Venom systems in bees have been primarily studied with a strong emphasis on the honeybee (Apis mellifera), yet this represents only a small part of the diversity in the Anthophila (20,000 bee species). The amphipathic pore-forming peptide melittin, is the main pain-causing toxin in honeybee venom, but it remains uncertain how widespread and functionally conserved this peptide is among other bee lineages.
Here, we investigated the evolution and functional diversification of melittin-like peptides across bees. Using genomic, transcriptomic and proteomic data from a total of 75 species, spanning all major bee families, we identified a diverse suite of melittin orthologues as well as novel venom peptides. From this, we synthesized 35 representative melittin-family peptides and tested their activity at mammalian sensory neurons, as a proxy for pain-causing activity.
Our results reveal a diverse family of melittin orthologues that are distributed across all bees. We show that these peptides share common ancestry yet exhibit variation in primary structure and pain-causing activity. The most potent orthologues were from highly eusocial Apis species, suggesting lineage-specific adaptation associated with colony-level defence against vertebrate predators.
This study redefines melittin not as a taxonomically-restricted molecule, but as one member of a large, evolutionarily-dynamic toxin family. Our findings provide new insights into the origin and diversity of pain-causing toxins in bees and highlight a wealth of unexplored peptide diversity.