Isochore chromosome maps of eukaryotic genomes
Isochore chromosome maps of eukaryotic genomes
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DOI：
10.1016/s0378-1119(01)00641-2
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发表时间：
2001-10-03
期刊：
影响因子：
3.5
通讯作者：
Román-Roldán, R
中科院分区：
文献类型：
--
作者：
Oliver, JL;Bernaola-Galván, P;Román-Roldán, R
分析性DNA超离心发现真核生物基因组是同位异位的嵌合体：长DNA片段（平均bb0 bb1 300 kb）在G + c中相对均匀。重要的基因组特征依赖于这种等位结构，例如基因主要存在于gc -最丰富的等位类中。然而，目前还没有可靠的方法将基因组序列严格划分为不同组成的相对均匀的区域，从而在序列水平上揭示染色体的同工质结构。均匀区域目前是通过对任意长度的移动窗口的简单统计来确定的，或者简单地通过观察G + C图来确定。相反，熵分割方法能够将DNA序列划分为相对均匀的、统计上显著的区域。该算法的早期版本只产生平均长度远低于典型等差大小的结构域。在这里，我们展示了一种改进的分割方法，专门用于确定每个尺度上序列中最具统计意义的分割，能够识别显示同工的典型特征的长均匀基因组区域之间的边界。该算法精确定位了人类主要组织相容性复合体的II类和III类，这是两个在序列水平上具有较好特征的等差，它们之间的边界是第一个在序列水平上具有实验特征的等差边界。然后将分析扩展到人类大组合的集合。我们发现相对均匀的区域显示了许多特征（G + C范围，等质粒类别的相对比例，大小分布以及与基因密度的关系）通过DNA离心鉴定的等质粒。在基因组学中有许多潜在的应用，然后绘制所有完全测序的真核生物基因组。(C) 2001 Elsevier Science B.V.版权所有
Analytical DNA ultracentrifugation revealed that eukaryotic genomes are mosaics of isochores: long DNA segments ( >> 300 kb on average) relatively homogeneous in G + C. Important genome features are dependent on this isochore structure, e.g. genes are found predominantly in the GC-richest isochore classes. However, no reliable method is available to rigorously partition the genome sequence into relatively homogeneous regions of different composition, thereby revealing the isochore structure of chromosomes at the sequence level. Homogeneous regions are currently ascertained by plain statistics on moving windows of arbitrary length, or simply by eye on G + C plots. On the contrary, the entropic segmentation method is able to divide a DNA sequence into relatively homogeneous, statistically significant domains. An early version of this algorithm only produced domains having an average length far below the typical isochore size. Here we show that an improved segmentation method, specifically intended to determine the most statistically significant partition of the sequence at each scale, is able to identify the boundaries between long homogeneous genome regions displaying the typical features of isochores. The algorithm precisely locates classes II and III of the human major histocompatibility complex region, two well-characterized isochores at the sequence level, the boundary between them being the first isochore boundary experimentally characterized at the sequence level. The analysis is then extended to a collection of human large contigs. The relatively homogeneous regions we find show many of the features (G + C range, relative proportion of isochore classes, size distribution, and relationship with gene density) of the isochores identified through DNA centrifugation. Isochore chromosome maps, with many potential applications in genomics, are then drawn for all the completely sequenced eukaryotic genomes available. (C) 2001 Elsevier Science B.V. All rights reserved.