ArticleProceedings of the National Academy of Sciences of the United States of America2012
Community-wide convergent evolution in insect adaptation to toxic cardenolides by substitutions in the Na,K-ATPase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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117 citing papers in PubMed, 301 citations in OpenAlex.
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- RECUR: identifying recurrent amino acid substitutions from multiple sequence alignments.Molecular biology and evolution · 2026Article
- Amino Acid Substitutions in the NaEcological entomology · 2026Article
- Substitutions in the cardiac glycoside binding site of the NaJournal of invertebrate pathology · 2026Article
- Estimates of molecular convergence reveal multiple genes with adaptive variation across teleost fish.Molecular biology and evolution · 2026Article
- Genomic basis of adaptation to cardiac glycosides in three insect orders.Frontiers in genetics · 2026Article
- Analysis of multi-trait evolution across independently evolved cavefish populations reveals shared and independent evolution of suites of cave-associated traits.bioRxiv : the preprint server for biology · 2025Article
- Repeatability of protein structural evolution following convergent gene fusions.Nature communications · 2025Article
- Odorant Receptors Mediating Avoidance of Toxic Mustard Oils in Drosophila melanogaster Are Expanded in Herbivorous Relatives.Molecular biology and evolution · 2025Article
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- Standing genetic variation and introgression shape the cryptic radiation of Aquilegia in the mountains of Southwest China.Communications biology · 2025Article
- Genome and Tissue-Specific Transcriptome of the Tropical Milkweed (Plant direct · 2025Article
- No detectable effect of urbanization on genetic drift or gene flow in specialist herbivorous insects of milkweed.PloS one · 2025Article
- Substrate Specificity of ABCB Transporters Predicted by Docking Simulations Can Be Confirmed by Experimental Tests.Molecules (Basel, Switzerland) · 2024Article
- Evolutionary Rate Shifts in Coding and Regulatory Regions Underpin Repeated Adaptation to Sulfidic Streams in Poeciliid Fishes.Genome biology and evolution · 2024Article
57 more citing papers are in PubMed but not listed here.
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4 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
The extent of convergent molecular evolution is largely unknown, yet is critical to understanding the genetics of adaptation. Target site insensitivity to cardenolides is a prime candidate for studying molecular convergence because herbivores in six orders of insects have specialized on these plant poisons, which gain their toxicity by blocking an essential transmembrane carrier, the sodium pump (Na,K-ATPase). We investigated gene sequences of the Na,K-ATPase α-subunit in 18 insects feeding on cardenolide-containing plants (spanning 15 genera and four orders) to screen for amino acid substitutions that might lower sensitivity to cardenolides. The replacement N122H that was previously shown to confer resistance in the monarch butterfly (Danaus plexippus) and Chrysochus leaf beetles was found in four additional species, Oncopeltus fasciatus and Lygaeus kalmii (Heteroptera, Lygaeidae), Labidomera clivicollis (Coleoptera, Chrysomelidae), and Liriomyza asclepiadis (Diptera, Agromyzidae). Thus, across 300 Myr of insect divergence, specialization on cardenolide-containing plants resulted in molecular convergence for an adaptation likely involved in coevolution. Our screen revealed a number of other substitutions connected to cardenolide binding in mammals. We confirmed that some of the particular substitutions provide resistance to cardenolides by introducing five distinct constructs of the Drosophila melanogaster gene into susceptible eucaryotic cells under an ouabain selection regime. These functional assays demonstrate that combined substitutions of Q(111) and N(122) are synergistic, with greater than twofold higher resistance than either substitution alone and >12-fold resistance over the wild type. Thus, even across deep phylogenetic branches, evolutionary degrees of freedom seem to be limited by physiological constraints, such that the same molecular substitutions confer adaptation.
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