Adaptive evolution of the vertebrate skeletal muscle sodium channel

Abstract

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.

Genome-wide analysis of GRAS transcription factor gene family in Gossypium hirsutum L.

“…Then, the aligned sequences were converted to the original cDNA sequences by the PAL2NAL program [ 57 ] ( http://www.bork.embl.de/pal2nal/ ). Finally, The CODEML program of the PAML package [ 58 ] was used to estimate the synonymous (Ks) and nonsynonymous (Ka) substitution rates.…”

Animal Models in an Age of Personalized Medicine

“…Independent evolution has also resulted in various frogs, newts and fish that utilize tetrodotoxin from bacteria to block sodium channels in their prey or enemies. However, these animals have evolved mutations in the genes coding for sodium channels such that the channels are resistant to the toxin [203,204,310].…”

Large Scale Analyses and Visualization of Adaptive Amino Acid Changes Projects

“…Amino acid changes in protein sequences can be adaptive, and when changes at few amino acid sites are the target of selection they can be detected using maximum-likelihood methods based on the models of codon substitution [ 1 – 3 ]. This approach has been applied numerous times to infer positively selected amino acid sites at numerous proteins including, but not limited to: interleukin-3 (IL3), a protein associated with brain volume variation in general human populations [ 4 ]; formyl peptide receptors in mammals [ 5 ]; scorpion sodium channel toxins [ 6 ]; the Mimulus plant CENH3 protein [ 7 ]; the oyster Crassostrea gigas peptidoglycan recognition proteins [ 8 ]; host immune response genes [ 9 , 10 ]; the envelope glycoprotein of dengue viruses [ 11 ]; the attachment glycoprotein of respiratory syncytial virus [ 12 ]; measles virus hemagglutinin [ 13 ]; influenza B virus hemagglutinin [ 14 ]; HIV proteins [ 15 ]; hemagglutinin-neuraminidase protein of Newcastle disease virus [ 16 ]; Trypanosoma brucei proteins [ 17 ]; the vertebrate skeletal muscle sodium channel protein [ 18 ]; the p53 protein [ 19 ]; the fruitless protein in Anastrepha fruit flies [ 20 ]; CC chemokine receptor proteins [ 21 ]; or the proteins encoded by plant genes that are involved in gametophytic self-incompatibility specificity determination [ 22 – 25 ]. Recently, it has been argued that pharma and biotech industries can successfully use the knowledge generated by such an approach to deal with real-life problems [ 26 ].…”