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Mutations
A mutation is a spontaneous change in the genetic material. Generally it occurs either when DNA is
copied or when cells divide. Only if mutations happen in the germ cells (those that produce the
gametes) can they be passed on to the next generation. If they happen in somatic or body cells,
mutations cannot be passed on. However, an accumulation of mutations during the lifetime of an
individual may contribute to the ageing process and cancer.
Mutations in the DNA which result in a different allele or gene are referred to as gene mutations whilst
those that cause changes to the structure or number of chromosomes are known as chromosome
mutations. Mutations can happen randomly but are increased by certain environmental factors, e.g.
ionising radiation (α, β, and γ-radiation), ultra violet (UV) radiation and chemicals like benzene, phenols,
furans and tobacco tar (a mixture of many noxious chemicals). These are all mutagens.
Gene Mutations
These are changes in base sequence in the DNA. 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
Quite simply one base is substituted for another. For example the DNA triplet AAA might be changed to
AAG.
Q. What would be the effect of such a change?
Note: Substituting a single base often has no effect on the amino acid coded for because the DNA code
is degenerate, i.e. the same amino acid may have several codes. For example CAA, CAG, CAT and CAC
all code for valine. In such a case any mutation is referred to as a silent mutation as it has no effect on
the phenotype. However it may have a significant effect if the substitution results in a different amino
acid being coded for (as happens in sickle cell disease) or a code that gives a totally different instruction.
Q. What would be the effect of a base substitution changing the DNA triplet ACA to ACT or ACC?
Base Addition
Here an extra base is inserted into the DNA sequence and so upsets the coding for every amino acid
after the insertion.
Base Deletion
Here a base is removed from the DNA sequence and similarly upsets the coding for every amino acid
from the deletion onwards.
Base additions and deletions always have larger effects because they cause a ‘frame shift’ in the code.
Instead of a single amino acid being affected, every amino acid 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).
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Chromosome Mutations
Chromosome mutations are gross changes to the structure of chromosomes. These can arise in a
number of ways, but one way is the failure of chromosomes to separate during cell division – this is
termed non-disjunction. In humans a failure in separation of chromosome 21 during meiosis results in
an egg cell receiving two copies of this chromosome. Consequently fertilisation results in a zygote with
three copies of the 21st chromosome – trisomy 21 causing Down’s syndrome. Other examples are
Klinefelter’s syndrome (XXY), XYY syndrome and Turner’s syndrome (XO).
Sometimes whole sets of chromosomes fail to separate. If this happens during meiosis a diploid gamete
will result which upon fertilisation will produce a triploid cell. If it happens during a mitotic division in the
zygote, a tetraploid will result. Polyploid plants are common and have been important in the evolution of
modern wheat (Triticum aestivum) and a salt marsh grass (Spartina townsendii). If such polyploidy
happens in animals, the embryo fails to develop properly and aborts.
Examples of Gene Mutations
Sickle Cell Anaemia
Sickle cell anaemia is an inherited blood disorder that affects a significant number of people of AfroCaribbean and African descent. You will recollect from F212 (Molecules, Biodiversity, Food and Health)
that 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 the change in
amino acid 6 of the β polypeptide chain, and in the homozygous state causes sickle cell anaemia.
A possible code for the first seven amino acids of normal haemoglobin is:
CAT-GTA-AAT-TGA-GGA-CTT-CTC- - However, a base substitution results in a changed sequence:
CAT-GTA-AAT-TGA-GGA-CAT-CTC- - Q. Which amino acids are coded for by both of these sequences?
Q. Which is the changed amino acid and what is it replaced by?
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.
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Phenylketonuria (PKU)
Phenylketonuria is another genetic disease caused by an abnormal base sequence that codes for the
enzyme phenylalanine hydroxylase. Consequently the enzyme is not made. Phenylalanine is an amino
acid found in many foodstuffs and is usually metabolised to tyrosine. The tyrosine can be further
metabolised making for example melanin and thryroxine:
Phenylalanine hydroxylase
phenylalanine
tyrosine
melanin
thyroxine
Q. What are the potential consequences of PKU if it is not identified and treated?
• Build-up of phenylalanine
• Lack of tyrosine
Q. How is PKU identified?
Q. How is PKU treated?
Q. Why do some low-calorie drinks containing aspartame carry the message ‘warning this drink contains
a source of phenylalanine’?
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 that can accumulate in the lungs, causing respiratory infection,
and block secretion of pancreatic enzymes.
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Q. In CF, suggest why failure to transfer chloride ions results in thick mucus.
Industrial Melanism
Before the industrial revolution, trees and rocks were covered with
lichens and many insects had colour patterns that allowed them to
be camouflaged against them. Burning coal produced pollution (SO2
and smoke) which killed the lichens and blackened trees and rocks.
Variants with a darker colour (melanics) were favoured. 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?
The peppered moth (Biston betularia) on a
birch tree. The melanic form (top left) and the
peppered form (middle right).
Martinowksy. Image licensed under the
Creative Commons Attribution-Share Alike 3.0
Unported license.
Q. How did selection pressure change with the industrial revolution?
Q. Suggest what effect clean air legislation has had upon the frequency of melanic insects, such as the
peppered moth in Britain.
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