MOLECULAR & EVOLUTIONARY GENETICS OF SEGREGATION DISTORT

黑腹果蝇的分离畸变蛋白（SD）是 在染色体上研究得最好的减数分裂驱动系统， 人口水平。 我们现在准备研究分子基础 的SD。 分子克隆也将使我们更好地了解 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： 基因座被广泛地分类为敏感的或不敏感的。 我们 我发现一个100- 1000个重复序列的串联阵列 迄今为止检测了8条敏感染色体。 阵列 重复序列在所有八条不敏感染色体中均不存在。 已经对重复序列的七个拷贝进行了测序， 一种新型的卫星DNA及其在 染色质凝聚和分离。 一种异常的 冷凝是生精失败的一个非常可能的原因， 导致偏析变形。 我们建议研究Rsp的三个方面。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 为了使用各种构建体的染色体，例如缺失， 易位自由复制以及自然发生的 变种，以实现这一目标。 序列足够， 敏感性的必要性将得到确认。 我们的数据表明， 序列不是别的， 我们将进一步验证这一假设， 灵敏度是串联的大小的直接结果 阵 将对大量重复序列进行测序 用于分子进化研究。 （二）进化与人口 将研究SD的遗传方面。 我们将描述 近缘物种的Rsp结构。 Rsp等位基因在自然 将对人口进行调查。 四个实验群体将 设置和监控。 这些人口将代表 敏感和不敏感染色体之间的竞争， 在有无SD染色体的情况下。 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）分子机制 将探索潜在的扭曲。 我们将调查，如果 Rsp等位基因在畸变和非畸变条件下转录 条件 我们已制订长远计划，研究 与Rsp卫星DNA相关的染色质结构。 在细胞系中和细胞中测定与这种DNA结合的蛋白质， 设计了不同的组织。

Segregation Distorter (SD) of Drosophila melanogasteris one of the best studied meiotic drive systems at the chromosomal and population level. We are now ready to study the molecular basis of SD. 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 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 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 study 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 genetic 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 explain 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.