10 research outputs found
Adaptive evolution of the vertebrate skeletal muscle sodium channel
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
Gene duplications and evolution of vertebrate voltage-gated sodium channels
Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Molecular Evolution 63 (2006): 208-221, doi:10.1007/s00239-005-0287-9.Voltage-gated sodium channels underlie action potential generation in excitable tissue.
To establish the evolutionary mechanisms that shaped the vertebrate sodium channel
a-subunit (SCNA) gene family and their encoded Nav1 proteins, we identified all SCNA
genes in several teleost species. Molecular cloning revealed that teleosts have eight
SCNA genes, comparable to the number in another vertebrate lineage, mammals.
Prior phylogenetic analyses had indicated that teleosts and tetrapods share four
monophyletic groups of SCNA genes and that tandem duplications selectively
expanded the number of genes in two of the four mammalian groups. However, the
number of genes in each group varies between teleosts and tetrapods suggesting
different evolutionary histories in the two vertebrate lineages. Our findings from
phylogenetic analysis and chromosomal mapping of Danio rerio genes indicate that
tandem duplications are an unlikely mechanism for generation of the extant teleost
SCNA genes. Instead, analysis of other closely mapped genes in D. rerio supports the
hypothesis that a whole genome duplication was involved in expansion of the SCNA
gene family in teleosts. Interestingly, despite their different evolutionary histories,
mRNA analyses demonstrated a conservation of expression patterns for SCNA
orthologues in teleosts and tetrapods, suggesting functional conservation.The authors’ work was supported by NIH grants (NS 38937; AEN,
ADT and ABR, NS 25513; HHZ and YL and NSF IBN 0236147; MCJ)