What makes me tick…tock?
Lesson 3: How can genetics change your clock?
June 2012
DNA synthesis, replication, and mutation
DNA holds the code for every protein assembled in the body. InPart 1 of this activity, you will
work in groups to construct a double-stranded model of a circadian gene, per2, replicate the
per2 gene, and mutate the per2gene.
Constructing your DNA model
For the DNA model, you will be using pipecleaners and colored Velcro. The pipecleaners
represent the backbone of the DNA and the colored Velcro pieces are base pairs. In this model,
each base pair is represented by a different color of Velcro:
Adenine –red
Thymine –yellow
Guanine – green
Cytosine – blue
1. Before you start assembling your DNA model, use masking tape to label one end of the
pipe cleaner 5’ coding strand. The desired protein product corresponds to the gene on
the coding strand. That is, the coding strand represents the gene that is being
transcribed and later translated into a protein.
2. Once you have this end labeled, start assembling your DNA model by sliding colored
Velcro pieces onto the pipecleaner. The genetic code for the gene is: 5’ GCC GAG AGT
GTG GCG TCC CTC 3’. Label the other end of the strand 3’ coding strand. Use the table
below to write out the sequence of the template strand with the corresponding base
pairs.
Coding Strand
5’ end
Template Strand
3’ end
GCC
GAG
AGT
GTG
GCG
TCC
CTC
3’ end
5’ end
3. Now that you have one coding strand assembled, construct the template strand with
the sequence you determined above. Make sure to also label the 3’ and 5’ ends of your
template strands you did in step 2. Remember that the template strand is the strand of
DNA that will be transcribed. This is because mRNA transcription must occur in the 5’ to
3’ direction and must have a complementary base pair sequence with the template DNA
strand, in the 3’ to 5’ direction.

Looking at your double-stranded DNA models, what do you notice about the structure?
For example, do you see any patterns that may make it easier or harder to replicate
(copy) genes?
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What makes me tick…tock?
Lesson 3: How can genetics change your clock?
June 2012
DNA mutation
1. Carefully un-Velcro your two strands of DNA.
2. Now that you have two single strands of DNA, get a set of Gene Mutation cards from
your teacher and break into pairs.
3. Each pair should take a Gene Mutation card and follow the instructions on the card.
Each group should work separately when mutating the per2 gene.
4. After your group and your partner group have mutated your single strand of per2DNA,
build the other strand so you have a double-stranded per2DNA model.
***Note: make sure you are mutating the correct strand. One card has instructions for the
coding strand and the other has instructions for the template strand.
5. When both pairs have completed the instructions on the Gene Mutation card, compare
your double-stranded mutated gene sequence to the other group’s model.

When you compare the two models, is there anything about the mutation that surprises
you? What does this tell you about the replication of DNA mutations?

Do you think this gene mutation will have a noticeable effect on the animal’s ability to
function? Explain your answer.
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What makes me tick…tock?
Lesson 3: How can genetics change your clock?
June 2012
Transcription of DNA to RNA
In part 2 of this activity, you will transcribe theper2 DNA to mRNA, the second step in the
process of making proteins from DNA.
1. Before starting the transcription of DNA to RNA, one group of students will be assigned
to transcribe the wild type DNA and their partner group will be assigned to transcribe
the mutant DNA.
2. Make sure to use a different colored backbone pipecleaner so that it is easy to tell the
difference between DNA and mRNA.
3. To transcribe your gene, unzip your double-strandedper2 DNA model.
4. Using the template strand, build your corresponding RNA sequence.
***Note: Since uracil replaces thymine in the RNA strand, you now have a new Velcro color.
Use the orange Velcro for uracil in your per2 mRNA model.
Wild type
DNA
Wild type
RNA
Mutant
DNA
Mutant
RNA
GCC
GAG
AGT
GTG
GCG
TCC
CTC
GCC
GAG
GGT
GTG
GCG
TCC
CTC
5’ end
5’ end
5. When both partner groups have completed transcribing the genes, compare your RNA
sequence to the other partner group’s model.

When you compare the two mRNA sequences, is there anything that surprises you?
What similarities/differences do you notice between the two sequences?

