Is there more than one way to skin a newt? Convergent toxin resistance in snakes is not due to a common genetic mechanism

Feldman, Chris R.; Durso, Andrew M.; Hanifin, Charles T.; Pfrender, Michael E.; Ducey, Peter K.; Stokes, Amber N.; Barnett, Karen; Brodie, Edmund D.

doi:10.1038/hdy.2015.73

Cited by 29 publications

(29 citation statements)

References 56 publications

(87 reference statements)

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“…, ; Feldman et al. ). Consequently, there may be other unknown mechanisms that contribute to a trade‐off between physiological resistance and crawl speed.…”

Section: Resultsmentioning

confidence: 99%

Large-effect mutations generate trade-off between predatory and locomotor ability during arms race coevolution with deadly prey

et al. 2018

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Adaptive evolution in response to one selective challenge may disrupt other important aspects of performance. Such evolutionary trade‐offs are predicted to arise in the process of local adaptation, but it is unclear if these phenotypic compromises result from the antagonistic effects of simple amino acid substitutions. We tested for trade‐offs associated with beneficial mutations that confer tetrodotoxin (TTX) resistance in the voltage‐gated sodium channel (NaV1.4) in skeletal muscle of the common garter snake (Thamnophis sirtalis). Separate lineages in California and the Pacific Northwest independently evolved TTX‐resistant changes to the pore of NaV1.4 as a result of arms race coevolution with toxic prey, newts of the genus Taricha. Snakes from the California lineage that were homozygous for an allele known to confer large increases in toxin resistance (NaV1.4LVNV) had significantly reduced crawl speed compared to individuals with the ancestral TTX‐sensitive channel. Heterologous expression of native snake NaV1.4 proteins demonstrated that the same NaV1.4LVNV allele confers a dramatic increase in TTX resistance and a correlated decrease in overall channel excitability. Our results suggest the same mutations that accumulate during arms race coevolution and beneficially interfere with toxin‐binding also cause changes in electrophysiological function of the channel that may affect organismal performance. This trade‐off was only evident in the predator lineage where coevolution has led to the most extreme resistance phenotype, determined by four critical amino acid substitutions. If these biophysical changes also translate to a fitness cost—for example, through the inability of T. sirtalis to quickly escape predators—then pleiotropy at this single locus could contribute to observed variation in levels of TTX resistance across the mosaic landscape of coevolution.

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“…, ; Feldman et al. ). Consequently, there may be other unknown mechanisms that contribute to a trade‐off between physiological resistance and crawl speed.…”

Section: Resultsmentioning

confidence: 99%

Large-effect mutations generate trade-off between predatory and locomotor ability during arms race coevolution with deadly prey

et al. 2018

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“…The pharmacological effects of most of ant and termite compounds are also poorly understood, and thus it is uncertain whether the same mutations to Na þ /K þ -ATPase that confer resistance to BDs would protect against those prey. However, evidence of resistance to both BDs and alkaloids has been demonstrated in Heterodon platirhinos, a highly bufophagous species that is also resistant to TTX in newts, although the mechanism for its resistance to TTX remains unknown [58]. Clearly, additional sequencing of diverse scolecophidian species is needed, together with a better understanding of the physiological effects of their prey's defensive toxins.…”

Section: Discussionmentioning

confidence: 99%

Toxin-resistant isoforms of Na⁺/K⁺-ATPase in snakes do not closely track dietary specialization on toads

et al. 2016

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Toads are chemically defended by bufadienolides, a class of cardiotonic steroids that exert toxic effects by binding to and disabling the Na/K-ATPases of cell membranes. Some predators, including a number of snakes, have evolved resistance to the toxic effects of bufadienolides and prey regularly on toads. Resistance in snakes to the acute effects of these toxins is conferred by at least two amino acid substitutions in the cardiotonic steroid binding pocket of the Na/K-ATPase. We surveyed 100 species of snakes from a broad phylogenetic range for the presence or absence of resistance-conferring mutations. We found that such mutations occur in a much wider range of taxa than previously believed. Although all sequenced species known to consume toads exhibited the resistance mutations, many of the species possessing the mutations do not feed on toads, much less specialize on that food source. This suggests that either there is little performance cost associated with these mutations or they provide an unknown benefit. Furthermore, the distribution of the mutation among major clades of advanced snakes suggests that the origin of the mutation reflects evolutionary retention more than dietary constraint.

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“…Because of the fundamental physiological role of the targets of tetrodotoxin in nerve transmission, the viable pathways to resistance are seemingly heavily constrained in terms of what changes to the proteins remain consistent with their function (Feldman et al, 2012;Brodie and Brodie, 2015), resulting in a classic example of convergent molecular evolution. However, other snakes have since been demonstrated to have evolved resistance to tetrodotoxin via completely different, Nav channel-independent, mechanisms (Feldman et al, 2016), indicating that multiple pathways to resistance exist for this model. Our final example of this mode of resistance is that of cardiac glycosides.…”

Section: Resistance Via Target-site Insensitivitymentioning

confidence: 99%

Coevolution takes the sting out of it: Evolutionary biology and mechanisms of toxin resistance in animals

Arbuckle

Vega

Casewell

2017

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Understanding how biotic interactions shape the genomes of the interacting species is a long-sought goal of evolutionary biology that has been hampered by the scarcity of tractable systems in which specific genomic features can be linked to complex phenotypes involved in interspecific interactions. In this review we present the compelling case of evolved resistance to the toxic challenge of venomous or poisonous animals as one such system. Animal venoms and poisons can be comprised of few or of many individual toxins. Here we show that resistance to animal toxins has evolved multiple times across metazoans, although it has been documented more often in phyla that feed on chemically-armed animals than in prey of venomous predators. We review three types of gene-product based resistance: 1) toxin scavenging, where molecules produced by the envenomed organism bind and inactivate the toxins; 2) target-site insensitivity, including landmark cases of convergent changes that make the molecules normally targeted by animal toxins refractory, and; 3) off-target repurposing, where envenomed organisms overcome toxicity by exploiting the function of toxins to alter their physiological effect. We finish by discussing the evolutionary processes that likely played a role in the origin and maintenance of toxin resistance. We conclude that antagonistic interactions involving poisonous or venomous animals are unparalleled models for investigating microevolutionary processes involved in coevolution and linking them to macroevolutionary patterns.

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Is there more than one way to skin a newt? Convergent toxin resistance in snakes is not due to a common genetic mechanism

Cited by 29 publications

References 56 publications

Large-effect mutations generate trade-off between predatory and locomotor ability during arms race coevolution with deadly prey

Large-effect mutations generate trade-off between predatory and locomotor ability during arms race coevolution with deadly prey

Toxin-resistant isoforms of Na⁺/K⁺-ATPase in snakes do not closely track dietary specialization on toads

Coevolution takes the sting out of it: Evolutionary biology and mechanisms of toxin resistance in animals

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Is there more than one way to skin a newt? Convergent toxin resistance in snakes is not due to a common genetic mechanism

Cited by 29 publications

References 56 publications

Large-effect mutations generate trade-off between predatory and locomotor ability during arms race coevolution with deadly prey

Large-effect mutations generate trade-off between predatory and locomotor ability during arms race coevolution with deadly prey

Toxin-resistant isoforms of Na+/K+-ATPase in snakes do not closely track dietary specialization on toads

Coevolution takes the sting out of it: Evolutionary biology and mechanisms of toxin resistance in animals

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Toxin-resistant isoforms of Na⁺/K⁺-ATPase in snakes do not closely track dietary specialization on toads