Dosage compensation and the rewiring of regulatory netoworks in Drosophila

进化的创新和适应往往需要迅速和协调一致的变化， 在许多位点的基因表达。转座因子（Transposable elements，TE）是转座因子中最具活力的部分。 真核生物基因组，转座因子的插入可以影响表达， 通过提供新的调控元件来包围基因。一个由来已久的假设， 作者芭芭拉·麦克林托克（Barbara McClintock），假设转座因子的分散可能允许相同的 调节基序将在许多基因组位置被招募，从而将多个基因吸引到基因组中。 同样的监管网络。然而，这种模式的经验证据很少，而且大多数都是假定的 TE介导的调节网络重新布线的例子依赖于以下之间的统计关联： 在基因或基因组区域的子集处的TE的残余物。我们最近提供了第一个直接 一个活跃的TE重新布线监管网络的功能证据，通过显示收购 在年轻的新性染色体上的剂量补偿复合物的新结合位点， 果蝇是由驯化TE的传播驱动的。在这里，我们建议量化 TE的参与与通过其他突变获得调节位点在重新连接调节中的作用 网络，通过系统地研究剂量补偿结合位点的演变， 12个独立形成的年轻的新性染色体。我们详细的 了解果蝇的剂量补偿如何在分子水平上起作用， 理想的模型系统，研究重新布线的监管网络，和最近的方法 开发研究了新形成的X染色体上结合位点的进化， 非模式果蝇物种的可行性，使这是一个及时和令人兴奋的建议。

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.