Convergent Evolution of Tetrodotoxin-Resistant Sodium Channels in Predators and Prey

Toledo, Gabriela; Hanifin, Charles T.; Geffeney, Shana L.; Brodie, Edmund D.

doi:10.1016/bs.ctm.2016.07.006

Cited by 24 publications

(24 citation statements)

References 69 publications

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“…The lesser sensitivity of macroinvertebrates is consistent with the ability of some insect taxa to buffer the effects of poisons by investing energetic resources into cuticle deposition, thereby decreasing the need to upregulate transcription of more enzymes to catalyze metabolism (Wood et al, 2010). Correspondingly, several macroinvertebrate taxa have been shown to consume larval or embryonic Taricha without notably ill effects, including larvae of Trichoptera, Zygoptera, and Anisoptera (Gall et al, 2012, 2011; Toledo et al, 2016). For instance, caddisfly larvae consume the eggs of T. granulosa (maximum of 1.53 µg TTX/egg) (Gall et al, 2012; Mebs et al, 2016) while dragonfly nymphs will eat larvae of both T. granulosa and T. torosa (0.296 ± 0.103 µg TTX/larva) (Bucciarelli and Kats, 2015; Mebs et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Adult Taricha are hypothesized to use TTX as a chemical defense against predators, including birds, fishes, and garter snakes (Brodie III et al, 2005; Brodie Jr, 1968; Farner and Kezer, 1953; Storm, 1948). Predation on newts has often been studied as part of a coevolutionary framework positing that adult Taricha have evolved greater toxicity in response to predation by garter snakes, which can develop genetic resistance to the toxin (Brodie III et al, 2005; Brodie III and Brodie Jr, 1999, 1990; Toledo et al, 2016; Williams et al, 2003). …”

Section: Introductionmentioning

confidence: 99%

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Noxious newts and their natural enemies: Experimental effects of tetrodotoxin exposure on trematode parasites and aquatic macroinvertebrates

Calhoun

Bucciarelli

Kats

et al. 2017

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The dermal glands of many amphibian species secrete toxins or other noxious substances as a defense strategy against natural enemies. Newts in particular possess the potent neurotoxin tetrodotoxin (TTX), for which the highest concentrations are found in species within the genus Taricha. Adult Taricha are hypothesized to use TTX as a chemical defense against vertebrate predators such as garter snakes (Thamnophis spp.). However, less is known about how TTX functions to defend aquatic-developing newt larvae against natural enemies, including trematode parasites and aquatic macroinvertebrates. Here we experimentally investigated the effects of exogenous TTX exposure on survivorship of the infectious stages (cercariae) of five species of trematode parasites that infect larval amphibians. Specifically, we used dose-response curves to test the sensitivity of trematode cercariae to progressively increasing concentrations of TTX (0.0 [control], 0.63, 3.13, 6.26, 31.32, and 62.64 nmol L−1) and how this differed among parasite species. We further compared these results to the effects of TTX exposure (0 and 1,000 nmolL−1) over 24 hr on seven macroinvertebrate taxa commonly found in aquatic habitats with newt larvae. TTX significantly reduced the survivorship of trematode cercariae for all species, but the magnitude of such effects varied among species. Ribeiroia ondatrae – which causes mortality and limb malformations in amphibians – was the least sensitive to TTX, whereas the kidney-encysting Echinostoma trivolvis was the most sensitive. Among the macroinvertebrate taxa, only mayflies (Ephemeroptera) showed a significant increase in mortality following exogenous TTX exposure, despite the use of a concentration 16x higher than the maximum used for trematodes. Our results suggest that maternal investment of TTX into larval newts may provide protection against certain trematode infections and highlight the importance of future work assessing the effects of newt toxicity on both parasite infection success and the palatability of larval newts to invertebrate predators.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Noxious newts and their natural enemies: Experimental effects of tetrodotoxin exposure on trematode parasites and aquatic macroinvertebrates

Calhoun

Bucciarelli

Kats

et al. 2017

Toxicon

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“…Changes to the Na V 1.4 pore probably reflect a delicate balance between TTX-resistant properties and the maintenance of Na V channel function (Feldman et al 2012;Toledo et al 2016). Na V channels play the highly conserved role of signaling in muscle and nerve tissue (Goldin 2002).…”

Section: Potential Drivers Of Historical Convergencementioning

confidence: 99%

“…The p-loops form the selectivity filter at the channel pore, which is critically responsible for the selective influx of Na + ions that propagate action potentials. Consequently, only a limited number of mutations can confer TTX resistance without disrupting Na V ion channel function (Feldman et al 2012;Toledo et al 2016). Consequently, only a limited number of mutations can confer TTX resistance without disrupting Na V ion channel function (Feldman et al 2012;Toledo et al 2016).…”

Section: Potential Drivers Of Historical Convergencementioning

confidence: 99%

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Convergent adaptation to dangerous prey proceeds through the same first‐step mutation in the garter snake Thamnophis sirtalis

2017

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Convergent phenotypes often result from similar underlying genetics, but recent work suggests convergence may also occur in the historical order of substitutions en route to an adaptive outcome. We characterized convergence in the mutational steps to two independent outcomes of tetrodotoxin (TTX) resistance in separate geographic lineages of the common garter snake (Thamnophis sirtalis) that coevolved with toxic newts. Resistance is largely conferred by amino acid changes in the skeletal muscle sodium channel (Na 1.4) that interfere with TTX-binding. We sampled variation in Na 1.4 throughout western North America and found clear evidence that TTX-resistant changes in both lineages began with the same isoleucine-valine mutation (I1561V) within the outer pore of Na 1.4. Other point mutations in the pore, shown to confer much greater resistance, accumulate later in the evolutionary progression and always occur together with the initial I1561V change. A gene tree of Na 1.4 suggests the I1561V mutations in each lineage are not identical-by-decent, but rather they arose independently. Convergence in the evolution of channel resistance is likely the result of shared biases in the two lineages of T. sirtalis-only a few mutational routes can confer TTX resistance while maintaining the conserved function of voltage-gated sodium channels.

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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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Convergent Evolution of Tetrodotoxin-Resistant Sodium Channels in Predators and Prey

Cited by 24 publications

References 69 publications

Noxious newts and their natural enemies: Experimental effects of tetrodotoxin exposure on trematode parasites and aquatic macroinvertebrates

Noxious newts and their natural enemies: Experimental effects of tetrodotoxin exposure on trematode parasites and aquatic macroinvertebrates

Convergent adaptation to dangerous prey proceeds through the same first‐step mutation in the garter snake Thamnophis sirtalis

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

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