title: A simple formula for obtaining markedly improved mutation rate estimates.
abstract: In previous work by M. E. Jones and colleagues, it was shown that mutation rate estimates can be improved and corresponding confidence intervals tightened by following a very easy modification of the standard fluctuation assay: cultures are grown to a larger-than-usual final density, and mutants are screened for in only a fraction of the culture. Surprisingly, this very promising development has received limited attention, perhaps because there has been no efficient way to generate the predicted mutant distribution to obtain non-moment-based estimates of the mutation rate. Here, the improved fluctuation assay discovered by Jones and colleagues is made amenable to quantile-based, likelihood, and other Bayesian methods by a simple recursion formula that efficiently generates the entire mutant distribution after growth and dilution. This formula makes possible a further protocol improvement: grow cultures as large as is experimentally possible and severely dilute before plating to obtain easily countable numbers of mutants. A preliminary look at likelihood surfaces suggests that this easy protocol adjustment gives markedly improved mutation rate estimates and confidence intervals.
authors.affiliation: Instituto Gulbenkian de Ciencia, 2780-156 Oeiras, Portugal. pgerrish@unm.edu
authors.forename: Philip
authors.initials: P
authors.lastname: Gerrish
mesh_terms: D000818:Animals; D003198:Computer Simulation; D014644:Genetic Variation; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D015233:Models, Statistical; D009154:Mutation / Q000235:genetics*