Section 6.3
Mutations
Objectives
• Identify different changes to DNA within both genes and chromosomes
• Evaluate effects of changes to DNA on proteins produced and
organisms’ overall survival
New Vocabulary
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Gene mutation
Insertion
Deletion
Substitution
Chromosomal mutation
Chromosomal deletion
Amplification
Inversion
Chromosomal insertion
Translocation
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Non-disjunction
Silent mutation
Missense mutation
Nonsense mutation
Frameshift mutation
Overexpression
Beneficial mutation
Harmful mutation
Neutral mutation
Mutagen
The nucleotides of DNA are often compared to letters in an alphabet. By
using different combinations of letters, typographers can create different
printed words. Similarly, by using different combinations of nucleotides,
different proteins can be created. What happens to a word if a letter is copied
incorrectly? Sometimes the reader can understand the word, but sometimes
the word’s meaning changes completely. Something similar can happen to
strands of DNA: mutations.
6.3 - Mutations
Types of Mutations
Gene Mutations
A mutation that only affects one gene is a gene mutation. There are three different types of gene mutations: insertion, deletion, and substitution. An insertion
occurs when one or more new nucleotides are added within a DNA sequence for a gene. A deletion occurs when one or more nucleotides are removed from a
DNA sequence for a gene. A substitution (also called a point mutation) occurs when a nucleotide is replaced with a different nucleotide. The three types of gene
mutations are summarized in Table 6.3-1.
Type
Definition
Insertion
A new nucleotide is added
Deletion
A nucleotide is removed
Substitution (point mutation)
Example
"
...TAGCCAGATA...
"
...TAGCGCAGATA...
"
...TAGCCAGATA...
"
...TAGCAGATA...
A nucleotide is replaced with
"
...TAGCCAGATA...
a different nucleotide
"
...TAGCCAGTTA...
Table 6.3-1 There are three major types of gene mutations: insertions, deletions, and substitutions.
The type of gene mutation occurring can be easily determined using the steps below.
Step 1 | Write the wild-type allele above the mutated allele so that the bases line up.
"
Reasoning: This will allow you to easily compare the two alleles. (Note: this step might already be done for you.)
Step 2 | Starting on the right, look along both strands and underline the first base that is different in the mutated allele.
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Reasoning: This will allow you to identify where the change occurred.
Step 3 | Based on the difference between the two strands, identify the mutation that occurred.
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Reasoning: The types of gene mutations are defined by the change that occurred.
Step 4 | If possible, use the overall lengths of the two strands to check your answer.
!
Reasoning: An insertion will increase the length, a deletion will decrease the length, and a substitution will keep the length the same.
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6.3 - Mutations
Example problem | Which of the three gene mutations occurred to change the sequence
ACTAGATAGGCAT into ACTAGATAGCAGCAT?
Step 1 | Write the wild-type allele above the mutated allele so that the bases line up.
"
"
"
"
"
Wild-type" ACTAGATAGGCAT
"
"
"
"
"
Mutated"
ACTAGATAGCAGCAT
Step 2 | Starting on the right, look along both strands and underline the first base that is different
in the mutated allele.
"
"
"
"
"
Wild-type" ACTAGATAGGCAT
"
"
"
"
"
Mutated"
ACTAGATAGCAGCAT
Step 3 | Based on the difference between the two strands, identify the mutation that occurred.
"
An insertion occurred (a cytosine and an adenine were inserted after the ninth nucleotide).
Step 4 | If possible, use the overall lengths of the two strands to check your answer.
"
The mutated strand is two bases longer than the wild-type. Longer mutated strands reflect
an insertion.
Does the answer make sense? | Yes. This result makes sense because the mutated strand contains
two extra bases, an insertion occurred.
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6.3 - Mutations
Chromosomal Mutations
A mutation that affects multiple genes is a chromosomal mutation. There are several
different types of chromosomal mutations, including deletions, insertions,
amplifications, translocations, non-disjunctions, and crossing over.
