Cambridge International A Level Biology Revision Guide

Cambridge International A Level Biology
388
In gene mutations, there are three different ways in
which the sequence of bases in a gene may be altered.
These are:
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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 additions or deletions usually have a very significant
effect on the structure, and therefore the function, of
the polypeptide that the allele codes for. If you look up
in Appendix 2 the amino acids that are coded for by the
‘normal’ sequence shown above, you will see that it is Gly
Leu Leu. But the new sequence resulting from the base
addition codes for Gly Thr Pro, and that resulting from
the base deletion is Gly Ser. 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 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 (see
Appendix 2 again), 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.
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. (We have
already looked at the difference between the Hb A and Hb S
alleles on page 374 and the inheritance of this disease on
pages 374–376.)
You will remember that 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 Hb A allele:
Val-His-Leu-Thr-Pro-Glu-Glu-Lys-
But in people with the Hb S 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 (Figure 2.25b, page 34).
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. You can read about the
reasons for this distribution on pages 407–408.
Albinism
Albinism provides an example of the relationship between
a gene, an enzyme and a human phenotype.
In albinism, the dark pigment melanin is totally or
partially missing from the eyes, skin and hair. In humans
this results in pale blue or pink irises in the eyes and very
pale skin and hair (Figure 16.22). The pupils of the eyes
appear red. The condition is often accompanied by poor
Figure 16.22 An albino boy with his classmates in South Africa.