Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, OR 97403, USA.
Mol Cell Endocrinol. 2011 Mar 1;334(1-2):31-8. doi: 10.1016/j.mce.2010.09.003. Epub 2010 Sep 15.
Members of the steroid hormone receptor (SR) family activate transcription from different DNA response elements and are regulated by distinct hormonal ligands. Understanding the evolutionary process by which this diversity arose can provide insight into how and why SRs function as they do. Here we review the characteristics of the ancient receptor protein from which the SR family descends by a process of gene duplication and divergence. Several orthogonal lines of evidence - bioinformatic, phylogenetic, and experimental - indicate that this ancient SR had the capacity to activate transcription from DNA estrogen response elements in response to estrogens. Duplication and divergence of the ancestral SR gene subsequently generated new receptors that were activated by other steroid hormones, including progestagens, androgens, and corticosteroids. The androgen and progesterone receptors recruited as their ligands steroids that were previously present as biochemical intermediates in the synthesis of estrogens. This process is an example of molecular exploitation--the evolution of new molecular interactions when an older molecule, which previously had a different function, is co-opted as a binding partner by a newly evolved molecule. The primordial interaction between the ancestral steroid receptor and estrogens may itself have evolved due to an early molecular exploitation event.
甾体激素受体（SR）家族的成员从不同的 DNA 反应元件激活转录，并受不同的激素配体调节。了解这种多样性产生的进化过程，可以深入了解 SR 如何以及为何发挥作用。在这里，我们通过基因复制和分化的过程，回顾了 SR 家族衍生的古老受体蛋白的特征。有几条相互印证的证据——生物信息学、系统发育和实验——表明这种古老的 SR 能够在雌激素的作用下，从 DNA 雌激素反应元件激活转录。祖先 SR 基因的复制和分化随后产生了新的受体，这些受体被其他甾体激素激活，包括孕激素、雄激素和皮质类固醇。雄激素和孕激素受体招募的配体是以前作为雌激素合成生化中间产物存在的类固醇。这个过程是分子利用的一个例子——当一个以前具有不同功能的旧分子被新进化的分子作为结合伴侣共同利用时，就会产生新的分子相互作用的进化。祖先甾体激素受体和雌激素之间的原始相互作用本身可能是由于早期的分子利用事件而进化的。
