Evolution of neuropeptide signalling systems

Abstract

Neuropeptides are a diverse class of neuronal signalling molecules that regulate physiological processes and behaviour in animals. However, determining the relationships and evolutionary origins of the heterogeneous assemblage of neuropeptides identified in a range of phyla has presented a huge challenge for comparative physiologists. Here, we review revolutionary insights into the evolution of neuropeptide signalling that have been obtained recently through comparative analysis of genome/transcriptome sequence data and by 'deorphanisation' of neuropeptide receptors. The evolutionary origins of at least 30 neuropeptide signalling systems have been traced to the common ancestor of protostomes and deuterostomes. Furthermore, two rounds of genome duplication gave rise to an expanded repertoire of neuropeptide signalling systems in the vertebrate lineage, enabling neofunctionalisation and/or subfunctionalisation, but with lineage-specific gene loss and/or additional gene or genome duplications generating complex patterns in the phylogenetic distribution of paralogous neuropeptide signalling systems. We are entering a new era in neuropeptide research where it has become feasible to compare the physiological roles of orthologous and paralogous neuropeptides in a wide range of phyla. Moreover, the ambitious mission to reconstruct the evolution of neuropeptide function in the animal kingdom now represents a tangible challenge for the future.

Keywords: Evolution; Invertebrate; Neuropeptide; Phylogeny; Receptor; Vertebrate.

Fig. 1.

Animal phylogeny. Phylogenetic tree showing relationships of selected animal phyla. The Metazoa comprise non-bilaterian phyla and bilaterian phyla. The non-bilaterians include phyla that lack nervous systems (Porifera and Placozoa) and phyla that have nervous systems (Ctenophora and Cnidaria). The bilaterians comprise two super-phyla: the deuterostomes, which include vertebrates, and the protostomes, which include lophotrochozoans (e.g. the mollusc Aplysia californica) and ecdysozoans (e.g. the arthropod Drosophila melanogaster and the nematode Caenorhabditis elegans). Note that the branch lengths in the tree are arbitrary.

Fig. 2.

Phylogenetic analysis of bilaterian rhodopsin-type and secretin-type neuropeptide receptors. This figure is an updated version of a figure presented previously by Mirabeau and Joly (2013). Maximum-likelihood trees of bilaterian rhodopsin β-type (A), rhodopsin γ-type (B) and secretin-type (C) neuropeptide receptors are shown. The trees contain sub-trees comprising clusters of protostome (blue) and deuterostome (pink) groups of sequences. At the root of blue–pink sub-trees (shown as solid black circles), a prototypic receptor of each subtype was already present in the common ancestor of protostomes and deuterostomes. The bilaterian (b-), protostomian (p-), deuterostomian (d-), chordate (c-), lophotrochozoan (-l) or arthropod (a-) origin is indicated by an initial letter before each peptide GPCR acronym. Trissin receptors are shown with alternating pink and blue stripes because the receptors do not group together in distinct protostomian and deuterostomian clades. Bilaterian clusters where no receptor ligands had been identified by 2013, but which have been identified since 2013 are labelled with green lettering (i.e. elevenin and achatin). Likewise, the post-2013 identification of lophotrochozoan FMRFamide receptors as members of a clade of protostome-specific receptors that include short NPF receptors is also labelled with green lettering. The numbers assigned to each receptor clade correspond to the order in which they are presented in Fig. 3, which provides more-detailed information on the occurrence and characterisation of neuropeptide signalling systems in different taxa. In A, there is additional labelling (outer circle) of groups of receptors that are activated by neuropeptides that share similar characteristics or are derived from precursor proteins that have common characteristics. Photoreceptors and aminergic receptors were used as an outgroup for rhodopsin-β receptors (A), and human adhesion GPCRs were used as an outgroup for the secretin receptors (C).

Fig. 3.

Occurrence and characterisation of neuropeptide signalling pathways in bilaterians. This figure is an expanded and updated version of a figure presented previously by Mirabeau and Joly (2013). The occurrence of 30 bilaterian neuropeptide signalling systems in different taxa is shown, with deuterostomian phyla or sub-phyla (pink) shown on the left side, and protostomian phyla/classes shown on the right side (light blue). PS, peptidergic systems. Abbreviated names of neuropeptide signalling systems are used (see Table S1 for full names), which in some cases are the same in all taxa and in other cases can be different; for example, neuropeptide signalling system number 10 comprises neuropeptide-S in vertebrates, NG peptides in deuterostomian invertebrates and CCAP-type neuropeptides in protostomes, which are all ligands for orthologous NPS-, NG peptide- and CCAP-type receptors. A square half-filled with grey indicates that only the receptor of a neuropeptide-receptor signalling pathway has been identified in a taxonomic group. A full grey square indicates that both a peptide ligand and a receptor for a neuropeptide signalling pathway has been identified in a taxonomic group. A full green square indicates that, for at least one member of that taxonomic group, binding between a peptide and its receptor has been demonstrated experimentally. Inclusion of an asterisk in a green full square indicates that binding between a peptide and its receptor has been reported since publication of Mirabeau and Joly (2013). An empty (white) square indicates that a neuropeptide signalling pathway has been lost in a taxonomic group. Inclusion of the letter F in a grey square indicates that experimental insights into the physiological function(s) of the neuropeptide have been obtained. Details of publications that support the conclusions shown here are presented in Table S1.

Fig. 4.

Chordate phylogeny. Phylogenetic tree showing relationships of the major chordate lineages. The phylum Chordata comprises three sub-phyla: Cephalochordate, Urochordata and Vertebrata. The vertebrates are sub-divided into the jawless vertebrates (cyclostomes; lampreys and hagfish) and the jawed vertebrates, which are further sub-divided into chondrichthyes (cartilaginous fish) and osteichthyes (bony vertebrates). The bony vertebrates are sub-divided into the Actinopterygii (ray-finned fish) and Sarcopterygii (lobe-finned fish and tetrapods). 1R, 2R and 3R denote first, second and third rounds of genome duplication, respectively.

Fig. 5.

Impact of genome doublings on six neuropeptide signalling systems in vertebrates. (A–F) Gene duplications are shown for six peptide–GPCR systems, each including the deduced ancestral single chromosome and the deuterostome predecessor of the vertebrate lineage, followed by the predicted situation in the gnathostome ancestor after the two rounds of genome doubling (2R). Underneath these are two examples of extant species, the spotted gar Lepisosteus oculatus, a ray-finned fish representing a lineage that branched off before the teleosts underwent 3R, and Homo sapiens. As the NPY system (C) has not yet been reported for the spotted gar, the coelacanth Latimeria chalumnae is shown instead because it too has a genome that evolves slowly. Each box corresponds to a single gene. Boxes with crosses denote losses. Genes linked by a line are syntenic. However, there can be several other genes in-between; these have been omitted to highlight the similarities between chromosomes. The ψ symbol for NPY6R in human (C) marks that it has become a pseudogene. A dotted line in C connects the PP duplication in coelacanth and human to mark that this was a single event in their common ancestor. The opioid receptor named L1 in F is the nociceptin (orphanin) receptor, originally named L1 for ‘opioid-receptor-like’. For explanations of other abbreviations and for references, see descriptions in the main text.