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Lesson 4


Using Evolution to Understand Influenza

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Elaborate


At a Glance

Overview

In this Elaborate activity, students use what they learned about evolution and how it affects medicine to better understand influenza. The main question that drives the lesson is this: Why is a new flu vaccine needed every few years? Students answer this question and gather other information about evolution and influenza as they create an outline of a brochure for a biotechnology company. After examining introductory information about influenza, students align portions of the sequence from the hemagglutinin gene from three influenza viruses. Students then learn about genomic resources, see an alignment and an evolutionary tree for 11 influenza viruses for a larger portion of the hemagglutinin gene, and compute the number of changes that have accumulated in 35 years. After learning more about how the influenza virus interacts with the immune system, students describe how natural selection influences the evolution of influenza. The rapid rate of evolution in influenza helps explain why a new flu vaccine is needed every few years.

Major Concepts

  • Natural selection is a powerful process of evolution and is the only mechanism to consistently yield adaptations.
  • Understanding mechanisms of evolution, particularly adaptation by natural selection, provides many insights that enhance medical practice and understanding.
  • Evolutionary comparisons are important for studying biomedical problems.
  • Understanding evolution helps explain the emergence and spread of infectious diseases.

Objectives

After completing this lesson, students will

  • be able to explain how comparisons of genetic sequences can help inform public health decisions,
  • recognize that the rates of evolutionary change in genetic sequences give clues about the role of purifying and diversifying selection on that region,
  • have used the major principles of natural selection to describe how influenza viruses evolve in response to the human immune system, and
  • understand that evolutionary theory helps explain aspects of vaccines.

Teacher Background

Consult the following sections in Information about Evolution and Medicine:
4.0 Students’ Prior Conceptions about Evolution
5.0 Featured Examples of Evolution and Medicine

In Advance
Web-Based Activities
Activity Web Component?
1 Yes
Photocopies, Transparencies, Equipment, and Materials
Photocopies and Transparencies
For Classes Using Web-Based Activity:
1 transparency of Masters 4.1 and 4.5
1 copy of Masters 4.2, 4.3, 4.6, and 4.11 for each student
1 copy of Master 4.4 on two separate pages for each group of two students
Photocopies and Transparencies
For Classes Using Print-Based Activity:
1 transparency of Masters 4.1 and 4.5, 4.7, 4.8, and 4.10
1 copy of Masters 4.2, 4.3, 4.6, and 4.11 for each student
1 copy of Masters 4.4 and 4.9 for each group of two students
Equipment and Materials
Each group of two students will need one pair of scissors, one roll of tape, and one piece of blank paper.
Preparation

Provide scissors, tape, and blank paper so students can cut out and align the sequences from page 2 of Master 4.4, Influenza Sequences. Make the other necessary copies and overhead transparencies.

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For classes using the Web version, verify that the computer lab is reserved for your classes or that the classroom computers are set up for the activities. Check that the Internet connection is working properly. Set the computers to the opening screen for the activity. Log on to the “Student Activities” section of the Web site by entering the following URL:

http://science.education.nih.gov/supplements/evolution/student

Select “Lesson 4: Using Evolution to Understand Influenza.”


Procedure

Activity 1: Using Evolution to Understand Influenza

Estimated time: 100 minutes

Note: Lesson 4 is an Elaborate activity, designed to have students go deeper into the major concepts they have learned and apply them to additional real-life examples. With further experience with the major concepts, students should increase their understandings of how the concepts apply more broadly. In this lesson, students explore the evolution of influenza viruses over time, using genomic resources and bioinformatic tools. With the help of a fictional genome database, students create an outline of a brochure for a fictional biotechnology company. The fictional database is a simplified version of the publicly available one housed by the National Center for Biotechnology Information (NCBI). We chose a fictional database to help students stay focused on the main learning goals of the activity. You may wish to show students the actual genome database maintained by NCBI for influenza in the “Database” link at http://www.ncbi.nlm.nih.gov/genomes/FLU/.

