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Nuclear receptors: the evolution of diversity
John W R Schwabe1, Sarah A Teichmann
1MRC-Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. john.schwabe@mrc-lmb.cam.ac.uk
Science'S STKE : Signal Transduction Knowledge Environment
|January 30, 2004
Summary
The study suggests nuclear receptors evolved before ligand regulation. Cloning a snail
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Genetics
Background:
- Nuclear receptors are ancient transcription factors with diverse regulatory mechanisms.
- Some nuclear receptors bind ligands, while others are constitutively active or repressive.
- The evolutionary origins of nuclear receptor ligand regulation remain unclear.
Purpose of the Study:
- To investigate the evolutionary history of nuclear receptors.
- To determine if the ancestral nuclear receptor was ligand-regulated.
- To explore mechanisms of ligand-independent nuclear receptor function.
Main Methods:
- Comparative genomics and molecular evolution analyses.
- Cloning and characterization of nuclear receptors from diverse species.
- Functional assays to assess ligand binding and transcriptional activity.
Main Results:
- Identified an estrogen receptor in a snail that does not bind estrogen.
- Demonstrated that steroid receptors may be more ancient than previously believed.
- Provided evidence for a mechanism by which nuclear receptors can lose ligand-binding capacity.
Conclusions:
- The ancestral nuclear receptor may not have been ligand-regulated.
- Nuclear receptors can evolve to become ligand-independent.
- This finding offers insights into the diversification of nuclear receptor function over evolutionary time.