Episodic evolution of prolactin receptor gene in mammals: coevolution with its ligand

Abstract

Divergence of proteins in signaling pathways requires ligand and receptor coevolution to maintain or improve binding affinity and/or specificity. In this paper we show a clear case of coevolution between the prolactin (PRL) gene and its receptor (prolactin receptor, PRLR) in mammals. First we observed episodic evolution of the extracellular and intracellular domains of the PRLR, which is closely consistent with that seen in PRL. Correlated evolution was demonstrated both between PRL and its receptor and between the two domains of the PRLR using Pearson's correlation coefficient. On comparing the ratio of the nonsynonymous substitution rate to synonymous substitution rate ( =d N /d S ) for each branch of the star phylogeny of mammalian PRLRs, separately for the extracellular domain (ECD) and the transmembrane domain/intracellular domain (TMD/ICD), we observed a lower ratio for ECD than TMD/ICD along those branches leading to pig, dog and rabbit but a higher ratio for ECD than TMD/ICD on the branches leading to primates, rodents and ruminants, on which bursts of rapid evolution were observed. These observations can be best explained by coevolution between PRL and its receptor and between the two domains of the PRLR.

A Residue Quartet in the Extracellular Domain of the Prolactin Receptor Selectively Controls Mitogen-activated Protein Kinase Signaling

“…Whether GHR Tyr-200 also specifically tunes MAPK signaling is unknown because the functional importance of this residue was revealed using a c-fos luciferase reporter construct that integrates both STAT5 and ERK1/2 signaling (40). With respect to the PRLR, it is noteworthy that three of the four residues constituting the quartet were fully conserved across evolution, whereas the regulatory position 170 harbors either a Phe (rat, mouse, cow, sheep, red deer, and possum) or a Leu (primates, pig, dog, and rabbit) (41). This raises the question of the potential physiological benefit of having intrinsically higher levels of ERK1/2 activation in some species versus others.…”

Cloning and expression of a unique short form of the porcine prolactin receptor

“…The PRL gene for primates, rodents, and ruminants/pigs diverged from each other at least 75 million years ago, while the pig PRL gene diverged from the ruminant PRL gene only 55 million years ago (Wallis 2000). The divergence in the PRLR is presumed to have occurred at the same time (Forsyth & Wallis 2002), given the co-evolution of PRL with its receptor (Li et al 2005). In fact, the phylogenetic tree comparing full-length PRLR-LF from birds, mammals, marsupials, and fish (Fig.…”

Natural selection and adaptive evolution of leptin

“…In contrast to other cytokines and their receptors, e.g., growth hormone (GH) and the growth hormone receptor (GHR) [119,120], and prolactin (PRL) and the prolactin receptor (PRLR) [121], the evolutionary pattern of leptin/receptor signaling system is still largely unknown. Some cytokines and their receptors have been shown to evolve in a coordinated manner [121], which is consistent with the ligand-receptor co-evolution hypothesis.…”