Читать книгу Cell Biology - Stephen R. Bolsover - Страница 80

A mutation that changes the codon from one amino acid to that for another by substitution of one base for another is a missense mutation (Figure 3.11). As shown in Figure 3.9, the second base of each codon shows the most consistency with the chemical nature of the amino acid it encodes. Amino acids with hydrophobic side chains, shown in black in Figure 3.9, have a U or a C – a pyrimidine – in the second position. With two exceptions, serine and threonine, amino acids with hydrophilic side chains, shown in green in Figure 3.9, have a G or an A – a purine – in the second position. This has implications for mutations of the second base. Substitution of a purine for a pyrimidine is very likely to change the chemical nature of the amino acid side chain significantly and can therefore seriously affect the protein. Sickle cell anemia is an example of such a mutation. At position 6 in the β‐globin chain of hemoglobin, the mutation in DNA changes a glutamate residue encoded by GAG to a valine residue encoded by GTG (GUG in RNA). The shorthand notation for this mutation is E6V, meaning that the glutamate (E) at position 6 of the protein becomes a valine (V). This change in amino acid alters the overall charge of the chain and the hemoglobin tends to precipitate in the red blood cells of those affected. The cells adopt a sickle shape and therefore tend to block blood vessels, causing sickle cell anemia with painful cramp‐like symptoms and progressive damage to vital organs.