Genetics and Molecular Biology
Print version ISSN 1415-4757
LU, Jian et al. Adaptive evolution of the vertebrate skeletal muscle sodium channel. Genet. Mol. Biol. [online]. 2011, vol.34, n.2, pp.323-328. ISSN 1415-4757. http://dx.doi.org/10.1590/S1415-47572011000200026.
Tetrodotoxin (TTX) is a highly potent neurotoxin that blocks the action potential by selectively binding to voltage-gated sodium channels (Nav). The skeletal muscle Nav (Nav1.4) channels in most pufferfish species and certain North American garter snakes are resistant to TTX, whereas in most mammals they are TTX-sensitive. It still remains unclear as to whether the difference in this sensitivity among the various vertebrate species can be associated with adaptive evolution. In this study, we investigated the adaptive evolution of the vertebrate Nav1.4 channels. By means of the CODEML program of the PAML 4.3 package, the lineages of both garter snakes and pufferfishes were denoted to be under positive selection. The positively selected sites identified in the p-loop regions indicated their involvement in Nav1.4 channel sensitivity to TTX. Most of these sites were located in the intracellular regions of the Nav1.4 channel, thereby implying the possible association of these regions with the regulation of voltage-sensor movement.
Keywords : skeletal muscle voltage-gated Na (Nav1.4) channel; tetrodotoxin (TTX); positive selection; pufferfish; garter snake.