Final answer:
Sickle cell anemia is caused by a substitution of glutamic acid by valine in the hemoglobin protein due to a single nucleotide mutation. This single change in the protein's structure results in the sickling of red blood cells and the symptoms of the disease.
Step-by-step explanation:
The amino acid substitution that is responsible for sickle cell anemia is the replacement of glutamic acid by valine at the sixth position in the beta chain of hemoglobin.
This point mutation occurs due to a change in a single nucleotide in the DNA sequence encoding the beta chain of hemoglobin, specifically, replacing adenine (A) with thymine (T) at the 17th nucleotide position. As a result, instead of the codon GAG which encodes glutamic acid, the mutant gene has the codon GTG, which encodes valine.
Consequently, the altered structure of hemoglobin S (HbS) leads to the sickling of red blood cells, impaired blood flow, and the various symptoms of sickle cell disease. The remarkable aspect of sickle cell anemia is that out of the approximately 600 amino acids that make up the hemoglobin molecule, it is the alteration of just one that leads to this significant change in the molecule's properties and the resultant disease.