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
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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.
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.
Reviewing Editor
- Lauren A O'Connell, Stanford University, United States
Publication history
- Received: May 6, 2019
- Accepted: August 24, 2019
- Accepted Manuscript published: August 27, 2019 (version 1)
- Accepted Manuscript updated: August 29, 2019 (version 2)
- Version of Record published: September 9, 2019 (version 3)
- Version of Record updated: September 30, 2019 (version 4)
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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Further reading
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- Evolutionary Biology
- Microbiology and Infectious Disease
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- Evolutionary Biology
- Genetics and Genomics
