Speaker
Description
The repeated evolution of resistance to widespread toxins collectively known as cardiotonic steroids represents one of the clearest examples of natural selection. Numerous plants and animals across the globe are chemically defended by these toxins, which target the vital transmembrane protein Na+K+-ATPase (NKA). In response, many herbivores and predators evolved resistance through target-site insensitivity of NKA. This adaptation has been repeatedly achieved by one or two amino acid substitutions at the same sites in the protein and has demonstrated remarkable patterns of convergence, divergence, and parallelism. Such patterns are expected to be shaped by the degree of pleiotropy (i.e. the effect of a mutation on multiple traits) and intramolecular epistasis (i.e. nonadditive interactions between mutant sites in the same protein). We evaluate the extent to which these factors constrained the evolution of this adaptation in a group of animals that have repeatedly gained it: snakes. We asked whether substitutions gained over time at other sites in the NKA permitted the adaptive effects of resistance-producing ones and/or allowed the protein to tolerate any deleterious effects of resistance on its normal function. We answer this question by statistically reconstructing and experimentally resurrecting ancestral snake NKA at key evolutionary steps and moving modern resistance-producing substitutions onto the increasingly more ancient genetic backgrounds to measure how their effects on resistance and protein function change as they go back in time. We found compelling evidence that epistasis and pleiotropy were significant constraining factors in the evolution of resistance. Our results help explain the adaptation patterns observed in cardiotonic steroid-resistant snakes.
