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Genetic variation among individuals provides the raw material for evolution. Because genetics is the study of inherited differences, the genetic analysis would not be possible without variants—individuals that show phenotypic differences in one or more particular characters. In previous chapters we performed many analyses of the inheritance of such variants; now we consider their origin. How do genetic variants arise? Two major processes are responsible for genetic variation, mutation, and recombination. We have seen that mutation is a change in the DNA sequence of a gene. The mutation is the ultimate source of evolutionary change; new alleles arise in all organisms, some spontaneously, others as a result of exposure to radiation and chemicals in the environment. The new alleles produced

by mutation become the raw material for the second level of variation, affected by recombination. As its name suggests, recombination is the outcome of cellular processes that cause alleles of different genes to become grouped in new combinations. To use an analogy, mutation produces new playing cards, and then recombination shuffles them and deals them out as different hands. In the cellular environment, DNA molecules are not absolutely stable; each base pair in a DNA double helix has a certain probability of mutating. As we shall see, the term mutation covers a broad array of different kinds of changes. In the next chapter, we shall consider mutational changes that affect entire chromosomes or large pieces of chromosomes. In the present chapter, we focus on mutational events that take place

within individual genes. We call such events gene mutations. Many kinds of gene alterations can occur within DNA molecules. These events can be as simple as the swapping of one base pair for another. Alternatively, some mutations entail a change in the number of copies of a trinucleotide repeat sequence [as when (AGC)3 becomes (AGC)5]. Mutations can even be caused by the insertion of a transposable element from elsewhere in the genome (Chapter 13). In this chapter, we focus on mutations that do not involve transposable elements. We can view DNA as being subjected to a dynamic tug of war between the chemical processes that damage DNA and lead to new mutations and the cellular repair processes that constantly monitor DNA for such damage and correct it. 

Mutations often arise through the action of certain agents, called mutagens, that increase the rate at which mutations occur. Alternatively, mutations can occur “spontaneously.” Spontaneous mutations are much less frequent (and hence harder to study) than induced mutations, but they are evolutionarily more important. A host of different molecular mechanisms underlie mutation, ranging from the reaction of DNA with highly reactive products of cell metabolism to mistakes in the DNA replication process. Cells have evolved sophisticated systems to identify and repair damaged DNA, thereby preventing the occurrence of mutations. Most notably, there are a variety of re- pair systems, and most of them rely on DNA complementarity. That is, they use one DNA strand as a template for the correction of DNA damage. 

For example, in the type of repair called excision repair, damage in one strand is cut out along with adjacent nucleotides, and then the correct sequence is resynthesized using the undamaged complementary strand as a template (Figure 14-1, left column). Finally, we will see that what is potentially the most serious class of DNA damage, a double-strand break, is also an intermediate step in a normal cellular process, recombination via meiotic crossing-over. Thus, we can draw parallels between mutation and recombination at two levels. First, as mentioned above, mutation and recombination are the major sources of variation.