CRYPTIC SIMPLICITY IN DNA IS A MAJOR SOURCE OF GENETIC-VARIATION
CRYPTIC SIMPLICITY IN DNA IS A MAJOR SOURCE OF GENETIC-VARIATION
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DOI：
10.1038/322652a0
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发表时间：
1986-08-14
期刊：
影响因子：
64.8
通讯作者：
DOVER, GA
中科院分区：
文献类型：
--
作者：
TAUTZ, D;TRICK, M;DOVER, GA
DNA 区域由单个或相对较少的短序列基序组成，通常串联（“纯简单序列”），已在不同物种的基因组中报道过（综述见参考文献 1-4），并且与一系列功能有关，包括基因调控（综述见参考文献 5-7）、基因转换和重组信号 8-10 以及端粒复制 11。它们被认为是通过 DNA 滑移积累的 12-16 和单链末端复制和重组或延伸过程中的错配2,4,10,11。为了系统化 DNA 简单性范围和简单区域的遗传性质，我们对欧洲分子生物学实验室 (EMBL)17 的 DNA 序列库进行了广泛的计算机搜索。我们在这里表明，几乎所有可能的简单图案出现的频率比同等随机图案高 5-10 倍。此外，一种新的计算机算法揭示了编码和非编码 DNA 中广泛存在的新型“神秘简单性”。神秘的简单区域在核苷酸组成上存在偏差，并且由重复基序的乱序排列组成，这些重复基序在物种内部和物种之间存在差异。 DNA简单性的普遍存在，从单一基序的单调阵列到相对短命基序的可变排列，表明普遍存在的滑移机制是基因组所有区域遗传变异的主要来源，而经典突变过程是无法预测的。
DNA regions which are composed of a single or relatively few short sequence motifs usually in tandem (‘pure simple sequences’) have been reported in the genomes of diverse species (for reviews see refs 1–4), and have been implicated in a range of functions including gene regulation (for reviews see refs 5–7), signals for gene conversion and recombination8–10, and the replication of telomeres11They are thought to accumulate by DNA slippage12–16and mispairing during replication and recombination or extension of single-strand ends2,4,10,11. In order to systematize the range of DNA simplicity and the genetic nature of the regions that are simple, we have undertaken an extensive computer search of the DNA sequence library of the European Molecular Biology Laboratory (EMBL)17. We show here that nearly all possible simple motifs occur 5–10 times more frequently than equivalent random motifs. Furthermore, a new computer algorithm reveals the widespread occurrence of significantly high levels of a new type of ‘cryptic simplicity’ in both coding and noncoding DNA. Cryptically simple regions are biased in nucleotide composition and consist of scrambled arrangements of repetitive motifs which differ within and between species. The universal existence of DNA simplicity from monotonous arrays of single motifs to variable permutations of relatively short-lived motifs suggests that ubiquitous slippage-like mechanisms are a major source of genetic variation in all regions of the genome, not predictable by the classical mutation process.