MOLECULAR/EVOLUTIONARY GENETICS--SEGREGATION DISTORTION

果蝇的分离畸变蛋白（SD）是其中最好的一种 在染色体和种群水平上研究了减数分裂驱动系统。 我们 现在准备研究的分子克隆也将导致更好的 了解这个系统的群体遗传学。 的目标 分离畸变是应答者（Rsp）基因座; 基因座大致分为敏感型和不敏感型。 我们发现 在所有八个基因组中都存在着100- 1000个重复序列的串联阵列， 敏感的染色体。 重复序列不存在于 检查所有8条不敏感染色体。 七份重复的 已经被测序，代表了一类新的卫星DNA。 对这些重复序列的研究将弥合结构之间的差距 卫星DNA的特征及其在染色质中的假设作用 冷凝和离析。 一个异常的凝结过程是 很可能是精子生成失败的原因，导致分离 畸变 本文拟从三个方面对Rsp进行研究。I）其他分子 在一些实施方案中，Rsp基因座的特征描述了Rsp基因座的限制。 我们计划使用 各种结构的染色体，如缺失、易位、游离 复制以及自然发生的变异，以实现这一目标， 目标. 对于灵敏度来说，足够和必要的序列将 被识别。 我们的数据表明，这样的序列不是别人， 大量的重复序列，我们将进一步验证这一假设 该灵敏度是串联阵列尺寸的直接结果。 将对更大数量的重复序列进行测序，以用于分子生物学。 进化研究 二）SD的进化和群体遗传学方面 将被研究。 我们将密切关注Rsp的结构， 相关物种 将调查自然群体中的Rsp等位基因。 将建立四个实验种群并进行监测。 这些 种群将代表敏感和不敏感之间的竞争 在存在和不存在SD染色体的情况下的染色体。 一 卫星放大假说，提出来解释令人困惑的 将对SD的观察结果进行检验。 III）潜在的分子机制 将探索扭曲。 我们将研究Rsp等位基因是否 在扭曲和非扭曲条件下转录。 我们有 我制定了一个长期计划，研究染色质结构相关的 与Rsp卫星DNA进行比对 对结合这种DNA的蛋白质的测定， 细胞系和不同的组织中。

Segregation Distorter (SD) of Drosophilia melanogaster is one of the best studied meiotic drive systems at the chromosomal and population level. We are now ready to study the molecular cloning will also lead to a better understanding of the population genetics of this system. The target for segregation distortion is the Responder (Rsp) locus; the alleles at the locus are broadly classified as sensitive or insensitive. we have found that a tandem array of 100-1,000 repeats are present in all eight sensitive chromosomes so far examined. The array of repeats are absent in all eight insensitive chromosomes examined. Seven copies of the repeats have been sequenced which represent a novel class of satellite DNA. Studies of these repeats will bridge the gaps between structural characterizations of satellite DNA and its hypothetical roles in chromatin condensation and segregation. An aberrant process of condensation is a very likely cause of spermiogenic failure, resulting in segregation distortion. We propose to studies three aspects of Rsp. I) Further molecular characterization to delineate the limit of the Rsp locus. We plan to use chromosomes of various construct, such as deletions, translocations, free duplications as well as naturally-occurring variants, to achieve this goal. The sequences sufficient as well as necessary for sensitivity will be identified. Our data suggest such sequences are none other than the large array of repeats themselves and we will further test this hypothesis that sensitivity is a direct consequence of the size of the tandem array. Sequencing a larger number of repeats will be carried out for molecular evolution studies. II) Evolutionary and population genetics aspects of SD will be studied. We will characterize the structure of Rsp in closely related species. Rsp alleles in natural populations will be surveyed. Four experimental populations will be set up and monitored. These populations will represent competition between sensitive and insensitive chromosomes both in the presence and absence of SD chromosomes. A satellite amplification hypothesis, proposed to explained perplexing observations on SD, will be tested. III) Molecular mechanisms underlying distortion will be explored. We will investigate if the Rsp alleles are transcribed under distorting and nondistorting conditions. we have developed a long term plan to study the chromatin structure associated with the Rsp satellite DNA. Assays for proteins that bind to such DNA in cell lines and in different tissues are planned.