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      Convergent Substitutions in a Sodium Channel Suggest Multiple Origins of Toxin Resistance in Poison Frogs

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      Molecular Biology and Evolution

      Oxford University Press (OUP)

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          Abstract

          Complex phenotypes typically have a correspondingly multifaceted genetic component. However, the genotype-phenotype association between chemical defense and resistance is often simple: genetic changes in the binding site of a toxin alter how it affects its target. Some toxic organisms, such as poison frogs (Anura: Dendrobatidae), have defensive alkaloids that disrupt the function of ion channels, proteins that are crucial for nerve and muscle activity. Using protein-docking models, we predict that three major classes of poison frog alkaloids (histrionicotoxins, pumiliotoxins, and batrachotoxins) bind to similar sites in the highly conserved inner pore of the muscle voltage-gated sodium channel, Nav1.4. We predict that poison frogs are somewhat resistant to these compounds because they have six types of amino acid replacements in the Nav1.4 inner pore that are absent in all other frogs except for a distantly related alkaloid-defended frog from Madagascar, Mantella aurantiaca. Protein-docking models and comparative phylogenetics support the role of these replacements in alkaloid resistance. Taking into account the four independent origins of chemical defense in Dendrobatidae, phylogenetic patterns of the amino acid replacements suggest that 1) alkaloid resistance in Nav1.4 evolved independently at least seven times in these frogs, 2) variation in resistance-conferring replacements is likely a result of differences in alkaloid exposure across species, and 3) functional constraint shapes the evolution of the Nav1.4 inner pore. Our study is the first to demonstrate the genetic basis of autoresistance in frogs with alkaloid defenses.

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          Basic Local Alignment Search Tool

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            Detecting Correlated Evolution on Phylogenies: A General Method for the Comparative Analysis of Discrete Characters

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              The evolutionary ecology of insect resistance to plant chemicals.

              Understanding the diversity of insect responses to chemical pressures (e.g. plant allelochemicals and pesticides) in their local ecological context represents a key challenge in developing durable pest control strategies. To what extent do the resistance mechanisms evolved by insects to deal with the chemical defences of plants differ from those that have evolved to resist insecticides? Here, we review recent advances in our understanding of insect resistance to plant chemicals, with a special emphasis on their underlying molecular basis, evaluate costs associated with each resistance trait, and discuss the ecological and evolutionary significance of these findings.
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                Author and article information

                Journal
                Molecular Biology and Evolution
                Mol Biol Evol
                Oxford University Press (OUP)
                0737-4038
                1537-1719
                March 03 2016
                April 2016
                April 2016
                January 18 2016
                : 33
                : 4
                : 1068-1081
                Article
                10.1093/molbev/msv350
                26782998
                © 2016

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