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力中起着关键作用;然而，它被认为在更广泛的生物体健康或健康中起着相对较小的作用。最近的观察表明，数百至数千个基因的表达差异果蝇线之间的差异，只有在Y染色体表明，Y-连锁调控变异（YRV），可能归因于重复的差异，异染色质结合序列的Y染色体，是重要的和广泛的。这一提议试图回答关于这一新现象的两个基本问题。首先，在何种程度上不同物种之间的Y染色体的分歧有助于不同的基因表达（物种之间的许多表型差异的可能来源）？第二，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具有相当重要的意义）以及物种之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D. melanogaster，Y染色体来自D. sechellia将渐渗到D.模拟。通过使用定制设计的物种特异性微阵列比较天然D。simulans Y染色体和携带D. sechellia Y染色体，但在其他方面遗传上相同，将有可能鉴定仅由于这两个物种之间Y染色体的分歧而差异表达的基因。使用低成本的点样cDNA微阵列，靶向差异表达的基因在这个初步调查中确定，后续的实验将比较不同的D。sechellia和D. sechellia基因组背景和D. simulans的背景，以估计多态性和基因表达的分歧，进化建模的关键参数。使用这些数据，并结合修订后的模型Y染色体进化，纳入YRV的独特功能，基因表达分歧的模型将允许推断的进化力量，已统治的分歧Y-连锁基因表达物种之间。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表型的影响。了解Y染色体之间的差异如何影响生物体表型是了解Y染色体在人类健康和疾病中潜在作用的关键第一步。

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.