title: Evolutionary origin of GnIH and NPFF in chordates: insights from novel amphioxus RFamide peptides.
abstract: Gonadotropin-inhibitory hormone (GnIH) is a newly identified hypothalamic neuropeptide that inhibits pituitary hormone secretion in vertebrates. GnIH has an LPXRFamide (X = L or Q) motif at the C-terminal in representative species of gnathostomes. On the other hand, neuropeptide FF (NPFF), a neuropeptide characterized as a pain-modulatory neuropeptide, in vertebrates has a PQRFamide motif similar to the C-terminal of GnIH, suggesting that GnIH and NPFF have diverged from a common ancestor. Because GnIH and NPFF belong to the RFamide peptide family in vertebrates, protochordate RFamide peptides may provide important insights into the evolutionary origin of GnIH and NPFF. In this study, we identified a novel gene encoding RFamide peptides and two genes of their putative receptors in the amphioxus Branchiostoma japonicum. Molecular phylogenetic analysis and synteny analysis indicated that these genes are closely related to the genes of GnIH and NPFF and their receptors of vertebrates. We further identified mature RFamide peptides and their receptors in protochordates. The identified amphioxus RFamide peptides inhibited forskolin induced cAMP signaling in the COS-7 cells with one of the identified amphioxus RFamide peptide receptors expressed. These results indicate that the identified protochordate RFamide peptide gene is a common ancestral form of GnIH and NPFF genes, suggesting that the origin of GnIH and NPFF may date back to the time of the emergence of early chordates. GnIH gene and NPFF gene may have diverged by whole-genome duplication in the course of vertebrate evolution.
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda University, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Osugi
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda University, Tokyo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda University, Tokyo, Japan.
authors.forename: You Lee
authors.initials: YL
authors.lastname: Son
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda University, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohkubo
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda University, Tokyo, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ubuka
authors.affiliation: Aitsu Marine Station, Center for Marine Environmental Studies, Kumamoto University, Kumamoto, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Henmi
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda University, Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Tsutsui
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D019143:Evolution, Molecular; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D064175:Lancelets / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny
chemical_list: D006023:Glycoproteins; D009479:Neuropeptides; C416987:RFamide peptide; C014995:gonadotropin inhibitor