The chromosomal mutation deletion is similar to the gene mutation deletion.
Remember that in the gene mutation deletion, one or more nucleotides are
removed. In a chromosomal deletion, a piece of the chromosome (many
nucleotides) is lost. This mutation can remove one or more genes from the
chromosome.
In an amplification mutation (also called gene duplication), a large piece of the
chromosome is repeated. This mutation causes two or more copies of one or more
genes. In an inversion, a piece of a chromosome is removed and readded after being
flipped, reversing its orientation. Chromosomal deletions, amplifications, and
inversions are summarized in Figure 6.3-1.
Figure 6.3-1 Chromosomal deletions, amplifications, and inversions each
affect the genes in one part of a chromosome. Deletions remove these
genes, amplifications multiply the genes, and inversions flip the orientation
of bases within the genes.
Segments of DNA can also move from chromosome to chromosome. In
chromosomal insertions, a piece of one chromosome is removed and inserted into
another chromosome. In translocation, two pieces of different chromosomes are
interchanged. These two mutations are illustrated in Figure 6.3-2.
Some chromosomal mutations occur during meiosis. Remember that during
meiosis, homologous chromosomes are separated so that one goes to each gamete.
If they do not separate correctly and both chromosomes go to the same daughter
cell, this is called non-disjunction.
Jump to Meiosis
Figure 6.3-2 In an insertion, a segment of one chromosome is moved to
another. In translocation, two pieces from different chromosomes are
exchanged.
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6.3 - Mutations
Effects of Mutations
In the previous section, mutations were categorized by the change
to nucleotides. Remember that through transcription and
translation, these nucleotides will be used to form mRNA codons
that will be translated into a polypeptide chain. Because of this,
mutations can also be categorized by their effect on the
polypeptide chain made. In general, each type of change to the
nucleotides causes a certain type of effect on the polypeptide.
Jump to Translation
Effects of Gene Mutations
Gene mutations can affect a gene in multiple ways. Remember
that in a substitution, one nucleotide is replaced by a different
nucleotide, changing the mRNA strand. Because of redundancies
in the genetic code, a different codon does not always place a
different amino acid during translation (Figure 6.3-3). If the
substitution changes the mRNA codon into a codon coding for the
same amino acid, it is called a silent mutation because it has no
outwardly visible affect. If the substitution changes the mRNA
codon into a codon coding for a different amino acid, it is called a
missense mutation because one of the amino acids is now
different. Depending on the location of the amino acids, this could
change the protein created. If the substitution creates a stop
codon, the amino acid terminates early. This can greatly affect the
overall protein created and is therefore called a nonsense
Figure 6.3-3 The genetic code contains many redundancies, which allow silent mutations to occur.
For example, leucine will be used if the codon is UUA, UUG, CUU, CUC, CUA, or CUG.
mutation.
Jump to Substitution
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6.3 - Mutations
Insertions and deletions cause frameshift mutations. Since the codons are read
in groups of three nucleotides, the addition or removal of a nucleotide changes
the reading frame. Every codon past the mutation is affected, and a completely
different polypeptide chain can be produced. Effects of gene mutations are
summarized in (Figure 6.3-4).
Figure 6.3-4 As illustrated here, different mutations to the DNA can cause different
effects to the polypeptide.
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6.3 - Mutations
Effects of Chromosomal Mutations
Since chromosomal mutations affect multiple genes, they can cause large
impacts on an organism. Remember that in non-disjunction, the
homologous chromosomes do not separate. This creates one gamete
with an extra copy of a chromosome and one gamete with no
information for that chromosome. If either of these gametes fuses with a
normal gamete, the individual formed will not have the correct number
of chromosomes. For example, in Down syndrome, a human has three
copies of chromosome 21. This causes both physical and mental
retardation (Figure 6.3-5).
