Q.Based on your understanding of genetic code, explain the formation of any abnormal hemoglobin molecule. What are the known consequences of such a change?

Formation of Abnormal Hemoglobin and Its Consequences

Hemoglobin is a protein made of four polypeptide chains—two alpha and two beta chains. The genetic code in DNA determines the exact sequence of amino acids in these chains through transcription and translation. Any change in the DNA sequence, called a mutation, can alter the genetic code and lead to the incorporation of a wrong amino acid in the hemoglobin molecule.

The classic example is sickle cell anemia, where a single point mutation occurs in the gene coding for the beta chain of hemoglobin. At the sixth position of the beta chain, the codon GAG (which codes for glutamic acid) is changed to GUG (which codes for valine). This single amino acid substitution—glutamic acid replaced by valine—produces an abnormal hemoglobin called HbS instead of the normal HbA.

Consequences of this change:

• The abnormal hemoglobin molecules polymerize under low oxygen conditions, causing red blood cells to become sickle-shaped or elongated instead of their normal biconcave disc shape.
• These sickled cells are fragile and break down easily, leading to anemia. …

The genetic code operates with exquisite precision: each triplet of nucleotides (a codon) specifies one amino acid in a protein chain. Hemoglobin, the oxygen-carrying protein in red blood cells, consists of four polypeptide chains—two alpha and two beta chains. The beta-globin gene, located on chromosome 11, contains the instructions for building the β-chain. When transcription and translation proceed normally, the sixth amino acid in this chain is glutamic acid, a hydrophilic (water-loving) residue that sits on the protein's surface.

Now consider what happens when a single point mutation occurs in the DNA template strand of the β-globin gene. At the sixth codon position, the normal sequence GAG (which codes for glutamic acid) becomes GTG (which codes for valine) due to an A-to-T substitution in the DNA. This is a classic example of a missense mutation—one nucleotide change that alters a single amino acid in the final protein.

The consequences of this seemingly tiny change are profound. Valine is hydrophobic (water-repelling), unlike the glutamic acid it replaces. When this abnormal hemoglobin—called hemoglobin S (HbS)—releases oxygen in the tissues, the hydrophobic valine residues cause the hemoglobin molecules to stick together, forming long, rigid polymers. These polymers distort the red blood cells from their normal flexible, disc shape into rigid, crescent or sickle shapes.

The known consequences of this abnormal hemoglobin include:

• Sickle-cell anemia: The sickled cells are fragile and break apart easily, leading to chronic anemia (low red blood cell count). Patients experience fatigue, weakness, and shortness of breath.
• Vaso-occlusive crises: The rigid sickled cells cannot squeeze through small blood vessels. They block capillaries, cutting off blood supply to tissues and organs, causing episodes of severe pain.
• Organ damage: Repeated blockages over time damage the spleen, kidneys, liver, and other organs. Children with sickle-cell disease are particularly vulnerable to infections because their spleens become non-functional. …

Instead of tracing DNA -> mRNA -> protein forward, start from the observed abnormal protein and reason backward: a hydrophobic residue (valine) sits where a hydrophilic one (glutamic acid) should be, and by the genetic code table that substitution can only arise from a single base ch …