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Added by
Michael Baker Ph.D.
Publication date
2019
fields
Biology
and research's language is
English
Authors
Michael E. Baker
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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 receptors for estrogens and 3-ketosteroids first appearing in basal chordates (cephalochordates: amphioxus), which are close ancestors of vertebrates. An ancestral progesterone receptor and an ancestral corticoid receptor, the common ancestor of the glucocorticoid and mineralocorticoid receptors, evolved in jawless vertebrates (cyclostomes: lampreys, hagfish). This was followed by evolution of an androgen receptor and distinct glucocorticoid and mineralocorticoid receptors in cartilaginous fishes (gnathostomes: sharks). Adrenal and sex steroid receptors are not found in echinoderms: and hemichordates, which are ancestors in the lineage of cephalochordates and vertebrates. The presence of steroid receptors in vertebrates, in which these steroid receptors act as master switches to regulate differentiation, development, reproduction, immune responses, electrolyte homeostasis and stress responses, argues for 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).
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Cortisol, corticosterone and aldosterone activate full-length glucocorticoid receptor (GR) from elephant shark, a cartilaginous fish belonging to the oldest group of jawed vertebrates. Activation by aldosterone a mineralocorticoid, indicates partial divergence of elephant shark GR from the MR. Progesterone activates elephant shark MR, but not elephant shark GR. Progesterone inhibits steroid binding to elephant shark GR, but not to human GR. Deletion of the N-terminal domain (NTD) from elephant shark GR (Truncated GR) reduced the response to corticosteroids, while truncated and full-length elephant shark MR had similar responses to corticosteroids. Chimeras of elephant shark GR NTD fused to MR DBD+LBD had increased activation by corticosteroids and progesterone compared to full-length elephant shark MR. Elephant shark MR NTD fused to GR DBD+LBD had similar activation as full-length elephant shark MR, indicating that activation of human GR by the NTD evolved early in GR divergence from the MR.
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