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Modern Genetic Analysis Chapter 7. Gene Mutations
Summary

Gene mutations can arise through many different processes. Spontaneous mutations can result from replication errors or from spontaneous lesions, such as those generated by deamination or depurination. Mutagens can increase the frequency of mutations. Some of these agents act by mimicking a base and then mispairing in DNA replication. Others alter bases in the DNA and convert them into derivatives that mispair. A third class of mutagens, which includes most carcinogens, damages DNA in such a way that replication is blocked. The activation of an enzymatic pathway, termed the SOS system, is required to replicate past the blocking lesions. This results in mutations that arise across from the blocking lesion.

Repair enzymes present in living cells greatly minimize genetic damage, thus averting many mutations. Mutant organisms lacking certain repair enzymes have higher-than-normal mutation rates. In humans, repair deficiency leads to a variety of diseases and cancer susceptibilities.

Genes may mutate in somatic cells or germinal cells. Within these two broad categories, there are several kinds of mutations, including morphological, lethal, conditional, biochemical, and resistance mutations.

Mutations can be used to study the process of mutation itself or to permit genetic dissection of biological functions. To carry out such studies, however, it is necessary to have a system for detecting mutant alleles at the phenotypic level. In diploids, dominant mutations are easily detected. On the other hand, the detection of recessive mutations requires the use of special genotypes; otherwise, the mutations may never be manifested in the phenotype. For this reason, detection systems are much more straightforward in haploids, where the question of dominance does not arise.

Mutation events occur randomly at any time and in any cell. Therefore the size of a mutant clone is proportional to the developmental stage at which the mutation event occurred.

Mutations often result in loss of the normal function of the affected allele, either fully (null mutations) or partly (leaky mutations). Loss-of-function mutations are generally recessive, and this can be demonstrated in heterozygotes, in which the wild-type allele provides enough function to result in normal phenotype. Gain-of-function mutations are often dominant.

© 1999 by W. H. Freeman and Company. All rights reserved.