1. PowerPoint Presentation Materials to accompany
Genetics: Analysis and Principles
Robert J. Brooker
CHAPTER 16
GENE MUTION
AND DNA REPAIR
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2. INTRODUCTION
The term mutation refers to a heritable change in the genetic material
Mutations provide allelic variations
On the positive side, mutations are the foundation for evolutionary change
On the negative side, mutations are the cause of many diseases
Since mutations can be quite harmful, organisms have developed ways to repair damaged DNA
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3. 16.1 CONSEQUENCES OF MUTATIONS
Mutations can be divided into three main types
1. Chromosome mutations
Changes in chromosome structure
2. Genome mutations
Changes in chromosome number
3. Single-gene mutations
Relatively small changes in DNA structure that occur within a particular gene
Type 3 will be discussed in this chapter
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4. Gene Mutations Change the DNA Sequence
A point mutation is a change in a single base pair
It involves a base substitution
5’ AACGCTAGATC 3’
3’ TTGCGATCTAG 5’
5’ AACGCGAGATC 3’
3’ TTGCGCTCTAG 5’
A transition is a change of a pyrimidine (C, T) to another pyrimidine or a purine (A, G) to another purine
A transversion is a change of a pyrimidine to a purine or vice versa
Transitions are more common than transversions
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5. Gene Mutations Change the DNA Sequence
Mutations may also involve the addition or deletion of short sequences of DNA
5’ AACGCTAGATC 3’
3’ TTGCGATCTAG 5’
5’ AACGCGC 3’
3’ TTGCGCG 5’
Deletion of four base pairs
5’ AACGCTAGATC 3’
3’ TTGCGATCTAG 5’
5’ AACAGTCGCTAGATC 3’
3’ TTGTCAGCGATCTAG 5’
Addition of four base pairs
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6. Gene Mutations Can Alter the Coding Sequence Within a Gene
Silent mutations are those base substitutions that do not alter the amino acid sequence of the polypeptide
Due to the degeneracy of the genetic code
Missense mutations are those base substitutions in which an amino acid change does occur
If the substituted amino acids have similar chemistry, the mutation is said to be neutral
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7. Gene Mutations Can Alter the Coding Sequence Within a Gene
Nonsense mutations are those base substitutions that change a normal codon to a termination codon
Frameshift mutations involve the addition or deletion of nucleotides in multiples of one or two
This shifts the reading frame so that a completely different amino acid sequence occurs downstream from the mutation
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8. 16-8
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9. Figure 15-1 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 15-1 Analogy of the effects of substitution, deletion, and insertion of one letter in a sentence composed of three-letter words, demonstrating point and frameshift mutations.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

