Biology Teach Yourself Series - VCE Unit 3 & 4 biology - Home

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Biology Teach Yourself Series

Topic 11: Mutations

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Mutations ........................................................................................................................................................... 4

Initial terminology .......................................................................................................................................... 4

As it appears in Unit 4 ................................................................................................................................ 4 Somatic and germ line mutations ................................................................................................................... 5

As it appears in Unit 4 ................................................................................................................................ 5 Overview of somatic mutations ......................................................................................................................... 5

Review Questions .................................................................................................................................. 6 The link between DNA, proteins and mutations ............................................................................................ 7

As it appears in Unit 4 ................................................................................................................................ 7 Revising the genetic code ............................................................................................................................... 7

As it appears in Unit 4 ................................................................................................................................ 7 Review Questions .................................................................................................................................. 8

Point mutations ............................................................................................................................................... 9

As it appears in Unit 4 ................................................................................................................................ 9 Silent mutations .............................................................................................................................................. 9

As it appears in Unit 4 ................................................................................................................................ 9 Missense mutations ........................................................................................................................................ 9

As it appears in Unit 4 ................................................................................................................................ 9 Nonsense mutations ........................................................................................................................................ 9

As it appears in Unit 4 ................................................................................................................................ 9 Review Questions ................................................................................................................................ 10

What is the effect on the protein? ................................................................................................................. 11

As it appears in Unit 4 .............................................................................................................................. 11 Review Questions ................................................................................................................................ 11

The human genome project .......................................................................................................................... 12

As it appears in Unit 4 .............................................................................................................................. 12 Detection of molecular mutations ................................................................................................................ 12

As it appears in Unit 4 .............................................................................................................................. 12 Review Question .................................................................................................................................. 13

Frame shift mutations ................................................................................................................................... 14


Mutations involving sections of chromosomes ............................................................................................ 15

As it appears in Unit 4 .............................................................................................................................. 15 Review Question .................................................................................................................................. 16

Mutations involving whole chromosomes: Aneuploidy .............................................................................. 17

As it appears in Unit 4 .............................................................................................................................. 17 Mutations involving whole chromosomes: Polyploidy ................................................................................ 18


Detecting chromosomal mutations ............................................................................................................... 20

Contents


Review Questions ................................................................................................................................ 20 Solutions to Review Questions ........................................................................................................ 22


Mutations A mutation is a change in the genetic material of a cell. It may result in a change to an organism’s phenotype. Mutations are generally thought of as being harmful as they often decrease an individual’s ability to function and survive. However, they can also be neutral (have no effect) or have a beneficial effect, increasing an organism’s ability to function and survive.

Initial terminology As it appears in Unit 4 There are several terms that you need to be aware of. These relate to the type, cause and description of mutations. Molecular mutations: (also called gene mutations) are changes to the DNA sequence that have gone uncorrected. Chromosomal mutations: the structure or arrangement of one of more chromosomes has been altered. This includes mutations involving chromosomal fragments, individual chromosomes or whole sets of chromosomes. Spontaneous mutations: these are mutations that occur for no reason that we are currently aware of. There is no causative agent involved. Induced mutations: these mutations occur as a result of exposure to mutagenic environmental factors such as gamma rays, UV light and a variety of chemicals such as asbestos. Somatic mutations: these are either molecular or chromosomal mutations that occur in the somatic (body) cells. Somatic mutations are not inherited. Germ line mutations: these are either molecular of chromosomal mutations that occur in the germ line cells (gametes). A germ line mutation can be passed onto the next generation. Mutagens: these are chemicals or environmental factors that increase the chance of a mutation occurring. There are 4 groups of mutagens:

• Some viruses • Ionising radiation such as X rays. • Alcohol and other dietary inputs • Poisons and chemicals


Somatic and germ line mutations As it appears in Unit 4 Overview of germ line mutations

Overview of somatic mutations

There is an existing mutation in either the sperm or the ova

Fertilisation occurs

The fertilised cell doubles many times by mitosis.

All of the cells in the zygote have the mutation. This organism will pass on the mutation to their offspring.

Neither the sperm or ova have any mutations.

Fertilisation occurs

The fertilised cell doubles many times by mitosis

During the doubling process a mutation occurs in one of the cells.

Any daughter cell of the cell with the mutation will also have the mutation. The other cells will not.


