Occurrence of Two Distinct Urotensin II-Related Peptides in Zebrafish Provides New Insight into the Evolutionary History of the Urotensin II Gene Family

Abstract

The urotensin II (UII) family is currently known to consist of two paralogous peptides, namely UII and UII-related peptide (URP). In contrast to UII, which has been identified in all vertebrate classes so far, URP has only been characterized in tetrapods. We report here the occurrence of two distinct URP genes in teleosts, which we have named URP1 and URP2. Synteny analysis revealed that teleost URP1 and URP2 genes and tetrapod URP genes represent three distinct paralog genes that, together with the UII gene, probably arose from the two rounds of tetraploidization, which took place early in vertebrate evolution. The absence of URP in fish indicates that the corresponding gene has been lost in the teleost lineage, whereas it is likely that both the URP1 and URP2 genes have been lost in the tetrapod lineage. Quantitative RT-PCR analysis revealed that the URP2 gene is mainly expressed in the spinal cord and the brain in adult zebrafish. In situ hybridization experiments showed that in zebrafish embryos, URP2 mRNA-containing cells are located in the floor plate of the neural tube. In adult, URP2-expressing cells occur in close contact with the ventral side of the ependymal canal along the whole spinal cord, whereas in the brain, they are located below the fourth ventricle. These URP-expressing cells may correspond to cerebrospinal fluid-contacting neurons. In conclusion, our study reveals the occurrence of four distinct UII paralogous systems in vertebrates that may exert distinct functions, both in tetrapods and teleosts.

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

“…The URP1 gene was initially considered to be the teleost counterpart of the URP gene previously identified in tetrapods (Nobata et al 2011), but this view was invalidated when it appeared that several teleost species possess both the URP and the URP1 genes (Quan et al 2012). An ortholog of the URP1 gene has also been found in a chondrichthyan, the elephant shark (Callorhinchus milii; Parmentier et al 2011), in a non-teleost actinopterygian fish, the spotted gar (Lepisosteus oculatus; , and in coelacanth (Latimeria chalumnae), a representative of an early diverging lineage among the sarcopterygians . In contrast, it could not be found in tetrapod genomes.…”

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

“…As mentioned above (see section II.J), two additional paralogous genes of the UII family have been characterized in actinopterygians and sarcopterygians and have been called URP1 and URP2 (Nobata et al, 2011;Tostivint et al, 2013Tostivint et al, , 2014. In zebrafish, both URP1 and URP2 genes contain five exons and, for each gene, the coding sequence of the mature peptide is located on the last exon (Parmentier et al, 2011).…”

“…A blast search revealed the occurrence of the same peptide, now called URP1, in several other teleost species including the Brook trout, the Atlantic salmon, and the zebrafish. However, it also appeared that teleosts possess a second URP-like peptide named URP2 (Nobata et al, 2011;Parmentier et al, 2011). Recently, the URP1 and URP2 genes were also identified in the spotted gar, a nonteleost ray finned fish .…”

“…It has thus been hypothesized that the URP1 and URP2 genes were two co-orthologs of the tetrapod URP gene, in very much the same manner as the zebrafish and sucker UIIa (also called UIIA) and UIIb (also called UIIB) genes (Nobata et al, 2011), which are the two counterparts of the tetrapod UII gene. However, this view was recently invalidated by synteny analysis (Parmentier et al, 2011). Using this approach, it was found that the URP1 and URP2 genes, although present only in fish, emerged long before the tetrapod/fish split and thus represent two distinct paralogous genes, in addition to the UII and URP genes.…”

“…In contrast, the expression patterns of the URP1 and URP2 genes differ markedly from that of the URP gene. Although most URP1-and URP2-expressing cells are found in the spinal cord, these cells are located in close contact with the ventral aspect of the central canal (Parmentier et al, 2011;unpublished data). URP1 and URP2 mRNAs colocalize in the same cells that also express the glutamate decarboxylase gene, identifying them as Urotensin II and Its Receptor CSF-contacting neurons (Vigh and Vigh-Teichmann, 1998).…”