Sickling of Cells & Malaria

The high representation of the hemoglobin S gene in some populations reflect the protection it provides against malaria. The malaria parasite does not survive as well in the erythrocytes of people with the sickle trait as it does in the cells of normal people. The basis of the toxicity of sickle hemoglobin for the parasite is unknown. One possibility is that the malarial parasite produces extreme hypoxia in the red cells of people with the sickle trait. These cells then sickle and are cleared (along with the parasites they harbor) by the reticuloendothelial system. Another possible mechanism is that low levels of hemichromes are formed in sickle trait erythrocytes. Hemichromes are complexes containing heme moieties that have dissociated from the hemoglobin. Hemichromes catalyze the formation of reactive oxygen species, such as the hydroxyl radical, which can injure or even kill malarial parasites.

The malaria hypothesis maintains that during prehistory, on average, people without the sickle gene died of malaria at a high frequency. On the other hand, people with two genes for sickle hemoglobin died of sickle cell disease. In contrast, the heterozygotes (sickle trait) were more resistant to malaria than normal people and yet suffered none of the ill effects of sickle cell disease. This selection for heterozygotes is called balanced polymorphism. Support for this concept comes from epidemiological studies in malaria-endemic regions of Africa. The frequency of the sickle cell trait is lower in people coming for treatment to malaria clinics than is seen in the general population. The reasonable assumption is that relative protection from malaria is at work in this situation.

Although malaria remains a major health problem in many tropical regions of the world, the disease is not a significant threat to people in temperate zones. Consequently, the protection afforded by the sickle trait no longer has a survival advantage for many groups of people in whom the sickle cell gene is common. This has left sickle cell disease the major health issue in these populations.

Tags: Bio Technology, Bio Genetics, Siclkling of cells

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