- Spontaneous mutations occur in the absence of any added reagent to increase the mutation rate, as the result of errors in replication (or other events involved in the reproduction of DNA) or by environmental damage.
- The background level of mutation describes the rate at which sequence changes accumulate in the genome of an organism. It reflects the balance between the occurrence of spontaneous mutations and their removal by repair systems, and is characteristic for any species.
- Mutagens increase the rate of mutation by inducing changes in DNA sequence, directly or indirectly.
- Induced mutations result from the action of a mutagen. The mutagen may act directly on the bases in DNA or it may act indirectly to trigger a pathway that leads to a change in DNA sequence.
- All mutations consist of changes in the sequence of DNA.
- Mutations may occur spontaneously or may be induced by mutagens.
Mutations provide decisive evidence that DNA is the genetic material. When a change in the sequence of DNA causes an alteration in the sequence of a protein, we may conclude that the DNA codes for that protein. Furthermore, a change in the phenotype of the organism may allow us to identify the function of the protein. The existence of many mutations in a gene may allow many variant forms of a protein to be compared, and a detailed analysis can be used to identify regions of the protein responsible for individual enzymatic or other functions.
All organisms suffer a certain number of mutations as the result of normal cellular operations or random interactions with the environment. These are called spontaneous mutations; the rate at which they occur is characteristic for any particular organism and is sometimes called the background level. Mutations are rare events, and of course those that damage a gene are selected against during evolution. It is therefore difficult to obtain large numbers of spontaneous mutants to study from natural populations.
The occurrence of mutations can be increased by treatment with certain compounds. These are called mutagens, and the changes they cause are referred to as induced mutations. Most mutagens act directly by virtue of an ability either to modify a particular base of DNA or to become incorporated into the nucleic acid. The effectiveness of a mutagen is judged by how much it increases the rate of mutation above background. By using mutagens, it becomes possible to induce many changes in any gene (for review see Drake and Balz, 1976).
Spontaneous mutations that inactivate gene function occur in bacteriophages and bacteria at a relatively constant rate of 3-4 × 10–3 per genome per generation (Drake, 1991). Given the large variation in genome sizes between bacteriophages and bacteria, this corresponds to wide differences in the mutation rate per base pair. This suggests that the overall rate of mutation has been subject to selective forces that have balanced the deleterious effects of most mutations against the advantageous effects of some mutations. This conclusion is strengthened by the observation that an archaeal microbe that lives under harsh conditions of high temperature and acidity (which are expected to damage DNA) does not show an elevated mutation rate, but in fact has an overall mutation rate just below the average range (Grogan, Carver, and Drake, 2001).
Figure 1.19 shows that in bacteria, the mutation rate corresponds to ~10–6 events per locus per generation or to an average rate of change per base pair of 10–9-10–10 per generation. The rate at individual base pairs varies very widely, over a 10,000 fold range. We have no accurate measurement of the rate of mutation in eukaryotes, although usually it is thought to be somewhat similar to that of bacteria on a per-locus per-generation basis (Drake et al., 1998).