Do you think this gene mutation will have a noticeable effect on the animal’s ability to
function? Explain your answer.
3
What makes me tick…tock?
Lesson 3: How can genetics change your clock?
June 2012
Translation of RNA to protein
In part 3 of this activity, you will translate the per2 mRNA into amino acids, the third step in the
process of making proteins from DNA.
1. Work in groups to build amino acid chains.
2. The groups who transcribed the wild type DNA will translate the wild type gene
sequence and the other groups who transcribed the mutant DNA will translate the
mutated gene sequence.
3. In the chart below, the per2 mRNA sequence you created is written. Translate the mRNA
sequence below by writing the corresponding amino acid below the RNA codon.
Wild type
Amino acid 5’ end
sequence
GCC
GAG
AGU
GUG
GCG
UCC
CUC
Mutant
Amino acid 5’ end
sequence
GCC
GAG
GGU
GUG
GCG
UCC
CUC
http://biology.kenyon.edu/courses/biol114/Chap05/Chapter05.html
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What makes me tick…tock?
Lesson 3: How can genetics change your clock?
June 2012
4. Once you have translated your per2 mRNA sequence, start building your assigned amino
acids. For this activity, you will be using a longer amino acid chain than what you have
translated. The code below is a shorthand to record the name of proteins: each protein
is assigned a three letter code.
Wild type Per2:
Ser- Leu-Ala-Leu-Pro-Gly-Lys-Ala-Glu-Ser-Val-Ala-Ser-Leu-Thr-Ser-Gln-Cys-Ser-Tyr
Mutant Per2:
Ser- Leu-Ala-Leu-Pro-Gly-Lys-Ala-Glu-Gly-Val-Ala-Ser-Leu-Thr-Ser-Gln-Cys-Ser-Tyr
5. Write down your group’s assigned amino acids _________________________________
6. Each amino acid will be built using candy, wire, and pipe cleaners. The candy amino
acids are built on wires that you will string on a pipe cleaner that represents the peptide
bonds between the amino acids. Use the attached amino acid guide to build the amino
acids. The peptide chain that you create is a small piece of the larger Per2 protein.
7. After all groups have constructed their candy amino acids, combine the amino acids into
a long peptide chain. The sequence of amino acids in a peptide chains referred to as
primary structure.

When you compare the two peptide chains, is there anything that surprises you? What
are the noticeable differences between the two models?

Do you think this amino acid mutation will have a noticeable effect on the animal’s
ability to function? Explain your answer.

Does the gene mutation lead to a bigger difference in amino acid sequence than you
expected? Explain your answer.
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What makes me tick…tock?
Lesson 3: How can genetics change your clock?
June 2012
Protein Folding
1. After you have compared your amino acid primary structures (sequence of amino acids),
fold your amino acid chains into a three-dimensional protein, using the following rules
of thumb:
 Hydrophobic amino acids will be on the inside of proteins away from the cytosol.
They tend to be close to other hydrophobic amino acids.
 Hydrophilic amino acids will be on the outside of proteins near the cytosol. They
tend to be close to other hydrophilic amino acids.
 Amphipathic amino acids will do whatever the surrounding amino acids are doing
(hydrophobic if surrounded by hydrophobic amino acids, hydrophilic if surrounded
by hydrophilic amino acids).
 Proline will induce a β(beta)-turn in the protein structure. β sheets consist of βstrands connected laterally by at least two or three backbone hydrogen bonds,
forming a twisted, pleated sheet.
The manner in which a strand of amino acids takes shape is referred to as secondary and
tertiary structure. Secondary structure refers to local patterns (such as helices and
sheets), whereas tertiary structure refers to the protein as a whole unit.
***Note: Some proteins have a defined structure that helps determine its biological function.
However, in essence, a protein is a strand of amino acids (like beads on a string) and the threedimensional structure is determined by the interactions of the amino acids with one another.
There is inherent variability in protein shape and even when scientists know the amino acid
sequence (primary structure) of a protein, they can often only make educated predictions
about the protein’s ultimate shape (secondary and tertiary structure). Note areas of potential
variability as you fold your peptide chain.
2. After both groups have folded their candy amino acid sequences, compare your proteins.

When you compare the two protein structures, is there anything that surprises you?
What is a major difference between the two structures?

Do you think this protein mutation will have a noticeable effect on the animal’s ability to
function? Explain your answer.
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What makes me tick…tock?
Lesson 3: How can genetics change your clock?
June 2012
A final level of protein structure is quaternary structure. This level refers to the biophysical and
chemical interactions among proteins. Some proteins assemble into groups and act together.
Mutations, even single amino acid mutations, may influence the ability of one protein to bind
to another by altering the protein’s structure. Change in structure may ultimately lead to
change in function.

Some mutations do not cause large changes in protein structure or folding, but change
how the protein interacts with other proteins. Now that you know that point mutations
like the one you created can change how the protein interacts with other proteins, how
has your answer to the previous question changed?

Now that you have created the known Per2 mutation, create a new mutation that
causes a greater change in the structure of the Per2 gene. How might this mutation you
have created affect the function of the protein?
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