Luria-Delbruck fluctuation experiments: Design and analysis

Abstract

Luria and Delbruck, in a seminal paper, introduced fluctuation analysis primarily as a means to elucidate the timing of mutation in relation to the imposition of selective conditions. Their work, and subsequently that of Lea and Coulson, established also a basis for measuring the frequency of mutational events. The several estimators proposed by these authors differ both in complexity and in efficiency, and the published literature relies mainly on the less efficient but computationally trivial estimators. The estimators as originally proposed assume that all mutants occurring in culture will be counted in the subsequent assay, but a relaxation of this assumption suggests an alternative experimental design and alternative estimators which offer advantages over those currently in common use.