NUCLEOTIDE SUBSTITUTION, INSERTION AND DELETION
1.3 Genome: (b) i Point mutations: nucleotide substitution,
insertion and deletion
From the Arrangements
(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.
Teacher’s notes
There are two parts to this section.
Part one is supported by a short PowerPoint called Genetic mutations, which
illustrates point mutations (substitution, insertion and deletion) and
summarises their main attributes whilst finishing with a slide on their
frequency, causes and relevance.
There is a student activity called Gene mutations that allows students to see
how substitutions may have little effect compared to frame -shift mutations.
However, you should emphasise that some substitutions may be very
damaging if they impact on the protein’s final conformation (shape) and
hence function, eg sickle cell disease.
The second part is a research-based extension activity that allows students to
find out about some of the diseases caused by mutations. A good starting
place to direct less-able students may be the Your Genes Your Health website
(www.ygyh.org). The prompt for sickle cell anaemia is included to encourage
students to investigate this disease since carrying the mutation gives a
selective advantage in malarial areas.
UNIT 1, PART (III) GENOME (H, BIOLOGY)
© Learning and Teaching Scotland 2011
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NUCLEOTIDE SUBSTITUTION, INSERTION AND DELETION
Student activities
Gene mutations (point mutations)
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 protein 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 reading frame.
Example 1
Original
Mutation
the
the
old
olb
man
dma
ran
nra
for
nfo
the
rth
red
ere
bus
dbus
the
the
old
olm
man
anr
ran
anf
for
ort
the
her
red
edb
bus
us
the
the
old
old
man
nan
ran
ran
for
for
the
the
red
red
bus
bus
Example 2
Original
Mutation
Example 3
Original
Mutation
For each example highlight or circle where the mutation has occurred.
1.
For each example say whether it is a substitution, deletion and
insertion?
2.
Explain which has the greatest effect on the meaning of the sentence (or
which would have the greatest effect on the final protein sequence ).
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UNIT 1, PART (III) GENOME (H, BIOLOGY)
© Learning and Teaching Scotland 2011
NUCLEOTIDE SUBSTITUTION, INSERTION AND DELETION
3.
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 the re could be failure of exons to
be correctly spliced, with huge consequences on the translation of the mRNA.
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.
4.
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. Howeve r, 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.
UNIT 1, PART (III) GENOME (H, BIOLOGY)
© Learning and Teaching Scotland 2011
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NUCLEOTIDE SUBSTITUTION, INSERTION AND DELETION
Mutations which do not have any effect on the protein’s function are also
known as neutral mutations.
Can you find real-life examples of genetic disorders caused by misse nse,
nonsense or frame-shift point mutations?
What is the frequency of these mutations?
Are any of the mutations 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?
Look at this video clip: Embryo hope for inherited diseases
http://news.bbc.co.uk/1/hi/health/8621046.stm
Sickle cells
Red blood
cells
Present your results in the form of a spider diagram. In th e 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.
Why not start with sickle-cell trait?
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UNIT 1, PART (III) GENOME (H, BIOLOGY)
© Learning and Teaching Scotland 2011