| Summary: | In this study, we performed the genome-wide domain analysis and sequence alignment on the genome of <i>Styela clava</i>, and obtained a repertoire of 204 putative GPCRs, which exhibited a highly reduced gene number compared to vertebrates and cephalochordates. In this repertoire, six Class C GPCRs, including four metabotropic glutamate receptors (Sc-GRMs), one calcium-sensing receptor (Sc-CaSR), and one gamma-aminobutyric acid (GABA) type B receptor 2-like (Sc-GABA<sub>B</sub>R2-like) were identified, with the absence of type 1 taste and vomeronasal receptors. All the Sc-GRMs and Sc-CaSR contained the typical “Venus flytrap” and cysteine-rich domains required for ligand binding and subsequent propagation of conformational changes. In swimming larvae, <i>Sc-grm3</i> and <i>Sc-casr</i> were mainly expressed at the junction of the sensory vesicle and tail nerve cord while the transcripts of <i>Sc-grm4</i>, <i>Sc-grm7a</i>, and <i>Sc-grm7b</i> appeared at the anterior trunk, which suggested their important functions in neurotransmission. The high expression of these Class C receptors at tail-regression and metamorphic juvenile stages hinted at their potential involvement in regulating metamorphosis. In adults, the transcripts were highly expressed in several peripheral tissues, raising the possibility that <i>S. clava</i> Class C GPCRs might function as neurotransmission modulators peripherally after metamorphosis. Our study systematically characterized the ancestral chordate Class C GPCRs to provide insights into the origin and evolution of these receptors in chordates and their roles in regulating physiological and morphogenetic changes relevant to the development and environmental adaption.
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