1.

Begin the lesson by asking students if they have any questions about influenza, or the “flu.”

Ask students to record their answers to the questions in their notebooks. We included this step to help students understand that issues related to evolution and medicine are likely to affect them personally because most students will suffer from the flu at some point in their lives. Many students will recognize that improved hygiene, such as frequent hand washing, is important in preventing the flu, as is receiving a yearly vaccination.

2.

Write three to four student questions on the board. Explain to students that throughout most of human history, the cause of influenza was unknown. In temperate regions, it suddenly appeared in the fall or winter, affected and even killed people, then went away in the spring. Explain that in this activity, students will explore some of their questions about the flu.

3.

Project Master 4.1, E-mail from Viroformatics, to the class. Ask for a volunteer to read the email aloud to the class. Ask students whether they have any questions. Explain that they will compile the information for Viroformatics throughout the rest of the activity.

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The questions posed on Master 4.2 ask students to record their initial ideas as well as their ideas after completing the investigation. These responses give you an opportunity to assess students’ relative understandings of some major concepts about evolution and the flu and to see how the ideas change after students complete the work.

4.

Give each student one copy of Master 4.2, Notes about Influenza and Evolution. Give students a few minutes to review and start answering the “what I think before” questions on their own. Before they begin answering Question 5, explain that researchers formulated 19 different vaccines for influenza from 1975 to 2008. During the same time period, no new vaccines were needed for other diseases caused by viruses, such as polio and the measles. Question 5 asks students to write an initial explanation for why so many new influenza vaccines are needed. Reinforce that students should use what they learned about evolution to develop the initial explanation. They will fill out the “what I think after” questions as they proceed through the activity.

The full explanation for why multiple vaccines are needed over time for influenza involves both natural selection by the human immune system and the transmission dynamics of the virus. Influenza is infectious for a relatively short time. Additionally, the viruses that are in circulation change relatively rapidly. This helps explain why there is limited diversity in influenza at any one time. Students will only explore the role of natural selection. One hypothesis for the usefulness of the measles, mumps, and rubella vaccination over many decades is that these viruses interact with the immune system in multiple ways. Therefore, a virus that has a mutation that allows it to overcome one immune response is blocked from replicating because the vaccination has provided protection through additional immune responses.

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Tip from the field test: Many students struggled to apply the terms “individual” and “population” to viruses. By the end of the activity, you should check to see whether students understand that mutations occur in individual viruses. If an individual with a specific mutation replicates more successfully than other viruses, the population of viruses will have a higher frequency of that mutation in future generations.
Note: If you’re interested in helping students develop a deeper understanding of vaccines, consider using Activity 4: Protecting the Herd from the NIH curriculum supplement Emerging and Re-emerging Infectious Diseases (available at http://science.education.nih.gov/customers.nsf/HSDiseases.htm).

5.

Ask students to work with a partner to briefly share their answers to the questions on Master 4.2.

Allow only about five minutes for this task. As you listen to groups sharing their ideas, insist that students be explicit about how they think evolution is involved in many of the answers.

6.

Explain to students that to complete the task for Viroformatics, they need to have a deeper understanding of both evolution and influenza. To help construct these understandings, students will use some of the tools that scientists use to study evolution in influenza viruses.

7.

Hand out one copy of Master 4.3, Introduction to Influenza, to each student. Ask students to read it individually. As they read, they should add at least five total facts from the reading to the appropriate questions on Master 4.2 in the “what I think after” sections. Students should also record in their notebooks at least one question they have about the reading.

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Content Standard F: The severity of disease symptoms is dependent on many factors, such as human resistance and the virulence of the disease-producing organism. Many diseases can be prevented, controlled, or cured. Some diseases, such as cancer, result from specific body dysfunctions and cannot be transmitted.


8.

Students should meet with their groups again. Ask them to share and try to answer their questions within their groups. They should note questions that the group cannot answer and raise them in a brief class discussion about the reading on Master 4.3. Make sure that you address all five of the questions from Master 4.2, but do not provide full explanations at this point in the lesson.

