Molecular Evolution of Drosophila Y Chromosome

果蝇 Y 染色体的分子进化

• 批准号: 7653062
• 负责人: ANDREW G CLARK
• 金额: $ 31.5万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7653062
• 关键词: Alleles; Base Sequence; Binding; Bioinformatics; Biological Models; Characteristics; Chromosomes; Chromosomes, Human, 13-15; Code; Collection; DNA; DNA Sequence Rearrangement; Data; Diploidy; Drosophila genus; Elements; Evolution; Face; Female; Fertility; Frequencies; Gene Expression; Genes; Genetic; Genetic Epistasis; Genetic Models; Genetic Polymorphism; Genetic Recombination; Genome; Genomics; Haploidy; Heterochromatin; Learning; Link; Meiosis; Methods; Modeling; Molecular Evolution; Mutation; Pattern; Phylogeny; Polymorphism Analysis; Population; Population Genetics; Positioning Attribute; Proteins; RNA Interference; Race; Recurrence; Reporting; Research; Resources; Rest; Reverse Transcriptase Polymerase Chain Reaction; Role; Sex Chromosomes; Shapes; Shotguns; Site; Surveys; System; Testing; Variant; Work; X Chromosome; Y Chromosome; autosome; design; genome sequencing; knock-down; loss of function mutation; male; public health relevance; purge; research study; sample fixation; sperm cell; theories; transmission process

DESCRIPTION (provided by applicant): Because the Y chromosome is present in just one copy and only in males, it faces a diminished capacity to purge deleterious mutations. Our understanding of the complete set of functional elements on the Y chromosome lags far behind the rest of the genome, and this is especially true for the Drosophila model system. There are now 12 complete genome sequences for species of Drosophila whose well-known phylogeny provides a rich resource for analysis of Y chromosome dynamics. A major recent finding is that among these 12 species the gene gains largely outnumber gene losses, which is at odds with the view that the Y is simply degenerating. In this proposal, we aim first, to complete the annotation of Y-linked genes across the Drosophila species whose genomes have been sequenced. We have devised and perfected a highly efficient Illumina/Solexa-sequence based method for identifying Y-specific contigs, and plan to use it to identify, assemble, and annotate the Y-linked contigs and their embedded genes. RNAi knock-down will be used to identify the genes on the D. melanogaster and D. pseudoobscura Y that are essential for male fertility. Second, we will quantify and model intraspecific polymorphism in protein- coding genes on the Y chromosome of D. melanogaster, D. simulans, and D. pseudoobscura, as well as interspecific divergence among the 12 species. Analysis of polymorphism and divergence has started to place bounds on the levels of background selection acting on Drosophila Y chromosomes. The roles of Muller's ratchet, hitchhiking by selective sweeps, and the Hill-Robertson effect will also be assessed by fitting models of sequence evolution to site frequency data using approximate Bayesian computation. D. simulans is included as a second and more polymorphic cosmopolitan species to compare to melanogaster, and D. pseudoobscura's Y chromosome is derived within the past 18 Myr from formerly autosomal sequences. Third, we will assemble and finish the Y-to-autosome translocated region of D. pseudoobscura genome. This is motivated by the translocation of heterochromatic, Y-linked genes onto the dot chromosome in this species, presenting a fortuitous opportunity to study the effect of the loss of male-restricted transmission and the loss of heterochromatin in this region. This project will entail BAC sequencing, RT-PCR tests of expression, and analysis of polymorphism in this region. Finally, the fourth aim is to characterize and quantify functional variation associated with the Y chromosome. Simple population genetic models predict rapid fixation of favored Y chromosomal alleles, and yet there is compelling evidence that functional polymorphism is maintained. Theory further shows that interactions between Y and other chromosomes are more likely to be able to retain polymorphism, and recent work has demonstrated large effects of Y-linked variation on gene expression throughout the genome. Experiments designed specifically to quantify the role of epistasis in Y chromosomal evolution are well motivated. PUBLIC HEALTH RELEVANCE: The Y chromosome of Drosophila provides an ideal system for testing many concepts related to the evolution of sex chromosomes. The proposed study entails primary discovery of most of the Y- linked genes across a group of 12 species and a detailed study of their evolutionary divergence.

描述（由申请人提供）：由于Y染色体仅以一个拷贝存在，并且仅存在于男性中，因此它面临清除有害突变的能力减弱。我们对Y染色体上完整的功能元件的理解远远落后于基因组的其他部分，尤其是果蝇模型系统。目前，果蝇属的12个物种的全基因组序列已被确定，其著名的染色体遗传学为Y染色体动力学的分析提供了丰富的资源。最近的一项重大发现是，在这12个物种中，基因获得的数量大大超过了基因丢失的数量，这与Y染色体只是退化的观点不一致。在这个提议中，我们的目标首先是完成Y连锁基因的注释，这些基因组已经被测序的果蝇物种。我们已经设计并完善了一种高效的基于Illumina/Solexa序列的方法来识别Y特异性重叠群，并计划使用它来识别，组装和注释Y连锁重叠群及其嵌入的基因。RNAi敲低将用于鉴定D.黑腹果蝇D. pseudobscura Y是男性生育所必需的。其次，我们将量化和模型的种内多态性蛋白编码基因的Y染色体上的D。melanogaster、黑腹果蝇D. simulans和D. pseudobscura，以及种间分化。对多态性和趋异的分析已经开始限制果蝇Y染色体上背景选择的水平。穆勒的棘轮，搭便车的选择性扫描，和希尔-罗伯逊效应的作用也将通过拟合模型的序列进化的网站频率数据，使用近似贝叶斯计算进行评估。D. simulans作为第二个和更多的多态性世界性种被包括在内，与melanogaster相比，和D.伪暗的Y染色体是在过去的1800万年内从以前的常染色体序列中衍生出来的。第三，我们将组装并完成D.拟暗基因组这是由易位的异染色质，Y-连锁基因的斑点染色体在这个物种，提出了一个偶然的机会，研究男性限制传输的损失和损失的异染色质在这个地区的影响。该项目将需要BAC测序，RT-PCR检测表达，并分析该区域的多态性。最后，第四个目标是表征和量化与Y染色体相关的功能变异。简单的群体遗传学模型预测了有利的Y染色体等位基因的快速固定，然而有令人信服的证据表明功能多态性得以维持。理论进一步表明，Y和其他染色体之间的相互作用更有可能保持多态性，最近的工作已经证明了Y连锁变异对整个基因组的基因表达的巨大影响。专门设计的实验来量化上位性在Y染色体进化中的作用是有充分动机的。公共卫生关系：果蝇的Y染色体提供了一个理想的系统来测试与性染色体进化有关的许多概念。这项拟议中的研究需要初步发现一组12个物种中的大多数Y连锁基因，并详细研究它们的进化分歧。