Genomic Mechanisms of Chromosomal Rearrangements in Drosophila Pseudoobscura

果蝇染色体重排的基因组机制

• 批准号: 8706183
• 负责人: STEPHEN W SCHAEFFER
• 金额: $ 11.61万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8706183
• 关键词: Adult; Alleles; Biological Models; Biology; Birth; Chromosomal Rearrangement; Chromosome inversion; Chromosomes; Climate; Code; DNA Transposable Elements; Data; Disease; Drosophila genus; Environment; Equilibrium; Evolution; Exons; Fertility; Frequencies; Future; Gene Expression; Gene Expression Profile; Gene Mutation; Gene Order; Gene Structure; Genes; Genetic; Genetic Crossing Over; Genetic Drift; Genetic Polymorphism; Genetic Recombination; Genome; Genomics; Germ Cells; Goals; Hereditary Disease; Human; Individual; Laboratories; Larva; Lead; Lesion; Life; Linkage Disequilibrium; Linkage Disequilibrium Mapping; Location; Maintenance; Maps; Messenger RNA; Modeling; Molecular; Molecular Abnormality; Molecular Genetics; Mutation; Nature; Nucleotides; Paracentric Inversion; Pattern; Population; Population Genetics; Pregnancy; Proteins; Repetitive Sequence; Reproduction; Research Design; Seasons; Sequence Analysis; Series; Southwestern United States; Staging; Symptoms; System; Technology; Testing; Transcript; Variant; base; comparative genomics; design; egg; fitness; genetic analysis; improved; next generation; next generation sequencing; research study; sperm cell; tool; transcriptome sequencing

DESCRIPTION (provided by applicant): Chromosomal inversions are often detected in humans when individuals present symptoms of genetic diseases. Individuals with two different inversions can have lower fertility because genetic exchange between inverted chromosomes can lead to the formation of sperm or eggs with less or more genetic information. Inversions, however, can also be present in populations at high frequencies with no apparent negative effects on viability or reproduction. This proposal will test hypotheses about how inversions arise, spread, and are maintained in populations. Drosophila pseudoobscura is a model system for the study of inversions because its third chromosome is polymorphic for over 30 different gene arrangements in populations. These arrangements were generated through a series of overlapping paracentric inversions. The inversion frequencies vary among populations forming clines or gradients whose major frequency shifts occur with major climatic zones in the southwestern United States. The gene arrangement frequencies cycle with the seasons and show altitudinal clines. Population cage experiments in the laboratory have shown that different gene arrangements are maintained at stable equilibrium frequencies. This study will use next generation technologies to re-sequence 50 strains of D. pseudoobscura that carry one of six major chromosomal arrangements. Next generation sequencing analysis of mRNA will be used to quantify expression differences among the six different inversion backgrounds for two different Drosophila life stages, larvae and adults. The re-sequencing data will identify inversion breakpoint sequences and improve the D. pseudoobscura genome assembly. The transcriptome data will be used to improve the annotation of gene models in D. pseudoobscura. Molecular population genetic analyses of nucleotide polymorphism and gene expression data will test four classes of hypotheses about how a new inversion spreads through a population: (1) indirect effects due to reduced recombination leading to chromosomes free of deleterious mutations or enhancing the linkage of adaptive genes; (2) genetic drift that fixes underdominant arrangements; (3) direct effects of the chromosomal lesion such as alteration of gene structure or expression; or (4) genetic hitchhiking with an adaptive allele. These analyses will test two hypotheses about how inversions are maintained in populations: (1) by overdominance; or (2) as a protected polymorphism. Genes that show differential expression or protein variation may be manipulated in future experiments designed to understand the molecular genetic basis that underpins inversion evolution.

描述（由申请人提供）： 当个体出现遗传病症状时，通常会在人类中检测到染色体倒位。具有两种不同倒位的个体的生育能力可能较低，因为倒位染色体之间的遗传交换可能导致形成具有较少或较多遗传信息的精子或卵子。然而，倒位也可能以高频率出现在种群中，而对生存或繁殖没有明显的负面影响。该提案将测试有关倒置如何在群体中产生、传播和维持的假设。 假暗果蝇是研究倒位的模型系统，因为其第三条染色体在群体中具有 30 多种不同基因排列的多态性。这些排列是通过一系列重叠的同心倒转产生的。逆温频率因形成斜线或梯度的种群而异，其主要频率变化发生在美国西南部的主要气候带。基因排列频率随季节循环并表现出海拔梯度。实验室的群体笼实验表明，不同的基因排列保持在稳定的平衡频率。 这项研究将使用下一代技术对 50 个携带六种主要染色体排列之一的 D.pseudoobscura 菌株进行重新测序。下一代 mRNA 测序分析将用于量化两个不同果蝇生命阶段（幼虫和成虫）的六种不同倒置背景之间的表达差异。重测序数据将识别反转断点序列并改进 D.pseudoobscura 基因组组装。转录组数据将用于改进 D.pseudoobscura 基因模型的注释。对核苷酸多态性和基因表达数据的分子群体遗传分析将测试关于新倒位如何在群体中传播的四类假设：（1）由于重组减少导致染色体不含有害突变或增强适应性基因的连锁而产生的间接影响; (2) 修复劣势排列的遗传漂变； (3) 染色体病变的直接影响，例如基因结构或表达的改变； (4) 具有适应性等位基因的遗传搭便车。这些分析将检验关于种群中倒置如何维持的两个假设：（1）通过过度显性；或（2）作为受保护的多态性。显示差异表达或蛋白质变异的基因可以在未来的实验中被操纵，这些实验旨在了解支持反转进化的分子遗传基础。

项目成果

The relevance of chromatin architecture to genome rearrangements in Drosophila.

果蝇染色质结构与基因组重排的相关性。

• DOI: 10.1098/rstb.2021.0206
• 发表时间: 2022
• 期刊: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
• 作者: Wright,Dynisty;Schaeffer,StephenW
• 通讯作者: Schaeffer,StephenW