Genome rearrangements that occur during evolution impose major challenges on regulatory mechanisms that rely on three-dimensional genome architecture. Here, we developed a scaffolding algorithm and generated chromosome-length assemblies from Hi-C data for studying genome topology in three distantly related Drosophila species. We observe extensive genome shuffling between these species with one synteny breakpoint after approximately every six genes. A/B compartments, a set of large gene-dense topologically associating domains (TADs), and spatial contacts between high-affinity sites (HAS) located on the X chromosome are maintained over 40 million years, indicating architectural conservation at various hierarchies. Evolutionary conserved genes cluster in the vicinity of HAS, while HAS locations appear evolutionarily flexible, thus uncoupling functional requirement of dosage compensation from individual positions on the linear X chromosome. Therefore, 3D architecture is preserved even in scenarios of thousands of rearrangements highlighting its relevance for essential processes such as dosage compensation of the X chromosome.

中文翻译：

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尽管进行了广泛的基因组改组，Hi-C指导的组装仍显示了X和常染色体上的保守调控拓扑。

进化过程中发生的基因组重排对依赖三维基因组架构的调节机制提出了重大挑战。在这里，我们开发了一个脚手架算法，并从Hi-C数据生成了染色体长度装配，用于研究三种远缘果蝇物种的基因组拓扑。我们观察到大约每六个基因后，在一个物种的同一个转折点之间，这些物种之间的基因组大量改组。A / B隔室，一组大型的基因密集的拓扑关联域（TAD）以及位于X染色体上的高亲和力位点（HAS）之间的空间接触保持了4000万年以上，这表明在各种层次上的建筑保护。进化保守基因簇集在HAS附近，而HAS位置在进化上似乎很灵活，因此，从线性X染色体上的各个位置解开剂量补偿的功能要求。因此，即使在成千上万次重排的情况下，仍保留了3D体系结构，从而突出了其与基本过程（例如X染色体的剂量补偿）的相关性。