microbial genetics

Missense mutations involve a single base substitution that changes a codon for one amino acid into a codon for another. For example, the codon GAG, which specifies glutamic acid, could be changed to GUG, which codes for valine. The effects of missense mutations vary. They alter protein structure, but the effect of this change may range from complete loss of activity to no change at all. This is because the effect of missense mutations on protein function depends on the type and location of the amino acid substitution. For instance, replacement of a nonpolar amino acid in the protein's interior with a polar amino acid can drastically alter the protein's three-dimensional structure and therefore its function. Similarly the replacement of a critical amino acid at the active site of an enzyme often destroys its activity. However, the replacement of one polar amino acid with another at the protein surface may have little or no effect. Missense mutations play a very important role in providing new variability to drive evolution because they often are not lethal and therefore remain in the gene pool.

Nonsense mutations convert a sense codon (i.e., one that codes for an amino acid) to a nonsense codon (i.e., a stop codon: one that does not code for an amino acid). This causes the early termination of translation and therefore results in a shortened polypeptide. Depending on the location of the mutation in the gene, the phenotype may be more or less severely affected. Most proteins retain some function if they are shortened by only one or two amino acids; complete loss of normal function usually results if the mutation occurs closer to the beginning or middle of the gene.