The evolution of endothermy is explained by thyroid hormone-mediated responses to cold in early vertebrates.

The evolution of endothermy is one of the most intriguing and consistently debated topics in vertebrate biology, but the proximate mechanisms that mediated its evolution are unknown. Here, we suggest that the function of thyroid hormone in regulating physiological processes in response to cold is key to understanding the evolution of endothermy. We argue that the capacity of early chordates to produce thyroid hormone internally was the first step in this evolutionary process. Selection could then act on the capacity of thyroid hormone to regulate metabolism, muscle force production and cardiac performance to maintain their function against the negative thermodynamic effects of decreasing temperature. Thyroid-mediated cold acclimation would have been the principal selective advantage. The actions of thyroid hormone during cold acclimation in zebrafish are very similar to its role during endothermic thermogenesis. The thyroid-mediated increases in metabolism and locomotor performance in ectotherms eventually resulted in sufficient heat production to affect body temperature. From this point onwards, increased body temperature per se could be of selective advantage and reinforce thyroid-induced increases in physiological rates. Selection for increased body temperature would promote those mechanisms that maximise heat production, such as increased Na(+)/K(+)-ATPase activity, futile cycling by SERCA, and mitochondrial uncoupling, all of which are regulated by thyroid hormone. The specific end point of this broader evolutionary process would be endothermic thermoregulation. However, considering the evolution of endothermy in isolation is misleading because the selective advantages that drove the evolutionary process were independent from endothermy. In other words, without the selective advantages of thyroid-mediated cold acclimation in fish, there would be no endotherms.