Mechanisms of meiotic recombination

我的研究计划的目标是进一步了解减数分裂的分子机制。在目前的建议中，我将确定在秀丽隐杆线虫中建立减数分裂重组模式所涉及的基因功能。秀丽隐杆线虫为我的研究项目提供了许多独特的优势。通常每个常染色体只有一次交叉，因此可以确定交叉发生的位置以及在事件群体中的频率。这种模式在突变体Rec-1中被消除，在染色质修饰体突变体中被改变。对减数分裂的分子组成进行了大量的研究；然而，减数分裂重组模式的基础尚不清楚。虽然减数分裂交叉可以发生在任何两个核苷酸对之间，但在染色体的某些区域它优先发生。因此，每个DNA长度的交叉频率因区域而异，秀丽隐杆线虫常染色体的某些区域多达10倍。减数分裂交换的分布导致减数分裂标记的明显聚类。Rec-1突变体消除了这种模式，表明它受进化选择的影响，并对遗传编码的分子决定因素作出反应。在与Michael Smith BC基因组测序中心的Steven Jones博士的合作下，我们获得了Rec-1的整个基因组序列。使用基因组序列，我们可以确定负责表型的分子变化，并表征所涉及的途径的性质。

The goal of my research program is to further our understanding of the molecular mechanisms of meiosis. In the current proposal I will determine gene functions involved in the establishment of the meiotic recombination pattern in Caenorhabditis elegans. C. elegans provides many unique advantages for my research program. There is normally only one crossover per autosome making it possible to determine where that crossover occurred and how frequently in a population of events. The pattern is eliminated in the mutant, Rec-1, and altered in mutants in chromatin modifiers. A large body of research exists on the molecular components of meiosis; however the basis of the meiotic recombination pattern is not understood. Although meiotic crossing over can happen between any two nucleotide pairs, there are regions of the chromosome where it occurs preferentially. Thus, the frequency of crossing over per length of DNA differs from region to region, as much as ten-fold for certain regions of the C. elegans autosomes. Distribution of meiotic exchange results in an apparent clustering of meiotic markers. The Rec-1 mutant, which eliminates the pattern, demonstrates that it is subject to evolutionary selection, and responds to molecular determinants encoded genetically. In collaboration with Dr. Steven Jones of the Michael Smith BC Genome Sequencing Center, we have the entire genomic sequence of Rec-1. Using the genomic sequence we can identify the molecular change responsible for the phenotype and characterize the nature of the pathways involved.