HOW DO GENE MUTATIONS CAUSE CHARACTER DIFFERENCES?

The expression of genetic information involves two steps. The first step is the transcription and translation of the
information into a polypeptide. The second step is concerned with the action of the polypeptide:

information flow action

gene --------------------------- polypeptide ------------------------------ character

When a mutation takes place the information in the gene is changed and it is then expressed differently:

different different different

mutation --------- new allele ----------- altered polypepetide ---------- character difference
coding information action

Sickle-cell anaemia in man

Sickle-cell anaemia is a genetically transmitted disease of the blood caused by an abnormal form of the adult haemoglobin.

Haemoglobin is a transport protein which carries oxygen. In normal humans the protein is composed of four polypeptides
two identical alpha chains and two identical beta chains. These four chains associate together to give the structure of
haemoglobin. An abnormal form of haemoglobin in some people causes them to suffer from the blood disorder sickle-cell
anaemia.

The difference between normal haemoglobin and abnormal haemoglobin is due to a difference in only one amino acid.
Valanine (GUA) is replaced by glutamic acid (GCA).

-chain HbA
Val His Leu Thr Pto Glu - Glu .....

Val His Leu Thr Pro Val - Glu .....

HbS

This discovery showed that mutations alter the phenotype because they affect the amino acid sequence.

Mutations and their role in evolution

Now we know about the structure of haemoglobin and the molecular basis of the defect whi8ch causes sickle-cell anaemia.
The gene which controls this character has two alleles and three genotypic classes. The alleles are Hb A (normal) and HbS
(sickle) This allows for three genotypes and their corr4esponding phenotypes:
HbA HbA - normal
HbA HbS - carrier with normal phenotype
S S
Hb Hb - sickle cell
Blood of people with sickle cell has crescent shaped red cells. The cells tend to clump together and are rapidly destroyed in
the body. This results in anaemia, damage to vital organs and death.

It is therefore surprising to find this allele occurring in very high frequencies (10% to 20%) in West Africa, parts of the
Mediterranean and India. The allele, in fact, is only found in areas where malaria is regularly found too. What happens is as
follows:
1. People with sickle-cell are at a disadvantage due to the high death rate from anaemia.
2. People with normal blood are fed on by many species of mosquitoes, including those which carry the protozoan
plasmodium which causes malaria.
3. People who carry one sickle cell allele have an advantage over both the above. They are normally free of sickle-
cell anaemia and have resistance to malaria.

In this example we can see how natural selection can act to maintain potentially harmful alleles of a gene in a population. It
is also a nice demonstration of how natural selection work on a population, rather than individuals.