Module 3
The Chemical Basis of Heredity
Time Frame: 5 Hours Lesson 4
Learning Objectives Gene Mutation and DNA Repair
At the end of this lesson, you are
expected to: Introduction
Describe the nature of This lesson is about how errors arise in genetic
mutation instructions and how those errors are occasionally
Discuss mutagenesis repaired. It begins with the nature of mutation which
Describe the processes of include its categories, types, effects on phenotype and
DNA repair causes of mutation. We will also explore mutagens and
Key Concepts learn how they alter DNA sequences. The last part of this
DNA Mutation lesson discusses the different methods in DNA repair.
DNA Repair
Activity
Activity 3.4
1 The biological impacts of the Fukushima nuclear
accident on the pale grass blue butterfly
A disastrous nuclear accident happened in Japan’s Fukushima Nuclear Power Plant after a
powerful earthquake on March 2011. This result to genetic mutation in pale grass blue butterfly.
In this activity, you will understand how radiation causes mutation in living organisms.
Procedure:
Read the article “The biological impacts of the Fukushima nuclear accident on the pale grass
blue butterfly”.
Analysis
1. Briefly summarize the article.
2. Describe the impacts of nuclear radiation exposure to the genotypic and
phenotypic constitution of the blue grass butterfly
Mutation
Inheritable change in genetic material
Cells from cell division; offspring from reproduction
Categories of Mutation
Somatic mutations
o Mitosis yields genetically identical cells
o can lead to mosaicism
o Tumor – uncontrolled growth
Germ-line mutations
o Arise in cells destined to become gametes
o Passed to offspring; present in every cell of organism
Gene mutations
o Affect a single gene
Chromosomal mutations
o Large-scale changes
o May be observable with a microscope
Figure 3.4.1. Two basic classes of mutations: somatic mutations and germ-line mutations. [Pierce, B. (2009).
Genetics: A Conceptual Approach, Third Edition. W.H. Freeman and Company.]
Types of mutations
Base substitution/point mutation
o One base is replaced by
another
o Transition
o One purine
replaced by another
purine; one
pyrimidine replace
by another
pyrimidine
o Transversion Figure 3.4.2. A transition is the substitution of a purine for
o Purine replaced by a a purine or a pyrimidine for a pyrimidine; a transversion is
pyrimidine, or vice the substitution of a pyrimidine for a purine or a purine for
versa a pyrimidine. [Pierce, B. (2009). Genetics: A Conceptual Approach, Third
Edition. W.H. Freeman and Company.]
Insertion or deletion
o One or more nucleotides
o Frameshift mutation
o
o In mRNA genes, affect all amino
acids downstream, unless in
groups of three in normal codon
place
Expanding trinucleotide repeats
o Certain genes contain tandem
repeats
o Number of repeats can increase
in offspring due to strand
slippage or uneven crossing
over.
Phenotypic effects
Missense mutation
o Causes incorrect amino acid
to be placed in polypeptide
o Neutral mutation – protein
function is not affected due Figure 3.4.3. Types of mutation. [Pierce, B. (2009).
Genetics: A Conceptual Approach, Third Edition. W.H. Freeman
to amino acids having and Company.]
similar properties
Nonsense mutation
o Introduces a premature STOP codon
o Results in a truncated polypeptide
Silent mutation
o Due to codon redundancy, mutation still codes for the same amino acid
Loss of function
o Functional polypeptide is not made
o Recessive
o Normal gene still makes correct polypeptide
Gain of function
o Abnormal polypeptide is produced
o dominant
Figure 3.4.4. Base substitutions can cause (a) missense, (b) nonsense, and (c) silent mutations. [Pierce,
B. (2009). Genetics: A Conceptual Approach, Third Edition. W.H. Freeman and Company.]
Causes of mutations
Spontaneous
o Natural changes/errors
o Replication errors or
chemical changes
Induced
o Caused by environmental
agents
Chemical,
radiation
Spontaneous replication errors
Tautomers
Wobble
Strand slippage
Unequal crossing over
Tautomers
Various forms of nitrogenous
bases
o Position change of a proton
(hydrogen ion)
Can exhibit unconventional base
pairing
o Rare form of C can bond with
A; rare form of G can bond
with T
Originally thought to be major
source of mutation – no
supporting evidence
Wobble
Flexibility in DNA helix
Incorporated error
o TA base pair becomes CA
• One new molecule will have
correct TA, other will have
CG
o Since all bases are correctly
paired, no repair
mechanism can fix Figure 3.4.5. Purine and pyrimidine bases exist in
different forms called tautomers. [Pierce, B. (2009).
Genetics: A Conceptual Approach, Third Edition. W.H. Freeman and
Company.]
