A major source of spontaneous mutations is errors in DNA replication. Normally such errors are quite rare due to a variety of mechanisms that ensure the fidility of DNA replication. Inactivation of any of the gene products responsible for mechanisms that limit errors following DNA replication results in an increased spontaneous mutation rate -- this is called a "mutator" phenotype. Examples of several types of mutations that yield a mutator phenotype are shown in the following Table.
|Repair systemb||Mutations||Increase in mutation frequency||Major types of mutation|
|Mismatch repair||mutHSL||102-103||Transition, Frameshifts|
|Proofreading||mutDc||103-104||Transitions, Transversions, Frameshifts|
|G-A mismatch repair||mutT||103-104||AT to CG Transversions|
|G-A mismatch repair||mutY||> 102||GC to TA transversions|
The frequency of mutations in dnaQ mutants depend upon the growth medium, temperature, and salt concentration. Growth in LB results in about 10-100 fold greater mutagenesis than occurs during growth in minimal medium. It is widely assumed that faster growth conditions result in greater mutation frequencies because under these conditions saturation of the mismatch repair system prevents repair of the accumulated mutations. However, Degnen and Cox showed that the increased mutagenesis observed in LB is not simply due to the faster growth conditions, but is caused by thymidine (or closely related compounds) present in rich media. When added back to minimal medium, these compounds reproduce the effect of rich medium without increasing the growth rate.
In addition, the particular allele of dnaQ used affects the mutation frequency. For example, the widely used dominant mutD5 allele has a higher mutation rate than a recessive mutD null allele.
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Last modified July 15, 2002