Interspecific divergence of Y chromosome effects on gene expression in Drosophila

Y染色体种间分歧对果蝇基因表达的影响

• 批准号: 8005042
• 负责人: Timothy Sackton
• 金额: $ 5.13万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8005042
• 关键词: Affect; Binding; Biological Models; Chromosomes; Chromosomes, Human, 13-15; Custom; Data; Disease; Drosophila genus; Drosophila melanogaster; Evolution; Fertility; Gene Expression; Gene Expression Regulation; Genes; Genetic Polymorphism; Genetic Variation; Genomics; Health; Heterochromatin; Human; Link; Maintenance; Maps; Mediating; Modeling; Phenotype; Play; Population Dynamics; Process; Rice; Role; Sex Chromosomes; Source; Spottings; Surveys; Testing; Theoretical model; Variant; Work; Y Chromosome; cDNA Arrays; cost; design; fitness; male; novel; research study; theories

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.

描述（由申请人提供）：众所周知，Y 染色体在男性生育能力中发挥着关键作用；然而，人们认为它在机体健康或更广泛的健康方面发挥的作用相对较小。最近观察到，果蝇品系之间数百至数千个基因的表达存在差异，且仅在 Y 染色体上存在差异，这表明 Y 连锁调控变异 (YRV) 很重要且广泛存在，这可能归因于 Y 染色体上重复的异染色质结合序列的差异。该提案旨在回答有关这一新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非常重要）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。利用与黑腹果蝇密切相关的现有果蝇种群，将来自黑腹果蝇的 Y 染色体基因渗入到模拟果蝇中。通过使用定制设计的物种特异性微阵列来比较具有天然拟果蝇 Y 染色体的品系和携带真果蝇 Y 染色体但在其他方面遗传上相同的渗入品系之间的基因表达，将有可能鉴定出仅由于这两个物种之间 Y 染色体的差异而差异表达的基因。使用针对初步调查中确定的差异表达基因的低成本斑点 cDNA 微阵列，后续实验将比较 D. sechellia 基因组背景和 D. simulans 背景中的不同 D. sechellia Y 染色体，以估计基因表达的多态性和分歧，这是进化模型的关键参数。利用这些数据，并结合包含 YRV 独特特征的修订版 Y 染色体进化模型，基因表达差异模型将能够推断出控制物种间 Y 连锁基因表达差异的进化力量。这里提出的工作使用果蝇模型系统来区分 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。