Dosage compensation and the rewiring of regulatory netoworks in Drosophila

进化中的创新和适应往往需要在监管方面迅速和协调地改变 基因在多个基因座上的表达。转座元件(TES)构成了最具活力的部分 真核基因组和可转座元件的插入可影响其表达 通过捐赠新的调控元件来包围基因。一个长期存在的假说，首次提出 由芭芭拉·麦克林托克提出的假设是，转座元件的扩散可能会允许同样的情况 调控基序将在许多基因组位置招募，从而将多个基因吸引到 同样的监管网络。然而，该模型的经验证据很少，而且最具推测性。 TE介导的调控网络重新布线的例子依赖于 在基因或基因组区域的子集上的TE残留物。我们最近提供了第一个直接 主动TE重新布线监管网络的功能证据，表明收购 剂量补偿复合体在幼年新性体染色体上的新结合位点 果蝇是由一只驯化的TE的扩散驱动的。在这里，我们建议将 TES的参与与通过其他突变获得监管部位的重组监管 通过系统地研究剂量补偿结合位点在超过一年的时间内的演变 十几条独立形成的幼小果蝇新性别染色体。我们的详细信息 在分子水平上了解果蝇的剂量补偿是如何工作的，这使它成为 研究监管网络重新布线的理想模型系统和最新方法 新近形成的X染色体结合位点进化的研究 非模式果蝇物种是可行的，这使这一提议及时而令人兴奋。

Evolutionary innovations and adaptations often require rapid and concerted changes in regulation of gene expression at many loci. Transposable elements (TEs) constitute the most dynamic part of eukaryotic genomes, and insertions of transposable elements can influence the expression of surrounding genes by donating new regulatory elements. A longstanding hypothesis, first proposed by Barbara McClintock, postulates that the dispersal of transposable elements may allow for the same regulatory motif to be recruited at many genomic locations, thereby drawing multiple genes into the same regulatory network. Empirical evidence for this model is however scarce, and most putative examples of TE-mediated rewiring of regulatory networks rely on a statistical association between remnants of a TE at a subset of genes or genomic regions. We recently provided the first direct functional evidence of an active TE rewiring a regulatory network by showing that the acquisition of novel binding sites for the dosage compensation complex at young neo-sex chromosomes in Drosophila was driven by dispersal of a domesticated TE. Here we propose to quantify the involvement of TEs vs. acquisition of regulatory sites by other mutations in rewiring regulatory networks, by systematically studying the evolution of dosage compensation binding sites at over a dozen independently formed young neo-sex chromosomes in Drosophila. Our detailed understanding of how dosage compensation in Drosophila works at the molecular level makes it an ideal model system to study the rewiring of regulatory networks, and recent methodological development make the investigation of binding site evolution at newly formed X chromosomes in non-model Drosophila species feasible, making this a timely and exciting proposal.