Molecular and Evolutionary Genetics of Meiotic Drive

减数分裂驱动的分子和进化遗传学

• 批准号: 10316220
• 负责人: DANIEL A BARBASH
• 金额: $ 32.06万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-16 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10316220
• 关键词: Adult; Alleles; Animals; Biological Assay; Candidate Disease Gene; Centromere; Chromosome Mapping; Chromosome Segregation; Chromosomes; Conflict (Psychology); DNA; DNA Sequence; Data; Dependence; Detection; Development; Drosophila genus; Drosophila melanogaster; Evolution; Female; Fertility; Frequencies; Funding; Future; Gene Frequency; Genes; Genetic; Genetic Polymorphism; Genome; Genotype; Germ Cells; Health; Human; Individual; Laws; Life Cycle Stages; Maps; Measures; Meiosis; Meiotic Recombination; Methodology; Methods; Mitotic Recombination; Molecular; Molecular Analysis; Molecular Genetics; Mothers; Mutation; Oogenesis; Organism; Orthologous Gene; Parasites; Population; Population Genetics; Population Heterogeneity; Process; Production; Reagent; Recombinants; Recording of previous events; Recovery; Research; Resolution; Selfish DNA; Selfish Genes; Series; Standardization; System; Technology; Testing; Variant; Work; base; egg; experimental study; fitness; genetic analysis; insight; novel; novel strategies; offspring; precursor cell; pressure; response; segregation; sperm cell; theories; transmission process

Project Summary/Abstract Mendel's first law describes how the two alleles in a heterozygous individual have equal chances of being transmitted to its progeny. Decades of work have revealed that different types of selfish DNAs can parasitize host species and subvert Mendel's first law to increase their transmission to offspring and their frequency in populations. These selfish DNAs are deleterious as they can reduce fertility and distort allele frequencies of host genes in populations. The asymmetric meiosis found in the females of many species including humans is particularly prone to attack by selfish DNAs because only one meiotic product forms an egg while the remainder become polar bodies. Meiotic drivers exploit this asymmetry by biasing their transmission to the egg. Moderate-strength meiotic drivers that bias their transmission by a few percent may be prevalent in populations but have been challenging to identify due to the necessity of distinguishing them from viability effects. This proposal will determine the identity and mechanism of a recently discovered candidate meiotic driver discovered in a natural population of the fruit fly Drosophila melanogaster that causes an approximately 4% deviation from normal Mendelian segregation. This candidate maps broadly to a centromeric region, leading to the working hypothesis that it corresponds to a variant in heterochromatic repetitive DNA. Novel methods will first be used to track the genotype and state of development of individuals throughout the life cycle, from meiosis in their mothers through adulthood, in order to determine the mechanism of meiotic drive. Heterochromatic regions have long been considered inaccessible to conventional genetic mapping approaches due to their complete suppression of meiotic recombination. A new approach is developed here to generate recombinants across the centromeric region in order to perform a high-resolution association study of repeat type and abundance relative to meiotic drive. Importantly, this approach does not require genome assembly across the centromere. We will also apply both short-read and long-read sequencing technologies to identify candidate sequences responsible for drive. Following these mapping and sequencing approaches, experimental manipulation will be used to test and confirm identity of the meiotic driver. Evolutionary theory predicts that meiotic drive will vary in degree between populations. This proposal will investigate the magnitude of drive in both related and unrelated populations, and then map and identify major-effect modifier alleles. Other candidate meiotic drivers will also be characterized by the approaches developed here. This proposal will provide an unprecedented level of information about the identity and mechanism of meiotic drivers that are segregating in natural populations, and provide a framework and series of methods that can be applied to other types of non-Mendelian transmission in a wide range of organisms.

