• 2 Structure and function of DNA
(a) Structure and replication of DNA
• (i) Structure of DNA — nucleotides contain
deoxyribose sugar, phosphate and base. DNA
has a sugar–phosphate backbone,
complementary base pairing — adenine with
thymine and guanine with cytosine. The two
DNA strands are held together by hydrogen
bonds and have an antiparallel structure, with
deoxyribose and phosphate at 3' and 5' ends of
each strand.
• (ii) Chromosomes consist of tightly coiled DNA
and are packaged with associated proteins.
• DNA intro- gd!:
• http://www.glowscience.org.uk/mindmap#!/biology/cells_
and_dna/dna or found at
http://www.twigonglow.com/mindmap/#205/dna?&_suid=13463252177810749224693863
6337
• DNA rap: http://www.youtube.com/watch?v=wdhLT6tQco
• What is DNA – Bozemanbiology:
• http://www.youtube.com/watch?v=q6PPC4udkA&list=UUEikU3T6u6JA0XiHLbNbOw&index=90&feature=plpp_video
CHROMOSOMES
•Chromosomes are thread-like
structures found in the
nucleus of the cell.
•They are made up of tightly
coiled DNA (deoxyribonucleic
acid) along with associated
proteins
•A molecule of DNA consists
of two strands of repeating
units called NUCLEOTIDES.
• http://biomodel.uah.es/en/model3/adn.htm
Videos of discoverers of DNA
structure
• http://www.dnai.org/a/index.html
A DNA NUCLEOTIDE
PHOSPHATE
BASE
DEOXYRIBOSE
SUGAR
CHAIN OF NUCLEOTIDES
THE DOUBLE HELIX
• http://courses.scholar.hw.ac.uk/vle/scholar/
session.controller?action=viewContent&ba
ck=topic&contentGUID=f830259e-992e5044-e201-75cf99b5a3e1
DNA structure
• The basic units of DNA are called nucleotides.
They contain deoxyribose sugar, phosphate
and a base. The sugar and phosphate join
together to form the DNA’s backbone.
• There are four possible bases which join in
complementary base pairs: adenine (A) always
joins with thymine (T) and guanine (G) always
joins with cytosine (C). The two DNA strands
are held together by weak hydrogen bonds
between the bases.
Antiparallel patterns
• At one end of the chain,
called the 5‘ end is a
phosphate
• At the other end of the
chain, called the 3'end,is
a deoxyribose sugar
• The reason for this
antiparallel arrangement
is that this is the only
way in which the two
strands can fit
together.
• The two strands stand alongside each
other but run in antiparallel directions, i.e.
they run in opposite directions.
• At the end of one strand, the end finishes
with a phosphate molecule and is named
the 5-prime (5’) end.
• At the end of the other strand, the end
finishes with a deoxyribose sugar molecule
and is named 3-prime (3’) end.
• (d rhymes with 3!)
Describe the location and structure
of DNA. (8 marks)
Describe the location and structure of DNA. (maximum of 8
marks):
–
–
–
–
–
–
–
–
–
–
DNA is located on chromosomes in the nucleus.
A DNA molecule consists of two strands wound in a double helix.
Each strand consists of subunits called nucleotides.
A nucleotide consists of a deoxyribose sugar molecule, a phosphate
group and an organic / nitrogenous base.
The deoxyribose and phosphate are linked to their neighbours to form
a sugar-phosphate backbone.
There are four organic bases: adenine (A), thymine (T), guanine (G)
and cytosine (C).
Bases are linked in complementary pairs A-T and G-C.
Bases link the two DNA strands by hydrogen bonds.
The two DNA strands have an antiparallel structure / explanation.
Deoxyribose is found at the 3 end of each strand and phosphate is
found at the 5 end.
• (iii) Replication of DNA by DNA polymerase and
primer. DNA is unwound and unzipped to form
two template strands. DNA polymerase needs a
primer to start replication and can only add
complementary DNA nucleotides to the
deoxyribose (3') end of a DNA strand. This
results in one strand being replicated
continuously and the other strand replicated in
fragments which are joined together by ligase.
3 proposed theories of how
DNA replicates....
