Chapter 14. Genes In Action
Section 1
Mutations
“Warm Up”
• Define mutation.
• What is a genetic mutant?
• Remember, genes are incredibly
precise DNA sequences. Recall how
DNA is eventually translated into a
protein. Discuss with your group what
you think will happen if the sequence
was somehow changed…
•
Mutants among us?
• What do all of these comic book
legends have in common?
• Right.
• They are all mutants!
Objectives: Mutations
• Identify the primary mechanism for
genetic change and differences among
organisms.
• List the kinds of mutations.
• Describe the characteristics of each
mutation.
• Identify a mutation present in given
DNA strands.
Vocabulary
•
•
•
•
•
•
•
•
•
•
•
•
Mutation
Point mutation
Insertion mutation
Deletion mutation
Silent mutation
Missense mutation
Frameshift mutation
Nonsense mutation
Duplication mutation
Inversion mutation
Translocation mutation
Gene rearrangement
Section 14.1 Exercise
Write down the word CASH. How many more
words can you make from that word by
substituting, adding, or subtracting only
one letter with a different letter?
-Bash
-Mash
-Dash
-Gash
-Hash
-Lash
-Nash
-Rash
-Sash
-Wash
-Cast
-Case
-Casa
-Cask
-Casi
-Crash
-Clash
-Ash
•What if the directions asked you to change one
letter out of these new words you’ve created…
•Then asked you to do this again, and again,
(maybe 10 times per new word). In addition,
every once in awhile you were allowed to
rearrange the letters.
•How many new words do you think you could
have?
•If CASH was a gene, the new words you wrote
would be mutations of CASH
The Role of Mutations
• Mutation is a fundamental and
inevitable aspect of heredity.
• Without it we would never see
genetic diversity.
2 Possible Outcomes of
Changing DNA Sequences
DNA
C
G
A
T
G
C
C
T
C
G
A
A
G
C
C
T
C
G
A
T
C
Changes in the DNA
could lead to:
Nothing (the change
could result in the
same amino acid
Or
The amino acid could
be changed as well.
Mutations…Some Facts…
• Can have no impact and may not be detectable.
– These have no effect and are lost in the dominant –
recessive allele interaction.
– Remember, carriers don’t know they have the mutation &
don’t display the phenotype.
• A very small percentage can be good, or
advantageous, and make life better, though.
– These are how species evolve.
• Most mutations that are detected are so because
they are deleterious…meaning they result in
something bad & many times death.
• Do you know of any?
• Does your family have any particular cases that may
have some significance in this discussion?
An Affect of Mutation
• Does anyone know what sickle cell
anemia is?
• Does anyone know of someone
afflicted?
• Can anyone describe the significant
symptom of this disease?
Sickle cell anemia
• These are RBC’s
• They transport 02 in
your bloodstream to
cells that need it (for
aerobic respiration)
• The abnormal cell is a
sickle cell.
• It isn’t nearly as
efficient in delivering
oxygen throughout the
body.
• It is a co-dominant trait
that was caused by a
mutation.
Sickle Cell Anemia
• Sickle Cell Anemia:
– Can have troublesome
side affects including:
•
•
•
•
•
•
•
Bone & abdominal pain
Fatigue
Fever
Delayed growth
Blood clots in arteries
Chest pain
And possibly
death…especially in low
oxygen levels (at high
altitudes).
A Strange Twist of Fate
• Malaria is a parasitic disease that attacks RBC’s.
• 40% of the world’s population has a high risk of contracting
this (Asia, Africa, Central/South America).
• Spread by infected mosquitoes, persons contracting
malaria can come down with life threatening fevers, liver
failure, and death. (#1 killer in 3rd world youth)
• Whereas children who inherit full-fledged sickle cell anemia
(both mutated alleles = homozygous recessive) can have
both sickle cell and malarial complications, those who
inherit just one mutated allele (therefore partially
affected…remember, it’s co-dominant) have a “survival
advantage” to malaria and usually have no major sickle cell
complications.
• Most mutations are bad, and sickle cell anemia is, but
sometimes mutations actually can have hidden benefits.
Instituto Gulbenkian de Ciencia. "Mystery solved: How sickle hemoglobin protects against malaria." ScienceDaily, 29 Apr.
2011. Web. 31 Jul. 2012.
Tie To Prior Learning
Complete the Punnett Square & Determine the % that
will have the Sickle Cell Trait and who will be carriers.
Two carriers of the
sickle cell trait
produce offspring.
What % will be
carriers?
S
S
s
SS
Ss
Full sickle cell ½ Sickle cell
s
Ss
ss
Mutation: The Basis of
Genetic Change
• In genetics, a mutation is a change in the
structure or amount of the genetic material of an
organism.
