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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0034v1 201/3/329    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gorissen, M. Articles by Huising, M. Search for Related Content PubMed PubMed Citation Articles by Gorissen, M. Articles by Huising, M.

M Gorissen, Organismal Animal Physiology, Radboud University Nijmegen, Nijmegen, Netherlands
N Bernier, Department of Integrative Biology, University of Guelph, Guelph, Ontario, Canada
S Nabuurs, Dept. of Molecular design and informatics, Organon NV, Oss, Netherlands
G Flik, Organismal Animal Physiology, Radboud University Nijmegen, Nijmegen, Netherlands
M Huising, Organismal Animal Physiology, Radboud University Nijmegen, Nijmegen, Netherlands

Correspondence: Marnix Gorissen, Email: M.Gorissen{at}science.ru.nl

Abstract

We describe duplicate leptin genes in zebrafish (Danio rerio) that share merely 24% amino acid identity with each other and only 18% with human leptin. We were also able to retrieve a second leptin gene in medaka (Oryzias latipes). The presence of duplicate leptin genes in these two distantly related teleosts suggests that duplicate leptin genes are a common feature of teleostean fishes. Despite low primary sequence conservation, we are confident in assigning orthology between mammalian and zebrafish leptins for several reasons. Firstly, both zebrafish leptins share their characteristic gene structure and display key features of conserved synteny with mammalian leptin genes. Secondly, the cysteine residues that make up leptin’s single disulphide bridge are equally spaced in mammals and zebrafish leptins and are unique among all members of the class-I helical cytokine family. Thirdly, the zebrafish leptins cluster with other fish leptins and mammalian leptins in phylogenetic analysis, supported by high bootstrap values. Within the leptin cluster, leptin-b forms a separate clade with the leptin-b orthologue from medaka. Finally, our prediction of the tertiary structures shows that both leptins conform to the typical four -helix bundle structure of the class-I -helical cytokines. The zebrafish leptins are differentially expressed; the liver shows high leptin-a expression (in concordance with what we observed for carp leptins), while leptin-b is expressed at much lower levels, which are downregulated further upon fasting. The finding of duplicate leptin genes in teleosts adds to our understanding of the evolution of leptin physiology in the early vertebrate lineage.