Engineering Memorandum

The NANOMED Company created nanobots that can help maintain homeostasis in all individuals that lack the ability to create certain proteins. These Nanobots
can circulate throughout the body and manufacture and deliver proteins where needed.

Our engineering firm is hired to create the protein instructions for these nanobots; in other words, recreate the DNA model.

Our instructions can only be made of two nitrogen bases. Cytosine and Guanine, but must still be able to code for all amino acids, start and stop codons.

Your team will need to recreate codons and match each new codon to an amino acid, start, and stop signal. There is no limit to how long a codon can be. We
understand that mutations can’t be avoided, but we believe the number of amino acid changes can be limited with the proper design.

Your team’s new DNA model will be tested with one of the three types of mutations: Substitution, Deletion, and/or Insertion. The design that has the least
change in the amino acid sequence will be the design we choose.

In addition, the real DNA model will be given the same rigorous mutation tests as ours so that we have data to compare and report to NANOMED.

Good luck.
 Explain: Analyze the Genetic Code

Now your team needs to perform mutation simulations on DNA as it exists in nature. The results of these simulations will be used as a control later on in the
design process when you test the effectiveness of your synthetic DNA code.

Our firm has chosen the following Amino Acid sequence for your team to analyze.

Amino
Acid Met-Ala-Pro-Ser-Asp-His-Gly-Thr-Leu-Stop
Sequence

1. Begin by working backwards to create the original DNA strand. Add to the stand to the chart below.

2. Your team will mutate the original DNA strand three ways using your assigned mutation: See instructions below. BE SURE TO ALWAYS MUTATE THE
ORIGINAL DNA STRAND.

Instructions for Substitution:

● Mutation 1: substitute every third base in the DNA sequence. Transcribe and translate.
● Mutation 2 substitute every fourth base in the DNA sequence. Transcribe and translate.
● Mutation 3 substitute every fifth base in the DNA sequence. Transcribe and Translate
Instructions for Deletion:
● Mutation 1: remove every third base in the DNA sequence. Transcribe and translate.
● Mutation 2 remove every fourth base in the DNA sequence. Transcribe and translate.
● Mutation 3 remove every fifth base in the DNA sequence. Transcribe and Translate.
Instructions for Insertion:
● Mutation 1: add a base after every third base in the DNA sequence. Transcribe and translate.
● Mutation 2 add a base after every fourth base in the DNA sequence. Transcribe and translate.
● Mutation 3 add a base after every fifth base in the DNA sequence. Transcribe and Translate.
3. Compare the amino acid sequence of each mutation to the original amino acid sequence. Record the number of amino acids that are different.
Type of mutation Tested ______________________________

Original DNA
Strand

Mutation 1 # of changes to
Transcribe amino acid
sequence
Translate

____

Mutation # of changes to
2 amino acid
sequence
Transcribe
Translate
____

Mutation # of changes to
3 amino acid
sequence
Transcribe
Translate
____
 Engineer: Design A Synthetic Genetic Code Model

Now it is time to recreate DNA with the following constraints and parameters:

● The code can only include two bases. Use the letters X and O to identify each base.
● It must code for all amino acids, start, and stop codons.
● There is no limit on how long a codon can be
● You design must try to limit amino acid changes that occur with mutations.

Individual Brainstorm:
Below are copies of an amino acid/possible codons chart to help you decide on codons. This will help you translate your synthetic DNA later on.
Use the charts to individually, brainstorm different ways you could design a model of a synthetic genetic code. Consider the constraints and ways your model
could fit within those constraints.

Option 1:

Amino Possible codons Amino Possible Codons

Acid Acid
Ala Lys
Asn Met
Asp Phe
Arg Pro
Cys Ser
Gln STOP
Glu Thr
Gly Trp
His Tyr
Ile Val
Leu
Option 2:

Amino Possible codons Amino Possible Codons

Acid Acid
Ala Lys
Asn Met
Asp Phe
Arg Pro
Cys Ser
Gln STOP
Glu Thr
Gly Trp
His Tyr
Ile Val
Leu

Option 3:

Amino Possible codons Amino Possible Codons

Acid Acid
Ala Lys
Asn Met
Asp Phe
Arg Pro
Cys Ser
Gln STOP
Glu Thr
Gly Trp
His Tyr
Ile Val
Leu

Option 4:

Amino Possible codons Amino Possible Codons

Acid Acid
Ala Lys
Asn Met
Asp Phe
Arg Pro
Cys Ser
Gln STOP
Glu Thr
Gly Trp
His Tyr
Ile Val
Leu

Group Brainstorm:

As a group, discuss all the individual designs and choose one for your group’s synthetic genetic code model. Below, write the codons for this code in the chart
below. Then justify why your team selected this design. Include: How does it meet the overall goal of limiting amino acid changes with mutations?

Justification statement:
Group Design of Synthetic Genetic Code Model (Write your final group model design here):

Amino Possible codons Amino Possible Codons

Acid Acid
Ala Lys
Asn Met
Asp Phe
Arg Pro
Cys Ser
Gln STOP
Glu Thr
Gly Trp
His Tyr
Ile Val
Leu
Engineer: Testing Your Encoding System

It is now time to run some mutation simulations on your new genetic code Using the amino acid sequence as before. Start by working backwards to find the
Original Synthetic DNA code. Then test your synthetic DNA. Your group was either assigned a substitution, deletion, or insertion mutation. Follow the same
procedure and previous and fill in the data chart below.

Amino Acid
Sequence Met-Ala-Pro-Ser-Asp-His-Gly-Thr-Leu-Stop
Type of mutation Tested ______________________________

Original Synthetic
DNA Strand

Mutation 1 # of changes to
Transcribe amino acid
sequence
Translate

____

Mutation # of changes to
2 amino acid
sequence
Transcribe
Translate
____

Mutation # of changes to
3 amino acid
sequence
Transcribe
Translate
____
Elaborate: Analyze Your Synthetic Encoding System

Now that you have put your synthetic DNA through the tests, it is time to analyze it with the Natural DNA. NanoMed will want you to be able to answer the
following questions.

1. Compare the data you generated from the Explain and Engineer sections. How does your Synthetic Code compare to the real thing?

2. Are the changes in Amino acid sequence similar or not? Explain.

3. Justify the number of bases you chose for each codons.

4. Justify how many codons code for each amino acid.

5. Was there any point in your design process that you had to redesign your coding system? If so, why?

6. What are the strengths and weaknesses of the model of your coding system?
Evaluate: Comparing Class Data

Each of you did a fantastic job on engineering a new synthetic DNA code. However, NanoMed only wants one solution. It is now time to compile each group’s
data on their individual coding system in order to figure out which system best fits the parameters of the task.

Compile class results into the following data chart:

1. Substitution Mutation: Class Results

Group Name Bases per Codons per Every third # of amino acid Every fourth # of amino acid Every fifth base # of amino acid
codon amino acid base changes base changes changes

2. Insertion Mutation: Class Results

Group Name Bases per Codons per After every # of amino acid After Every # of amino acid After every # of amino acid
codon amino acid third base changes fourth base changes fifth base changes

3. Deletion Mutation: Class Results

Group Name Bases per Codons per every third # of amino acid Every fourth # of amino acid every fifth base # of amino acid
codon amino acid base changes base changes changes
4. Which group best met the criteria? Why?

5. How has the number of bases each codon contains influence how many amino acids changed?