• What is this “genetic material”?
• DNA
• So what this means is that a mutation is a change
in the structure or quantity of DNA in an
organism.
• A genetic mutant is an individual whose DNA or
chromosomes differ from some original, previous,
or normal state.
• Don’t be alarmed…we are mutants of some sort.
• If any one of these combinations were
to be changed by a mutagen the results
could be devastating.
What are the colored
“sticks”
representative of?
Nitrogenous base
paring…right?
It could change this…
To this
Mutation: The Basis of
Genetic Change
• Mutation has had a profound affect on
evolution.
• For the most part, genetic differences among
organisms originated as some kind of
genetic mutation.
– This is responsible for what’s called
speciation…or the different species on earth
• As it is, every unique version of every gene
(or every gene for that matter) began as a
mutation of the original gene.
– As an analogy, we all started as CASH…We are
now all variations of this…Now we’re money.
The Original “CASH”
• There is an interesting book from Dr. Richard
Hawking titled “The Selfish Gene”.
• In it he discusses the likely origination of nucleic
acids found floating around in what’s called a
“primordial soup”.
• Imagine a gene the size of the word CASH floating
around and mutations similar to the ones you
performed in the opening exercise occurred over
millions, possibly billions of years.
• This may explain the initial variety of genetic
material available to start the first organism.
• What kind of organism could that be?
The Primordial Soup Theory
• Imagine you were
transported billions of
years back into Earth's
history.
• Instead of sunny skies and
clouds and trees and
beaches and birds and
beasts of the environment,
evolutionists theorize that
the Earth looked something
like this, with ammonia,
sulfur, methane, water, and
amino acids…just the basic
components of life around.
• It’s from this that the first
mutations are believed to
have created life… if you
believe in such.
Mutation
Several Kinds of Mutations
• DNA and chromosomes are involved in many
processes, so there are many kinds of mutations.
• Most mutations involve a misplacement of a SINGLE
nucleotide in a DNA segment.
• A mutation may change the results of a gene (when
the gene is translated and transcribed), but not all
mutations do so.
• Different kinds of mutations are recognized as either
changes in DNA or changes in the results of genes.
Several Kinds of Mutations
Mutations as Changes in DNA
• During DNA replication, the wrong nucleotide may be
paired or placed in a sequence.
1. Point mutation:
• A point mutation is a change of a single nucleotide in
a sequence from one kind of base to another.
2. Insertion or Deletion:
• Rarely, errors in replication can cause the insertion or
deletion of one or more nucleotides in a sequence.
• The CASH exercise we just performed illustrates what
results from these types.
Several Kinds of Mutations
Mutations as Changes in Results of Genes
• Changes in a DNA sequence may affect the
results of genes in many ways.
1. Silent Mutation:
• A mutation is silent when it has no effect on
a gene’s function.
• Point mutations are often silent because the
genetic code is redundant (some amino
acids have multiple codons).
Several Kinds of Mutations
Mutations as Changes in Results of Genes
2. Missence (Replacement) Mutation:
• Results when a codon is changed (bases are
switched) such that the new codon codes for a
different amino acid.
3. Frameshift:
• The reading frame of a sequence depends on the
starting point for reading (the start codon).
• This sets up the rest if the gene’s codons.
• An insertion or deletion can shift the reading frame,
or cause a frameshift.
• In frameshift mutations, the remaining sequence may
be “read” as different codons.
Several Kinds of Mutations
Mutations as Changes in Results of Genes
4. Nonsense:
• Results when an internal codon is changed to a “stop” signal.
• In this case, the resulting string of amino acids may be cut short,
and the protein may fail to function.
5. More or fewer Amino acids:
• If an insertion or deletion is a multiple of 3, the reading frame will
be preserved. It causes the resulting protein to have more or less
amino acids than originally.
• An insertion or deletion of many codons is likely to disrupt the
resulting protein’s structure and function.
Chromosomal Mutations
Chromosomal Mutations
• In eukaryotic cells, the process of meiosis creates the chance
of mutations at the chromosomal level.
• Recall that during meiosis, chromosomes pair up and may
undergo crossover. Usually, the result is an equal exchange of
alleles between homologous chromosomes.
• Sometimes there is an unequal exchange that can cause
chromosomal mutations.
• There are 5 main types of chromosomal mutations.
Chromosomal Mutations
Chromosomal Mutations
1. A deletion occurs when a piece of a chromosome is
lost. At the end of meiosis, one of the cells will lack
the genes from that missing piece. Such deletions
are usually harmful.
2. A duplication occurs when a piece remains attached
to its homologous chromosome after meiosis. One
chromosome will then carry both alleles for each of
the genes in that piece.
