There are two basic types of mutations:

• base substitutions - this is the replacement of one base by another. For example, if a DNA molecule usually contains guanine at a certain position, but adenine takes the place of the guanine, then a base substitution has occurred. There are two types of base substitutions:
  • transitions - these involve the replacement of a purine with the other purine, or the replacement of a pyrimidine with the other pyrimidine.
  • transversions - these involve the replacement of a purine with a pyrimidine or vice versa.

(Question: if a transition occurs on one strand of DNA, what type of change must occur on the complementary strand in order to maintain complementary base pairing?)

• frameshift mutations - these change the reading frame of a gene. There are two types of framehift mutations:
  • insertions - as the name implies, these involve the insertion of one or more extra nucleotides into a DNA chain.
  • deletions - these result from the loss of one or more nucleotides from a DNA chain.

To illustrate the effects of these mutations, consider the following phrase, read as a triplet code (just like the genetic code!):

A base substitution might have an effect like this:

or perhaps:

In each case, the phrase still makes sense, but the meaning has been slightly changed.

An insertion, on the other hand, would have a more profound effect:

Insertion of a single letter ('m' in this case) causes the phrase to become gibberish, because the reading frame has been changed. A deletion would have the same effect:

(Insertion or deletion of one or two nucleotides will change the reading frame of the genetic code. What would happen to the reading frame if three nucletides were inserted or deleted? To further consider the effects of frameshift mutations on reading of the genetic code, go to the genetic code module.)

Base substitutions and insertions or deletions of one nucleotide are also known as point mutations (because they occur at a single point on a chromosome).

Causes of Mutations

Base substitutions are generally caused by changes in the way that nucleotides base pair. One way this occurs is through tautomeric shifts. The chemical nature of the bases of DNA is such that rare but natural, spontaneous fluctuations in the bonds of the bases can occur. These fluctuations can briefly affect the way a base forms hydrogen bonds. For example, adenine, when it undergoes a tautomeric shift, will base pair with cytosine. Therefore, if a tautomeric shift occurs during replication, the wrong nucleotide can be inserted in the newly-synthesized DNA. The bases usually switch back to their normal form quickly, but by that time, it might be too late.

Base substitutions can also be caused by chemical modification of the bases. One type of chemical modification is caused by alkylating agents, such as ethylmethane sulfonate and methylmethane sulfonate. These agents donate alkyl groups (such as methyl and ethyl groups) to bases, affecting their base pairing. For example, when guanine is alkylated, producing 7-ethylguanine, it will base pair with thymine. Once again, if this occurs during replication, the wrong nucleotide can be inserted in the molecule being synthesized, leading to a mutation.