What is the relationship between maleria and sickle cell anaemi?

Malaria is caused by a parasite which infects and reproduces within red blood cells. It eventually lyses the red blood cells which causes the parasite to be in the blood (causing a lot of the symptoms) and the destruction of red blood cells leads to anemia. Individuals with Sickle Cell Anemia have an advantage as the parasite doesn't proliferate so well in their blood and blood cells.

The most-studied influence of the malaria parasite upon the human genome is a hereditary blood disease, sickle-cell disease. The sickle-cell trait causes disease, but even those only partially affected by sickle-cell have substantial protection against malaria.

In sickle-cell disease, there is a mutation in the HBB gene, which encodes the beta-globin subunit of haemoglobin. The normal allele encodes a glutamate at position six of the beta-globin protein, whereas the sickle-cell allele encodes a valine. This change from a hydrophilic to a hydrophobic amino acid encourages binding between haemoglobin molecules, with polymerization of haemoglobin deforming red blood cells into a "sickle" shape. Such deformed cells are cleared rapidly from the blood, mainly in the spleen, for destruction and recycling.

In the merozoite stage of its life cycle, the malaria parasite lives inside red blood cells, and its metabolism changes the internal chemistry of the red blood cell. Infected cells normally survive until the parasite reproduces, but, if the red cell contains a mixture of sickle and normal haemoglobin, it is likely to become deformed and be destroyed before the daughter parasites emerge. Thus, individuals heterozygous for the mutated allele, known as sickle-cell trait, may have a low and usually-unimportant level of anaemia, but also have a greatly reduced chance of serious malaria infection. This is a classic example of heterozygote advantage.

Individuals homozygous for the mutation have full sickle-cell disease and in traditional societies rarely live beyond adolescence. However, in populations where malaria is endemic, the frequency of sickle-cell genes is around 10%. The existence of four haplotypes of sickle-type hemoglobin suggests that this mutation has emerged independently at least four times in malaria-endemic areas, further demonstrating its evolutionary advantage in such affected regions. There are also other mutations of the HBB gene that produce haemoglobin molecules capable of conferring similar resistance to malaria infection. These mutations produce haemoglobin types HbE and HbC, which are common in Southeast Asia and Western Africa, respectively.

You get sickle cell anaemia when you have 2 copies of a gene which produces abnormal red blood cells. 1 copy of the defective gene means that you have an inbuilt resistance to malaria. Fewer people with this single copy get malaria, fewer die of it as children so it becomes more common. When it gets sufficiently common 2 carriers of single copies are more likely to marry. Of their children, on average, one in four will have no defective genes, 2 in four will carry one copy and 1 in four will have 2 copies and sickle cell anaemia.