Mutation

Most genes have several different variants, called alleles. A gene is made up of a
sequence of nucleotides, each with its own base. The different alleles of a gene
contain slightly different sequences of bases. These different alleles originally
arose by a process called mutation.
Mutation is an unpredictable change in the genetic material of an organism.
A change in the structure of a DNA molecule, producing a different allele of a
gene, is a gene mutation.
Mutations may also cause changes in the structure or number of whole
chromosomes in a cell, in which case they are known as chromosome mutations
(or chromosome aberrations).
Mutations may occur completely randomly, with no obvious cause. However,
there are several environmental factors that significantly increase the chances of
a mutation occurring:
 All types of ionizing radiation (alpha, beta and gamma radiation) can
damage DNA molecules, altering the structure of the bases within them.
 Ultraviolet radiation has a similar effect, as do many chemicals – for
example, mustard gas. A substance that increases the chances of mutation
occurring is said to be a mutagen.
In gene mutations, there are three different ways in which the sequence of bases
in a gene may be altered. These are:
 base substitution, where one base simply takes the place of another; for
example, CCT GAG GAG may change to CCT GTG GAG
 base addition, where one or more extra bases are added to the sequence;
for example, CCT GAG GAG may change to CCA TGA GGA G
 base deletion, where one or more bases are lost from the sequence; for
example, CCT GAG GAG may change to CCG AGG AG.
Base Addition and Deletion
Base additions or deletions usually have a very significant effect on the structure,
and therefore the function, of the polypeptide that the allele codes for.
For example, the amino acids that are coded for by the ‘normal’ sequence shown
above, you will see that it is Gly Leu Leu.
Base additions or deletions always have large effects, because they alter every set
of three bases that ‘follows’ them in the DNA molecule.
Base additions or deletions are said to cause frame shifts in the code. Often, the
effects are so large that the protein that is made is totally useless.
Or the addition or deletion may introduce a ‘stop’ triplet part way through a gene,
so that a complete protein is never made at all.

Base Substitution
Base substitutions, on the other hand, often have no effect at all. A mutation that
has no apparent effect on an organism is said to be a silent mutation.
Base substitutions are often silent mutations because many amino acids have
more than one triplet code, so even if one base is changed, the same amino acid
is still coded for. You have seen above that a change from CCT to CCA or CCG
makes no difference – the amino acid that will be slotted into the chain at that
point will still be Gly.
However, base substitutions can have very large effects. Suppose, for example,
the base sequence ATG (coding for Tyr) mutated to ATT. This is a ‘stop’ triplet, so
the synthesis of the protein would stop at this point.
 The table above shows all the possible triplets of bases in a DNA molecule and
what each code represents. The three-letter abbreviation for each amino acid is,
in most cases, the first three letters of its full name

The table above shows all the possible triplets of bases in a mRNA molecule and
what each code represents
Sickle cell anaemia
One example of a base substitution that has a significant effect on the phenotype
is the one involved in the inherited blood disorder, sickle cell anaemia.
The gene that codes for the amino acid sequence in the β-globin polypeptide is
not the same in everyone. In most people, the β-globin polypeptide begins with
the amino acid sequence coded from the HbA allele:
Val-His-Leu-Thr-Pro-Glu-Glu-Lys4
But in people with the HbS allele, the base sequence CTT is replaced by CAT, and
the amino acid sequence becomes:
Val-His-Leu-Thr-Pro-Val-Glu-Lys
This small difference in the amino acid sequence makes little difference to the
haemoglobin molecule when it is combined with oxygen. But when it is not
combined with oxygen, the ‘unusual’ β-globin polypeptides make the
haemoglobin molecule much less soluble. The molecules tend to stick to each
other, forming long fibres inside the red blood cells. The red cells are pulled out of
shape, into a half-moon or sickle shape. When this happens, the distorted cells
become useless at transporting oxygen. They also get stuck in small capillaries,
stopping any unaffected cells from getting through.
A person with this unusual β-globin can suffer severe anaemia (lack of oxygen
transported to the cells) and may die. Sickle cell anaemia is especially common in
some parts of Africa and in India.