The Genetics Behind Sickle Cell Anemia

Sickle cell anemia is caused by a mutation in the gene encoding the beta chain of hemoglobin. There are two alleles:

• A: Normal hemoglobin allele

• S: Sickle cell hemoglobin allele

Individuals can have three possible genotypes:

• AA: Normal hemoglobin

• AS: Carrier (sickle cell trait)

• SS: Sickle cell anemia

Why Is the S Allele Maintained at High Frequency?

In regions of Africa where malaria is common, the S allele remains at a high frequency due to a phenomenon known as heterozygote advantage. Here’s how it works:

• AS individuals (carriers) are less likely to suffer from severe malaria compared to those with two normal alleles (AA). The presence of one S allele provides enough protection against malaria without causing the full-blown disease seen in SS individuals.

• AA individuals are susceptible to malaria, which can be fatal, especially in childhood.

• SS individuals suffer from sickle cell anemia, a serious and often life-shortening disease.

Because AS individuals have a survival advantage in malaria-endemic regions, they are more likely to survive to adulthood and pass on their genes. This selective advantage ensures that the S allele remains at a relatively high frequency in these populations, despite its harmful effects when inherited from both parents.

Scientific Evidence for Heterozygote Advantage

Numerous studies have shown that the sickle cell trait (AS) confers significant resistance to malaria. In some African regions, up to 10–20% of people carry at least one S allele, a frequency much higher than would be expected if the allele were only harmful. This is because the evolutionary benefit of malaria resistance in carriers outweighs the negative impact of sickle cell disease in homozygotes.

Why Not Other Evolutionary Processes?

• Homozygote advantage: This would predict that either AA or SS individuals have the highest fitness, which is not the case.

• Dominance: This term refers to how alleles express themselves, not to the maintenance of allele frequencies.

• Genetic drift: While genetic drift can influence allele frequencies, the consistent high frequency of the S allele in malaria-endemic regions points to natural selection, not random chance.

Conclusion

The high frequency of the S allele in some African populations is a classic case of heterozygote advantage. This evolutionary mechanism maintains genetic diversity by favoring individuals who are carriers of the sickle cell trait, as they are more resistant to malaria and thus have a better chance of surviving and reproducing in regions where the disease is a major threat.

Correct answer:
(2) heterozygote advantage