Earlier in this chapter we discussed the ways in which biologists can detect regions of genes that are under positive selection for change. What are the practical uses of this information? Consider the evolution of the family of genes encoding *voltage-gated sodium channels. Sodium channels have many functions, including the control of nerve impulses in the nervous system. Sodium channels can be blocked by various toxins, such as tetrodotoxin (TTX), a neurotoxin present in the tissues of some puffer fish and several other animals. A human who eats those tissues of a puffer fish that contain TTX can become paralyzed and die because the toxin blocks sodium channels and prevents nerves and muscles from functioning.

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But puffer fish have sodium channels too, so why doesn’t the TTX cause paralysis in the puffer fish themselves? The sodium channels of puffer fish (and of other animals that sequester TTX, such as the rough-skinned newt shown in Figure 20.20) have evolved to become resistant to the toxin. Nucleotide substitutions in the puffer fish genome have resulted in changes in the proteins that make up the sodium channels, and those changes prevent TTX from binding to the sodium channel pore.

Several different substitutions that result in TTX resistance have evolved in the various duplicated sodium channel genes of the many species of puffer fish. Many other changes that have nothing to do with the evolution of TTX resistance have occurred in these genes as well. Biologists who study the function of sodium channels can learn a great deal about how the channels work (and about neurological diseases that are caused by mutations in the sodium channel genes) by understanding which changes have been selected for TTX resistance. They do this by comparing the rates of synonymous and nonsynonymous substitutions across the genes in various lineages that have evolved TTX resistance. In a similar manner, molecular evolutionary principles are used to understand function and diversification of function in many other proteins.