Replication slippage versus point mutation rates in short tandem repeats of the human genome
Replication slippage versus point mutation rates in short tandem repeats of the human genome
复制标题
DOI：
10.1007/s00438-007-0294-1
复制
发表时间：
2007
影响因子：
3.1
通讯作者：
D. Pumpernik;B. Oblak;B. Borštnik
中科院分区：
文献类型：
--
作者：
D. Pumpernik;B. Oblak;B. Borštnik
短串联重复序列 (STR) 会受到两种突变修饰：点突变和复制滑移。后者被发现是 STR 修饰的更常见原因，但尚未确定对这两个过程的比率的令人满意的定量测量。对足够密切相关的物种的整个基因组序列进行比较，使人们能够通过计算 STR 区域的差异来获得足够的统计数据。我们分析了人类与黑猩猩 DNA 序列比对，以获得点突变和复制滑移修饰的计数。将结果与计算机模拟的结果进行比较，并确定量化复制滑动概率以及重复内点突变概率的参数。研究发现，在由 1、2 或 3 个核苷酸组成的重复单元的 STR 中，点突变发生的频率大约是基于人类和黑猩猩基因组之间 1.2% 差异所预期的两倍。正如预期的那样，复制滑动概率低于 10 bp 阈值时可以忽略不计，但高于该水平时会增长。复制滑动事件的数量比点突变多一两个数量级，但相对于用于基因分型目的的标记的突变性仍然低一个数量级。
Short tandem repeats (STRs) are subjected to two kinds of mutational modifications: point mutations and replication slippages. The latter is found to be the more frequent cause of STR modifications, but a satisfactory quantitative measure of the ratio of the two processes has yet to be determined. The comparison of entire genome sequences of closely enough related species enables one to obtain sufficient statistics by counting the differences in the STR regions. We analyzed human–chimpanzee DNA sequence alignments to obtain the counts of point mutations and replication slippage modifications. The results were compared with the results of a computer simulation, and the parameters quantifying the replication slippage probability as well as the probabilities of point mutations within the repeats were determined. It was found that within the STRs with repeated units consisting of one, two or three nucleotides, point mutations occur approximately twice as frequently as one would expect on the basis of the 1.2% difference between the human and chimpanzee genomes. As expected, the replication slippage probability is negligible below a 10-bp threshold and grows above this level. The replication slippage events outnumber the point mutations by one or two orders of magnitude, but are still lower by one order of magnitude relative to the mutability of the markers that are used for genotyping purposes.