Sickle cell anaemia: The selective forces that a population experiences can vary

Question

Sickle cell anaemia: The selective forces that a population experiences can vary by context, especially by geographic place.

a) Explain in your own words how natural selection affects the evolution of haemoglobin in humans and how and why the selective pressures differ among human populations.

b) For your answer to part a, which are examples of disruptive, stabilizing or directional selection?

c) For human populations living in regions of the world without malaria, do you expect the HS allele to eventually go extinct? Explain.

Explanation / Answer

Sickle-cell disease is a hereditary disease affecting hemoglobin molecules in the blood. The disorder arises as a result of a single nucleotide change in the gene encoding b-hemoglobin, one of the key proteins used by red blood cells to transport oxygen. The sickle-cell mutation changes the sixth amino acid in the b-hemoglobin chain (position B6) from glutamic acid (very polar) to valine (nonpolar). The unhappy result of this change is that the nonpolar valine at position B6, protruding from a corner of the hemoglobin molecule, fits nicely into a nonpolar pocket on the opposite side of another hemoglobin molecule; the nonpolar regions associate with each other. As the two-molecule unit that forms still has both a B6 valine and an opposite nonpolar pocket, other hemoglobins clump on, and the result is the deformed “sickle-shaped” red blood cell.

The defective allele has not been eliminated from Central Africa because people who are heterozygous for the sickle-cell allele are much less susceptible to malaria, one of the leading causes of death in Central Africa. Natural selection has favored the sickle-cell allele in Central Africa and other areas hit by malaria because the payoff in survival of heterozygotes more than makes up for the price in death of homozygotes. This phenomenon is an example of heterozygote advantage.

The prevalence of sickle-cell disease in African populations is thought to reflect the action of natural selection. Natural selection favors individuals carrying one copy of the sickle-cell allele, because they are resistant to malaria, common in Africa.

Stabilizing selection occurs because malarial resistance counterbalances lethal sickle-cell disease. Malaria is a tropical disease that has essentially been eradicated in the United States since the early 1950s, and stabilizing selection has not favored the sickle-cell allele here. Africans brought to America several centuries ago have not gained any evolutionary advantage in all that time from being heterozygous for the sickle-cell allele. There is no benefit to being resistant to malaria if there is no danger of getting malaria anyway. As a result, the selection against the sickle-cell allele in America is not counterbalanced by any advantage, and the allele has become far less common among African Americans than among native Africans in Central Africa.

certain parts of Africa today, the frequency of the mutant gene for sickle-cell (HbS) is very high (5-20%). Studies were carried to know the African frequencies of the HbS gene were so high. If natural selection were working to eliminate the recessive mutant gene, it would be necessary to invoke a mutation rate (from HbA to HbS) 1000 times higher than known for any other human gene in order to explain the continued high frequencies of HbS in the popluation. This seemed so unlikely he reasoned that some other forces must be at work.

Homozygous recessive individuals (HbSHbS) may also have an advantage against malaria, but they have all the other problems associated with sickle cell disease, and hence are severely selected against and seldom reproduce.The situation in which the heterozygote in any population is selectively favored over either homozygote is what is known as balanced polymorphism. It works to maintain a high frequency of the recessive mutant gene even though that gene is highly deleterious in the homozygous recessive form. In a non-malarial environment such as the United States, the heterozygotes would not have a selective advantage, and hence both hetero- and homo-zygote recessives would be selected against. Thus, in accordance with the data, sickle-cell was lower in frequency in the U.S. because there was no advantage to the heterozygote or the homozygote recessive. In malarial environments, heterozygotes (with sickle-cell trait) have an increased fitness (chance of leaving offspring) of 15% over those with normal hemoglobin.

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