The Lethal Toxin from Australian Funnel-Web Spiders Is Encoded by an Intronless Gene

Abstract

Australian funnel-web spiders are generally considered the most dangerous spiders in the world, with envenomations from the Sydney funnel-web spider Atrax robustus resulting in at least 14 human fatalities prior to the introduction of an effective anti-venom in 1980. The clinical envenomation syndrome resulting from bites by Australian funnel-web spiders is due to a single 42-residue peptide known as δ-hexatoxin. This peptide delays the inactivation of voltage-gated sodium channels, which results in spontaneous repetitive firing and prolongation of action potentials, thereby causing massive neurotransmitter release from both somatic and autonomic nerve endings. Here we show that δ-hexatoxin from the Australian funnel-web spider Hadronyche versuta is produced from an intronless gene that encodes a prepropeptide that is post-translationally processed to yield the mature toxin. A limited sampling of genes encoding unrelated venom peptides from this spider indicated that they are all intronless. Thus, in distinct contrast to cone snails and scorpions, whose toxin genes contain introns, spiders may have developed a quite different genetic strategy for evolving their venom peptidome.

Toxin structures as evolutionary tools: Using conserved 3D folds to study the evolution of rapidly evolving peptides

“…However, this would imply secondary loss of plant/fungi-type ICK peptides in animals, because animals and fungi form a monophyletic clade (Opisthokonta) with respect to plants (Plantae) [65]. Moreover, gene structure does not appear to be particularly well conserved in ICK-encoding genes since spider ICK toxins are encoded by genes that are either intronless [66] or have a variety of intron-exon architectures [67,68]. While gene structure alone does not provide strong support for multiple origins of the ICK fold, structural data do suggest it may have evolved twice.…”

Weaponization of a Hormone: Convergent Recruitment of Hyperglycemic Hormone into the Venom of Arthropod Predators

“…A search of the recently published genome of the velvet spider Stegodyphus mimosarum (Araneomorphae) (Sanggaard et al, 2014), revealed an ITP/CHH-like gene (Genbank: AZAQ01021694.1) containing an unusually large intron ($9.7 kb) in the same position within the mature peptide as in S. maritima. Moreover, unlike araneomorph spiders (Krapcho et al, 1995), mygalomorphs appear to express intronless toxin genes Pineda et al, 2012;Tang et al, 2010), possibly indicating an inability to splice transcripts expressed in the toxin-producing regions of the venom gland.…”

Structure of the yellow sac spider Cheiracanthium punctorium genes provides clues to evolution of insecticidal two‐domain knottin toxins

“…For some spider species, silk (Prosdocimi et al ., ) and venom gland (Kozlov et al ., ; Quintero‐Hernandez et al ., ) transcriptome data are available; however, no full spider genome has been sequenced yet. The majority of short spider toxin genes known to date do not contain introns (Qiao et al ., ; Tang et al ., ; Pineda et al ., ). As for two‐domain spider toxins, we have recently reported the structure of OlTx toxin genes from Oxyopes lineatus , which were also found to be intronless (Sachkova et al ., ).…”