Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
Genome Res. 2010 Feb;20(2):212-27. doi: 10.1101/gr.095406.109. Epub 2009 Nov 30.
Transposable elements (TEs) are mobile DNA sequences that make up a large fraction of eukaryotic genomes. Recently it was discovered that PIWI-interacting RNAs (piRNAs), a class of small RNA molecules that are mainly generated from transposable elements, are crucial repressors of active TEs in the germline of fruit flies. By quantifying expression levels of 32 TE families in piRNA pathway mutants relative to wild-type fruit flies, we provide evidence that piRNAs can severely silence the activities of retrotransposons. We incorporate piRNAs into a population genetic framework for retrotransposons and perform forward simulations to model the population dynamics of piRNA loci and their targets. Using parameters optimized for Drosophila melanogaster, our simulation results indicate that (1) piRNAs can significantly reduce the fitness cost of retrotransposons; (2) retrotransposons that generate piRNAs (piRTs) are selectively more advantageous, and such retrotransposon insertions more easily attain high frequency or fixation; (3) retrotransposons that are repressed by piRNAs (targetRTs), however, also have an elevated probability of reaching high frequency or fixation in the population because their deleterious effects are attenuated. By surveying the polymorphisms of piRT and targetRT insertions across nine strains of D. melanogaster, we verified these theoretical predictions with population genomic data. Our theoretical and empirical analysis suggests that piRNAs can significantly increase the fitness of individuals that bear them; however, piRNAs may provide a shelter or Trojan horse for retrotransposons, allowing them to increase in frequency in a population by shielding the host from the deleterious consequences of retrotransposition.
转座元件 (TEs) 是可移动的 DNA 序列，它们构成了真核生物基因组的很大一部分。最近发现，PIWI 相互作用 RNA (piRNAs)，一种主要从转座元件产生的小 RNA 分子，是果蝇生殖系中活跃转座元件的关键抑制剂。通过相对于野生型果蝇量化 piRNA 途径突变体中 32 个 TE 家族的表达水平，我们提供了证据表明 piRNAs 可以严重抑制逆转录转座子的活性。我们将 piRNAs 纳入逆转录转座子的群体遗传框架，并进行正向模拟以模拟 piRNA 位点及其靶标的群体动态。使用针对黑腹果蝇优化的参数，我们的模拟结果表明：(1) piRNAs 可以显著降低逆转录转座子的适应性成本；(2) 产生 piRNAs 的逆转录转座子 (piRTs) 具有选择性优势，并且此类逆转录转座子插入更容易达到高频率或固定；(3) 然而，被 piRNAs 抑制的逆转录转座子 (targetRTs) 也更容易在群体中达到高频率或固定，因为它们的有害影响被减弱。通过调查九个黑腹果蝇品系中 piRT 和 targetRT 插入的多态性，我们用群体基因组数据验证了这些理论预测。我们的理论和实证分析表明，piRNAs 可以显著提高携带它们的个体的适应性；然而，piRNAs 可能为逆转录转座子提供庇护所或特洛伊木马，使它们通过屏蔽宿主免受逆转录转座的有害后果而在群体中增加频率。