Take an educated guess of which model and
WHY!
• DNA replication – Bozemanbiology
• http://www.youtube.com/watch?v=FBmO_r
mXxIw&list=UUEikU3T6u6JA0XiHLbNbOw&index=28&featur
e=plpp_video
DNA replication animation!
• http://highered.mheducation.com/olcweb/cgi/pluginpop.c
gi?it=swf::535::535::/sites/dl/free/0072437316/120076/mi
cro04.swf::DNA%20Replication%20Fork.
• http://www.lpscience.fatcow.com/jwanamaker/animations
/DNA%20Lecture.html
DNA REPLICATION
A
C
T
G
G
• DNA replication takes
place prior to cell
division (mitosis and
meiosis)
Requirements:• DNA to act as a
template
• Primer
• Enzymes: DNA
polymerase and ligase
• Free nucleotides
• ATP for energy
• DNA Helicase untwists the helix at
locations called replication origins. The
replication origin forms a Y shape, and is
called a replication fork.
DNA Replication
• Before replication can occur, the length
of DNA to be copied must be unwound
to form two separate template
strands.
• The two strands must be separated by
breaking the weak hydrogen bonds that
link the paired bases.
• DNA polymerase requires the assistance of a
primer, a previously existing short strand of
RNA that is complementary to the first part
of the DNA segment being copied.
• This small strand of nucleotides binds by
complementary base pairing to the beginning
of the area being copied.
• With the primer in place, DNA polymerase is
then able to continue adding the rest of the
pairs of the segment until a new double
strand of DNA is completed.
The leading strand
• Since DNA replication moves along the parent strand
in the 5' to 3' direction, replication can occur very
easily on the leading strand.
• The DNA polymerase simply sits near the replication
fork, moving as the fork does, adding nucleotides one
after the other.
• This sort of replication, since it involves one
nucleotide being placed right after another in a
series, is called continuous.
• http://www.nobel.se/medicine/educational/dna/a/rep
lication/replication_ani.html
The lagging strand
• Synthesis on the lagging strand is
slightly delayed in relation to synthesis
on the leading strand.
• http://www.nobel.se/medicine/educational/
dna/a/replication/lagging_ani.html
What you should know
DNA Replication
• DNA polymerase – the enzyme that carries out
replication - needs a primer to start replication.
• DNA polymerase only functions in the 5’ to 3’
direction as it can only add complementary DNA
nucleotides to the deoxyribose sugar (3') end of a
DNA strand, so a DNA strand is always synthesized in
the 5’ to 3’ direction.
• This results in one strand being replicated
continuously and the other strand replicated in
fragments which are joined together by the enzyme
ligase.
DNA Polymerase
Helicases
Primer
Okazaki Fragments
DNA Polymerase
DNA Ligase
• As the replication is completed, the two
new strands, each consisting of one new
strand bonded to one from the original
molecule, now fall away from each other
and form two separate identical DNA
strands. They each coil into their helical
shape and the process is complete.
Give an account of the replication
of DNA. (maximum of 7 marks):
–
–
–
–
–
–
–
–
–
DNA is unwound and unzipped…
…by the enzyme helicase…
…to form two template strands.
DNA polymerase is the enzyme which adds nucleotides to the
new DNA strand.
DNA polymerase needs a primer to start replication.
DNA polymerase can only add complementary nucleotides to
the deoxyribose / 3 end of the DNA strand.
This results in one strand / the leading strand being
continuously replicated,
and the other strand / the lagging strand being replicated in
fragments,
which are joined together (by the enzyme ligase).
• (b) Gene expression. Phenotype is determined
by the proteins produced as the result of gene
expression. Only a fraction of the genes in a cell
are expressed.
• Gene expression is influenced by intra- and
extra-cellular environmental factors. Gene
expression is controlled by the regulation of both
transcription and translation.
Big Question
Gene Expression; On and Off
Once a cell becomes
differentiated – the genes that
code for only specific proteins to
the workings of that cell are
turned on.
Only 3-5% of genes expressed in
a typical human cell
Gene expression
• A cell’s genotype is determined by the
sequence of DNA bases in its genes
• An organism’s phenotype is determined
by the proteins produced as the result
of genes being switched on.
