Biogeography and phylogeny of tarantula spider venoms

The venoms of the ca. 40000 described spider species represent a largely unexplored source of novel neurotoxic and insecticidal peptides. In the group of orthognath spiders, the family Theraphosidae, or << true tarantulas >>, represents the largest group with ca. 800 described species. The large size of these spiders and their ability to prey on vertebrates make them a particularly attractive biological material for the discovery of new pharmacological tools. We have conducted a toxicity study by intracerebroventricular injection in mice, and an investigation of venom composition in 55 species, by reversed-phase HPLC and MALDI-TOF (Matrix-Assisted Laser Desorption-Ionization Time-of-flight) mass spectrometry. The selection of venoms is representative of the biological, taxonomic and biogeographic diversity of tarantulas. The analysis of venoms showed interesting correlation between composition, toxicity, distribution and taxonomy, New world spiders (Theraphosinae and Aviculariinae) possess weaker venoms against mice, with the notable exception of Chilean species. In particular, North and Central American species have the weakest venoms but remarkably, display a consistent intoxication pattern with a slow onset of symptoms (20 to 40 min.). African (Eumenophorinae, Harpactirinae) and asian (Ornithoctoninae, Selenocosmiinae) species possess more toxic venoms which induce rapid death in mice (3-20 min. post-injection), The differences in activity are correlated with the presence of urticating hairs in new world species, and a greater aggressiveness of old world species. Stronger neurotoxic symptoms are also observed for several of the arboreal species. In all cases, toxicity is marked by a variety of neurotoxic effects (excitotoxicity, convulsions, paralysis) which indicate complex effects on the central nervous system. The analysis by RP-HPLC shows the constant presence of a peptide fraction as well as a variable << polyamine >> fraction. MALDI-TOF MS analysis of the venoms shows a striking homogeneity and the presence of peptides in the 3500-8000 molecular weight range, in all venoms. The molecular weight distribution is centered on the 3500-5000 range and appears to suggest structural homogeneity of the toxins. Fractionation, pharmacological and physico-chemical analysis of several venoms are in progress and have led to the discovery of several novel peptide toxins.