Adaptive substitutions underlying cardiac glycoside insensitivity in insects exhibit epistasis in vivo
- Princeton University, United States
- University of Pittsburgh, United States
- Columbia University, United States
- Justus-Liebig-Universität Gießen, Germany
Abstract
Predicting 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.
Data availability
Sequence data as been deposited in Genbank and the details of all accession numbers of this and previously published data are tabulated in Supplementary Table S1.
Article and author information
Author details
Funding
National Institutes of Health (R01 GM115523)
- Peter Andolfatto
National Institutes of Health (T32 GM008424)
- Bartholomew P Roland
National Institutes of Health (R01 GM108073)
- Michael J Palladino
National Institutes of Health (R01 AG027453)
- Michael J Palladino
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Taverner et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Adaptive substitutions underlying cardiac glycoside insensitivity in insects exhibit epistasis in vivo
eLife 8:e48224.
https://doi.org/10.7554/eLife.48224
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