Abstract:
Evolution is a continuous and historical process that can be studied experimentally in
organisms with rapid generation times. Because evolution ultimately depends on the
generation and inheritance of phenotypic variation, a key unresolved question is the
extent to which environmental factors can produce heritable changes. Therefore,
environmental effects on trait inheritance remain debated because it is often difficult
to distinguish true transgenerational inheritance from short-term parental influences.
While mammalian systems face technical limitations, nematodes provide powerful
experimental models. In this work, I investigated transgenerational epigenetic
inheritance (TEI) of environmentally induced traits using Pristionchus pacificus, a
nematode that exhibits mouth-form plasticity, including predation. I established long-
term environmental induction experiments with alternative diets by propagating 110
isogenic lines over 101 generations, together with complementary food-reversal
assays. I found that a Novosphingobium diet enriched in vitamin B12 induces the
predatory mouth morph, which is subsequently transmitted across generations and
occasionally becomes canalized at low frequency. To uncover the underlying
mechanisms, I performed large-scale genetic screening and identified the target-
directed microRNA degradation (TDMD) factor EBAX-1/ZSWIM8. I showed that Ppa-
EBAX-1 specifically destabilizes the expanded miR-35/miR-2235a microRNA cluster
in P. pacificus, revealing an unexpected repressive role of microRNAs in regulating
TEI of the predatory morph. By defining the dietary trigger landscape, I further
demonstrated that vitamin B12 is sufficient to induce TEI in a concentration-dependent
manner and uncovered a complex regulatory network of potential RNA triggers linked
to TDMD-like processes. Overall, my work over the past five years provides
conceptual and experimental advances on nematode TEI. This expeirmental
framework leverages the natural organismal readout of plasticity in P. pacificus and
offers key insights into developmental plasticity, its transgenerational inheritance, and
low-frequency canalization of traits. Together, these findings establish a foundation for
addressing broader evolutionary questions and provide a mechanistic link between
environmental responsiveness and heritable phenotypic change.
Phenotypic plasticity