Diet-derived vitamin B12 induces transgenerational inheritance of nematode predation through elevated vitellogenin provisioning

Dietary and nutritional effects can alter organismal phenotypes and influence trait inheritance over generations, so-called transgenerational epigenetic inheritance. However, the chemical nature of the stimuli and the downstream events inducing such memory remain largely elusive. The nematode Pristionchus pacificus exhibits mouth-form plasticity including predation and was recently shown to respond to a multigenerational Novosphingobium diet with the induction and subsequent transgenerational inheritance of the predatory morph. Here, we show that bacteria-derived vitamin B12 is both necessary and sufficient for transgenerational memory. Different vitamin B12 concentrations are required for the original induction and the subsequent transgenerational inheritance of the predatory morph. Mutant analysis revealed that vitamin B12 functions through methionine-synthase and involves methionine but not vitamin B9. The inherited effect acts through increased multigenerational vitellogenin transcription indicating elevated nutrient provisioning. Consistently, mutants in the vitellogenin receptor Ppa-rme-2 are memory-defective. Thus, vitamin B12 induces vitellogenin provisioning to control organismal physiology and behavior.