The first completed genome sequence from a teleost fish (Fugu rubripes) adds significant diversity to the nuclear receptor superfamily.
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 LXRbeta (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, LXRalpha/beta, CAR, PXR, VDR and PPARalpha/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.
Maglich
Jodi M
JM
Nuclear Receptor Discovery Research, Research Triangle Park, NC 27709, USA.
Caravella
Justin A
JA
Lambert
Millard H
MH
Willson
Timothy M
TM
Moore
John T
JT
Ramamurthy
Lakshman
L
D000595:Amino Acid Sequence; D000818:Animals; D000090702:Constitutive Androstane Receptor; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D016678:Genome; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D023741:Takifugu / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D000090702:Constitutive Androstane Receptor; C000716327:NR1I3 protein, human; C000716328:Nr1i3 protein, mouse; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors