C. elegans pathogenic learning confers multigenerational pathogen avoidance

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Journal Article

The ability to pass on learned information to progeny could present an evolutionary advantage for many generations. While apparently evolutionarily conserved, transgenerational epigenetic inheritance (TEI) is not well understood at the molecular or behavioral levels. Here we describe our discovery that C. elegans can pass on a learned pathogenic avoidance behavior to their progeny for several generations through epigenetic mechanisms. Although worms are initially attracted to the gram-negative bacteria P. aeruginosa (PA14), they can learn to avoid this pathogen. We found that prolonged PA14 exposure results in transmission of avoidance behavior to progeny that have themselves never been exposed to PA14, and this behavior persists through the fourth generation. This form of transgenerational inheritance of bacterial avoidance is specific to pathogenic P. aeruginosa, requires physical contact and infection, and is distinct from CREB-dependent long-term associative memory and larval imprinting. The TGF-beta ligand DAF-7, whose expression increases in the ASJ upon initial exposure to AP14, is highly expressed in the ASI neurons of progeny of trained mothers until the fourth generation, correlating with transgenerational avoidance behavior. Mutants of histone modifiers and small RNA mediators display defects in naive PA14 attraction and aversive learning. By contrast, the germline-expressed PRG-1/Piwi homolog is specifically required for transgenerational inheritance of avoidance behavior. Our results demonstrate a novel and natural paradigm of TEI that may optimize progeny decisions and subsequent survival in the face of changing environmental conditions.