Mutations can be spontaneous or induced

It is useful to distinguish two types of mutations in terms of their causes. Spontaneous mutationsare permanent changes in the genome that occur without any outside influence. In other words, they occur simply because the machinery of the cell is imperfect. Induced mutationsoccur when some agent outside the cell—a mutagen—causes a permanent change in DNA. Spontaneous mutations may occur by several mechanisms:

- The four nucleotide bases of DNA are somewhat unstable. They can exist in two different forms (called tautomers), one of which is common and one rare. When a base temporarily forms its rare tautomer, it can pair with a different base. For example, C normally pairs with G. But if C is in its rare tautomer at the time of DNA replication, it pairs with (and DNA polymerase will insert) A. The result is a point mutation:

G →A.

- Bases may change because of a chemical reaction. For example, loss of an amino group in cytosine (a reaction called deamination) forms uracil. When DNA replicates, instead of a G opposite what was C, DNA polymerase adds an A (base-pairs with U).

- DNA polymerase makes errors in replication for example, inserting a T opposite a G. Most of these errors are repaired by the proofreading function of the replication complex, but some errors escape and become permanent.

- Meiosis is not perfect. Nondisjunction can occur, leading to one too many or one too few chromosomes. Random chromosome breaks and rejoining can produce deletions, duplications and inversions, or, when involving nonhomologous chromosomes, translocations.

Mutagens can also alter DNA by several mechanisms:

- Some chemicals can covalently alter the nucleotide bases. For example, nitrous acid (HNO₂) and its relatives can turn cytosine in DNA into uracil by deamination: they convert an amino group on cytosine (—NH₂) into a keto group. This alteration has the same result as a spontaneous deamination: instead of a G, DNA polymerase inserts an A (base-pairs with U).

- Some chemicals add groups to the bases. For instance, benzpyrene, a component of cigarette smoke, adds a large chemical group to guanine, making it unavailable for base pairing. When DNA polymerase reaches such a modified guanine, it inserts any of the four bases; of course, three-fourths of the time the inserted base will not be cytosine, and a mutation results.

- Radiation damages the genetic material in two ways. Ionizing radiation (X rays) produces highly reactive chemical species called free radicals, which can change bases in DNA to unrecognizable (by DNA polymerase) forms or break the sugar–phosphate backbone causing chromosoma l abnormalities. Ultraviolet radiation from the sun (or a tanning lamp) is absorbed by thymine in DNA, causing it to form interbase covalent bonds with adjacent nucleotides. This, too, plays havoc with DNA replication. Mutations have both benefits and costs. Germ line mutations provide genetic diversity for evolution to work on, as we will see below. But they usually produce an organism that does more poorly in its current environment. Somatic mutations do not affect the organism’s offspring but they can lead to cancer.

Mutations are the raw material of evolution

Without mutation, there would be no evolution. Mutation does not drive evolution, but it provides the genetic diversity on which natural selection and other agents of evolution act. All mutations are rare events, but mutation frequencies vary from organism to organism and from gene to gene within a given organism. The frequency of mutation is usually much lower than one mutation per 104 base pairs per DNAduplication, and sometimes as low as one mutation per 109 base pairs per duplication. Most mutations are point mutations in which one nucleotide is substituted for another during the synthesis of a new DNA strand. Mutations can harm the organism that carries them, or they can be neutral (have no effect on the organism’s ability to survive or produce offspring). Once in a while, a mutation improves an organism’s adaptation to its environment or it becomes favorable when environmental conditions change. Most of the complex creatures living on Earth have more DNA, and therefore more genes, than the simpler creatures do. Humans, for example, have 20 times more genes than prokaryotes have. How did these new genes arise? If whole genes were sometimes duplicated by the mechanisms described in the previous section, the bearer of the duplication would have a surplus of genetic information that might be turned to good use. Subsequent mutations in one of the two copies of the gene might not have an adverse effect on sur- vival because the other copy of the gene would continue to produce functional protein. The extra gene might mutate over and over again without ill effect because its original function would be fulfilled by the original copy. If the random accumulation of mutations in the extra gene led to the production of a useful protein (for example, an enzyme with an altered specificity for the substrates it binds, allowing it to catalyze different — but related — reactions), natural selection would tend to perpetuate the existence of this new gene. New copies of genes may also arise through the activity of transposable elements.