Unit 1: DNA and the Genome Sub-topic 6: Mutation · The mutation could occur within the protein...

CfE Higher Biology Pupil Course Notes

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Unit 1: DNA and the Genome

Sub-topic 6: Mutation


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On completion of this topic I will be able to state that:

mutations are random changes in the genome, causing no protein or an

altered protein to be produced

mutation frequency is low but can be induced by mutagenic agents mutations can be classified as either chromosome or gene mutations

mutations are important in the evolutionary pathway of organisms and can

offer a selective advantage or disadvantage to the organism

single gene mutation results from a change in the DNA nucleotide sequence

single nucleotide substitutions include neutral, missense, nonsense and

splice site mutations

insertion and deletion gene mutation results in frame-shift mutation or

expansion of a nucleotide sequence repeat

regulatory sequence mutations can alter gene expression

splice sites mutations can alter the mRNA mature transcript produced by

affecting the splicing of introns

mutations can cause abnormal replication of repeat sequences which can

result in disease (such as Huntington’s disease)

different chromosome structure mutations are; duplication, deletion,

translocation and inversion

non-disjunction during the separation of chromosomes during cell division can

result in cells with extra chromosomes or whole genome duplications

polyploidy has a beneficial impact on plants especially crops.

Prior Learning for this Topic.

Unit 1.5 Proteins and Enzymes

The variety of protein shapes and different functionality arise from their specific sequence of amino acids.

Unit 3.4 Adaption, natural selection and the evolution of species

a mutation is a random change to genetic material mutations can be neutral, or confer an advantage or a disadvantage on an

organism

mutations are spontaneous and the only source of new alleles environmental factors, such as radiation can increase the rate of mutation.


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The Genome and Mutations

The genome of an organism is its genetic information encoded in DNA. When irreversible changes occur to the genome this changes the genetic code which changes the protein it encodes. Mutations can occur randomly or be induced and can alter alleles, genes, gene expression or the number or structure of the chromosomes. Living cells undergo frequent chemical change especially during replication. Most of these changes are quickly repaired by the cell’s DNA machinery. Those that are not result in mutation.

When a change in the organism’s genotype causes a change to the phenotype the individual affected is called a mutant. Changes in the genetic code due to mutation can lead to genetic variation and are therefore the driving force of evolution. Without mutation there would be no variation, without variation there would be no evolution. Some mutations however have the potential to develop disease.

Mutations could result from:

a change in the genes

or change in the chromosomes

Although mutations can occur naturally they can also be

induced by mutagenic agents such as;

radiation: ganmma rays, X rays, UV rays

high temperatures

chemicals such as colchicine.

Chromosome mutation

Gene mutation

Mutations are changes in the genome that can result in no protein or an

altered protein being expressed.


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Gene Mutations

Single Gene Mutation

The mutation could occur within the protein coding region of a gene causing an

alteration in the type of amino acid coded for, or in one of the DNA sequences

elsewhere on the chromosome that is involved in the regulation of the gene. A gene

mutation at a regulatory gene site could therefore alter the expression of the gene

by resulting in the absence or over production of a protein.

For a protein to function properly it is essential that it has the correct amino acids. If

the nucleotide base sequence is changed, it could change the amino acid coded for

and therefore affect the structure and functionality of the protein produced.

During protein synthesis, DNA is transcribed into mRNA and then translated into

proteins. Any alteration to the nucleotide base sequence most often results in a

different protein or non-functioning protein being synthesised.

If the mutation occurs at a point that affects the regulation of the gene then no

protein is synthesised and this would alter the phenotype. This is outlined in the

diagram below.

Diagram

Single gene mutations involve the alteration of a DNA nucleotide sequence as

a result of the substitution, insertion or deletion of nucleotides.


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Single Gene Mutations

There are different categories of substitution and their names describe the affect

they each have on the protein synthesised.

If the substitution mutation has no effect on the protein produced it is said to be

neutral, whereas others such as; missense, nonsense and splice- site can have a

significant impact on the protein manufactured.

Substitution Mutations

Substitution mutation occurs when one nucleotide base pair is replaced for

another. This affects only one codon. Sickle cell anaemia is a disease that is caused

by a substitution mutation and it’s affect is shown below.

