Fluctuation Analysis Task

References

http://fangman-brewer.genetics.washington.edu/fluctuation.html
- QUOTE: The basic idea of the fluctuation analysis is to start growing many replicate cultures of cells that initially have no mutation of interest, to let them go through a certain number of cell divisions to saturation — so as to limit the number of generations — in a permissive medium, and to measure how many of the cultures have not acquired the mutations. There are two successive selections: the first one selects for absence of the mutation while the second one selects for presence of the mutation.

(Jones et al., 1994) ⇒ M. E . Jones, S. M . Thomas, and A. Rogers . (1994). “Luria-Delbrück Fluctuation Experiments: Design and Analysis." Genetics 136, no. 3
- ABSTRACT: Luria and Delbrück, 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.

(Stewart et al., 1990) ⇒ Frank M. Stewart, D. M . Gordon, and B. R . Levin. (1990). “Fluctuation Analysis: The Probability Distribution of the Number of Mutants under Different Conditions." Genetics 124, no. 1
- ABSTRACT: In the 47 years since fluctuation analysis was introduced by Luria and Delbrück, it has been widely used to calculate mutation rates. Up to now, in spite of the importance of such calculations, the probability distribution of the number of mutants that will appear in a fluctuation experiment has been known only under the restrictive, and possibly unrealistic, assumptions: (1) that the mutation rate is exactly proportional to the growth rate and (2) that all mutants grow at a rate that is a constant multiple of the growth rate of the original cells. In this paper, we approach the distribution of the number of mutants from a new point of view that will enable researchers to calculate the distribution to be expected using assumptions that they believe to be closer to biological reality. The new idea is to classify mutations according to the number of observable mutants that derive from the mutation when the culture is selectively plated. This approach also simplifies the calculations in situations where two, or many, kinds of mutation may occur in a single culture.

(Luria & Delbrück, 1943) ⇒ Salvador E. Luria, and Max Delbrück. (1943). “Mutations of Bacteria from Virus Sensitivity to Virus Resistance." Genetics 28, no. 6