Principles of Biochemistry, Volume 3 - A. Lehninger 1985

Molecular Mechanisms of Genetic Information Transfer
More on Genes: Repair, Mutation, Recombination, and Cloning
A change in a single base pair causes a point mutation

Despite the efficiency of DNA proofreading and repair mechanisms, some damage or Replication errors inevitably remain uncorrected. This, in turn, leads to genomic alterations that can persist and be inherited. Permanent, heritable changes arising during replication are known as Mutations.

Mutations caused by the replacement of a single base pair are called substitution mutations. In such a mutation, the alteration affects only a single codon of the affected Gene. Consequently, this may result in the substitution of one amino acid for another in the polypeptide encoded by that gene, or the Amino Acid Sequence may remain unchanged. Examples of point Mutations and their consequences are given in Table 30-1. Often, the substitution of one amino acid for another does not significantly alter the biological Properties of the Translation product, namely the protein. Such substitutions are referred to as “silent” mutations. In other cases, however, the substituted amino acid may be crucial, rendering the protein completely incapable of performing its normal biological function. Such mutations are frequently lethal to Cells. For example, a point mutation in the codon for a specific Serine residue—a critical component of the enzyme's Active Site (such Enzymes are known as serine enzymes; see Section 9.12; Table 30-1)—results in the complete loss of enzymatic activity. If this enzyme participates in a major metabolic pathway, the mutation can prove lethal.

Class="center">Table 30-1. Effect of some hypothetical substitution point mutations on the biological activity of the final protein product

It may also happen that, despite The amino acid substitution, the mutant protein retains its function but differs in its properties from the normal protein, making it less efficient than the wild type. For instance, if the mutation affects an enzyme, it may exhibit a higher K_M, a lower V_max, or both. Mutants that synthesize such altered yet partially functioning Proteins are called leaky mutants (Table 30-1). Occasionally, a gene mutation may yield a polypeptide product better adapted to perform its function under the specific environmental conditions encountered by the Organism. Such mutations confer a selective advantage on the progeny, and a succession of such mutations can ultimately lead to The Emergence of a new species.

Point substitution mutations account for only a small fraction of the mutations observed in Bacteria. Far more numerous and hazardous to cells are mutations involving Nucleotide insertions and deletions.