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; 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）：剂量补偿是一种性别中X连锁基因表达的过程，以抵消杂型物种中男性和女性之间X染色体数的差异。非重组Y染色体的变性是性染色体进化的一般方面。 Y染色体变性会产生选择性压力，以使两个性别中X连锁基因的表达水平均衡，从而推动了剂量补偿的演变。 D. pseudoobscura的近亲（可用的基因组序列）具有新形成的性染色体系统。它的新染色体正在从普通的自生体过渡到退化Y。为了作出反应，Neo-X正在不断发展的部分剂量补偿。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剂量补偿“行动中”的演变。 比较序列分析与新性别链接基因的表达谱相结合，将使我们能够将发生在新性别染色体上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按基因的基础演变而来的 - 响应于Y染色体上的退化副本的形成，还是沿X染色体的离散块中的剂量补偿会演变，一次涉及几个基因。我们将测试疾病或剂量补偿基因在新Y上表达的表达水平降低，哪些类型的变化降低了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变性。最后，我们将尝试在募集剂量补偿机械的Neo-X染色体上绘制从头cis作用的结合位点。我们将研究这些结合位点的分子性质，并测试它们是否是通过阳性选择固定的。这项研究将在我们对果蝇剂量补偿机理及其演变中的剂量补偿机理方面构成重大进展。