Phylogenetic analysis of bilaterian rhodopsin β-type (A) and rhodopsin γ-type (B) receptors. The red arcs highlight four groups that include receptors that are known to be activated by RFamide-type peptides. These include a large group of receptors for QRFP (pyroglutamylated RFamide peptide), SIFa (SIFamide), NPFF (Neuropeptide FF and Gonadotropin-inhibitory hormone), PrRP (Prolactin-releasing peptide), NPY/NPF (Neuropeptide Y/F), sNPF (short Neuropeptide F), and Luqin, and two isolated groups of RFamide-type receptors, CCK/SK (Cholecystokinin/Sulfakinin), and Kiss1 (Kisspeptin) receptors. In (A) rhodopsin α-type receptors (photoreceptors and aminergic receptors) are included as an outgroup. The prefixes b-, d-, p- designate subgroups of, respectively, bilaterian, deuterostomian, and protostomian receptors. Deuterostomian and protostomian clades have been colored in pink and blue, respectively. Gray sections of the trees correspond to groups of receptors for which either only deuterostomian or protostomian ligands are known. The fact that most of the rhodopsin β-type RFamide receptors fall in the same region of the tree suggests that these probably originated from a common ancestral RFamide-type neuropeptide signaling system. However, the occurrence of other groups of receptors that are activated by RFamides (CCK, Kiss1) indicates that RFamide-type neuropeptides have evolved independently at least three times in bilaterian history. Figure adapted from Ref. (8).