q3 DNA RNA
q3 DNA RNA
q3 DNA RNA
Module 2
Central Dogma of Biology: Protein Synthesis And
Mutation
Learning Competency:
Explain how mutations may cause changes in the structure and function of a
protein. (S10LT-IIIe-38)
Lesson
Replication of DNA
1
What’s New
DNA (Deoxyribonucleic Acid) is the genetic material of all organisms on Earth from
microbes to plants and human beings. An organism’s complete set of DNAs, including all of its
genes is called genome. A genome contains a complete set of information which
determines inherited physical characteristics such as height, skin, eye and hair color and many
others. Every cell in a human body nearly
has similar DNA and in eukaryotic cells (cells
that contain a nucleus and organelles, and
are enclosed by a plasma membrane). The
DNA is a thin long molecule found in the
cell’s nucleus which is made up of
nucleotides. The basic structure of
nucleotide consists of a phosphate group,
sugar and a nitrogenous base which will be
further discussed in the next lessons. The
four different type of nucleotides of DNA are
adenine, thymine, guanine
and cytosine which are represented by
their first letter A, T, G, C. These four
nucleotides are paired as (Adenine-
Thymine) and (Guanine-Cytosine)
into billions to organize a
double helix structure. Try to look closely
given structure of DNA. at the
DNA molecules fold into paired packages called chromosomes that are stored in the
nucleus of the cell. Different species have different numbers of chromosomes, and humans have
23 pairs. Chromosome contain many genes and on each string of DNA contains the gene which
is the basic unit of heredity and a segment that describes how a certain protein is made.
James Watson and Francis Crick in 1953, worked out that DNA is double helix which
appears like a staircase. The sides of the double helix structure are the sugar phosphate
backbones and the steps or rungs are the base pairs.
DNA Replication is the process of DNA duplication from an existing DNA. The replication of
DNA is important for the growth repair and reproduction of cells of an organism.
This process occurs in the nucleus of eukaryotic cells before a cell divides either by mitosis of meiosis.
When a cell divides, each resulting cell keeps a copy of all of your chromosomes.
The major key players in DNA replication are the enzymes helicase, primase, DNA
polymerase and ligase. Helicase is the unzipping enzyme and unzips the two strands of
DNA in the double helix through the hydrogen bond that holds the two base pairs together.
Primase will initialize the process and directs the DNA polymerase for it to figure out where
it gets to start. This primer is the starting point for DNA synthesis. The primers are made of
RNA (Ribonucleic Acid). Its major role is to act as a messenger carrying instructions from DNA
for controlling the synthesis of proteins. DNA polymerase is the builder enzyme which
replicates DNA molecules in order to build a new strand of DNA. Ligase is the gluer. which
helps glue DNA fragments together to form the new strand of DNA.
Let us now proceed to the three major steps of DNA replication (initiation, elongation and
termination) and see what happens in each stage.
Step 1: Initiation
DNA replication starts at the Origin of Replication. The unzipping enzyme Helicase,
causes the DNA strand separation, which leads to the formation of the replication fork. It breaks
the hydrogen bond between the base pairs to separate the strand, thus separating the DNA
into individual strands.
Step 2: Elongation
During elongation, DNA Polymerase III makes the new DNA strand by reading the
nucleotides on the template strand and binding one nucleotide after the other to generate a
whole new complementary strand. It helps in the proofreading and repairing the new strand.
DNA Polymerase is able to identify and back track any mis paired nucleotides and corrects it
immediately. The bases attached to each strand then pair up with the three nucleotides found
in the cytoplasm. If it finds an Adenine (A) on the template, it will only add a Thymine (T). If
it finds a Guanine (G) on the template, it will only add a Cytosine (C).
Step 3. Termination
In the previous steps of DNA replication, at the Origin, a Primer helps the DNA
Polymerase to initiate the process. As the strand is created, the primer has to be removed. This
is when DNA Polymerase I comes into the picture to replace the RNA nucleotides from the
Primer with DNA nucleotides to make sure it is DNA all the way through. When DNA Polymerase
III adds nucleotides to the lagging strand and forms Okazaki fragments, it leaves a gap or two
between the fragments. These gaps are filled by the enzyme ligase and makes sure that
everything else is connected.
