www.ck12.org
_3cyBhbmQgVHJhbnNsYXRpb24.
1
www.ck12.org
2
DNA
Brent Stickrath
Douglas Wilkin, Ph.D.
Jean Brainard, Ph.D.
Say Thanks to the Authors
Click http://www.ck12.org/saythanks
(No sign in required)
www.ck12.org
To access a customizable version of this book, as well as other
interactive content, visit www.ck12.org
AUTHORS
Brent Stickrath
Douglas Wilkin, Ph.D.
Jean Brainard, Ph.D.
CK-12 Foundation is a non-profit organization with a mission to
reduce the cost of textbook materials for the K-12 market both
in the U.S. and worldwide. Using an open-content, web-based
collaborative model termed the FlexBook®, CK-12 intends to
pioneer the generation and distribution of high-quality educational
content that will serve both as core text as well as provide an
adaptive environment for learning, powered through the FlexBook
Platform®.
Copyright © 2013 CK-12 Foundation, www.ck12.org
The names “CK-12” and “CK12” and associated logos and the
terms “FlexBook®” and “FlexBook Platform®” (collectively
“CK-12 Marks”) are trademarks and service marks of CK-12
Foundation and are protected by federal, state, and international
laws.
Any form of reproduction of this book in any format or medium,
in whole or in sections must include the referral attribution link
http://www.ck12.org/saythanks (placed in a visible location) in
addition to the following terms.
Except as otherwise noted, all CK-12 Content (including CK-12
Curriculum Material) is made available to Users in accordance
with the Creative Commons Attribution-Non-Commercial 3.0
Unported (CC BY-NC 3.0) License (http://creativecommons.org/
licenses/by-nc/3.0/), as amended and updated by Creative Commons from time to time (the “CC License”), which is incorporated
herein by this reference.
Complete terms can be found at http://www.ck12.org/terms.
Printed: October 1, 2013
iii
Contents
www.ck12.org
Contents
1
iv
Molecular Biology
1.1
Central Dogma of Molecular Biology .
1.2
DNA, the Genetic Material . . . . . .
1.3
DNA Structure and Replication . . . .
1.4
RNA . . . . . . . . . . . . . . . . . .
1.5
Transcription of DNA to RNA . . . .
1.6
Genetic Code . . . . . . . . . . . . .
1.7
Translation of RNA to Protein . . . . .
1.8
Mutation Types . . . . . . . . . . . .
1.9
Mutation Causes . . . . . . . . . . . .
1.10
Mutation Effects . . . . . . . . . . . .
1.11
Gene Expression . . . . . . . . . . . .
1.12
Prokaryotic Gene Regulation . . . . .
1.13
Eukaryotic Gene Regulation . . . . .
1.14
References . . . . . . . . . . . . . . .
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
1
2
5
8
13
16
21
24
28
32
36
39
42
45
49
www.ck12.org
Chapter 1. Molecular Biology
C HAPTER
1
Molecular Biology
Chapter Outline
1.1
C ENTRAL D OGMA OF M OLECULAR B IOLOGY
1.2
DNA, THE G ENETIC M ATERIAL
1.3
DNA S TRUCTURE AND R EPLICATION
1.4
RNA
1.5
T RANSCRIPTION OF DNA TO RNA
1.6
G ENETIC C ODE
1.7
T RANSLATION OF RNA TO P ROTEIN
1.8
M UTATION T YPES
1.9
M UTATION C AUSES
1.10
M UTATION E FFECTS
1.11
G ENE E XPRESSION
1.12
P ROKARYOTIC G ENE R EGULATION
1.13
E UKARYOTIC G ENE R EGULATION
1.14
R EFERENCES
Introduction
What molecule determines many of your traits?
Biology of the Molecule. This chapter focuses on DNA and proteins, and specifically how the "instructions" in DNA
are used to make proteins. This model depicts a protein binding to DNA. Notice the "spiral staircase" shape of the
DNA molecule, with the globular wrapped protein around it.
1
1.1. Central Dogma of Molecular Biology
www.ck12.org
1.1 Central Dogma of Molecular Biology
• State the central dogma of molecular biology.
Is it always DNA to RNA to proteins?
The central dogma of molecular biology. Coined by Francis Crick. And in his own words, "I called this idea the
central dogma, for two reasons, I suspect. I had already used the obvious word hypothesis in the sequence hypothesis,
and in addition I wanted to suggest that this new assumption was more central and more powerful."
Central Dogma of Molecular Biology
Your DNA, or deoxyribonucleic acid, contains the genes that determine who you are. How can this organic molecule
control your characteristics? DNA contains instructions for all the proteins your body makes. Proteins, in turn,
determine the structure and function of all your cells. What determines a protein’s structure? It begins with the
sequence of amino acids that make up the protein. Instructions for making proteins with the correct sequence of
amino acids are encoded in DNA.
2
www.ck12.org
Chapter 1. Molecular Biology
DNA is found in chromosomes. In eukaryotic cells, chromosomes always remain in the nucleus, but proteins are
made at ribosomes in the cytoplasm. How do the instructions in DNA get to the site of protein synthesis outside
the nucleus? Another type of nucleic acid is responsible. This nucleic acid is RNA, or ribonucleic acid. RNA is a
small molecule that can squeeze through pores in the nuclear membrane. It carries the information from DNA in the
nucleus to a ribosome in the cytoplasm and then helps assemble the protein. In short:
DNA → RNA → Protein
Discovering this sequence of events was a major milestone in molecular biology. It is called the central dogma of
molecular biology. You can watch a video about the central dogma and other concepts in this lesson at this link:
http://www.youtube.com/watch?v=ZjRCmU0_dhY&feature=fvw (8:07).
The vocabulary of DNA, including the two processes involved in the central dogma, transcription and translation,
is discussed at http://www.youtube.com/user/khanacademy#p/c/7A9646BC5110CF64/6/s9HPNwXd9fk (18:23).
MEDIA
Click image to the left for more content.
An overview of protein synthesis can be viewed at http://www.youtube.com/watch?v=-ygpqVr7_xs&feature=relat
ed (10:46).
Summary
• The central dogma of molecular biology states that DNA contains instructions for making a protein, which are
copied by RNA.
• RNA then uses the instructions to make a protein.
• In short: DNA → RNA → Protein, or DNA to RNA to Protein.
Making Connections
MEDIA
Click image to the left for more content.
Practice I
Use this resource to answer the questions that follow.
• What Makes a Firefly Glow? at http://learn.genetics.utah.edu/content/begin/dna/firefly/.
1.
2.
3.
4.
What happens during transcription?
What happens to the mRNA after transcription?
What is a ribosome?
What happens during translation?
3
1.1. Central Dogma of Molecular Biology
www.ck12.org
Practice II
• How Do Cells Make Proteins? at http://ca.pbslearningmedia.org/content/lsps07.sci.life.stru.lpbiosystems
/#content/4dd2fb6badd2c73bce006585.
• DNA to Protein at http://www.concord.org/activities/dna-protein.
Review
1. State the central dogma of molecular biology.
2. What are transcription and translation?
4
www.ck12.org
Chapter 1. Molecular Biology
1.2 DNA, the Genetic Material
• Outline discoveries that led to identification of DNA as the genetic material.
The spiral structure in the picture is a large organic molecule. What type of organic molecule is it?
Here’s a hint: molecules like this one determine who you are. They contain genetic information that controls your
characteristics. They determine your eye color, facial features, and other physical attributes. What molecule is it?
