Download Variation – Mutations

1.3 Genome:
(b) i Point mutations: nucleotide substitution, insertion and deletion
(b) Mutation
Mutations are random changes in the genome.
Mutations can alter alleles, genes, gene expression or chromosomes.
(i) Point mutations: nucleotide substitution, insertion and deletion
Mutation within genes and impact on protein structure.
Regulatory sequence mutations can alter gene expression.
Splice site mutations can alter post-transcriptional processing.
Importance of point mutation in evolution.
MUTATIONS
A mutation is defined as a change in the structure or quantity of genetic material in an organism.
Mutations are:
 Spontaneous
 Random
 Rare events
BAD:
Most mutations are harmful.
GOOD:
1. Mutations result in the variations that create a heterozygous genotype
and allow a population to adapt to a changing environment.
2. Harmful mutations tend to be eliminated from a population by natural
selection against them.
3. Most mutations are recessive and are therefore not expressed until two
occur together in the homozygous recessive individual. When such a
change occurs and the individual expresses the mutation in the
phenotype that individual is known as a mutant.
The rate at which mutations occur can be increased by using mutagenic agents.
Examples of mutagenic agents:


Certain chemicals e.g. lead oxide, mustard gas
Radiation e.g. UV-light, x-rays and gamma rays.
Experiment: Aim to compare the germination of cress seeds or growth of yeast cultures in response to
mutagenic agents
Types of Mutations
There are 3 types of mutations. These are:



Gene Mutations/point mutations.
Changes in the chromosome number
Changes in the structure of one chromosome
Gene mutations (point mutations)
Gene mutations involve a change in one or more nucleotides on one DNA strand, which change gene
structure.
One amino acid change can have a huge effect on the protein shape. In the following messages each letter
represents a nucleotide.
This shows the normal order of the bases for one of the strands in the
area highlighted in the DNA molecule.
Only one DNA strands is involved in protein synthesis. A change from the
normal order of bases leads to different types of gene mutation.
Substitution: One base out and another swapped in.
Insertion: One base added in to the sequence causes a frame shift.
Deletion: One base is deleted from the sequence causing a frame shift
Inversion: Two bases swap position with the base immediately
adjacent
Sometimes the point mutation only affects one gene e.g. Substitution and Inversion. The effects are less lethal
as there is more than one gene for each amino acid. Therefore the effects only show in the phenotype if the
original sequence was for an essential amino acid.
Example: Sickle cell anaemia
The diagram above
shows the difference
in the synthesis of
haemoglobin in
normal DNA and
abnormal DNA. The
top strand shows the
normal DNA, mRNA
and amino acid
sequences.
A single substitution mutation has changed the base sequence in the DNA. The base
sequence on the mRNA produced by the DNA is altered.
As a result, a codon on the
mRNA is altered. A different
amino acid is inserted into the
protein chain. The amino acid
valine is inserted instead of
glutamic acid, which is shown
by the bottom strand of DNA.
The protein synthesised is
altered and no longer functions normally. These sequences result in sickle-shaped red blood cells. This blood disorder
is known as sickle cell anaemia.
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Phenylketonuria
The diagram represents part of the normal metabolic pathway involving the
amino acid phenylalanine within human cells. The gene controls the synthesis
of the enzyme and the enzyme converts the amino acid phenylalanine to
tyrosine.
If a gene mutation occurs then individuals with this mutation can no longer
produce the normal enzyme. This in turn means that they can no longer
convert phenylalanine to tyrosine. The failure to bring about the normal
enzyme conversion is called a metabolic block.
In newly born babies this metabolic block leads to the condition phenylketonuria (PKU).
The effects of the condition if undetected and treated at birth are that:



phenylalanine concentration builds up within the body of the new born baby
phenylaline is converted into toxic substances
the toxic substances cause irreversible damage to the developing brain
FRAMESHIFT
Due to the triplet nature of gene expression by codons, the insertion or deletion can result in a FRAMESHIFT.
A frameshift is a change in the reading frame (the grouping of the codons). This means all of the triplet
sequences after the mutation are changed resulting in a completely different translation from the original.
Mutations resulting in a frame shift are lethal.
