BIOLOGY 12
MUTATIONS
What is a Mutation?
A mutation is a permanent change in the DNA sequence of a gene. Mutations in a gene's
DNA sequence can alter the amino acid sequence of the protein encoded by the gene.
How does this happen? Like words in a sentence, the DNA sequence of each gene
determines the amino acid sequence for the protein it encodes. The DNA sequence is
interpreted in groups of three nucleotide bases, called codons. Each codon specifies a single
amino acid in a protein.
Mutate a sentence!
We can think about the DNA sequence of a gene as a sentence made up entirely of threeletter words. In the sequence, each three-letter word is a codon, specifying a single amino
acid in a protein. Have a look at this sentence:
Thesunwashotbuttheoldmandidnotgethishat.
If you were to split this sentence into individual three-letter words, you would probably
read it like this:
The sun was hot but the old man did not get his hat.
This sentence represents a gene. Each letter corresponds to a nucleotide base, and each
word represents a codon.
There are two types of mutations: frameshift and point.
FRAMESHIFT MUTATIONS
What if you shifted the three-letter "reading frame?" You would end up with
hes unw ash otb utt heo ldm and idn otg eth ish at.
Or
TTh esu nwa sho tbu tth eol dma ndi dno tge thi sha t.
Insertion mutations and deletion mutations add or remove one or more DNA
bases. Insertion and deletion mutations cause frameshift mutations, which
change the grouping of nucleotide bases into codons. This results in a shift
of "reading frame" during protein translation.
The proteins are completely nonfunctional.
POINT MUTATIONS:
Point mutations are single nucleotide base changes in a gene's DNA
sequence. This type of mutation can change the gene's protein product in
the following ways:
• Missense mutations are point mutations that result in a single amino acid change within
the protein. UAC – CAC – this leads to a change in shape of protein and its function. The
fat cat. – The rat cat.
• Nonsense mutations are point mutations that create a premature "translation stop signal"
(or "stop" codon), causing the protein to be shortened. UAC – UAG. The fat cat. – the cat
cat.
• Silent mutations are point mutations that do not cause amino acid changes within the
protein. A silent mutation changes a nucleotide without changing the codon. For many amino
acids the third nucleotide of the codon can be variable. For example, CCT, CCC, CCA and
CCG all code for Proline. The fat cat. - The fat rat.
What Causes DNA Mutations?
Mutations in DNA sequences generally occur through one of two processes:
1.
DNA damage from environmental agents such as ultraviolet light (sunshine), nuclear
radiation or certain chemicals called mutagens.
2. Mistakes that occur when a cell copies its DNA (in replication) in preparation for cell
division.
1. DNA damage from environmental agents
Modifying nucleotide bases
Ultraviolet light, nuclear radiation, and certain chemicals can damage DNA by altering
nucleotide bases so that they look like other nucleotide bases.
When the DNA strands are separated and copied, the altered base will pair with an incorrect
base and cause a mutation. In the example below a "modified" G now pairs with T, instead of
forming a normal pair with C.
Breaking the phosphate backbone
Environmental agents such as nuclear radiation can damage DNA by breaking the bonds
between oxygens (O) and phosphate groups (P).
Breaking the phosphate backbone of DNA within a gene creates a mutated form of the gene.
It is possible that the mutated gene will produce a protein that functions differently.
Cells with broken DNA will attempt to fix the broken ends by joining these free ends to
other pieces of DNA within the cell. This creates a type of mutation called "translocation."
If a translocation breakpoint occurs within or near a gene, that gene's function may be
affected.
2. Mistakes created during DNA duplication
Prior to cell division, each cell must duplicate its entire DNA sequence. This process is called
DNA replication.
DNA replication begins when a protein called DNA helicase separates the DNA molecule into
two strands.
Next, a protein called DNA polymerase copies each strand of DNA to create two doublestranded DNA molecules.
Mutations result when the DNA polymerase makes a mistake, which happens about once
every 100,000,000 bases.
Actually, the number of mistakes that remain incorporated into the DNA is even lower than
this because cells contain special DNA repair proteins that fix many of the mistakes in the
DNA that are caused by mutagens. The repair proteins see which nucleotides are paired
incorrectly, and then change the wrong base to the right one.
What are Genetic Disorders?
Genetic disorders are medical conditions caused by mutations in a gene or a set of genes.
Mutations are changes in the DNA sequence of a gene. They can happen at any time, from when
we are a single cell to when we are 90. Or even older!
Some people say that there are disorder genes. It is not a gene, or genes, however, that cause
the illness, but a mutation that causes the normal genes to operate improperly. It is better to
say that there are mutated genes that cause genetic disorders.
We can separate genetic disorders into four categories:
1. Chromosome Abnormalities
2. Single-Gene Disorders
In some disorders, entire chromosomes, or large
segments of them, are missing, duplicated, or
otherwise altered. Down Syndrome and Turner's
Syndrome are examples of this type of disorder.
Some disorders result when a mutation causes the
protein product of a single gene to be altered or
missing. An example of this kind of disorder is sickle
cell anemia.
3. Multifactorial Disorders
4. Mitochondrial Disorders
Multifactorial disorders result from mutations in
multiple genes, often coupled with environmental
causes. The complicated bases of these diseases
make them difficult to study and to treat. Heart
disorder, diabetes and cancer are examples of this
type of disorder.
These relatively rare disorders are caused by
mutations in non-chromosomal DNA located within
subcellular organelles, the mitochondria. There are
multiple copies in a single cell's cytoplasm, all
transmitted by the mother in the ovum.
Some mutations cause disorders, but others do not. Why not?
Some mutations do not cause disorders because the mutations are repaired. Our cells have
mechanisms for repairing DNA if mistakes are made in the sequence or if the DNA is
damaged.
We have two copies of every chromosome (one from Mom and one from Dad), and therefore
we have two copies of every gene. If one gene copy is mutant, the other copy usually can
provide enough gene product to the organism for normal function.
Most of our DNA does not encode genes. Therefore most mutations do not cause changes in
functional gene products, and do not cause genetic disorders. Even among the DNA sequences
that serve as blueprints for gene products, many changes in the DNA do not cause significant
changes in the protein sequence translated from that DNA, and therefore cause no detriment
to the organism.