Answer Key to Short Answer Questions for
“Dangerously Thin: A Case Study on the Genetic Code”
1. Why would someone with this type of mutation be at a much higher risk for
overdosing on a prescribed drug?
When a drug is prescribed, it is prescribed at a dose that assumes that the person’s
body would be metabolizing (breaking down) the drug at a specific rate. If the person
lacks the enzymes (or enzyme functions) that are responsible for this metabolism, a
“normal” dose can become an “overdose” because the drug does not break down. In
addition, if the drug is prescribed as “multiple” or “daily” doses, the problem can
become amplified because new doses are being applied before the previous dose has
been removed from the body.
2. The underlying problem in this case resides in Henry’s “genes.” From what you know
about the function of a gene, explain how this problem led to a malfunction in one of
Henry’s proteins (the CYP2C9 enzyme).
A gene is a DNA sequence that a cell uses as an instruction for the construction of
other molecules. Most genes code for the construction of proteins by defining the
amino acid sequence that is required to build a fully functional protein. If the DNA
sequence has an error in it, this has the potential to lead to an error in the amino acid
sequence of that protein. This error could have an impact on the function of that
protein—in this case, Henry’s CYP2C9 enzyme.
3. The DNA changes that are described in Henry’s story are changes to the coding
strands of the CYP2C9 genes. What is the function of the coding strand and how does
it differ from the function of the template strand of Henry’s CYP2C9 gene?
The coding strand of the DNA molecule (gene) represents the actual instruction for
how to assemble the enzyme during translation. The gene must first be transcribed and
converted into a piece of mRNA. RNA polymerase uses the template strand to build the
mRNA molecule by assembling mRNA nucleotides that are complementary to the DNA
nucleotides in the template strand. Since the coding strand of the DNA is also
complementary to the template strand, the mRNA that is constructed will be an exact
copy of the coding strand, with uracil (U) in place of thymine (T).
4. Consider the following DNA sequence found on a different portion the coding strand
of Henry’s CYP2C9 gene: TTACCGAGA
a. What would be the sequence of the template strand on this portion of the
gene?
AATGGCTCT
b. How many triplet codes does this DNA sequence contain?
There are three triplet codes in this sequence: AAT GGC and
TCT
c. What would be the sequence of the mRNA after this sequence is
transcribed?
The mRNA sequence would be UUACCGAGA
d. How many amino acids does this portion of Henry’s coding stand actually
code for?
3 -- The three triplet codes each correspond to a single amino
acid in the enzyme
5. In the first mutation of the CYP2C9 gene described in Henry’s story, the 1075th
nucleotide had changed from an adenine (A) to a cytosine (C). This mutation converts
an ATT triplet code in the coding strand of the DNA molecule to CTT. Beginning
with this triplet code on the DNA, describe the effect that this change would have on
the following:
a. The nucleotide sequence on the template strand of the gene.
If ATT is changed to CTT on the coding strand, then the
template strand would change from TAA to GAA.
b. The mRNA codon that results after this triplet code is transcribed.
The mRNA codon would change from AUU to CUU.
c. The anticodon on the tRNA molecule that is complementary to the mRNA
codon described above.
A tRNA molecule with an anticodon of TAA corresponded to the
AUU codon, but now a tRNA molecule with an anticodon of
GAA will be complementary to the mRNA codon CUU.
d. The amino acid that would be carried by the tRNA molecule described
above.
The tRNA molecule with an anticodon of TAA would have
carried Isoleucine (Ile) because the mRNA codon AUU codes for
this amino acid. The change would result in a tRNA molecule
carrying leucine (Leu).
6. In Henry’s other CYP2C9 gene, the 430th nucleotide had changed from a cytosine
(C) to a thymine (T). This mutation converts a CGT triplet code in the coding strand
of the DNA molecule to TGT. Beginning with this triplet code on the DNA, describe
the effect that this change would have on the following:
a. The nucleotide sequence on the template strand of the gene.
If CGT is changed to TGT on the coding strand, then the
template strand would change from GCA to ACA.
b. The mRNA codon that results after this triplet code is transcribed.
The mRNA codon would change from CGU to UGU.
c. The anticodon on the tRNA molecule that is complementary to the mRNA
codon described above.
A tRNA molecule with an anticodon of GCA corresponded to the
CGU codon, but now a tRNA molecule with an anticodon of
ACA will be complementary to the mRNA codon UGU.
d. The amino acid that would be carried by the tRNA molecule described
above.
The tRNA molecule with an anticodon of GCA would have
carried arginine (Arg) because the mRNA codon CGU codes for
this amino acid. The change would result in a tRNA molecule
carrying cysteine (Cys).
7. From what you understand about enzymes, explain why a change in an amino acid
would cause Henry’s enzyme to lose its function.
Protein function is coupled very tightly to the shape of the molecule. For enzymes, the
proper shape of the molecule can have measurable impacts on the active site and the
ability of the enzyme to catalyze the reaction. A change in an amino acid can have a
dramatic impact on the shape, and therefore, the function of the enzyme.
8. In both of Henry’s mutations, it is the first nucleotide in the DNA triplet code that has
been changed.
a. Using the genetic code chart below, create a list of single nucleotide
changes in the two affected triplet codes described for Henry’s genes that
could occur WITHOUT resulting in a change in the amino acid in the
enzyme.
NOTE: The code chart below contains mRNA codons and the amino acids
associated with those codons. Your list should contain DNA triplet codes.
First of Henry’s two mutations described in the case
Triplet
Codons
Amino
Comment
codes
acid
ATT
AUU
Ile
Original code (wild type)
CTT
CUU
Leu
First of Henry’s mutations
GTT
GUU
Val
TTT
UUU
Phe
ACT
ACU
Thr
AGT
AGU
Ser
AAT
AAU
Asn
ATC
AUC
Ile
Amino acid conserved
ATG
AUG
Met
ATA
AUA
Ile
Amino acid conserved
Second of Henry’s two mutations described in the case
Triplet
Codons
Amino
Comment
codes
acid
CGT
CGU
Arg
Original code (wild type)
TGT
UGU
Cys
Second of Henry’s
mutations
AGT
AGU
Ser
GGT
GGU
Gly
CAT
CAU
His
CCT
CCU
Pro
CTT
UUU
Leu
CGA
CGA
Arg
Amino Acid conserved
CGC
CGC
Arg
Amino Acid conserved
CGG
CGG
Arg
Amino Acid conserved
b. How many triplet code changes did you find that could occur WITHOUT
resulting in an amino acid change in the enzyme?
From the charts above, there are a total of 5 mutations that could
have occurred in Harry’s two genes WITHOUT resulting in a
change in the amino acid (amino acid conserved).
c. Which position (first, second, or third) did the changes occur within the
DNA triplet codes you listed above?
In all 5 of the mutations identified above, it was the third nucleotide
in the DNA triplet code that was changed.
d. What would you conclude from the pattern that emerged?
An amino acid may be coded by more than one triplet code. With 64
total triplet codes, and only 20 amino acids, this redundancy is an
inevitable result. The DNA code is considered “degenerate” because
of this character. The degeneracy is primary driven by the third
nucleotide in the triplet codes, which means that if you change that
nucleotide, there is less of a likelihood of that change resulting in an
amino acid change. Changing the first or second nucleotide in the
DNA triplet code would mean that there is a much greater chance of
creating an amino acid change. Both of Harry’s mutations were a
change in the first nucleotide of the triplet code, and both resulted in
an amino acid change within the enzyme.