Preprint: prion-like protein conformations transmit heritable states across generations in C. elegans

A preprint posted to bioRxiv investigates whether prion-like, self-replicating protein conformations can act as vehicles for transgenerational epigenetic inheritance in a metazoan animal. In fungi, prion conformers transmit through mitosis and meiosis to produce heritable phenotypic variation without DNA sequence change. Whether analogous mechanisms operate in multicellular animals has remained an open question.

Working in *Caenorhabditis elegans* — a nematode worm widely used in genetics because of its short generation time, optical transparency, and tractable genetics — the authors demonstrate that specific protein conformational states can be transmitted from parent to offspring over multiple generations, generating heritable phenotypic differences. The work suggests that protein-based inheritance is not confined to unicellular organisms and may represent a more broadly conserved mechanism of non-DNA epigenetic transmission in animals.

The findings carry implications for understanding age-related neurodegenerative diseases, in which protein aggregates with prion-like properties — including those formed by tau and alpha-synuclein — spread between cells and may influence organismal phenotypes over time. They are also relevant to the broader field of epigenetic inheritance, which examines how information beyond DNA sequence can be passed between generations. The preprint has not been peer-reviewed. Researchers in epigenetics, molecular genetics, and neurodegenerative disease biology will find the conceptual and experimental scope of the study of considerable interest.