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Biology subjects

Pan, K. C.

Publications and source records attributed to Pan, K. C..

2 recordsLinked to original sources

piRNA loss unleashes episodic transposition bursts

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.

genetics↗

Escalation of genome defense capacity enables control of an expanding meiotic driver

SummaryFrom RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity1,2. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, which controls selfish elements in the metazoan germline, diverse target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases via enzymatic cleavage1,3. Such a binary architecture allows the defense systems to be readily adaptable, where new targets can be captured via the innovation of new specificity factors4,5. Thus, our current understanding of genome defense against lineage-specific selfish genes has been largely limited to the evolution of specificity factors, while it remains poorly understood whether other types of innovations are required. Here, we describe a new type of innovation, which escalates the defense capacity of the piRNA pathway to control a recently expanded selfish gene in Drosophila melanogaster. Through an in vivo RNAi screen for repressors of Stellate--a recently evolved and expanded selfish meiotic driver6-8--we discovered a novel defense factor, Trailblazer. Trailblazer is a transcription factor that promotes the expression of two PIWI-clade nucleases, Aub and AGO3, to match Stellate in abundance. Recent innovation in the DNA-binding domain of Trailblazer enabled it to drastically elevate Aub and AGO3 expression in the D. melanogaster lineage, thereby escalating the silencing capacity of the piRNA pathway to control expanded Stellate and safeguard fertility. As copy-number expansion is a recurrent feature of diverse selfish genes across the tree of life9-12, we envision that augmenting the defense capacity to quantitatively match selfish genes is likely a repeatedly employed defense strategy in evolution.

genetics↗