Selfish conflict underlies RNA-mediated parent-of-origin effects

Genomic imprinting, the nonequivalence of maternal and paternal genomes, is a critical process that has independently evolved in numerous plant and mammalian species. According to kinship theory, imprinting is the inevitable consequence of conflictive selective forces acting on differentially expressed parental alleles. Yet, how these epigenetic differences evolve in the first place is poorly understood. Here we report the discovery and molecular dissection of a novel parent-of-origin effect on gene expression that clarifies this fundamental question. Toxin-antidote elements (TAs) are selfish elements that spread in populations by poisoning non-carrier individuals. In reciprocal crosses between two Caenorhabditis tropicalis wild isolates, we found that the slow-1/grow-1 TA is specifically inactive when paternally inherited. This parent-of-origin effect stems from transcriptional repression of the slow-1 toxin by the piRNA host defense pathway. The repression requires PIWI (Argonaute) and SET-32 histone methyltransferase activities and is transgenerationally inherited via small RNAs. Remarkably, when slow-1/grow-1 is maternally inherited, slow-1 repression is halted by a translation-independent role of its maternal mRNA. That is, slow-1 transcripts loaded into eggs, but not SLOW-1 protein, are necessary and sufficient to counteract piRNA-mediated repression. Our findings show that parent-of-origin effects can evolve by co-option of the piRNA pathway and hinder the spread of selfish genes that require sex for their propagation.