GEPHE SUMMARY Print
Gephebase Gene
Entry Status
Published
GepheID
GP00001574
Main curator
Prigent
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Frogs susceptible to alkaloids
Trait State in Taxon B
Poison frog Phyllobates terribilis (Dendrobatidae) resistant to toxin
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Latin Name
Common Name
frogs and toads
Synonyms
Salientia; frogs and toads; anurans; frogs
Rank
order
Lineage
Show more ... Opisthokonta; Metazoa; Eumetazoa; Bilateria; Deuterostomia; Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amphibia; Batrachia
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Common Name
-
Synonyms
-
Rank
species
Lineage
Show more ... iata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi; Sarcopterygii; Dipnotetrapodomorpha; Tetrapoda; Amphibia; Batrachia; Anura; Neobatrachia; Hyloidea; Dendrobatidae; Dendrobatinae; Phyllobates
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
T>G p.S429A in DI-S6 domain
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid - - -
Authors
Tarvin RD; Santos JC; O'Connell LA; Zakon HH; Cannatella DC
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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Additional References
RELATED GEPHE
Related Haplotypes
15
COMMENTS
Non-null mutation
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