title: Diversification of a single ancestral gene into a successful toxin superfamily in highly venomous Australian funnel-web spiders.
abstract: BACKGROUND
  Spiders have evolved pharmacologically complex venoms that serve to rapidly subdue prey and deter predators. The major toxic factors in most spider venoms are small, disulfide-rich peptides. While there is abundant evidence that snake venoms evolved by recruitment of genes encoding normal body proteins followed by extensive gene duplication accompanied by explosive structural and functional diversification, the evolutionary trajectory of spider-venom peptides is less clear.
  
  
  RESULTS
  Here we present evidence of a spider-toxin superfamily encoding a high degree of sequence and functional diversity that has evolved via accelerated duplication and diversification of a single ancestral gene. The peptides within this toxin superfamily are translated as prepropeptides that are posttranslationally processed to yield the mature toxin. The N-terminal signal sequence, as well as the protease recognition site at the junction of the propeptide and mature toxin are conserved, whereas the remainder of the propeptide and mature toxin sequences are variable. All toxin transcripts within this superfamily exhibit a striking cysteine codon bias. We show that different pharmacological classes of toxins within this peptide superfamily evolved under different evolutionary selection pressures.
  
  
  CONCLUSIONS
  Overall, this study reinforces the hypothesis that spiders use a combinatorial peptide library strategy to evolve a complex cocktail of peptide toxins that target neuronal receptors and ion channels in prey and predators. We show that the ω-hexatoxins that target insect voltage-gated calcium channels evolved under the influence of positive Darwinian selection in an episodic fashion, whereas the κ-hexatoxins that target insect calcium-activated potassium channels appear to be under negative selection. A majority of the diversifying sites in the ω-hexatoxins are concentrated on the molecular surface of the toxins, thereby facilitating neofunctionalisation leading to new toxin pharmacology.
authors.forename: Sandy S
authors.initials: SS
authors.lastname: Pineda
authors.forename: Brianna L
authors.initials: BL
authors.lastname: Sollod
authors.forename: David
authors.initials: D
authors.lastname: Wilson
authors.forename: Aaron
authors.initials: A
authors.lastname: Darling
authors.forename: Kartik
authors.initials: K
authors.lastname: Sunagar
authors.forename: Eivind A B
authors.initials: EA
authors.lastname: Undheim
authors.forename: Laurence
authors.initials: L
authors.lastname: Kely
authors.forename: Agostinho
authors.initials: A
authors.lastname: Antunes
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, 306 Carmody Road, St Lucia, QLD 4072, Australia. bgfry@uq.edu.au.
authors.forename: Bryan G
authors.initials: BG
authors.lastname: Fry
authors.forename: Glenn F
authors.initials: GF
authors.lastname: King
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001315:Australia; D003062:Codon; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005260:Female; D015870:Gene Expression; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D010802:Phylogeny; D056510:Position-Specific Scoring Matrices; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D013111:Spider Venoms / Q000737:chemistry / Q000235:genetics*; D013112:Spiders / Q000145:classification / Q000235:genetics
chemical_list: D003062:Codon; D010455:Peptides; D011498:Protein Precursors; D013111:Spider Venoms