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Transthyretin expression evolved more recently in liver than in brain
G Schreiber1, T M Pettersson, B R Southwell
1Russell Grimwade School of Biochemistry, University of Melbourne, Parkville, Australia.
Summary
Transthyretin (TTR) is synthesized in the choroid plexus across diverse vertebrates. Liver synthesis of TTR evolved independently in mammals and birds, emerging significantly later than its presence in ancient reptiles.
Area of Science:
- Evolutionary Biology
- Biochemistry
- Comparative Genomics
Background:
- Transthyretin (TTR) is a pleiotropic protein with roles in thyroid hormone and retinol transport.
- The evolutionary origins and differential expression of TTR across vertebrate classes remain incompletely understood.
- Investigating TTR synthesis provides insights into the evolution of vertebrate physiology and gene regulation.
Purpose of the Study:
- To investigate the evolutionary history of transthyretin (TTR) synthesis across various vertebrate species.
- To determine the sites of TTR production, specifically focusing on the choroid plexus and liver.
- To elucidate the evolutionary timeline of TTR gene expression and its independent emergence in different lineages.
Main Methods:
- Comparative analysis of TTR synthesis and secretion in choroid plexus and liver tissues.
- Detection of TTR presence in blood samples from representative species across mammals, birds, reptiles, and amphibians.
- Phylogenetic analysis to infer the evolutionary origins and divergence of TTR gene expression patterns.
Main Results:
- Transthyretin (TTR) synthesis was confirmed in the choroid plexus of rats, echidnas, and lizards, but not toads.
- TTR was detected in the blood of placental mammals, birds, and marsupials, but absent in reptiles and monotremes.
- Liver-based TTR synthesis appears to have evolved independently in placental mammals/marsupials and birds, diverging from earlier choroid plexus expression in stem reptiles.
Conclusions:
- The choroid plexus is a conserved site for transthyretin (TTR) synthesis across a broad range of vertebrates.
- Hepatic TTR synthesis represents a later evolutionary innovation, with independent origins in mammalian and avian lineages.
- The data suggest TTR gene expression in the mammalian liver emerged approximately 200 million years after its initial appearance in the choroid plexus of stem reptiles.