Convergent Evolution of Tetrodotoxin-Resistant Sodium Channels in Predators and Prey

Convergent evolution of similar adaptive traits may arise from either common or disparate molecular and physiological mechanisms. The forces that determine the degree of underlying mechanistic similarities across convergent phenotypes are highly debated and poorly understood. Some garter snakes are able to consume newts that possess the channel blocking compound tetrodotoxin (TTX). Despite belonging to unrelated lineages, both the predators and prey have independently evolved remarkably similar physiological mechanisms of resistance to TTX that involve chemical and structural changes in voltage-gated sodium channels (NaV). The evolution of TTX resistance in this predator-prey pair constitutes a natural experiment that allows us to explore the causes of molecular convergence. Here, we review broad patterns of convergence at the level of amino acid changes in NaV channels of animals that evolved TTX resistance and make comparisons to known TTX-resistant channels that did not evolve under the selective pressures imposed by TTX. We conclude that convergence likely stems from the interplay of the target specificity of TTX and functional constraints of NaV that are shared among taxa. These and other factors can limit channel evolution to favor a few functionally permissible paths of adaptation, which can explain the observed predictability of changes to channel structure. By studying the functional causes of convergence in NaV channels, we can further our understanding of the role of these important channel proteins at the center of the evolution of the nervous system.