Review Questions

1. A person is born with a birthmark on their face (the skin appears redder than the surrounding skin). Is

this an example of a germ line mutation or a somatic mutation? Provide a reason to justify your answer. _________________________________________________________________________________ _________________________________________________________________________________

_________________________________________________________________________________ _________________________________________________________________________________

2. Which type of mutation is considered to be more serious? Provide a reason to justify your answer.

_________________________________________________________________________________ _________________________________________________________________________________

_________________________________________________________________________________

_________________________________________________________________________________

_________________________________________________________________________________


The link between DNA, proteins and mutations As it appears in Unit 4 Although mutations occur at a molecular or chromosomal level the impact of the mutation is seen in the phenotype of the individual. The reason for this is that genes code for proteins. The phenotype of an individual is caused by the expression of the proteins.

Revising the genetic code As it appears in Unit 4 Information about the genetic code was previously covered in topic 10 but is relevant here as well. When reading the codon table you always start from the left, then go across the top and then read from the right. It is important to remember that the codon table is all about translation. It shows the mRNA codon and the amino acid it codes for. Sometimes in an exam you will be given either a DNA sequence or tRNA data so you need to make sure that you have read the question correctly.

U C A G

U

UUU

UUC

UUA

UUG

Phe

Phe

Leu

Leu

UCU

UCC

UCA

UCG

Ser

UAU

UAC

UAA

UAG

Tyr

Tyr

Stop

Stop

UGU

UGC

UGA

UGG

Cys

Cys

Stop

Trp

U

C

A

G

C

CUU

CUC

CUA

CUG

Leu

CCU

CCC

CCA

CCG

Pro

CAU

CAC

CAA

CAG

His

His

Gln

Gln

CGU

CGC

CGA

CGG

Arg

U

C

A

G

A

AUU

AUC

AUA

AUG

Ile

Ile

Ile

Met

ACU

ACC

ACA

ACG

Thr

AAU

AAC

AAA

AAG

Asn

Asn

Lys

Lys

AGU

AGC

AGA

AGG

Ser

Ser

Arg

Arg

U

C

A

G

G

GUU

GUC

GUA

GUG

Val

GCU

GCC

GCA

GCG

Ala

GAU

GAC

GAA

GAG

Asp

Asp

Glu

Glu

GGU

GGC

GGA

GGG

Gly

U

C

A

G


Remember when you do a translation exercise it is important to be able to see the codon. If you are provided with a sequence like this

AUGGACCUUCAAA….. it is always a good idea to draw a line between each of the codons so you are less likely to make a mistake as shown below:

AUGGACCUUCAAA…….

Review Questions

3. Identify what will be produced when the following codons are read: GAU _____________________ AUA__________________________ UCU _____________________ UGG__________________________

4. Identify the amino acid sequence that will be produced when the following mRNA sequence is read.

AUGGACCUUCAA

__________________________________________________________________________________ The following information shows a section of an exon. The sequence of both DNA strands is shown; the leading strand is shown in bold.

TACGATACCCGAGCA ATGCTATGGGCTCGT

5. Identify the amino acid sequence that will be produced in this example.

__________________________________________________________________________________


Point mutations As it appears in Unit 4 Point mutations are also known as substitution mutations. They occur when a single nucleotide is changed to a different nucleotide. The consequences vary from having no effect on the protein to having a substantial effect. There are three categories of substitution mutations: silent, missense and nonsense mutations. In an exam you should refer to each of them as a point or substitution mutation.

Silent mutations As it appears in Unit 4 This type of mutation occurs if the codon has been changed but the amino acid remains the same (this is an example of the genetic code being redundant or degenerate). For example, if UAU was changed to UAC then both codons still code for tyrosine (Tyr) so there would be no change to the structure of the protein or its ability to carry out its function.

Missense mutations As it appears in Unit 4 This type of mutation occurs if the codon has been changed and as a result the amino acid is changed. For example if UAU was changed to UGU the amino acid that would be added would be Cysteine (Cys) instead of tyrosine. Changing one amino acid means that the primary structure of the protein has also been altered; this will affect all of the other structural levels. This means that the protein is less likely to fulfill its function.

Nonsense mutations As it appears in Unit 4 This type of mutation occurs if the codon has been changed from a codon that codes for an amino acid to a stop codon which codes for a release factor. For example, if UAU were changed to UAA this results in the placement of the release factor instead of the amino acid. The result is a truncated (shortened) protein which will not fulfill its function.


