Interspecific divergence of Y chromosome effects on gene expression in Drosophila

描述(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起关键作用；然而，它被认为在更广泛的身体健康或健康中起到的作用相对较小。最近的观察表明，仅在Y染色体上存在差异的果蝇品系之间有成百上千个基因的表达差异，这表明Y连锁调节变异(YRV)是重要的和普遍的，可能归因于Y染色体上重复的异染色质结合序列的差异。这项提议试图回答关于这一新奇现象的两个基本问题。首先，物种间Y染色体的差异在多大程度上导致了基因表达的差异(物种间许多表型差异的一个可能来源)？其次，YRV如何影响我们对Y染色体如何进化的理解(对于理解性染色体的进化退化是相当重要的)，以及物种之间的基因表达差异是如何进化的？为了回答这些问题，我们将采用实验和理论相结合的方法。利用现有的与黑腹果蝇密切相关的物种种群，来自黑腹果蝇的Y染色体将被导入到拟果蝇中。通过使用定制设计的物种特异性微阵列比较具有天然拟态D染色体的品系和具有D.sechellia Y染色体但在其他方面相同的导入系之间的基因表达，将有可能识别仅由于Y染色体在这两个物种之间的差异而差异表达的基因。使用低成本的斑点cDNA微阵列来定位在最初调查中发现的差异表达的基因，后续的实验将比较D.sechellia基因组背景和D.Simans背景中不同的D.sechellia Y染色体，以估计基因表达的多态和差异，这是进化建模的关键参数。利用这些数据，并结合结合YRV独特特征的Y染色体进化修订模型，基因表达差异模型将允许推断支配物种间Y连锁基因表达差异的进化力量。这里提出的工作使用一个果蝇模型系统来分离Y染色体与其他染色体对生物表型的影响。了解Y染色体之间的差异如何影响生物表型，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.