"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。全基因组表达谱中出现的一个有趣模式是具有性别偏见表达的基因，即在性别之间差异表达的基因在性染色体上显示出偏见分布。特别是，果蝇X染色体中偏向雄性的基因被耗尽，使得X染色体变得去雄性化。男性偏好基因的缺失可以部分解释为男性基因从X染色体上移动。这些模式背后的进化力量是有争议的，可能涉及男性生殖系X失活，性拮抗，或剂量补偿机制。果蝇米兰达-一个物种，我们最近产生了从头基因组序列组装-有一个新形成的性染色体系统。它的neo-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。作为回应，neo-X正在进化分化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-源自其neo-X的过量基因易位。D.因此，米兰达提供了一个独特的系统，研究机制的基因贩运的一个不断演变的X染色体和其演变的原因，在行动中使用比较和功能基因组学的方法。 公共卫生相关性：遗传因素在男性生育力中的重要性的证据正在积累，并且通常与睾丸中表达的基因有关。比较基因组分析表明，睾丸基因在物种之间表现出快速的更替（也就是说，许多人类特有的新基因表现出睾丸特异性表达），并且通常避免与性染色体连锁。我们将使用模式物种果蝇来研究睾丸基因的快速进化及其在基因组中的偏向性分布的潜在原因，这将有助于理解与睾丸基因缺陷相关的男性不育。

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.