The Replication process is considered complete once all the Primers are removed and
Ligase has filled in all the remaining gaps between the Okazaki Fragments. This process gives
us two identical copies of the original DNA molecule. This whole replication process is happening
in billions of cells in your body even at this very moment. The original DNA is called the template
DNA, while the replicate DNA is called the complement DNA, both templates IDENTICAL as
shown in Figure 4!
Now, you might ask this question; ‘Why is it important for DNA TO UNDERGO
Lesson
Transcription of DNA to RNA
2
REPLICATION?” Well, it is important for DNA present in the nucleus to be replicated so that every
new cell receives the appropriate number of chromosomes. This process is necessary for cell repair
and growth and reproduction in living organisms.
RNA (Ribonucleic Acid), unlike the double stranded DNA, is a nucleic acid polymer with
a single strand. It is composed of the four nucleotides adenine, uracil (replaced thymine in
DNA), guanine and cytosine which are represented by their first letter A, U, G, C. (The only
difference with DNA is the Uracil). RNA is the first intermediate in converting the information
from the DNA into proteins which is important for proper cellular function. Below is a short
RNA falls into three major categories: Messenger RNA (mRNA), Transfer RNA
(tRNA) and Ribosomal RNA (rRNA). mRNA copies the genetic code from the DNA into a
form that can be read and used to make proteins. mRNA transmits genetic information from
the nucleus to the cell’s cytoplasm. rRNA is situated in the cytoplasm of a cell, where we can
find the ribosomes. rRNA leads the translation of mRNA into proteins. tRNA transfers amino
acids to the ribosome that matches to each three-nucleotide codon of rRNA. The amino acids
then can be combined together and processed to make polypeptides and proteins.
Transcription in protein synthesis is the process where RNA is made from the DNA by
copying the base sequence of the double stranded DNA into a piece of a single stranded nucleic
acid. This transcription process is catalyzed by the enzyme RNA Polymerase.
Transcription of DNA to form RNA takes place in the cell’s nucleus. This process uses
DNA as a model to make an RNA (mRNA) molecule. During transcription, a strand of mRNA is
made that corresponds to a strand of DNA. Just like DNA replication, transcription also occurs
in three major steps: initiation, elongation and termination.
1. Initiation
Initiation is the start of transcription. It transpires when the enzyme RNA polymerase
binds to a specific region of a gene which is called the promoter with the help of proteins called
‘transcription factors’. This signals the DNA double strand to unwind and open so the RNA
polymerase enzyme can ‘‘read’’ the bases found in one of the DNA strands. With the open
strands, one is considered as the template strand (anti-sense strand) and this will be used to
generate the mRNA. The other is called the non-template strand (sense strand). After reading
the bases, the RNA polymerase enzyme is now ready to make a strand of mRNA with a
complementary sequence of bases.
2. Elongation
Elongation is the adding of nucleotides to the mRNA strand. RNA polymerase reads
the opened DNA strand and forms the mRNA molecule with the use of complementary base
pairs. There is a short time during this process when the newly formed RNA is bound to the
opened DNA. During this process of elongation, an adenine (A) in the DNA binds to an uracil
(U) in the RNA. RNA polymerase does not need a primer during this process. It simply initiates
the mRNA synthesis from the starting point and then moves downstream reading the antisense
strand from 3’ to 5’ and generating the mRNA from the 5’ to 3’ end as it goes. Unlike helicase
enzyme in DNA replication, RNA polymerase zips DNA back up as it goes keeping only 1020
bases exposed one at a time.
3. Termination
Termination is the last step of the transcription process. This happens when RNA
polymerase enzyme reaches a stop or termination sequence in the gene. When the stop sequence
or stop codon is reached, the enzyme detaches from the gene. The mRNA strand is now produced
and it detaches from DNA. It carries with it the information encoded in the gene.
Lesson
Translation of RNA to Protein
3
Remember to take note of the transcription pattern: Thymine to Adenine, Adenine to Uracil,
Cytosine to Guanine, Guanine to Cytosine. Uracil is being synthesized instead of Thymine as compared
during DNA replication.
