| RRC ID |
15504
|
| 著者 |
Howarth DL, Law SH, Barnes B, Hall JM, Hinton DE, Moore L, Maglich JM, Moore JT, Kullman SW.
|
| タイトル |
Paralogous vitamin D receptors in teleosts: transition of nuclear receptor function.
|
| ジャーナル |
Endocrinology
|
| Abstract |
The availability of multiple teleost (bony fish) genomes is providing unprecedented opportunities to understand the diversity and function of gene duplication events using comparative genomics. Here we describe the cloning and functional characterization of two novel vitamin D receptor (VDR) paralogs from the freshwater teleost medaka (Oryzias latipes). VDR sequences were identified through mining of the medaka genome database in which gene organization and structure was determined. Two distinct VDR genes were identified in the medaka genome and mapped to defined loci. Each VDR sequence exhibits unique intronic organization and dissimilar 5' untranslated regions, suggesting they are not isoforms of the same gene locus. Phylogenetic comparison with additional teleosts and mammalian VDR sequences illustrate that two distinct clusters are formed separating aquatic and terrestrial species. Nested within the teleost cluster are two separate clades for VDRalpha and VDRbeta. The topology of teleost VDR sequences is consistent with the notion of paralogous genes arising from a whole genome duplication event prior to teleost radiation. Functional characterization was conducted through the development of VDR expression vectors including Gal4 chimeras containing the yeast Gal4 DNA binding domain fused to the medaka VDR ligand binding domain and full-length protein. The common VDR ligand 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)(2)D(3)] resulted in significant transactivation activity with both the Gal4 and full-length constructs of medaka (m) VDRbeta. Comparatively, transactivation of mVDRalpha with 1alpha,25(OH)(2)D(3) was highly attenuated, suggesting a functional divergence between these two nuclear receptor paralogs. We additionally demonstrate through coactivator studies that mVDRalpha is still functional; however, it exhibits a different sensitivity to 1alpha,25(OH)(2)D(3), compared with VDRbeta. These results suggest that in mVDRalpha and VDRbeta have undergone a functional divergence through a process of sub- and/or neofunctionalization of VDR nuclear receptor gene pairs.
|
| 巻・号 |
149(5)
|
| ページ |
2411-22
|
| 公開日 |
2008-5-1
|
| DOI |
10.1210/en.2007-1256
|
| PII |
en.2007-1256
|
| PMID |
18258682
|
| PMC |
PMC2329287
|
| MeSH |
Amino Acid Sequence
Animals
Cells, Cultured
Cloning, Molecular
Cricetinae
Cricetulus
Evolution, Molecular*
Female
Fishes / genetics*
Humans
Male
Molecular Sequence Data
Oryzias / genetics
Phylogeny
Receptors, Calcitriol / genetics
Receptors, Calcitriol / metabolism
Receptors, Calcitriol / physiology*
Receptors, Cytoplasmic and Nuclear / physiology*
Sequence Homology, Amino Acid
Tissue Distribution
Trans-Activators / metabolism
|
| IF |
3.934
|
| 引用数 |
25
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| メダカ |
database
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