Diament Alon, Tuller Tamir
Biomedical Engineering Dept., Tel Aviv University, Tel Aviv 6997801, Israel.
The Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel.
Nucleic Acids Res. 2017 May 5;45(8):4330-4343. doi: 10.1093/nar/gkx205.
It has recently been shown that the organization of genes in eukaryotic genomes, and specifically in 3D, is strongly related to gene expression and function and partially conserved between organisms. However, previous studies of 3D genomic organization analyzed each organism independently from others. Here, we propose an approach for unified inter-organismal analysis of gene organization based on a network representation of Hi-C data. We define and detect four classes of spatially co-evolving orthologous modules (SCOMs), i.e. gene families that co-evolve in their 3D organization, based on patterns of divergence and conservation of distances. We demonstrate our methodology on Hi-C data from Saccharomyces cerevisiae and Schizosaccharomyces pombe, and identify, among others, modules relating to RNA splicing machinery and chromatin silencing by small RNA which are central to S. pombe's lifestyle. Our results emphasize the importance of 3D genomic organization in eukaryotes and suggest that the evolutionary mechanisms that shape gene organization affect the organism fitness and phenotypes. The proposed algorithms can be utilized in future studies of genome evolution and comparative analysis of spatial genomic organization in different tissues, conditions and single cells.
最近研究表明，真核生物基因组中的基因组织，尤其是三维空间中的基因组织，与基因表达和功能密切相关，并且在不同生物体之间部分保守。然而，以往对三维基因组组织的研究都是独立分析每个生物体。在此，我们提出了一种基于Hi-C数据网络表示的基因组织统一跨生物体分析方法。我们基于距离的差异和保守模式，定义并检测了四类空间共进化直系同源模块（SCOMs），即在三维组织中共同进化的基因家族。我们用酿酒酵母和粟酒裂殖酵母的Hi-C数据展示了我们的方法，并识别出了与RNA剪接机制和小RNA介导的染色质沉默相关的模块，这些模块对粟酒裂殖酵母的生活方式至关重要。我们的结果强调了真核生物中三维基因组组织的重要性，并表明塑造基因组织的进化机制会影响生物体的适应性和表型。所提出的算法可用于未来基因组进化研究以及不同组织、条件和单细胞中空间基因组组织的比较分析。
