Wu Wenjie, Niles Edward G, Hirai Hirohisa, LoVerde Philip T
Department of Microbiology and Immunology, School of Medicine and Biomedical Science, State University of New York, Buffalo, NY 14214, USA.
BMC Evol Biol. 2007 Feb 23;7:27. doi: 10.1186/1471-2148-7-27.
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 co-regulators bound to the ligand binding domain (LBD). NRs typically have a single DBD with a LBD.
Three 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 Sm2DBDalpha 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.
2DBD-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.
核受体（NRs）是后生动物中重要的转录调节因子，它们通过DNA结合域（DBD）与靶基因的启动子区域结合来调节转录，并通过与配体结合域（LBD）结合的共调节因子激活或抑制mRNA合成。NRs通常具有单个带有LBD的DBD。
从曼氏血吸虫这种扁形虫中鉴定出三种名为2DBD-NRs的核受体，它们各自拥有一组新颖的串联的两个DBD以及一个LBD。它们代表了一种新颖的NR模块化结构：A/B-DBD-DBD-铰链-LBD。2DBD-NRs形成了NRs的一个新亚家族，即亚家族VII。通过数据库挖掘，还鉴定出了来自其他扁形虫物种（地中海涡虫和日本三角涡虫）、软体动物（巨人笠贝）和节肢动物（大型溞）的2DBD-NR基因。所有2DBD-NRs在第一个DBD中都拥有独特的CEACKK的P盒序列，在第二个DBD中拥有CEGCKG的P盒序列。对DBD和配体结合域序列的系统发育分析表明，2DBD-NR基因起源于一个共同的含两个DBD的祖先基因。在节肢动物、扁形动物和软体动物中发现了单个2DBD-NR直系同源物。随后，软体动物和扁形动物中的2DBD-NR基因进化涉及基因复制。通过荧光原位杂交（FISH）对曼氏血吸虫2DBD-NR基因进行染色体定位表明，2DBD-NR基因在扁形动物的不同染色体上发生了复制。Sm2DBDα的二聚化表明2DBD-NRs可能作为同二聚体起作用，这表明2DBD-NRs的每个DBD与靶基因结合可能需要两个半位点重复，或者每个2DBD-NR可以识别多个位点。
2DBD-NRs共享一个共同的祖先基因，该基因拥有一个可能由重组事件产生的额外DBD。在节肢动物、软体动物和扁形动物分化后，2DBD-NR在软体动物的一个共同祖先中经历了近期的复制，而在扁形动物的一个共同祖先中发生了两轮复制。这表明在原口动物和后口动物分化后，某些NR基因在原口动物谱系中经历了近期的复制。
