Division of Nephrology-Hypertension, Department of Medicine, 0693, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0693, USA.
Mol Cell Endocrinol. 2019 Oct 1;496:110526. doi: 10.1016/j.mce.2019.110526. Epub 2019 Jul 31.
Considering that life on earth evolved about 3.7 billion years ago, vertebrates are young, appearing in the fossil record during the Cambrian explosion about 542 to 515 million years ago. Results from sequence analyses of genomes from bacteria, yeast, plants, invertebrates and vertebrates indicate that receptors for adrenal steroids (aldosterone, cortisol), and sex steroids (estrogen, progesterone, testosterone) also are young, with an estrogen receptor and a 3-ketosteroid receptor first appearing in basal chordates (cephalochordates: amphioxus), which are close ancestors of vertebrates. Duplication and divergence of the 3-ketosteroid receptor yielded an ancestral progesterone receptor and an ancestral corticoid receptor, the common ancestor of the glucocorticoid and mineralocorticoid receptors, in jawless vertebrates (cyclostomes: lampreys, hagfish). This was followed by evolution of an androgen receptor, distinct glucocorticoid and mineralocorticoid receptors and estrogen receptor-α and -β in cartilaginous fishes (Chondrichthyes: sharks). Further evolution of mineralocorticoid signaling occurred with the evolution of aldosterone synthase in lungfish, a forerunner of terrestrial vertebrates. Adrenal and sex steroid receptors are not found in echinoderms and hemichordates, which are ancestors in the lineage of cephalochordates and vertebrates. The evolution of steroid receptors at key nodes in the evolution of vertebrates, in which steroid receptors act as master switches to regulate differentiation, development, reproduction, immune responses, electrolyte homeostasis and stress responses, suggests an important role for steroid receptors in the evolutionary success of vertebrates, considering that the human genome contains about 22,000 genes, which is not much larger than genomes of invertebrates, such as Caenorhabditis elegans (18,000 genes) and Drosophila (14,000 genes).
考虑到地球上的生命大约在 37 亿年前进化，脊椎动物是年轻的，在大约 5.42 亿至 5.15 亿年前的寒武纪大爆发中出现在化石记录中。对来自细菌、酵母、植物、无脊椎动物和脊椎动物的基因组序列分析的结果表明，肾上腺类固醇（醛固酮、皮质醇）和性激素（雌激素、孕酮、睾丸素）的受体也很年轻，雌激素受体和 3-酮类固醇受体首先出现在脊索动物的基础（头索动物：文昌鱼）中，文昌鱼是脊椎动物的近亲。3-酮类固醇受体的复制和分化产生了一个祖先的孕酮受体和一个祖先的皮质醇受体，这是糖皮质激素和盐皮质激素受体的共同祖先，在无颌脊椎动物（圆口纲：七鳃鳗、盲鳗）中。随后，在软骨鱼类（软骨鱼纲：鲨鱼）中进化出了雄激素受体、独特的糖皮质激素和盐皮质激素受体以及雌激素受体-α和 -β。在肺鱼中，进一步进化出了盐皮质激素信号，肺鱼是陆地脊椎动物的先驱。在棘皮动物和半索动物中没有发现肾上腺和性激素受体，它们是头索动物和脊椎动物谱系的祖先。在脊椎动物进化的关键节点上，类固醇受体的进化，其中类固醇受体作为主开关调节分化、发育、繁殖、免疫反应、电解质稳态和应激反应，表明类固醇受体在脊椎动物的进化成功中具有重要作用，考虑到人类基因组包含大约 22000 个基因，这与无脊椎动物如秀丽隐杆线虫（18000 个基因）和果蝇（14000 个基因）的基因组没有太大区别。