Describe how the type of mutation shown above arises and its effect on the protein

produced:

____________________________________________________________________

____________________________________________________________________

Normal haemoglobin DNA Mutant haemoglobin DNA

Normal haemoglobin Sickle cell haemoglobin


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Generally, substitution causes only a minor alteration to the protein as it only

affects one codon therefore one amino acid. However, if this occurs at a critical

point in the protein then it could cause a major defect. e.g. sickle cell anaemia.

(1) Missense mutation

Missense mutation alters the nucleotide sequence by changing a base pair. This

means that the codon is on the mature transcript is changed and now codes for a

different amino acid. The change may not affect the protein, may be beneficial to

protein function, or may be dangerous e.g. If the codon for leucine CUU is changed

to CCU, the amino acid proline will be produced instead of leucine.

Missense DNA strand DNA strand

mRNA UUUCUUACAAAU mutation UUUCCUACAAAU

amino acid phe leu thr aspn phe pro thr aspn

Why is this type of point mutation called missense?

_________________________________________________________________________

_________________________________________________________________________

(2) Nonsense mutation

This type of mutation alters the nucleotide sequence so that a stop codon is coded

for in place of an amino acid.

A stop codon signals the end of the translation process and stops protein production.

If this process is ended too soon, the amino acid sequence is cut short and the

resulting protein is shorter than it should be. As a result of the missing amino

acids the protein is most often non-functional.

http://biology.about.com/od/cellularprocesses/ss/protein-synthesis-translation.htm


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Nonsense DNA strand DNA strand

mRNA CGUAGUUAUGGC mutation CGUAGUUAAGGC

amino acid gly ser tyr gly gly ser STOP

Explain why this term is used to describe a nonsense mutation?

____________________________________________________________________

____________________________________________________________________

_________________________________________________________________________

How does it affect the protein made?

____________________________________________________________________

(3) Splice- site mutation

From Unit 1.3 you learned that non coding regions of DNA called introns are cut

from the primary transcript of mRNA and the exons are spliced together during

transcription. This forms a continuous mRNA coding sequence of nucleotides in the

mature mRNA transcript. This ensures that the correct amino acids are coded for

and in their correct order to produce the desired protein.

If a mutation occurs at a splice site one or more introns may be left in the

mature mRNA transcript. The altered mRNA code could translate into an

altered protein which is non-functional or doesn’t function correctly. Thalassemia

(type of anaemia) results from a mutation at a splice- site which causes a defect in

the manufacture of the protein haemoglobin.

Explain how a mutation in a splice- site could affect the protein produced.

____________________________________________________________________

____________________________________________________________________


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Frame-shift Mutations

Since the nucleotide sequences are read in groups of three bases (a codon), any

addition or deletion of a base pair will cause a shift in the whole 'reading frame'

of the mature mRNA transcript i.e. every amino acid coded for after the site of the

mutation will be altered. Insertion and deletion both lead to major change in the

protein since each causes a large proportion of the mRNA to be misread. The protein

structure will contain many different amino acids and it is usually rendered non-

functional.

For example, if the original transcribed DNA sequence is CGA CCA ACG GCG ..., if

base G is inserted between the first and second groupings, the reading frame will be

shifted as shown below.

Original sequence:

Amino acids produced:

Base G inserted:

Amino acids produced:

site of mutation

Every codon is altered after the point of the mutation which could result in many

amino acids being changed in the resultant protein. This alters both the structure

and function of the protein.

C G A C C A A C G G C G

Arginine Proline Theonine Alanine

C G A G C C A A C G G C G Arginine Alanine Asparagine Glycine

Nucleotide insertions and deletions result in the frame -shift mutations or

an expansion of the nucleotide sequence repeat.


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Identify the types of frame-shift mutations shown below:

Describe how mutations

Describe how mutations 1 and 2 arise and their effect on the protein produced:

Mutation 1

____________________________________________________________________

____________________________________________________________________

____________________________________________________________________

Mutation 2

____________________________________________________________________

____________________________________________________________________

____________________________________________________________________

Mutation type 1

_____________________

Mutation type 2

__________________

Normal


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Activity: ‘Reading the frame.’

The exercise below uses the analogy of simple text to demonstrate the impact of

different point mutations on the protein produced. Each word represents a triplet of

bases or codon which codes for a particular amino acid. To help you visualise the

protein coding sequence the "codons" have been placed in a "reading frame".

For each example below circle where the mutation has occurred and state the type

of mutation above each example.