Review Questions

6. Produce a flow chart diagram showing the difference between the three outcomes of substitution

mutations.

7. A sequence of DNA is initially ATGCTATGGGCTCGT but is then altered to ATGCTATGAGCTCGT. What type of mutation has occurred? Give a reason for your answer.

__________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________

SUBSTITUTION MUTATION: One nucleotide is changed to another


What is the effect on the protein? As it appears in Unit 4 This is a fairly common question on a Unit 4 examination paper. In order to answer this question fully you need to make the following points:

• The original codon codes for amino acid X. • The altered codon codes for amino acid Y (or a release factor depending on the codon). • The primary sequence of the protein is changed (describe how). • As a result the ability of the protein to function is either affected or unaffected depending on the type

of mutation. Sample question: The original mRNA sequence is AUGGACCUUCAAAGAGGGCAG. Explain what will happen if the 8th nucleotide is altered from U to C. Sample answer The original codon codes for Leu, the altered codon codes for Pro. As a result the primary sequence of the protein differs by one amino acid, affecting its overall shape and making it less likely that it will fulfill its function.

Review Questions

8. Establish the amino acid sequence that will be produced when the following sequence is translated.

AUGGACCUUCAAAGAGGGCAG

__________________________________________________________________________________

9. Explain the effect on the protein if the 6th nucleotide is changed from C to U.

__________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________

10. Explain the effect on the protein if the 10th nucleotide is changed from C to A.

__________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________


11. Explain the efffect on the protein if the 16th nucleotide is changed from G to A.

______________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________

The human genome project As it appears in Unit 4 The goal of the human genome project was to establish the base sequence of an entire human genome. This project was completed in 2003. The project is significant in a number of ways. In particular it allows the identification of molecular mutations in individuals.

Detection of molecular mutations As it appears in Unit 4 One of the methods of detecting molecular mutations is by the use of restriction enzymes and electrophoresis as covered in topic 11 (molecular biology). Restriction enzymes recognise, bind to and cut specific DNA sequences. If the sequence of DNA is altered an existing recognition site may be removed or a new restriction site may be added. Once the DNA has been exposed to a restriction enzyme the fragments are loaded into an electrophoresis gel and the results are then used to determine whether there is a mutation or not. For example, Gene X is 2500bp long. It normally has a restriction site for the restriction enzyme EcoRI at the 400bp point.

ENZYME SOURCE RECOGNITION SEQUENCE

FRAGMENTS PRODUCED

EcoRI Escherichia coli 5’ GAATTC 3’ CTTAAG

5’ G AATTC 3’ 3’ CTTAA G 5’

The piece of DNA would be cut like this: This means that when the DNA is exposed to the enzyme two fragments will be produced, one 400bp long and one 2100 bp long.

400bp


In the mutated form of gene X an alteration has occurred as follows:

5’ GAATTC 5’ GACTTC 3’ CTTAAG 3’ CTGAAG

When the mutated gene is exposed to EcoRI there will only be one fragment; 2500bp.

Review Question

12. Explain why two fragments are produced when the normal gene is exposed to EcoRI and only one

fragment is produced when the mutated gene is exposed to EcoRI.

______________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Now the 2 sets of fragments would be run on an electrophoresis gel. It would look roughly like this: You can see that the band pattern in the electrophoresis gel can be used to detect which individual has the mutation and which individual does not.

Normal gene

2500bp

400bp

2100bp

Mutated gene

Negative end

Positive end


Frame shift mutations As it appears in Unit 4 Frameshift mutations are a type of point mutation where a nucleotide is either added or removed. The term “reading frame” refers to the fact that mRNA is read one codon at a time.

UUU AGG CCA GUC AUA GGA CAA As each codon is read the appropriate amino acid is brought in to join the growing chain. In this case the amino acid sequence would be: Phe Arg Pro Val Ile Gly Gln In a particular mutation the 6th nucleotide is removed like this:

UUU AGG CCA GUC AUA GGA CAA

UUU AG CCA GUC AUA GGA CAA

As a result all of the nucleotides after this point move up one, like this:

UUU AGC CAG UCA UAG GAC AA…. The sequence of codons or reading frame has been changed. The sequence of amino acids will now be: Phe Ser Gln Ser Stop

Remove


Review Questions

13. Identify what will happen to the sequence of amino acids if the following insertion is made?

UUU AGG CCA GUC AUA GGA CAA __________________________________________________________________________________

14. Identify the type of mutation shown in question 11. __________________________________________________________________________________

15. Which type of gene mutation is most likely to have the greatest effect on a protein? Provide a reason for your choice.