Results of frameshift:
1. The earlier in the sequence the deletion or insertion occurs, the more altered the protein.
2. The reading of the codons after the mutation to code for different amino acids.
3. The first stop codon ("UAA", "UGA" or "UAG") encountered in the sequence could be altered.
4. The polypeptide being created could be abnormally short or abnormally long, and will not be functional.
Frameshift mutations are apparent in severe genetic diseases such as Cystic Fibrosis; they increase
susceptibility to certain cancers.
QUESTIONS
1. Complete the following diagram on the next page by inserting the appropriate letters (normal and mutant
mRNA).
Normal
Mutant
DNA
Transcription
C T T
C A T
mRNA
Substituted
nucleotide
Translation
Amino Acids
Glutamic acid
new amino acid
b. Complete the following sentence:
The example of a gene mutation, shown above, is called ________________. It is where one
_________________ is replaced by a different _________________.
c. How will this mutation affect the protein molecule produced?
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2. Complete the diagram by inserting the normal and mutant mRNA and add in
the names of amino acids made (use the wheel diagram in your notes).
DNA
A
Normal
Mutant
A GAGT C GG G GAT
A GAT G CG GG GAT
Transcription
mRNA
AA
Translation
Amino
Acids
a) Complete the following sentence:
The example of a gene mutation, shown above, is called gene ________________.
It is where _____________________________________.
b) What effect does this mutation have on the amino acids in the protein molecule?
3. Complete the diagram by inserting the normal and mutant mRNA and add in the names of amino acids
made:
Normal
Mutant
DNA
AGAG T CG GG GA T
A
Transcription
mRNA
Translation
AA
Amino
Acids
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AGA GTT C GGG GA
a) Complete the following sentence:
The example of a gene mutation, shown above, is called gene ________________.
It is where _____________________________________.
b) What effect does this mutation have on the amino acids in the protein molecule?
4. Complete the diagram by inserting the normal and mutant mRNA and add in
the names of amino acids made:
Normal
Mutant
DNA
AGAG T CG GG GA T
A
Transcription
AGA TC GG GG A TG
mRNA
AA
Translation
Amino
Acids
a) Complete the following sentence:
The example of a gene mutation, shown above, is called gene ________________.
It is where _____________________________________.
b) What effect does this mutation have on the amino acids in the protein molecule?
Learning objectives
The three types of mutations you need to know about are nucleotide substitution, insertion and deletion.
By completing this exercise you should understand how these mutations affect p rotein structure.
This exercise uses the analogy of simple text to show you how different types of point mutations can impact
on the final product: in this example it is if the sentence makes sense rather than the structure of a protein
that is being examined.
Copy out the following three examples of text. Each word represents a triplet of bases, or codon, which
codes for a different amino acid. To help you visualise the protein coding sequence the codons have been
placed in a table, or reading frame. The part of the gene that codes for protein is referred to as the open
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reading frame.
Example 1
Original
the
Mutation The
old
olb
man
dma
ran
nra
for
nfo
the
rth
red
ere
bus
dbus
Example 2
Original
the
Mutation the
old
olm
man
anr
ran
anf
for
ort
the
her
red
edb
bus
us
Example 3
Original
the
Mutation The
old
old
man
nan
ran
ran
for
for
the
the
red
red
bus
bus
1. For each example highlight or circle where the mutation has occurred.
2. For each example say whether it is a substitution, deletion an d insertion.
3. Explain which has the greatest effect on the meaning of the sentence (or which would have the
greatest effect on the final protein sequence).
4. Which mutations are frame-shift mutations? Explain why.
In a real gene there are potentially a number of regulatory sequences of DNA and possibly several exons on
a chromosome that could be damaged, or changed, by a mutation. Post transcription there could be failure
of exons to be correctly spliced, with huge consequences on the translation of the mRN A.
If a lethal or very damaging mutation occurs then the mutation will be removed from the gene pool or the
chances of the mutated gene being reproduced will be less than that of the gene from an unaffected
individual. In other words, essential genes and their expression are under stiff selection pressure to remain
functional, hence they are conserved within a species and across species.
