Origin of the prolactin-releasing hormone (PRLH) receptors: evidence of coevolution between PRLH and a redundant neuropeptide Y receptor during vertebrate evolution.
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.
Lagerström
Malin C
MC
Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden.
Fredriksson
Robert
R
Bjarnadóttir
Thóra K
TK
Fridmanis
Davids
D
Holmquist
Tomas
T
Andersson
Jan
J
Yan
Yi-Lin
YL
Raudsepp
Terje
T
Zoorob
Rima
R
Kukkonen
Jyrki P
JP
Lundin
Lars-Gustav
LG
Klovins
Janis
J
Chowdhary
Bhanu P
BP
Postlethwait
John H
JH
Schiöth
Helgi B
HB
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
C487625:Prlhr protein, mouse; D043562:Receptors, G-Protein-Coupled; D017476:Receptors, Neuropeptide Y