Biogeography and phylogeny of tarantula spider venoms

The venoms of the ca. 40000 described spider species represent a largely un explored 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 siz e of these spiders and their ability to prey on vertebrates make them a par ticularly attractive biological material for the discovery of new pharmacol ogical 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-Io nization Time-of-flight) mass spectrometry. The selection of venoms is repr esentative of the biological, taxonomic and biogeographic diversity of tara ntulas. The analysis of venoms showed interesting correlation between compo sition, toxicity, distribution and taxonomy, New world spiders (Theraphosinae and Aviculariinae) possess weaker venoms a gainst 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 (Ornithocto ninae, Selenocosmiinae) species possess more toxic venoms which induce rapi d 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 symptom s are also observed for several of the arboreal species. In all cases, toxi city is marked by a variety of neurotoxic effects (excitotoxicity, convulsi ons, paralysis) which indicate complex effects on the central nervous syste m. The analysis by RP-HPLC shows the constant presence of a peptide fraction a s well as a variable << polyamine >> fraction. MALDI-TOF MS analysis of the venoms shows a striking homogeneity and the presence of peptides in the 35 00-8000 molecular weight range, in all venoms. The molecular weight distrib ution is centered on the 3500-5000 range and appears to suggest structural homogeneity of the toxins. Fractionation, pharmacological and physico-chemi cal analysis of several venoms are in progress and have led to the discover y of several novel peptide toxins.