Although a specialised cell has a complete
set of the organism's genes, only those
needed for its specialised functions are
switched on. All other genes are
switched off.
Gene expression in specialised
cells
Cell type
Activity of genes coding for production of:
antibodies
lysosome
enzymes
enzymes for synthesis of
urea
pepsin
phagocyte
off
on
off
off
liver
off
off
on
off
stomach
lining
off
off
off
on
lymphocyte
on
off
off
off
Gene expression
Although a specialised cell has a complete set of the
organism's genes, only those genes needed for its
specialised functions are switched on. All other are
switched off.
Gene expression is the activation of a gene that results
in the formation of a protein. Gene expression is
influenced by intra- and extra-cellular environmental
factors. Gene expression is controlled by the regulation
of both transcription and translation.
Only a fraction of the genes in a cell are expressed. An
organism’s appearance - its phenotype – is determined
by the proteins produced.
• (i) Structure and functions of RNA.
• RNA is single stranded, contains uracil
instead of thymine and ribose instead of
deoxyribose sugar. mRNA carries a copy
of the DNA code from the nucleus to the
ribosome. Ribosomal RNA (rRNA) and
proteins form the ribosome. Each transfer
RNA (tRNA) carries a specific amino acid.
DNA to Protein
RNA Structure
RNA
• RNA is single stranded, contains the
base uracil (U) instead of thymine (T)
and a ribose instead of a deoxyribose
sugar.
Types of RNA
• Messenger RNA (mRNA) – carries the genetic
information from the nucleus to the ribosome
for protein synthesis
• Ribosomal RNA (rRNA) – along with proteins,
form the ribosome
• Transfer RNA (tRNA) – Carries specific
amino acids to the ribosome to build into
proteins
Venn diagram
DNA
both
RNA
• (ii) Transcription of DNA into primary and mature
RNA transcripts to include the role of RNA
polymerase and complementary base pairing.
• The introns of the primary transcript of mRNA
are non-coding and are removed in RNA
splicing. The exons are coding regions and are
joined together to form mature transcript. This
process is called RNA splicing.
• How does DNA make protein?:
http://www.twigonglow.com/mindmap/#205/dna?&_suid=13463252177810749224693863
6337
• DNA transcription and translation – Bozemanbiology
• http://www.youtube.com/watch?v=h3b9ArupXZg&list=UU
EikU3T6u6JA0XiHLbNbOw&index=27&feature=plpp_video
•
• DNA RNA
• http://www.youtube.com/watch?v=xZaMi6OhsSU
&feature=plcp
DNA to protein
www.yourgenome.org/downloads/animations.shtml
Overview of Protein Synthesis
NUCLEUS
RIBOSOME
Protein synthesis stage 1:
TRANSCRIPTION
• As DNA is too large to leave the nucleus
through pores in the nucleus, a copy of it is
made by producing a similar molecule called
mRNA. This process is called transcription
and requires:
•
•
•
•
DNA to act as template
Free RNA nucleotides
Enzymes including RNA polymerase
ATP for energy
Transcription
• http://courses.scholar.hw.ac.uk/vle/scholar/
session.controller?action=viewContent&ba
ck=topic&contentGUID=16a5d6c5-d5751e21-9bb0-f2454c2547c3
• http://www.carolina.com/teacherresources/Video/dna-transcriptionvideo/tr28274.tr
TRANSCRIPTION
• RNA polymerase unwinds the DNA and breaks
hydrogen bonds between bases to separate the
strands and expose the gene required.
• Free RNA nucleotides match up along the strand
by complementary base pairings:
DNA
mRNA
A
U
G
T C A G T
C A G U C A
C
G
codon
Each triplet of 3 bases on mRNA is called a codon.
• RNA polymerase then joins up the sugar
phosphate backbone to form what is called
the primary transcript of mRNA.
• The hydrogen bonds between bases then
reform and the DNA coils back up into a
double helix.
RNA splicing
• JUHTHEHFGBOYHSKYRSATANDLETHJDFK
ETHEJKFICATUFNAPDFGFORSDSTHEDAY
• You have been given a strip of paper
containing a sentence interspersed with
letters.