Translation is the final process of protein synthesis that takes place in the cytoplasm.
The genetic information of the DNA is used as the origin to form messenger RNA (mRNA) by
the transcription process. The single stranded mRNA then serves as a template during
translation. Ribosomes are the facilitators of the translation process in the cytoplasm.
Ribosomes induce the binding of complimentary transfer RNA (tRNA) anticodon sequences to
the mRNA. The tRNAs contain particular amino acids linked together by the ribosome. During
translation, the mRNA sequence is decoded to produce a specific amino acid chain called the
polypeptide. Folding of the polypeptide produces an active protein which is able to perform
important functions within the cell.
Protein Structure. Proteins may generally have globular or fibrous structure depending on
its particular role in the bodily functions. Globular proteins are spherical, compact and soluble.
Fibrous proteins are elongated and insoluble. However, these two structure types may exhibit one
or more types of protein structures.
The protein building block is the amino acid. Amino acids combine through a dehydration
link called a peptide bond. When several groups of amino acids are joined together, a protein
macromolecule is formed. This is why proteins are considered as polymers of amino acids. Proteins
are typically made of a chain of 20 amino acids. The human body makes any protein it needs by
using a combination of these 20 amino acids. Most amino acids have a structural template where
an alpha carbon is bonded to the following forms:
The “variable” group is most responsible for difference as all of them have hydrogen,
carboxyl group, and amino group bonds. Amino acids are linked through dehydration synthesis
peptide bonds are formed. Amino acids linked together by polypeptide bonds forms a
polypeptide chain. When polypeptide chains are twisted, a 3-D shape forms a protein.
These amino acids are grouped as: essential and non-essential. Non-essential amino
acids are those which the human body is capable of synthesizing, whereas essential amino acids
must be obtained from the diet.
serine Ser
tyrosine Tyr
Since the proteins formed by amino acids are incredibly huge and bulky molecules, it is
very time consuming and difficult to draw out their chemical structure in similar way we draw
smaller molecules. The common amino acids that make up proteins are given codes that
represent them as shown in the table above. This makes describing the molecules so much
easier.
Proteins are synthesized in the human body through a process called translation.
Translation occurs in the cytoplasm and involves converting genetic codes into proteins. Genetic
codes are assembled during DNA transcription, where DNA is decoded into RNA. Cell structures called
ribosomes then help transcribe RNA into polypeptide chains that need to be modified to become
functioning. The key components required for translation are mRNA, tRNA, ribosomes, and
aminoacyl tRNA synthetases. These four structures are briefly explained below:
*Ribosome
The ribosome is a complex organelle, present in the cytoplasm, which serves as the site
of action for protein synthesis. It provides the enzymes needed for peptide bond formation.
The nucleotide sequence in mRNA is recognized in triplets, called codons. The ribosome moves
along the single strand mRNA, and when a complimentary codon sequence belonging to amino
acid bearing tRNA bonds with the mRNA, the amino acid is added to the chain.
The mRNA possesses a stop codon, a sequence of three nucleotides that indicates that
translation is complete. Upon reaching the stop codon, the ribosome ceases translation and
releases the mRNA and newly generated polypeptide.
mRNA is used to convey information from DNA to the ribosome. It is a single strand
molecule, complimentary to the DNA template, and is generated through transcription. Strands
of mRNA are made up of codons, each of which signifies a particular amino acid to be added to
the polypeptide in a certain order. mRNA must interact with ribosomal RNA (rRNA), the central
component of ribosomal machinery that recognizes the start and stop codons of mRNA, and
transfer RNA (tRNA), which provides the amino acid once bound with a complimentary mRNA
codon.
These are enzymes that link each amino acid to their corresponding tRNA with the help
of a two-step process. Each amino acid has a unique synthetase and the active site of each
enzyme fits only one specific combination of the amino acid and tRNA. (14)
There are three major steps in translation: initiation, elongation, and termination. These
steps are briefly discussed below:
1. Initiation
After mRNA is formed in the nucleus, it leaves and moves to the cytoplasm where it finds the
ribosome. Small ribosomal subunits then bind to mRNA. The initiator tRNA which is equipped
with the anticodon (UAC) also binds to the start codon (AUG) of the mRNA. Let us say we have
the mRNA codon AUG-UGC-AAG-UCC-GGA-CAG, the tRNA anticodon would be UACACG-UUCAGG-
CCU-GUC. The resulting large complex forms a complete ribosome and initiates protein synthesis.
