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Chapter Summary

In earlier chapters, we saw how genes produce the enzymes that control specific biochemical reactions. Normal development depends on these information coding and regulatory systems working properly. But DNA replication is not perfect. Biochemical mistakes happen. Most replication errors are corrected by repair enzymes, but those that are missed become new mutations. In the broadest sense, then, a mutation is a heritable genetic change passed from one cell to another. For that reason, the biochemical correction mechanisms that work in parallel with replication are important for biological continuity.

Unfortunately, repair systems themselves can mutate, as in a patient with xeroderma pigmentosum (Figure 7-1). These patients have an increased mutation rate, as seen for example in higher rates of skin cancer, because of an inability to repair genetic damage caused by ultraviolet radiation. Other kinds of mutation repair deficiency are also known. Clearly, mutation rate is not a mathematical constant. Mutation rates can change.

Figure 7-1.

An individual showing the effects of xeroderma pigmentosum, a defect in one of the genes involved in the process of nucleotide excision repair. Individuals with this condition are unable to repair UV-induced mutations, which gives them a predisposition to skin cancer and related problems. (Reprinted with permission from Rünger TM, DiGiovanna JJ, Kraemer KH: Chapter 139. Hereditary Disorders of Genome Instability and DNA Repair. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Dallas NA, eds. Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: McGraw-Hill; 2012.)

Consider the following question. Would it be good if the process of mutation could be reduced? Would it be better if no new genetic changes ever occurred again? At first thought, the logical answer would probably be "yes." Eliminating mutation would be good. When you consider the many who must deal with developmental or physiological disabilities due to harmful mutations, it is easy to see the negative side of the process. But the environment in which we live is not constant. We continue to face new biologic challenges. Exposure to novel disease pathogens is only one obvious example. Physiological processes allow us to respond to changes in the environment. But genetic diversity adds another mechanism of response. In theory, therefore, the genetic diversity created by mutation may be fundamentally good—at least for the long-term survival of the species.

One way to think about this question is to consider biochemical pathways controlled by proteins under allosteric regulation. Binding with cofactors can change protein conformation within limits affected by environmental variables like temperature. A heterozygote for a key regulatory step can produce alternate protein forms with slightly different temperature optima. For that reason, a heterozygote is better able to handle the range of environmental conditions it naturally encounters. This can lead to the establishment of a polymorphism (literally "poly," many or multiple; "morph," ...

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