• Cut the nonsense sections out and stick
together the words to make a sentence.
It should read:THE BOY SAT AND LET THE CAT NAP FOR
THE DAY
But you may also have come up with:• THE BOY SAT FOR THE DAY
• THE BOY LET THE CAT NAP
• THE BOY LET THE CAT NAP FOR THE DAY
Introns and exons
• The primary transcript of mRNA is composed of introns
and exons.
Non coding region
Coding region
RNA splicing
• The introns of the primary transcript of
mRNA are non-coding regions of the gene and
are removed in RNA splicing. The exons are
coding regions of the gene and are joined
together to form the mature transcript of
mRNA. This process is called RNA splicing.
• (iii) Translation of mRNA into a polypeptide by
tRNA at the ribosome.
• tRNA folds due to base pairing to form a triplet
anticodon site and an attachment site for a
specific amino acid. Triplet codons on mRNA
and anticodons translate the genetic code into a
sequence of amino acids. Start and stop codons
exist. Codon recognition of incoming tRNA,
peptide bond formation and exit of tRNA from
the ribosome as polypeptide is formed.
Protein synthesis stage 2:
TRANSLATION
Changing the code on mRNA into a
sequence of amino acids to form a
specific protein.
Tranlasation film
• http://www.carolina.com/teacherresources/Video/mrna-translationvideo/tr28275.tr
tRNA
tRNA
amino acid
attachment
site
tRNA
carries a
specific
amino acid
to the
ribosome
• tRNA required for translation are found in
the cytoplasm. They contain an attachment
site to carry a specific amino acid to the
ribosome. As there are 20 different amino
acids, 20 different tRNA molecules exist.
• They also have a site where a triplet of 3
bases are exposed, called an anti-codon.
• http://courses.scholar.hw.ac.uk/vle/scholar/
session.controller?action=viewContent&ba
ck=topic&contentGUID=ec041196-3cb0c55a-f4fe-e839978b92dc
TRANSLATION
AMINO
ACID
tRNA
U C G
START
CODON!
RIBOSOME
CODON
A G C A U U A G C C C U A G A G G
mRNA
ANTICODON
TRANSLATION
U A A
U C G
A G C A U U A G C C C U A G A G G
TRANSLATION
PEPTIDE
BOND
U C G U A A
A G C A U U A G C C C U A G A G G
TRANSLATION
U C G
U A A
U C G
A G C A U U A G C C C U A G A G G
TRANSLATION
U C G
G G A
U C G
A G C A U U A G C C C U A G A G G
U A A
TRANSLATION
U A A
U C U
G G A
A G C A U U A G C C C U A G A G G
U C G
TRANSLATION
POLYPEPTIDE
CHAIN
G G A
A G C A U U A G C C C U A G A G G
U C U
STOP
CODON!
Translation
• During translation, the mRNA strand passes through the
ribosome which ‘reads’ the mRNA as it goes through.
• Certain mRNA codons act as ‘start’ codons to tell the
ribosome where to start and stop reading the strand.
• The ribosome identifies each mRNA codon and then
matches it up with the correct tRNA anticodon according
to complementary base pairs (A-U, C-G)
• The appropriate tRNA brings its amino acid to the
ribosome as it moves along the mRNA.
• Adjacent amino acids then join with a peptide bond to
form a polypeptide.
• Each tRNA then leaves the ribosome.
• This process continues until a stop ‘codon’ is reached
which tells the ribosome where to end the polypeptide.
• The polypeptide is finally released.
DNA – mRNA – tRNA - Protein
DNA - TTACGGCAATGCGGTACCGTTGGGGGCAG
mRNA Codons (set of 3 bases)
tRNA Anti-codons (set of 3 matching bases)
DNA – mRNA – tRNA - Protein
DNA - TTACGGCAATGCGGTACCGTTGGGGGCAG
mRNA - AAUGCCGUUACGCCAUGGCAACCCCCGUC
Codons (set of 3 bases)
tRNA - UUACGGCAAUGCGGUACCGUUGGGGGCAG
Anti-codons (set of 3 matching bases)
Amino - aspn– ala – val – thr – pro – try – glu – pro – pro
acid
Protein synthesis animation!
