Measuring Spontaneous Mutation Rates

Abstract

Spontaneous mutations are mutations that occur in the absence of exogenous causes. Of particular interest are the spontaneous mutation rates of organisms that live in environments so extreme that the coding properties of their DNA should be destroyed. This chapter provides a guide to methods used for calculating mutation rates in the hope that it will be useful to scientists and students who wish to use mutation rates in their research. In addition, the Luria-Delbruck distribution applies to other cases in which a rare initiating event is amplified in a population. There are two basic methods to determine mutation rates: mutant accumulation and fluctuation analysis. All methods to estimate spontaneous mutation rates are based on theoretical models of mutational processes and cell growth. Of the less complicated methods, the Lea-Coulson method of the median and the Jones median estimator are reliable if mutation rates are low to moderate; if mutation rates are very low (m = 1), only the p0 method is applicable. Drake's formula is based on the same assumption as the Luria-Delbruck method of the mean, i.e., that mutations occur only during the deterministic period of mutant accumulation. All the methods for calculating mutation rates from fluctuation tests are discussed and are dependent for their applicability on the model of expansion of mutant clones originally described by Luria and Delbruck and extended by Lea and Coulson.