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Mutagenesis

The Johns Hopkins University, Baltimore, Maryland

It is now generally accepted that the simplest mutation involves a change in a single base of DNA, so a different amino acid is coded. The new amino acid alters the tertiary structure of the protein on which the catalytic activity of enzymes depend. For enzymes that are critical for the cell, the mutation will probably result in reduced growth or death of the cell unless the addition of a nutrient to the medium compensates for the reduced enzyme function.

Purine and pyrimidine bases as components of DNA almost certainly exist in solution in more than 1 structural form. The common forms pair specifically with their partners, i.e., A with T and G with C. When an uncommon form, which is in equilibrium with the common one, pairs with a different base, a mutation is produced.

Some chemical mutagens change one base of DNA into another, as nitrous acid converts cytosine to uracil and this changes the base pairing during replication. Other agents modify the bases so the proportion of the form pairing with a different base is increased.

Base analogs are mutagenic because they are incorporated in place of normal bases and then pair more frequently with one of the unexpected partners than the normal base.

Acridine mutations are importantly different from those described above. They have played a critical role in a test of the coding mechanism but mutations have not been produced as readily by acridines in biologic units other than bacteriophage.