You probably answered "DNA." Today, it is commonly known that DNA is the genetic material. For a long time,
scientists knew such molecules existed. They were aware that genetic information was contained within organic
molecules. However, they didn’t know which type of molecules play this role. In fact, for many decades, scientists
thought that proteins were the molecules that carry genetic information. In this section, you will learn how scientists
discovered that DNA carries the code of life.
DNA, the Genetic Material
DNA, deoxyribonucleic acid, is the genetic material in your cells. It was passed on to you from your parents and
determines your characteristics. The discovery that DNA is the genetic material was another important milestone in
molecular biology.
Griffith Searches for the Genetic Material
Many scientists contributed to the identification of DNA as the genetic material. In the 1920s, Frederick Griffith
made an important discovery. He was studying two different strains of a bacterium, called R (rough) strain and S
(smooth) strain. He injected the two strains into mice. The S strain killed (virulent) the mice, but the R strain did
not (nonvirulent) (see Figure 1.1). Griffith also injected mice with S-strain bacteria that had been killed by heat. As
5
1.2. DNA, the Genetic Material
www.ck12.org
FIGURE 1.1
Griffith’s Experimental Results.
Griffith
showed that a substance could be transferred to harmless bacteria and make
them deadly.
expected, the killed bacteria did not harm the mice. However, when the dead S-strain bacteria were mixed with live
R-strain bacteria and injected, the mice died.
Based on his observations, Griffith deduced that something in the killed S strain was transferred to the previously
harmless R strain, making the R strain deadly. He called this process transformation, as something was "transforming" the bacteria from one strain into another strain. What was that something? What type of substance could
change the characteristics of the organism that received it?
Avery’s Team Makes a Major Contribution
In the early 1940s, a team of scientists led by Oswald Avery tried to answer the question raised by Griffith’s results.
They inactivated various substances in the S-strain bacteria. They then killed the S-strain bacteria and mixed the
remains with live R-strain bacteria. (Keep in mind, the R-strain bacteria usually did not harm the mice.) When they
inactivated proteins, the R-strain was deadly to the injected mice. This ruled out proteins as the genetic material.
Why? Even without the S-strain proteins, the R strain was changed, or transformed, into the deadly strain. However,
when the researchers inactivated DNA in the S strain, the R strain remained harmless. This led to the conclusion that
DNA is the substance that controls the characteristics of organisms. In other words, DNA is the genetic material.
You can watch an animation about the research of both Griffith and Avery at this link: http://www.dnalc.org/view/16
375-Animation-17-A-gene-is-made-of-DNA-.html.
Hershey and Chase Seal the Deal
The conclusion that DNA is the genetic material was not widely accepted at first. It had to be confirmed by other
research. In the 1950s, Alfred Hershey and Martha Chase did experiments with viruses and bacteria. Viruses are
not made of cells. They are basically DNA inside a protein coat. To reproduce, a virus must insert its own genetic
material into a cell (such as a bacterium). Then it uses the cell’s machinery to make more viruses. The researchers
used different radioactive elements to label the DNA and proteins in viruses. This allowed them to identify which
molecule the viruses inserted into bacteria. DNA was the molecule they identified. This confirmed that DNA is the
genetic material.
6
www.ck12.org
Chapter 1. Molecular Biology
Summary
• The work of several researchers led to the discovery that DNA is the genetic material.
• Along the way, Griffith discovered the process of transformation.
Practice I
Use this resource to answer the questions that follow.
• Bacteria and viruses have DNA too at http://www.dnalc.org/resources/nobel/hershey.html
1.
2.
3.
4.
5.
What is a bacteriophage?
How do phages reproduce?
Why was DNA labeled with radioactive phosphorus?
After the experiment, where was the radioactive phosphorus found?
What is the genetic material? Why?
Practice II
• A gene is made of DNA at http://www.dnaftb.org/17/animation.html and http://www.dnaftb.org/17/problem
.html.
Review
1. Outline research that determined that DNA is the genetic material.
2. What is transformation?
7
1.3. DNA Structure and Replication
www.ck12.org
1.3 DNA Structure and Replication
• Outline discoveries that led to knowledge of DNA’s structure and function.
How do these four structures form DNA?
In an extremely elegant model, that’s how. As you will soon see, the model predicts how the DNA sequence can
code for proteins, and how the molecule can be replicated.
DNA Structure and Replication
Chargaff’s Rules
Other important discoveries about DNA were made in the mid-1900s by Erwin Chargaff. He studied DNA from
many different species. He was especially interested in the four different nitrogen bases of DNA: adenine (A),
guanine (G), cytosine (C), and thymine (T) (see Figure 1.2). Chargaff found that concentrations of the four bases
differed from one species to another. However, within each species, the concentration of adenine was always about
the same as the concentration of thymine. The same was true of the concentrations of guanine and cytosine. These
observations came to be known as Chargaff’s rules. The significance of the rules would not be revealed until the
structure of DNA was discovered.
8
www.ck12.org
Chapter 1. Molecular Biology
FIGURE 1.2
Nitrogen Bases in DNA. The DNA of all species has the same four nitrogen bases.
The Double Helix
After DNA was found to be the genetic material, scientists wanted to learn more about it. James Watson and Francis
Crick are usually given credit for discovering that DNA has a double helix shape, like a spiral staircase (see Figure
1.3). The discovery was based on the prior work of Rosalind Franklin and other scientists, who had used X rays to
learn more about DNA’s structure. Franklin and these other scientists have not always been given credit for their
contributions. You can learn more about Franklin’s work by watching the video at this link: http://www.youtube.c
om/watch?v=s3whouvZYG8 (7:47).
FIGURE 1.3
The DNA molecule has a double helix shape. This is the same basic
shape as a spiral staircase. Do you see the resemblance? Which parts of
the DNA molecule are like the steps of the spiral staircase?
9
1.3. DNA Structure and Replication
www.ck12.org
The double helix shape of DNA, together with Chargaff’s rules, led to a better understanding of DNA. DNA, as a
nucleic acid, is made from nucleotide monomers, and the DNA double helix consists of two polynucleotide chains.
Each nucleotide consists of a sugar (deoxyribose), a phosphate group, and a nitrogen-containing base (A, C, G, or
T).
Scientists concluded that bonds (hydrogen bonds) between complementary bases hold together the two polynucleotide chains of DNA. Adenine always bonds with its complementary base, thymine. Cytosine always bonds with
its complementary base, guanine. If you look at the nitrogen bases in Figure 1.2, you will see why. Adenine and
guanine have a two-ring structure. Cytosine and thymine have just one ring. If adenine were to bind with guanine
and cytosine with thymine, the distance between the two DNA chains would be variable. However, when a one-ring
molecule binds with a two-ring molecule, the distance between the two chains is kept constant. This maintains the
uniform shape of the DNA double helix. These base pairs (A-T or G-C) stick into the middle of the double helix,
forming, in essence, the steps of the spiral staircase.
DNA Replication
Knowledge of DNA’s structure helped scientists understand how DNA replicates. DNA replication is the process
in which DNA is copied. It occurs during the synthesis (S) phase of the eukaryotic cell cycle. DNA replication
begins when an enzyme breaks the bonds between complementary bases in DNA (see Figure 1.4). This exposes the
bases inside the molecule so they can be “read” by another enzyme and used to build two new DNA strands with
complementary bases. The two daughter molecules that result each contain one strand from the parent molecule and
one new strand that is complementary to it. As a result, the two daughter molecules are both identical to the parent
molecule. DNA replication is a semi-conservative process because half of the parent DNA molecule is conserved
in each of the two daughter DNA molecules. The process of DNA replication is actually much more complex than
this simple summary. You can see a detailed animation of the process at this link: http://www.youtube.com/watch
?v=-mtLXpgjHL0&NR=1 (2:05).
