Introductory Microbiology

Mutagens

• The chemical, physical and biological agents that can induce the mutation are referred as mutagens.

Chemical mutagens:
The chemicals can be divided into four groups based on their action namely.
* Base analogs – incorporate in the DNA instead of particular N base.
* DNA reacting chemicals – react with DNA nucleotide.
* Alkylating agents – change the structure of DNA and,
* Intercalating dyes – these chemicals will insert between base pairs of DNA.
The most revealing findings about mutation in recent years have come from studies on the mutagenic effects of various chemicals. There are three main types of mutagenic chemicals. The first consists of compounds that can react chemically with DNA. Since the specificity of DNA replication depends upon purine-pyrimidine binding which results from hydrogen bonding between the amino and hydroxyl groups of the purines and pyrimidines, chemical modification of these amino and hydroxyl groups can cause mutation. Nitrous acid, which can remove amino groups from purines and pyrimidines is such a mutagen. The second type of mutagenic chemicals consists of base analogs.
There are chemicals sufficiently similar in structure to normal DNA bases to be substituted for them during DNA replication. Although similar in structure, base analogs don’t have the same hydrogen bonding properties as the normal bases. They can therefore introduce errors in replication which results in mutation. A third type of mutagenic chemicals is intercalating agents. These are flat molecules that can intercalate between base pairs in the central stack of the DNA helix. By this means they distort the structures and cause subsequent replication erreors. Examples of such agents are acridine orange proflavin and nitrogen mustards.

Physical agents:
Ionizing and non-ionizing radiation:
Mutations most commonly occur during DNA replication. Some mutations occur as the result of damages inflicted by ultraviolet (UV) light or x-rays. Since these agents are an inescapable part of the environment (for eg, UV light is a component of sunlight), they probably account for many spontaneous mutations. However, mutation rates can be increased substantailyby deliberately exposing a culture to such radiation.
Any agent that increases the mutation rate is called a mutagen. Mutations obtained by use of a mutatgen are said to be induced rather than spontaneous, though they may differ only in frequency not is kind. For example, UV light causes mutation under both natural and laboratory conditions. The number of mutants obtained by laboratory conditions is much higher, however, because of the high dosage of UV light used.
The major effect of UV light is to cause the formation of dimmers by cross linking between adjacent pyrimidine, especially thymine, residues in DNA. These cross linked residuse disrupt the normal process of replication by preventing the various polymerases from functioning. When x-rays interact with DNA, the result is usually a break in the phosphodiester back bone of the nucleic acid.
Both non-ionizing and ionizing radiations able to cause mutation. Non-ionizing radiation has wider use in the microbial mutations.
* U.V. light: This non ionizing radiation can be absorbed by purine and pyrimidine strongly at 260 um. Two adjacent pyrimidines form a dimer, by which covaleatly joint. During replication, the DNA polymerase wrongly recognize the pyrimidine and add a wrong pair which leads to mutation called dimerization of thymine.
* Gamma rays: This ionizing radiation at low concentrations react as free radical attack and DNA breakage which leads to mutation. Gamma rays are not commonly used for microbial mutations, instead highly useful for mutating plant materials.

Biological agents:
Transposable element, insertion sequences and Mu phage are some of the biological agents cause mutation.
* Transposable element: A genetic element that can move from one place of chromosomal DNA to another place. Such elements insertion leads to mutation which is referred as transposon mutagenesis.
* Insertion sequences: The simplest type of transposable sequence (about 700-1000 bp) which has the transposable gene alone, which causes the mutation.
* Mu-phage: This double strand DNA containing temperate bacteriophage can able to act as transposable elements, causes mutation by transposition.

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