Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Big Data Institute, University of Oxford, Oxford, UK.
Science. 2019 Mar 22;363(6433). doi: 10.1126/science.aau8861.
Recombination is critical to meiosis and evolution, yet many aspects of the physical exchange of DNA via crossovers remain poorly understood. We report an approach for single-cell whole-genome DNA sequencing by which we sequenced 217 individual hybrid mouse sperm, providing a kilobase-resolution genome-wide map of crossovers. Combining this map with molecular assays measuring stages of recombination, we identified factors that affect crossover probability, including PRDM9 binding on the non-initiating template homolog and telomere proximity. These factors also influence the time for sites of recombination-initiating DNA double-strand breaks to find and engage their homologs, with rapidly engaging sites more likely to form crossovers. We show that chromatin environment on the template homolog affects positioning of crossover breakpoints. Our results also offer insights into recombination in the pseudoautosomal region.
重组对于减数分裂和进化至关重要，但通过交叉进行 DNA 物理交换的许多方面仍未得到很好的理解。我们报告了一种用于单细胞全基因组 DNA 测序的方法，通过该方法我们对 217 个单个杂交小鼠精子进行了测序，提供了交叉点的千碱基分辨率全基因组图谱。将该图谱与测量重组阶段的分子分析相结合，我们确定了影响交叉概率的因素，包括非起始模板同源物上的 PRDM9 结合和端粒接近性。这些因素还影响了重组起始 DNA 双链断裂的位点找到并与同源物结合的时间，快速结合的位点更有可能形成交叉。我们表明，模板同源物上的染色质环境会影响交叉断裂点的位置。我们的结果还为假常染色体区域的重组提供了深入的了解。
