Quantitative Analysis of Meiotic Chromosome Motion and Pairing

项目摘要 同源染色体配对是孟德尔遗传的核心过程，但 许多遗传学研究已经揭示了与同源识别和重组有关的基因，物理 染色体在密集排列的细胞核内聚集的过程仍然很差。 明白了。减数分裂染色体的端粒锚定在核膜上，并附着在 细胞骨架，它施加随机定向的拉力。一个关键问题是随机引导的力量是如何 可以方便同源搜索过程。使用一系列计算模型，我们已经证明 随机定向的端粒力在理论上可以通过几种方式促进搜索：驱动超扩散运动 染色质，克服纠缠，取消错误配对的区域以提高保真度，以及相反 染色体的熵分解。我们建议使用活细胞来测试这些不同的预测功能 成像和定量图像分析，结合酵母菌遗传学来改变施加在 染色体。我们的结果不仅应该影响对减数分裂同源配对作为一种物理现象的理解 过程，还包括一般的染色体运动的物理生物学以及广义的活跃概念 生物学中的随机运动。

Project Summary Homologous chromosome pairing is a central process underlying Mendelian inheritance, but while many genetic studies have revealed genes involved in homology recognition and recombination, the physical process by which the chromosomes come together inside the densely packed nucleus remains poorly understood. Telomeres of meiotic chromosomes are anchored on the nuclear envelope and attached to the cytoskeleton, which exerts randomly directed pulling forces. A key question is how randomly directed forces can facilitate the homology search process. Using a series of computational models, we have shown that randomly directed telomere forces can in theory promote search in several ways: driving superdiffusive motion of chromatin, overcoming entanglement, unpairing incorrectly paired regions to improve fidelity, and opposing entropic de-mixing of chromosomes. We propose to test these distinct predicted functions using live cell imaging and quantitative image analysis, combined with yeast genetics to alter the forces applied to the chromosomes. Our results should impact not only the understanding of meiotic homolog pairing as a physical process, but also the physical biology of chromosome motion in general as well as the broad concept of active random motion in biology.