RT Journal Article SR Electronic T1 Diversification of small RNA pathways underlies germline RNAi incompetence in wild C. elegans strains JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.08.21.457212 DO 10.1101/2021.08.21.457212 A1 Han Ting Chou A1 Francisco Valencia A1 Jacqueline C. Alexander A1 Avery Davis Bell A1 Diptodip Deb A1 Daniel A. Pollard A1 Annalise B. Paaby YR 2022 UL http://biorxiv.org/content/early/2022/02/22/2021.08.21.457212.abstract AB The discovery that experimental delivery of dsRNA can induce gene silencing at target genes revolutionized genetics research, by both uncovering essential biological processes and creating new tools for developmental geneticists. However, the efficacy of exogenous RNAi varies dramatically within the C. elegans population, raising questions about our understanding of RNAi in the lab relative to its activity and significance in nature. Here, we investigate why some wild-type strains fail to mount a robust RNAi response to germline targets. We observe diversity in mechanism: in some strains, the response is stochastic, either on or off among individuals, while in others the response is consistent but delayed. Increased activity of the Argonaute PPW-1, which is required for germline RNAi in the laboratory strain N2, rescues the response in some strains, but dampens it further in others. Among wild-type strains, genes known to mediate RNAi exhibited very high expression variation relative to other genes in the genome as well as allelic divergence and strain-specific instances of pseudogenization at the sequence level. Our results demonstrate functional diversification in the small RNA pathways in C. elegans, and suggest that RNAi processes are evolving rapidly and dynamically in nature.Competing Interest StatementThe authors have declared no competing interest.