FIGURE 1.4
DNA Replication. DNA replication is a semi-conservative process. Half of
the parent DNA molecule is conserved in each of the two daughter DNA
molecules.
Summary
• Chargaff’s rules state that the amount of A is similar to the amount of T, and the amount of G is similar to the
amount of C.
• Watson and Crick discovered that DNA has a double helix shape, consisting of two polynucleotide chains held
together by bonds between complementary bases.
10
www.ck12.org
Chapter 1. Molecular Biology
• DNA replication is semi-conservative: half of the parent DNA molecule is conserved in each of the two
daughter DNA molecules.
Making Connections
MEDIA
Click image to the left for more content.
Practice I
Use these resources to answer the questions that follow.
• http://www.hippocampus.org/Biology → Biology for AP* → Search: Discovery
1.
2.
3.
4.
5.
6.
Define bacterial transformation.
Describe the results of Griffith’s experiment.
Who first determined that DNA is the transforming agent?
Describe the structure of a bacteriophage.
Why did Hershey and Chase use radioactive phosphorus to "label" DNA?
Explain the results and conclusion of the Hershey and Chase experiment.
• http://www.hippocampus.org/Biology → Non-Majors Biology → Search: DNA Structure and Function
1.
2.
3.
4.
5.
Describe the structure of a single strand of DNA.
The phrase "sides of the ladder" refers to what structure(s)?
Why is there a specific pairing pattern among the bases?
Why are the two strands of the double helix "perfect and specific compliments"?
List three functions of DNA that are based on its structure.
• http://www.hippocampus.org/Biology → Non-Majors Biology → Search: Replication
1.
2.
3.
4.
5.
Why must DNA be replicated?
When does replication occur?
Describe the first step of replication.
Why is each strand of DNA able to serve as a template for replication?
Explain the meaning of semi-conservative replication.
Practice II
• Label the Diagram of a Cell and DNA at http://www.neok12.com/diagram/Genetics-01.htm.
• Genetics at http://www.neok12.com/jigsaw-puzzle/Genetics-03.htm.
• DNA Replication at http://johnkyrk.com/DNAreplic.swf.
• Build a DNA Molecule at http://learn.genetics.utah.edu/content/begin/dna/builddna/.
11
1.3. DNA Structure and Replication
www.ck12.org
Review
1. What are Chargaff’s rules?
2. Identify the structure of the DNA molecule.
3. Why is DNA replication said to be semi-conservative?
4. Create a diagram that shows how DNA replication occurs.
5. Explain why complementary base pairing is necessary to maintain the double helix shape of the DNA molecule.
12
www.ck12.org
Chapter 1. Molecular Biology
1.4 RNA
• Describe the structure of RNA, and identify the three main types of RNA.
How does the information move from the nucleus, where the DNA is located, to the cytoplasm, where the
ribosomes are?
RNA, the other nucleic acid, that’s how. Specifically mRNA. RNA, the middle player in the central dogma. This
image is an abstract representation of tRNA. Without tRNA, mRNA, and rRNA, proteins cannot be made.
RNA
DNA alone cannot “tell” your cells how to make proteins. It needs the help of RNA, ribonucleic acid, the other main
player in the central dogma of molecular biology. Remember, DNA "lives" in the nucleus, but proteins are made on
the ribosomes in the cytoplasm. How does the genetic information get from the nucleus to the cytoplasm? RNA is
the answer.
RNA vs. DNA
RNA, like DNA, is a nucleic acid. However, RNA differs from DNA in several ways. In addition to being smaller
than DNA, RNA also
• consists of one nucleotide chain instead of two,
• contains the nitrogen base uracil (U) instead of thymine,
• contains the sugar ribose instead of deoxyribose.
13
1.4. RNA
www.ck12.org
Types of RNA
There are three main types of RNA, all of which are involved in making proteins.
1. Messenger RNA (mRNA) copies the genetic instructions from DNA in the nucleus, and carries them to the
cytoplasm.
2. Ribosomal RNA (rRNA) helps form ribosomes, where proteins are assembled.
3. Transfer RNA (tRNA) brings amino acids to ribosomes, where they are joined together to form proteins.
FIGURE 1.5
Shown are the three types of RNA and
their roles: (1) mRNA contains the genetic
message, (2) tRNA transfers the amino
acids to the ribosome, (3) rRNA is the
main component of the ribosome. More
on the roles of the RNAs will be discussed
in the "Protein Synthesis" concepts.
Summary
• RNA differs from DNA in several ways.
• There are three main types of RNA: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA
(tRNA).
• Each type plays a different in role in making proteins.
Making Connections
MEDIA
Click image to the left for more content.
Practice I
Use this resource to answer the questions that follow.
14
www.ck12.org
Chapter 1. Molecular Biology
• http://www.hippocampus.org/Biology → Biology for AP* → Search: RNA Structure and Function
1. List three structural differences between DNA and RNA.
2. What is the function of mRNA?
Practice II
• About RNA at http://johnkyrk.com/DNAtranscription.html.
Review
1. What are the three main types of RNA?
2. Compare and contrast DNA and RNA.
15
1.5. Transcription of DNA to RNA
www.ck12.org
1.5 Transcription of DNA to RNA
• Give an overview of transcription.
How does a cell use the information in its DNA?
To transcribe means "to paraphrase or summarize in writing." The information in DNA is transcribed - or summarized
- into a smaller version - RNA - that can be used by the cell. This process is called transcription.
Transcription
The process in which cells make proteins is called protein synthesis. It actually consists of two processes: transcription and translation. Transcription takes place in the nucleus. It uses DNA as a template to make an
RNA molecule. RNA then leaves the nucleus and goes to a ribosome in the cytoplasm, where translation occurs.
Translation reads the genetic code in mRNA and makes a protein.
Transcription is the first part of the central dogma of molecular biology: DNA → RNA. It is the transfer of genetic
instructions in DNA to messenger RNA (mRNA). During transcription, a strand of mRNA is made that is comple16
www.ck12.org
Chapter 1. Molecular Biology
mentary to a strand of DNA. Figure 1.6 shows how this occurs. You can watch an animation of the process at this
link: http://www.biostudio.com/d_%20Transcription.htm.
• A detailed video about transcription is available at this link: http://vcell.ndsu.edu/animations/transcription/m
ovie-flash.htm.
FIGURE 1.6
Overview of Transcription. Transcription
uses the sequence of bases in a strand
of DNA to make a complementary strand
of mRNA. Triplets are groups of three successive nucleotide bases in DNA. Codons
are complementary groups of bases in
mRNA.
Steps of Transcription
Transcription takes place in three steps: initiation, elongation, and termination. The steps are illustrated in Figure
1.7.
1. Initiation is the beginning of transcription. It occurs when the enzyme RNA polymerase binds to a region of
a gene called the promoter. This signals the DNA to unwind so the enzyme can "read" the bases in one of the
DNA strands. The enzyme is now ready to make a strand of mRNA with a complementary sequence of bases.
