The Evolution and Variety of RFamide-Type Neuropeptides: Insights from Deuterostomian Invertebrates

Abstract

Five families of neuropeptides that have a C-terminal RFamide motif have been identified in vertebrates: (1) gonadotropin-inhibitory hormone (GnIH), (2) neuropeptide FF (NPFF), (3) pyroglutamylated RFamide peptide (QRFP), (4) prolactin-releasing peptide (PrRP), and (5) Kisspeptin. Experimental demonstration of neuropeptide–receptor pairings combined with comprehensive analysis of genomic and/or transcriptomic sequence data indicate that, with the exception of the deuterostomian PrRP system, the evolutionary origins of these neuropeptides can be traced back to the common ancestor of bilaterians. Here, we review the occurrence of homologs of vertebrate RFamide-type neuropeptides and their receptors in deuterostomian invertebrates – urochordates, cephalochordates, hemichordates, and echinoderms. Extending analysis of the occurrence of the RFamide motif in other bilaterian neuropeptide families reveals RFamide-type peptides that have acquired modified C-terminal characteristics in the vertebrate lineage (e.g., NPY/NPF), neuropeptide families where the RFamide motif is unique to protostomian members (e.g., CCK/sulfakinins), and RFamide-type peptides that have been lost in the vertebrate lineage (e.g., luqins). Furthermore, the RFamide motif is also a feature of neuropeptide families with a more restricted phylogenetic distribution (e.g., the prototypical FMRFamide-related neuropeptides in protostomes). Thus, the RFamide motif is both an ancient and a convergent feature of neuropeptides, with conservation, acquisition, or loss of this motif occurring in different branches of the animal kingdom.

Demonstration of a Functional Kisspeptin/Kisspeptin Receptor System in Amphioxus With Implications for Origin of Neuroendocrine Regulation

“…Sixteen putative Kissr-like genes were reported in amphioxus B. floridae (38,40). However, we identified 27 putative gpr54-like genes by extensive BLAST survey.…”

“…Four putative kisspeptin-like genes have been reported in amphioxus B. floridae (38,40). One of the genes encoded three putative peptides whereas other genes encoded one peptide (38).…”

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

“…Unfortunately, the genomes of a number of important species such as coelacanth, a basal tetrapod (Amemiya et al ., 2010); elephant shark, the slowest known evolving vertebrate (Venkatesh et al ., 2014); and Branchiostoma floridae , a basal chordate and a useful outgroup for vertebrate analysis (Elphick and Mirabeau, 2014), have not yet been arranged into chromosomes and instead are available as short DNA sequences on scaffolds which diminishes their use for synteny analysis. Other species such as lamprey or hagfish, which could provide important perspectives on inter-2R genome evolution (Caputo Barucchi et al ., 2013; Mehta et al ., 2013), and Asymmetron lucayanum , which may be the most basal chordate discovered (Yue et al ., 2014), have only partial genomes available.…”

In the picture: disulfide-poor conopeptides, a class of pharmacologically interesting compounds

“…The RFamide motif appears to be both an ancient and a convergent feature of neuropeptide evolutions [51]. …”