"Gene Trafficking on an Evolving X Chromosome in Drosophila"

描述（由申请人提供）：基因在基因组中非随机分布。从全基因组表达谱中出现的一个有趣的模式是，具有性别偏倚表达的基因，即在两性之间表达差异的基因，在性染色体上表现出偏倚分布。特别是，果蝇X染色体上的雄性偏向基因被耗尽，因此X染色体已经失去了男性特征。男性偏倚基因的缺失可以部分解释为男性基因从X染色体上移走。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、性拮抗或剂量补偿机制。我们最近为米兰达果蝇（Drosophila miranda）生成了一个全新的基因组序列组装，它有一个新形成的性染色体系统。它的新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。因此，新X正在进化出分化X的典型特性，包括获得部分剂量补偿，以及——正如初步数据所表明的——源自其新X的过量基因易位。因此，米兰达博士提供了一个独特的系统来研究进化中的X染色体上的基因运输机制及其进化原因，使用比较和功能基因组学方法。

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.