Evolution of a novel subfamily of nuclear receptors with members that each contain two DNA binding domains

Wenjie Wu,Edward G Niles,Philip T Loverde,Hirohisa Hirai

doi:10.1186/1471-2148-7-27

Wenjie Wu, Edward G Niles + Show 2 more

Open Access

PDF Available

https://doi.org/10.1186/1471-2148-7-27

Copy DOI

Export

Save

Cite

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

BackgroundNuclear receptors (NRs) are important transcriptional modulators in metazoans which regulate transcription through binding to the promoter region of their target gene by the DNA binding domain (DBD) and activation or repression of mRNA synthesis through co-regulators bound to the ligand binding domain (LBD). NRs typically have a single DBD with a LBD.ResultsThree nuclear receptors named 2DBD-NRs, were identified from the flatworm Schistosoma mansoni that each possess a novel set of two DBDs in tandem with a LBD. They represent a novel NR modular structure: A/B-DBD-DBD-hinge-LBD. The 2DBD-NRs form a new subfamily of NRs, VII. By database mining, 2DBD-NR genes from other flatworm species (Schmidtea mediterranea and Dugesia japonica), from Mollusks (Lottia gigantean) and from arthropods (Daphnia pulex) were also identified. All 2DBD-NRs possess a P-box sequence of CEACKK in the first DBD, which is unique to 2DBD-NRs, and a P-box sequence of CEGCKG in the second DBD. Phylogenetic analyses of both DBD and ligand binding domain sequences showed that 2DBD-NR genes originate from a common two DBD-containing ancestor gene. A single 2DBD-NR orthologue was found in Arthropoda, Platyhelminths and Mollusca. Subsequent 2DBD-NR gene evolution in Mollusks and Platyhelminths involved gene duplication. Chromosome localization of S. mansoni 2DBD-NR genes by Fluorescent in situ hybridization (FISH) suggests that 2DBD-NR genes duplicated on different chromosomes in the Platyhelminths. Dimerization of Sm2DBDα indicates that 2DBD-NRs may act as homodimers, suggesting either that two repeats of a half-site are necessary for each DBD of 2DBD-NRs to bind to its target gene, or that each 2DBD-NR can recognize multiple sites.Conclusion2DBD-NRs share a common ancestor gene which possessed an extra DBD that likely resulted from a recombination event. After the split of the Arthropods, Mollusks and Platyhelminths, 2DBD-NR underwent a recent duplication in a common ancestor of Mollusks, while two rounds of duplication occurred in a common ancestor of the Platyhelminths. This demonstrates that certain NR gene underwent recent duplication in Prostostome lineages after the split of the Prostostomia and Deuterostomia.

Highlights

Nuclear receptors (NRs) are important transcriptional modulators in metazoans which regulate transcription through binding to the promoter region of their target gene by the DNA binding domain (DBD) and activation or repression of mRNA synthesis through coregulators bound to the ligand binding domain (LBD)
NRs regulate transcription through binding to the promoter region of their target gene by the DBD and activation or repression of mRNA synthesis through co-regulators bound to the LBD [5]
Since the results show that there is only one Arthropod, Mollusk and Platyhelminth 2DBDNR orthologue, the duplication of the ancient 2DBD-NR first occurred after the split of Arthropods, Mollusks and Platyhelminths (Fig. 7B)

Summary

Introduction

Nuclear receptors (NRs) are important transcriptional modulators in metazoans which regulate transcription through binding to the promoter region of their target gene by the DNA binding domain (DBD) and activation or repression of mRNA synthesis through coregulators bound to the ligand binding domain (LBD). There is a conserved sequence element in the DBD, called the P-box, which confers target DNA binding specificity. Another moderately conserved region is the LBD [1,2,3]. NRs regulate transcription through binding to the promoter region of their target gene by the DBD and activation or repression of mRNA synthesis through co-regulators bound to the LBD [5]

Methods

Results

Conclusion