• Have a go yourself:
• http://www.zerobio.com/drag_oa/protein/tr
anslation.htm
• Google ‘transcription and translation
activity’ – look for zerobio.com
•
•
http://learn.genetics.utah.edu/content/begin/dna/transcribe/
Google ‘transcribe and translate a gene’
• (iv) One gene, many proteins as a result of RNA
splicing and post-translational modification.
Different mRNA molecules are produced from
the same primary transcript depending on which
RNA segments are treated as exons and introns.
Post-translation protein structure modification by
cutting and combining polypeptide chains or by
adding phosphate or carbohydrate groups to the
protein.
One gene, many proteins
One gene, many proteins
Golgi body animation
• http://www.kscience.co.uk/animations/golgi
.htm
Post-translational
modification of
insulin
The hormone insulin consists of two
polypeptide chains that originate as
one chain.
Disulphide bridges form in the
original polypeptide chain, known as
pro-insulin.
A protease enzyme (an enzyme
which cuts protein at a peptide bond)
cuts the polypeptide chain in two
places.
The middle section of the protein is
then removed.
Modification by the addition of a
carbohydrate
• Mucus adheres to many
epithelial surfaces, where
it serves as a diffusion
barrier against contact
with noxious substances
and as a lubricant
• Mucus is a glycoprotein
consisting of protein and
an added carbohydrate
From one gene, many different proteins may be
produced. This is due to:
1. RNA splicing
Different mature transcripts of mRNA may produced
from the same primary transcript of mRNA depending
on which RNA segments are treated as exons and
introns.
2. Post-translational modification
The protein may be further cut, combined with other
polypeptide chains or have phosphate or carbohydrate
groups added to the protein. This will occur in the
Golgi body.
• Give an account of gene expression under
the following headings.
• Transcription (6 marks)
• Post-translational modification (PTM) (4
marks)
•
Transcription (maximum of 6 marks):
–
–
–
–
–
–
–
–
•
Transcription is the formation of a mRNA molecule on a DNA
template.
DNA unwinds, and strands separate by the action of helicase.
RNA nucleotides attach to exposed bases of DNA.
DNA A pairs with RNA U, DNA T - RNA A, DNA G - RNA C and
DNAC - RNA G.
RNA polymerase joins nucleotides (to each other).
This produces the primary transcript.
Which contains introns and exons.
Exons are protein coding sections of mRNA and introns are noncoding sections.
Post-translational modification (PTM) (maximum of 4 marks):
–
–
–
–
–
–
It takes place after the polypeptide has been completed on the
ribosome.
It allows several proteins to be formed from one gene.
It may involve enzyme cutting and combining of polypeptide chains.
e.g. insulin from pro-insulin.
It may involve adding of phosphate or carbohydrate groups.
Addition of phosphate enables enzymes / receptors to be switched
'on' and 'off'.
Protein synthesis storyboard
• c) Genes and proteins in health and
disease.
• (i) Proteins are held in a three dimensional
shape by peptide bonds, hydrogen bonds,
interactions between individual amino
acids.
• Polypeptide chains fold to form the three
dimensional shape of the protein.
Protein function
• You will have come across many proteins
before and covered some of the many
roles they undertake in living organisms.
• Research one of the proteins listed below
and complete its ID, which will be used to
create a classroom display.
helicase
keratin
kinase
oxytocin
integrins
phosphorylase
tubulin
insulin
actin
catalase
antibody
collagen
porin
elastin
polymerase
pepsin
myosin
cytochromes
haemoglobin
amylase
Protein name
Structure:
__(globular/fibrous)__
Location: _____where it is found!_______
Function: ______what it does!_________
_____________________________
______________________________
Simple
diagram of
the protein
itself or
showing what
it does.
