title: Evolutionary origin and divergence of PQRFamide peptides and LPXRFamide peptides in the RFamide peptide family. Insights from novel lamprey RFamide peptides.
abstract: Among the RFamide peptide groups, PQRFamide peptides, such as neuropeptide FF (NPFF) and neuropeptide AF (NPAF), share a common C-terminal Pro-Gln-Arg-Phe-NH(2) motif. LPXRFamide (X = L or Q) peptides, such as gonadotropin-inhibitory hormone (GnIH), frog growth hormone-releasing peptide (fGRP), goldfish LPXRFamide peptide and mammalian RFamide-related peptides (RFRPs), also share a C-terminal Leu-Pro-Leu/Gln-Arg-Phe-NH(2) motif. Such a similar C-terminal structure suggests that these two groups may have diverged from a common ancestral gene. In this study, we sought to clarify the evolutionary origin and divergence of these two groups, by identifying novel RFamide peptides from the brain of sea lamprey, one of only two extant groups of the oldest lineage of vertebrates, Agnatha. A novel lamprey RFamide peptide was identified by immunoaffinity purification using the antiserum against LPXRFamide peptide. The lamprey RFamide peptide did not contain a C-terminal LPXRFamide motif, but had the sequence SWGAPAEKFWMRAMPQRFamide (lamprey PQRFa). A cDNA of the precursor encoded one lamprey PQRFa and two related peptides. These related peptides, which also had the C-terminal PQRFamide motif, were further identified as mature endogenous ligands. Phylogenetic analysis revealed that lamprey PQRFamide peptide precursor belongs to the PQRFamide peptide group. In situ hybridization demonstrated that lamprey PQRFamide peptide mRNA is expressed in the regions predicted to be involved in neuroendocrine and behavioral functions. This is the first demonstration of the presence of RFamide peptides in the agnathan brain. Lamprey PQRFamide peptides are considered to have retained the most ancestral features of PQRFamide peptides.
authors.affiliation: Laboratory of Brain Science, Faculty of Integrated Arts and Sciences, Hiroshima University, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Osugi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ukena
authors.forename: Stacia A
authors.initials: SA
authors.lastname: Sower
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawauchi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Tsutsui
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D014644:Genetic Variation; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009292:Narcotic Antagonists / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D009490:Neurosecretory Systems / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D048428:Petromyzon / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D009292:Narcotic Antagonists; D009479:Neuropeptides; D009842:Oligopeptides; C416987:RFamide peptide; D012333:RNA, Messenger; C042219:leucyl-prolyl-leucyl-arginyl-phenylalaninamide; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide