Mutations

Mutations

Mutation is a random, undirected, and heritable variation seen in DNA of the cell. This is caused by a change in base sequence of DNA due to addition, deletion, or substitution of one or more bases in the nucleotide sequence of DNA. It can involve any of the genes present in the bacterial chromosome. Mutation results in insertion of a different amino acid into a protein, resulting in the appearance of an altered phenotype.

Types of Mutations

Mutations are a natural event occurring in dividing cells. The frequency of mutations ranges from 10⁻² to 10⁻¹⁰ per bacterium per division. These occur spontaneously or are enhanced by different mutagens. Mutations are of three types: (a) base sub-stitution, (b) frame-shift mutation, and (c) mutations due to transposons or insertion sequences.

◗ Mutation due to base substitution

This type of mutation occurs when one base in the nucleotide sequence is inserted in place of another. This occurs during replication of DNA either due to an error in the function of DNA polymerase or due to a mutagen that alters the hydrogen bonding of the base being used as a template in such a manner that the wrong base is inserted. The base substitution mutation may be of two types: missense mutation and nonsense mutation.

a)        Missense mutation: It is one in which the base substitutionresults in a codon that specifies a different amino acid to be inserted.

b)       Nonsense mutation: It is another type of mutation inwhich the base substitution produces a terminal codon that stops synthesis of protein prematurely. Entire protein function is destroyed during the process of nonsense mutation.

◗ Frame-shift mutation

It is the second type of mutation. This occurs when one or more base pairs are added or deleted in the DNA. This, therefore, leads to shifting of the reading frame of the ribosome that results in incorporation of the wrong amino acids downstream from the mutation. Result of the frame-shift mutation ends in production of an inactive protein.

◗ Mutation due to transposons or insertion sequence

This is the third type of mutation that occurs when transpo-sons or insertion sequences are integrated into the DNA. These newly inserted pieces of DNA cause profound changes in the gene into which they are inserted and also causes changes in the adjacent genes.

Causative Agents of Mutation

Mutation can be caused by (a) viruses, (b) radiation, or (c) chemicals.

◗ Viruses

Bacterial viruses (mutator bacteriophage) are an example of viruses that cause a high frequency of mutation by inserting their DNA into the bacterial chromosome. Mutations can occur in various genes as viral DNA can insert bacterial chromosome at many different sites. The mutations caused by these viruses may be either frame-shift mutations or deletions.

◗ Radiations

X-rays and ultraviolet light are the examples of radiation that can cause mutation in chromosomal DNA.

      X-rays: X-rays damage DNA in many ways. They causedamage by producing free radicals that can attack the bases or alter them in the strand, thereby changing their hydro-gen bonding. They also damage DNA by breaking the cova-lent bonds that hold the ribose phosphate together.

      Ultraviolet light: Ultraviolet radiation causes damage inDNA by cross-linking of the adjacent pyrimidine bases to form dimers. For example, the cross-linking of adjacent thymine to form thymine dimers results in the inability of DNA to replicate properly.

◗ Chemicals

Various chemicals, such as nitrous acid, alkylating agents, benzpyrene, and base analogs, such as 5-bromouracil cause mutation in several different ways:

      Benzpyrene: This is commonly present in tobacco smokethat binds to existing DNA bases and causes frame-shift mutations. The benzpyrene, which is a carcinogen as well as a mutagen, intercalates between the adjacent bases, thereby distorting and offsetting the nucleotide sequence in the DNA.

      Nitrous acid and alkylating agents: They act by alteringthe existing base in the DNA. This results in formation of a hydrogen bond with a wrong base. For example, adenine does not form bond with thymine but makes wrong pair with cytosine.

      Base analogs: Base analogs, such as 5-bromouracil, haveless hydrogen bonding capacity than thymine, so they bind to guanine with better frequency. This results in a mutation due to a transition from AT base pair to a GC base pair. Iododeoxyuridine, an antiviral drug, also acts as a base-pair analog.

Effects of Mutations

Mutations in the bacteria cause a lot of changes in their various properties. Mutation alter drug susceptibility, anti-genic structure, and virulence of mutant bacteria. It also alter susceptibility of bacteria to bacteriophages, alter their colony morphology and pigment productions, and affect their ability to produce capsule or flagella. Development of drug resistance due to mutations in bacteria is a major health concern.

Conditional Lethal Mutation

Lethal mutations occur when some mutations involve vital functions, resulting in production of nonviable mutants. On the other hand, a conditional lethal mutation is a form of lethal mutation, in which mutation is expressed only under certain conditions, resulting in production of viable mutants. This is of medical importance, because it is made use for preparation of vaccine strains. Temperature-sensitive strains are the most common example of conditional lethal mutations.

The temperature-sensitive organisms have the unique property of replicating at a low permissive temperature, such as 328C but cannot grow at a higher restrictive temperature, such as 378C. This is due to a mutation that causes changes in an amino acid in an essential protein, allowing these organisms to function at 328C but not at 378C. Temperature-sensitive influenza virus strain used in experimental vaccine is an example of conditional lethal mutations. This influenza vaccine contains a virus that can grow at 328C and infect nose and can replicate and induce immunity. But the virus cannot grow at 378C, hence cannot infect the lungs and does not cause pneumonia.