Zheng Wen-Xin, Zhang Chun-Ting
Department of Physics, Tianjin University, Tianjin 300072, China.
J Biomol Struct Dyn. 2008 Feb;25(4):327-36. doi: 10.1080/07391102.2008.10507181.
The human genome is composed of large sequence segments with fairly homogeneous GC content, namely isochores, which have been linked to many important functions; biological implications of most isochore boundaries, however, remain elusive, partly due to the difficulty in determining these boundaries at high resolution. Using the segmentation algorithm based on the quadratic divergence, we re-determined all 79 boundaries of previously identified human isochores at single-nucleotide resolution, and then compared the boundary coordinates with other genome features. We found that 55.7% of isochore boundaries coincide with termini of repeat elements; 45.6% of isochore boundaries coincide with termini of highly conserved sequences based on alignment of 17 vertebrate genomes, i.e., the highly conserved genome sequence switches to a less or non-conserved one at the isochore boundary; some isochore boundaries coincide with abrupt change of CpG island distribution (note that one boundary can associate with more than one genome feature). In addition, sequences around isochore boundaries are highly conserved. It seems reasonable to deduce that the boundaries of all the isochores studied here would be replication timing sites in the human genome. These results suggest possible key roles of the isochore boundaries and may further our understanding of the human genome organization.
人类基因组由具有相当均匀GC含量的大序列片段组成，即等密度区，这些等密度区与许多重要功能相关联；然而，大多数等密度区边界的生物学意义仍然难以捉摸，部分原因是难以在高分辨率下确定这些边界。使用基于二次散度的分割算法，我们在单核苷酸分辨率下重新确定了先前鉴定的人类等密度区的所有79个边界，然后将边界坐标与其他基因组特征进行比较。我们发现55.7% 的等密度区边界与重复元件的末端重合；基于17种脊椎动物基因组的比对，45.6% 的等密度区边界与高度保守序列的末端重合，即在等密度区边界处，高度保守的基因组序列转变为较少保守或非保守的序列；一些等密度区边界与CpG岛分布的突然变化重合（注意，一个边界可以与多个基因组特征相关联）。此外，等密度区边界周围的序列高度保守。由此推断，这里研究的所有等密度区的边界可能是人类基因组中的复制时间位点，似乎是合理的。这些结果表明了等密度区边界可能具有的关键作用，并可能增进我们对人类基因组组织的理解。
