Conclusion

Two general categories of mutation at the level of the DNA molecule are base mutations (also called point mutations) and frameshift mutations.

Base mutations involve the replacement of one base with another. These mutations may lead to a change in the gene product or, because of the redundancy of the genetic code, they may not.

Base mutations can be generated by tautomeric shifts of bases, substitution of base analogues in the DNA molecule, or chemical mutagens that alter the composition and structure of bases thereby altering bonding affinities.

Mismatch repair and/or subsequent rounds of DNA replication can result in the base substitution becoming incorporated in daughter DNA molecules.

Tautomers are structural isomers of organic molecules that differ in the bonding location of a single hydrogen atom. The stable tautomers which result in the standard base pairings of the DNA molecule are the keto forms of thymine and guanine and the amino forms of cytosine and adenine. A tautomeric shift of keto to enol or amino to imino results in altered bonding affinities.

Base analogues are molecules that can substitute for a base in the DNA molecule. The keto tautomer of 5-bromouracil (a derivative of uracil) is a base analogue for thymine. The presence of bromine in the molecule increases the likelihood that a tautomeric shift will change keto 5-bromouracil to the enol tautomer. The enol tautomer forms three hydrogen bonds, therefore has greater bonding affinity for guanine than for adenine (the standard pairing with thymine or its analogue keto 5-bromouracil).

Chemical mutagens can alter the structure and bonding properties of bases by adding or removing functional groups from the molecule. One class of chemical mutagens are the alkylating agents, which alter bases by adding an alkyl group to the molecule. An example of this is alkylation of guanine by sulfur-containing molecules in the family of compounds known as mustard gases. Alkylation of guanine produces 6-ethyl guanine which is a base analogue for adenine.

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