Evidence for myxobacterial origin of eukaryotic defensins

Antimicrobial defensins with the cysteine-stabilized alpha-helical and beta-sheet (CS alpha beta) motif are a large family of ancient, evolutionarily related innate immunity effectors of multicellular organisms. Although the widespread distribution in plants, fungi, and invertebrates suggests their uniqueness to Eukarya, it is unknown whether these eukaryotic defensins originated before or posterior to the emergence of eukaryotes. In this study, we provide evidence in support of the existence of defensin-like peptides (DLPs) in myxobacteria based on structural bioinformatics analysis, which recognized two bacterial peptides with a conserved cysteine-stabilized alpha-helical motif, a nested structural unit of the CS alpha beta motif. Similarity in sequence and structure to fungal DLPs together with restricted distribution to the myxobacteria as well as central role of the myxobacteria in the origin of eukaryotes suggest that the bacterial DLPs represent the ancestor of the eukaryotic defensins and could mediate immune defense of early eukaryotes after gene transfer to the proto-eukaryotic genome. Our work thus offers a basis for further investigation of prokaryotic origin of eukaryotic immune effector molecules.