In 2020, we initiated a novel long-term environmental induction (LTEI) experiment to study environmental influences on mouth-form. Using food-reversal experiments, we started to analyse environmental influences on trait expression. In a massive LTEI experiment, we established 110 parallel, genetically-identical lines and exposed them to a new diet. These lines were propagated for 101 generations by single worm decent, a procedure that allows capturing stochastic, epigenetic effects. In parallel, starting in generation 15, all lines were reverted back to the original diet in a total of 9 reversal experiments. This LTEI experiment resulted in three totally unexpected findings. First, the new diet induced the predatory mouth form i) immediately (in the first generation), ii) completely (in all individuals), iii) systemic (in all 110 lines) and iv) permanent (for the complete duration of the experiment). Second, after reversal back to the original diet, worms remained predatory for multiple generations before returning to their baseline, the preferential non-predatory phenotype. These findings indicated transgenerational epigenetic inheritance (TEI) in the context of a natural biological, and thus ecologically-relevant, readout. While TEI is increasingly studied in other model systems, such studies often rely on artificial settings, i.e. transgene silencing; whereas the Pristionchus example represents a natural readout of biological significance. Finally, this TEI requires a minimal exposure to the new diet of five generations, indicating that signalling information has to reach a certain threshold to initiate the memory process. Together, these findings represent a unique example of transgenerational memory, which allows detailed molecular insight given the technical features of P. pacificus hermaphrodites.
Indeed, forward genetic screens to identify the machinery establishing memory in the worm (Quiobe et al., 2025). The Cullin-RING E3 ubiquitin ligase EBAX-1 was shown to be essential for transgenerational memory of the predatory mouth form and Ppa-ebax-1 mutants are memory-defective. Interestingly, the human and mouse ortholog of EBAX-1, ZSWIM8 had been implemented in target-directed microRNA degradation (TDMD). The TDMD process reverses the canonical logic of messenger RNA degradation and results in the decay of the miRNA instead. Indeed, Ppa-EBAX-1 regulates a miRNA family that is organized in a large cluster of more than 40 miRNAs and deletions of this cluster result in precocious and extended transgenerational memory. Currently, we are continuing this work by characterizing triggers and targets of TDMD using this unique model system for transgenerational inheritance and the associated organismal phenotype.
On the bacterial side, we could show that bacteria-derived vitamin B12 induces the predatory mouth form and its transgenerational memory in the worm (Quiobe et al., 2026). First, we showed that vitamin B12 is necessary and sufficient to induce memory of the predatory morph. Second, vitamin B12 induces vitellogenin provisioning, the yolk protein conserved from cnidarians to birds. Vitellogenin proteins cross the Weismann barrier as they are synthesized in the intestine (in nematodes) and are then transported into the germ line. Indeed, mutations in the vitellogenin germ line uptake receptor, rme-2, resulted in memory-deficient animals. This work demonstrated for the first time that a bacterial-derived vitamin can cause strong organismal phenotypes which are transmitted for multiple generations. These findings are of general importance all the way to the human famines and their multi-generational consequences on humans.
Yoshida, K., Rödelsperger, C., Röseler, W., Riebesell, M., Sun, S., Kikuchi, T. & Sommer, R. J. (2023): Chromosome fusions repatterned recombination rate and facilitated reproductive isolation during nematode speciation. Nature Ecology & Evolution, 7, 424-439.
