Adaptive substitutions underlying cardiac glycoside insensitivity in insects exhibit epistasis in vivo.

摘要: Abstract Predicting how species will respond to selection pressures requires understanding the factors that constrain their evolution. We use genome engineering of Drosophila investigate constraints on repeated evolution unrelated herbivorous insects toxic cardiac glycosides, which primarily occurs via a small subset possible functionally-relevant substitutions Na+,K+-ATPase. Surprisingly, we find frequently observed adaptive at two sites, 111 and 122, are lethal when homozygous adult heterozygotes exhibit dominant neural dysfunction. identify phylogenetically correlated substitution, A119S, partially ameliorates deleterious effects 122. Despite contributing little glycoside-insensitivity in vitro, like substantially increases survivorship upon glycoside exposure. Our results demonstrate importance epistasis constraining paths. Moreover, by revealing distinct vitro vivo, our underscore evaluating fitness interactions whole organisms.