Answer Key to Short Answer Questions for



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.

[pic]

|First of Henry’s two mutations described in the case |

|Triplet codes |Codons |Amino acid |Comment |

|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 codes |Codons |Amino acid |Comment |

|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.

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