10. Gene Mutations and Their Effects on Genotype and Phenotype
In a natural population, the wild-type is the most common genotype
A forward mutation changes the wild-type genotype into some new variation
A reverse mutation has the opposite effect
It is also termed a reversion
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11. Variants are characterized by their differential ability to survive:
When a mutation alters an organism’s phenotypic characteristics, it is said to be a variant
Variants are characterized by their differential ability to survive:
Deleterious mutations decrease the chances of survival
The most extreme are lethal mutations
Beneficial mutations enhance the survival or reproductive success of an organism
Conditional mutants: affect the phenotype only under a defined set of conditions
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12. Second-site mutations: suppressor mutations
Intragenic suppressors
The second mutant site is within the same gene as the first mutation
Intergenic suppressors
The second mutant site is in a different gene from the first mutation
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13. Gene Mutations in Noncoding Sequences
A mutation, may alter the sequence within a promoter
Up promoter mutations make the promoter more like the consensus sequence
They may increase the rate of transcription
Down promoter mutations make the promoter less like the consensus sequence
They may decrease the rate of transcription
Refer to Table 16.2 for other examples
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14. 16-13
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15. Changes in Chromosome Structure Can Affect Gene Expression
A chromosomal rearrangement may affect a gene because the break occurred in the gene itself
A gene may be left intact, but its expression may be altered because of its new location
This is termed a position effect
There are two common reasons for position effects:
1. Movement to a position next to regulatory sequences
Refer to Figure 16.2a
2. Movement to a position in a heterochromatic region
Refer to Figure 16.2b AND 16.3
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16. Regulatory sequences are often bidirectional
Figure 16.2
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17. Mutations Can Occur in Germ-Line or Somatic Cells
Germ-line mutations are those that occur directly in a sperm or egg cell, or in one of their precursor cells
Refer to Figure 16.4a
Somatic mutations are those that occur directly in a body cell, or in one of its precursor cells
Refer to Figure 16.4b AND 16.5
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18. The size of the patch will depend on the timing of the mutation
The earlier the mutation, the larger the patch
An individual who has somatic regions that are genotypically different from each other is called a genetic mosaic
Therefore, the mutation can be passed on to future generations
Therefore, the mutation cannot be passed on to future generations
Figure 16.4
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19. 16.2 OCCURRENCE AND CAUSES OF MUTATION
Mutations can occur spontaneously or be induced
Spontaneous mutations
Result from abnormalities in cellular/biological processes
Errors in DNA replication, for example
Induced mutations
Caused by environmental agents
Agents that are known to alter DNA structure are termed mutagens
These can be chemical or physical agents
Refer to Table 16.4
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20. 16-24
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21. Spontaneous Mutations Are Random Events
Are mutations spontaneous occurrences or causally related to environmental conditions?
This is a question that biologists have asked themselves for a long time 
Jean Baptiste Lamarck
Proposed that physiological events (e.g. use and disuse) determine whether traits are passed along to offspring
Charles Darwin
Proposed that genetic variation occurs by chance
Natural selection results in better-adapted organisms
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22. These two opposing theories of the 19th century were tested in bacteria in the 1940s and 1950s
Salvadore Luria and Max Delbruck studied the resistance of E. coli to bacteriophage T1
tonr (T one resistance)
They wondered if tonr is due to spontaneous mutations or to a physiological adaptation that occurs at a low rate?
The physiological adaptation theory predicts that the number of tonr bacteria is essentially constant in different bacterial populations
The spontaneous mutation theory predicts that the number of tonr bacteria will fluctuate in different bacterial populations
Their test therefore became known as the fluctuation test
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23. 16-27 Figure 16.6 The Luria-Delbruck fluctuation test
E.. coli is grown in the absence of T1 phages
20 million cells each
20 million cells each
Plates containing T1 phages
Relatively even distribution of tonr colonies
Great fluctuation in the number of tonr colonies
Several independent tonr mutations occurred during different stages
These are mixed together in a big flask to give an average value of tonr cells
No tonr bacteria
Many tonr bacteria
Spontaneous mutation did not occur
Mutation occurred at an early stage of population growth, before T1 exposure
The Luria-Delbruck fluctuation test
Figure 16.6
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24. Random Mutations Can Give an Organism a Survival Advantage
Joshua and Ester Lederberg were also interested in the relation between mutations and the environment
At that time (1950s), there were two new theories
Directed mutation theory
Selected conditions could promote the formation of specific mutations allowing the organism to survive
This was consistent with Lamarck’s viewpoint
Random mutation theory
Environmental factors simply select for the survival of those individuals that happen to possess beneficial mutations
This was consistent with Darwin’s viewpoint
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25. The Lederbergs developed a technique to distinguish between these two theories
A few tonr colonies were observed at the same location on both plates!!!
This indicates that mutations conferring tonr occurred randomly on the primary (nonselective plate)
The presence of T1 in the secondary plates simply selected for previously occurring tonr mutants
This supports the random mutation theory
Figure Replica plating
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26. Mutation Rates and Frequencies
The term mutation rate is the likelihood that a gene will be altered by a new mutation
It is commonly expressed as the number of new mutations in a given gene per generation
It is in the range of 10-5 to 10-9 per generation
The mutation rate for a given gene is not constant
It can be increased by the presence of mutagens
Mutation rates vary substantially between species and even within different strains of the same species
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27. Mutation Rates and Frequencies
Within the same individual, some genes mutate at a much higher rate than other genes
Some genes are larger than others
This provides a greater chance for mutation
Some genes have locations within the chromosome that make them more susceptible to mutation
These are termed hot spots
Note: Hot spots can be also found within a single gene
Refer to Figure 6.20
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28. Contain many mutations at exactly the same site within the gene
Figure 6.20
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29. Table 15-2 Copyright © 2006 Pearson Prentice Hall, Inc.
Table 15.2 Rates of Spontaneous Mutations at Various Loci in Different Organisms
Table Copyright © 2006 Pearson Prentice Hall, Inc.

30. Mutation Rates and Frequencies
The mutation frequency for a gene is the number of mutant genes divided by the total number of genes in a population
If 1 million bacteria were plated and 10 were mutant
The mutation frequency would be 1 in 100,000 or 10-5
The mutation frequency depends not only on the mutation rate, but also on the
Timing of the mutation
Likelihood that the mutation will be passed on to future generations
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31. Figure 15-8 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 15-8 The components of the electromagnetic spectrum and their associated wavelengths.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

32. Figure 15-9 Copyright © 2006 Pearson Prentice Hall, Inc.
Figure 15-9 Induction of a thymine dimer by UV radiation, leading to distortion of the DNA. The covalent crosslinks occur between the atoms of the pyrimidine ring.
Figure Copyright © 2006 Pearson Prentice Hall, Inc.

33. Nucleotide Excision Repair
Figure 16.19
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34. Recombination during DNA replication
DNA strands A and C have the same sequence
DNA strands B and D have the same sequence
Note: Recombinational repair occurs while the two DNA copies are being made
Figure 16.22
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35. The gap has been repaired; but the thymine dimer remains
Figure 16.22
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