# Convergent Substitutions in a Sodium Channel Suggest Multiple Origins of Toxin....



## ryangreenway (Apr 30, 2010)

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

If not available through the publisher website, here is the link to the pdf in one of the author's website:
http://oconnell.fas.harvard.edu/files/oconnell/files/tarvin2016.pdf


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## Ravage (Feb 5, 2016)

Fascinating.
Now be truthful: have you ever wished your froggies were still toxic in captivity? I'm always surprised when someone comes over and freaks out because they think the Darts are as deadly as plutonium.


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## Trojan (Oct 15, 2014)

This is really cool stuff. I work for a biochemist and so we look at stuff like this on occassion but I have never considered this in frogs. So of the four major toxin groups would they (the frogs of each group) be somewhat resistant to each other toxins since I imagine that the toxin act on protiens within the ion channel specific to its predators? Also do we know much about if the pitohui bird has similar replacement proteins within the ion channels since they also use a similar toxin? So for the sake of relating it to human medicine, are there any applications to therapeutics? 

Really really cool stuff. Thanks for posting


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