Gene duplications circumvent trade-offs in enzyme function: Insect adaptation to toxic host plants

Dalla, Safaa; Dobler, Susanne

doi:10.1111/evo.13077

Cited by 44 publications

(71 citation statements)

References 64 publications

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“…Our results demonstrate epistasis between substitutions at sites 119 and 111/122 at the level of enzyme function. Previous studies have demonstrated increased survival of cell lines expressing Q111V, N122H, and Q111T+Q111H , and substantial insensitivity to CGinhibition despite little effect on ATPase activity for N122H, Q111T+Q111H and Q111V+Q111H (Dalla et al 2013;Dalla and Dobler 2016). Given that these substitutions were engineered on a D. melanogaster background lacking A119S, our results suggest such substitutions are likely to be associated with substantial enzyme dysfunction.…”

Section: Introductionsupporting

confidence: 52%

“…In all cases examined to date, species with two or more copies retain one minimally altered copy that is more highly expressed in nervous tissue, and have evolved one or more insensitive copies that are more highly expressed in the gut, the site of absorption of CGs Yang et al 2019). Further support for negative pleiotropic effects is provided by the expression of engineered ATPa1 constructs in cell lines, suggesting that some duplicate-specific CG-insensitivity substitutions appear to reduce NKA activity (Dalla and Dobler 2016). Based on these findings, the frequent parallel substitutions observed at sites 111 and 122 in specialists lacking duplicate ATPa1 copies plausibly reflect the fact that substitutions at these sites are minimally pleiotropic.…”

Section: Introductionmentioning

confidence: 99%

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

Taverner

Yang

Barile

et al. 2019

Preprint

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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.

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Section: Introductionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

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

Taverner

Yang

Barile

et al. 2019

Preprint

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“…This basal level of resistance might have increased further in species adapted to feeding on cardenolide-producing plants. Physiological evidence supporting this idea has been found in several moth species (Petschenka et al, 2013), and the finding that Na/K-ATPase activity in BBB-protected neural tissue of the milkweed bug is less sensitive to cardenolides than activity in cell cultures expressing cardenolide-resistant Na/K-ATPase alleles also points to a protective effect of transporters in specialists (Dalla and Dobler, 2016). Our study provides a foundation for testing this evolutionary scenario via comparative functional genomics (Groen and Whiteman, 2016).…”

Section: Discussionmentioning

confidence: 80%

“…), oleander ( Nerium oleander ), lily of the valley ( Convallaria majalis ) and many other plant species comprise a model system to study convergent evolution at the molecular, physiological, morphological and behavioral levels (Agrawal et al, 2012; Dobler et al, 2015; Stern, 2013; Storz, 2016). Much molecular and genetic work has focused on putatively adaptive amino acid substitutions in the Na/K-ATPase that block cardenolides from binding to this essential pump (Dalla et al, 2013; Dalla and Dobler, 2016; Dobler et al, 2012, 2015; Zhen et al, 2012). However, recent findings indicate that the amino acid substitutions in the Na/K-ATPase may not be the only adaptations to reduce sensitivity to dietary cardenolides.…”

Section: Introductionmentioning

confidence: 99%

Multidrug transporters and organic anion transporting polypeptides protect insects against the toxic effects of cardenolides

Groen

LaPlante

Alexandre

et al. 2017

Insect Biochemistry and Molecular Biology

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In the struggle against dietary toxins, insects are known to employ target site insensitivity, metabolic detoxification, and transporters that shunt away toxins. Specialized insects across six taxonomic orders feeding on cardenolide-containing plants have convergently evolved target site insensitivity via specific amino acid substitutions in the Na/K-ATPase. Nonetheless, in vitro pharmacological experiments have suggested a role for multidrug transporters (Mdrs) and organic anion transporting polypeptides (Oatps), which may provide a basal level of protection in both specialized and non-adapted insects. Because the genes coding for these proteins are evolutionarily conserved and in vivo genetic evidence in support of this hypothesis is lacking, here we used wildtype and mutant Drosophila melanogaster (Drosophila) in capillary feeder (CAFE) assays to quantify toxicity of three chemically diverse, medically relevant cardenolides. We examined multiple components of fitness, including mortality, longevity, and LD50, and found that, while the three cardenolides each stimulated feeding (i.e., no deterrence to the toxin), all decreased lifespan, with the most apolar cardenolide having the lowest LD50 value. Flies showed a clear non-monotonic dose response and experienced high levels of toxicity at the cardenolide concentration found in plants. At this concentration, both Mdr and Oatp knockout mutant flies died more rapidly than wildtype flies, and the mutants also experienced more adverse neurological effects on high-cardenolide-level diets. Our study further establishes Drosophila as a model for the study of cardenolide pharmacology and solidifies support for the hypothesis that multidrug and organic anion transporters are key players in insect protection against dietary cardenolides.

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“…If selection acts on the context-dependent expression levels of individual genes, then adaptation could be limited by epistatic interactions between regulatory mutations, as shown in elegant work on E. coli by Poelwijk et al (7). Selection on coding variants might be even more constrained, as resolution most likely requires both gene duplication and regulatory divergence (8,9).…”

mentioning

confidence: 99%

Evolving Plastic Responses to External and Genetic Environments

et al. 2017

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Phenotypic plasticity can mitigate adaptive trade-offs in fluctuating environments but how plasticity arises is little known. New research documents this process in a bacterial system. We highlight remarkable parallels to the evolution of sexual dimorphism and argue that their approach can aid our understanding of adaptive conflicts between the sexes. Main textVirtually all organisms are subject to varying environmental conditions, be it seasonal differences in climate, different stages of the life cycle, or phases of population growth. These environmental fluctuations can create varying and sometimes conflicting demands on the phenotype. One way of accommodating these is to modulate the phenotype according to environmental conditions, a phenomenon known as phenotypic plasticity. A large body of literature has been dedicated to exploring the conditions under which plasticity is selectively favourable, and empirically documenting the extent to which plasticity occurs and has a heritable genetic basis (1).What is less well known is how the gene regulatory networks that mediate phenotypic plasticity evolve in response to opposing selection pressures. A recent article by Yi and Dean now sheds some light on these questions (2). They used an experimental evolution approach to explore adaptation in Escherichia coli to a cyclical environment that alternated between two selection pressures, one for rapid growth and one for chemotaxis. These contrasting regimes pose opposing demands on the phenotype, generating a trade-off in energy allocation between cell division and motility. Using models of population growth as a function of division rate in the growth-environment and motility in the chemotaxisenvironment, Yi and Dean were able to construct a fitness landscape on which to map the evolutionary trajectory of the experimental populations (3). They found that adaptation proceeded in three phases (Figure 1). In phase 1, populations moved quickly up the fitness gradient as they adapted to the specific experimental setup. In phase 2, further adaptation was constrained by the trade-off between growth and chemotaxis. Here, mutations that improved fitness in one of the environments decreased fitness in the other, with populations moving principally along the fitness isocline while changing minimally in overall fitness. Finally, the evolutionary constraint imposed by the trade-off was overcome in phase 3, where the populations were able to occupy novel regions of the fitness landscape.

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Gene duplications circumvent trade-offs in enzyme function: Insect adaptation to toxic host plants

Cited by 44 publications

References 64 publications

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

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

Multidrug transporters and organic anion transporting polypeptides protect insects against the toxic effects of cardenolides

Evolving Plastic Responses to External and Genetic Environments

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