Abstract
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.
Highlights
Evolutionary trade-offs are commonly expected to arise during the process of adaptation
We found that trade-offs at multiple levels of biological organization occur due to beneficial mutations that confer tetrodotoxin (TTX) resistance in
As a population evolves toward a new adaptive peak, phenotypic compromises are expected to arise if an underlying allele impacts multiple aspects of organismal performance (Felsenstein 1976; Hedrick et al 1976; Hedrick 1986, 2006; Kawecki and Ebert 2004; Bono et al 2017)
Summary
Evolutionary trade-offs are commonly expected to arise during the process of adaptation. The same set of TTX-resistant mutations reduces the overall excitability of voltage-gated sodium channels, a critical component of the vertebrate nervous system These results suggest that the antagonistic effects of just a small number of amino acid substitutions at a single locus have the potential to influence broader ecological trade-offs and drive mosaic patterns of adaptation across the landscape. At an underlying molecular level, these trade-offs must be driven to a degree by specific changes in protein function and biomechanics, such that the biophysical changes of a single mutation may be beneficial in one sense, but disruptive to other important aspects of performance (Wang et al 2002; DePristo et al 2005; Weinreich et al 2006; Harms and Thornton 2013; Natarajan et al 2016; Storz 2016) In this respect, pleiotropy is thought to be an important driver of broader phenotypic patterns of adaptation; a functional link between changes in the structure of individual proteins and population variation in phenotypic trade-offs remains tenuous (Hall et al 2010; Anderson et al 2011, 2013; Savolainen et al 2013; Agren et al 2013, 2017; Bono et al 2017). We predict that as beneficial mutations accrue in response to one selective challenge, their pleiotropic effects will generate trade-offs observable in landscape patterns of phenotypic variation
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