When properly determined, spontaneous mutation rates are a more accurate an
d biologically meaningful reflection of underlying mutagenic mechanisms tha
n are mutant frequencies. Because bacteria grow exponentially and mutations
arise stochastically. methods to estimate mutation rates depend on theoret
ical models that describe the distribution of mutant numbers among parallel
cultures, as in the original Luria-Delbruck fluctuation analysis. An accur
ate determination of mutation rate depends on understanding the strengths a
nd limitations of these methods, and how to design fluctuation assays to op
timize a given method. In this paper we describe a number of methods to est
imate mutation rates, give brief accounts of their derivations, and discuss
how they behave under various experimental conditions. (C) 2000 Academic P
ress.