Mutations and DNA Repair Help

By — McGraw-Hill Professional
Updated on Aug 21, 2011


Mutations are changes in the sequence of DNA. Mutations can occur in any region of the genome; however, phenotypic changes may be observed in the organism only if a mutation occurs in the coding sequence of a gene (see Table 3-3 for specific examples). Recall that there can be different alleles at each genetic locus and the wildtype allele is the one causing the most common phenotype in a population. Alleles are distinguished from each other based on their DNA sequence; the wild-type allele having one sequence and all mutant alleles having slightly different sequences.

EXAMPLE 3.3 The normal (wild-type) human hemoglobin protein (Hb A) has about 140 amino acid residues in each of its α- and β-chains. The sequence of the β-chain has been determined to be

An abnormal (mutant) hemoglobin protein (Hb S) is produced by individuals with a mutant allele, resulting in a deformity of the red blood cell called ''sickling."" In a heterozygous condition this allele produces a mild anemia; in a homozygous condition the severity of the anemia may be lethal, resulting in sickle cell disease. The difference between Hb A and Hb S is that the latter has valine substituted for glutamic acid in the sixth position of the βs-chain.

Another potentially lethal abnormal hemoglobin (Hb C) is known in which the glutamic acid of the sixth position is replaced by lysine.

One of the codons for glutamic acid is GAA. If a mutation occurred that changed the first A to a U, then the codon GUA (a missense mutation, see Table 3-3) would be translated as valine. The substitution of A for G would produce the missense codon AAA, which codes for lysine. Thus, a change in a single nucleotide in the hemoglobin gene can produce a substitution of one amino acid in a chain of about 140 residues with profound phenotypic consequences!

Alleles that differ at the same nucleotide site are referred to as homoalleles. Intragenic recombination between homoalleles cannot result in production of new alleles. Alleles that differ due to nucleotide mutations at different sites are called heteroalleles. Intragenic recombination between two heteroalleles can result in production of new alleles, one wild-type and one containing two different nucleotide mutations.

EXAMPLE 3.4 An individual with a mutant phenotype has two mutant sites, m1, and m2, within homologous genes (diagrammed as boxes). These heteroalleles can recombine and be transmitted to the progeny as either a doubly mutant gene or as a wild-type gene.


Fortunately, most genes are relatively stable and mutation is a rare event. The great majority of genes have mutation rates of 1 × 10_6; i.e., 1 gamete in 100,000 to 1 gamete in a million would contain amutation at a given locus. However, in a higher organism containing 10,000 genes, 1 gamete in 10 to 1 gamete in 100 would be expected to contain at least one mutation. The rate at which a given gene mutates under specified environmental conditions is as much a characteristic of the gene as is its phenotypic expression. The mutation rate of each gene is probably dependent to some extent upon the residual genotype. The only effect that some genes seem to exhibit is to increase the mutation rate of another locus. These kinds of genes are called mutator genes.

EXAMPLE 3.5 A dominant gene called ''dotted"" (Dt) on chromosome 9 in corn causes a recessive gene a governing colorless aleurone, on chromosome 3, to mutate quite frequently to its allele A for colored aleurone. Plants that are aaDt- often have kernels with dots of color in the aleurone produced by mutation of a to A. The size of the dot will be large or small depending

Mutations that are deleterious to the organism are kept at a low frequency in the population by the action of natural selection. Organisms harboring these types of mutation are generally unable to compete equally with wild-type individuals. Even under optimal environmental conditions, many mutants appear less frequently than expected. Mendel"s laws of heredity assume equality in survival and/or reproductive capacity of different genotypes. Observed deviations from the expected Mendelian ratios would be proportional to the decrease in survival and/or reproductive capacity of the mutant type relative to wild type. The ability of a given mutant to survive and reproduce in competition with other genotypes is an extremely important phenotypic characteristic from an evolutionary point of view.

EXAMPLE 3.6 In Drosophila, white-eyed flies are produced by a sex-linked recessive gene (see Example 5.6). White-eyed flies may be only 60% as viable as wild-type flies. Among 100 zygotes from w+w (wildtype females) crossed to wY (white-eyed males), the Mendelian zygotic expectation is 50 wild type: 50 white eyed (see Example 5.7). If only 60% of white-eyed flies survive, then we would observe 50 × 0:6 = 30 white : 50 wild type.

Ionizing radiation such as X-rays are known to cause mutations in genes in direct proportion to the radiation dosage. A linear relationship between dosage (in roentgen units) and the induction of sex-linked recessive lethal mutations in Drosophila is shown in Fig. 3-13.


This indicates that there is no level of dosage that is safe from the genetic standpoint. If a given amount of radiation is received gradually in small amounts over a long period of time (chronic dose) the genetic damage is sometimes less than if the entire amount is received in a short time interval (acute dose). Treatment with ionizing radiation produces mutations most frequently by inducing small deletions in the DNA of the chromosome. Other types of mutagenic agents, such as the chemicals or other types of radiation, are also known to induce mutations.

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