Quantitative Analysis of Meiotic Chromosome Motion and Pairing

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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.