Example 1: _________________________

Original the old man ran for the red bus

Mutation the olb dma nra nfo rth ere dbus

Example 2: __________________________


Mutation the old man ran for her edb us

Example 3: _________________________


Mutation the old nan ran for the red bus

Answer the following questions:

Q1) Which type of mutation has the least effect on the meaning of the sentence i.e. if

this was mRNA which example would have the least effect on the final protein

sequence? Give a reason for your answer.

____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________


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Q2) Which of the examples of mutations given are frame-shift mutations? Give a

reason for your answer.

____________________________________________________________________

____________________________________________________________________

____________________________________________________________________

____________________________________________________________________

____________________________________________________________________

Q3) The table below shows some data on mutation in corn.

Calculate the average number of mutations per million.

Gene Number of gametes tested

Number of mutations

Average number of mutations per million gamete

Rr 554,786 273

Ii 265,391 28

Susu 1,678,736 4

Shsh 2,469,285 3

Why is it necessary to convert to ‘per million’?

___________________________________________________________

From this information, what can you say about mutation frequency?

___________________________________________________________


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Mutation and Disease

According to the 'National Human Genome Institute', most diseases have some sort

of genetic factor. These disorders can be caused by a mutation in a single gene,

multiple gene mutations, combined gene mutation and environmental factors, or by

chromosome mutation or damage.

DNA Repeat Sequences

Nucleotide sequences can be repeated a number of times in a row in the DNA

sequence. However, insertion could cause an abnormal number of these repeat

sequences to occur. Repeat expansion disorders are a group of human diseases that

are caused by the abnormal elongation of a DNA repeat sequence.

See the diagram below showing a trinucleotide repeat which is made up of repeating

3 base pair sequences.

This type of mutation increases the number of times that the short DNA sequence is

repeated and can cause the resulting protein to function improperly. An example of

a disease caused by this type of mutation is Huntington’s disease.

Gene mutations have been identified as the cause of many disorders including;

Sickle Cell Anaemia, Cystic Fibrosis, Tay-Sachs disease, Huntington’s disease,

Haemophilia, and some Cancers.

Activity: Using web sites such as; www.ygyh.org and classroom resources,

make notes on a few of the genetic diseases mentioned above.

Include;

what type of mutation has caused it?

what is the frequency of occurrence?

is the mutation confined to a specific area or ethnic race?

what are the symptoms associated with each mutation?

are any of the mutations beneficial or are they detrimental?

http://biology.about.com/od/genetics/ss/chromosome-mutation.htm


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Disease 1: Disease 2:

Diseases caused by mutation

Disease 3: Disease 4:


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Chromosome Mutations

During gamete formation (meiosis) the homologous (matching) pairs of

chromosomes line up at the equator of the cell. This is the stage where

mutations involving changes to the chromosome structure can occur.

There are 2 types of chromosome mutation:

changes in the chromosome structure

changes in the chromosome number

Changes in Chromosome Structure

Write a statement describing each chromosome mutation shown below;

a. Translocation

b. Inversion

N

o

r

m

a

l

h

a

e

m

Chromosome structure mutations are;

Duplication

Inversion

Deletion

Translocation

Memory Aid:

DID T


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c. Deletion

d. Duplication

The four diagrams below show different chromosome mutations that can affect a

chromosome. Write the name of each mutation shown in the correct box.

a)

b)

c)

d)


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Change in Chromosome Number

Mutation can cause the chromosome number to be changed e.g. whole extra sets

of chromosomes in the gamete.

Most chromosome mutations are harmful; however, some provide advantages to the

organism.

Mutation and Evolution

Polyploidy

Most organisms have two sets of chromosomes in their body cells. They are diploid

(2n). When an organism has cells with more than two sets of chromosomes it is

referred to as polyploidy (multiple sets of 3n or above). Polyploidy is rare in

animals but common in plants.

During gamete formation (meiosis) the homologous pairs (matching parental

pairs) of chromosomes line up at the equator of the cell. It is at this point where

mutations involving changes to the chromosome number can occur.

If the spindle fibres fail to pull the chromosomes apart, they remain together and

move as one into the new gamete. Spindle fibre failure is known as

non-disjunction. This can happen to whole sets of chromosomes if all the spindle

fibres fail as shown in the diagram below. This is called complete non-disjunction.

Diagram

All spindle fibres fail. All

chromosomes move together

into a gamete.

Mutations and gene duplication are important in evolution as they result in polyploidy.

Errors during the separation of chromosomes during cell division can result in cells with

whole genome duplications.


