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

eLife

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[1] Department of Biological Sciences, Columbia University, New York, United States;Department of Ecology and Evolutionary Biology, Princeton University, Princeton, United States;Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, United States;Pittsburgh Institute for Neurodegenerative Diseases (PIND), University of Pittsburgh School of Medicine, Pittsburgh, United States;Institute for Insect Biotechnology, Justus-Liebig-Universität Gießen, Hesse, Germany;Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States;

关键词: adaptation;    natural selection;    pleiotropy;    protein evolution;    epistasis;    ecological genetics;    D. melanogaster;   

DOI  :  10.7554/eLife.48224

来源: publisher

【 摘 要 】

10.7554/eLife.48224.001Predicting how species will respond to selection pressures requires understanding the factors that constrain their evolution. We use genome engineering of Drosophila to investigate constraints on the repeated evolution of unrelated herbivorous insects to toxic cardiac glycosides, which primarily occurs via a small subset of possible functionally-relevant substitutions to Na+,K+-ATPase. Surprisingly, we find that frequently observed adaptive substitutions at two sites, 111 and 122, are lethal when homozygous and adult heterozygotes exhibit dominant neural dysfunction. We identify a phylogenetically correlated substitution, A119S, that partially ameliorates the deleterious effects of substitutions at 111 and 122. Despite contributing little to cardiac glycoside-insensitivity in vitro, A119S, like substitutions at 111 and 122, substantially increases adult survivorship upon cardiac glycoside exposure. Our results demonstrate the importance of epistasis in constraining adaptive paths. Moreover, by revealing distinct effects of substitutions in vitro and in vivo, our results underscore the importance of evaluating the fitness of adaptive substitutions and their interactions in whole organisms.

【 授权许可】

CC BY