Origin of the prolactin-releasing hormone (PRLH) receptors: evidence of coevolution between PRLH and a redundant neuropeptide Y receptor during vertebrate evolution.
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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.
author list (cited authors)
Lagerstrm, M. C., Fredriksson, R., Bjarnadttir, T. K., Fridmanis, D., Holmquist, T., Andersson, J., ... Schith, H. B.
complete list of authors
Lagerström, Malin C||Fredriksson, Robert||Bjarnadóttir, Thóra K||Fridmanis, Davids||Holmquist, Tomas||Andersson, Jan||Yan, Yi-Lin||Raudsepp, Terje||Zoorob, Rima||Kukkonen, Jyrki P||Lundin, Lars-Gustav||Klovins, Janis||Chowdhary, Bhanu P||Postlethwait, John H||Schiöth, Helgi B