5. Explain why most single nucleotide polymorphisms, or point mutations, are found within
…..non-coding regions of the genome.
Research-based extension task
Within a DNA sequence several different codons can code for the same amino acid so a single base
substitution may not result in the amino acid being changed, ie the protein would be normal.
This is known as a silent mutation.
A substitution may result in only one amino acid being changed without any major effects on the protein
structure and hence function. However, if the mutation occurs at a critical point in the sequence, an amino
acid vital in determining the proteins shape will no longer stabilise the protein and it will lose its function.
This is a missense mutation.
Nonsense mutations introduce a stop codon early in the sequence, resulting in a shortened, usually non functional, protein.
Mutations which do not have any effect on the protein’s function are also known as neutral mutations.
1. Can you find real-life examples of genetic disorders caused by missense, nonsense or frame -shift
point mutations?
2. What is the frequency of these mutations?
3. Are any of the mutations confined to a specific area or ethnic race?
4. What are the symptoms associated with each mutation?
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5. Are any of the mutations beneficial or are they detrimental?
Look at this video clip: Embryo hope for inherite d diseases: http://news.bbc.co.uk/1/hi/health/8621046.stm
Present your results in the form of a spider diagram.
In the centre of the page put a short appropriate
title. Use colours to group information around the
title. Each outer branch should have at least one
diagram. Do not cut and paste text – write in your
own words.
Sickle cells
Red blood
cells
Why not start with sickle-cell trait?
Chromosome Mutations
Chromosome mutations involve the change in the structure of one chromosome; they involve a change in the
number or sequence of genes in a chromosome.
The following are 4 types of chromosome mutations:
1. Inversions
2. Deletions
3. Translocations
4. Duplications.
Table summarising chromosome mutations. Each gene on a chromosome is given a letter or number.
Normal chromosome Mutation type
Deletion
Translocation
12345678
Inversion
Duplication
Altered chromosome
1234678
Gene 5 is missing
12345678 + ABCDE = 12345 + ABCDE678
One section of chromosome joins to another chromosome
12543678
A segment of chromosome breaks off, turns around and joins
again
1234565678
Sets of genes become repeated
Effects
Terminal
or
harmful
May be
beneficial
EXAMPLES OF CHROMOSOME STRUCTURE MUTATIONS:
1. Deletion on chromosome 5: results in Cri du Chat Syndrome:
Symptoms: Severe learning difficulties, small head, widely spaced eyes and distinctive cry
2. Translocation: Results in problems during gamete formation, resulting in
non-viable gametes or cancer
3. Duplication:
- Formation of the 4 sub-units of haemoglobin
New DNA sequences means increased selective advantage.
4. Inversion: Results in problems during gamete formation, resulting in viable offspring which may have benificail
characteristics
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QUESTIONS ON CHROMOSOME MUTATIONS
Each of the diagrams, represent a type of chromosome mutation.
For each, name the type of mutation and briefly describe what has happened.
MUTATION TYPE:_________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
MUTATION TYPE:_________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
MUTATION TYPE:_________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
MUTATION TYPE:_________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
___________________________________________
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_____________________________
Chromosome mutations1. Change in the structure of a chromosome due to a change in the number/order of the genes i.e
translocation, inversion, duplication and deletion (TIDD)
2. Can be a change in chromosome number due to spindle failure during meiosis.
Changes in the number of chromosomes within a cell
Normally during meiosis (gamete formation), homologous chromosomes come together and then segregate
into separate cells. The gametes therefore end up with one of each type of chromosome.
Non-Disjunction
This is a chromosome mutation caused by spindle failure.
Non-disjunction results in the addition or loss of one or more chromosome.
Changes in chromosome number occur when the spindle fibres fail to form properly which prevents the separation
of the chromosomes during meiosis. This may effect one chromosome e.g. Down's Syndrome, or may be
complete spindle failure as seen in polyploid plants. Failure of spindle formation is called non-disjunction.
Label the diagrams show the difference between normal meiosis and meiosis where non-disjunction has
occurred.
Normal
meiosis
Nondisjunction
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DISEASE EXAMPLE: 1 Down's syndrome
Down's Syndrome is due to non disjunction resulting in an individual
with an extra chromosome 21. The affected individual is mentally
retarded and has distinct physical features.
