How did the HbS mutation evolve and why it persists today among certain populations?

Based on experimental evidence of a reduced incidence of malaria among people carrying sickle cells in their blood stream, it is now assumed that the presence of the sickle cell trait protects individuals against malaria. Malaria parasites that invade red blood cells of individuals carrying the trait die with the cells when the latter assume the sickle shape and adhere to the walls of the blood vessels.

The hemoglobin S (HbS) mutation that protects against malaria did not develop as a response to malaria itself. It occurred by chance. Those people without the mutation, living in areas where malaria epidemics were common, were at an increased risk to contract this infectious disease, getting symptoms of high fevers, headache, muscle pain, enlarged spleen, and anemia. People carrying only two HbA (non-sickle cell) genes often died in their first few year of life. Those who were lucky enough to carry the HbS gene when malaria struck, had a better chance of living. They would survive to produce children, and their HbS-carrying children in turn would have more HbS-carrying children.

Those with sickle cell disease (two HbS genes) would also die early in life due to complications from the disease itself. The result? After multiple generations of this natural selection, more and more people who had a single HbS gene and a single HbA gene survived to pass on their genes.

Although hemoglobin S is the most common adaptation that occurs in malaria-infested areas, others have also developed. Hemoglobin C and the Thalassemias have also evolved. Thalassemia affects the amount rather than the type of hemoglobin produced. Those people having one HbS and one HbC gene have a milder form of sickle cell disease than those with two HbS genes. And depending on the nature of the thalassemia mutation, those people born with one HbS gene and one beta-thalassemia gene can have conditions ranging from ordinary sickle cell disease to living almost symptom-free.

Adapted from Ragusa, et al

Sickle Cell Disease today is found in North America, Southern Italy, Northern Greece, Southern Turkey, the Middle East, Saudi Arabia, the Eastern Province of Central India, and primarily in equatorial Africa. It is believed that sickle cell started in four different regions, and from three different mutations. One of the mutations is believed to have occurred randomly in two different locations. Scientists have examined the haplotypes of individuals with Sickle Cell to trace where it is these different mutations came from. It is currently believed there are four haplotypes:

1. Senegal haplotype from the Atlantic Coast of West Africa
2. Benin haplotype from Central West Africa, Angola, and Kenya
3. Bantu/Central African Republic haplotype from Zaire, the Central African Republic, Angola, and Kenya
4. Asian haplotype from Eastern Province of Saudi Arabia, and Central India

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