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Transthyretin gene expression in choroid plexus first evolved in reptiles
M G Achen1, W Duan, T M Pettersson
1Russell Grimwade School of Biochemistry, University of Melbourne, Victoria, Australia.
The American Journal of Physiology
|November 1, 1993
Summary
Transthyretin (TTR) first evolved in the brain's choroid plexus, not the liver, in early reptiles. This finding helps explain TTR's later role as a plasma protein in mammals and birds.
Area of Science:
- Evolutionary biology
- Molecular biology
- Biochemistry
Background:
- Transthyretin (TTR) presence in mammals and birds, but not amphibians, suggested its origin in stem reptiles.
- Previous studies indicated TTR's evolutionary history was unclear, particularly its initial site of synthesis.
Purpose of the Study:
- To investigate the evolutionary origin of transthyretin (TTR) synthesis.
- To determine if TTR synthesis first occurred in the brain or liver.
- To characterize TTR in reptiles.
Main Methods:
- Studied TTR synthesis in the choroid plexus of the lizard Tiliqua rugosa using radioactive amino acid incorporation.
- Employed polymerase chain reaction (PCR) with specific oligonucleotides and screened a cDNA library to isolate and sequence TTR cDNA.
- Generated a three-dimensional model of lizard TTR via homology modeling.
Main Results:
- Demonstrated TTR synthesis in the lizard choroid plexus, but not in the liver.
- Isolated and sequenced a full-length TTR cDNA clone from the lizard.
- Confirmed complete conservation of the central channel and thyroxine-binding site between lizard and mammalian TTR.
Conclusions:
- Transthyretin (TTR) likely first evolved in the brain's choroid plexus.
- A later evolutionary shift in gene expression led to TTR becoming a liver-synthesized plasma protein.