2. Elongation is the addition of nucleotides to the mRNA strand.
3. Termination is the ending of transcription, and occurs when RNA polymerase crosses a stop (termination)
sequence in the gene. The mRNA strand is complete, and it detaches from DNA.
Processing mRNA
In eukaryotes, the new mRNA is not yet ready for translation. It must go through additional processing before it
leaves the nucleus. This may include splicing, editing, and polyadenylation. These processes modify the mRNA in
various ways. Such modifications allow a single gene to be used to make more than one protein.
• Splicing removes introns from mRNA (see Figure 1.8). Introns are regions that do not code for proteins. The
remaining mRNA consists only of regions that do code for proteins, which are called exons. You can watch
a video showing splicing in more detail at this link: http://vcell.ndsu.edu/animations/mrnasplicing/movie-flas
h.htm.
17
1.5. Transcription of DNA to RNA
www.ck12.org
FIGURE 1.7
Steps of Transcription. Transcription occurs in the three steps - initiation, elongation, and termination - shown here.
• Editing changes some of the nucleotides in mRNA. For example, the human protein called APOB, which
helps transport lipids in the blood, has two different forms because of editing. One form is smaller than the
other because editing adds a premature stop signal in mRNA.
• Polyadenylation adds a “tail” to the mRNA. The tail consists of a string of As (adenine bases). It signals the
end of mRNA. It is also involved in exporting mRNA from the nucleus. In addition, the tail protects mRNA
from enzymes that might break it down.
Summary
• Transcription is the DNA → RNA part of the central dogma of molecular biology.
• Transcription occurs in the nucleus.
• During transcription, a copy of mRNA is made that is complementary to a strand of DNA. In eukaryotes,
mRNA may be modified before it leaves the nucleus.
Practice I
Use these resources to answer the questions that follow.
• http://www.hippocampus.org/Biology → Biology for AP* → Search: The Initiation of Transcription
1. What is a transcription unit?
2. Describe the importance of the template strand.
18
www.ck12.org
Chapter 1. Molecular Biology
FIGURE 1.8
Splicing. Splicing removes introns from mRNA. UTR is an untranslated region of the mRNA.
3.
4.
5.
6.
What enzyme is used in transcription? What does this enzyme do?
What are the promoter and initiation site?
Describe the TATA box.
How does RNA polymerase bind to the DNA?
• http://www.hippocampus.org/Biology → Biology for AP* → Search: Elongation, Termination, and Processing
1.
2.
3.
4.
Describe elongation of the RNA during transcription.
What must happen to the RNA prior to translation? Why?
Distinguish between an intron and exon.
What is the role of the GTP cap?
Practice II
• Protein Synthesis at http://www.wisc-online.com/Objects/ViewObject.aspx?ID=AP1302
• DNA Transcription at http://johnkyrk.com/DNAtranscription.html
• How Do Cells Make Proteins? at http://ca.pbslearningmedia.org/content/lsps07.sci.life.stru.lpbiosystems
/#content/4dd2fb6badd2c73bce006585
• What is a Gene? at http://learn.genetics.utah.edu/content/begin/dna/
19
1.5. Transcription of DNA to RNA
www.ck12.org
• Transcribe and Translate a Gene at http://learn.genetics.utah.edu/content/begin/dna/transcribe/
Review
1. What is protein synthesis?
2. Describe transcription.
3. How may mRNA be modified before it leaves the nucleus?
20
www.ck12.org
Chapter 1. Molecular Biology
1.6 Genetic Code
• Describe the genetic code.
How do you go from four letters to 20 amino acids?
You need a code. And the code that changes the information embedded in DNA and RNA into ordered amino acids
and proteins is the genetic code. And every living organism uses the same genetic code.
The Genetic Code
How is the information in a gene encoded? The answer is the genetic code. The genetic code consists of the
sequence of nitrogen bases—A, C, G, U—in an mRNA chain. The four bases make up the “letters” of the genetic
code. The letters are combined in groups of three to form code “words,” called codons. Each codon stands for
(encodes) one amino acid, unless it codes for a start or stop signal. There are 20 common amino acids in proteins.
There are 64 possible codons, more than enough to code for the 20 amino acids. The genetic code is shown in Figure
1.9. To see how scientists cracked the genetic code, go to this link: http://www.dnalc.org/view/16494-Animation-22
-DNA-words-are-three-letters-long-.html.
Reading the Genetic Code
As shown in Figure 1.9, the codon AUG codes for the amino acid methionine. This codon is also the start codon
that begins translation. The start codon establishes the reading frame of mRNA. The reading frame is the way the
letters are divided into codons. After the AUG start codon, the next three letters are read as the second codon. The
next three letters after that are read as the third codon, and so on. This is illustrated in Figure 1.10. The mRNA
molecule is read, codon by codon, until a stop codon is reached. UAG, UGA, and UAA are all stop codons. They
do not code for any amino acids. Stop codons are also known as termination codons.
21
1.6. Genetic Code
www.ck12.org
FIGURE 1.9
The Genetic Code. To find the amino acid
for a particular codon, find the cell in the
table for the first and second bases of the
codon.
Then, within that cell, find the
codon with the correct third base. For example CUG codes for leucine, AAG codes
for lysine, and GGG codes for glycine.
FIGURE 1.10
Reading the Genetic Code. The genetic code is read three bases at a
time. Codons are the code words of the genetic code. Which amino acid
does codon 2 in the drawing stand for?
Characteristics of the Genetic Code
The genetic code has a number of important characteristics.
• The genetic code is universal. All known living organisms use the same genetic code. This shows that all
organisms share a common evolutionary history.
• The genetic code is unambiguous. Each codon codes for just one amino acid (or start or stop). What might
happen if codons encoded more than one amino acid?
• The genetic code is redundant. Most amino acids are encoded by more than one codon. In Figure 1.9, how
many codons code for the amino acid threonine? What might be an advantage of having more than one codon
for the same amino acid?
22
www.ck12.org
Chapter 1. Molecular Biology
Summary
•
•
•
•
The genetic code consists of the sequence of bases in DNA or RNA.
Groups of three bases form codons, and each codon stands for one amino acid (or start or stop).
The codons are read in sequence following the start codon until a stop codon is reached.
The genetic code is universal, unambiguous, and redundant.
Making Connections
MEDIA
Click image to the left for more content.
Practice I
Use this resource to answer the questions that follow.
• http://www.hippocampus.org/Biology → Biology for AP* → Search: Decoding RNA
1.
2.
3.
4.
5.
6.
7.
8.
9.
What is a polypeptide?
How do the 4 nucleotides code for 20 amino acids?
What is the meaning of a "triplet code"?
Describe the 4 properties of codons.
Describe how the genetic code was "cracked."
What is the start codon?
How many stop codons are there? What do these codons signal?
What is a reading frame? Why are reading frames important?
What amino acid do the following codons encode: UUC, UCU, CUU?
Practice II
• Transcribe and Translate a Gene at http://learn.genetics.utah.edu/content/begin/dna/transcribe/.
Review
1. What is the genetic code? What are codons?
2. Use the genetic code to translate the following segment of RNA into a sequence of five amino acids: GUC-GCGCAU-AGC-AAG
3. The genetic code is universal, unambiguous, and redundant. Explain what this means and why it is important.
23
1.7. Translation of RNA to Protein
www.ck12.org
1.7 Translation of RNA to Protein
• Explain how translation occurs.
RNA to proteins. How?