Structure:
_____________________________
Location:
_____________________________
Function:
_____________________________
_____________________________
_____________________________
• http://courses.scholar.hw.ac.uk/vle/scholar/
session.controller?action=viewContent&ba
ck=topic&contentGUID=9df68c88-6cf3866f-f253-96ce94e448ac
PROTEIN PRIMARY STRUCTURE
• The primary
structure of a
protein is the
polypeptide chain of
amino acids
PROTEIN SECONDARY
STRUCTURE
• Weak hydrogen bonds
form between various
amino acids.
• This causes the
polypeptide chain to
become coiled into an
 helix (coiled) or
folded into a 
pleated sheet (folded)
PROTEIN TERTIARY
STRUCTURE
• The tertiary structure is
the final structure of the
protein due to hydrogen
bonding and sulphide
bonding between amino
acids.
• tertiary structure can
form either fibrous
proteins or globular
proteins.
PROTEIN QUARTERNARY
STRUCTURE
• Quarternary structure
is formed when
several polypeptides
become bonded
together
FIBROUS PROTEIN
• Formed when
several polypeptide
chains are bonded
together in long
parallel strands
• examples include
collagen (skin),
keratin (hair) and
actin and myosin
(muscle)
GLOBULAR PROTEINS
• Look like a tangled
ball of string
• Enzymes, hormones
and antibodies are all
globular proteins
• http://courses.scholar.hw.ac.uk/vle/scholar/
session.controller?action=viewContent&ba
ck=topic&contentGUID=2ce36382-0b0b5ccc-ac7c-dcdd0e2453d4
CONJUGATED PROTEIN
• Contains polypeptide
chains and a nonprotein part
• E.g. haemoglobin
consists of 4
polypeptide chains
and 4 iron atoms
Proteins
• Proteins are long polypeptide chains, folded to
form a specific three dimensional shape.
• These chains of amino acids are held in a
three dimensional shape by peptide bonds,
hydrogen bonds and sometimes additional
bonds with other non protein molecules.
• Do protein power electrophoresis protocol
• (ii) Mutations result in no protein or a faulty
protein being expressed.
• Single gene mutations involve the alteration of a
DNA nucleotide sequence as a result of the
substitution, insertion or deletion of nucleotides.
Single-nucleotide substitutions include:
missense, nonsense and splice-site mutations.
Nucleotide insertions or deletions result in
frame-shift mutations or an expansion of a
nucleotide sequence repeat.
• The effect of these mutations on the structure
and function of the protein synthesised and the
resulting effects on health.
•
What is a mutation?
• It’s a change in the DNA sequence.
Gene Mutations
• Changes in one or more nucleotides in
the DNA of the cell
MUTATIONS
• Occur naturally in every population
• They can occur spontaneously (at
random)
• An individual with a mutation is termed
a mutant
EXAMPLES
• Polydactyly –
presence of extra
finger or toes
• Liam Gallagher and
Marilyn Monroe!!
LIAM’S EXTRA TOE!
MARILYN’S EXTRA TOE!
Mutations
• Mutations are random changes to the
DNA’s normal nucleotide base sequence.
• This causes the section (gene) involved
to produce either a faulty protein or not
to produce any protein at all.
• http://courses.scholar.hw.ac.uk/vle/scholar/
session.controller?action=viewContent&ba
ck=topic&contentGUID=f0af9519-17b3a64f-e476-23cff5db50e6
Substitution Mutations
Only this amino acid
altered
Mutations
• Mutations involving only one gene are
called single gene mutations. There are
three different types of single gene
mutations:
• 1. Substitution mutations
An individual nucleotide is replaced by a
different nucleotide. This changes the
bases in an mRNA codon.
Single nucleotide substitution
mutations
• There are different types of
substitution mutations, depending
on where the substitution occurs:
– Nonsense
– Missense
– Splice site
Non sense mutations
•Substitution of a single nucleotide that leads to the
appearance of a stop codon where previously there was a
codon specifying an amino acid. A much shortened protein
is produced eg sickle cell anaemia.
Nonsense mutations
• Duchenne muscular dystrophy:
• https://www.youtube.com/watch?v=CQP
LxNsN1J0&list=UUhUIp7xnLfBcNKTTj
HdypfQ
• Sickle cell anaemia:
• https://www.youtube.com/watch?v=LlF_
8oRs6Bw&list=UUhUIp7xnLfBcNKTTjH
dypfQ
Missense mutations
• Substitution of a single
nucleotide causes the
formation of a different
amino acid in the
resulting protein.
