Department of Molecular Biology and Genetics, Cornell University, NY, USA.
Mol Biol Evol. 2013 Aug;30(8):1816-29. doi: 10.1093/molbev/mst081. Epub 2013 Apr 26.
The Piwi-interacting RNA (piRNA) pathway defends animal genomes against the harmful consequences of transposable element (TE) infection by imposing small-RNA-mediated silencing. Because silencing is targeted by TE-derived piRNAs, piRNA production is posited to be central to the evolution of genome defense. We harnessed genomic data sets from Drosophila melanogaster, including genome-wide measures of piRNA, mRNA, and genomic abundance, along with estimates of age structure and risk of ectopic recombination, to address fundamental questions about the functional and evolutionary relationships between TE families and their regulatory piRNAs. We demonstrate that mRNA transcript abundance, robustness of "ping-pong" amplification, and representation in piRNA clusters together explain the majority of variation in piRNA abundance between TE families, providing the first robust statistical support for the prevailing model of piRNA biogenesis. Intriguingly, we also discover that the most transpositionally active TE families, with the greatest capacity to induce harmful mutations or disrupt gametogenesis, are not necessarily the most abundant among piRNAs. Rather, the level of piRNA targeting is largely independent of recent transposition rate for active TE families, but is rapidly lost for inactive TEs. These observations are consistent with population genetic theory that suggests a limited selective advantage for host repression of transposition. Additionally, we find no evidence that piRNA targeting responds to selection against a second major cost of TE infection: ectopic recombination between TE insertions. Our observations confirm the pivotal role of piRNA-mediated silencing in defending the genome against selfish transposition, yet also suggest limits to the optimization of host genome defense.
Piwi 相互作用 RNA (piRNA) 途径通过小 RNA 介导的沉默来防止转座元件 (TE) 感染对动物基因组造成的有害后果。由于沉默是由 TE 衍生的 piRNA 靶向的，因此 piRNA 的产生被认为是基因组防御进化的核心。我们利用了来自黑腹果蝇的基因组数据集，包括 piRNA、mRNA 和基因组丰度的全基因组测量，以及年龄结构和异位重组风险的估计，以解决关于 TE 家族及其调节 piRNA 之间的功能和进化关系的基本问题。我们证明，mRNA 转录本丰度、“乒乓”扩增的稳健性以及在 piRNA 簇中的代表性共同解释了 TE 家族之间 piRNA 丰度变化的大部分，为流行的 piRNA 生物发生模型提供了第一个强有力的统计支持。有趣的是，我们还发现，最具转座活性的 TE 家族，即最有能力诱导有害突变或破坏配子发生的家族，在 piRNA 中不一定是最丰富的。相反，piRNA 靶向的水平在很大程度上独立于活跃 TE 家族的最近转位率，但对于非活跃的 TEs 则迅速丧失。这些观察结果与群体遗传理论一致，该理论表明宿主抑制转位的选择优势有限。此外，我们没有发现证据表明 piRNA 靶向会响应对 TE 感染的第二个主要代价的选择：TE 插入之间的异位重组。我们的观察结果证实了 piRNA 介导的沉默在保护基因组免受自私转座侵害方面的关键作用，但也表明了宿主基因组防御的优化存在限制。
