Mutations File

• A mutation is a spontaneous change in the genetic
• Generally they occur when DNA is copied or when cells
• Can only be passed to the next generation if they
happen in the germ cells
– those that produce the gametes
• If they happen in somatic or body cells, they cannot be
passed on.
• An accumulation of mutations may contribute to:
– ageing
– cancer
• Mutations can happen randomly.
• Mutation rate increased by certain environmental
– ionising radiation
• α, β, and γ-radiation
– UV radiation
– chemicals:
tobacco tar (a mixture of many noxious chemicals)
all of these are mutagens
There are two basic types of mutation:
Gene mutation:
• changes in the DNA
• result in a different
allele or gene
• e.g. sickle cell
anaemia and cystic
Chromosome mutation:
• cause changes to the
structure or number
of chromosomes
• e.g. Down’s syndrome
Gene Mutations
• These are changes in base sequence in the
• If it is a change in a single base, such a
mutation is known as a point mutation.
• There are three basic ways in which a base can
be changed:
– base substitution
– base addition
– base deletion
Base Substitution
• Quite simply one base is substituted for another.
• Example:
– the DNA triplet AAA might be changed to AAG
• Q. What would be the effect of such a change?
– AAA codes for phenylalanine
– AAG codes for phenylalanine
• This substitution causes no change in the amino
acid coded for
– it is a silent mutation
• Substituting a single base often has no effect on the
amino acid coded for:
– this is because the DNA code is degenerate
– i.e. the same amino acid may have several codes
– example: CAA, CAG, CAT and CAC all code for valine
• In such cases any mutation is a silent mutation
– it has no effect on the phenotype
• Alternatively, a point mutation may have a significant
– substitution results in a different amino acid being coded for
(as happens in sickle cell disease)
– a code that gives a totally different instruction (e.g. Stop)
Q. What would be the effect of a base
substitution changing the DNA triplet ACA to
• ACA codes for cysteine
• ACT codes for the stop instruction
• ACC codes for tryptophan
Base Addition and Deletion
• An extra base is inserted into the DNA sequence.
• Upsets the coding for every amino acid after the
• A base is removed from the DNA sequence.
• Upsets the coding for every amino acid from the
deletion onwards.
• Base additions and deletions always have
larger effects than substitutions:
– they cause a ‘frame shift’ in the code
• Instead of a single amino acid being affected,
every one after the change could be affected.
• That said, even a single changed amino acid
can have profound consequences.
– (See sickle cell anaemia and cystic fibrosis.)
Chromosome Mutations
• Chromosome mutations are gross changes to the
structure of chromosomes.
• Non-disjunction is responsible for some
chromosome mutations, i.e. failure of
chromosomes to separate during cell division.
• Example:
– Down’s syndrome
• chromosome 21 fails to separate during meiosis
• an egg cell receives two copies of this chromosome
• fertilisation results in a zygote with three copies of the 21st
• trisomy 21, causes Down’s syndrome
• Other examples are:
– Klinefelter’s syndrome (XXY)
– XYY syndrome
– Turner’s syndrome (XO)
 Sometimes whole sets of chromosomes fail to separate
during cell division.
If it’s during meiosis:
• a diploid gamete is
• fertilisation of which
produces a triploid cell
If it’s during mitosis in the
• a tetraploid results
 Such polyploid plants are relatively common.
 If such polyploidy happens in animals, the embryo
fails to develop properly and aborts.
• Polyploid plants are relatively common.
• They are important in the evolution of:
– modern wheat (Triticum aestivum)
– a salt marsh grass (Spartina townsendii)
Wheat (Triticum asestivum) in a
field untreated with selective
Spartina townsendii, a common
grass of salt marshes.
Examples of Gene Mutations
• There are several examples of gene mutation
that you may already be familiar with:
– sickle cell anaemia
– phenyl ketonuria
– cystic fibrosis
– industrial melanism in insects
• Details of these will be examined on the
following slides.
Sickle Cell Anaemia
• Sickle cell anaemia is an inherited blood disorder.
• It affects a significant number of people of AfroCaribbean and African descent.
– Haemoglobin is a globular protein made from four
polypeptide chains, each of which has an iron
containing haem group.
– There are two α and two β polypeptides.
• A mutation causes a change in amino acid 6 of
the β polypeptide chain.
– In the homozygous state this causes sickle cell
• A possible code for the first seven amino
acids of normal haemoglobin in the
transcribing strand of DNA is:
CAT-GTA-AAT-TGA-GGA-CTT-CTC- - • However, a base substitution results in a
changed sequence:
Q. Which amino acids are coded for by both of
these sequences?
