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

Andrew M. Taverner, Lu Yang, Zackery J. Barile, Becky Lin, Julie Peng, Ana Pinharanda, Arya Rao, Bartholomew P. Roland, Aaron D. Talsma, Daniel Wei, Georg Petschenka, Michael J. Palladino, View ORCID ProfilePeter Andolfatto
doi: https://doi.org/10.1101/621185
Andrew M. Taverner
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544
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Lu Yang
Dept. of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544
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Zackery J. Barile
Dept. of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261Pittsburgh Institute for Neurodegenerative Diseases (PIND), University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
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Becky Lin
Dept. of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261Pittsburgh Institute for Neurodegenerative Diseases (PIND), University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
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Julie Peng
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544
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Ana Pinharanda
Department of Biological Sciences, Columbia University, New York, NY 10027
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Arya Rao
Department of Biological Sciences, Columbia University, New York, NY 10027
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Bartholomew P. Roland
Dept. of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261Pittsburgh Institute for Neurodegenerative Diseases (PIND), University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
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Aaron D. Talsma
Dept. of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261Pittsburgh Institute for Neurodegenerative Diseases (PIND), University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
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Daniel Wei
Dept. of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261Pittsburgh Institute for Neurodegenerative Diseases (PIND), University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
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Georg Petschenka
Institute for Insect Biotechnology, Justus-Liebig-Universität Gießen, Hesse, Germany
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Michael J. Palladino
Dept. of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261Pittsburgh Institute for Neurodegenerative Diseases (PIND), University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
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  • For correspondence: pa2543@columbia.edu mp44@upitt.edu
Peter Andolfatto
Department of Biological Sciences, Columbia University, New York, NY 10027
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  • ORCID record for Peter Andolfatto
  • For correspondence: pa2543@columbia.edu mp44@upitt.edu
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Abstract

Predicting how species will respond to selection pressures requires identifying the factors that constrain their evolution. The repeated evolution of unrelated herbivorous insects to toxic cardiac glycosides primarily occurs via a small subset of possible functionally-relevant substitutions to Na+,K+-ATPase. We used genome engineering of Drosophila to evaluate the phenotypic effects of frequently observed adaptive substitutions at two sites (111 and 122). Surprisingly, these substitutions exhibit recessive lethality and 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. 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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted April 28, 2019.
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Adaptive substitutions underlying cardiac glycoside insensitivity in insects exhibit epistasis in vivo
Andrew M. Taverner, Lu Yang, Zackery J. Barile, Becky Lin, Julie Peng, Ana Pinharanda, Arya Rao, Bartholomew P. Roland, Aaron D. Talsma, Daniel Wei, Georg Petschenka, Michael J. Palladino, Peter Andolfatto
bioRxiv 621185; doi: https://doi.org/10.1101/621185
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Adaptive substitutions underlying cardiac glycoside insensitivity in insects exhibit epistasis in vivo
Andrew M. Taverner, Lu Yang, Zackery J. Barile, Becky Lin, Julie Peng, Ana Pinharanda, Arya Rao, Bartholomew P. Roland, Aaron D. Talsma, Daniel Wei, Georg Petschenka, Michael J. Palladino, Peter Andolfatto
bioRxiv 621185; doi: https://doi.org/10.1101/621185

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