What advantage does the sickle cell trait offer to people living in areas where malaria is prevalent?
What is Sickle Cell Anemia?
Red blood cells with normal hemoglobin (HbA) move easily through the bloodstream, delivering oxygen to all of the cells of the body. Normal red blood cells are shaped like jelly- filled doughnuts with a depression in the center and they are soft and flexible. Sickle cell anemia occurs when an abnormal form of hemoglobin (HbS) is produced. HbS molecules tend to clump together, making red blood cells sticky, stiff, and more fragile. Red blood cells containing HbS can clog blood vessels, deprive the body’s tissues and organs of the oxygen they need, and are short-lived. Normal red blood cells last about 4 months in the bloodstream but sickle cells only last 10 to 20 days, which causes anemia (a low number of red blood cells). People who are anemic tire more easily and often feel weak (NIH, 2007).
Sickle cell anemia is not contagious and cannot be passed from one person to another like a cold or other infection. People with sickle cell anemia have inherited two sickle cell alleles, one from each parent. A child who has inherited the sickle cell allele from only one parent will not develop the disease, but they do carry the sickle cell trait. People carrying a single sickle cell allele can pass the trait to their own children.
One would think that there is little reason for sickle cell disease to remain in the any human population since natural selection should favor reduction of the frequency of the sickle cell allele to near zero. For example, individuals who carry two copies of the sickle cell allele typically die before reaching reproductive age, which will reduce the frequency of the allele in a population and minimize its transfer between generations. Why does the disease exist at all? An understanding of the origin of sickle cell disease and several other red blood cell disorders requires knowledge of a few of the basics about genetics and something about the process of natural selection. There is also another piece of the puzzle: malaria.
MalariaThe plasmodium parasite that causes malaria in humans is transmitted by mosquitos and the parasite spends part of their life cycle in mosquitos and part of it in human hosts. The parasite enters the human bloodstream via the saliva of an infected female mosquito obtaining a blood meal. Once in the blood stream and liver the parasites replicate to the point that the liver cells are filled with new copies of the parasite. These are then released into the bloodstream where they invade circulating red blood cells. After penetrating the red blood cells, the parasites consume hemoglobin in the red blood cells and enlarge until they fill the cell completely. During their growth these plasmodia particles reproduce forcing red blood cells to lyse (break apart) releasing new copies into the blood stream where they continue to infect new red blood cells. A mosquito taking a blood meal from a person whose red cells contain malaria-causing parasites then becomes a host furthering the transmission cycle.
Defenses Against Malaria
One point at which the life cycle of the malarial parasite can be stopped in humans is at the phase of red blood cell invasion and multiplication. Red blood cells are constantly created and destroyed as part of their life cycle. Any defense mechanism that could somehow destroy both the infected red blood cells and the parasite could potentially eliminate the malaria parasite because healthy red blood cells would eventually replace infected cells.
Interestingly enough, carrying just one copy of the sickle cell allele trait provides a survival advantage over people with normal hemoglobin in regions where malaria is endemic. People (and particularly children) infected with the malarial parasite are more likely to survive the acute illness if they possess just one copy of the abnormal allele than are people with two normal hemoglobin alleles. These individuals are therefore more likely to reach reproductive age and pass their genes on to the next generation. On the other hand, people carrying two copies of the abnormal allele encoding hemoglobin have a significant chance of dying of acute malarial infection in childhood. The precise mechanism by which sickle cell trait imparts resistance to malaria is unknown but a number of factors likely are involved.
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