Spontaneous Mutations

DNA polymerase replicates DNA by making complementary copies of each of the double strands. If done perfectly, this process produces exact copies of the original double-stranded DNA. However, nothing is perfect. Consider that we have over 3 billion base pairs of DNA in each cell. Each time a cell divides, whether to produce more of the same cells, like our skin or blood cells by the process of mitosis, or to make sperm and egg through meiosis, all 3 billion base pairs must be replicated. Given this enormous number, DNA polymerase occasionally makes mistakes. Because it is so important to make as few mistakes as possible in copying our genetic material, cells possess proofreading enzymes that "check" newly replicated DNA. These proofreading enzymes make sure that the newly made double-stranded DNA mole cules have complementary base pairs: A facing T and G facing C. But in spite of the fidelity of the DNA polymerase enzyme and the action of the proofreading enzymes, rare errors remain in newly replicated DNA. It is estimated that during the replication process, there is approximately one wrong base in one million to one hundred million bases incorporated into DNA. That is a very low percentage of error, but the process is still not perfect. So, just in the normal process of copying DNA, errors, or mutations, accidentally occur. This is an important concept: mutations can take place without anything being out of the ordinary. This phenomenon is called spontaneous mutation. Although the spontaneous mutation rate is low, it is not negligible.

Another source of mutation that is often categorized as spontaneous mutation is oxidative damage. You may have heard that vitamins C and E and other foods are antioxidants and that people take them to reduce oxidative damage to their cells. As its name implies, oxidation involves oxygen. Our cells require oxygen to live, yet oxygen is a very reactive molecule and can be damaging to chemicals in our body. For example, oxidative damage changes guanine in our DNA to a chemical called oxoguanine. Because oxoguanine can pair with A, adenine, oxidative damage changes a G-C base pair in DNA to an oxoG-A pair, which after replication ends up as a T-A base pair. Proofreading enzymes can, however, spot and repair oxoG.

The two types of spontaneous mutations described above occur just as a fact of life. That is, there are no extraneous factors that cause these mutations: DNA polymerase makes errors, we cannot totally avoid oxidative damage, and not all errors are caught by proofreading enzymes.

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