Val – His – Leu – Thr – Pro – Glu – Glu - CAT-GTA-AAT-TGA-GGA-CAT-CTC- - -
Val – His – Leu – Thr – Pro – Val – Glu - -
Val – His – Leu – Thr – Pro – Glu – Glu - Val – His – Leu – Thr – Pro – Val – Glu - Q. Which is the changed amino acid and what is it
replaced with?
• Sixth amino acid is changed:
– from glutamate to valine
• The replacement of acidic glutamate with non-polar
valine results in the haemoglobin becoming
insoluble under low oxygen concentrations.
Q. In small groups discuss why such an apparently
minor change might have such a big effect.
• Things you may want to consider: effect on
overall protein structure; effect on haemoglobin
solubility, especially at low O2 concentration;
effect on red blood cell shape; whether the allele
is present in homozygous or heterozygous state…
• Summarise the main points.
Effect on protein
(Hb) structure
The sixth amino acid of the β polypeptide
(glutamic acid or glutamate) is replaced
by valine.
Effect on
The haemoglobin molecule is made
insoluble under low O2 conditions and
forms fibres in the cytoplasm.
Effect on red blood The red blood cell can be pulled into a
cell shape
sickle or crescent moon shape by the
Effect on oxygen
Sickled red cells cannot carry O2.
Furthermore, they can get trapped in
capillaries and reduce O2 supply further.
homozygous or
The effect is more severe in the
homozygous state, i.e. two copies of the
allele. Suffer from sickle cell anaemia.
Phenylketonuria (PKU)
• Phenylketonuria is a genetic disease caused by an
abnormal base sequence that codes for the
enzyme phenylalanine hydroxylase.
• Consequently:
– the enzyme is not made
– phenylalanine is not metabolised and its
concentration builds up – damages nerve cells
• The amino acid phenylalanine is found in many
foodstuffs and is usually metabolised to tyrosine.
– Tyrosine can be further metabolised into melanin and
Phenylalanine hydroxylase
an important pigment
a key hormone controlling
Q. What are the potential consequences of PKU if it is
not identified and treated?
Build up of phenylalanine
• Damage to nerve cells and severe mental
Lack of tyrosine
• Other metabolites not made:
– lack of melanin
– lack of thyroxine and retarded growth
Q. How is PKU identified?
• Screened for at birth
• Heel prick blood test done within 2–3 days of birth
Q. How is PKU treated?
• Special diet with phenylalanine levels reduced so
that normal brain cell development occurs.
Q. Why do low-calorie drinks containing aspartame
carry the message ‘warning this drink contains a
source of phenylalanine’?
• The sweetener is metabolised by the liver into
• If drunk by those with PKU...
This type of warning is for PKU sufferers.
Cystic Fibrosis
• Cystic fibrosis is an inherited genetic condition.
• It is an autosomal recessive (carried on
chromosome number 7) and so must be present
in the homozygous state to be expressed.
• People with cystic fibrosis are unable to make a
chloride transfer protein that is normally present
in the cell surface membranes.
• Consequently, a thick mucus is produced:
– can accumulate in the lungs, causing respiratory
– can block secretion of pancreatic enzymes
Q. Suggest why failure to transfer chloride ions
results in a thick mucus.
• Chloride ions are osmotically active:
– when secreted into the mucus they lower its
water potential
– water is drawn into the mucus, thinning it
– if less chloride is secreted, water is not drawn into
the mucus which remains thick and viscous
Industrial Melanism
• Before the Industrial Revolution, trees and rocks
were covered with lichens. Many insects had
colour patterns that camouflaged them against
the background.
• Burning coal produced pollution (SO2 and smoke)
which killed the lichens and blackened the trees
and rocks.
• Variants with a darker colour (melanics) were
• The case of the peppered moth (Biston betularia)
is well documented.
• The normal, pre-industrial form had a speckled
appearance and was camouflaged, protecting it
from predatory birds during the day.
• Speckled or peppered appearance is recessive.
• A dominant mutation that codes for dark colour
occurs fairly frequently, but individuals with this
mutation were at a selective disadvantage and so
did not survive.
• After the industrial revolution, selection pressure
changed and the melanic form had a selective
advantage. The rest is history.
Q. What selection pressure operated against the melanic
variants before the Industrial Revolution?
• Predation:
– birds could see the melanics against the lichen covered
trees and rocks
Q. How did selection pressure change with the industrial
• Lichens disappeared (sensitive to SO2) and the trees and
rocks were blackened with soot.
• Peppered variants were visible.
Q. Suggest what effect clean air legislation has had upon
the frequency of melanic insects such as the peppered
moth in Britain.
• Melanic frequency reduced.
• No soot blackening of trees and lichens recover.
Melanic or
carbonaria form is
visible against the
pale background
Speckled or typica
form is well
camouflaged against
the pale background
Melanic and peppered forms of Biston betularia on a birch tree.
Image licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

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