Mercy Guillaume, Mozziconacci Julien, Scolari Vittore F, Yang Kun, Zhao Guanghou, Thierry Agnès, Luo Yisha, Mitchell Leslie A, Shen Michael, Shen Yue, Walker Roy, Zhang Weimin, Wu Yi, Xie Ze-Xiong, Luo Zhouqing, Cai Yizhi, Dai Junbiao, Yang Huanming, Yuan Ying-Jin, Boeke Jef D, Bader Joel S, Muller Héloïse, Koszul Romain
Spatial Regulation of Genomes, Department of Genomes and Genetics, Institut Pasteur, Paris 75015, France.
UMR3525, Centre National de la Recherche Scientifique (CNRS), Paris 75015, France.
Science. 2017 Mar 10;355(6329). doi: 10.1126/science.aaf4597.
Although the design of the synthetic yeast genome Sc2.0 is highly conservative with respect to gene content, the deletion of several classes of repeated sequences and the introduction of thousands of designer changes may affect genome organization and potentially alter cellular functions. We report here the Hi-C-determined three-dimensional (3D) conformations of Sc2.0 chromosomes. The absence of repeats leads to a smoother contact pattern and more precisely tractable chromosome conformations, and the large-scale genomic organization is globally unaffected by the presence of synthetic chromosome(s). Two exceptions are synIII, which lacks the silent mating-type cassettes, and synXII, specifically when the ribosomal DNA is moved to another chromosome. We also exploit the contact maps to detect rearrangements induced in SCRaMbLE (synthetic chromosome rearrangement and modification by -mediated evolution) strains.
尽管合成酵母基因组Sc2.0的设计在基因内容方面高度保守，但几类重复序列的缺失以及数千个设计性改变的引入可能会影响基因组组织，并有可能改变细胞功能。我们在此报告通过Hi-C技术确定的Sc2.0染色体的三维（3D）构象。重复序列的缺失导致更平滑的接触模式和更易于精确处理的染色体构象，并且大规模基因组组织总体上不受合成染色体存在的影响。两个例外是缺少沉默交配型盒的synIII，以及特别是当核糖体DNA被转移到另一条染色体时的synXII。我们还利用接触图谱来检测在SCRaMbLE（通过介导进化进行合成染色体重排和修饰）菌株中诱导的重排。