• This amino acid
substitution may have no
effect, or it may render
the protein nonfunctional.
• E.g. Duchenne muscular
dystrophy.
Splice site mutations
• Alters the specific
sequence which
identifies the site
at which the
splicing of mRNA
occurs
• May lead to
retention of large
segments of
introns, or the
incorrect removal
of exons from the
mRNA.
• May result in
production of a nonfunctional protein
e.g. beta
thalassemia.
Beta thalassemia:
•Reduces the production of hemoglobin.
•Shortage of red blood cells (anaemia),
which can cause pale skin, weakness,
fatigue, and more serious complications.
Substitutions mutations
Different types of substitution mutations occur, depending on where
the substitution occurs:
a) Missense – a nucleotide in a codon is substituted, causing a different
amino acid to be produced. This may lead to the final protein not
functioning e.g. Duchenne muscular dystrophy
b) Nonsense –a nucleotide in a codon is substitutes, changing it from
coding for an amino acid coding for a stop codon. This causes a
shorter (usually non functioning) protein e.g. sickle cell anaemia
c) Splice-site- the nucleotide at which mRNA splicing occurs is
substituted, causing the location of the splice site to change. This
leaves non coding regions (introns) left in and coding regions
(extrons) removed from the mature mRNA, thus producing non
functioning proteins e.g. beta thalassemia
Insertion Mutations
All amino acids altered
Mutations
2. Insertion mutations
A nucleotide is added to the DNA
Nucleotide insertions cause a frame-shift mutation.
This is where adding a nucleotide causes that mRNA
codon and all of the codons that follow on the mRNA
to change and thus produce the wrong amino acids.
This leads to a very different and generally nonfunctional protein product. E.g. Tay-Sachs syndrome
• Expansion of a nucleotide repeat:
• http://www.hhmi.org/biointeractive/trinucleotide-repeat
• E.g. Huntingdon’s disease:
• https://www.youtube.com/watch?v=xguyxdme
UK8&list=UUhUIp7xnLfBcNKTTjHdypfQ
Repeated nucleotide insertions may also
cause many of the same codons to be
copied, resulting in many extra copies of
a single amino acid being produced . This
is called a nucleotide sequence repeat
expansion. E.g. Huntingdon’s disease.
Deletion
A
A
B
B
New
C chromosome
C
G
D
E
F
G
H
Original
chromosome
BREA
K
H
D
E Deleted
genes
F
Deletion Mutations
All amino acids altered
Single nucleotide deletions
• Called frame shift mutations
Cystic Fibrosis
Mutations
3. Deletion mutations
A nucleotide is removed from the DNA
Nucleotide deletions also cause frame
shift mutations.
• Experiments investigating the effects of
UV radiation on UV sensitive yeast.
Genetic Disorders
Definition;
Genetic disorders are
caused by changes to
genes or chromosomes
that result in the proteins
not being expressed or
the proteins expressed
not functioning correctly.
Examples;
Sickle cell anaemia
Duchenne muscular dystrophy
Tay-Sachs syndrome
Cystic fibrosis
Huntingdons
Fragile X syndrome
Beta thalassemia
PKU
Cri-du-chat syndrome
Chronic myeloid leukaemia
Down’s syndrome
Single gene mutation case studies:
•
•
•
•
•
•
•
•
• Huntingdon's disease (nucleotide sequence repeat expansion) - Individuals with large numbers
of repeats show progressive degeneration of the nervous system, affecting muscle coordination
and cognitive ability. It typically only becomes noticeable in mid-adult life.
• Fragile X syndrome (nucleotide sequence repeat expansion) - leads to autism and intellectual
disability. As with any condition controlled by genes on the X-chromosome, it affects males at a
higher rate than females.
• Sickle-cell disease (missense) – leads to the production of abnormally rigid and sickle cell
haemoglobin causing obstructions in small vessels as well as a wide range of other serious
effects.