You must translate. To go from one language to another. Spanish to English, French to German, or nucleotides to
amino acids. Which type is the translation of molecular biology? Obviously, the type of translating discussed here
translates from the language of nucleotides to the language of amino acids.
Translation
Translation is the second part of the central dogma of molecular biology: RNA → Protein. It is the process in which
the genetic code in mRNA is read, one codon at a time, to make a protein. Figure 1.11 shows how this happens.
After mRNA leaves the nucleus, it moves to a ribosome, which consists of rRNA and proteins. The ribosome reads
the sequence of codons in mRNA. Molecules of tRNA bring amino acids to the ribosome in the correct sequence.
To understand the role of tRNA, you need to know more about its structure. Each tRNA molecule has an anticodon
for the amino acid it carries. An anticodon is a sequence of 3 bases, and is complementary to the codon for an
amino acid. For example, the amino acid lysine has the codon AAG, so the anticodon is UUC. Therefore, lysine
would be carried by a tRNA molecule with the anticodon UUC. Wherever the codon AAG appears in mRNA, a UUC
anticodon on a tRNA temporarily binds to the codon. While bound to the mRNA, the tRNA gives up its amino acid.
Bonds form between adjacent amino acids as they are brought one by one to the ribosome, forming a polypeptide
chain. The chain of amino acids keeps growing until a stop codon is reached. To see how this happens, go the link
below. http://www.youtube.com/watch?v=B6O6uRb1D38&feature=related (1:29)
After a polypeptide chain is synthesized, it may undergo additional processes. For example, it may assume a folded
shape due to interactions among its amino acids. It may also bind with other polypeptides or with different types
of molecules, such as lipids or carbohydrates. Many proteins travel to the Golgi apparatus to be modified for the
24
www.ck12.org
Chapter 1. Molecular Biology
FIGURE 1.11
Translation. Translation of the codons in mRNA to a chain of amino acids occurs at a ribosome. Find the different
types of RNA in the diagram. What are their roles in translation?
specific job they will do. You can see how this occurs by watching the animation at this link: http://vcell.ndsu.ed
u/animations/proteinmodification/movie-flash.htm.
Summary
•
•
•
•
Translation is the RNA → Protein part of the central dogma.
Translation occurs at a ribosome.
During translation, a protein is synthesized using the codons in mRNA as a guide.
All three types of RNA play a role in translation.
Making Connections
25
1.7. Translation of RNA to Protein
www.ck12.org
FIGURE 1.12
The tRNA structure is a very important aspect in its role. Though the molecule folds into a 3-leaf clover structure,
notice the anticodon in the lower segment of the molecule (shown in red [left]), with the amino acid attached at
the opposite end of the molecule (shown in yellow [right]).
MEDIA
Click image to the left for more content.
Practice I
Use this resource to answer the questions that follow.
• http://www.hippocampus.org/Biology → Non-Majors Biology → Search: Translation
1.
2.
3.
4.
5.
26
Translation needs what three components?
Describe the structure of a ribosome.
Describe the structure and role of a tRNA molecule.
Define codon and anticodon.
How does termination occur?
www.ck12.org
Chapter 1. Molecular Biology
Practice II
• Protein Synthesis at http://www.wisc-online.com/Objects/ViewObject.aspx?ID=AP1302.
• RNA Translation at http://johnkyrk.com/DNAtranslation.html.
• How Do Cells Make Proteins? at http://ca.pbslearningmedia.org/content/lsps07.sci.life.stru.lpbiosystems
/#content/4dd2fb6badd2c73bce006585.
• Transcribe and Translate a Gene at http://learn.genetics.utah.edu/content/begin/dna/transcribe/.
Review
1. Outline the steps of translation.
2. Discuss the structure of a tRNA molecule, and its role in translation.
3. How are transcription and translation related to the central dogma of molecular biology?
27
1.8. Mutation Types
www.ck12.org
1.8 Mutation Types
• Compare and contrast types of mutations.
What causes albinism?
This rare albino alligator must have the specific "instructions," or DNA, to have this quality. The cause of albinism
is a mutation in a gene for melanin, a protein found in skin and eyes. Such a mutation may result in no melanin
production at all or a significant decline in the amount of melanin.
Mutations
A change in the sequence of bases in DNA or RNA is called a mutation. Does the word mutation make you think
of science fiction and bug-eyed monsters? Think again. Everyone has mutations. In fact, most people have dozens
or even hundreds of mutations in their DNA. Mutations are essential for evolution to occur. They are the ultimate
source of all new genetic material - new alleles - in a species. Although most mutations have no effect on the
organisms in which they occur, some mutations are beneficial. Even harmful mutations rarely cause drastic changes
in organisms.
Types of Mutations
There are a variety of types of mutations. Two major categories of mutations are germline mutations and somatic
mutations.
• Germline mutations occur in gametes. These mutations are especially significant because they can be
transmitted to offspring and every cell in the offspring will have the mutation.
28
www.ck12.org
Chapter 1. Molecular Biology
• Somatic mutations occur in other cells of the body. These mutations may have little effect on the organism
because they are confined to just one cell and its daughter cells. Somatic mutations cannot be passed on to
offspring.
Mutations also differ in the way that the genetic material is changed. Mutations may change the structure of a
chromosome or just change a single nucleotide.
Chromosomal Alterations
Chromosomal alterations are mutations that change chromosome structure. They occur when a section of a
chromosome breaks off and rejoins incorrectly or does not rejoin at all. Possible ways these mutations can occur are
illustrated in Figure 1.13. Go to this link for a video about chromosomal alterations: http://www.youtube.com/w
atch?v=OrXRSqa_3lU&feature=related (2:18).
FIGURE 1.13
Chromosomal Alterations. Chromosomal
alterations are major changes in the genetic material.
Chromosomal alterations are very serious. They often result in the death of the organism in which they occur. If
the organism survives, it may be affected in multiple ways. An example of a human chromosomal alteration is the
mutation that causes Down Syndrome. It is a duplication mutation that leads to developmental delays and other
abnormalities.
Point Mutations
A point mutation is a change in a single nucleotide in DNA. This type of mutation is usually less serious than a
chromosomal alteration. An example of a point mutation is a mutation that changes the codon UUU to the codon
29
1.8. Mutation Types
www.ck12.org
UCU. Point mutations can be silent, missense, or nonsense mutations, as shown in Table 1.1. The effects of point
mutations depend on how they change the genetic code. You can watch an animation about nonsense mutations at
this link: http://www.biostudio.com/d_%20Nonsense%20Suppression%20I%20Nonsense%20Mutation.htm.
TABLE 1.1: Point Mutations and Their Effects
Type
Silent
Missense
Nonsense
Description
mutated codon codes for
the same amino acid
mutated codon codes for a
different amino acid
mutated codon is a premature stop codon
Example
CAA (glutamine) → CAG
(glutamine)
CAA (glutamine) → CCA
(proline)
CAA (glutamine) →
UAA (stop)
Effect
none
variable
usually serious
Frameshift Mutations
A frameshift mutation is a deletion or insertion of one or more nucleotides that changes the reading frame of the
base sequence. Deletions remove nucleotides, and insertions add nucleotides. Consider the following sequence of
bases in RNA:
AUG-AAU-ACG-GCU = start-asparagine-threonine-alanine
Now, assume an insertion occurs in this sequence. Let’s say an A nucleotide is inserted after the start codon AUG:
AUG-AAA-UAC-GGC-U = start-lysine-tyrosine-glycine
Even though the rest of the sequence is unchanged, this insertion changes the reading frame and thus all of the
codons that follow it. As this example shows, a frameshift mutation can dramatically change how the codons in
mRNA are read. This can have a drastic effect on the protein product.
