Q.It is said, that the harmful alleles get eliminated from population over a period of time, yet sickle cell anaemia is persisting in human population. Why?

The harmful allele for sickle cell anaemia persists because, in its heterozygous form, it offers a survival advantage against malaria. A person who inherits one normal allele and one sickle cell allele (carrier) has red blood cells that are less hospitable to the malaria parasite. In regions where malaria is common, these carriers are more likely to survive and reproduce than individuals with two normal alleles. This selective advantage keeps the sickle cell allele in the population despite the severe disease it causes in homozygous individuals.

• The allele is not eliminated because natural selection favours the heterozygote over both homozygotes in malaria-endemic areas. …

To understand why sickle cell anaemia remains common in certain human populations, we must first revisit the basics of Mendelian genetics and how natural selection works. In a typical scenario, a harmful allele — one that causes a severe, often fatal disease — would be expected to disappear over generations. Individuals carrying two copies of such an allele (homozygous) would have reduced survival or reproductive success, so the allele’s frequency should drop. Yet sickle cell anaemia defies this expectation. Why?

The answer lies in the peculiar nature of the sickle cell allele and its interaction with an environmental factor: malaria. Sickle cell anaemia is caused by a mutation in the haemoglobin gene, leading to abnormal haemoglobin (HbS). Individuals who are homozygous for the sickle cell allele (HbS HbS) suffer from severe anaemia, pain crises, and often die young. That much fits the “harmful allele” story. But the twist is in the heterozygotes — those with one normal allele (HbA) and one sickle cell allele (HbS). These individuals have sickle cell trait, not the full disease. They are largely healthy, and crucially, they are resistant to malaria.

Malaria, caused by the Plasmodium parasite, has been a major cause of death in many tropical and subtropical regions, including parts of Africa, India, and the Mediterranean. The parasite spends part of its life cycle inside red blood cells. In individuals with sickle cell trait, the red blood cells are less hospitable to the parasite — they tend to sickle slightly under low oxygen conditions, which kills the parasite or prevents its multiplication. This gives heterozygotes a strong survival advantage in malaria-endemic areas.

Now, here is the key point from the NCERT textbook: natural selection does not act on the allele alone; it acts on the phenotype — the physical expression of the genotype. In a malaria-prone region, the heterozygous genotype (HbA HbS) has a higher fitness than either homozygote. The normal homozygote (HbA HbA) is susceptible to malaria and may die. The sickle cell homozygote (HbS HbS) dies from anaemia. But the heterozygote survives and reproduces. So the sickle cell allele is maintained in the population because it is beneficial in the heterozygous state, even though it is harmful when homozygous. …

Model it as a three-way fitness comparison in a malaria zone — HbAHbA individuals are vulnerable to malaria, HbSHbS individuals suffer sickle-cell disease, HbAHbS individuals survive both threats — so the allele's persistence follows directly from the heterozygo …