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Genetics. Aug 1994; 137(4): 1139–1146.
PMCID: PMC1206060

Fluctuation Tests: How Reliable Are the Estimates of Mutation Rates?

Abstract

Fifty one years ago, Luria and Delbruck published in Genetics a paper that was to become a classic. In it they proved, beyond all reasonable doubt, that bacteria were mutating to phage resistance long before they could have encountered any bacteriophage. Luria and Delbruck also showed how the same experimental data could be used to estimate bacterial mutation rates. Since that time and in many different contexts the methods that they introduced have been used to estimate mutation rates. However, little seems to be known about the errors to be expected in such estimates. In what follows I examine how much uncertainty in the estimates is to be expected merely on the basis of the stochastic variability inherent in the sampling process. On the basis of this examination I question a few traditional ideas and conclude with some practical suggestions. The results were obtained by simulation. It is my hope that they may inspire others to provide a rigorous theoretical basis for such calculations.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Luria SE, Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics. 1943 Nov;28(6):491–511. [PMC free article] [PubMed]
  • Sarkar S. Haldane's solution of the Luria-Delbrück distribution. Genetics. 1991 Feb;127(2):257–261. [PMC free article] [PubMed]
  • Sarkar S, Ma WT, Sandri GH. On fluctuation analysis: a new, simple and efficient method for computing the expected number of mutants. Genetica. 1992;85(2):173–179. [PubMed]
  • Stewart FM, Gordon DM, Levin BR. Fluctuation analysis: the probability distribution of the number of mutants under different conditions. Genetics. 1990 Jan;124(1):175–185. [PMC free article] [PubMed]

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