Ancient Grandeur of the Vertebrate Neuropeptide Y System Shown by the Coelacanth Latimeria chalumnae

Abstract

The neuropeptide Y (NPY) family receptors and peptides have previously been characterized in several tetrapods, teleost fishes, and in a holocephalan cartilaginous fish. This has shown that the ancestral NPY system in the jawed vertebrates consisted of the peptides NPY and peptide YY (PYY) and seven G-protein-coupled receptors named Y1–Y8 (Y3 does not exist). The different vertebrate lineages have subsequently lost or gained a few receptor genes. For instance, the human genome has lost three of the seven receptors while the zebrafish has lost two and gained two receptor genes. Here we describe the NPY system of a representative of an early diverging lineage among the sarcopterygians, the West Indian Ocean coelacanth Latimeria chalumnae. The coelacanth was found to have retained all seven receptors from the ancestral jawed vertebrate. The receptors display the typical characteristics found in other vertebrates. Interestingly, the coelacanth was found to have the local duplicate of the PYY gene, called pancreatic polypeptide, previously only identified in tetrapods. Thus, this duplication took place very early in the sarcopterygian lineage, before the origin of tetrapods. These findings confirm the ancient complexity of the NPY system and show that mammals have lost more NPY receptors than any other vertebrate lineage. The coelacanth has all three peptides found in tetrapods and has retained the ancestral jawed vertebrate receptor repertoire with neither gains or losses.

Neuropeptide Y family receptors Y1 and Y2 from sea lamprey, Petromyzon marinus

“…Note that Y1 and Y5 are indeed located close to each other in the elephant shark as reported in the present study (see Fig. 4), like in the coelacanth Latimeria chalumnae (Larhammar and Bergqvist, 2013). Y1, Y2 and Y5 are syntenic in chicken as are Y6 and Y7, supporting the scenario shown (Bromee et al, 2006). we have found lamprey Y1.…”

“…Due to the uncertainty inherent in sequencebased phylogenetic analyses between lampreys and gnathostomes, we also compared synteny. Because the new lamprey gene is located close to Y5, like Y1 is in gnathostomes, we conclude that (Larsson et al, 2009;Larhammar and Bergqvist, 2013). Human Y6 is a pseudogene as indicated by orange color.…”

“…It was found to be located on the same scaffold as the ortholog of the Y5 sequence that we recently characterized in P. marinus (Xu et al, 2013) (see below). As only a single Y5 gene has been found in all vertebrate genomes so far analyzed (Larhammar and Bergqvist, 2013;Larsson et al, 2009), we assume that these are orthologous to each other. From this follows that the neighboring Y1-subfamily sequence located adjacently should be orthologous to Y1.…”

“…After the loss of some of the duplicates, seven NPY-family receptors remained ( Fig. 1) when the classes of gnathostomes began to diverge from one another, and all seven subtypes have been found in representatives for cartilaginous fishes (Larsson et al, 2009), lobe-finned fishes (Larhammar and Bergqvist, 2013) and ray-finned fishes (unpublished). These seven receptor subtypes can be grouped into three subfamilies based on their ancestry and sequence similarity: the Y1 subfamily (with members Y1, Y4, Y6, Y8), the Y2 subfamily (Y2, Y7) and the Y5 (alone) subfamily.…”

“…Later PP (pancreatic polypeptide) appeared in the early lobe-finned lineage as a copy of PYY (Larhammar and Bergqvist, 2013). Duplicates of both NPY and PYY arose in the teleost fish ancestor as a result of another tetraploidization named 3R (Jaillon et al, 2004) and these genes are therefore named NPYa, NPYb, PYYa and PYYb .…”