Evolution of the thyroid hormone-binding protein, transthyretin

Area of Science:

• Biochemistry
• Evolutionary Biology
• Comparative Genomics

Background:

• Transthyretin (TTR) is a key protein involved in thyroid hormone and vitamin A transport.
• TTR is synthesized in the liver and choroid plexus in mammals and birds, but primarily in the choroid plexus in reptiles.
• Previous hypotheses suggested extrahepatic TTR synthesis evolved early, based on reptilian expression patterns.

Purpose of the Study:

• To investigate the evolutionary origins of transthyretin (TTR) synthesis.
• To explore alternative models of TTR evolution based on its presence in diverse vertebrate species.
• To analyze structural differences in TTR that may affect its binding properties.

Main Methods:

• Identification and cloning of TTR from amphibian (Rana catesbeiana) and fish (Sparus aurata).
• Comparative analysis of TTR expression patterns across vertebrates (reptiles, amphibians, fish, mammals, birds).
• Protein modeling to assess electrostatic characteristics and hormone-binding preferences.

Main Results:

• TTR was identified in the liver of an amphibian and a teleost fish, but not in their choroid plexus.
• This finding challenges the hypothesis of early extrahepatic TTR evolution.
• Protein modeling revealed distinct electrostatic properties in fish and bird TTR, influencing triiodothyronine binding.

Conclusions:

• The evolution of TTR synthesis likely involves alternative pathways, with evidence supporting both hepatic and extrahepatic origins.
• Structural variations in TTR across species correlate with differential binding affinities for thyroid hormones.
• Further research is needed to fully elucidate the complex evolutionary history of TTR.