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

Malin C. Lagerström, Robert Fredriksson, Thóra K. Bjarnadóttir, Davids Fridmanis, Tomas Holmquist, Jan Andersson, Yi Lin Yan, Terje Raudsepp, Rima Zoorob, Jyrki P. Kukkonen, Lars Gustav Lundin, Janis Klovins, Bhanu P. Chowdhary, John H. Postlethwait, Helgi B. Schiöth

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)688-703
Number of pages16
JournalGenomics
Volume85
Issue number6
DOIs
Publication statusPublished - Jun 2005
Externally publishedYes

Keywords

  • Binding
  • Cloning
  • Coevolution
  • Evolution
  • Hormone
  • Neuropeptide Y
  • PRLHR
  • Pharmacology
  • Prolactin
  • prrp

ASJC Scopus subject areas

  • Genetics

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