Evolutionary Origin of GnIH and NPFF in Chordates: Insights from Novel Amphioxus RFamide Peptides

Abstract

Gonadotropin-inhibitory hormone (GnIH) is a newly identified hypothalamic neuropeptide that inhibits pituitary hormone secretion in vertebrates. GnIH has an LPXRFamide (X = L or Q) motif at the C-terminal in representative species of gnathostomes. On the other hand, neuropeptide FF (NPFF), a neuropeptide characterized as a pain-modulatory neuropeptide, in vertebrates has a PQRFamide motif similar to the C-terminal of GnIH, suggesting that GnIH and NPFF have diverged from a common ancestor. Because GnIH and NPFF belong to the RFamide peptide family in vertebrates, protochordate RFamide peptides may provide important insights into the evolutionary origin of GnIH and NPFF. In this study, we identified a novel gene encoding RFamide peptides and two genes of their putative receptors in the amphioxus Branchiostoma japonicum. Molecular phylogenetic analysis and synteny analysis indicated that these genes are closely related to the genes of GnIH and NPFF and their receptors of vertebrates. We further identified mature RFamide peptides and their receptors in protochordates. The identified amphioxus RFamide peptides inhibited forskolin induced cAMP signaling in the COS-7 cells with one of the identified amphioxus RFamide peptide receptors expressed. These results indicate that the identified protochordate RFamide peptide gene is a common ancestral form of GnIH and NPFF genes, suggesting that the origin of GnIH and NPFF may date back to the time of the emergence of early chordates. GnIH gene and NPFF gene may have diverged by whole-genome duplication in the course of vertebrate evolution.

Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone

“…These three mature peptides were identified in lamprey by immunoaffinity purification and mass spectrometry (Table 1). Osugi et al (2014) further searched for an orthologous LPXRFamide peptide precursor gene and mature peptides in amphioxus, one of the most basal chordates (protochordates), to investigate the evolutionary origin of LPXRFamide peptides. An orthologous LPXRFamide peptide precursor genes was identified in amphioxus.…”

GnIH Control of Feeding and Reproductive Behaviors

“…To demonstrate this hypothesis, Tsutsui and colleagues further cloned a precursor cDNA of PQRFamide peptide, which encodes three putative PQRFamide peptides in amphioxus (67). Mature forms of these three endogenous amphioxus PQRFamide peptides were identified by immunoaffinity purification as well as mass spectrometry (67) (Table 2).…”

“…Mature forms of these three endogenous amphioxus PQRFamide peptides were identified by immunoaffinity purification as well as mass spectrometry (67) (Table 2). Phylogenetic analysis suggested that the amphioxus PQRFamide peptide precursor occurred before the divergence of GnIH and NPFF groups in vertebrates (67).…”

Review: evolution of GnIH and related peptides structure and function in the chordates

“…Within these groups, GnIH and NPFF, and Kiss1 and Kiss2 are thought to be paralogous (Felip et al, 2009; Lee et al, 2009; Osugi et al, 2012, 2013, 2014; Pasquier et al, 2012). It is of interest to investigate the evolutionary relationship between RF-amide peptide groups, and search the common origin of these RF-amide peptides.…”

“…Recently we further identified the ancestral form of GnIH in amphioxus, the most basal chordates (Osugi et al, 2014). These studies suggest that the origin of GnIH-like peptides may date back to the time of the emergence of early chordates.…”