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首页> 外文期刊>Endocrinology >Functional Diversification of Vitamin D Receptor Paralogs in Teleost Fish After a Whole Genome Duplication Event
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Functional Diversification of Vitamin D Receptor Paralogs in Teleost Fish After a Whole Genome Duplication Event

机译：全基因组复制事件后硬骨鱼中维生素D受体旁系同源物的功能多样化

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The diversity and success of teleost fishes (Actinopterygii) has been attributed to three successive rounds of whole-genome duplication (WGD). WGDs provide a source of raw genetic material for evolutionary forces to act upon, resulting in the divergence of genes with altered or novel functions. The retention of multiple gene pairs (paralogs) in teleosts provides a unique opportunity to study how genes diversify and evolve after a WGD. This study examines the hypothesis that vitamin D receptor (VDR) paralogs (VDR alpha and VDR beta) from two distantly related teleost orders have undergone functional divergence subsequent to the teleost-specific WGD. VDR alpha and VDR beta paralogs were cloned from the Japanese medaka (Beloniformes) and the zebrafish (Cypriniformes). Initial transactivation studies using 1 alpha, 25-dihydroxyvitamin D3 revealed that although VDR alpha and VDR beta maintain similar ligand potency, the maximum efficacy of VDR alpha was significantly attenuated compared with VDR alpha in both species. Subsequent analyses revealed that VDR alpha and VDR beta maintain highly similar ligand affinities; however, VDR alpha demonstrated preferential DNA binding compared with VDR beta. Protein-protein interactions between the VDR paralogs and essential nuclear receptor coactivators were investigated using transactivation and mammalian two-hybrid assays. Our results imply that functional differences between VDR alpha and VDR beta occurred early in teleost evolution because they are conserved between distantly related species. Our results further suggest that the observed differences may be associated with differential protein-protein interactions between the VDR paralogs and coactivators. We speculate that the observed functional differences are due to subtle ligand-induced conformational differences between the two paralogs, leading to divergent downstream functions.
机译：硬骨鱼类（Actinopterygii）的多样性和成功归因于三轮连续的全基因组复制（WGD）。 WGD为进化力作用提供了原始遗传物质的来源，从而导致功能改变或新颖的基因发生分化。硬骨鱼中多个基因对（旁系同源物）的保留提供了一个独特的机会来研究WGD后基因如何多样化和进化。这项研究检验了以下假设：硬骨特异性WGD之后，来自两个远缘硬骨鱼类订单的维生素D受体（VDR）旁系同源物（VDRα和VDRβ）经历了功能分散。 VDR alpha和VDR beta旁系同源物是从日本（Beloniformes）和斑马鱼（Cypriniformes）克隆的。最初使用1α，25-二羟基维生素D3进行的反式激活研究表明，尽管VDRα和VDRβ保持相似的配体效价，但与两种物种相比，VDRα的最大功效均显着减弱。随后的分析表明，VDR alpha和VDR beta保持高度相似的配体亲和力。然而，与VDR beta相比，VDR alpha表现出优先的DNA结合。 VDR旁系同源物和必需的核受体共激活因子之间的蛋白-蛋白相互作用使用反式激活和哺乳动物两杂交试验进行了研究。我们的结果表明，VDR alpha和VDR beta之间的功能差异发生在硬骨鱼类进化的早期，因为它们在远缘物种之间是保守的。我们的结果进一步表明，观察到的差异可能与VDR旁系同源物和共激活因子之间差异的蛋白质-蛋白质相互作用有关。我们推测观察到的功能差异是由于两个旁系同源物之间细微的配体诱导的构象差异，导致下游功能的差异。

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