Evolutionary dynamics of collateral gene silencing by piRNA

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Transposable elements (TE) are DNA sequences that can change their position in the genome and thereby produce a variety of harmful mutations. Animals, including fruit flies, have evolved a defense mechanism to guard against TE movement whereby small RNAs, called piRNAs, can destroy essential RNA intermediates produced by the TEs. Exactly how piRNAs work is not well understood, and the overall aim of this project is to study how piRNAs specifically target TE RNAs without destroying beneficial RNAs. The research has the potential to provide valuable insights into prevention of harmful mutations that could cause genetic defects or death. The project will have broader impacts for undergraduates, graduate students and a postdoctoral researcher, who will receive training in genetics, evolution and bioinformatics. Added benefit will derive from production of internet videos that will serve as general tools for education about various topics in genetics and evolution. piRNAs play a critical role in genome defense by destroying TE RNAs. This research will determine how the piRNA defense mechanism is constrained by the harm that occurs when piRNAs mistakenly target RNAs from normal genes and thus result in off-target, or collateral, gene silencing. Using different species of Drosophila as a model, the work will test the hypothesis that species with high TE content are more affected by these collateral effects. One series of experiments will determine whether species with higher TE content have less variation in expression of the piRNA machinery, increased silencing by piRNA, and stronger maternal effects on gene expression. Other experiments, in which piRNA expression is artificially increased, will reveal whether there is a functional tradeoff between genome defense and off-target effects. This work will provide important information about how the mechanisms that protect the genome are governed by the harmful effects of collateral gene silencing, which can be considered to be a form of "genomic autoimmunity".