Case Study Questions: Genetic Code

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.

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).

Gene is like a map for the cell to use when creating other molecules. It provides the DNA sequence and if the DNA has an error, the molecules and proteins will have a malfunction as well.

genes are made from nucleotides being translated by a ribosome with tRNA to form an amino acid chain(protein)

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).

Consider the following DNA sequence found on a different portion of 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?

b. How many triplet codes does this DNA sequence contain?

c. What would be the sequence of the mRNA after this sequence is transcribed?

d. How many amino acids does this portion of Henry's coding stand actually code for?

A) AATGGCTCT

B) There are three triplet codes in this sequence: AAT GGC and TCT

C) The mRNA sequence would be UUACCGAGA

D) The three triplet codes each correspond to a single amino acid in the enzyme

In the first mutation of the CYP2C9 gene described in Henry's story, the 1075th nucleotide has been 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.

b. The mRNA codon that results after this triplet code is transcribed. c. The anticodon on the tRNA molecule that is complementary to the mRNA codon described above. d. The amino acid that would be carried by the tRNA molecule described above.

A) If ATT is changed to CTT on the coding strand, then the template strand would change from TAA to GAA.

B) The mRNA codon would change from AUU to CUU.

C) 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 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).

In Henry's other CYP2C9 gene, the 430th nucleotide has been 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.

b. The mRNA codon that results after this triplet code is transcribed. c. The anticodon on the tRNA molecule that is complementary to the mRNA codon described above. d. The amino acid that would be carried by the tRNA molecule described above.

A) If CGT is changed to TGT on the coding strand, then the template strand would change from GCA to ACA.

B) The mRNA codon would change from CGU to UGU.

C) 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 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.

From what you understand about enzymes, explain why a change in an amino acid would cause Harry'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.

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.

b. How many triplet code changes did you find that could occur WITHOUT resulting in an amino acid change in the enzyme?

c. Which position (first, second, or third) did the changes occur within the DNA triplet codes you listed above?

d. What would you conclude from the pattern that emerged?

A) ATT- AUU- AUUCTT CUU LeuGTT GUU ValTTT UUU PheACT ACU ThrAGT AGU SerAAT AAU AsnB) 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) In all 5 of the mutations identified above, it was the third nucleotide in the DNA triplet code that was changed.D) 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.