在这里，我们分析了纽形动物、腕足动物和帚虫动物的肽能系统。我们从 13 种纽形动物、6 种腕足动物和 4 种帚虫动物的转录组中筛选出前神经肽和神经肽 GPCR。通过对纽形动物 Lineus longissimus 的质谱分析，我们验证了几个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描绘螺旋动物神经肽的进化。我们发现，大多数软体动物和环节动物的肽能系统也存在于纽形动物、腕足动物和帚虫动物中。我们揭示了以前隐藏的关系，包括螺旋动物 CCWamide 与节肢动物 agatoxin-like 肽的同源性，以及软体动物 APGWamide 与环节动物 RGWamide 的同源性，在纽形动物、腕足动物和帚虫动物中都有同源系统。我们发现以前只在软体动物中发现的 pleurin 神经肽也存在于纽形动物和腕足动物中。我们还发现了基因家族的复制和丢失的情况。其中包括 RFamide/Wamide 信号的原体特异性扩张，与 GnRH 相关肽的螺旋扩张，以及在腕足动物、帚虫动物和纽形动物分化之前血管加压素/催产素的复制。这项分析扩展了我们对螺旋动物和其他原体肽能信号的认识。我们近 1300 个前神经肽序列和 600 个 GPCR 的注释数据集为进一步研究神经肽信号提供了有用的资源。
