Spontaneous mutations for a given gene in a wild-type back ground generally occur with a frequency of 10⁻⁶ – 10⁻⁸ in a population derived from a single bacterium (depending on the bacterial species and conditions used to identify the mutation). The mutations include base substitutions, deletions, insertions, and rearrangements. Base substitutions can arise because of mispairing between complementary bases during replication. In E. coli, this occurs about once every 10¹⁰ times the DNA polymerase incorporates a nucleotide—a remarkably rare process. Occurrence of a mispaired base is minimized by enzymes associated with mismatch repair, a mechanism that essentially proofreads a newly synthesized strand to ensure that it perfectly complements its template. Mismatch repair enzymes distinguish the newly synthesized strand from the preexisting strand based on methylation of adenine in GATC sequences of the preexisting strand. When DNA damage is too extensive, a special DNA repair system, the SOS response, rescues cells. The SOS response is a postreplication DNA repair system that allows DNA replication to bypass extensive DNA errors.

Many base substitutions escape detection at the phenotypic level because they do not significantly disrupt the function of the gene product. For example, missense mutations, which result in substitution of one amino acid for another, may be without discernible phenotypic effect. On the other hand, nonsense mutations terminate synthesis of proteins and thus result in a protein truncated at the site of mutation. The gene products of nonsense mutations are inactive.

Rearrangements are the result of deletions that remove large portions of genes or even sets of genes. These large deletions involve recombination between directly repeated sequences (eg, IS elements) and almost never revert. Other mutations cause duplication, frequently in tandem, of com parable lengths of DNA. Such mutations usually are unstable and readily revert. Still other mutations can invert lengthy DNA sequences or transpose such sequences to new loci. Comparative gene maps of related bacterial strains have shown that such rearrangements can be fixed in natural populations. These observations point to the fact that linear separation of DNA loci on a bacterial chromosome does not completely disrupt possibilities for physical and chemical interaction among them.

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مواضيع ذات صلة

Mechanisms of Gene Transfer in Bacteria

Phage Replication

Genotoxicity Through Potential Off-target Nuclease - Induced Double - Strand Breaks

A Broad Range of Genomic Changes by Homologous Recombination–Mediated Genome Editing

Early Transcription of Genes N and Cro

Lambda’s Relatives and Lambda Hybrids

The Genetic Structure of Lambda

The Physical Structure of Lambda

Other Attenuated Systems: Operons, Bacillus subtilis and HIV

Coupling Translation to Termination

trp Multiple Secondary Structures in trp Leader RNA

Early Explorations of the Hypersynthesis