Chromosomal Mutations
Chromosomal Mutations
3. An inversion occurs when a piece reattaches to its
original chromosome, but in a reverse direction.
4. A translocation occurs when a chromosome piece
ends up in a completely different, non-homologous
chromosome.
5. A gene rearrangement can move an entire gene to a
new location. Such a chromosomal mutation is likely to
disrupt the gene’s function in other ways.
Chromosomal Mutations
What is the WORST?
No affect
• Most proteins can
Little affect function normally
Major Affects
with only one
amino acid
change.
• The more amino
acids changed, the
more of an affect.
• What is the worst?
• Tough to say as each scenario is
unique, however, mutations that
dramatically alter the protein will have
severe affects on protein effectiveness.
What Causes Mutations?
• A variety of factors influence changes in DNA.
1. Problems in Meiosis
1.
2.
Transposable elements.
1.
3.
Jumping Genes that move from chromosome to chromosome.
Spontaneous errors in replication.
1.
4.
Nondisjunction & Polyploidy
Usually corrected by DNA Polymerase but can, at times, be
passed down to next-generation cells. If this happens in gametes,
children can be affected with gene-based abnormalities.
Harmful environmental agents.
1.
2.
3.
Ionizing radiation: X-rays and gamma rays can break
chromosome pieces or cause free-radicals (highly reactive
hydroxide ions that damage DNA)
Non-ionizing Radiation: cause adjacent thymine bases to bond,
kinking DNA
Natural or Synthetic Chemicals: a.k.a. Carcinogens
Transposable Elements
Nobel Prize winner in
1983, Barbara
McClintock discovered
that certain genes can
slip from one place on
a chromosome to
another, sometimes
disrupting the target
site.
Errors In Replication
Environmental Influences
• Ionizing Radiation:
• Non-Ionizing Radiation:
• Carcinogens:
http://www.cancer.org/cancer/cancercauses/othercarcinogens/gener
alinformationaboutcarcinogens/known-and-probable-humancarcinogens
What Kind of Mutation Illustrated?
In your groups, first identify the problem, make the mRNA, the amino acids,
then name the type of mutation. You have 5 minutes for discussion and
conclusions.
Normal = Wildtype Gene
Problem
TACGGTAGC
Problem
TACGGAAGC
TACGTTAGC
Problem
TACCGGTAGC
Each of the following is a
modification of the sentence
THECATATETHERAT
1. THERATATETHECAT
2. THEKATATETHERAT
3. THETACATETHERAT
4. THECATARETHERAT
5. THECATATTHERATS
6. HECATATETHERATS
Which one(s) is/are:
1. A FRAMESHIFT mutation?
2. A SILENT mutation?
3. A DELETION mutation?
4. An INVERSION mutation?
5. A POINT mutation?
Mutation Detection (25pts)
• You, as a microbiologist or a geneticist, have the ability to look at
the sequence of an organism. You would do so to detect
differences between “normal” DNA and mutations.
• Your research objective today is to study the following mutant
DNA sequences to detect the type of mutation and where it takes
place. The mutations are changes in the DNA that result in the
changes of their genes (not their pants). First study the given DNA
sequence. Then you will need to determine the reading frame (the
active gene within) and transcribe it into mRNA (remember, the
mRNA has the codons). Translate the mRNA into a polypeptide so
you know the original gene product. Next determine what type of
mutation the mutants are by comparing the original DNA strand
and the mutant DNA. You will need to use a codon chart (pg307)
for help. MIND THE START & STOP CODONS!!!
•
Mutation Detection
Original “given” DNA sequence
GGCTACGAGCTTCGAAATTTGCCGATCCCA
1. (5 pts) First identify the start sequence in the DNA
above. Transcribe the DNA into mRNA & group into 3’s
until you reach the stop codon. Use the codon chart on
pg 307 to identify any changes in amino acids.
Translate the mRNA into a polypeptide chain. Use this
to compare to the mutants.
2. Mutant one: Mutation type? (3) Where? (1) Give
support! (1)
GGCTACGAGCTTCGAAAATTTGCCGATCCCA
Gene
TAC
GAG
mRNA
AUG
A.A.
MET
Mutation Detection
•
CTT
CGA
AAT
TTG
CCG
ATC
CUC
GAA
GCI
UUA
AAC
GGC
STOP
LEU
GLU
ALA
LEU
ASN
GLY
NONE
Original “given” DNA sequence
GGC[TAC]GAGCTTCGAAATTTGCCGATCCCA
mRNA: AUG CUC GAA GCU UUA AAC GGC Stop
Polypeptide: Met Leu Glu Ala Leu AsP Gly Stop
1. (5 pts) First identify the start sequence in the DNA above.
