title: Origin of the prolactin-releasing hormone (PRLH) receptors: evidence of coevolution between PRLH and a redundant neuropeptide Y receptor during vertebrate evolution.
abstract: We present seven new vertebrate homologs of the prolactin-releasing hormone receptor (PRLHR) and show that these are found as two separate subtypes, PRLHR1 and PRLHR2. Analysis of a number of vertebrate sequences using phylogeny, pharmacology, and paralogon analysis indicates that the PRLHRs are likely to share a common ancestry with the neuropeptide Y (NPY) receptors. Moreover, a micromolar level of NPY was able to bind and inhibit completely the PRLH-evoked response in PRLHR1-expressing cells. We suggest that an ancestral PRLH peptide started coevolving with a redundant NPY binding receptor, which then became PRLHR, approximately 500 million years ago. The PRLHR1 subtype was shown to have a relatively high evolutionary rate compared to receptors with fixed peptide preference, which could indicate a drastic change in binding preference, thus supporting this hypothesis. This report suggests how gene duplication events can lead to novel peptide ligand/receptor interactions and hence spur the evolution of new physiological functions.
authors.affiliation: Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden.
authors.forename: Malin C
authors.initials: MC
authors.lastname: Lagerström
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.forename: Thóra K
authors.initials: TK
authors.lastname: Bjarnadóttir
authors.forename: Davids
authors.initials: D
authors.lastname: Fridmanis
authors.forename: Tomas
authors.initials: T
authors.lastname: Holmquist
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Yan
authors.forename: Terje
authors.initials: T
authors.lastname: Raudsepp
authors.forename: Rima
authors.initials: R
authors.lastname: Zoorob
authors.forename: Jyrki P
authors.initials: JP
authors.lastname: Kukkonen
authors.forename: Lars-Gustav
authors.initials: LG
authors.lastname: Lundin
authors.forename: Janis
authors.initials: J
authors.lastname: Klovins
authors.forename: Bhanu P
authors.initials: BP
authors.lastname: Chowdhary
authors.forename: John H
authors.initials: JH
authors.lastname: Postlethwait
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D017476:Receptors, Neuropeptide Y / Q000235:genetics*; D014714:Vertebrates
chemical_list: C487625:Prlhr protein, mouse; D043562:Receptors, G-Protein-Coupled; D017476:Receptors, Neuropeptide Y