The evolution of dosage compensation in Drosophila

果蝇剂量补偿的演变

• 批准号: 7014718
• 负责人: Doris Bachtrog
• 金额: $ 22.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7014718
• 关键词: DNA damage; Drosophilidae; arthropod genetics; artificial chromosomes; binding sites; computer assisted sequence analysis; evolution; gene expression; genetic mapping; genetic recombination; molecular dynamics; polymerase chain reaction; population genetics; sex chromosomes; transcription factor

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.

描述（由申请人提供）：剂量补偿是改变一种性别中 X 连锁基因的表达以平衡异配物种中雄性和雌性之间 X 染色体数量差异的过程。非重组 Y 染色体的退化是性染色体进化的一个普遍方面。 Y染色体变性产生选择压力，以平衡两性中X连锁基因的表达水平，从而推动剂量补偿的进化。米兰达果蝇 (Drosophila miranda) 是拟暗果蝇 (D.pseudoobscura) 的近亲（其基因组序列已公开），具有新形成的性染色体系统。它的 neo-Y 染色体正在从普通常染色体转变为简并 Y。作为响应，neo-X 正在进化出部分剂量补偿。我们将利用 D. miranda 系统，使用比较和功能基因组学方法来研究“实际”剂量补偿的演变。 比较序列分析与新性相关基因的表达谱相结合，将使我们能够将新性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在逐个基因的基础上进化——响应Y染色体上简并拷贝的形成——或者剂量补偿是否沿着X染色体以离散块的形式进化，一次涉及多个基因。我们将测试适应不良或剂量补偿的基因是否表现出neo-Y上表达水平降低，什么类型的变化降低了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，我们将尝试在 neo-X 染色体上重新绘制顺式作用结合位点，以招募剂量补偿机制。我们将研究这些结合位点的分子性质，并测试它们是否通过正选择被固定。这项研究将在我们对果蝇剂量补偿机制及其演变的理解方面取得重大进展。