Each different tRNA is covalently linked to a particular amino acid.
2. Elongation
Following initiation, a new tRNA-amino acid complex enters the codon next to the AUG
codon. If the anticodon of the new tRNA matches the mRNA codon, base pairing occurs and
the two amino acids are linked by the ribosome through a peptide bond.
If the anticodon does not match the codon, base pairing cannot happen and the tRNA is
rejected. Then, the ribosome moves one codon forward making space for a new tRNAamino acid
complex to enter. This process is repeated several times until the entire polypeptide has been
translated.
3. Termination
As the ribosome moves along the mRNA, it encounters one of the three stop codons for
which there is no corresponding tRNA. Terminator proteins present at the stop codon bind to
the ribosome and trigger the release of the newly synthesized polypeptide chain. The ribosome
then disengages from the mRNA. On release from the mRNA, the small and large subunits of
the ribosome dissociate and prepare for the next round of translation. The
polypeptide chains produced during translation undergo some post-translational modifications,
such as folding, before becoming a fully active protein.
Below is a chart of all the mRNA codons and the amino acids they code for. Decoding codons
is a task made simple because of the codon chart.
Just start at the center of the chart for the first letter. Move to the outside next ring for the second
letter and finally, find the final letter among the smallest set of letters in the third ring.
Then you can read the amino acid in that sector
To decode the codon for CAC, find the first letter C in the set of bases at the center of the
circle. Then find the letter A in the second ring, then C in the third ring. There, you will read the
amino acid in this sector as Histidine. Some of these codons are special. AUG is the start codon
which initiates translation by coding for Methionine. And these three are stop codons: UAA, UAG and
UGA. These are the ones that terminate translation.
b. INSERTION or DUPLICATION
- one or more base pair is added to a sequence
Normal Sequence Mutated Sequence
DNA
CGA TGG CCC CGA ATG GCC
mRNA GCU ACC GGG GCU UAC CGG
rRNA CGA UGG CCC CGA AUG GCC
Amino Acid Ala Try Pro Ala Met Arg
c. DELETION
- one or more pairs is lost from a sequence
Normal Sequence Mutated Sequence
DNA
A
GCT ACC TTT
GCT CCT TTA
development of the organisms. Some individuals will have reproductive problems because abnormal
chromosomes result to a child with birth defects. Some changes will cause medical problems, while
others may have no effect on person’s health.
Le
Lesson
Diseases and Abnormalities 5
Caused by Mutation
Gene mutations are most commonly caused as a result of two types of occurrences.
Environmental factors such as chemicals, radiation, and ultraviolet light from the sun can cause
mutations. These mutagens alter DNA by changing nucleotide bases and can even change the
shape of DNA. These changes result in errors in DNA replication and transcription.
Other mutations are caused by errors made during mitosis and meiosis. Common errors
that occur during cell division can result in point mutations and frame-shift mutations. Mutations
during cell division can lead to replication errors which can result in the deletion of genes,
translocation of portions of chromosomes, missing chromosomes, and extra copies of
chromosomes.
Genetic Disorders
According to the National Human Genome Institute, almost all disease has some sort of
genetic factor. These disorders can be caused by a mutation in a single gene, multiple gene
mutations, combined gene mutation, and environmental factors, or by chromosome mutation or
damage. Gene mutations have been identified as the cause of several disorders including sickle cell
anemia, cystic fibrosis, Tay-Sachs disease, Huntington disease, hemophilia, and some cancers. a.
Sickle Cell Anemia
Sickle cell anemia is a genetic disease common among those who are from Africa. This
genetic disease is the result of a point mutation where there is a change in just one nucleotide
in the gene for hemoglobin. The mutation causes the hemoglobin in red blood cells to transform
to a sickle shape when de-oxygenated. Since the shape is altered, it cuts of blood circulation
and clogs the capillaries.
