Owen G I, Zelent A
Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, UK.
Cell Mol Life Sci. 2000 May;57(5):809-27. doi: 10.1007/s000180050043.
Nuclear receptors (NRs), which include those for steroid and thyroid hormones as well as retinoids, are encoded by a large gene superfamily that has evolved to regulate nearly every facet of metazoan life, from development to basic metabolism. This article reviews the conservation in structure and function of distinct receptors across different species and attempts to draw conclusions as to the evolution of this gene superfamily. Although sequences related to NRs can be found in plants and yeast, gene sequence analyses suggest that the NR ancestor(s) first appeared in the early metazoans and subsequently diversified into the six receptor sub-families, which were already recognisable at the time of the Arthropoda-Chordata split over 700 million years ago. At the time when a primitive NR emerged, the basic components of the transcription regulatory machinery, which are conserved from yeast to vertebrates, were already in place and the ancestral NR must have evolved with the ability to communicate with them. The first such NRs likely acted as monomers and in a ligand-independent fashion. As members of the NR superfamily acquired the ability to hetero- and homodimerise, and to bind and be regulated by ligands, the functional complexity of the NR superfamily increased. This exponentially increasing complexity subsequently provided a potential driving force for evolution of higher organisms by supplying a sophisticated regulatory gene network that could control complex physiological processes during development and in adult organisms.
核受体（NRs），包括类固醇、甲状腺激素以及视黄酸的受体，由一个庞大的基因超家族编码，该超家族已经进化到可调节后生动物生命的几乎每个方面，从发育到基础代谢。本文综述了不同物种间不同受体在结构和功能上的保守性，并试图就这个基因超家族的进化得出结论。尽管在植物和酵母中可以找到与核受体相关的序列，但基因序列分析表明，核受体的祖先最早出现在早期后生动物中，随后分化为六个受体亚家族，早在7亿多年前节肢动物 - 脊索动物分化时就已经可以识别。在原始核受体出现时，从酵母到脊椎动物都保守的转录调控机制的基本组成部分已经存在，并且祖先核受体一定是随着与它们交流的能力而进化的。最早的这类核受体可能以单体形式且以不依赖配体的方式发挥作用。随着核受体超家族成员获得异源和同源二聚化的能力，以及结合配体并受其调控的能力，核受体超家族的功能复杂性增加。这种呈指数增长的复杂性随后通过提供一个复杂的调控基因网络为高等生物的进化提供了潜在驱动力，该网络可以控制发育过程中和成年生物体中的复杂生理过程。
