Mutations are heritable changes in the genetic material that give rise to
alternative forms of any gene. These alternate forms are called alleles.
There are two broad types of mutations, those that affect the gene and
those that affect whole chromosomes (chromosomal aberrations). Gene
mutations at the nucleotide level are called point mutations.
Any errors in the replication of a gene within the DNA molecule resulting
in the insertion, deletion, or substitution of one or more bases will
give rise to a mutation. Even though the cell has mechanisms to improve
the fidelity of DNA replication, every once in a while a spontaneous mistake
is made leading to a heritable change in the DNA sequence. In the
laboratory, mutation rates can be greatly increased by exposing cells to
chemicals or physical agents called mutagens.
Many mutations are due to the instability of the nucleotide bases in
the DNA . Nucleotide bases may undergo structural changes called tautomeric
shifts (Figure 6-1), which result in the redistribution of electrons
and protons so that the bases no longer pair normally. G may pair with T or A with C, resulting in heritable changes in the nucleotide sequence.
Transitions occur when the mispairing results in the replacement of
one purine for another or one pyrimidine for another. Transversions result
when a purine is replaced by a pyrimidine or vice versa. Because the
structural changes leading to transitions are relatively small, they occur
more frequently than transversions, which require more substantial modifications
of a molecule.
|Figure 6-1 Tautomeric shifts and abnormal base pairing.
Point mutations resulting from base substitutions in a gene that code
for a polypeptide may result in missense, nonsense, or silent muations.
Missense mutations result in the replacement of one sense codon for
another, altering the amino acid encoded in that position. Anonsense mutation
creates one of the three stop codons (UGA, UAA, UAG) and results
in polypeptides that are shorter than the normal ones. Silent mutations
are changes in the sequence of the codon that do not alter the
encoded amino acid.
Frameshift mutations are the result of nucleotide or base insertions
or deletions within the coding region of a gene. The genetic code is translated
by the protein synthesis apparatus by reading sequential groups of
three bases that make up a codon, beginning from the start codon. If a single
base is added or removed, all of the codons from that point on will be
changed. A truncated protein may result if a codon is mutated to one of
the three stop codons.
Sickle cell anemia results from a GAG → GUG
transversion within a glutamine codon. The mutant
hemoglobin protein has valine in its place, and
these cells become crescent shaped under low