Work

piRNA loss unleashes episodic transposition bursts

Year: 2026

Type: article

Abstract: ABSTRACT In Metazoa, transposon expression is suppressed by the piRNA pathway, and disruption of this pathway leads to rampant transposon expression. However, it remains unclear whether increased transposon expression results in actual transposition, and if so, which and how frequently transposons mobilize upon piRNA loss. Here, we developed a framework to track transposon copy accumulation across generations on a single set of nonrecombining haploid genome in the Drosophila male germline, with or without the piRNA biogenesis factor HP1D/Rhino. Single-fly Nanopore DNA sequencing revealed that multiple transposon families mobilized after 10-45 generations of piRNA loss. Among them, the most prolific across all replicates was copia , producing dozens of new insertions that were distributed across chromosome arms. With genomic DNA collected at every generation, we validated and dated each copia insertion, revealing episodic bursts of transposition that deviated strongly from a Poisson process. Using phylogenetic analysis, we further showed that multiple copia loci—both autonomous and nonautonomous copies—can mobilize. Interestingly, two additional transposon families, mdg3 and invader3 , also mobilized episodically, but with distinct timing and magnitude, highlighting the stochastic nature of transposition bursts. Because we did not observe a single transposition event for these elements in controls, our results provide direct evidence that the piRNA pathway tightly suppresses germline transposition. More importantly, our findings argue that disruption of the piRNA pathway does not simply elevate transposition rates, but it instead unleashes punctuated and stochastic bursts of transposon movement that may radically reshape the timing and magnitude of mutational input during evolution. SIGNIFICANCE STATEMENT Virtually all animal genomes contain transposons and a small RNA system active in their germline called the piRNA pathway, which is thought to suppress transposition. While it is clear that piRNAs target transposon mRNAs, very few study has explicitly shown that the pathway actually prevents transposition. Rather, the common belief that piRNAs safeguard the germline from transposition comes largely from studies showing that loss of piRNAs leads to increased transposon mRNA expression, but they do not monitor transposon movement. Thus, it remains unclear whether piRNAs broadly control transposition—a central question in the field since the discovery of piRNAs. Here, we follow defined chromosomes through single germline lineages to track transposition and find that piRNA loss unleashes episodic transposition bursts.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2623866123