Ancient origin and dynamic evolution of bivalent spider toxins

Area of Science:

• Evolutionary biology
• Genomics
• Biochemistry

Background:

• Bivalent peptide toxins, with two cysteine-rich domains, offer enhanced molecular target selectivity and avidity.
• The evolutionary pathways leading to multi-domain toxin architectures from single-domain precursors are not well understood.

Purpose of the Study:

• Investigate the genomic and evolutionary processes behind bivalent inhibitor cystine knot (ICK) toxins in spider venom.
• Understand the transitions between single- and multi-domain toxin structures.

Main Methods:

• Genome assembly of Hadronyche cerberea.
• De novo transcriptome assemblies from 86 spider species.
• Venom proteomic data analysis.

Main Results:

• Massive expansion of ICK toxin genes in H. cerberea, including bivalent π-hexatoxin-Hc1a.
• Ancient origin of bivalency in the Hc1a subfamily via intra-exonic duplication.
• Domain expansion and loss driven by mutations, deletions, and unequal crossing-over.

Conclusions:

• Intra-exonic duplication is a key mechanism for bivalent toxin evolution.
• Gene instability and selective retention shape complex evolutionary trajectories of spider venom toxins.
• Transposable elements may play a role in gene expansion and domain loss.