__________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________

Mutations involving sections of chromosomes As it appears in Unit 4 These mutations tend to occur as a result of the chromosomes moving and coiling around each other during meiosis, particularly during crossing over. Deletions: these occur when a chromosome breaks into three pieces and the middle section falls out. As a result the chromosome is shorter than it should be and the genes on the removed fragment are lost. This type of mutation either has serious effects or is frequently fatal.

Insert an A at this point

A B C D E F G H

G H

C D E

A B

Break points

Fragments

Original chromosome

A B

G H

Missing fragment

Resultant chromosome

C D E

+


Inversions: during crossing over a fragment becomes detached and rotates through 180°. Translocations: when crossing over occurs two sister chromatids exchange genetic information. Translocation occurs when the fragment from one chromosome ends up on a completely different chromosome e.g. a fragement from chromosome 1 may end up on chromosome 12.

Review Question

16. Draw and label a diagram showing what happens as a result of translocation. Duplication: this occurs when a chromosome replicates in such a way that segments of the gene repeats. It can also happen during crossing over when one sister chromatid ends up with two copies of the material that should have been exchanged. Review Question

17. Of the four types of mutations mentioned, which one would you expect to have the least effect on an individual? Provide a reason for your answer.

______________________________________________________________________________

__________________________________________________________________________________ __________________________________________________________________________________

A B C D E F G H

Break point

AB

BA

BA C D E F G H

Original chromosome

Resultant chromosome


Mutations involving whole chromosomes: Aneuploidy As it appears in Unit 4 These mutations occur as a result of an error that occurs during cell division. During meiosis homologous pairs of chromosomes come together and then segregate into different daughter cells. Sometimes the chromosomes do not separate. This is called non-disjunction. As a result some daughter cells have insufficient chromosomes and some have too many. This is called aneuploidy, which means the individual does not have an exact multiple of the haploid number. This diagram is an overview of what should happen during meiosis. If an individual has three copies of a chromosome this is called trisomy e.g. a common cause of Down syndrome is when people have three copies of the 21st chromosome; Down syndrome is also called trisomy 21.

Tetraploid cell after DNA replication has occurred.

Two diploid intermediate cells

Four haploid daughter cells


This diagram is an overview of non disjunction. Daughter cells 1 and 2 have too many chromosomes (n + 1) and daughter cells 3 and 4 have insufficient chromosomes (n – 1). All of the offspring of this parent will be aneuploid.

Mutations involving whole chromosomes: Polyploidy As it appears in Unit 4 Sometimes cell division goes completely wrong. Instead of one pair of chromosomes failing to separate, the entire set fails to separate. If an individual has one or more complete sets of chromosomes they are referred to as being polyploid. If a diploid gamete fuses with a normal haploid gamete the offspring will be triploid (3n). If a diploid gamete fuses with another diploid gamete then the offspring will be tetraploid (4n).

Tetraploid cell after DNA replication has occurred.

One pair of chromosomes fails to separate.


Review Questions

18. Identify whether the following are aneuploid or polyploid.

i. A pollen nuclei fertilises 2 combined haploid polar bodies.

__________________________________________________________________________________

ii. A man has a condition called Klinefelters syndrome. He has 2 copies of the X chromosome and 1 copy of the Y chromosome.

__________________________________________________________________________________

19. Occasionally “metafemales” are produced. These women have 3 or 4 copies of the X chromosome. Explain how a metafemale with 3 X chromosomes could be produced.

_________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________

20. Explain the difference between a molecular mutation and a chromosome mutation. __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________


Detecting chromosomal mutations As it appears in Unit 4 The majority of the chromosomal mutations mentioned are the result of an observable change in the structure of a chromosome or in the numbers of chromosomes present. Karyotypes are “chromosome maps”. The chromosomes of a dividing cell (usually a white blood cell in the metaphase stage of mitosis) are dyed and viewed under a microscope. The image is then photographed and enlarged giving a picture of the individual chromosomes, which can be cut up and matched based on the size of the chromosome, the location of the centromere and the banding pattern. Karyotyping may be performed on foetuses. Amniotic fluid contains some foetal cells which can be analysed.

