"Gene Trafficking on an Evolving X Chromosome in Drosophila"

“果蝇进化 X 染色体上的基因贩运”

• 批准号: 7866777
• 负责人: Doris Bachtrog
• 金额: $ 29.51万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7866777
• 关键词: Alternative Splicing; Base Sequence; Computer Analysis; Data; Defect; Dosage Compensation (Genetics); Drosophila genus; Evolution; Fertility; Gene Duplication; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Polymorphism; Genome; Genomics; Head; Human; Larva; Location; Male Infertility; Modeling; Molecular; Molecular Profiling; Movement; Ovary; Pattern; Population; Population Genetics; Property; Relative (related person); Sex Bias; Sex Chromosomes; System; Testing; Testis; Tissues; X Chromosome; X Inactivation; Y Chromosome; autosome; comparative; driving force; duplicate genes; fly; functional genomics; genome sequencing; genome-wide; improved; male; novel; pressure; public health relevance; response; sample fixation; sex; trafficking; transcriptomics

DESCRIPTION (provided by applicant): Genes are distributed non-randomly across the genome. One intriguing pattern to emerge from genome-wide expression profiling is that genes with sex-biased expression that is, genes that are differentially expressed between the sexes show a biased distribution on sex chromosomes. In particular, male-biased genes are depleted from the Drosophila X chromosome, such that the X has become demasculinized. The deficiency of male-biased genes can partly be explained by movement of male genes off the X chromosome. The evolutionary forces underlying these patterns are controversial and may involve male germline X inactivation, sexual antagonism, or dosage compensation mechanisms. Drosophila miranda - a species for which we recently generated a de novo genome sequence assembly - 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 the stereotypical properties of a differentiated X, including the acquisition of partial dosage compensation and - as suggested by preliminary data - an excess of gene translocations originating from its neo-X. D. Miranda therefore provides a unique system to study the mechanisms of gene trafficking on an evolving X chromosome and its evolutionary causes in action using a comparative and functional genomics approach. PUBLIC HEALTH RELEVANCE: Evidence for the importance of genetic factors in male fertility is accumulating, and is often associated with genes that are expressed in testis. Comparative genome analysis has shown that testis genes show rapid turnover between species (that is, many novel genes unique to humans show testis-specific expression) and often avoiding linkage to sex chromosomes. We will use the model species Drosophila to investigate the underlying causes for the rapid evolution of testis genes and their biased distribution in the genome, which will help to understand male infertility associated with defects in testis genes.

描述（由申请人提供）：基因在基因组中非随机分布。全基因组表达谱中出现的一个有趣的模式是，具有性别偏向表达的基因，即在两性之间差异表达的基因在性染色体上表现出偏向分布。特别是，果蝇 X 染色体中偏雄性的基因被耗尽，使得 X 变得去男性化。男性基因的缺乏可以部分解释为男性基因离开X染色体。这些模式背后的进化力量是有争议的，可能涉及雄性生殖系 X 失活、性对抗或剂量补偿机制。米兰达果蝇——我们最近为其生成了从头基因组序列组装的物种——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。作为回应，neo-X 正在进化出分化 X 的刻板特性，包括获得部分剂量补偿，以及（如初步数据所示）源自 Neo-X 的过量基因易位。因此，D. Miranda 提供了一个独特的系统，使用比较和功能基因组学方法来研究进化 X 染色体上的基因贩运机制及其进化原因。 公共卫生相关性：越来越多的证据表明遗传因素对男性生育力的重要性，并且通常与睾丸中表达的基因有关。比较基因组分析表明，睾丸基因在物种之间表现出快速的更替（即，许多人类特有的新基因表现出睾丸特异性表达），并且常常避免与性染色体连锁。我们将利用模式物种果蝇来研究睾丸基因快速进化的根本原因及其在基因组中的偏向分布，这将有助于了解与睾丸基因缺陷相关的男性不育症。