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