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Quantitative characterization of meiotic chromosome organization

  • Author(s): Cheveralls, Keith Charles
  • Advisor(s): Dernburg, Abby F
  • et al.
Abstract

Sexual reproduction relies on a specialized program of cell division called meiosis to generate haploid gametes from diploid germ cells. In order for chromosome segregation to occur accurately, homologous chromosomes must pair, synapse, and undergo crossover recombination. These physical and biochemical interactions occur in coordination with large-scale reorganization of meiotic chromosomes. To understand the relationship between chromosome organization and the regulation of recombination, we developed an automated image analysis pipeline that combines the throughput of population-based biochemical assays with the temporal and contextual information provided by cytological methods. This new technique enables us to monitor temporal changes in the distribution of meiotic double strand breaks (DSBs) on a chromosome-wide basis and to correlate that distribution with features of meiotic chromosome organization. We applied this technique to meiotic chromosomes in the nematode Caenorhabditis elegans and observed that the distribution of DSBs is dynamic during prophase and shifts from a distribution that mirrors the distribution of crossovers to one that is more uniform. This shift correlates with isotropic, recombination-independent elongation of chromosomes along the axis and is insensitive to defects in recombination, variation in the number of DSBs, and variation in chromosome axis length. This work reveals a novel dynamic aspect of meiotic DSB formation and quantifies, for the first time, statistical features of meiotic chromosome organization in C. elegans.

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