The goal of the class discussion is for students to become aware of their initial ideas and the ideas of their classmates. This step helps students take control of their own learning about influenza. Students will revise and improve their answers to the questions throughout the lesson.

9.

Explain to students that they will begin the investigation of influenza and evolution by examining a segment of the gene that codes for the hemagglutinin protein. They will examine three sequences taken from type A influenza viruses, subtype H3N2. The samples were collected from patients in 2003, 1997, and 1993. Hand out scissors, tape, a blank piece of paper, and one copy of Master 4.4, Influenza Sequences, to each group. Instruct students to follow the directions on the handout.

This portion of the investigation gives students a feel for how scientists align genetic sequences. Students may notice that the sequences are recorded as DNA, but influenza is an RNA virus. The reason is that public databases of genetic sequences store information only as DNA.

10.

Ask each group to compare their alignment to that of another group. After they discuss the alignment each group developed, project Master 4.5, Aligned Influenza Sequences. Ask students to compare their alignments with your alignment and to report the total number of changes they observe.

Students should find that there are four differences among the sequences.

11.

Explain that scientists often compare sequences from thousands of influenza viruses that are thousands of nucleotides long. Ask students if they think it would be reasonable to align the sequences by hand. Get students to agree that this task would best be completed by using a computer.

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(For print version, skip to Step 12a-p.)

In classrooms using the web version of this activity:

12-w.

Explain that students will now get access to the Viral Genome Database at Viroformatics. Hand out one copy of Master 4.6, Exploring a Genetic Database, to each student. Have students go to http://science.education.nih.gov/supplements/evolution/student.

Students should click on “Lesson 4: Using Evolution to Understand Influenza.”

13-w.

Ask students to work with a partner to accomplish all the tasks on Master 4.6.

Now would be a good time to mention that the National Center for Biotechnology Information (NCBI) maintains an extensive genome database that is free and available for use by the public. All federally funded researchers and most private companies submit sequences to the database. NCBI was established in 1988 as a division of the National Library of Medicine at the National Institutes of Health. NCBI’s mission is to develop information technologies to help researchers understand the molecular and genetic processes that affect health. NCBI stores sequence information for a large range of organisms across the Tree of Life, including humans. You may want to show students the actual NCBI Influenza Virus Resource Web site at http://www.ncbi.nlm.nih.gov/genomes/FLU/FLU.html. After accessing this page, click on “Database.”

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Content Standard A: Scientists rely on technology to enhance the gathering and manipulation of data. New techniques and tools provide new evidence to guide inquiry and new methods to gather data, thereby contributing to the advance of science. The accuracy and precision of the data, and therefore the quality of the exploration, depends on the technology used.

Steps 1 and 2 on Master 4.6 help students get a sense of the massive amount of genetic data available to study influenza. More broadly, students should recognize that the availability of sequence data from a range of organisms is increasing almost exponentially. Multiple career opportunities exist for students who are interested in both computation and biology. You can repeat this activity’s search at the NCBI Influenza Virus Resource Web site. Input the following selections: Type, “A”; Host, “human”; Country/Region, “any”; Protein, “HA”; Subtype, “any.” Then click on “Show results.”

14-w.

Hold a class discussion about the answers to the questions on Master 4.6.

The questions on the handout ask students to perform simple calculations. To complete the tasks, students need to use division. Some students may need help setting up the problem. Questions 6 through 8 use scientific notation. If your students are not comfortable with scientific notation, simply write out the answer using decimal places. The main concept students need to understand is that the rate of change in genetic sequences can differ by many orders of magnitude. Ultimately, students will understand the role of selection in shaping some of the differences in rates.

Answer key for questions on Master 4.6, Exploring a Genetic Database

  1. Your first goal is to get a sense of the types and amount of data stored in the database. Click on “Viral Genome Database,” then “Full Virus Database.” Once there, explore the number of sequences available for influenza in humans for the hemagglutinin gene. Record the number available in this database for types A, B, and C. (You can explore the data for specific sequences by clicking on the accession number. By convention, the genetic sequences are recorded as DNA. Influenza viruses store their genetic information as RNA.)

