MUTATION: Changes in the Genetic Code When you copy from the blackboard, sometimes you

may make mistakes. In a similar way, mistakes may occur when DNA is replicated. Look at
Figure 8 to see some common mistakes in replication. Changes in the DNA sequence may delete
such protein or change its structure.

When the code in a gene is changed, a different

message may result. Any change in the sequence of nitrogenous bases in the DNA, any mistake
in the transcription of genetic information from DNA to RNA or pairing of the codon and
anticodon, may cause changes in the kind, sequence and number of amino acids of proteins
synthesized by cells. Changes in the protein structure or level of expression may lead to changes
in cellular properties and behavior, as a result, the organism is affected. Changes in the genes can
occur for a variety of reasons. Mutation may be induced by factors called mutagens. Mutagens
are commonly in the form of toxic chemicals, and harmful radiation. Sometimes, mistakes occur
in DNA replication, mitosis, and meiosis. All of these can alter the DNA
sequence and length.

Mutations can occur in two different types of cells: reproductive cells and
body cells. Only mutations in sex cells pass on to offspring. Mutations
affect the reproductive cells of an organism by changing the sequence of
nucleotides within a gene in a sperm or an egg cell. If these cells are
fertilized, then the mutated gene becomes a part of the genetic makeup of the offspring as shown
in Figure 9. If mutation is severe, the resulting protein may be nonfunctional, and the embryo
may not develop. There are two types of mutations that can occur in gamete cells:

• Gene mutation is a permanent change in the DNA sequence that makes up a gene.

• Chromosomal mutation occurs at the chromosome level resulting in gene deletion, duplication
or rearrangement that may occur during the cell cycle and meiosis. It maybe caused by parts of
chromosomes breaking off or rejoining incorrectly.

Most mutations are harmful. Some mutations in a body cell are known to cause cancer, while
mutations in sex cells can cause birth defects. A severe mutation may lead to cell death and may
have no effect on the body. Sometimes mutations may be useful for the species. For example, a
mutation in blood proteins prevents viruses or parasites to thrive in host organisms.

• When is mutation inherited? Why are mutations in sex cells heritable? Many diseases are
caused by the effects of inherited genes. In most cases, there is only a small difference between
DNA sequences in the defective gene and a normal one. This difference is enough to cause
serious and often fatal diseases. These disease-causing genes are the result of a mutation. They
may be passed from one generation to the next if present in gametes. Figure 10 shows changes in
the sequences of bases in normal hemoglobin and the one affected by mutation. A recessive gene
causes sickle- cell anemia, where most of the red blood cells stiffen and become sickle shape in
affected people. These diseased cells carry less oxygen than normal cells. People affected by the
disease eventually die.

Consider what might happen if an incorrect amino acid was inserted in a growing protein chain
during the process of translation. Do you think this will affect the structure of the entire
molecule? This can possibly happen in point mutation where a change in a single base pair
occurs. Read the two sentences below. What happens when a single letter in the first sentence is
changed? THE DOG BIT THE CAT. THE DOG BIT THE CAR. Did you see that changing a
single letter also changes the meaning of the sentence? A change in nitrogenous base in a protein
may yield a different amino acid and a corresponding change in the protein structure and
function.

What will happen if a single base is deleted from a DNA strand? You learned in Activity 3 and 4
that an mRNA corresponds to a DNA sequence translated by ribosomes into proteins. If the new
sequence with a deleted base was transcribed, then every codon after the deleted base would be
different. Deletion or insertion of a base may change the reading frame of the codon leading to
frameshift mutation. Read again the two sentences below. THE DOG BIT THE CAT. THE DOB
ITT HEC AT. What was deleted? Would the result be the same if there would be an addition of a
single base? Mutations in chromosomes may occur in a variety of ways. Sometimes parts of
chromosomes are broken off and lost during mitosis or meiosis. Now, you will work on an
activity that will help you visualize some chromosomal mutations using models.

Breakage of Chromosomes

Breakage of chromosomes during meiosis can result in:

o Deletion: this occurs when an entire region of a chromosome is accidentally deleted.

o Translocation: a portion of one chromosome accidentally switches places with a

separate, non-homologous chromosome (e.g. Philadelphia Chromosome).

o Inversion: a portion of a chromosome can break, and re-join into the original
chromosome but after inverting itself, resulting in a change in sequence.

Abnormalities in chromosomal structure may occur during meiosis. The normal process of
crossing-over and recombination may be affected, such that chromosomes break and reunite the
wrong segments. If there is a loss or gain of chromosomal material, there can be significant
clinical consequences. Changes that affect the structure of chromosomes can cause problems
with growth, development, and function of the body’s systems. These changes can affect many
genes along the chromosome and disrupt the proteins made from these genes. Structural changes
can occur during the formation of egg or sperm cells in fetal development, or in any cell after
birth. Pieces of DNA can be rearranged within one chromosome or transferred between two or
more chromosomes.

The effects of structural changes depend on their size and location, and whether any genetic
material is gained or lost. Some changes cause medical problems, while others may have no
effect on a person’s health. The gain or loss of chromosome material can lead to a variety of
genetic disorders. Human examples are the following on the next page:

a. “Cri du chat” is caused by the deletion of part of the short arm of

chromosome 5. “Cri du chat” is French, and the condition is so named
because affected babies make high-pitched cries that sound like a cat.
Affected individuals have wide-set eyes, a small head and jaw, are
moderately to severely mentally retarded, and very short.

b. Down’s syndrome is usually caused by an extra copy of

chromosome 21(trisomy 21). Characteristics include decreased
muscle tone, stockier build, asymmetrical skull, slanting eyes and
mild to moderate mental retardation.

c. Edwards syndrome, which is the second most common trisomy

after Down’s syndrome, is a trisomy of chromosome 18. Symptoms
include mental and motor retardation and numerous congenital
anomalies causing serious health problems. About 99% die in
infancy. However, those who live past their first birthday, usually are
quite healthy thereafter. They have a characteristic hand appearance
with clenched hands and overlapping fingers.

(d) Jacobsen syndrome is also called terminal 11q deletion disorder. This is a very rare disorder.
Those affected have normal intelligence or mild mental retardation, with poor or excessive
language skills. Most have a bleeding disorder called Paris-Trousseau syndrome.

e) Klinefelter’s syndrome (XXY). Men with this condition are usually

sterile and tend to have longer arms and legs and to be taller than their
peers. They are often shy and quiet and have a higher incidence of speech
delay.
(f) Turner’s syndrome (X instead of XX or XY). Female sexual characteristics are present but
underdeveloped. They often have a short stature, low hairline,
abnormal eye features and bone development and a “caved-in”
appearance to the chest.