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

2019 ◽  
Vol 37 (2) ◽  
pp. 607-607
Author(s):  
Rebecca D Tarvin ◽  
Juan C Santos ◽  
Lauren A O'Connell ◽  
Harold H Zakon ◽  
David C Cannatella
Keyword(s):  
Sodium Channel ◽  
Poison Frogs ◽  
Toxin Resistance ◽  
Multiple Origins

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

2016 ◽  
Vol 33 (4) ◽  
pp. 1068-1080 ◽  
Author(s):  
Rebecca D Tarvin ◽  
Juan C Santos ◽  
Lauren A O'Connell ◽  
Harold H Zakon ◽  
David C Cannatella
Keyword(s):  
Amino Acid ◽  
Sodium Channel ◽  
Chemical Defense ◽  
Protein Docking ◽  
Genetic Changes ◽  
Poison Frogs ◽  
Toxin Resistance ◽  
Multiple Origins ◽  
Inner Pore

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 five 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.

scholarly journals Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on “toxin sponge” proteins

2021 ◽  
Vol 153 (9) ◽  
Author(s):  
Fayal Abderemane-Ali ◽  
Nathan D. Rossen ◽  
Megan E. Kobiela ◽  
Robert A. Craig ◽  
Catherine E. Garrison ◽  
...  
Keyword(s):  
Ion Channel ◽  
Sodium Channel ◽  
Small Molecule ◽  
Resistance Mechanism ◽  
Poison Frog ◽  
Poison Frogs ◽  
Toxin Resistance ◽  
Voltage Gated ◽  
Primary Driver ◽  
Toxin Sequestration

Many poisonous organisms carry small-molecule toxins that alter voltage-gated sodium channel (NaV) function. Among these, batrachotoxin (BTX) from Pitohui poison birds and Phyllobates poison frogs stands out because of its lethality and unusual effects on NaV function. How these toxin-bearing organisms avoid autointoxication remains poorly understood. In poison frogs, a NaV DIVS6 pore-forming helix N-to-T mutation has been proposed as the BTX resistance mechanism. Here, we show that this variant is absent from Pitohui and poison frog NaVs, incurs a strong cost compromising channel function, and fails to produce BTX-resistant channels in poison frog NaVs. We also show that captivity-raised poison frogs are resistant to two NaV-directed toxins, BTX and saxitoxin (STX), even though they bear NaVs sensitive to both. Moreover, we demonstrate that the amphibian STX “toxin sponge” protein saxiphilin is able to protect and rescue NaVs from block by STX. Taken together, our data contradict the hypothesis that BTX autoresistance is rooted in the DIVS6 N→T mutation, challenge the idea that ion channel mutations are a primary driver of toxin resistance, and suggest the possibility that toxin sequestration mechanisms may be key for protecting poisonous species from the action of small-molecule toxins.

scholarly journals Sodium channel toxin-resistance mutations do not govern batrachotoxin (BTX) autoresistance in poison birds and frogs

2020 ◽  
Author(s):  
Fayal Abderemane-Ali ◽  
Nathan D. Rossen ◽  
Megan E. Kobiela ◽  
Robert A. Craig ◽  
Catherine E. Garrison ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Small Molecule ◽  
Resistance Mechanism ◽  
Resistance Mutations ◽  
Poison Frog ◽  
Poison Frogs ◽  
Toxin Resistance ◽  
Voltage Gated ◽  
Channel Function ◽  
Toxin Sequestration

