Unit 2: Genetics
Lesson 12 Mutations (Teacher Notes)
Your body makes billions of cells a day. During this process, DNA is replicated billions of times.
What happens if there is a mistake during the replication process? This is when mutations occur.
Mutations are changes in the genetic code of an allele. Mutations can be caused by environmental agents
such as damaging radiation and certain chemicals, or as errors during cell division. Mutations can have
either positive, negative or neutral effects on the phenotype of the individual. Some of the gene
mutations result in a new cell dying and being recycled. [When cells die, they will be recycled by
phagocytes (white blood cells)]. However, sometimes cells carrying mutations survive and replicate.
1) Point Mutations:
A small-scale change in the nitrogenous base sequence of DNA. A point mutation is a failure by the
replicating cell to copy the genetic information accurately. Point mutations may be beneficial, harmful,
or neutral (having no effect on the organism). There are three major point mutations.
a) Base Pair Substitution:
In a base-pair substitution, one nitrogenous base is accidentally replaced with a
different base. Draw an example of a base-pair substitution.
T
A
C
A
T
G
G
T
A
G
A
T
G
G
b) Insertions:
In an insertion, one or more nitrogenous bases are inserted during the copying
process. Draw an example of an insertion mutation.
T
A
C
A
T
G
G
T
A
C
A
A
T
G
c) Deletions:
In a deletion, one or more nitrogenous bases are deleted during the copying
process. Draw an example of a deletion mutation.
T
A
C
A
T
G
G
T
2) Chromosome Mutations:
An error that involves an entire chromosome or a large
part of a chromosome are known as chromosome mutations. An
example of a chromosome mutation is non-disjunction. Nondisjunction occurs when sister chromatids fail to separate
during meiosis which results in the production of gametes that
contain too many or too few chromosomes. Down Syndrome is a
genetic disorder that results from non-disjunction of
chromosome 21.
A
A
T
G
G
G
Inheritance of Mutations:
Mutations can occur during the cell's replication process. Most mutations occur in parts of the DNA that
are 'non-coding'. (98% of the genome is non-coding). Many mutations can be corrected as the replication
process continues, but as an organism gets older, the rate of mutations becomes more frequent
potentially leading to cancer. Mutations that occur in somatic cells (body cells) will not get passed on to
offspring, but mutations in the gametes (sex cells) do. Mutations that are dominant (such as
Huntington's disease) will show up in the first generation of offspring, but mutations that are recessive
may take several generations to show up phenotypically, and that too, only if by chance two individuals
with the same mutation produce offspring.
Are all mutations harmful?
Mutations that have been passed on through the generations can be harmful, beneficial or neutral.
Sometimes, mutations might be a combination of the three.
Sickle Cell Anemia:
Individuals with sickle cell anemia have inherited a mutated gene in which a single adenine base is
substituted for a thymine. The result of this point mutation is that when oxygen levels are low,
individuals acquire red blood cells that are c-shaped (or sickle shaped) instead of the round, donut-like
shape that they normally are. The sickle-shaped red blood cells do not pass through blood vessels easily
causing poor blood flow. In addition, the shape of these red blood cell prevent oxygen atoms from
properly binding.
Even though, sickle cell anemia is problematic, this mutation allows for a different kind of
benefit. People with sickle cell anemia are essentially immune to malaria. When a red blood cell of an
anemic person is infected by the malaria parasite, the cell becomes sickle-shaped and is destroyed along
with the parasite. In this example,
the mutation of having sickle celled
anemia gives the individual a
benefit which is why sickle cell
anemia is so prevalent in various
countries in Africa where malaria is
so common.
Lactose Tolerance and Lactose Intolerance:
Lactose intolerance is the inability to digest the sugars (lactose) in milk as individuals do not have
the enzyme to do this. Throughout human history, before the domestication and milking of animals,
adults never consumed milk. Babies are born with the enzyme that allows them to be lactose tolerant so
that they may consume and digest their mother's milk. As children get older, they lose their ability to
produce this enzyme and become lactose intolerant. About 75% of the adults worldwide are lactose
intolerant. Those adults that can tolerate lactose can do so because of a genetic mutation. Individuals
who have inherited the mutated gene for lactose tolerance continue to produce the enzymes that
breakdown lactose.
