6533b86ffe1ef96bd12cd239

RESEARCH PRODUCT

Origin of the prolactin-releasing hormone (PRLH) receptors: evidence of coevolution between PRLH and a redundant neuropeptide Y receptor during vertebrate evolution.

Yi-lin YanJohn H. PostlethwaitHelgi B. SchiöthDāvids FridmanisDavids FridmanisRima ZoorobBhanu P. ChowdharyMalin C. LagerströmRobert FredrikssonJanis KlovinsJanis KlovinsLars-gustav LundinJyrki P. KukkonenTomas HolmquistJan AnderssonThóra K. BjarnadóttirTerje Raudsepp

subject

Prolactin-releasing hormoneGeneticsBase SequenceMolecular Sequence DataBiologyNeuropeptide Y receptorProlactinReceptors G-Protein-CoupledReceptors Neuropeptide YEvolution MolecularPhylogeneticsMolecular evolutionHormone receptorGene DuplicationGene duplicationVertebratesGeneticsAnimalsHumansReceptorPhylogeny

description

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.

10.1016/j.ygeno.2005.02.007https://pubmed.ncbi.nlm.nih.gov/15885496