    There are 17,387 sequences available for type A, 2,945 sequences for type B, and none for type C.
  2. Why do you think the number of sequences for each type is different?

    Students may recall from their reading that type A influenza is responsible for pandemic outbreaks, which explains why researchers are very interested in this type. Types A and B cause the seasonal flu that sweeps around the globe every year. Type C causes only a mild illness and does not cause epidemics, so it’s not studied as intensely. We didn’t include genome data for type C in our database, although there were 948 sequence entries in the NCBI database when it was accessed in March, 2011.
  1. Calculate the number of changes per nucleotide in this 100-nucleotide sequence by using the following formula:

    eqn1
  2. The viruses in this study were collected over a span of 35 years. Calculate the number of changes per nucleotide per year by using the following formula:

    eqn2
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Content Standard A: Mathematics is essential in scientific inquiry. Mathematical tools and models guide and improve the posing of questions, gathering data, constructing explanations and communicating results.

  1. In Lesson 3, you investigated the sequence of a gene called Irf6 that is involved in the development of the head and face. Use the same formulas you used in Steps 5 and 6 to calculate the expected number of changes per nucleotide per year in this sequence.

    eqn3
  2. Compare the rate of change per nucleotide per year for the hemagglutinin gene in influenza to the rate for the Irf6 gene. Do this by dividing the rate for the hemagglutinin region by the rate for the Irf6 gene. The number you calculate will show how many times faster one region changes compared to the other.

    eqn4

    The rate of change in the hemagglutinin gene is 70 million times faster than the rate of change in the Irf6 gene for the regions compared.
  3. To see a diagram that summarizes the relationships among the viruses, click on “Build a Tree.” Does this diagram show evidence that the influenza virus is changing over time?

    Students should note that the relationships of the samples relate to time. For example, the sample from 2003 is more closely related to the sample from 1997, which is the closest sample in terms of date. Students may also note that there is a large distance between the sample from 1968 and the sample from 2003.
10a, b. How do the number of changes to the sequence relate to time? What do you think this means?


Students should see the pattern that the number of changes to the sequences increases with time. This is strong evidence that the influenza virus keeps changing over time.

Note: If you would like students to gain additional practice graphing and interpreting results, consider having them generate a graph that shows the number of years’ difference between two viruses on the x-axis and the number of changes in the hemagglutinin gene on the y-axis. Students could plot five to ten data points and describe the pattern they observe.

15-w.

Ask students to revise and improve their answers to Question 3 on Master 4.2: Not all individual influenza viruses are identical. What causes viruses to differ from one another? Hold a brief class discussion about students’ answers.

Students should be able to describe that the variation originally came about through mutation. You may want to directly ask students whether the variation came about because the virus “wanted” or “needed” it. Again, this is a common misconception.

Continue with Step 16.


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Content Standard C: Natural selection and its evolutionary consequences provide a scientific explanation for the fossil record of ancient life forms, as well as for the striking molecular similarities observed among the diverse species of living organisms.


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Understanding the role of mutation in generating diversity is essential. By this stage of the learning cycle, students have had multiple opportunities to learn about the importance of mutation.

In classrooms using the print version of this activity: Logo5.eps

12a-p.

Explain that students will now get access to the Viroformatics Viral Genome Database to help them gain experience with the data that scientists use to learn about influenza and evolution. Then project Master 4.7, Viroformatics Virus Database. Explain that Viroformatics scientists use the database, which contains thousands of nucleotide and protein sequences from different influenza viruses collected over decades. On the site are tools to obtain and align sequences and to investigate the relationships among sequences.

Now would be a good time to mention that the National Center for Biotechnology Information (NCBI) maintains an extensive genome database that is free and available for use by the public. All federally funded researchers and most private companies submit sequences to the database. NCBI was established in 1988 as a division of the National Library of Medicine at the National Institutes of Health. NCBI’s mission is to develop information technologies to help researchers understand the molecular and genetic processes that affect health. NCBI stores sequence information for a large range of organisms across the Tree of Life, including humans. You may want to show students the actual NCBI Influenza Virus Resource Web site at http://www.ncbi.nlm.nih.gov/genomes/FLU/. After accessing this page, click on “Database.”

12b-p.

Explain to students that a search for the hemagglutinin gene in type A influenza resulted in 17,387 sequences and that the hemagglutinin gene codes for a protein in influenza that the human immune system recognizes. Then, project Master 4.8, Influenza Hemagglutinin Sequence. Point out that the database stores information about both the RNA sequence (though it is recorded as DNA by convention) and the amino acids in the protein.

This step helps students get a sense of the massive amount of genetic data available about influenza. More broadly, you may want to tell students that the availability of sequence data from a range of organisms is increasing almost exponentially. Many career opportunities exist for students who are interested in both computation and biology. You can repeat this activity’s search at the NCBI Influenza Virus Resource Web site. Input the following selections: Type, “A”; Host, “human”; Country/Region, “any”; Protein, “HA”; Subtype, “any.” Then click on “Show results.”

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Content Standard A: Scientists rely on technology to enhance the gathering and manipulation of data. New techniques and tools provide new evidence to guide inquiry and new methods to gather data, thereby contributing to the advance of science. The accuracy and precision of the data, and therefore the quality of the exploration, depends on the technology used.

13-p.

Explain to students that scientists at Viroformatics are studying how influenza viruses change over time. They obtained the genetic sequence for hemagglutinin from 11 viruses isolated from people around the world at different points in time. Scientists store influenza samples from the past in freezers. This way, future scientists have access to the influenza “fossil record.” The scientists aligned the sequences, and the results are on Master 4.9, Influenza Over Time Alignment. Hand out one copy of Master 4.9 to each group. Instruct students to follow the directions on the handout.

The questions on the handout ask students to perform simple calculations using division. Some students may need help setting up the problem. Questions 2 through 4 use scientific notation. If your students are not comfortable with scientific notation, simply write out the answer using decimal places. The main concept that students need to understand is that the rate of change in genetic sequences can differ by many orders of magnitude. Ultimately, students will understand the role of selection in shaping some of the differences in rates.

You may wish to mention to students that the sequences in this alignment were selected from samples used in actual research (Smith et al., 2004).

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Content Standard A: Mathematics is essential in scientific inquiry. Mathematical tools and models guide and improve the posing of questions, gathering data, constructing explanations and communicating results.


Answer key for questions on Master 4.9, Influenza Over Time Alignment

  1. Calculate the number of changes per nucleotide in this 100-nucleotide sequence by using the following formula:

  2. The viruses in this study were collected over a span of 35 years. Calculate the number of changes per nucleotide per year by using the following formula:

  3. In Lesson 3, you investigated a portion of the sequence of a gene called Irf6 that is involved in the development of the head and face. Use the same formulas you used in Steps 1 and 2 to calculate the expected number of changes per nucleotide per year in this sequence.

  4. Compare the rate of change per nucleotide per year for the hemagglutinin gene in influenza to the rate for the Irf6 gene. Do this by dividing the rate for the hemagglutinin region by the rate for the Irf6 gene. The number you calculate will show how many times faster one region changes than the other.



    The rate of change in the hemagglutinin gene is 70 million times faster than the rate of change in the Irf6 gene for the regions compared.
  5. The number of changes in the hemagglutinin gene for six samples compared with the sample from Finland in 2003 is as follows.
    • Hong Kong, 1968 = 140 changes
    • Victoria, Australia, 1975 = 128 changes
    • Philippines, 1982 = 95 changes
    • Singapore, 1989 = 74 changes
    • Madrid, Spain, 1993 = 71 changes
    • Auckland, New Zealand, 1997 = 34 changes
  1. How do the number of changes to the sequence relate to time?
  2. What do you think this means?

Students should see that the number of changes to the sequences increases with time. This is strong evidence that the influenza virus keeps changing over time.

Note: If you would like students to gain additional practice graphing and interpreting results, consider having them generate a graph that shows the number of years’ difference between two viruses on the x-axis and the number of changes in the hemagglutinin gene on the y-axis. Students could plot six data points and describe the pattern they observe.

14-p.

Ask students to revise and improve their answers to Question 3 on Master 4.2: Not all individual influenza viruses are identical. What causes viruses to differ from one another? Hold a brief class discussion about students’ answers.

Students should be able to describe that the variation originally came about through mutation. You may want to directly ask students whether the variation came about because the virus “wanted” or “needed” it. Again, this is a common misconception.

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Content Standard C: Natural selection and its evolutionary consequences provide a scientific explanation for the fossil record of ancient life forms, as well as for the striking molecular similarities observed among the diverse species of living organisms.

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Understanding the role of mutation in generating diversity is essential. By this stage of the learning cycle, students have had multiple opportunities to learn about the importance of mutation.


15-p.

Explain to students that they can use the data in the alignment of the 11 sequences to estimate the relationships among the viruses. Project Master 4.10, Relationships among Influenza Viruses. Ask, “Does this diagram show further evidence that the influenza virus is changing over time?” Students should record their answers in their notebooks. Ask two or three students to share what they wrote.

Students should note that the relationships of the samples relate to time. For example, the sample from 2003 is more closely related to the sample from 1997, which is the closest sample in terms of date. Students may also note that there is a large distance between the sample from 1968 and the sample from 2003.

16.

Hand out one copy of Master 4.11, Influenza and the Immune System to each student. Ask students to read the questions at the end of the handout first and then complete the reading. Students should work with a partner to answer the questions.

Answer key for questions on Master 4.11, Influenza and the Immune System

  1. Assume there is a change in the gene for hemagglutinin in the influenza virus. Describe how this change could alter the ability of an animal’s antibodies to bind to the virus.

    A mutation in the gene for hemagglutinin could change the shape of the protein. Antibodies that previously matched up with hemagglutinin would no longer bind.
  2. Imagine an influenza virus that has a mutation that changes the shape of its hemagglutinin protein. Because of this change, antibodies no longer bind to the virus. A second virus does not have the mutation, and antibodies can bind to its hemagglutinin protein. Which virus would leave more descendants? Describe why you answered as you did.

    Antibodies will not bind to the influenza virus that has the mutation. The virus will be able to infect cells and make new viruses. Thus, it will leave more descendants than the virus that the antibodies recognize.
  3. How does learning about the immune system help explain the rapid rate of change in the hemagglutinin sequences you observed?

    Influenza viruses adapt to the human immune system. After a strain sweeps around the globe, many people develop immunity to that strain. Viruses that have a mutation that changes the hemagglutinin protein have an advantage because antibodies made previously do not match, and therefore these viruses can gain access to human cells.
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This discussion helps students review what they have learned as they prepare for the Evaluate activity in Lesson 5. You may want to review students’ answers to find out whether they are ready for the Evaluate activity.


17.

Ask students to work with their partners to write the “what I think after” answers to the questions on Master 4.2, Notes about Influenza and Evolution. After students turn in the handouts, hold a class discussion about the answers.

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Tip from the field test: You may want to assign this step as homework.






Answer key for questions on Master 4.2, Notes about Influenza and Evolution

  1. What is influenza, or the “flu”?
Students may list the following information about influenza:
  • Influenza is a respiratory disease caused by a virus.
  • Influenza is a major world health concern.
  • The influenza virus uses RNA to store its genetic information.
  • Three main types of influenza exist.
  • Influenza is considered a bird disease.
  • Influenza is highly infectious.
  1. How do scientists use data to explore how influenza genes evolve?

    Scientists are able to store influenza viruses in freezers and thus preserve the virus’s “fossil record” over time. Scientists can collect data on the genetic sequences in influenza viruses and explore how the sequences have changed over time.
  2. Not all individual influenza viruses are identical. What causes viruses to differ from one another?

    Students revisited their answers to this question during Step 14. Variation in viruses comes about through mutation. Reassortment among different influenza viruses is an additional source of variation among viruses, but this is beyond what we expect students to know.
  3. How does natural selection help explain the evolution of influenza?

    Ask students to use the major principles of natural selection as they develop answers to this question. They should note that the variation among influenza viruses arises from mutation. These mutations can be passed from one generation to the next. Some of the viruses are better able to avoid detection by the immune system, and these viruses leave more descendants. As a result, the frequency of influenza viruses with certain traits will increase over time.
  4. How does evolution help explain why researchers need to make a new vaccine for influenza every few years?

    Students should now be able to give a richer answer to this question, which is one of the most important questions in the lesson. Students should recognize that influenza viruses will eventually adapt to the antibody “environment” induced by human immunity (sometimes stimulated by vaccines). Individual viruses with mutations to the hemagglutinin gene that change the shape so that antibodies no longer bind will have an advantage over other viruses. Eventually, some of these new strains will become more frequent and spread throughout the population, which prompts the creation of a new vaccine. Unfortunately, this process is extremely hard to predict. Researchers use large amounts of epidemiological, genetic, and antigenic data and expertise to decide what strains to include in the influenza vaccine.

Lesson 4 Organizer: Web Version

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Activity 1: Using Evolution to Understand Influenza
Estimated time: 100 minutes
Page and Step
Ask students whether they have questions about influenza, or the “flu.” Write three to four questions on the board. Tell students they will explore some of their questions about the flu. Page 138
Steps 1 and 2
Project Master 4.1, and ask for a volunteer to read the email on it aloud. Ask students whether they have any questions about it. Page 138
Step 3
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Give one copy of Master 4.2 to each student.
  • Have students answer the questions on their own.
  • Before students reach Question 5, explain that researchers formulated 19 different vaccines for influenza from 1975 to 2008. During the same time period, no new vaccines were needed for other diseases caused by viruses, such as polio and the measles.
  • Ask students to provide an initial explanation to the “what I think before” questions.
  • Have students share their answers with a partner.
Pages 138–139
Steps 4 and 5
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Explain to students that they will use tools that scientists use to understand influenza and evolution.
  • Give each student 1 copy of Master 4.3.
  • Students should record on Master 4.2 at least five total facts for the “what I think after” questions and record in their notebooks one question they have.
Page 139
Steps 6 and 7
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Ask students to meet with their groups to share and try to answer their questions. Hold a brief class discussion about Master 4.3 and the questions the group could not answer. Page 139
Step 8
Explain that students will examine a segment of the gene that codes for the hemagglutinin protein taken from three type A influenza viruses, subtype H3N2. Give each pair of students one copy of Master 4.4 plus scissors, tape, and a blank piece of paper to accomplish the tasks described on Master 4.4. Page 140
Step 9
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Ask each group to compare their alignment with that of another group. Project Master 4.5 and ask students to compare this alignment with the one they created. Ask whether aligning thousands of nucleotides by hand is reasonable. Explain that computer programs help scientists align long sequences. Page 140
Steps 10 and 11
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Explain that students will use the Viral Genome Database at Viroformatics to learn more about the data scientists use to study influenza and evolution.
  • Give one copy of Master 4.6 to each student.
  • Ask students to work with a partner to complete Master 4.6.
  • Have students log on to the Web site and click on “Lesson 4: Using Evolution to Understand Influenza.”
Page 141
Steps 12-w and 13-w
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Hold a class discussion on the answers to Master 4.6. Page 141
Step 14-w
Ask students to revise and improve their answers to Question 3 on Master 4.2. Lead a discussion to emphasize the importance of revisions. Page 144
Step 15-w
Give one copy of Master 4.11 to each student and have students first read the questions at the end of the reading. Have them work with a partner to answer the questions after completing the reading. Page 147
Step 16
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Student pairs should work together to complete Master 4.2. After they turn in their answers, lead a class discussion about the activity. Page 148
Step 17

Logo6.eps = Involves copying a master.       = Involves making a transparency.       Logo3.eps = Involves using the Internet.