AbstractPoisonous organisms carry small molecule toxins that alter voltage-gated sodium channel (Na✓) function. Among these, batrachotoxin (BTX) from Pitohui toxic birds and Phyllobates poison frogs, stands out because of its lethality and unusual effects on Nav function. How these toxin-bearing organisms avoid autointoxication remains poorly understood. In poison frogs, a Nav DIVS6 pore-forming helix N→T mutation has been proposed as the BTX resistance mechanism. Here, we show that this variant is absent from Pitohui and poison frog Navs, incurs a strong cost that compromises channel function, and fails to produce BTX-resistant channels when tested in the context of poison frog Navs. We further show that captive-raised poison frogs are BTX resistant, even though they bear BTX-sensitive Navs. Hence, our data refute the hypothesis that BTX autoresistance is rooted in Nav mutations and instead suggest that more generalizable mechanisms such as toxin sequestration act to protect BTX-bearing species from autointoxication.

scholarly journals Multiple Origins of the Sodium Channel kdr Mutations in Codling Moth Populations

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e43543 ◽  
Author(s):  
Pierre Franck ◽  
Myriam Siegwart ◽  
Jerome Olivares ◽  
Jean-François Toubon ◽  
Claire Lavigne
Keyword(s):  
Sodium Channel ◽  
Codling Moth ◽  
Multiple Origins

Assessment of the Nav1.2 sodium channel activity of Aconitum diterpene and norditerpene alkaloids

Planta Medica ◽  
2013 ◽  
Vol 79 (13) ◽  
Author(s):  
B Borcsa ◽  
L Fodor ◽  
D Csupor ◽  
P Forgo ◽  
J Hohmann
Keyword(s):  
Sodium Channel ◽  
Channel Activity ◽  
Norditerpene Alkaloids

The Voltage-Gated Sodium Channel Nav1.2 Contributes to Neurodegeneration in an Animal Model of Multiple Sclerosis

2016 ◽  
Vol 47 (S 01) ◽  
Author(s):  
W. Fazeli ◽  
B. Schattling ◽  
B. Engeland ◽  
M. Friese ◽  
D. Isbrand
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

Comparative Analysis of Genetic and Morphological Variation within the Platanthera hyperborea Complex (Orchidaceae)

2020 ◽  
Vol 45 (4) ◽  
pp. 767-778
Author(s):  
Eranga Wettewa ◽  
Nick Bailey ◽  
Lisa E. Wallace
Keyword(s):  
North America ◽  
Diploid Species ◽  
Morphological Characters ◽  
Evolutionary Patterns ◽  
Founding Population ◽  
Multiple Origins ◽  
Geographic Structure ◽  
Species Complexes ◽  
Nuclear Its ◽  
Cryptic Taxa

Abstract—Species complexes present considerable problems for a working taxonomy due to the presence of intraspecific variation, hybridization, polyploidy, and phenotypic plasticity. Understanding evolutionary patterns using molecular markers can allow for a more thorough assessment of evolutionary lineages than traditional morphological markers. In this study, we evaluated genetic diversity and phylogenetic patterns among taxa of the Platanthera hyperborea (Orchidaceae) complex, which includes diploid (Platanthera aquilonis) and polyploid (Platanthera hyperborea, P. huronensis, and P. convallariifolia) taxa spanning North America, Greenland, Iceland, and Asia. We found that three floral morphological characters overlap among the polyploid taxa, but the diploid species has smaller flowers. DNA sequence variation in a plastid (rpL16 intron) and a nuclear (ITS) marker indicated that at least three diploid species have contributed to the genomes of the polyploid taxa, suggesting all are of allopolyploid origin. Platanthera convallariifolia is most like P. dilatata and P. stricta, whereas P. huronensis and P. hyperborea appear to have originated from crosses of P. dilatata and P. aquilonis. Platanthera huronensis, which is found across North America, has multiple origins and reciprocal maternal parentage from the diploid species. By contrast, P. hyperborea, restricted to Greenland and Iceland, appears to have originated from a small founding population of hybrids in which P. dilatata was the maternal parent. Geographic structure was found among polyploid forms in North America. The area of Manitoba, Canada appears to be a contact zone among geographically diverse forms from eastern and western North America. Given the geographic and genetic variation found, we recommend continued recognition of four green-flowered species within this complex, but caution that there may be additional cryptic taxa within North America.

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