A karyotype is a display of matching chromosomes showing their
number, form and size.
Look at the karyotypes of a normal individual and a Down's
syndrome individual. Which is which? Underneath each karyotype
comment on whether it is normal or down’s and explain your choice.
Questions:
1. Explain how Down’s syndrome occurs?
2. What is Down's syndrome caused by the presence of?
Non-Disjunction of the sex chromosomes
DISEASE EXAMPLE: 2 Turners's syndrome
No sex chromosome fuses with normal X gamete.
Zygote chromosome complement 2n = 45 (44 + X)
Always female
Infertile as –
ovaries fail to
develop.
Klinefelter’s Syndrome
XX egg fertilised by normal sperm Y, or normal X egg is fertilised by an XY sperm. Zygote formed 2n = 47
(44+XXY).
Individuals are always male and have male organs.
They are infertile – testes develop to half normal
size and fail to produce sperm.
‘Complete’ non-disjunction or polyploidy
This is due to the failure of all spindle fibres during meiosis in a gamete mother cell. This results in 2 gametes which
are diploid and two with no chromosomes.
Complete non-disjunction will result in diploid gametes i.e. they have two of each chromosome instead of one
of each pair (the gametes which gain no chromosomes will die)
Diagram showing complete non-disjunction
Diploid gametes 2n
All chromosomes go
into one cell
Mitotic Division
Meiotic Division
Diploid Gamete
Mother Cell
Gametes without
chromosomes die
If a diploid gamete (2n) fuses with a normal haploid gamete (n) a triploid (3n) individual is
formed. This individual has three sets of chromosomes.
Complete the diagram below by inserting the chromosomes, showing the joining of a ‘2n’
gamete with an ‘n’ gamete where n=2.
2n
gamete
n
gamete

Cell
Division
Sterile
organism
If the diploid gametes are fertilised by a normal haploid gamete a triploid known as a polyploidy plant is produced.
The organism shown above cannot produce gametes and is therefore sterile, as meiosis cannot occur because
homologous pairs cannot be formed.
If two diploid gametes fuse a tetraploid (4n) individual is formed.
chromosomes. It is fertile as they are able to form homologous pairs.
The organism has four sets of
Often these polyploidy plants have an economical advantage, for example they may have/be:





Larger plants
Increased seed and fruit size
Resistance to disease
Increased yield
Hybrid Vigour (better in some way than the parent plants)
Example of Polyploidy
An example of polyploidy is in the species of grass, Spartina townsendii, which is formed by crossing Spartin
stricta and Spartina alterniflora.
Spartina townsendii is fertile but it is formed as a result of the cross between S. stricta and S. alterniflora
which are two different species.
Remember: When two different species are crossed the resulting offspring should not be fertile!
Complete the polyploidy example below by inserting the correct numbers for the haploid and diploid state.
Polyploid example
Spartina stricta
2n=56
N=


Sterile Hybrid
2n=
Spindle failure causing
polyploidy

Spartina townsendii
2n=
n=
Explain why the hybrid is sterile.
Spartina alterniflora
2n=72
n=
Formation of human chromosome 2 and evolution of monkey and homosapiens
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_______________________________________________
_______________________________________________
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Mutations Dictionary
Chromosome mutations-Can be a change in chromosome number due to spindle failure during meiosis. Or a
change in the structure of a chromosome due to a change in the number/order of the genes i.e translocation,
inversion, duplication and deletion (TIDD)
Down’s Syndrome-An example of a chromosome mutation involving a change in the number of
chromosomes. Down’s syndrome individuals have 47 chromosomes instead of 46 due to non-disjunction
happening at pair 21.
Frameshift mutations-Type of gene mutations, which lead to a major change in the gene’s DNA i.e. insertion
and deletion
Gene mutations-type of mutation, which involves a change in one or more of the actual nucleotides in a
strand of DNA. Four types of gene mutation are deletion, insertion, substitution and inversion (DISI)
Karyotype-a display of the complete set of chromosomes (which shows their number, form and size)
Klinefelter’s syndrome-this is a condition that arises when non-disjunction happens in the sex chromosomes.