Transcribe the DNA into mRNA & group into 3’s until you reach
the stop codon. Use the codon chart on pg 307 to identify any
changes in amino acids. Translate the mRNA into a polypeptide
chain. Use this to compare to the mutants.
2. Mutant one: Mutation type? (3) Where? (1) Give support! (1)
GGCTACGAGCTTCGAAAATTTGCCGATCCCA
Mutant one: FRAMESHIFT the original reading frame is affected
GGCTACGAGCTTCGAAAATTTGCCGATCCCA…
AUG CUC GAA GCU UU[U] AAA CGG CUA GGG U
mRNA: AUG CUC GAA GCU UUA AAC GGC Stop ORIGINAL
Polypeptide:Met Leu Glu Ala Leu Asp Gly Stop ORIGINAL
New: Met Leu Glu Ala Phe Lys Arg Leu Gly…
The new polypeptide will be MUCH bigger than the original creating a very new gene
product…one that most likely won’t be a useable protein.
•
Mutation Detection
Original “given” DNA sequence
GGCTACGAGCTTCGAAATTTGCCGATCCCA
GGC[TACGAGCTTCGAAATTTGCCGATC]CCA
AUG CUC GAA GCU UUA AAC GGC Stop
1. (5 pts) First identify the start sequence in the DNA above.
Transcribe the DNA into mRNA & group into 3’s until you reach
the stop codon. Use the codon chart on pg 307 to identify any
changes in amino acids. Translate the mRNA into a polypeptide
chain. Use this to compare to the mutants.
2. Mutant one: Mutation type? (3) Where? (1) Give support! (what
is the change in the amino acid sequence…1)
GGCTACGAGCTTCGAAAATTTGCCGATCCCA
Homework (5 points each)
1. Mutant 2: Mutation type? Where? Give support!
GGCTACGAGCTTCGAACTTTGCCGATCCCA
2. Mutant 3: Mutation type? Where? Give support!
GGCTACGAGCCTCGAAATTTGCCGATCCCA
3. Mutant 4: Mutation type? Where? Give support!
GGCTACGACCTTCGAAATTTGCCGATCCCA
Summary: Please Write
The…
• 2 types of DNA mutations
• 5 types of gene mutations
• 5 types of chromosome mutations
•
Mutation Detection: Answers
•
•
•
1.
2.
Original DNA sequence
GGC[TACGAGCTTCGAAATTTGCCGATC]CCA
mRNA:AUG – CUC – GAA – GCU – UUA – AAC – GGC – UAG
A.A.s MET – LEU – GLU – ALA - LEU – ASP – GLY – STOP
Identify the reading frame by transcribing the DNA &
identifying the start codon. Then group the codons in 3’s until
you reach the stop codon.
Mutant one: FRAMESHIFT the original reading frame is affected
GGCTACGAGCTTCGAAAATTTGCCGATCCCA…
UUU – AAA – CGG – CUA – GGG 
MET – LEU – GLU – ALA – PHE – LYS – ARG – LEU – GLY
Homework
1. Mutant 2: NONSENSE an internal stop codon is inserted
GGCTACGAGCTTCGAACTTTGCCGATCCCA
MET – LEU – GLU – ALA – STOP
2.
Mutant 3: MISSENSE a new amino acid is made with the mutation
GGCTACGAGCCTCGAAATTTGCCGATCCCA
MET – LEU – GLU – ALA – GLU  GLY
3.
Mutant 4: SILENT the gene isn’t affected as GAC & GAG both code for the
same amino acid GGCTACGACCTTCGAAATTTGCCGATCCCA
MET – LEU – GLU – ALA – LEU  LEU
Assignment Rubric
Number of
points
5
4
3
2
1
Correctly
identifies the
mutation (3
points).
Correctly
identifies the
mutation
location.
Correctly
gives
support.
Correctly
identifies the
mutation (3)
and one of
the following:
identifies the
mutation
location (1) or
gives correct
support (1).
Correctly
identifies the
mutation (3)
OR identifies
the mutation
location AND
gives correct
support.
Correctly
identifies the
location of
the mutation
(1) AND
gives support
(1).
Identifies the
location of
the mutation
(1) OR gives
correct
support (1).
Assignment is worth a total of 25 points. 5 points are awarded per question. The
first question the student must identify the start codon (1). Transcribe the DNA into
mRNA (1) until they reach the stop codon (1). Then translate the mRNA into a
polypeptide chain (1).
Group “Think-Pair-Share”
What causes mutations?
• (1 min) First, think about what things in
the environment that could cause
mutations. List 5 possibilities.
• (1 min) Next, share with your partner
and come up with a list of 5 things that
could cause mutations.
• (1 min) Finally, share with your group
and come up with a consensus list of 5
possibilities.