Jump to Non-Disjunction
When a segment of a chromosome is duplicated in amplification, the
organism might have an overexpression of those genes and create more
copies of protein than normal. In contrast, if a segment of a chromosome
is deleted or inversed, the organism might not be able to express any of
these genes.
Jump to Chromosomal Mutations
Effects of Mutations on Fitness
Any mutation can be categorized by its effect on fitness. A beneficial
Figure 6.3-5 Caused by a non-disjunction event, Down syndrome causes both physical and
mental retardation. One common trait is a wide gap between the large and second toe.
mutation increases an organism’s fitness. For example, a mutation might
cause an organism’s fur color to be closer to the environment, allowing it
to avoid predators. A harmful mutation decreases an organism’s fitness.
For example, a mutation might make the protein responsible for
carrying oxygen in the blood less efficient. A neutral mutation does not
affect an organism’s fitness. For example, a mutation might not change
the proteins created. All silent mutations are neutral mutations.
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Lab – DNA Mutations
The effect of a gene mutation depends on the type and severity of change. The following virtual lab will provide you the opportunity to modify a gene and
evaluate the effects.
By creating different changes in the gene, you should have been able to create silent, missense, nonsense, and frameshift mutations.
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6.3 - Mutations
Spotlight on Sickle-cell Anemia
Sickle-cell disease is a generic name for a number of conditions resulting from a mutation in the genetic
code. The most common of these conditions is sickle-cell anemia. As seen in Figure 6.3-6, the condition
results in red blood cells with a hardened sickle shape instead of the normal flexible disk shape. Since
healthy red blood cells carry oxygen to body tissues, sickle-cell anemia causes breathing problems,
paleness, and fatigue. The abnormal blood cells also tend to clump together in the bloodstream. This
can cause pain, infections, organ damage, and swelling.
A primary component of red blood cells is hemoglobin, a specialized protein that can chemically bond
to and transport oxygen and carbon dioxide through the bloodstream. As seen in Table 6.3-2, a single
base substitution mutation causes a missense mutation in one of the polypeptide chains of
hemoglobin. The substitution of the amino acid valine for glutamic acid causes a “sticky spot” in the
Figure 6.3-6 This 3D rendering contrasts normal
red blood cells with sickle-shaped red blood cells
that result from sickle-cell disease.
hemoglobin beta polypeptide chain. This results in the sickle shape of the red blood cell. The mutant
strain is HbS, and the wild-type is HbA. Jump to Globular Proteins
Wild-Type DNA (HbA)
CTG
ACT
CCT
GAG
GAG
AAG
TCT
Leucine
Threonine
Proline
Glutamic acid
Glutamic acid
Lysine
Serine
Substitution Mutation (HbS)
CTG
ACT
CCT
GTG
GAG
AAG
TCT
Leucine
Threonine
Proline
Valine
Glutamic acid
Lysine
Serine
Table 6.3-2 A mutation in the nucleotides for hemoglobin results in a different amino acid and misshapen red blood cells.
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6.3 - Mutations
Remember that each person contains two copies of each gene, one from the mother and one from the
father. Two copies of the mutant HbS gene, one from each parent, are needed to cause sickle-cell
anemia. Only one copy of the HbS gene causes sickle-cell trait, in which the person is a carrier of the
gene. However, the presence of only one HbS gene does not usually cause problems for carriers. Since
this gene shows codominance, some red blood cells may contain some abnormal hemoglobin, but most
red blood cells will be normally shaped because of the presence of the wild-type gene. Jump to Codominance
In most parts of the world, the HbS gene is rare. However, the sickle-cell gene is found in those of
Central African or Indian ancestry. These locations are also where the highest rates of a deadly form of
malaria occur. This overlap is because carriers of the sickle-cell gene are more likely to survive malaria
(the reasons are still being researched). Since these carriers are more likely to survive, they are more
likely to have children. If two carriers have a child, this creates a monohybrid cross. In this cross, there
is only a 25% chance that the child will be homozygous dominant and not have the sickle-cell gene to
pass on.
