A note on the evolution of spider toxins containing the ICK-motif

Most spider neurotoxins comprise a large group of structurally related polypeptides adopting the inhibitor cystine knot motif (ICK). The plethora of interesting biological functions they perform makes them worthy to study the evolutionary patterns that have been shaping their functional diversification. However, such a task remains elusive due to the lack of significant sequence similarities among the full set of spider neurotoxins. In this communication the phylogenetic relationships of a comprehensive set of spider neurotoxins with the ICK motif is analyzed by Bayesian inference. This procedure satisfactorily resolves terminal clusters, though high-order relationships remain poorly defined. Both paralogous expansion and orthologous diversification are well represented during the evolution of these ICK motif-containing peptides. Phylogenetic relationships are discussed in the light of what is known about spider neurotoxin functionalization.