Interspecific divergence of Y chromosome effects on gene expression in Drosophila

描述（由申请人提供）：Y染色体长期以来一直被认为在男性生育能力中发挥关键作用；然而，人们一直认为它在机体健康或更广泛的健康中起的作用相对较小。最近的观察发现，在黑腹果蝇系中，数百到数千个基因的表达存在差异，而这些基因仅在Y染色体上存在差异，这表明，Y连锁调节变异（Y -linked regulatory variation， YRV）可能归因于Y染色体上重复异染色质结合序列的差异，这是重要而广泛的。这个提议试图回答关于这个新现象的两个基本问题。首先，物种之间Y染色体的差异在多大程度上导致了基因表达的差异（物种之间许多表型差异的可能来源）？其次，YRV如何影响我们对Y染色体如何进化（对于理解性染色体的进化退化相当重要）以及物种间基因表达差异如何进化的理解？为了回答这些问题，将采用实验和理论相结合的方法。利用与黑腹果蝇亲缘关系密切的现有果蝇种群，将来自黑腹果蝇的Y染色体渗入到拟南果蝇中。通过使用定制设计的物种特异性微阵列来比较具有原生拟南稻Y染色体的品系和携带黑稻Y染色体但在其他方面基因相同的渗入品系之间的基因表达，将有可能鉴定出仅仅由于这两个物种之间的Y染色体差异而导致的基因表达差异。利用低成本斑点cDNA微阵列，针对在初步调查中发现的差异表达基因，随后的实验将比较不同的白莲子Y染色体在白莲子基因组背景和白莲子模拟背景下的多态性和基因表达差异，这是进化模型的关键参数。利用这些数据，并结合包含YRV独特特征的Y染色体进化修正模型，基因表达差异模型将允许对控制物种间Y连锁基因表达差异的进化力量进行推断。这里提出的工作使用果蝇模型系统来解开Y染色体与其他染色体对生物体表型的影响。了解Y染色体之间的差异如何影响机体表型是了解Y染色体在人类健康和疾病中的潜在作用的关键的第一步。

DESCRIPTION (provided by applicant): The Y chromosome has long been known to play a critical role in male fertility; however, it has been thought to play relatively little role in organismal fitness or health more broadly. The recent observation that hundreds to thousands of genes differ in expression between Drosophila melanogaster lines that differ only at the Y chromosome suggests that Y-linked regulatory variation (YRV), likely attributable to differences in repetitive, heterochromatin-binding sequences on the Y chromosome, is important and widespread. This proposal seeks to answer two fundamental questions about this novel phenomenon. First, to what extent does the divergence of Y chromosomes between species contribute to divergent gene expression (a likely source of many phenotypic differences between species)? Second, how does YRV affect our understanding of how Y chromosomes evolve (of considerable importance for understanding the evolutionary degeneration of sex chromosomes) and of how gene expression differences between species evolve? In order to answer these questions, a combined experimental and theoretical approach will be employed. Using existing Drosophila stocks of species closely related to D. melanogaster, Y chromosomes from D. sechellia will be introgressed into D. simulans. By comparing gene expression using custom-designed species-specific microarrays between lines with native D. simulans Y chromosomes and introgression lines that carry a D. sechellia Y chromosome but are otherwise genetically identical, it will be possible to identify genes that are differentially expressed due solely to divergence of the Y chromosome between this two species. Using low-cost spotted cDNA microarrays that target the differentially expressed genes identified in this initial survey, subsequent experiments will compare different D. sechellia Y chromosomes in both a D. sechellia genomic background and a D. simulans background to estimate polymorphism and divergence in gene expression, crucial parameters for evolutionary modeling. Using these data, and combined with revised models Y chromosome evolution that incorporate the unique features of YRV, models of gene expression divergence will allow inference about the evolutionary forces that have governed the divergence of Y-linked gene expression between species. The work proposed here uses a Drosophila model system to disentangle the effects of the Y chromosome from other chromosomes on organismal phenotypes. Understanding how differences among Y chromosomes affect organismal phenotype is a critical first step towards understanding the potential role of the Y chromosome in human health and disease.