Unrestrained
transposon mobilization threatens genome integrity. To survive, organisms have evolved silencing pathways capable of distinguishing self from non-self. This review emphasizes
Caenorhabditis elegans genome defense with a particular emphasis on systems-level detection of foreign DNA and the balance between silencing and protective pathways. Abundant small RNAs (piRNAs and siRNAs), aberrant
DNA structures (e.g., introns), and
heterochromatin domains largely mediate silencing. For example, CRISPR-based manipulation of endogenous piRNAs has elucidated precise targeting rules and a novel, conserved role in tuning endogenous
germline gene expression. Protective pathways are only just becoming clear: small RNA pathways (CSR-1),
deamination of endogenous dsRNA, and a pervasive, embedded DNA watermark (PATCs) can all counteract silencing to protect endogenous genes.