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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Thornton, J. W. |
| Description | Author Affiliation: Thornton JW ( The Earth Institute and Department of Biological Sciences, Columbia University, M.C. 2430, New York, NY 10027, USA. jt121@columbia.edu); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 10 |
| Volume Number | 98 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2001-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Evolution, Molecular Lampreys Genetics Receptors, Estrogen Receptors, Steroid Animals Ligands Molecular Sequence Data Phylogeny Metabolism Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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