Community-wide convergent evolution in insect adaptation to toxic cardenolides by substitutions in the Na,K-ATPase.

Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE

Original Publication: Washington, DC : National Academy of Sciences

Evolution, Molecular* ; Models, Molecular*; Adaptation, Biological/*genetics ; Cardenolides/*toxicity ; Drug Resistance/*genetics ; Insecta/*genetics ; Sodium-Potassium-Exchanging ATPase/*genetics; Adaptation, Biological/physiology ; Amino Acid Sequence ; Analysis of Variance ; Animals ; Base Sequence ; Cardenolides/chemistry ; Computational Biology ; DNA Primers/genetics ; Molecular Sequence Data ; Mutation, Missense/genetics ; North America ; Phylogeny ; Sequence Analysis, DNA ; Sodium-Potassium-Exchanging ATPase/chemistry ; Species Specificity

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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GENBANK HE956736; HE956737; HE956738; HE956739; HE956740; HE956741; HE956742; HE956743; HE956744; HE956745; HE956746; HE956747; HE956748; HE956749; HE956750; HE956751; HE956752; HE956753; HE956754; HE956755; HE956756

0 (Cardenolides)
0 (DNA Primers)
EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)

Date Created: 20120725 Date Completed: 20121015 Latest Revision: 20211021

20240829

PMC3420205

10.1073/pnas.1202111109

22826239