Jump to Dihybrid Cross
Although some people with sickle-cell anemia can be cured through stem cell transplants, for most
people, this disease is managed, not cured. Fortunately, a number of treatments and medications are
available to lessen symptoms and complications of the disease.
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6.3 - Mutations
Causes of Mutations
Mutations have three primary causes. The first is
mistakes that happen during DNA replication.
Although cells have double-checking mechanisms
during DNA replication, errors can still occur. The
second cause is mutagens, environmental agents that
can damage existing DNA. Examples of mutagens are
ultraviolet radiation and chemical toxins. For
example, UV radiation can damage a group of bases
on one of the DNA strands (Figure 6.3-7). This
damage causes the bases to pair with each other
instead of with their complementary bases on the
other DNA strand.
The final primary cause of DNA mutations is
spontaneous damage by molecules known as free
radicals. Free radicals are reactive forms of molecules
produced by normal metabolic processes. Free
radicals cause damage directly to nitrogenous bases
in DNA. Antioxidants, chemicals found in many
healthy foods, are thought to neutralize free radicals
and prevent damage.
Figure 6.3-7 UV radiation can cause bases on one strand to pair with one another instead of the other strand.
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6.3 - Mutations
Repairing DNA
Despite the various mutations possible, cells and
tissues usually replicate their DNA without
accumulating harmful mutations. This is because
cells have several procedures to detect and repair
mistakes. These procedures have been identified in
both unicellular and multicellular organisms.
Primarily, checkpoint procedures during the cell
cycle prevent cell division if mistakes are found in
DNA. Cells that do not pass the checkpoint may be
marked for destruction by white blood cells or die
naturally. Mutations can accumulate if the
checkpoint system breaks down. If a mutation
removes a checkpoint, cells with damaged DNA
may undergo mitosis, as illustrated in Figure 6.3-8.
This causes damaged DNA to be passed on to
daughter cells.
Figure 6.3-8 If the checkpoint system fails, damaged DNA is passed on.
Jump Control of Cell Cycle
Cells can also repair their own damage. UV radiation damage is detected because it causes a change in
the shape of the DNA molecule. These changes are repaired through a complex method in which the
damaged section is removed and the strand is repaired. Prokaryotes, fungi, plants, some insects, and
even some vertebrates also use another system not present in humans. In these organisms, energy from
light, enzymes, and other chemical molecules is used to change the DNA back into its original,
undamaged shape.
In another method of DNA repair, damage caused by free radicals and other cellular molecules is fixed.
In this process, enzymes identify abnormal nitrogenous bases and chemically cut them out.
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6.3 - Mutations
Sometimes the cell is unable to repair the damage.
Some forms of ionizing radiation (such as that emitted
from X-ray machines) cause physical breaks in one or
both strands of DNA. In these mutations, pieces of the
chromosome can be lost or become attached to other
chromosomes. Although the cell attempts to repair
these breaks, the damage is so great that the repairs
themselves can cause even more damage. Ionizing
radiation is very dangerous, and protection should be
used when exposure is necessary (Figure 6.3-9).
Special care should be given to babies and young
children to avoid preventable causes of mutations.
Their rapidly dividing cells are more susceptible to
radiation, UV light, and even possibly the effects of
free radicals. This is why pregnant women are
cautioned against smoking tobacco, drinking alcohol,
and even eating certain foods. Extra precautions are
taken during medical testing if there is even a
possibility of pregnancy. While it is true that damage
from mutagens tends to accumulate as we age, there
are some ways to avoid the damage. One is to avoid
known mutagens, such as UV light. Recent research
Figure 6.3-9 A lead apron is used to protect body structures during an X-ray.
has shown that a healthy lifestyle can prevent and, in
some cases, even repair or reverse damage from mutations.
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