Paper Clip PCR
PURPOSE
The purpose of this activity is to reinforce basic DNA concepts and to
introduce students to the technique of PCR and its many uses. Part one of the
activity uses a virtual PCR animation that takes students through the steps
involved in PCR. Part two of this activity allow students to perform PCR
using paper clips to represent individual nucleotides.
MATERIALS
Note that this activity assumes students have some prior knowledge of DNA,
its basic structure, and function. For a tutorial of DNA basics, see box at right.
Go Online!
For this activity you will need:
For: A tutorial of DNA basics
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Visit: http://
learn.genetics.utah.edu/
content/begin/tour/
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Access to the internet and a projector
Small colored paper clips (blue, red, green, yellow and white)
Each group will need about 25 paper clips of each color in a separate bag/
cup, and about 6 white paper clips
Label cups/bags with A, T, G, or C according to color key in activity
Copies of the “Paper Clip PCR” activity for each student
LESSON PLAN
Engagement (30 minutes)
Begin by asking students what they know about DNA. As students answer,
write their information on the board. Be sure that your discussion includes
the following questions/points:
1. What role does DNA perform in a living organism?
2. What is the basic shape or structure of DNA?
3. What are the four nucleotide bases or “letters” that make up DNA? How
do they pair together?
4. What is a gene? What do genes code for?
Paper Clip PCR v.1 • 1
Next, introduce students to the technique of PCR (Polymerase Chain
Reaction). PCR is a method used in the lab to make many copies of a
specific piece of DNA that we want to study. This process uses repeated
cycles of heating and cooling to separate DNA strands and make new
copies of the desired DNA segment.
Project for students the Virtual PCR lab found on the University of Utah
Website: http://learn.genetics.utah.edu/content/labs/pcr/
Slowly click through the virtual PCR lab, being sure to note the various
components or “ingredients” used to perform PCR and why they are
used:
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Extracted DNA - the “Template”
Primers (two different primers are used in a PCR reaction)
Nucleotides (A, T, G, and C for building new DNA strands)
Polymerase enzyme (to catalyze the building of new DNA strands)
Fact Files
The FBI and PCR
PCR is the method of choice
used by the FBI to perform
DNA profiling in order to
identify individuals. For more
on how this works, visit
www.dnai.org and click on
“Applications” and “Profiling.
Finish clicking through the virtual PCR lab, noting to students how the
target DNA sequence, usually a gene or a piece of a gene, is copied many
times in the thermal cycler. Address any questions as they arise,
reinforcing that the goal of PCR is to produce many copies of a desired
segment of DNA.
Paper Clip Tip
Exploration (30 minutes)
Arrange students in groups of three. Pass out to each group a set of
colored paper clips. Tell the students that they are now going to perform
two rounds of PCR using paper clips as their DNA. Each color paper clip
represents one of the four nucleotides in the DNA code. Students should
follow their “Paper Clip PCR” activity, with all members of the group
sharing the various steps. At the end of the activity, students should have
a copy of the desired DNA segment.
Make sure that students
keep track of the
orientation of their paper
clip DNA strands.
Keeping the paper clips
strands flat and straight
on their desk will help.
Explanation and Assessment (5 minutes)
After each group has completed the Paper Clip PCR activity, go around
the room to check each group’s final PCR product.
In class or for homework (if permitted) have each student pick one topic
area below and ask each student to research and do a brief write-up of
how PCR is useful in the following areas:
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DNA profiling
Detecting Genetically Modified Organisms
Disease diagnosis
Phylogeny
Paper Clip PCR v.1 • 2
Go Online!
For: Great DNA resources
Visit: http://www.dnai.org
Name: _________________________________
Paper Clip PCR
In this activity you will be performing PCR (polymerase chain reaction) using paper clips to
represent DNA. Each colored paper clip represents a particular nucleotide in the DNA code:
Blue - Adenine (A)
Red - Thymine (T)
Green - Guanine (G)
Yellow - Cytosine (C)
White - hydrogen bonds to connect DNA strands
1. Start by creating your template or starting DNA strand out of paper clips. Connect the proper
colors of paper clips to represent the following DNA sequence:
A-G-A-T-C-G-C-A-A-A-G-C-A-T-T
Keep all strands flat on your desk!
