Dataset Information

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.

SUBMITTER: Feldman CR

PROVIDER: S-EPMC3311348 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Constraint shapes convergence in tetrodotoxin-resistant sodium channels of snakes.

Feldman Chris R CR Brodie Edmund D ED Brodie Edmund D ED Pfrender Michael E ME

Proceedings of the National Academy of Sciences of the United States of America 20120305 12

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 ...[more]

PMID: 22392995

Similar Datasets

Project description:Seemingly unrelated traits often share the same underlying molecular mechanisms, potentially generating a pleiotropic relationship whereby selection shaping one trait can simultaneously compromise another. While such functional trade-offs are expected to influence evolutionary outcomes, their actual relevance in nature is masked by obscure links between genotype, phenotype, and fitness. Here, we describe functional trade-offs that likely govern a key adaptation and coevolutionary dynamics in a predator-prey system. Several garter snake (Thamnophis spp.) populations have evolved resistance to tetrodotoxin (TTX), a potent chemical defense in their prey, toxic newts (Taricha spp.). Snakes achieve TTX resistance through mutations occurring at toxin-binding sites in the pore of snake skeletal muscle voltage-gated sodium channels (NaV1.4). We hypothesized that these mutations impair basic NaV functions, producing molecular trade-offs that should ultimately scale up to compromised organismal performance. We investigate biophysical costs in two snake species with unique and independently evolved mutations that confer TTX resistance. We show electrophysiological evidence that skeletal muscle sodium channels encoded by toxin-resistant alleles are functionally compromised. Furthermore, skeletal muscles from snakes with resistance genotypes exhibit reduced mechanical performance. Lastly, modeling the molecular stability of these sodium channel variants partially explains the electrophysiological and muscle impairments. Ultimately, adaptive genetic changes favoring toxin resistance appear to negatively impact sodium channel function, skeletal muscle strength, and organismal performance. These functional trade-offs at the cellular and organ levels appear to underpin locomotor deficits observed in resistant snakes and may explain variation in the population-level success of toxin-resistant alleles across the landscape, ultimately shaping the trajectory of snake-newt coevolution.

Dataset Information

Constraint shapes convergence in tetrodotoxin-resistant sodium channels of snakes.

Publications

Constraint shapes convergence in tetrodotoxin-resistant sodium channels of snakes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets