Name: _________________________________________________________________________ Pd: _______
Decoding the Flu: A Case Study in Viral Gene Expression
adapted by B. Franckowiak from the National Center for Case Study Teaching in Science
Introduction
Jason was worried. He had landed a summer internship at the National Center for Preparedness,
Detection, and Control of Infectious Diseases (NCPDCID). His boss also let him tag along on a CDC
research trip to rural Mexico. However, what had appeared to be a wonderful opportunity didn’t
seem so great when the team contracted one of the flu viruses they had been studying. So far, he
was the only one other than the team leader, Dr. Phillips, who was not sick.
Earlier that morning, Dr. Phillips told Jason she had a job for him. “Normally, I would give this to a
senior staffer, but they’re all sick. We think there may be a problem with the flu virus the team has
caught. Here’s some background. I’ll be right back with your assignment.”
Dr. Phillips came back a few minutes later. “Here is the situation. The team appears to have
contracted an atypical flu virus. For starters, the symptoms are worse than usual and even healthy
adults are getting severely ill. Also, none of the team’s vaccinations protected them from this virus.
We’re worried that we are dealing with a new strain of influenza we haven’t seen before. We need
to figure out how this virus is different.”
“The hemagglutinin (HA) protein helps the flu virus infect cells and the structure of this protein
can vary in different virus strains. I want you to compare the HA gene for the viruses the team was
examining with a typical flu virus. Because we don’t have power right now, you will have to do this
the old-fashioned way with pencil and paper. I will get you the nucleotide sequence for a typical
HA gene. You can start by finding the coding region for the gene.”
Check for Understanding:
1. What is the most convincing evidence that Dr. Phillips has to indicate that her staff has
been infected by an “atypical [unusual] flu virus?”
2. What does the HA protein do?
3. What is one way that flu strains can vary from one another?
4. Why will looking at the nucleotide sequence for the HA gene help Jason determine whether
the team has been affected by a new flu strain?
Finding Genes
Recall that a gene is a stretch of DNA sequence that codes for a protein. Genes actually have 2
general regions: a coding region and a regulatory region:
Fig. 1: Regulatory and coding regions of double-stranded DNA
The coding region contains nucleotide sequence that actually determines the amino acid sequence
of the final protein. The regulatory region contains nucleotide sequence that signals to the cell
where the gene is and when the gene should be expressed. RNA polymerase recognizes specific
sequences in the regulatory region and binds at those sites to begin transcription.
Fig. 2: Binding of RNA polymerase and transcription of coding region
Transcription is similar to DNA replication in that one strand of DNA is used as a template strand,
and complementary base pairing rules determine the sequence of the newly synthesized nucleic
acid. However, transcription results in the production of single-stranded messenger RNA
(abbreviated mRNA).
1. Write the two possible mRNAs that could be produced from the DNA below. Indicate which
strand was used as the template strand for each of your mRNA sequences.
2. What is the term used for the stretch of DNA sequence RNA polymerase binds to?
Translation
Once the mRNA is formed, it exits the nucleus through a
nuclear pore. A ribosome then assembles around the
mRNA. (Remember from quarter 2 that ribosomes are
small, non-membrane-bound organelles used for protein
synthesis.) Ribosomes are made of protein and of special
structural RNA called ribosomal RNA (rRNA). Once the
ribosome is assembled, protein synthesis can begin.
The ribosome holds the mRNA in place while molecules
called transfer RNAs (tRNA) carry amino acids to the
mRNA/ribosome complex. Each tRNA has an
anticodon—a sequence of three consecutive bases that
recognize and base pair with the mRNA codons. At the
other end of the tRNA is an amino acid. Complementary
base pairing allows the tRNA molecules to “translate” the
mRNA codons into a polypeptide. Translation occurs in
the 5’3’ direction.
Fig. 3 : Interaction of mRNA codon and
tRNA anticodon
Fig. 4: Translation occurring in the ribosome
1. If the mRNA codon is AUG, what is the corresponding anticodon?
2. In Fig. 4, what is the difference between the “incoming tRNA” and the “outgoing tRNA”
(besides anticodon sequence)?
3. What do the pink circles with three letters in them (“Trp,” “Lys,” “Asp,” etc) represent in
Fig. 4?
The code has “punctuation” too—codons signaling “start” and “stop.” On the back of this page is a
chart indicating which mRNA codons correspond with which amino acids.
4. Use the chart on the back to translate the following mRNA. Pay attention to “start”
and“stop.”
5’CACGGUCGAUGAGGUUA
CAUAAC… 3’
Reading Frames
Because the genetic code is structured around codons that are three nucleotides in length, there
are three possible ways to read any particular mRNA sequence. Each possible interpretation is
called a reading frame.
Fig. 5: Illustration of three possible reading frames for a single mRNA sequence
1. In the mRNA sequence below, mark off the three different readings and indicate which
reading frame you think is most likely to contain a gene.
5’ G A U G A G A C C C U G U A A C C G C 3’
Analyzing Flu Virus Sequence
Dr. Phillips provides Jason with some DNA sequence from the influenza virus and the known
amino acid sequence of the protein:
1. Given this information, find the coding region of the DNA. This will involve transcription
and translation (and reading frame analysis); keep in mind that the coding region may be
in either the top or bottom strand, and that translation proceeds from 5’  3’ (so mind the
direction of your mRNA).
2. Below is an mRNA sequence from typical influenza hemagglutinin (HA), along with mRNA
from the suspected new strain (labeled strain #1). What is the difference between these
two mRNAs? (You may need to translate them to fully answer this question.)
3. Now compare the typical influenza HA with part of the HA gene from strain #2. How are
these two mRNAs different?
4. Same thing using strain #3:
5. Which of these identified strains--#1, #2, or #3—do you think is most likely causing the
vaccine-resistant illness on Dr. Phillips’ team? How did you decide?