Lesson 4 Organizer: Print Version

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Activity 1: Using Evolution to Understand Influenza
Estimated time: 100 minutes
Page and Step
Ask students whether they have questions about influenza, or the “flu.” Write three to four student questions on the board. Tell students they will explore some of their questions about the flu. Page 138
Steps 1 and 2
Project Master 4.1, and ask for a volunteer to read the email on it aloud. Ask students whether they have any questions about it. Page 138
Step 3
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Give 1 copy of Master 4.2 to each student.
  • Have students answer the questions on their own.
  • Before students reach Question 5, explain that researchers formulated 19 different vaccines for influenza from 1975 to 2008. During the same time period, no new vaccines were needed for other diseases caused by viruses, such as polio and the measles.
  • Ask students to provide an initial explanation to the “what I think before” questions.
  • Have students share their answers with a partner.
Pages 138–139
Steps 4 and 5
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Explain to students that they will use tools that scientists use to understand influenza and evolution.
  • Give each student one copy of Master 4.3.
  • Students should record on Master 4.2 at least five facts for the “what I think after” questions and record in their notebooks one question they have.
Page 139
Steps 6 and 7
Ask students to meet with their groups to share and try to answer their questions. Hold a brief class discussion about Master 4.3 and the questions the group could not answer. Page 139
Step 8
Explain that students will examine a segment of the gene that codes for the hemagglutinin protein taken from three type A influenza viruses, subtype H3N2. Give each pair of students one copy of Master 4.4 plus scissors, tape, and a blank piece of paper to accomplish the tasks described on Master 4.4. Page 140
Step 9
Logo6.eps
Ask each group to compare their alignment with that of another group. Project Master 4.5 and ask students to compare this alignment with the one they created. Ask whether aligning thousands of nucleotides by hand is reasonable. Explain that computer programs help scientists align long sequences. Page 140
Steps 10 and 11
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Explain that students will use the Viral Genome Database at Viroformatics to learn more about the data scientists use to study influenza and evolution. Project Master 4.7. Explain that the database has
  • thousands of nucleotide and protein sequences from different influenza viruses collected over decades and
  • tools to obtain, align, and explore relationships among sequences.
Page 144
Step 12a-p
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Explain that
  • a search for the hemagglutinin gene in type A influenza resulted in 17,387 sequences and
  • the hemagglutinin gene codes for a protein in influenza that the human immune system recognizes.
Project Master 4.8. Point out that the database has information about the RNA sequence (recorded as DNA by convention) and amino acids.
Page 144
Step 12b-p
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Explain that scientists at Viroformatics are studying how influenza viruses change over time. They aligned the genetic sequences for hemagglutinin from 11 viruses isolated from people around the world at different points in time.
  • Give each group one copy of Master 4.9.
  • Ask students to use the alignment on the first page of the master to answer the questions on the second page.

Page 145
Step 13-p
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Ask students to revise and improve their answers to Question 3 on Master 4.2. Lead a discussion to emphasize the importance of revisions. Page 147
Step 14-p
Explain that students can use the data in the alignment of the 11 sequences to estimate the relationships among the viruses.
  • Project Master 4.10.
  • Ask, “Does this diagram show further evidence that the influenza virus is changing over time?”
  • Have two or three students share their answers.
Page 147
Step 15-p
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Give one copy of Master 4.11 to each student and have students first read the questions at the end of the reading. Have them work with a partner to answer the questions after completing the reading. Page 147
Step 16
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Ask students to work with their partners to complete Master 4.2. After they turn in their answers, lead a class discussion about the activity. Page 148
Step 17

Logo6.eps = Involves copying a master.        Logo7.eps = Involves making a transparency.

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