Constraint shapes convergence in tetrodotoxin-resistant sodium channels of snakes

Abstract

Natural selection often produces convergent changes in unrelated lineages, but the degree to which such adaptations occur via predictable genetic paths is unknown. If only a limited subset of possible mutations is fixed in independent lineages, then it is clear that constraint in the production or function of molecular variants is an important determinant of adaptation. We demonstrate remarkably constrained convergence during the evolution of resistance to the lethal poison, tetrodotoxin, in six snake species representing three distinct lineages from around the globe. Resistance-conferring amino acid substitutions in a voltage-gated sodium channel, Na v 1.4, are clustered in only two regions of the protein, and a majority of the replacements are confined to the same three positions. The observed changes represent only a small fraction of the experimentally validated mutations known to increase Na v 1.4 resistance to tetrodotoxin. These results suggest that constraints resulting from functional tradeoffs between ion channel function and toxin resistance led to predictable patterns of evolutionary convergence at the molecular level. Our data are consistent with theoretical predictions and recent microcosm work that suggest a predictable path is followed during an adaptive walk along a mutational landscape, and that natural selection may be frequently constrained to produce similar genetic outcomes even when operating on independent lineages. coevolution | molecular evolution | pleiotropy

Community-wide convergent evolution in insect adaptation to toxic cardenolides by substitutions in the Na,K-ATPase

“…In several instances, molecular similarities go along with adaptations observed at the phenotypic level [e.g., lysozmyes of foregut fermenters (30), prestin genes of echolocating bats and toothed whales (31,32), and visual pigments of primates and cephalopods (33)]. However, in only few instances was the observed convergence at the genetic level experimentally connected to the functional phenotypes [e.g., for amino acid substitutions in the melanocortin-1 receptor responsible for light coloration in beach mice (34) and in tetrodotoxin-resistant sodium channels in snakes (1,35)]. …”

“…insect-plant interactions | specialist herbivores | target site insensitivity | toxin resistance | cardiac glycosides T he extent to which adaptive evolution is predictable at the molecular level is still highly debated (1,2). When evolution proceeds by alterations in genes of major effect, convergence at the molecular level is more likely than if many genes are involved (3).…”

Widespread convergence in toxin resistance by predictable molecular evolution

“…Epitomized by the writings of Gould (5) and Conway Morris (6), this debate centers on whether evolution is stochastic and unpredictable (5) or subject to constraints that limit the available options for evolution, resulting in frequent convergence and a degree of predictability (6). However, evidence of convergence at the genetic level, where similar molecular changes confer the same change in phenotype, is currently limited to only a few taxonomically restricted examples (7)(8)(9)(10)(11).…”

Evolutionary GEM: The Evolutionary Arms Race of Garter Snakes and Newts

“…Another expectation is that a toxin severe enough to drive a predator-prey arms race should produce similar parallel arms races between multiple distinct species pairs, where the prey share the same toxin 1,10 . Thamnophis sirtalis is the first predator known to be coevolving with toxic newts, but the distantly related aquatic garter snake (Thamnophis couchii) also exhibits increased TTX resistance in response to another TTX-producing prey, the California newt (Taricha torosa) 1 .…”

“…The newt and garter snake's arms race acts accordingly within these expectations; it is disadvantageous to exhibit either excessive TTX quantities or TTX resistance. TTX resistance in the common garter snake comes with a genetically based trade-off for slower crawl speed 8,10 . In the absence of toxic prey, this is a tremendous cost to the snake's ability to evade predators and hunt prey.…”