Transthyretin synthesis during development and evolution: What the marsupials revealed

Abstract

Many of our current concepts about biological systems are based on the data from eutherian mammals. Taking the comparative approach gives a broader evolutionary perspective. By analysing the situation also in fish, amphibians, reptiles, birds, monotremes and marsupials, we are forced to consider the differences in physiology (e.g. poikilothermic vs. endothermic, aquatic vs. terrestrial, carnivore vs. herbivore vs. omnivore, modes of reproduction and development, etc.) and we are forced to consider the selection pressures involved. This results in a greater understanding of the biological system in question. In the case of transthyretin (TTR), investigation into tissue specificity of synthesis during both development and evolution revealed that not only are the mammalian TTRs the exception (all other TTRs preferentially bind T3, not T4), but that TTR synthesis appears spatially and temporally where greater thyroid hormone (TH) distribution is required. In the case of TTR evolution, the study of marsupials provided several 'missing links', even regarding the structure-function relationships. Thus, we can now see a sequential change in the structure of the N-terminal regions of the TTR subunits, sequential change in affinity of TTRs for THs, and a sequential increase in affinity of TTR for THs from amphibians to mammals. Studying marsupials also allowed us to understand the evolution of TTR synthesis during ontogeny. By elucidating the evolutionary history of a protein in terms of its structure, function and sites of synthesis and timing of gene expression, this allowed us to obtain a comprehensive picture of its biological roles. © 2009 Springer-Verlag Berlin Heidelberg.