An XX egg is fertilised by a normal Y sperm then the resulting zygote has the chromosome complement 44 +
XXY. Such individuals are always male and possess male sex organs. However they are infertile.
Mutagenic agents-Factors that can artificially increase the rate of mutation e.g. chemicals (such as mustard
gas) and radiation (gamma rays, X-rays and UV light)
Mutant-When a mutation is actually expressed in the phenotype, the affected individual is called this.
Mutation-A change in the structure or quantity of genetic material in an organism. Mutation is the only
source of new variation
Non-disjunction-this can occur during meiosis and results in gametes with extra/less chromosomes than
normal. During the first meiotic division, spindle failure results in failure to separate a pair of homologous
chromosomes. As in Down’s syndrome
Point mutations- Type of gene mutations which lead to a minor change in the gene’s DNA i.e. inversion and
substitution
Polyploidy-Rare in animals, more common in plants. When all the spindle fibres in a gamete mother cell fail
during meiosis and none of the homologous pairs become separated. Results in gametes with double the
number of chromosomes. Fertilisation of these abnormal gametes results in mutant plants which have
complete extra sets of chromosomes.
Sickle cell anaemia-due to a type of gene mutation called substitution that results in the formation of sickle–
shaped red blood cells. An example of when a point mutation (which is usually not that harmful) can
occasionally cause a major defect
Turner’s syndrome- this is a condition that arises when non-disjunction happens in the sex chromosomes. A
gamete with no X/Y chromosomes is fertilised by a normal X gamete then the resulting zygote has the
chromosome complement 44 + XO. Such individuals are always female and are infertile.
Chromosome and Gene Mutation Questions
1)
2)
With the aid of an example, state clearly the difference between the terms mutation and mutant?
What name is given to the process by which a spindle fibre fails during
meiosis and one or more of the gametes produced receive an extra chromosome?
3a) If a normal human sperm fertilises an egg containing an extra copy of chromosome 21, what is the diploid
number of the zygote formed?
b) What name is given to the condition suffered by a person who develops from an abnormal zygote of
this type?
c) What relationship exists between the age of the mother and the incidence of this condition occurring?
4a) What is meant by the term Polyploidy?
b) Explain how a Polyploid Plant containing 3 separate sets of chromosomes could have arisen?
c) State 2 ways in which polyploid plants can be of an economic importance.
5) State the 4 different chromosome mutations
6)
7)
What name is given to a change that involves a chromosome breaking in two
places and a segment of genes dropping out?
Name the type of change that involves a chromosome breaking in two places and then the affected length
of genes rotates through 180°C before rejoining?
8) Name the type of change that involves a section of one chromosome
breaking off and joining onto another non-homologous one?
9) Name the 4 different gene mutations
10) Classify these four gene mutations into "frameshift" and "point" mutations
11) Is frameshift or point mutations most likely to lead to the formation of a
protein that is greatly changed and non-functional?
12) Name two mutagenic agents?
Variation – Mutations
Activity
State that a mutation is an error in the amount or structure of
genetic material in an organism
State that mutations in nature occur at random and at low
frequency
Define the term ‘mutagen’ and give examples
State that mutations can be grouped under three headings:
1. alteration to the sequence of bases making up a gene
2. alteration to chromosome structure
3. alteration to chromosome number
State that alterations to base sequence can be of 4 types:
Substitution; insertion; deletion; inversion
Describe what is involved in each of the above examples
State the effect of a gene mutation would have on an amino acid
sequence and subsequently a protein
State that alterations to chromosome structure can occur in one
of these ways:
deletion; inversion; duplication; translocation
Describe what is involved in each of the above examples
State that the number of chromosomes in a cell can be altered by
non-disjunction during meiosis/mitosis
Explain what happens to spindle fibres and chromosomes when nondisjunction occurs
Compare the chromosome number of people with & without Down’s
Syndrome
State that polyploidy arises when non-disjunction involves whole
sets of chromosomes because all the spindle fibres fail
State the benefit of polyploidy to crop breeders
Explain what a karyotype is
I can find
this in my
notes
I can do
this