Principles of Genetics and Breeding

6.1.3 Gene Mutations

Most information is available about point or gene mutations. Through base substitution, a base pair in the wild type allele may be replaced by another base in the mutant allele. Several kinds of changes are recognized.

• A transition is an exchange of a purine with another purine or a pyrimidine with another pyrimidine .
• A transversion refers to the substitution of a pyrimidine with a purine or vice versa .
• One characteristic of point mutation is that they can revert.
• Another category includes those called frameshift mutations,which result when one nucleotide or more is inserted or deleted, thus altering the reading frame in the following transcription and translation process, and leading to changed amino acid sequence in the resulting protein.
• Gene mutations result from alterations to the number, type, and arrangement of bases within a gene.
• Watson and Crick suggested that the base sequence in DNA acted as a code which determined the amino acid sequence of polypeptides.
• Triplet of bases determine a single amino acid. GAA specifies Leucine, but alteration of the first base to A converts the triplet to AAA, which specifies phenylalanine.

During DNA replication, old strands act as templates for the new ones, and base pairing is highly specific. Provided the bases never alter in any way, accurate replication is thus ensured. However, they do alter, and at an alarmingly high frequency. There are three kinds of alteration.

1. Depurination. A and G may break off, leaving gaps in the double helix.

   TCAGAAA TC -- GAAA TCGAAA

   AGTCTTT AG T CTTT AGCTTT 1Bp shorter

2. Deamination. C may lose its amino group, and so become U.The latter pairs with A, not G, so a switch from C:G to U:A may occur.

   TCAGAAA TUAGAAA TUAGAAA

   AGTCTTT AGTCTTT AATCTTT (A instead of G)

3. Tautomerism. Like many organic molecules, the bases may change their shape (isomerism).

• Thus, C may become C_R (-R= rarestate), and since C_R pairs with A, this can also result in a C:G to T:A switch. All these alterations are due to random chemical reaction occurring between DNA and the many substance found in the nucleus.

The following structural changes occur in DNA

1. Pyrimidine dimers, in which two adjacent pyrimidines on a DNA strand are coupled by additional covalent bonds and thus lose their ability to pair.
2. Chemical changes of single bases, such as alkylation or deamination, thus causing changes in the pairing properties of the DNA.
3. Crosslinks between the complementary DNA strands, which prevent their separation in replication.
4. Intercalation of mutagenic agents into the DNA, causing frameshift mutations.
5. Single-strand breaks.
6. Double-strand breaks.