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


  • 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.

published proceedings

  • Genomics

altmetric score

  • 3

author list (cited authors)

  • Lagerstrm, M. C., Fredriksson, R., Bjarnadttir, T. K., Fridmanis, D., Holmquist, T., Andersson, J., ... Schith, H. B.

citation count

  • 40

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

publication date

  • January 2005