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Point mutations typically refer to alterations of single base pairs of DNA or of a small number of adjacent base pairs—that is, mutations that map to a single location, or “point,” within a gene. Here we will focus on the point mutations that alter one base pair at a time. Essentially, these “point” mutations are the minimum changes that can be produced—changing only one “letter” in the “book of DNA.” The constellation of possible ways in which a point mutation could change a wild-type gene is very large. However, it is always true that such mutations are more likely to reduce or eliminate gene function (thus they are loss-of-function mutations) than to enhance it (gain-of-function mutations). The reason is simple: by randomly changing or removing one of the components of a machine, it is much easier to break it than to alter the way that it works. 

Conversely, mutations that increase a gene’s activity or alter the type of activity or change the location within a multicellular body where the gene is expressed are much rarer. The origin of point mutations Newly arising mutations is categorized as induced or spontaneous. Induced mutations are defined as those that arise after purposeful treatment with mutagens, environmental agents that are known to increase the rate of mutations. Spontaneous mutations are those that arise in the absence of known mutagen treatment. They account for the “background rate” of mutation and are presumably the ultimate source of natural genetic variation that is seen in populations. The frequency at which spontaneous mutations occur is low, generally in the range of one cell in 105 to 108. Therefore, if a large number of mutants are required for genetic analysis, mutations must be induced. 

The in- duction of mutations is accomplished by treating cells with mutagens. The production of mutations through exposure to mutagens is called mutagenesis, and the organism is said to be mutagenized. The most commonly used mutagens are high-energy radiation or specific chemicals; examples of these mutagens and their efficacy are given in Table 14-1. The greater the dose of mutagen, the greater the number of mutations induced, as shown in Figure 14-2. Note that Figure 14-2 shows a linear dose-response, which is often observed in the induction of point mutations. Recognize that the distinction between induced and spontaneous is purely operational. 

If we are aware that an organism was exposed to a mutagen, then we surmise that the bulk of the mutations that arise afterward was induced by that mutagen. However, this is not true in an absolute sense. The mechanisms that give rise to spontaneous mutations are also acting in this mutagenized organism. In reality, there will always be a subset of mutations recovered after mutagenesis that arose independently of the action of the mutagen. The proportion of mutations that fall into this subset depends on how potent a mutagen is. The higher the rate of induced mutations, the lower the proportion of recovered mutations that are actually “spontaneous” in origin.

Induced and spontaneous mutations arise by generally different mechanisms, and so they will be covered separately. After considering these mechanisms, we shall explore the subject of biological mutation repair. Without these repair mechanisms, the rate of mutation would be so high that cells would accumulate too many mutations to remain viable and capable of reproduction. Thus, the mutational events that do occur are those rare events that have somehow been overlooked or bypassed by the repair processes.