title: Molecular evolution of α-latrotoxin, the exceptionally potent vertebrate neurotoxin in black widow spider venom.
abstract: Black widow spiders (members of the genus Latrodectus) are widely feared because of their potent neurotoxic venom. α-Latrotoxin is the vertebrate-specific toxin responsible for the dramatic effects of black widow envenomation. The evolution of this toxin is enigmatic because only two α-latrotoxin sequences are known. In this study, ~4 kb α-latrotoxin sequences and their homologs were characterized from a diversity of Latrodectus species, and representatives of Steatoda and Parasteatoda, establishing the wide distribution of latrotoxins across the mega-diverse spider family Theridiidae. Across black widow species, α-latrotoxin shows ≥ 94% nucleotide identity and variability consistent with purifying selection. Multiple codon and branch-specific estimates of the nonsynonymous/synonymous substitution rate ratio also suggest a long history of purifying selection has acted on α-latrotoxin across Latrodectus and Steatoda. However, α-latrotoxin is highly divergent in amino acid sequence between these genera, with 68.7% of protein differences involving non-conservative substitutions, evidence for positive selection on its physiochemical properties and particular codons, and an elevated rate of nonsynonymous substitutions along α-latrotoxin's Latrodectus branch. Such variation likely explains the efficacy of red-back spider, L. hasselti, antivenom in treating bites from other Latrodectus species, and the weaker neurotoxic symptoms associated with Steatoda and Parasteatoda bites. Long-term purifying selection on α-latrotoxin indicates its functional importance in black widow venom, even though vertebrates are a small fraction of their diet. The greater differences between Latrodectus and Steatoda α-latrotoxin, and their relationships to invertebrate-specific latrotoxins, suggest a shift in α-latrotoxin toward increased vertebrate toxicity coincident with the evolution of widow spiders.
authors: Department of Biological Sciences, University of Massachusetts, Lowell, USA. Jessica_Garb@uml.edu
authors: Jessica E
authors: JE
authors: Garb
authors: Cheryl Y
authors: CY
authors: Hayashi
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D008962:Models, Theoretical; D009498:Neurotoxins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013111:Spider Venoms / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D009498:Neurotoxins; D013111:Spider Venoms; C020763:alpha-latrotoxin; C038599:black widow spider venom