Tarnopol, R.L., Tamsil, J.A., Cinege, G., Ha, J.H., Verster, K.I., Ábrahám, E., Magyar, L.B., Kim, B.Y., Bernstein, S.L., Lipinszki, Z., Andó, I., Whiteman, N.K. (2025). Experimental horizontal transfer of phage-derived genes to Drosophila confers innate immunity to parasitoids.  Curr. Biol. 35(3): 514--529.e7.

FBrf0261522

Research paper

Metazoan parasites have played a major role in shaping innate immunity in animals. Insect hosts and parasitoid wasps are excellent models for illuminating how animal innate immune systems have evolved to neutralize these enemies. One such strategy relies on symbioses between insects and intracellular bacteria that express phage-encoded toxins. In some cases, the genes that encode these toxins have been horizontally transferred to the genomes of the insects. Here, we used genome editing in Drosophila melanogaster to recapitulate the evolution of two toxin genes-cytolethal distending toxin B (cdtB) and apoptosis inducing protein of 56kDa (aip56)-that were horizontally transferred likely from phages of endosymbiotic bacteria to insects millions of years ago. We found that a cdtB::aip56 fusion gene (fusionB), which is conserved in D. ananassae subgroup species, dramatically promoted fly survival and suppressed parasitoid wasp development when heterologously expressed in D. melanogaster immune tissues. We found that FusionB was a functional nuclease and was secreted into the host hemolymph where it targeted the parasitoid embryo's serosal tissue. Although the mechanism of toxicity remains unknown, when expressed ubiquitously, fusionB resulted in delayed development of late-stage fly larvae and eventually killed pupating flies. These results point to the salience of regulatory constraint in mitigating autoimmunity during the domestication process following horizontal transfer. Our findings demonstrate how horizontal gene transfer can instantly provide new, potent innate immune modules in animals.

PMC11975398 (PMC) (EuropePMC)