Summary
•
•
•
•
Germline mutations occur in gametes. Somatic mutations occur in other body cells.
Chromosomal alterations are mutations that change chromosome structure.
Point mutations change a single nucleotide.
Frameshift mutations are additions or deletions of nucleotides that cause a shift in the reading frame.
Making Connections
MEDIA
Click image to the left for more content.
Practice
Use this resource to answer the questions that follow.
• Mutations are changes in genetic information at http://www.dnaftb.org/27/animation.html.
30
www.ck12.org
1.
2.
3.
4.
5.
Chapter 1. Molecular Biology
What is a point mutation?
What are the effects of a point mutation?
What is a frameshift mutation?
What causes a frameshift?
Who identified point mutations?
Review
1. Identify three types of chromosomal alterations.
2. Distinguish among silent, missense, and nonsense point mutations.
3. What is a frameshift mutation? What causes this type of mutation?
4. Assume that a point mutation changes the codon AUU to AUC. Why is this a neutral mutation?
5. Look at the mutation shown below. The base A was inserted following the start codon AUG. Describe how this
mutation affects the encoded amino acid sequence. AUG-GUC-CCU-AAA → AUG-AGU-CCC-UAA-A
6. Compare and contrast germline mutations and somatic mutations.
31
1.9. Mutation Causes
www.ck12.org
1.9 Mutation Causes
• Identify causes of mutation.
What does radiation contamination do?
It mutates DNA. The Chernobyl disaster was a nuclear accident that occurred on April 26, 1986. It is considered the
worst nuclear power plant accident in history. A Russian publication concludes that 985,000 excess cancers occurred
between 1986 and 2004 as a result of radioactive contamination. The 2011 report of the European Committee on
Radiation Risk calculates a total of 1.4 million excess cancers occurred as a result of this contamination.
Causes of Mutation
Mutations have many possible causes. Some mutations seem to happen spontaneously without any outside influence. They can occur when mistakes are made during DNA replication or transcription. Other mutations are caused
by environmental factors. Anything in the environment that can cause a mutation is known as a mutagen. Examples
of mutagens are pictured in Figure 1.14. For a video about mutagens, go the link below. http://www.youtube.com/w
atch?v=0wrNxCGKCws&feature=related (0:36)
Spontaneous Mutations
There are five common types of spontaneous mutations. These are described in the Table 1.2.
TABLE 1.2:
Mutation
Tautomerism
32
Description
a base is changed by the repositioning of a hydrogen
atom
www.ck12.org
Chapter 1. Molecular Biology
TABLE 1.2: (continued)
Mutation
Depurination
Deamination
Transition
Transversion
Description
loss of a purine base (A or G)
spontaneous deamination of 5-methycytosine
a purine to purine (A to G, G to A), or a pyrimidine to
pyrimidine (C to T, T to C) change
a purine becomes a pyrimidine, or vice versa
33
1.9. Mutation Causes
www.ck12.org
FIGURE 1.14
Examples of Mutagens.
Types of mu-
tagens include radiation, chemicals, and
infectious agents. Do you know of other
examples of each type of mutagen shown
here?
Summary
• Mutations are caused by environmental factors known as mutagens.
• Types of mutagens include radiation, chemicals, and infectious agents.
• Mutations may be spontaneous in nature.
Making Connections
MEDIA
Click image to the left for more content.
Practice
Use this resource to answer the questions that follow.
• What Causes DNA Mutations? at http://learn.genetics.utah.edu/archive/sloozeworm/mutationbg.html.
1.
2.
3.
4.
5.
34
Mutations in DNA sequences generally occur through two processes. What are they?
How might ultraviolet light cause a mutation?
How can nuclear radiation damage DNA?
How often does DNA polymerase make a mistake?
Are all of the mistakes by DNA polymerase incorporated into DNA? Why or why not?
www.ck12.org
Chapter 1. Molecular Biology
Review
1. Define mutation and mutagen.
2. List three examples of mutagens.
3. Distinguish between a transition and a transversion.
The Chernobyl Disaster: Follow-up
Though the area immediately around the Chernobyl disaster may not be safe for human life for thousands of years,
the Exclusion Zone around the Chernobyl nuclear power station has become a haven for wildlife. As humans were
evacuated from the area 25 years ago, existing animal populations multiplied and rare species not seen for centuries
have returned or have been reintroduced, for example lynx, wild boar, wolf, Eurasian brown bear, European bison,
Przewalski’s horse, and eagle owl. Birds nest inside the cracked concrete sarcophagus shielding in the shattered
remains of the nuclear reactor. The Exclusion Zone is so lush with wildlife and greenery that in 2007 the Ukrainian
government designated it a wildlife sanctuary. It is now one of the largest wildlife sanctuaries in Europe.
35
1.10. Mutation Effects
www.ck12.org
1.10 Mutation Effects
• Explain how mutations may affect the organisms in which they occur.
Is this rat hairless?
Yes. Why? The result of a mutation, a change in the DNA sequence. The effects of mutations can vary widely, from
being beneficial, to having no effect, to having lethal consequences, and every possibility in between.
Effects of Mutations
The majority of mutations have neither negative nor positive effects on the organism in which they occur. These
mutations are called neutral mutations. Examples include silent point mutations. They are neutral because they do
not change the amino acids in the proteins they encode.
Many other mutations have no effect on the organism because they are repaired before protein synthesis occurs.
Cells have multiple repair mechanisms to fix mutations in DNA. One way DNA can be repaired is illustrated in
Figure 1.15. If a cell’s DNA is permanently damaged and cannot be repaired, the cell is likely to be prevented from
dividing.
36
www.ck12.org
Chapter 1. Molecular Biology
FIGURE 1.15
DNA Repair Pathway.
This flow chart
shows one way that damaged DNA is
repaired in E. coli bacteria.
Beneficial Mutations
Some mutations have a positive effect on the organism in which they occur. They are called beneficial mutations.
They lead to new versions of proteins that help organisms adapt to changes in their environment. Beneficial mutations
are essential for evolution to occur. They increase an organism’s changes of surviving or reproducing, so they are
likely to become more common over time. There are several well-known examples of beneficial mutations. Here are
just two:
1. Mutations in many bacteria that allow them to survive in the presence of antibiotic drugs. The mutations lead
to antibiotic-resistant strains of bacteria.
2. A unique mutation is found in people in a small town in Italy. The mutation protects them from developing
atherosclerosis, which is the dangerous buildup of fatty materials in blood vessels. The individual in which
the mutation first appeared has even been identified.
Harmful Mutations
Imagine making a random change in a complicated machine such as a car engine. The chance that the random
change would improve the functioning of the car is very small. The change is far more likely to result in a car that
does not run well or perhaps does not run at all. By the same token, any random change in a gene’s DNA is likely to
result in a protein that does not function normally or may not function at all. Such mutations are likely to be harmful.
Harmful mutations may cause genetic disorders or cancer.
• A genetic disorder is a disease caused by a mutation in one or a few genes. A human example is cystic
fibrosis. A mutation in a single gene causes the body to produce thick, sticky mucus that clogs the lungs and
blocks ducts in digestive organs. You can watch a video about cystic fibrosis and other genetic disorders at
this link: http://www.youtube.com/watch?v=8s4he3wLgkM&feature=PlayList&p=397710758E9BCB24&p
laynext_from=PL&playnext=1&index=17 (9:31).