Figure 3.4.6. Wobble base pairing leads to a replicated error. [Pierce, B. (2009). Genetics: A Conceptual
Approach, Third Edition. W.H. Freeman and Company.]
Strand slippage
Causes small insertions or
deletions
One nucleotide loops out
o On new strand – results in
an insertion
o On old strand – results in a
deletion
Strand slippage in trinucleotide
repeats
Slippage of new strand can result
in expanded number of repeats in
offspring cells
Cause of anticipation Figure 3.4.7. Insertions and deletions may result
from strand slippage. [Pierce, B. (2009). Genetics: A
Conceptual Approach, Third Edition. W.H. Freeman and Company.]
Unequal crossing over
Incorrect alignment of
homologous chromosomes
Crossing over results in an insertion in one molecule and a deletion in the other
molecule
Can also cause expanded trinucleotide repeats
Spontaneous chemical changes
Depurination
o Nucleotide loses its purine base; apurinic
o Can’t act as a template
o A is usually the base placed in the new strand
Deamination
o Removal of an amino group
o Deaminated cytosine becomes uracil
Since U is not present in DNA, usually correctly by repair mechanisms
o Deaminated methylcytosine becomes thymine
Causes CG to AT – not detected by repair mechanisms
Mutagen
environmental agent with
ability to alter DNA sequence
Chemically Induced Mutagens
Base analogs
Alkylating agents
Deamination
Oxidative reactions
Intercalating agents
Base analogs
Have structure similar to normal
nucleotides
When ionized, exhibit
unconventional base pairing
Transition or transversion
mutation shown?
Alkylating agents
Donates alkyl groups to bases
Incorrectly base pair
Deamination
Can occur spontaneously or be
induced
Adenine becomes hypoxanthine
(pairs with C)
Guanine becomes xanthine (pairs
with T)
Oxidative reactions
Reactive forms of oxygen
Causes transversions Figure 3.4.8. 5-Bromouracil (a base analog)
G pairs with A resembles thymine, except that it has a bromine atom
Intercalating agents in place of a methyl group on the 5-carbon atom.
Insert themselves into DNA – Because of the similarity in their structures, 5-
bromouracil may be incorporated into DNA in place of
distorts molecule thymine. Like thymine, 5-bromouracil normally pairs
Often causes frameshift mutations with adenine but, when ionized, it may pair with
guanine through wobble. [Pierce, B. (2009). Genetics: A
Conceptual Approach, Third Edition. W.H. Freeman and Company.]
Radiation
Ionizing radiation
o High energy breaks
phosphodiester bonds
o
o Results in double-
stranded breaks
UV light
o Pyrimidine dimers –
usually thymine
dimers
o Causes TpT to
covalently bond
Replication of
DNA is blocked
and cell dies, or
transcription is blocked
DNA Repair
Mismatch repair
Direct repair
Base excision repair Figure 3.4.9. 5-Pyrimidine dimers result from
Nucleotide excision repair Ultraviolet light [Pierce, B. (2009). Genetics: A Conceptual
Approach, Third Edition. W.H. Freeman and Company.]
Mismatch Repair
Corrects replication errors/improper base pairing not fixed by DNA polymerase III
Recognizes structural distortions
New strand section is cut out and replaced
o Old strand is methylated – strand distinction
Direct Repair
Converts altered nucleotide back to original form
Methylguanine binds with A
o Enzymes remove methyl group to return to normal guanine
Photolyase
o Found in E. coli and some eukaryotes (not humans)
o Break covalent bonds of dimers
Base Excision Repair
Repairs abnormal/ modified bases
Nitrogenous base is first removed
o Apurinic or apyrimidic site
Followed by removal of rest of nucleotide
DNA polymerase replaces nucleotide; DNA ligase seals nick by forming phosphodiester
bond
Nucleotide excision repair (NER)
Removes lesions that distort DNA helix
Several enzymes/ genes involved
o Recognize distortion
DNA strand is separated; single-strand binding proteins stabilize
Large section is removed
DNA polymerase fills in; DNA ligase seals nicks
Application 3.41
Activity
Test Your Knowledge
1. What is the difference between somatic mutations and germ-line mutations?
2. What is the difference between a missense mutation and a nonsense mutation?
A silent mutation and a neutral mutation?
3. How do alkylating agents, nitrous acid, and hydroxylamine produce mutations?
4. What types of mutations are produced by ionizing and UV radiation?
5. List at least three different types of DNA repair and briefly explain how each is
carried out.
References
Pierce, B. (2017). Genetics: A Conceptual Approach, 6th edition. WH Freeman, New
York.
Tamarin, R. (2001). Principles of Genetics, 7th edition. The McGraw-Hill, New York.
Acquaah, J. (2012). Principles of Plant Genetics and Breeding, 2nd edition. Wiley-
Blackwell, United Kingdom
