Molecular and Evolutionary Genetics of Meiotic Drive

项目总结/摘要 孟德尔第一定律描述了一个杂合子个体中的两个等位基因是如何有相等的机会被遗传的。 传递给后代。几十年的研究表明，不同类型的自私DNA可以寄生在 宿主物种和颠覆孟德尔的第一定律，以增加他们的传播给后代和他们的频率， 人口。这些自私的DNA是有害的，因为它们可以降低生育力并扭曲等位基因频率。 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， 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，而另一个减数分裂产物形成卵子。 剩下的变成了极体。减数分裂驱动程序利用这种不对称性，将它们的传输偏向染色体。 蛋中等强度的减数分裂驱动程序，使其传输偏差百分之几，可能是普遍的， 种群，但由于必须将其与生存能力区分开来，因此识别起来具有挑战性 方面的影响.这一提议将确定最近发现的一个候选减数分裂的身份和机制 在果蝇自然种群中发现的一种驱动因子， 4%的偏离正常孟德尔分离。该候选者广泛地映射到着丝粒区域， 这导致了工作假设，即它对应于异染色质重复DNA中的变体。小说 方法将首先用于跟踪基因型和个体一生的发育状态 周期，从减数分裂在他们的母亲通过成年，以确定减数分裂驱动机制。 异染色质区域长期以来被认为是传统遗传作图方法无法达到的 因为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 为了进行重复序列的高分辨率关联研究， 类型和丰度相对于减数分裂驱动。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。在这些定位和测序方法之后， 将使用实验操作来测试和确认减数分裂驱动者的身份。进化论 预测减数分裂驱动在不同种群之间的程度会有所不同。这项提案将调查 在相关和不相关人群中的驱动力，然后映射和识别主效应修饰等位基因。 其他候选减数分裂驱动程序也将通过本文开发的方法进行表征。这项建议 将提供前所未有的信息水平的身份和机制的减数分裂驱动程序， 分离在自然群体中，并提供了一个框架和一系列的方法，可以应用于其他 在广泛的生物体中的非孟德尔传播类型。

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.