Gu X, Li W H
Center for Demographic and Population Genetics, University of Texas, Houston 77225.
J Mol Evol. 1994 May;38(5):468-75. doi: 10.1007/BF00178846.
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+C proportion in the nucleotide precursor pool, i.e., f approximately N, which is independent of the next-nucleotide effect; (2) an inverted-V-shaped distribution of mutation rates with respect to G+C contents is predicted, when the next-nucleotide effect is week, i.e., MC approximately 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.
基于DNA复制和诱变的生化动力学，包括错配掺入和校正，已开发出一个模型，用于研究突变率（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。还提出了一种用于衡量下一个核苷酸效应的指标，称为下一个核苷酸效应的最大容量（MC）。在哺乳动物生殖细胞的正常生理条件下，我们的结果表明：（1）序列中的平衡G+C含量大约等于核苷酸前体库中的G+C比例，即f约等于N，这与下一个核苷酸效应无关；（2）当下一个核苷酸效应较弱时，即MC约为1，预测突变率相对于G+C含量呈倒V形分布；（3）随着MC的增加，分布变得更平坦（即倒U形），但当MC<2时，仍可观察到GC含量为50%时的峰值；（4）当MC>2.8时，即当下一个核苷酸效应变强时，峰值消失。我们的结果表明，核苷酸前体相对浓度的变化可导致基因间在突变率和G+C含量上的差异，并且由于DNA片段复制时间的不同，基因组中可能会出现组成等容线（具有均匀G+C含量的DNA片段）。
