Combating tetrodotoxin: snakes win?

An interesting article by Chris Feldman and colleagues suggests that adaptive convergent evolution (in this case resistance to a potent toxin, tetrodotoxin)  can be constrained to “genetic hotspots”. When the target function is highly conserved (in this case the pores of muscle and nerve sodium channels) and if resistance requires changes to pore structure (reducing the capacity for tetrodotoxin to bind with the pore) there may be few options when it comes to retaining function while altering the structure enough to discourage binding.  For more see  Constraint shapes convergence in tetrodotoxin-resistant sodium channels of snakes by Chris R. Feldman et al. (2012) PNAS 109:4556-4561 The abstract is pasted below:

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, Nav1.4, 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 Nav1.4 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.

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