A MODEL FOR THE CORRELATION OF MUTATION-RATE WITH GC CONTENT AND THE ORIGIN OF GC-RICH ISOCHORES
A MODEL FOR THE CORRELATION OF MUTATION-RATE WITH GC CONTENT AND THE ORIGIN OF GC-RICH ISOCHORES
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DOI：
10.1007/bf00178846
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发表时间：
1994-05-01
影响因子：
3.9
通讯作者：
LI, WH
中科院分区：
文献类型：
--
作者：
GU, X;LI, WH
基于DNA复制和突变的生化动力学，包括错误掺入和校正，已经建立了一个模型来研究突变率（u）、序列的G + C含量（f）和核苷酸前体库中的G + C比例（N）之间的关系。还提出了一种测量下一个核苷酸效应的方法，称为下一个核苷酸效应的最大容量（MC）。在正常生理条件下，我们的结果表明：（1）序列中G + C的平衡含量近似等于核苷酸前体库中G + C的比例，即，f近似于N，与下一个核苷酸效应无关;（2）当下一个核苷酸效应为弱时，突变率相对于G f C含量呈倒V型分布，即，MC近似于1;（3）分布变得更平坦（即，（4）当MC > 2.8时，即，当下一个核苷酸效应变强时，峰消失。我们的研究结果表明，核苷酸前体的相对浓度的变化可能会导致基因之间的变异，在突变率和G + C含量和组成isochore（DNA片段具有同质G + C含量）可以出现在基因组中，由于DNA片段的复制时间的差异。
Based on the biochemical kinetics of DNA replication and mutagenesis, including misincorporation and correction, a model has been developed for studying the relationships among the mutation rate (u), the G + C content of the sequence (f), and the G + C proportion in the nucleotide precursor pool (N). Also a measure for the next-nucleotide effect, called the maximum capacity of the next-nucleotide effect (MC), has been proposed. Under the normal physiological conditions of mammalian germ cells, our results indicate: (1) the equilibrium G + C content in a sequence is approximately equal to the G f C proportion in the nucleotide precursor pool, i.e., f approximate to N, which is independent of the next-nucleotide effect; (2) an inverted-V-shaped distribution of mutation rates with respect to G f C contents is predicted, when the next-nucleotide effect is week, i.e., MC approximate to 1; (3) the distribution becomes flatter (i.e., inverted-U-shaped) as MC increases, but the peak at 50% GC is still observed when MC < 2; and (4) the peak disappears when MC > 2.8, that is, when the next-nucleotide effect becomes strong. Our results suggest that changes in the relative concentrations of nucleotide precursors can cause variations among genes both in mutation rate and in G + C content and that compositional isochores (DNA segments with a homogeneous G + C content) can arise in a genome due to differences in replication times of DNA segments.