Adaptive evolution of insect selective excitatory β-type sodium channel neurotoxins from scorpion venom

- Two insect selective excitatory β-NaScTxs, LmIT and ImIT, were characterized.
- Twelve amino acid sites of insect selective excitatory β-NaScTxs were involved in significant positive selection.
- Residues of the putative “hot spot” of insect selective excitatory β-NaScTxs seem to be neutral to selective evolution.
- Residues locating at the C-terminal region of insect selective excitatory β-NaScTxs are influenced by positive selection.

Insect selective excitatory β-type sodium channel neurotoxins from scorpion venom (β-NaScTxs) are composed of about 70-76 amino acid residues and share a common scaffold stabilized by four unique disulfide bonds. The phylogenetic analysis of these toxins was hindered by limited sequence data. In our recent study, two new insect selective excitatory β-NaScTxs, LmIT and ImIT, were isolated from Lychas mucronatus and Isometrus maculatus, respectively. With the sequences previously reported, we examined the adaptive molecular evolution of insect selective excitatory β-NaScTxs by estimating the nonsynonymous-to-synonymous rate ratio (ω = dN/dS). The results revealed 12 positively selected sites in the genes of insect selective excitatory β-NaScTxs. Moreover, these positively selected sites match well with the sites important for interacting with sodium channels, as demonstrated in previous mutagenesis study. These results reveal that adaptive evolution after gene duplication is one of the most important genetic mechanisms of scorpion neurotoxin diversification.