Predator-Prey Arms Race

The Brodie Lab continues to explore the coevolution of tetrodotoxin (TTX) toxicity in newts of the genus Taricha and resistance to TTX in garter snakes (Thamnophis). This work ranges from geographic studies of population genetics and structure across the landscape of the interaction molecular genetic studies of the basis of adaptive phenotypes, to biophysical studies of the pleiotropic effects of resistance phenotypes on nerve and muscle function. This work involves a broad network of collaborators at different institutions and some really creative and industrious students.

Recent work from Mike Hague (Graduate Student, 2018) demonstrated that TTX resistance in Thamnophis sirtalis arose twice through a common pathway of amino acid substitutions. A limited number of amino acid substitutions in the voltage-gated sodium channel in skeletal muscle (NaV1.4) confer resistance to TTX. In garter snakes, the two resistant alleles in different lineages both began with the same initial change of an isoleucine to a valine, suggesting that this substitution had permissive effects that allowed subsequent increases in resistance.

The evolution of TTX resistance provides some exceptional opportunities to evaluate the predictability of evolutionary adaptation. Together with Charles Hanifin and Shana Geffeney (Utah State University) and Gabriela Toledo (Brodie Lab Graduate Student, 2017), we are beginning to look at the resistance and biophysical impacts of individual amino acid substitutions using gene synthesis and the Xenopus heterologous expression system. By testing specific amino acid substitutions on different ancestral gene backgrounds, we plan to examine the convergence of adaptive walks in distantly related lineages (snakes, newts, fish, and octopus) that have all evolved TTX resistant NaV.

Collaborations with Joel McGlothlin (Virginia Tech) begun when he was a postdoc in the lab identified the diversity of NaV proteins expressed in garter snakes. Sequencing of the nine NaV paralogs in garter snakes revealed that the channels in peripheral nerves were also resistant to TTX, indicating that whole animal resistance requires changes in multiple proteins. A comparative study of NaV proteins across reptiles revealed that resistance of a peripheral nerve channel (NaV1.7) predates the evolution of snakes, and that another nerve channel (NaV1.6) became resistant roughly 50 MYA in four separate lineages. Exaggerated resistance of skeletal muscle (NaV1.4) only evolved in a few groups that already had resistant nerves. This pattern paints a picture of complex historical contingency dictating which species get caught in arms races.

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Brodie Lab

Department of Biology

University of Virginia

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485 McCormick Rd.

Charlottesville, VA 22904

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