Two copies of the mutated genes cause sickle cell anemia, while having just one copy
does not. One copy of it in facts protects against malaria. This is an example of how mutations
can sometimes be advantageous. b. Cystic Fibrosis
Cystic fibrosis (CF) is a progressive, genetic disease that affects the secretory glands,
including the mucus and sweat glands. Cystic fibrosis causes persistent lung infections and
limits the ability to breathe over time.
There is no cure for CF but treatments have greatly improved in recent years.
Medication, exercise, nutritional and respiratory therapies are some of the treatment options.
c. Tay-Sachs Disease
Tay-Sachs disease is a rare inherited disorder that causes progressive damage to the
nervous system and most commonly affects infants. It is mainly caused by the absence of a vital
enzyme called hexosaminidase-A (Hex-A). Symptoms usually appear between three to five
months of age. The development slows down and they gradually lose their ability to move.
Tay-Sachs is a recessively inherited disease that only occurs when both parents carry a
Tay-Sachs gene and each parent transmits the defective gene to their child. A child who inherits
two Tay-Sachs genes (one from each parent) produces no functional Hex-A enzyme and is
certain to develop Tay-Sachs disease. The Tay-Sachs genes are located on chromosome 15.
d. Hemophilia
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. i. “Cri Du Chat”
“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. j. Jacobsen Syndrome
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. k.
Klinefelter’s Syndrome
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. Karyotyping
Karyotyping is a laboratory procedure that allows your doctor to examine your set of
chromosomes. “Karyotype” also refers to the actual collection of chromosomes being examined.
Examining chromosomes through karyotyping allows your doctor to determine whether there
are any abnormalities or structural problems within the chromosomes. Chromosomes
are in almost every cell of your body. They contain the genetic material inherited from your
parents. They’re composed of DNA and determine the way every human develops.
When a cell divides, it needs to pass on a complete set of genetic instructions to each
new cell it forms. When a cell isn’t in the process of division, the chromosomes are arranged in
a spread out, unorganized way. During division, the chromosomes in these new cells line up in
pairs.
A karyotype test examines these dividing cells. The pairs of chromosomes are arranged
by their size and appearance. This helps your doctor easily determine if any chromosomes are
missing or damaged.
Babies can be karyotype tested before they’re born to diagnose genetic abnormalities
that indicate serious birth defects, such as Klinefelter syndrome. In Klinefelter syndrome, a boy
is born with an extra X chromosome.
A normal test result will show 46 chromosomes. Two of these 46 chromosomes are sex
chromosomes, which determine the sex of the person being tested, and 44 of them are
autosomes. The autosomes are unrelated to determining the sex of the person being tested.
Females have two X chromosomes, while males have one X chromosome and one Y
chromosome.
Abnormalities that appear in a test sample could be the result of any number of genetic
syndromes or conditions. Sometimes, an abnormality will occur in the lab sample that’s not
reflected in your body. The karyotype test may be repeated to confirm that there’s an
abnormality.
1. Chemical Factors
Certain man-made chemicals have been known to cause mutations, in most cases by
revising the basic chemical composition of a cell's DNA. Ethyl methane sulfonate, a compound
used in laboratory research, affects the way that one of DNA's four component bases behaves
chemically, resulting in mutant cells with sequences of DNA different from the parent cells.
Benzopyrene, a component of cigarette smoke, and vinyl chloride, an ingredient in plastics,
affect DNA similarly.
2. Radiative Factors
Our world contains different kinds of radiation, both occurring naturally and resulting
from human activity, that also encourage mutations. Ultraviolet radiation from the sun creates
bonds between bases that otherwise would not exist, causing the cell to synthesize abnormal
proteins when that section of DNA is read. Ionizing radiation, such as that emitted as X-rays,
breaks strands of DNA apart, which can lead to mutations when the cell tries to repair its DNA
using free-floating molecules.
3. Biological Factors
Similar to chemicals and radiation, biological agents can cause mutations by attacking DNA's
structure. Retroviruses like HIV can insert their genetic material into a host cell's DNA.
