The evolution of dosage compensation in Drosophila

描述（由申请方提供）：剂量补偿是一种改变一种性别中X连锁基因表达的过程，以平衡异配子物种中雄性和雌性之间X染色体数量的差异。非重组Y染色体的变性是性染色体进化的一个普遍方面。Y染色体变性产生了选择压力，使两性中X连锁基因的表达水平相等，从而推动了剂量补偿的进化。果蝇（米兰达）是D. pseudobscura（其基因组序列是可用的）具有新形成的性染色体系统。它的neo-Y染色体正处于从普通常染色体向简并Y染色体的转变过程中。作为回应，neo-X正在发展部分剂量补偿。我们将利用D。米兰达系统使用比较和功能基因组学方法研究剂量补偿"作用“的演变。 比较序列分析结合新性别连锁基因的表达谱将使我们能够将新性别染色体上发生的分子变化与基因表达的变化联系起来。我们将区分剂量补偿是否是在一个基因接一个基因的基础上进化的--对Y染色体上简并拷贝的形成做出反应--或者剂量补偿是否是沿着X染色体沿着离散块进化的，一次涉及几个基因。我们将测试适应不良或剂量补偿基因是否在neo-Y上显示出表达水平降低，什么类型的变化会降低neo-Y上的基因表达，以及某些类别的基因是否比其他基因更容易退化。最后，我们将试图重新绘制新的X染色体上的顺式作用结合位点，招募剂量补偿机制。我们将研究这些结合位点的分子性质，并测试它们是否被正选择固定。这项研究将构成我们对果蝇剂量补偿机制及其演变的理解的重大进展。

DESCRIPTION (provided by applicant): Dosage compensation is the process by which the expression of X-linked genes is altered in one sex to counterbalance the difference in X-chromosome number between males and females in a heterogametic species. Degeneration of the non-recombining Y chromosome is a general facet of sex chromosome evolution. Y-chromosome degeneration creates selective pressure to equalize expression levels of X-linked genes in the two sexes, thus driving the evolution of dosage compensation. Drosophila miranda, a close relative of D. pseudoobscura (whose genome sequence is available) has a newly formed sex chromosome system. Its neo-Y chromosome is in transition from an ordinary autosome to a degenerate Y. In response, the neo-X is evolving partial dosage compensation. We will exploit the D. miranda system to study the evolution of dosage compensation 'in action' using a comparative and functional genomics approach. Comparative sequence analysis combined with expression profiles of neo-sex linked genes will allow us to link molecular changes occurring on the neo-sex chromosomes to changes in gene expression. We will distinguish whether dosage compensation evolves on a gene-by-gene basis - in response to the formation of a degenerate copy on the Y chromosome - or whether dosage compensation evolves in discrete blocks along the X chromosome, involving several genes at a time. We will test whether maladapted or dosage- compensated genes show reduced levels of expression on the neo-Y, what types of changes reduce gene expression on the neo-Y, and whether certain classes of genes are more prone to degeneration than others. Finally, we will attempt to map de novo cis-acting binding sites on the neo-X chromosome that recruit the dosage compensation machinery. We will investigate the molecular nature of these binding sites, and test whether they were fixed by positive selection. This research will constitute significant progress in our understanding of the mechanism of dosage compensation in Drosophila and how it evolves.