Kimmel M, Axelrod D E
Department of Statistics, Rice University, Houston, TX 77251.
Mutat Res. 1994 Apr 1;306(1):45-60. doi: 10.1016/0027-5107(94)90166-x.
The determination of mutation rates is an important experimental procedure for characterizing mutation processes. The accepted method of determining mutation rates, the fluctuation test, was introduced by Luria and Delbrück in 1943. Since then it has been applied to various microorganisms and cells. The Luria-Delbrück test is based on a restrictive hypothesis of mutations being due to single irreversible events. However, some inherited changes in phenotype, like gene amplification, may be due to two or more genetic changes, some of which may be reversible. The Luria-Delbrück model of mutation was compared to other models which included reversibility and more than one mutation stage. The Luria-Delbrück model has been confirmed to be consistent with the original bacteriophage resistance data. However, for gene amplification this model gives incompatible estimates of mutation rates by the P0 and r methods. Relaxing the hypotheses of the single-stage models did not improve the fit. In contrast, a two-stage reversible model provided a fit. Analysis of gene amplification data by the two-stage reversible model provides new information, including estimates of rates for each of the two forward stages and of the reverse step.
确定突变率是表征突变过程的一项重要实验程序。1943年，卢里亚和德尔布吕克引入了确定突变率的公认方法——波动试验。从那时起，它就被应用于各种微生物和细胞。卢里亚 - 德尔布吕克试验基于一个限制性假设，即突变是由单个不可逆事件引起的。然而，一些表型的遗传变化，如基因扩增，可能是由于两个或更多的遗传变化，其中一些可能是可逆的。将卢里亚 - 德尔布吕克突变模型与其他包含可逆性和多个突变阶段的模型进行了比较。卢里亚 - 德尔布吕克模型已被证实与原始噬菌体抗性数据一致。然而，对于基因扩增，该模型通过P0和r方法给出了不相容的突变率估计。放宽单阶段模型的假设并没有改善拟合效果。相比之下，一个两阶段可逆模型提供了良好的拟合。通过两阶段可逆模型对基因扩增数据进行分析提供了新的信息，包括两个正向阶段各自的速率估计以及反向步骤的速率估计。