项目摘要/摘要 孟德尔第一定律描述了杂合子个体中的两个等位基因如何具有相等的机会 传给它的后代。数十年的研究表明，不同类型的自私DNA可以寄生 寄主物种和颠覆孟德尔第一定律增加它们对后代的传播和它们在 人口。这些自私的DNA是有害的，因为它们会降低生育力并扭曲等位基因频率 种群中的宿主基因。在包括人类在内的许多物种的雌性中发现的不对称减数分裂是 特别容易受到自私DNA的攻击，因为只有一个减数分裂产物形成卵子，而 其余的则成为极体。减数分裂驱动因素利用这种不对称性，将它们的传递偏向 蛋。中等强度的减数分裂驱动因素使其传递偏差几个百分点，可能在 种群，但由于有必要将它们与生存能力区分开来，识别一直具有挑战性 效果。这一提议将确定最近发现的候选减数分裂的身份和机制。 一名司机在果蝇的自然种群中发现了黑腹果蝇，它导致了大约 4%偏离正常的孟德尔分离。该候选基因广泛地映射到着丝粒区域， 这导致了一种工作假设，即它对应于异染色质重复DNA中的一个变体。小说 这些方法将首先用来跟踪个体一生中的基因和发育状态 从母体减数分裂到成年期，以确定减数分裂的驱动机制。 异染色质区域长期以来被认为是传统的遗传作图方法所不能达到的 由于它们完全抑制了减数分裂重组。这里开发了一种新的方法来生成 跨着丝粒区域的重组体，以便进行重复序列的高分辨率关联研究 相对于减数分裂驱动的类型和丰度。重要的是，这种方法不需要基因组组装。 穿过着丝粒。我们还将应用短读和长读测序技术来识别 负责驱动的候选序列。在这些映射和排序方法之后， 实验操作将用于测试和确认减数分裂驱动因素的身份。进化论 预测减数分裂的驱动力将在不同种群之间有所不同。这项提案将调查其规模 在相关和不相关群体中的驱动力，然后定位和识别主效修饰性等位基因。 其他候选减数分裂驱动因素也将以这里开发的方法为特征。这项建议 将提供前所未有的关于减数分裂驱动因素的身份和机制的信息 在自然种群中隔离，并提供了一个框架和一系列方法，可以应用于其他 在广泛的生物体中的非孟德尔传播类型。

项目成果

Stonewall prevents expression of ectopic genes in the ovary and accumulates at insulator elements in D. melanogaster.

• DOI: 10.1371/journal.pgen.1010110
• 发表时间: 2022-03
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Zinshteyn D;Barbash DA
• 通讯作者: Barbash DA

Normal segregation of a foreign-species chromosome during Drosophila female meiosis despite extensive heterochromatin divergence.

尽管存在广泛的异染色质分歧，但果蝇雌性减数分裂期间外来物种染色体的正常分离。

• DOI: 10.1534/genetics.114.172072
• 发表时间: 2015
• 期刊: Genetics
• 影响因子: 3.3
• 作者: Gilliland,WilliamD;Colwell,EileenM;Osiecki,DavidM;Park,Suna;Lin,Deanna;Rathnam,Chandramouli;Barbash,DanielA
• 通讯作者: Barbash,DanielA

The Hmr and Lhr hybrid incompatibility genes suppress a broad range of heterochromatic repeats.

• DOI: 10.1371/journal.pgen.1004240
• 发表时间: 2014-03
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Satyaki PR;Cuykendall TN;Wei KH;Brideau NJ;Kwak H;Aruna S;Ferree PM;Ji S;Barbash DA
• 通讯作者: Barbash DA

Limited gene misregulation is exacerbated by allele-specific upregulation in lethal hybrids between Drosophila melanogaster and Drosophila simulans.

• DOI: 10.1093/molbev/msu127
• 发表时间: 2014-07
• 期刊: Molecular biology and evolution
• 影响因子: 10.7
• 作者: K. Wei;A. Clark;D. Barbash

Structure and dynamics of cholesterol-containing polyunsaturated lipid membranes studied by neutron diffraction and NMR.

• DOI: 10.1007/s00232-010-9326-6
• 发表时间: 2011-01
• 期刊: JOURNAL OF MEMBRANE BIOLOGY
• 影响因子: 2.4
• 作者: Mihailescu, Mihaela;Soubias, Olivier;Worcester, David;White, Stephen H.;Gawrisch, Klaus
• 通讯作者: Gawrisch, Klaus