The purpose of this meeting is to discuss the source and regulation of variability in mutation rates,
both temporally and across the genome, and the significance of this variability in evolutionary processes.

For example, regulated temporal variability of mutation rate is the hallmark of somatic hypermutation
in vertebrate immunity (although the mechanism remains unknown): the mutation rate at the rearranged
V(D)J locus is about 10⁶ times higher than background for a one-week period shortly after immunization.
Furthermore, the regions within the gene that are the most diversified in (germline) evolution exhibit higher
mutation rates under somatic hypermutation (in non-selective conditions) than other regions.

In the E.coli SOS response, specific inducers increase the mutation rates dramatically.  But unlike somatic
hypermutation, the mechanism and regulation of SOS mutagenesis is well characterized biochemically;
its relevance as an evolutionary ``strategy'', however, remains unclear.

Yet another example of mutator phenotypes being induced in bacterial cultures seems to underlie the once
radically controversial phenomenon of directed mutation.

Data on these specific experimental systems can now be integrated with long-term studies of bacterial
cultures, which have given us the extraordinary opportunity to study the population dynamics of mutator
phenotypes in fluctuating environments.

Do these phenomena share important features in common?  Can useful insight be gained through the
cross-fertilization of ideas among these areas of study?  We believe that the answer to both questions
is ``yes'',  and that the present time is particularly auspicious for a workshop to attempt such an undertaking.
The participants in this workshop will be a group of experts on the above-mentioned systems, as well as
on the enzymology of mutagenesis and on the mathematical and statistical issues raised.  Each participant
will be asked to give a brief presentation of the relevant aspects of his or her work as well as to take part in the
ensuing discussions.  The hope is that, through a concerted approach, we will better understand the
mechanisms by which mutagenesis  is regulated, and the implications of this regulation for evolutionary dynamics.