Laudet V, Hänni C, Coll J, Catzeflis F, Stéhelin D
INSERM U186/CNRS URA 1160, Institut Pasteur, Lille, France.
EMBO J. 1992 Mar;11(3):1003-13. doi: 10.1002/j.1460-2075.1992.tb05139.x.
Nuclear receptor genes represent a large family of genes encoding receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. This family also contains genes encoding putative receptors for unknown ligands. Nuclear receptor gene products are composed of several domains important for transcriptional activation, DNA binding (C domain), hormone binding and dimerization (E domain). It is not known whether these genes have evolved through gene duplication from a common ancestor or if their different domains came from different independent sources. To test these possibilities we have constructed and compared the phylogenetic trees derived from two different domains of 30 nuclear receptor genes. The tree built from the DNA binding C domain clearly shows a common progeny of all nuclear receptors, which can be grouped into three subfamilies: (i) thyroid hormone and retinoic acid receptors, (ii) orphan receptors and (iii) steroid hormone receptors. The tree constructed from the central part of the E domain which is implicated in transcriptional regulation and dimerization shows the same distribution in three subfamilies but two groups of receptors are in a different position from that in the C domain tree: (i) the Drosophila knirps family genes have acquired very different E domains during evolution, and (ii) the vitamin D and ecdysone receptors, as well as the FTZ-F1 and the NGF1B genes, seem to have DNA binding and hormone binding domains belonging to different classes. These data suggest a complex evolutionary history for nuclear receptor genes in which gene duplication events and swapping between domains of different origins took place.
核受体基因代表了一个大家族的基因，这些基因编码各种疏水性配体的受体，如类固醇、维生素D、视黄酸和甲状腺激素。这个家族还包含编码未知配体假定受体的基因。核受体基因产物由几个对转录激活、DNA结合（C结构域）、激素结合和二聚化（E结构域）很重要的结构域组成。目前尚不清楚这些基因是通过基因复制从共同祖先进化而来，还是它们不同的结构域来自不同的独立来源。为了检验这些可能性，我们构建并比较了从30个核受体基因的两个不同结构域推导出来的系统发育树。由DNA结合C结构域构建的树清楚地显示了所有核受体的共同后代，可分为三个亚家族：（i）甲状腺激素和视黄酸受体，（ii）孤儿受体，（iii）类固醇激素受体。由参与转录调控和二聚化的E结构域中部构建的树在三个亚家族中显示出相同的分布，但两组受体在C结构域树中的位置不同：（i）果蝇knirps家族基因在进化过程中获得了非常不同的E结构域；（ii）维生素D和蜕皮激素受体，以及FTZ-F1和NGF1B基因，似乎具有属于不同类别的DNA结合和激素结合结构域。这些数据表明核受体基因具有复杂的进化历史，其中发生了基因复制事件和不同起源结构域之间的交换。
