New insight on scorpion divergence inferred from comparative analysis of toxin structure, pharmacology and distribution.

The divergence of Buthidae, the most abundant family of scorpions, has relied thus far on anatomical and morphological features, but still remains controversial. However, much information has accumulated on Buthidae long-chain scorpion toxins affecting neuronal sodium channel conductance (alpha- and beta-toxins) and their pharmacology. Therefore, we constructed a toxin evolutionary tree, which together with recent data on toxin gene organization, toxin structures, and worldwide dispersion, sheds light on toxin and hence, scorpion divergence. Based on these data, we suggest that in the ancient world, the ancestral long-chain toxins affecting sodium channels developed into beta-like toxins, which most likely developed into alpha- and beta-toxins before the separation of South America from Africa. Subsequently, in the Old World, mostly excitatory and depressant toxins developed from the ancestral beta-like toxin and in the New World a new type of toxin group with beta-toxin structure but alpha-toxin activity developed from the beta-toxins. Assisted by the worldwide distribution of toxins and the zoogeographical dispersion of the studied genera in Asia and Africa (Old World) and in South and North America (New World), we suggest a route of divergence for some of the Buthidae scorpions, a task that has reached a standstill when morphological and anatomical features were used.