Review Questions

21. The diagram below shows an example of a karyotype.

Is this individual euploid, aneuploid or polyploid? Provide a reason to support your answer. __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________


A translocation occurs in a person where the very small chromosome 21 is attached onto chromosome 15. Normally this person would have two copies of chromosome 15 and 2 copies of chromosome 21. However, as a result of the mutation they have one chromosome 15, one chromosome 21 and and a chromosome 15/21. Normal individual Individual with chromosomal mutation.

22. What type of mutation has occurred in this example?

__________________________________________________________________________________

23. Would you expect the individual with the mutation to have a normal phenotype? Explain why or why

not. __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________

24. There are four possible gametes that can be produced by this individual. Identify the combinations of chromosome in each possible gamete. Gamete 1 Gamete 2 Gamete 3 Gamete 4


Solutions to Review Questions 1. This has to be an example of a somatic mutation because only some cells are affected. . 2. Germ line mutations are considered to be more serious generally because somatic mutations only affect

the person with the mutation but germ line mutations can be passed on through several generations.

3. GAU = Asp AUA = Ile UCU = Ser UGG = Trp

4. Met Asp Leu Gln

5. To answer this question you need to work out the mRNA sequence from the leading strand.

This sequence will be: AUG CUA UGG GCU CGU which means that the amino acid sequence will be: Met Leu Trp Ala Arg

6. The flow chart should look like this:

SUBSTITUTION MUTATION: One nucleotide is changed to another.

SILENT MUTATION The altered codon still codes for the same amino acid. There will be no effect on the structure or function of the protein.

MISSENSE MUTATION The altered codon codes for a different amino acid. The primary sequence of the protein will be different and it is less likely that the protein will fulfil its function.

NONSENSE MUTATION The altered codon is a stop codon which codes for a release factor. The protein will be shorter than normal and will not fulfil its function.


7. This is an example of a point mutation. The 9th nucleotide has been changed from G to A.

8. Met Asp Leu Gln Arg Gly Gln.

9. The codon changes from GAC to GAU, both codons code for the amino acid Asp so there is no change to the structure of the protein and therefore no change to its function.

10. The codon has changed from CAA to UAA which is a stop codon which codes for a release factor. The

result is a shortened protein which is non-functional.

11. The codon has changed from GGG to AGG, so the amino acid has been changed from Gly to Arg. The primary sequence of the protein has been altered. As a result the altered protein is less likely to fulfill its function.

12. The normal gene has a recognition site for EcoRI which the enzyme is able to bind to and cut, resulting

in the production of two fragments. In the mutated gene the sequence has been altered so there is no longer a recognition site for EcoRI to bind to. As a result the DNA sequence is not cut so there is only one fragment.

13. The altered sequence will be:

UUU AGG CCA AGU CAU AGG ACA A……

14. This is a frame shift mutation.

15. A frameshift will have the greater effect. Point mutations generally only affect one amino acid in a

protein, however frameshift mutations will affect all of the amino acids after the mutation point.

16. The diagram should look like this:

17. The inversion mutation has the least effect because the chromosome with the inversion still has an entire complement of genetic material; nothing has been lost or gained.

18. As follows: i. Polyploid: the cell will have three copies of each chromosome. ii. Aneuploid. This man will have 47 chromosomes instead of 46.

1 2 3 4 5 6 7 8

ABC

The original chromosome is labeled 1 to 8, the top section labeled ABC is from a completely different chromosome.


19. Metafemales, like all aneuploid individuals, are the result of non-disjunction occurring during meiosis. A gamete from one of the parents contains two copies of the X chromosome and when it fuses with the other gamete, the result is a zygote with three copies of the X chromosome.

20. A molecular mutation is a mutation that occurs at the nucleic acid level which generally results in a

change to the protein.

A chromosomal mutation involves a change to a chromosomal segment or entire chromosomes, so many proteins will be affected.

21. This individual is aneuploid as they have three X chromosomes.

22. Translocation.

23. Yes, because there are still two copies of both chromosomes in every diploid cell.

24. The possibilities are:

Gamete 1: Chromosomes 21 and 15 Gamete 2: Chromosome 21 and 15/21 Gamete 3: Chromosome 15 and 15/21 Gamete 4: Chromosome 15/21 only It doesn’t matter which order you write these in as long as you have all of the combinations shown above.

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