Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions
Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions
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DOI：
10.1073/pnas.091553298
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发表时间：
2001-05-08
影响因子：
11.1
通讯作者：
Thornton, JW
中科院分区：
文献类型：
--
作者：
Thornton, JW
在紧密结合的生物系统中，如激素及其受体，新颖性的演变似乎挑战了自然选择理论：目前尚不清楚如何为任何一个部分(如配体)选择新的功能，除非该系统的其他成员(如受体)已经存在，在这里，我表明--基于对基础脊椎动物类固醇受体的鉴定和系统发育分析，以及对祖先蛋白质序列和功能属性的重建--第一个类固醇受体是雌激素受体，随后是孕激素受体。基因组图谱和系统发育分析表明，哺乳动物的全部类固醇受体是由这些古老的受体通过两次大规模的基因组扩张进化而来的，一次是在有颌骨脊椎动物出现之前，另一次是在雄性激素和皮质激素对生理过程的特定调节之后，是在这些重复之后出现的相对较新的创新。这些发现支持配体开发模型，在该模型中，生物合成途径中的末端配体是受体进化的第一个；尽管没有受体，但对这种激素的选择也选择合成中间体，复制的受体然后进化对这些物质的亲和力，这样就产生了新的激素-受体对，并阐述了一个日益复杂的集成系统。这一模型表明，在系统发育相关受体的配体合成过程中，可能会在中间体中发现一些“孤儿”受体的配体。
The evolution of novelty in tightly integrated biological systems, such as hormones and their receptors, seems to challenge the theory of natural selection: it has not been clear how a new function for any one part (such as a ligand) can be selected for unless the other members of the system (e.g,, a receptor) are already present, Here I show-based on identification and phylogenetic analysis of steroid receptors in basal vertebrates and reconstruction of the sequences and functional attributes of ancestral proteins-that the first steroid receptor was an estrogen receptor, followed by a progesterone receptor. Genome mapping and phylogenetic analyses indicate that the full complement of mammalian steroid receptors evolved from these ancient receptors by two large-scale genome expansions, one before the advent of jawed vertebrates and one after, Specific regulation of physiological processes by androgens and corticoids are relatively recent innovations that emerged after these duplications. These findings support a model of ligand exploitation in which the terminal ligand in a biosynthetic pathway is the first for which a receptor evolves; selection for this hormone also selects for the synthesis of intermediates despite the absence of receptors, and duplicated receptors then evolve affinity for these substances, In this way, novel hormone-receptor pairs are created, and an integrated system of increasing complexity elaborated. This model suggests that ligands for some "orphan" receptors may be found among intermediates in the synthesis of ligands for phylogenetically related receptors.