2012/03/05 by Chris R. Feldman, Edmund D. Brodie, Michael E. Pfrender · 7 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Environmental Science · Mathematics · Neuroscience · #Adaptation (eye) #Biology #Biophysics #Chemistry #Computer science #Constraint (computer-aided design) #Convergent evolution #Environmental Toxicology and Ecotoxicology #Evolutionary biology #Gene #Genetics #Marine Toxins and Detection Methods #Mathematics #Natural selection #Neuroscience #Phylogenetics #Selection (genetic algorithm) #Sodium #Sodium channel #Tetrodotoxin #Venomous Animal Envenomation and Studies
paper · pdf · doi:10.1073/pnas.1113468109
openalex publication_date 2012/03/05 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/02
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.