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Nucleic Acids Research, 2003, Vol. 31, No. 14 4051-4058
© 2003 Oxford University Press

The first completed genome sequence from a teleost fish (Fugu rubripes) adds significant diversity to the nuclear receptor superfamily

Jodi M. Maglich, Justin A. Caravella, Millard H. Lambert, Timothy M. Willson, John T. Moore* and Lakshman Ramamurthy1

Nuclear Receptor Discovery Research, 1 Bioinformatics, GlaxoSmithKline, Research Triangle Park, NC 27709, USA

*To whom correspondence should be addressed. Tel: +1 919 933 6916; Fax: +1 919 315 6720; Email: john.t.moore{at}gsk.com

Defining complete sets of gene family members from diverse species provides the foundation for comparative studies. Using a bioinformatic approach, we have defined the entire nuclear receptor complement within the first available complete sequence of a non-human vertebrate (the teleost fish Fugu rubripes). In contrast to the human set (48 total nuclear receptors), we found 68 nuclear receptors in the Fugu genome. All 68 Fugu receptors had a clear human homolog, thus defining no new nuclear receptor subgroups. A reciprocal analysis showed that each human receptor had one or more Fugu orthologs, excepting CAR (NR1I3) and LXRß (NR1H2). These 68 receptors add striking diversity to the known nuclear receptor superfamily and provide important comparators to human nuclear receptors. We have compared several pharmacologically relevant human nuclear receptors (FXR, LXR{alpha}/ß, CAR, PXR, VDR and PPAR{alpha}/{gamma}/{delta}) to their Fugu orthologs. This comparison included expression analysis across five Fugu tissue types. All of the Fugu receptors that were analyzed by PCR in this study were expressed, indicating that the majority of the additional Fugu receptors are likely to be functional.


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