"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）：基因在基因组中分布非随意分布。从全基因组表达分析中出现的一种有趣的模式是，性别偏置表达的基因是，性别之间差异表达的基因在性别染色体上表现出偏见的分布。尤其是，雄性偏见的基因是从果蝇X染色体中耗尽的，从而使X脱生。雄性偏见基因的缺乏可以部分通过X染色体的雄性基因移动来解释。这些模式的进化力是有争议的，可能涉及男性种系X灭活，性拮抗或剂量补偿机制。果蝇米兰达（Drosophila Miranda）是我们最近产生的从头基因组序列组装的物种 - 具有新形成的性染色体系统。它的新染色体正在从普通的雌体到退化的Y中过渡。为了响应，Neo-X正在发展差异化X的刻板印象特性，包括获得局部剂量补偿的获取，以及 - 根据初步数据的建议 - 从其NEO-X中的基因转换过多。 D. Miranda因此提供了一个独特的系统，可以使用比较和功能基因组学方法研究基因运输的机制及其在作用中的进化原因。 公共卫生相关性：证据表明遗传因素在男性生育能力中的重要性正在积累，并且通常与睾丸中表达的基因有关。比较基因组分析表明，睾丸基因显示物种之间的快速转移（即许多人类独有的新基因表现出特异性表达），并且通常避免与性染色体联系在一起。我们将使用果蝇模型来研究睾丸基因快速演变及其在基因组中的偏差分布的基本原因，这将有助于理解与睾丸基因缺陷有关的男性不育。