Minireview Hormones and receptors in fish: Do duplicates matter? Graeme J. Roch, Sheng Wu, Nancy M. Sherwood * Department of Biology, University of Victoria, Victoria, BC, Canada V8W 3N5 article info Article history: Received 12 August 2008 Revised 26 September 2008 Accepted 6 October 2008 Available online 1 November 2008 Keywords: Whole genome duplication Gene duplicates Secretin superfamily Hormones Family B receptors 7TM receptors PACAP GHRH-LP PRP VIP PHI Glucagon GLP-1 GLP-2 GHRH GIP Teleost fish Zebrafish Fugu Medaka Stickleback Salmonids Rainbow trout abstract Modern fish are the result of major changes in evolution including three possible duplications of the whole genome. Retained duplicate genes are often involved with metabolism, transcription, neurogenic processes and development. Here we examine the consequences of the most recent (350 mya) teleost- specific duplication in five fishes (zebrafish, fugu, medaka, stickleback and rainbow trout) in regard to duplicate copies of hormones and receptors in the secretin superfamily. This subset of genes was selected as the superfamily is limited to ten hormones and their receptors and includes some important members: glucagon, growth hormone-releasing hormone (GHRH), pituitary adenylate cyclase-activating polypep- tide (PACAP) and vasoactive intestinal polypeptide (VIP). We used reports from the literature and an extensive database search of the fish genomes to evaluate the status of the superfamily and its duplicate genes. We found that all five fish species have an almost complete set of orthologs with the human super- family of hormones, although they lack secretin and its receptor. Receptor orthologs are present in zebra- fish, fugu, medaka, stickleback and to a lesser extent in salmonids. Zebrafish retain duplicate copies for seven hormones and five receptors. Duplicated genes in fugu, medaka, stickleback and salmonids are also present, based mainly on genome annotation or mRNA transcription. Separate chromosome locations and synteny support zebrafish duplicates as the result of large-scale duplications. Novel changes in fish include the modification of a duplicate glucagon receptor to a GLP-1 receptor and, unlike humans, the presence of bioactive and specific PHI and GHRH-like peptide receptors. We conclude that fish duplicates in the secretin superfamily are a rich, mostly unexplored area for endocrine research. Ó 2008 Elsevier Inc. All rights reserved. 1. Introduction Genomes for several species of fishes are now available mak- ing it possible to consider new questions about the existence and function of duplicate copies of hormones and receptors. The current hypothesis is that the whole genome underwent two sequential rounds (1R and 2R) of duplication in the vertebrate stem well before the divergence of ray-finned and lobe-finned fishes (Ohno, 1970; Sidow, 1996; Holland, 1999; Hufton et al., 2008). Retained genes were potentially quadrupled (Furlong and Holland, 2002). Evidence suggests another round (3R) of whole genome duplication occurred near the origin of teleost fish or about 350 million years ago (Amores et al., 1998; Taylor et al., 2001; Hufton et al., 2008). The elapsed time since the fish-specific duplication is sufficient for various alternatives to have occurred for the duplicate genes. One gene copy may have been lost or silenced. However, if both copies of the duplicated gene survive in a functional state, one of the duplicates could evolve a novel function (neo-functionalization) or the duplicates could partition the ancestral functions between the two copies due to different mutations in their coding or regulatory regions (sub-functionali- zation) (Force et al., 1999; Lynch and Conery, 2000). Even silenc- ing may have an unexpected role in biodiversity. An argument has been presented that silencing of different copies of duplicate genes in geographically isolated populations could reduce the production of viable second generation offspring (double null mutations) if the two isolated populations are reintroduced. Two species could be created leading to species diversification (Lynch and Force, 2000). 0016-6480/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.ygcen.2008.10.017 * Corresponding author. Fax: +1 250 721 7120. E-mail address: nsherwoo@uvic.ca (N.M. Sherwood). General and Comparative Endocrinology 161 (2009) 3–12 Contents lists available at ScienceDirect General and Comparative Endocrinology journal homepage: www.elsevier.com/locate/ygcen