GENE CONVERSION IN MICE

拟议研究的目标是调查频率， 特性及其影响减数分裂和有丝分裂基因转化的因素 小鼠的种系。基因转化是非互惠的重组 遗传信息。这一过程的一个表现是非孟德尔式的 等位基因分离。这一结果可能对基因组产生深远的影响 进化和多样化。 减数分裂基因转化的频率和机制已被广泛研究 在真菌中研究，在那里人们可以获得并记录一种真菌的所有产物 单次减数分裂。类似的实验在哺乳动物身上是不可行的。事实上, 有证据表明，哺乳动物体内确实存在减数分裂基因转换 间接证据。本提案中描述的实验绕过了 到目前为止限制研究的技术和后勤问题 哺乳动物的基因转化：产生大量的后代和 转换事件的简单检测。我们设计并测试了一个 用于人为转换的小鼠雄配子群体的评分系统 事件。计划事件的发生会导致更正 报告基因突变与组织化学可检测报告的合成 精子细胞的活性。这一战略的修改将允许 细胞内减数分裂和有丝分裂的定量分析 生殖系中的染色体间基因转化。此外，我们打算 研究基因转化的大小和基因的影响 结构参数取决于这些过程的频率。 基因复制是进化变化的中心过程， 适应。基因转换显著影响所创建的基因家族 通过复制。这些实验将有助于评估 基因转换对人类进化和功能的影响 相关基因的分化。

The goals of the proposed research are to investigate the frequency, properties, and factors which affect meiotic and mitotic gene conversion in the germline of mice. Gene conversion is the non-reciprocal recombination of genetic information. One manifestation of this process is non-Mendelian segregation of alleles. The result can have profound effects upon genome evolution and diversification. The frequency and mechanism of meiotic gene conversion has been extensively studied in fungi, where one can obtain and score all the products of a single meiosis. Similar experiments are not feasible in mammals. In fact, evidence that meiotic gene conversion actually occurs in mammals is circumstantial. The experiments described in this proposal circumvent the technical and logistical problems which have heretofore limited the study of mammalian gene conversion: generating large numbers of progeny and simple detection of a conversion event. We have designed and tested a system to score populations of murine male gametes for contrived conversion events. The occurrence of a planned event results in correction of a mutated reporter gene and synthesis of histochemically detectable reporter activity in spermatids. Modifications of this strategy will allow a quantitative analysis of both meiotic and mitotic intra- and interchromosomal gene conversion in the germ line. In addition, we intend to investigate the size of gene conversions and the influence of gene structure parameters upon the frequency of these processes. Gene duplication is a central process for evolutionary change and adaptation. Gene conversion significantly influences gene families created through duplication. These experiments will be instrumental for assessing the evolutionary and functional ramifications of gene conversion upon the divergence of related genes.