Intermolecular Gene Conversion in halophilic Archaea.

基因转换被定义为信息从一个DNA序列到同源（但不相同）序列的非互惠转移。基因转换发生在生命的所有三个领域，也发生在病毒中。基因转换涉及许多不同的过程，从停止复制分叉的DNA修复到减数分裂中遗传多样性的产生。基因转换的研究主要集中在真核生物中，而对细菌的研究主要集中在分子内的基因转换，这导致了基因家族的协同进化或抗原变异。多倍体原核生物不同基因组拷贝间的分子间基因转换研究很少。它可以导致基因组拷贝的均等化，并代表了穆勒棘轮（一种预测多倍体原核生物不应该存在的理论）的逃脱。本项目将利用火山盐古菌研究基因组拷贝均衡的分子间基因转换的各个方面。已经建立了一种实验方法，可以对未选择的基因转换事件进行定量分析。本研究的目标如下：1)分析非选择基因转化的特征，如基因组差异程度对基因转化效率的影响；2)分析外部和环境参数对分子间基因转化的影响：3)鉴定与分子间基因转化相关或必需的蛋白质；4)分析不同物种基因间的分子间基因转化。总之，这些方法将导致对多倍体原核生物基因组拷贝均衡的分子间基因转换的前所未有的见解。

Gene conversion is defined as the non-reciprocal transfer of information from one DNA sequence to a homologous (but not identical) sequence. Gene conversion occurs in all three domains of life and also in viruses. Gene conversion is involved in many different processes, from DNA repair at stalled replication forks to the generation of genetic diversity in meiosis. Gene conversion has mostly been studied in eukaryotes, and the studies with bacteria concentrated on intramolecular gene conversion, which results in concerted evolution of gene families or in antigenic variation. Intermolecular gene conversion between different genome copies of polyploid prokaryotes has hardly been studied. It can lead to the equalization of genome copies and represents an escape from Muller’s ratchet (a theory predicting that polyploid prokaryotes should not be able to exist). In the proposed project the haloarchaeon Haloferax volcanii will be used to study various aspects of intermolecular gene conversion for the equalization of genome copies. An experimental approach has been established that enables the quantitative analysis of unselected gene conversion events. The following objectives will be pursuit: 1) Characteristic features of unselected gene conversion will be analyzed, e.g. the influence of the extent of genome differences on gene conversion efficiencies; 2) The influence of external and environmental parameters on intermolecular gene conversion will be analyzed: 3) Proteins will be identified, which are involved in or essential for intermolecular gene conversion; and 4) Intermolecular gene conversion between genes of different species will be analyzed. Together, these approaches will lead to an unprecedented insight into intermolecular gene conversion for the equalization of genome copies in polyploid prokaryotes.