Spontaneous or Induced Mutations:
Spontaneous mutations occur naturally and randomly whereas induced mutations are caused by
external, environmental factors. Induced mutations are a result of chemical or physical agents such as
radiation or cigarette smoke.
"Jumping Genes" or Transposons:
Point mutations are mutations that occur within a gene in fixed locations. Barbara McClintock's
work in genetics back in the 1940s, showed that genes do not always remain in fixed locations.
McClintock studied corn that produced a variety of different coloured kernels. Since each kernel is an
individual corn plant embryo, one cob produces a large sample of offspring; making it an ideal species for
genetic research.
McClintock's research showed that an organism's genome is not static, but rather there are
segments of DNA that can move as a unit from one location to another. These moveable segments are
called transposons (or 'jumping genes'). Transposons are specific segments of DNA that can move along
or between the chromosomes through the process of transposition. Transposition is the process of
moving a gene sequence from one part of the chromosome to another part of the chromosome.
McClintock learned that these transposons can affect the colour of the corn kernels. If a
transposon is inserted into the gene for purple kernels, the gene is disrupted and purple pigment cannot
be produced. Instead, the resulting kernel is white.
Barbara McClintock began her scientific career at Cornell University, where she pioneered the study of cytogenetics-a new field in the 1930susing maize as a model organism. Indeed, the marriage of cytology and genetics became official in 1931, when McClintock and graduate
student Harriet Creighton provided the first experimental proof that genes were physically positioned on chromosomes by
describing the crossing-over phenomenon and genetic recombination. Although Thomas Hunt Morgan was the first person to suggest the link
between genetic traits and the exchange of genetic material by chromosomes, 20 years elapsed before his ideas were scientifically proven,
largely due to limitations in cytological and experimental techniques (Coe & Kass, 2005). McClintock's own innovative cytogenetic techniques
allowed her to confirm Morgan's ideas, and these techniques are numbered among her greatest contributions to science.
Hemophilia and Transposons:
Hemophilia is an inherited X-linked disease that is caused by genetic mutation of the bloodclotting factor gene. In rare cases, hemophilia can also be caused by transposons. If a transposon inserts
itself into a normal blood factor VIII gene, then the individual (if male) will be affected by hemophilia.
For females to get hemophilia in this manner, both X-chromosomes would need to be affected.
Because of McClintock's pioneering work in the 1940s (before the structure of DNA was known),
scientists now recognize that transposons exist in all large genomes and are an important cause of
mutations. Her work was not fully acknowledged until much later in 1983 when she was awarded the
Nobel prize. She died in 1992.
Microarray Technology - Simplifying the search for Disease Causing Genes:
Currently, one major aspect of genetic research is focussed on the identification of genes that
lead to genetic disorders. Discovering and identifying genes that cause diseases like cystic fibrosis and
Huntington's disease enhances our understanding of how these diseases are inherited, and how they
ought to be treated. Microarray technology simplifies the search for disease causing genes. A
microarray consists of a small membrane or glass slide that contains samples of hundreds, or even
thousands of DNA fragments arranged in a regular pattern. Each fragment corresponds to a particular
gene. Samples with genetic material to be tested are spread over the microarray chip and interact with
these gene fragments.
Ex: A research can obtain cancer liver cells and normal liver cells and looks to see which genes
are active in both. If the same set of genes are active in normal cells and cancer cells, then there is no
evidence of genetic influence. If there is a gene that is active in normal cells, but not in cancer cells,
then this suggests that the cancer might be caused by the mutated inactive gene. As well, if there is a
gene that is active in cancer cells, but inactive in normal cells, this suggests that the cancer might be
caused by the mutated active gene.