• Phenylketonuria (PKU) (missense) - causes the production of an inactive form of an enzyme,
resulting in a range of symptoms including impaired brain function.
• Beta (β) thalassaemia (splice-site) - causes reduced, or no, production of one of the polypeptide
chains which make up haemoglobin. The symptoms range from none to severe anaemia.
• Duchenne muscular dystrophy (DMD) (nonsense) – caused by mutation to a gene on the X
chromosome, resulting in failure to produce an important structural protein in muscle. It causes
muscle degeneration and early death.
• Tay-Sachs syndrome (frameshift insertion) - results in progressive destruction of the central
nervous system and early death.
• Cystic fibrosis (frameshift deletion) - results in the secretory glands of the lungs producing very
sticky mucus, poor growth and frequent chest infections. Untreated, it leads to death in infancy.
Give an account of gene
mutation. (9 marks)
•
Give an account of gene mutation. (maximum of 9 marks)
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–
–
–
–
–
–
–
–
–
–
A gene mutation is a change in the base type or sequence in a gene.
In a substitution (mutation) one base is replaced by another.
If substitution produces a new stop codon it is a nonsense mutation.
If substitution affects introns and exons it is a splice-site mutation.
If substitution changes one mRNA codon it is a missense mutation.
In a deletion (mutation) a base is removed.
In an insertion (mutation) a base is added.
A change to a single nucleotide / base is a point mutation.
Insertion and deletion (mutations) can potentially cause frameshift
mutation.
A frameshift mutation alters all the triplets following it.
If any of these mutations occurs in a protein-coding gene, then the
protein produced may be altered (or not produced at all).
• Chromosome structure mutations —
deletion; duplication; translocation.
• The substantial changes in chromosome
mutations often make them lethal.
Chromosome structure mutations
• There are different types of
chromosome mutations, depending on
how the chromosome is altered,
including:
– Deletion
– Duplication
– Translocation
Chromosome deletion
Deletion
• The structure of a
chromosome can be
altered by:
– Deletion resulting in the
loss of a segment of the
chromosome
– Can result in Cri-du-chat
syndrome (deletion of
part of the short arm of
chromosome 5)
The name of this syndrome is
French for "cry of the cat,"
referring to the distinctive cry of
children with this disorder.
Chromosome duplication
Translocation
A
B
B
Chromosome 1
C
C
D
D
E
E
S
A
Translocat
ed genes
S
T
T
Chromosome 2
BREAK
U
U
V
V
Chromosome translocation
Part of chromosome
22 has been
translocated to
chromosome 9
This karyotype is from a woman with 45 chromosomes and a
translocation between chromosomes 13 and 14
No abnormal symptoms detected!
Translocation sufferer film
• http://www.youtube.com/watch?v=8FGYzZ
OZxMw
Familial Down’s syndrome
• The vast majority of Down’s
syndrome cases results
from an extra copy of
chromosome 21, however in
about 5% of cases one
parent has the majority of
chromosome 21
translocated to chromosome
14 resulting in Familial
Down’s syndrome
Chronic Myeloid Leukaemia
Form of cancer that affects stem cells that
give rise to white blood cells
These stem cells are affected by reciprocal
translocation of chromosomes 9 and 22
The translocation results in what is called a
cancer causing oncogene
An oncogene encodes for a protein that
promotes uncontrolled cell growth, cancer
Chromosome structure mutations
•
1.
There are different types of chromosome
mutations. The substantial changes which
occur often make them lethal.
Duplication – a part / whole chromosome is
duplicated (copied) e.g. common cancers
2. Translocation a part / whole chromosome is
moved to another chromosome e.g. Chronic
myeloid leukaemia (CML)
3. Deletion – a part / whole chromosome is
deleted E.g.Cri-du-chat syndrome
Chromosome mutation case
studies:
• Cri-du-chat syndrome (deletion of part of the
short arm of chromosome 5)
• Chronic myeloid leukaemia (CML) (reciprocal
translocation of a gene from chromosome 22
fused with a gene on chromosome 9)
• Familial Down’s syndrome (in 5% of cases one
parent has the majority of chromosome 21
translocated to chromosome 14).