Mutations

MUTATIONS
  • A change in the nucleotide sequence of a gene is called mutatiion.
  • Cell or organism which shows the effect of a mutation is called a mutant. Un mutated cells are called wild type.

Types

  • Point mutations 
  • Frameshift mutations

Point mutation

  • Substitution of one nucleotide for another is called point mutation.
  • Transition - replacement of a purine by purine or replacement of a pyrimidine by a pyrimidine
  • Transversion - replacement of a purine by pyrimidine or vice versa.
  • Point mutation can result in
    • Missense mutation – An altered protein is produced.
    • Nonsense mutation – Stop codon formed leading to non  production of protein
    • Neutral mutation - There is no change in the protein sequence.

Frame shift mutation

  • Addition or loss of one or more nucleotides in a gene is termed insertion or deletion. This results in a shift of the reading frame. Generally this causes production of nonfunctional proteins because an entirely new sequence of aminoacids is synthesized from a frame shift reading of nucleotide sequence of m RNA.

Mutagens

  • Mutations commonly occur during DNA replication. Some occur as result of damages caused by UV or X ray. Account for many spontaneous mutaions. Mutation rates can be increased by exposing the culture to radiation.
  • Any agent which increases the mutation rate is called a mutagen. Mutation obtained by the use of mutagens is called induced mutation.
  • UV light causes formation of dimmers by cross linking between adjacent pyrimidine especially thymine residues in DNA. X rays cause break in the phosphodiester back bone of nucleic acid.
  • Base analogues are chemicals similar in structure to normal DNA bases. They get substituted during DNA replication. But they donot have the hydrogen bonding properties as normal bases. This leads to introduction of errors in replication resulting in mutation eg: 5-bromouracil.
  • Intercalating agents distort the structures and cause subsequent replication errors. Eg; acridine orange, proflavin and nitrogen mustards.
  • Transposons cause deletions or inversions.

Repair mechanisms

  • When cells exposed to lethal doses of UV light are immediately exposed to visible light photoreactivation occurs. An enzyme designated PRE induced by visible light splits or unlinks the dimmers formed because of UV light. Endonucleases and exonucleases cut out the damaged segment of DNA. Then polymerases and ligases repair the break. This is called excision repair.
  • Inducible or SOS repair – It is used by E.coli. It is not a single discrete mechanism but diverse responses. All are coordinately regulated.
  • Mutation can also be corrected by reverse mutation.
Last modified: Tuesday, 21 September 2010, 4:12 AM