2. Using your first strand as a guide, create the complementary (matching) strand out of the
proper colors of paper clips. Hint: A pairs with T and G pairs with C. Use two white paper clips
to connect the ends of your two DNA strands together. Your template strand should be on top.
3. Create your Primers out of the following sequences:
Primer 1: T-A-G
Primer 2: G-C-A
4. Repeat step three to make a second pair of primers.
Now you are ready to perform PCR……..
OVER….
Paper Clip PCR v.1 • 3
Blue (A)
Red (T)
Green (G)
Yellow (C)
5. Begin by denaturing or separating your two DNA strands (remove white paper clips).
6. Attach (or anneal) Primer 1 to the template (top) strand in its proper place using a white paper
clip. Remember base pairing: A with T and G with C. Keep all strands in order and flat on the desk.
7. Attach (or anneal) Primer 2 to the bottom strand in its proper place using a white paper clip.
T - A - G
Primer 1
Top Strand
Bottom Strand
Primer 2
G - C - A
8. Now, using each DNA strand as a guide, finish building (extending) new top and bottom DNA
strands using the primers as the starting pieces.
T - A - G
New Strand
Top Strand
Bottom Strand
G - C - A
New Strand
9. Denature (separate) your new DNA strands by removing the white paper clips.
10. Next, anneal (attach) your second set of primers to the new DNA strands. This time, primer 2
will attach to the top strand, and primer 1 will attach to the bottom strand. (Other primers
would also attach to the original strands again, but for now, we will leave those out).
G - C - A
Primer 2
New Strand
Top Strand
Bottom Strand
New Strand
Primer 1
T - A - G
Paper Clip PCR v.1 • 4
Blue (A)
Red (T)
Green (G)
Yellow (C)
11. Finally, extend your two primers to create a second set of new DNA strands. These strands
represent our desired PCR product, the sequence we wish to make many copies of. The sequences
of the top and bottom PCR products should match (complement) each other.
PCR Product
New Strand
Top Strand
Bottom Strand
New Strand
PCR Product
How many nucleotides is our desired PCR Product? ______ .
What are the DNA sequences of our PCR Product? (hint: The top and bottom sequences should
pair with each other.)
PCR Product top strand :
________________________________________________________
PCR Product bottom strand: ________________________________________________________
Congratulations. You have just performed PCR. Remember, each round of PCR doubles the
number of DNA strands in the sample. A typical PCR will go through about 30 cycles of
replication to make millions of copies of our desired PCR product.
How long did it take you to replicate your paper clip DNA? Although it may have taken you
a few minutes to do this, your cells replicate DNA very quickly, at a rate of about 50 base pairs
per second!
How many mistakes did you make when replicating your DNA? Your cells make mistakes only
once for every 1,000 to 100,000 base pairs during replication. Not bad!
Paper Clip PCR v.1 • 5
Blue (A)
Red (T)
Green (G)
Yellow (C)
ANSWER KEY
11. Finally, extend your two primers to create a second set of new DNA strands. These strands
represent our desired PCR product, the sequence we wish to make many copies of. The sequences
of the top and bottom PCR products should match (complement) each other.
A
T
C
G
C
A
A
A
G
C
A
T
A
G
C
G
T
T
T
C
G
T
PCR Product
A
A
A
G
A
T
C
G
C
A
A
A
G
C
A
T
T
T
C
T
A
G
C
G
T
T
T
C
G
T
A
A
New Strand
Top Strand
Bottom Strand
A
G
A
T
C
G
C
A
A
A
G
C
A
New Strand
T
A
G
C
G
T
T
T
C
G
T
PCR Product
How many nucleotides long is our desired PCR Product? ____11__ .
What are the DNA sequences of our PCR Product?
Top PCR Product :
___ATCGCAAAGCA_________________________
Bottom PCR Product: ___TAGCGTTTCGT__________________________
Paper Clip PCR v.1 • 6