But some viruses and bacteria also produce mutations less directly. The long-lingering hepatitis B
virus can make the body secrete defensive chemicals that, over time, cause mutations, while the
prolonged cell damage and ongoing repair resulting from Helicobacter pylori infections may increase
mutations in cells lining the stomach.
4. Identifying Factors
To identify substances that may cause mutations, several biochemical tests exist,
including one that has been in use since 1973. That year, scientist Bruce Ames demonstrated
that a kind of Salmonella bacteria would grow only in the presence of mutation-causing
materials. The Ames test, in which substances are exposed to this strain of Salmonella, is still
used to identify mutagens today.
Direction: Based on the readings above, copy and fill in the table below.
DNA
RNA
A. Direction: Using the background information above, briefly answer the following
questions below.
Direction:
1. Copy and fill in the table.
2.Refer to the Genetic Code to identify the amino acid.
3. To determine the order of bases in the second row (codon), and the third row (anticodon),
consider the complementary base pairs in DNA: Adenine pairs with thymine and guanine
pairs with cytosine. While in RNA, adenine pairs with uracil and guanine pairs with
cytosine.
4.To identify the amino acid, look at the bases in the mRNA codon, e.g. AUG using the Genetic
Code Table. Look for the primary letter of the mRNA codon on the left side of the ordering
Table (A), the second letter column (U), and therefore the third letter on the right-side
column (G). AUG codes for the amino acid-methionine.
5. Do the same with the other codons in the chart.
mRNA (codon)
tRNA (anticodon)
Amino acid
2. GENE B
mRNA (codon)
tRNA (anticodon)
Amino acid
3. GENE C
DNA (code) TAC AAA GGG CCA ATC
mRNA (codon)
tRNA (anticodon)
Amino acid
QUESTIONS
Directions: Study the information in the given table, then answer the following questions.
1.
Mutated Gene TGT GGG CTC CTT TTT
Questions:
a. What type of gene mutation is shown in number 1?
b. Was the result a functional protein? Why?
2.
Mutated Gene TGT TGG GCT TCT TTT TCC
Questions:
Direction: Read and choose the letter of the best answer. Write the chosen letter on your
answer sheet of paper.
3. During DNA replication, the synthesis of DNA on the laggings strand takes place in
segments, these segments are called.
a. Satellite segments c. Kornberg segments
b. Double helix segments d. Okazaki segments
5. Eukaryotes differ from prokaryote in the mechanism of DNA replication due to:
a. Different enzyme for synthesis of leading and lagging strand
b. Use of DNA primer rather than RNA primer
c. Unidirectional rather than bidirectional replication
d. Discontinuous rather than semi discontinuous replication
6. If the DNA template reads “ATA”, then which of the following would be the corresponding
sequence on the mRNA?
a. UAU b. ATA c. TUT d. UCU
7. One similarity between DNA and messenger RNA molecules is that they both contain:
a. The same sugar. c. Genetic code based on base sequence.
b. Nitrogenous base known as Uracil. d. Double stranded polymers.
10. What is the complementary messenger-RNA sequence for the DNA template sequence
shown below? C-A-A-G-G-T
a. GTTCCA b. CAAGGU c. GUUCCA d. CAAGGT
11. A woman with one gene of hemophilia and one gene of color blindness on one of the X
chromosomes marries a normal man. How will the progeny be? a. 50% hemophilic
colorblind sons and 50% color blind daughters
b. 50% hemophilic and color-blind sons and 50% normal sons
c. All sons and daughters are hemophilic and color blind
d. Hemophilic and color-blind daughters
13. The most important example of point mutation is found in a disease called?
a. Thalassemia c. Down’s syndrome
b. Sickle cell anemia d. Night blindness
16. Which of the following is a possible result of chromosomal breakage that a fragment can
be reattached to the original chromosome in a reverse orientation?
a. Deletion b. Inversion c. Disjunction d. Translocation
17. Which of the following is the result when a segment of a chromosome has been copied?
a. Deletion b. Inversion c. Duplication d. Translocation
18. Which of the following results that has an error in the DNA base sequence?
a. Deletion b. Inversion c. Chromosomal Mutation d. Gene Mutation