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Polyploidy is responsible for the evolution of many of the 'modern and improved'

food crops we see today. Polyploidy can be induced in plants using mutatgenic

agents such as colchicines.

The diagram below outlines how polyploidy can occur in plants.

Plant Variety A

Plant Variety B

P 2n 2n

Gametes nn - n n

Gametes n n

- n n

nn nnn nnn

F1 possibilities

nnn nnn

The brassica family is shown in the diagram below. Each of the examples has been

produced as a result of polyploidy naturally in nature. Scientists have used this

ability to produce the many variations of different brassica we have today.

This type of mutation provides crop plants with a variety of different advantages

which are of economic importance.


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Polyploidy can be extremely useful to both the plants but also commercially as these

plants have many desirable characteristics.

Read Torrance p 72 ‘Economic Importance of polyploidy’ and list some of these

advantages below.

______________________________________________________________

______________________________________________________________

______________________________________________________________

______________________________________________________________

When polyploidy plants are produced by crossing different varieties the resulting

hybrid often shows the enhanced characteristics; improved growth, increased

fertility or resistance to disease. This we call hybrid vigour.

Many plants are polyploid e.g. Durum wheat used to make pasta is tetraploid while

White bread wheat is hexaploid.

How many sets of chromosomes does each of the wheat examples possess?

Durum wheat = ________ White bread wheat = _______


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The diagram below shows stages in the evolution of a species of modern wheat

(Triticum vulgare) through polyploidy.


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Decide if each of the following statements is true or false and give an explanation for

your decision below:

1. Hybrid A is sterile as it is unable to form homologous pairs in meiosis.

True False

Explanation: _________________________________________________________

____________________________________________________________________

2. The chromosome number of hybrid B is 21.

True False

Explanation: _________________________________________________________

____________________________________________________________________

3. The doubling of the chromosome number is due to fusion of gametes at

fertilisation.

True False

Explanation: __________________________________________________________

____________________________________________________________________

4. Two species that are fertile polyploids are T. durum and T. vulgare

True False

Explanation: __________________________________________________________


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Record your research notes below

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Activity 1:

Task A: Research polyploidy in plants and the importance in the

evolution of modern crop species.

Choose two to plants from the following polyploids; banana,

potato, swede/turnip, oil seed rape, wheat, strawberry.

Task B: Read Torrance p 73 and make notes of the rarity of

polyploidy in animals using the Viscacha rat.


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Activity2:

Collect a copy of the ‘Polyploidy and Evolution’ work booklet and

answer the questions.


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The different effects that a single gene mutation has on the protein can be described as:

Description Effect

i)

ii)

iii)

iv)

v)

Splice site mutation Could prevent a splice site or produce an additional splice causing introns to be left in the mature transcript.

Regulatory site mutation Can result in the absence or excess of the protein expressed.

Mutations Summary

Gene Mutation

Chromosome Mutation

Replacement of one base pair for another.

Addition or removal of a

base pair

Change in the number of

chromosomes

Change in the structure of

the chromosome

S

I

P

D

D

I

D

T


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1.6 Mutations

How well do you rate your knowledge and understanding?

1 2 3

A mutation is a random change in the genome, causing no protein or an

altered protein to be produced.

Mutation is random and the frequency is low but can be induced by

mutagenic agents.

Mutations can be classified as either chromosome or gene.

Mutations are important in the evolutionary pathway of organisms and can offer a selective advantage or disadvantage to the organism.

Single gene mutation results from a change in the DNA nucleotide

sequence or a single base pair.

Substitution, deletion and insertion are single gene point mutations which can result in missense, nonsense, neutral or splice site mutations

(altering post-transcriptional processing).

Insertions and deletions result in frame-shift mutations or expansion of a

nucleotide sequence repeat.

Regulatory sequence mutations can alter gene expression.

Mutations at splice sites can alter the mRNA mature transcript produced

affecting the splicing of introns.

Mutations can cause abnormal replication of repeat sequences which can

result in disease.

Different chromosome structure mutations are; duplication, deletion,

translocation, and inversion.

Non-disjunction during the separation of chromosomes during cell division can result in cells with whole genome duplications.

Polyploidy has a beneficial impact on plants, especially crops.

Complete:

Row 1 before your Unit assessment

Row 2 before your Prelim

Row 3 before your May exam

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Unit 1: DNA and the Genome Sub-topic 6: Mutation · The mutation could occur within the protein...

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