Evolution of a novel subfamily of nuclear receptors with members that each contain two DNA binding domainsReport as inadecuate




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BMC Evolutionary Biology

, 7:27

First Online: 23 February 2007Received: 22 August 2006Accepted: 23 February 2007

Abstract

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.

List of abbreviations2DBD-NRnuclear receptor containing two tandem DNA binding domains, BAC: bacterial artificial chromosome, DBD: DNA-binding domain, FISH: Fluorescent in situ hybridization, LBD: ligand binding domain, NR: nuclear receptor, WGS: whole genomic sequence.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2148-7-27 contains supplementary material, which is available to authorized users.

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Author: Wenjie Wu - Edward G Niles - Hirohisa Hirai - Philip T LoVerde

Source: https://link.springer.com/article/10.1186/1471-2148-7-27







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