Sickle cell anemia (141900) is caused by a specific mutation in the gene for β-globin, one of the two globin proteins that complex with heme to form hemoglobin. The sickle cell anemia mutation is known to produce a single amino acid change, glutamic acid to valine, at position 6 of the β-globin peptide chain. Which of the following is the most likely mechanism for this mutation?
1.Crossing over
2.Single-base substitution point mutation
3.Two base insertion
4.Three base deletion
5.Single base insertion
Solution
A change from one DNA codon to another is required to cause a replacement of amino acids such as the valine to glutamic acid change in the β-globin peptide chain of hemoglobin S (141900). A single nucleotide substitution (point mutation) could effect such an codon change, and involves a thymine to adenine substitution at the second position of the codon 6. The other answers would not change one DNA/RNA codon and its translated amino acid. Equal exchange (crossing over) among homologous β-globin genes could exchange alleles, replacing normal alleles with mutant partners or vice-versa (converting heterozygosity to homozygosity). Unequal crossing over could generate mutant alleles with duplicated or deficient nucleotides. One or two-base insertions would change the reading frame of the genetic code (frame-shift mutation) and produce a nonsense peptide or termination codon (chain-terminating mutation) after the point of insertion. Three-base deletions could also cause frame shifts if out of codon phase, or remove one codon and delete its corresponding amino acid from the peptide product.