• Cancer is a disease in which cells grow out of control and form abnormal masses of cells. It is generally
caused by mutations in genes that regulate the cell cycle. Because of the mutations, cells with damaged DNA
37
1.10. Mutation Effects
www.ck12.org
are allowed to divide without limits. Cancer genes can be inherited. You can learn more about hereditary
cancer by watching the video at the following link: http://www.youtube.com/watch?v=LWk5FplsKwM (4:29)
Summary
• Mutations are essential for evolution to occur because they increase genetic variation and the potential for
individuals to differ.
• The majority of mutations are neutral in their effects on the organisms in which they occur.
• Beneficial mutations may become more common through natural selection.
• Harmful mutations may cause genetic disorders or cancer.
Making Connections
MEDIA
Click image to the left for more content.
Practice I
Use these resources to answer the questions that follow.
• http://www.hippocampus.org/Biology → Non-Majors Biology → Search: Genetic Disorders
1. Define genetic disorders.
2. What are the two primary types of genetic aberrations?
• http://www.hippocampus.org/Biology → Non-Majors Biology → Search: Gene Defects
1. What are the results of a mutation or defect in a single gene?
2. Describe the causes and effects of cystic fibrosis, Huntington’s Disease, and hemophilia.
• http://www.hippocampus.org/Biology → Non-Majors Biology → Search: Chromosomal Abnormalities
1. What is a chromosomal disorder?
2. When and how do chromosomal errors occur?
3. Describe Cri-du-chat Syndrome and Down Syndrome.
Practice II
• Test Neurofibromin Activity in a Cell at http://learn.genetics.utah.edu/content/begin/dna/neurofibromin/.
Review
1. Why are mutations essential for evolution to occur?
2. What is a genetic disorder?
3. What is cancer?
38
www.ck12.org
Chapter 1. Molecular Biology
1.11 Gene Expression
• Identify general mechanisms that regulate gene expression.
Can your expression change at any moment?
As you know, a person’s expression can change moment by moment. The expression that is demonstrated is usually
appropriate for that moment’s feelings. Gene expression is the use of a gene whose product is necessary for that
moment. It may be a moment during development, it may be a moment of increased anxiety, or it may be in response
to an environmental change. Whenever a particular protein is needed, gene expression provides it.
Gene Expression
Each of your cells has at least 20,000 genes. In fact, all of your cells have the same genes. Do all of your cells
make the same proteins? Obviously not. If they did, then all your cells would be alike. Instead, you have cells with
different structures and functions. This is because different cells make different proteins. They do this by using, or
expressing, different genes. Using a gene to make a protein is called gene expression.
39
1.11. Gene Expression
www.ck12.org
How Gene Expression is Regulated
Gene expression is regulated to ensure that the correct proteins are made when and where they are needed. Regulation
may occur at any point in the expression of a gene, from the start of transcription to the processing of a protein after
translation. Following is a list of stages where gene expression is regulated:
•
•
•
•
•
•
•
Chemical and structural modification of DNA or chromatin
Transcription
Translation
Post-transcriptional modification
RNA transport
mRNA degradation
Post-translational modifications
As shown in Figure 1.16, transcription is controlled by regulatory proteins binding to the DNA. Specifically, gene
regulation at the level of transcription controls when transcription occurs as well as how much RNA is created. A
regulatory protein, or a transcription factor, is a protein involved in regulating gene expression. It is usually bound
to a cis-regulatory element, which is part of the DNA. Regulatory proteins often must be bound to a cis-regulatory
element to switch a gene on (activator), or to turn a gene off (repressor).
Transcription of a gene by RNA polymerase can be regulated by at least five mechanisms:
• Specificity factors (proteins) alter the specificity of RNA polymerase for a promoter or set of promoters,
making it more or less likely to bind to the promoter and begin transcription.
• Activator proteins enhance the interaction between RNA polymerase and a particular promoter.
• Repressor proteins bind to non-coding sequences on the DNA that are close to or overlap the promoter region,
impeding RNA polymerase’s progress along the strand.
• Basal factors are transcription factors that help position RNA polymerase at the start of a gene.
• Enhancers are sites on the DNA strand that are bound by activators in order to loop the DNA, bringing a
specific transcription factor to the initiation complex. An initiation complex is composed of RNA polymerase
and transcription factors.
As the organism grows more sophisticated, gene regulation becomes more complex, though prokaryotic organisms
possess some highly regulated systems. Some human genes are controlled by many activators and repressors working
together. Obviously, a mutation in a cis-regulatory region, such as the promoter, can greatly affect the proper
expression of a gene. It may keep the gene permanently off, such that no protein can be made, or it can keep the
gene permanently on, such that the corresponding protein is constantly made. Both of these can have detremental
effects on the cell.
Summary
• Gene transcription is controlled by regulatory proteins that bind to regulatory elements on DNA.
• The proteins usually either activate or repress transcription.
Practice
Use this resource to answer the questions that follow.
• http://www.hippocampus.org/Biology → Biology for AP* → Search: The Regulation of Gene Expression
1. What percentage of its genes does a typical human cell express?
40
www.ck12.org
Chapter 1. Molecular Biology
FIGURE 1.16
Regulation of Transcription.
Regulatory proteins bind to regulatory elements to control transcription.
The
regulatory elements are embedded within the DNA.
2.
3.
4.
5.
List three ways gene expression may be regulated.
Draw a diagram of an enhancer interacting with its promoter.
Compare euchromatin to heterochromatin.
Discuss how chromosomal rearrangements may effect gene expression.
Review
1. What is gene expression?
2. Describe how regulatory proteins regulate gene expression.
41
1.12. Prokaryotic Gene Regulation
www.ck12.org
1.12 Prokaryotic Gene Regulation
• Describe how gene regulation occurs in prokaryotes.
On or off?
When it comes to genes, that is an important question. And if you’re a single-celled organism like a bacterium,
conserving energy by not producing unnecessary proteins is very important.
Prokaryotic Gene Regulation
Transcription is regulated differently in prokaryotes and eukaryotes. In general, prokaryotic regulation is simpler
than eukaryotic regulation.
42
www.ck12.org
Chapter 1. Molecular Biology
The Role of Operons
Regulation of transcription in prokaryotes typically involves operons. An operon is a region of DNA that consists of
one or more genes that encode the proteins needed for a specific function. The operon also includes a promoter and
an operator. The operator is a region of the operon where regulatory proteins bind. It is located near the promoter
and helps regulate transcription of the operon genes.
The Lac Operon
A well-known example of operon regulation involves the lac operon in E. coli bacteria (see Figure 1.17 and the
video at the link below). The lac operon consists of a promoter, an operator, and three genes that encode the enzymes
needed to digest lactose, the sugar found in milk. The lac operon is regulated by lactose in the environment. http://w
ww.youtube.com/watch?v=oBwtxdI1zvk
• When lactose is absent, a repressor protein binds to the operator. The protein blocks the binding of RNA
polymerase to the promoter. As a result, the lac genes are not expressed.
• When lactose is present, the repressor protein does not bind to the operator. This allows RNA polymerase to
bind to the promoter and begin transcription. As a result, the lac genes are expressed, and lactose is digested.
Why might it be beneficial to express genes only when they are needed? (Hint: synthesizing proteins requires energy
and materials.)
