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

Abstract

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.

Ligand specificity and evolution of liver X receptors

“…Pufferfish LXR is more closely related to mammalian LXRα genes by sequence similarity, although the pattern of tissue expression more closely resembles mammalian LXRβ genes in the ubiquity of expression, including expression in brain, gill, gut, heart, ovary, and liver [9]. The current sequence data suggests that a single LXR gene duplicated before mammalian evolution or early in mammalian evolution [9].…”

“…LXRα is typically detected at high levels in macrophages, adipose tissues, kidney, lung, and spleen; in contrast, LXRβ is expressed at similar levels in a wide variety of tissues, the basis for an alternative name for this receptor as 'ubiquitous receptor' [8]. Based on the sequenced genomes of chicken, pufferfish (fugu; Takifugu rubripes) [9], freshwater pufferfish (Tetraodon nigroviridis), zebrafish (Danio rerio), and Western clawed frog (Silurana or Xenopus tropicalis), non-mammalian species appear to generally have only a single LXR gene.…”

“…For non-mammalian species, the pufferfish LXR has been the subject of the most detailed study [9]. Pufferfish LXR is more closely related to mammalian LXRα genes by sequence similarity, although the pattern of tissue expression more closely resembles mammalian LXRβ genes in the ubiquity of expression, including expression in brain, gill, gut, heart, ovary, and liver [9].…”

“…Pufferfish LXR is more closely related to mammalian LXRα genes by sequence similarity, although the pattern of tissue expression more closely resembles mammalian LXRβ genes in the ubiquity of expression, including expression in brain, gill, gut, heart, ovary, and liver [9]. The current sequence data suggests that a single LXR gene duplicated before mammalian evolution or early in mammalian evolution [9]. If this hypothesis is correct, then one of the duplicated genes maintained ubiquitous tissue expression (LXRβ) while the other (LXRα) carried out specific roles in cholesterol and lipid metabolism with more restricted expression in adipose tissue, liver, and macrophages.…”

Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR

“…Foremost, the two xenosensors, PXR and CAR have only been found in mammals whereas other vertebrate genomes including fish or chicken encode only one xenosensor [28,149,150]. Similarly, only one xenobiotic-sensing nuclear receptor has been found in the C. elegans genome [151].…”