119 Oral - Evolution II
Friday April 08, 6:15 PM - 6:30 PM

Authors:
Arya Rao; Peter Andolfatto

Affiliation: Columbia University

Keywords:
m. adaptation; k. genome-wide association studies

A significant number of unrelated herbivorous insects have repeatedly and independently evolved the ability to feed on plants that produce toxic secondary compounds called cardiac glycosides (CGs). CGs inhibit the function of Na+,K+-ATPase (NKA), a medically important enzyme in animals that is necessary for many processes including neural function and muscle contraction. Previous work identified a small number of adaptive amino acid substitutions in the alpha-subunit (ATPα) of NKA that confer the enzyme with resistance to CG inhibition. Further, engineering the native ATPα of D. melanogaster to carry one or more of these adaptive substitutions results in flies that are substantially resistant to CG toxicity. We show that wild-collected D. melanogaster strains harbor substantial genetic variation in sensitivity to CG-toxicity. By conducting GWAS on 180 Drosophila melanogaster Genome Reference Panel lines, we show that this CG resistance does not map to ATPα, but maps to a number of genes implicated in maintaining physiological barriers to solute diffusion and cellular and behavioral stress response. This information can be used to predict additional targets of recurrent adaptation in diverse CG-tolerant taxa. In addition, these results yield insight into the development of drugs to treat a number of Na+,K+-ATPase-associated neurological and physiological disorders in humans.