FIGURE 1.17
The three genes of the lac operon are lacZ, lacY, and lacA. They encode proteins needed to digest lactose. The
genes are expressed only in the presence of lactose.
Summary
• Regulation of transcription in prokaryotes typically involves an operon, such as the lac operon in E. coli.
• The lac operon is regulated by proteins that behave differently depending on whether lactose is present or
absent.
Practice I
Use this resource to answer the questions that follow.
• Genes can be turned on and off at http://www.dnalc.org/resources/nobel/jacob_monod.html.
43
1.12. Prokaryotic Gene Regulation
1.
2.
3.
4.
5.
www.ck12.org
How do bacteria break large sugars into smaller ones?
What is the role of lactose in gene regulation?
What happens when lactose is present? Or absent?
What is the operator?
What does "operon" refer to?
Practice II
Gene Machine: The Lac Operon at http://phet.colorado.edu/en/simulation/gene-machine-lac-operon.
MEDIA
Click image to the left for more content.
Review
1. Why might it be beneficial to express genes only when they are needed?
2. Draw a diagram to show how the lac operon is regulated.
44
www.ck12.org
Chapter 1. Molecular Biology
1.13 Eukaryotic Gene Regulation
• Give an overview of gene regulation in eukaryotes.
On or Off? On or Off? On or Off?
That is the key question. Gene regulation in eukaryotes is a highly regulated process usually involving many proteins,
which either bind to each other or bind to the DNA.
Eukaryotic Gene Regulation
In eukaryotic cells, the start of transcription is one of the most complicated parts of gene regulation. There may be
many regulatory proteins and regulatory elements involved. Regulation may also involve enhancers. Enhancers are
distant regions of DNA that can loop back to interact with a gene’s promoter.
The TATA Box
Different types of cells have unique patterns of regulatory elements that result in only the necessary genes being
transcribed. That’s why a skin cell and nerve cell, for example, are so different from each other. However, some
patterns of regulatory elements are common to all genes, regardless of the cells in which they occur. An example is
the TATA box, so named because it has a core sequence of TATAAA. This is a regulatory element that is part of the
promoter of most eukaryotic genes. A number of regulatory proteins bind to the TATA box, forming a multi-protein
complex. It is only when all of the appropriate proteins are bound to the TATA box that RNA polymerase recognizes
the complex and binds to the promoter. Once RNA polymerase binds, transcription begins. To see a video showing
the role of the TATA box in the initiation of transcription, go to this link: http://www.youtube.com/watch?v=6tqPs
I-9aQA&feature=related.
45
1.13. Eukaryotic Gene Regulation
www.ck12.org
Regulation During Development
The regulation of gene expression is extremely important during the development of an organism. Regulatory
proteins must turn on certain genes in particular cells at just the right time so the organism develops normal organs
and organ systems. Homeobox genes are an example of genes that regulate development. They code for regulatory
proteins that switch on whole series of major developmental genes. In insects, homeobox genes called hox genes
ensure that body parts such as limbs develop in the correct place. Figure 1.18 shows how a mutation in a hox gene
can affect an insect’s development. Other organisms, including humans, also have how genes. You can learn more
about homeobox genes at this link: http://www.youtube.com/watch?v=LFG-aLidT8s.
FIGURE 1.18
Effect of Hox Gene Mutation. Scientists
caused a mutation in a hox gene of this
fruit fly. As a result of the mutation, a leg
grew out of its head where an antenna
should have developed.
Gene Expression and Cancer
The mutations that cause cancer generally occur in two types of regulatory genes: tumor-suppressor genes and
proto-oncogenes (see Figure 1.19). These genes produce regulatory proteins that control the cell cycle. When the
genes mutate, cells with mutations divide rapidly and without limits, potentially resulting in a tumor and cancer.
Summary
• Regulation of transcription in eukaryotes is generally more complex than in prokaryotes. It involves unique
regulatory elements in different cells as well as common regulatory elements such as the TATA box.
• Regulation is especially important during development. It may involve regulatory genes such as homeobox
genes that switch other regulatory genes on or off.
• Mutations in regulatory genes that normally control the cell cycle cause cancer.
Practice
Use this resource to answer the questions that follow.
46
www.ck12.org
Chapter 1. Molecular Biology
FIGURE 1.19
How Cancer Develops. This flow chart
shows how a series of mutations in tumorsuppressor genes and proto-oncogenes
leads to cancer.
• Master genes control basic body plans at http://www.dnalc.org/resources/nobel/lewis_nauulein_wieschau
s.html.
1.
2.
3.
4.
5.
6.
How were genes that control early embryonic development identified?
Describe the polarity of the fertilized egg, as it relates to protein expression.
What does "segmentation" refer to in the developing fly?
What is a gap mutant?
Describe the antennapedia mutant.
What is a homeobox gene? A hox gene?
Review
1. Identify the TATA box and its function in transcription.
2. What is a homeobox gene?
3. Sketch how an insect with a mutated hox gene might look. Explain your sketch.
4. Why is gene regulation especially important during development?
47
1.13. Eukaryotic Gene Regulation
www.ck12.org
Summary
Molecular Biology focuses on DNA and how proteins are made. DNA contains the information used to make RNA.
RNA leaves the nucleus and, together with a ribosome, makes proteins. The genetic code is the universal code that
all life uses to turn the language of nucleotides into the language of amino acids. Mistakes in the DNA or RNA
sequence can have dangerous consequences for the organism, though these same "mistakes" are the driving force of
evolution. Regulating the specific timing of genes is an important process for cells in every organism to function
properly.
48
www.ck12.org
Chapter 1. Molecular Biology
1.14 References
1. CK-12 Foundation. . CC-BY-NC-SA 3.0
2. CK-12 Foundation. . CC-BY-NC-SA 3.0
3. DNA image by Michael Ströck; staircase image copyright 3drendering, 2010; composite created by CK-12
Foundation. . DNA image under GNU-FDL 1.2; staircase image used under license from Shutterstock.com
4. Madeleine Price Ball. . CC-BY-SA 2.5
5. Marilee Bailey, courtesy of U.S. Department of Energy. . Public Domain
6. CK-12 Foundation. . CC-BY-NC-SA 3.0
7. CK-12 Foundation. . CC-BY-NC-SA 3.0
8. CK-12 Foundation. . CC-BY-NC-SA 3.0
9. CK-12 Foundation. . CC-BY-NC-SA 3.0
10. TransControl. . GNU-FDL 1.2
11. Courtesy of National Human Genome Research Institute. . Public Domain
12. Yikrazuul. . CC-BY-SA 3.0
13. Dietzel65. . Public Domain
14. A) Beach Image Copyright Alexander Sabilin, 2010; B) X-ray Image Copyright VALIK-NOVIK, 2010; C)
Cigarette Image Copyright robertosch, 2010; D) BBQ Image Copyright valeriya_gold, 2010; E) Facial Cream
Image Copyright Lena Rozova, 2010; F) HPV Image Copyright Sebastian Kaulitzki, 2010; G) H. pylori Image
Copyright 3drenderings, 2010. . All images used under licenses from Shutterstock.com
15. CK-12 Foundation. . CC-BY-NC-SA 3.0
16. CK-12 Foundation. . CC-BY-NC-SA 3.0
17. CK-12 Foundation. . CC-BY-NC-SA 3.0
18. toony. . CC-BY-SA 3.0
19. CK-12 Foundation. . CC-BY-NC-SA 3.0
49