Moreno-Herrero Fernando, Seidel Ralf, Johnson Steven M, Fire Andrew, Dekker Nynke H
Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands.
Nucleic Acids Res. 2006 May 31;34(10):3057-66. doi: 10.1093/nar/gkl397. Print 2006.
Several bioinformatics studies have identified an unexpected but remarkably prevalent approximately 10 bp periodicity of AA/TT dinucleotides (hyperperiodicity) in certain regions of the Caenorhabditis elegans genome. Although the relevant C.elegans DNA segments share certain sequence characteristics with bent DNAs from other sources (e.g. trypanosome mitochondria), the nematode sequences exhibit a much more extensive and defined hyperperiodicity. Given the presence of hyperperiodic structures in a number of critical C.elegans genes, the physical characteristics of hyperperiodic DNA are of considerable interest. In this work, we demonstrate that several hyperperiodic DNA segments from C.elegans exhibit structural anomalies using high-resolution atomic force microscopy (AFM) and gel electrophoresis. Our quantitative analysis of AFM images reveals that hyperperiodic DNA adopts a significantly smaller mean square end-to-end distance, hence a more compact coil structure, compared with non-periodic DNA of similar length. While molecules remain capable of adopting both bent and straight (rod-like) configurations, indicating that their flexibility is still retained, examination of the local curvatures along the DNA contour length reveals that the decreased mean square end-to-end distance can be attributed to the presence of long-scale intrinsic bending in hyperperiodic DNA. Such bending is not detected in non-periodic DNA. Similar studies of shorter, nucleosome-length DNAs that survived micrococcal nuclease digestion show that sequence hyperperiodicity in short segments can likewise induce strong intrinsic bending. It appears, therefore, that regions of the C.elegans genome display a significant correlation between DNA sequence and unusual mechanical properties.
多项生物信息学研究在秀丽隐杆线虫基因组的某些区域发现了AA/TT二核苷酸出人意料但极为普遍的约10 bp周期性（超周期性）。尽管秀丽隐杆线虫的相关DNA片段与其他来源的弯曲DNA（如锥虫线粒体DNA）具有某些序列特征，但线虫序列表现出更为广泛和明确的超周期性。鉴于许多关键的秀丽隐杆线虫基因中存在超周期结构，超周期DNA的物理特性备受关注。在这项工作中，我们使用高分辨率原子力显微镜（AFM）和凝胶电泳证明，秀丽隐杆线虫的几个超周期DNA片段呈现出结构异常。我们对AFM图像的定量分析表明，与长度相似的非周期性DNA相比，超周期DNA的平均方端到端距离明显更小，因此具有更紧凑的螺旋结构。虽然分子仍能够呈现弯曲和直的（棒状）构型，表明它们仍保留灵活性，但沿DNA轮廓长度检查局部曲率发现，平均方端到端距离的减小可归因于超周期DNA中存在长尺度固有弯曲。在非周期性DNA中未检测到这种弯曲。对经微球菌核酸酶消化后存活的较短核小体长度DNA的类似研究表明，短片段中的序列超周期性同样可诱导强烈的固有弯曲。因此，秀丽隐杆线虫基因组区域似乎在DNA序列与异常机械特性之间呈现出显著相关性。
