Direct students to work independently to answer the questions at the end of Master 1.1.

Give students a few minutes to write their best ideas at this point. The questions in this step are designed to elicit the students’ initial ideas about the role of evolution in infectious diseases, including the evolution of antibiotic and antiviral resistance. You may need to reassure students that these questions are not part of a “test.” Do not correct individual answers or go over the correct answers with students at this point in the learning cycle. They will revisit their answers to these questions later in the supplement.

Examine students’ answers for common misconceptions such as ideas that the bacterial population purposefully changed or that it changed simply because it “needed to” or “wanted to.” Expect many students to be confused about mutations and the origin of genetic variation. Section 4.0 of the Information chapter contains a further explanation of students’ common misconceptions about evolution (here).

Optimally, answers to these questions should touch on the five principles of natural selection described in Box 1 (see also Section 1.0 of the Information chapter, here). However, it is likely that students won’t have this level of understanding yet. For your background information, the answers in the answer key incorporate the five principles.

Answer key for questions on Master 1.1, Information about MRSA

1. Researchers developed the antibiotic methicillin to treat people with infections of S. aureus that are resistant to penicillin. Within two years, populations of S. aureus that were resistant to methicillin started showing up in hospitals. How would a scientist explain how the change may have occurred in S. aureus populations?

Typical student responses (ranging from partially accurate to inaccurate) may include the following:

• The genetic information in the populations mutated.
• The populations changed or evolved.
• The population got stronger.
• Individuals in the population changed because they needed or wanted to.

A complete explanation of the evolution of resistance in S. aureus populations includes five major principles:

Note: A common misconception about antibiotic resistance is that the people who have the infection are resistant to antibiotics. In reality, it is the bacteria that are resistant, and these resistant bacteria are passed from person to person.

2. How can the study of evolution (such as the adaptation of bacterial populations to an antibiotic) help researchers improve people’s health? Explain your initial ideas.
   
   Students’ answers will vary. Use this question as a formative assessment of how students view the role of evolution within medicine.

Wrap up this activity by holding a brief class discussion about students’ ideas.

Do not provide the correct answers. The point of this discussion is to focus on differences of opinion among the students so that students recognize that their classmates may have different ideas.

Ask students to describe what they learned about mutations and disease from the MRSA case. Then ask them to consider how mutations in people might affect health.

This is an opportunity to further assess students’ developing understandings from the previous activity. In the case of MRSA, the mutations occurred in the S. aureus bacteria (not in the humans who developed the disease). The mutations in the bacteria (often in previous generations) enabled some of them to be resistant to methicillin.

Step 1 helps students transition from the idea of a mutation in a pathogen causing a human disease to the idea that mutations in people can cause a disease. Students will likely say that mutations will cause disease or even death. Step 1 enables you to gauge their understandings of mutations.

Explain to the class that they will now consider a human disease. The goal is for students to express ideas about how scientists can use their knowledge of evolution to inform medical research. Project Master 1.2, Aniridia: An Eye Disease. Ask for a volunteer to read the information aloud to the class. Then give students a few minutes to discuss the questions with a partner before participating in a class discussion.

In this brief vignette, students will read about a family affected by an eye disease called aniridia and deduce that it may have a genetic basis.

Answer key for questions on Master 1.2, Aniridia: An Eye Disease

1. Do you think the parents’ concern for their baby’s health is justified? Why?
   
   Most expectant parents are concerned about the baby’s health.
   These parents are understandably more anxious than normal because of the family history of aniridia (baby’s father and grandmother).
2. From the information provided, would you expect aniridia to be caused by an infection, an environmental factor, or a genetic factor? Explain your answer.
   
   The family history is a clue that aniridia has a genetic basis.

Confirm for students that aniridia is a genetic disease. Scientists have identified and isolated the gene that is mutated in aniridia. The gene is called “Pax6” and is important for the development of eyes in an embryo.

Pax6 plays an important role in the development of the brain and pancreas as well as the eyes. However, for the purpose of this activity, students will focus on the gene’s role in eye development.

Explain that students will now examine data about aniridia and consider how an understanding of evolution can inform medicine.

Give each student one copy of Master 1.3, Learning about Human Health from Other Organisms. Inform students that they will work in groups of three to four to analyze the information provided and respond to the questions.

Part 1 of the handout includes a portion of the amino acid sequence for the protein encoded by Pax6. This sequence uses the one-letter codes for the amino acids. Students may be more accustomed to the three-letter codes. If so, explain that this code is just a different abbreviation for the amino acids and is more commonly used by scientists. For the Pax6 example, there are six differences in this part of the fruit fly protein compared with the other organisms on Master 1.3.

Students simply need to recognize that the sequences for the Pax6 protein are very similar among these organisms. It is not essential that students know the specific changes in the protein sequence.

Part 2 on the handout requires looking at evidence captured in photographs. When students reach Part 2, project a color version of Master 1.4, Photographs of Pax6 Mutations. As students work, circulate among groups to monitor students’ discussions and ask guiding questions if necessary.

Because of the orientation of the photomicrographs, you may need to help students understand the images. The picture of the human eye will probably be understandable to students. The pictures of the mouse eye and zebrafish eye may confuse students. Instead of looking at the eye from the front (as in the picture of the human eye), the mouse and zebrafish images are cross sections of the developing eye; they show the eye from the side. The fruit fly (Drosophila) has compound eyes that look very different from the other organisms’ eyes. The purpose of students making these observations is to look at evidence for gene function (not to learn the anatomy of the eye). The main thing that students should observe is that, for all these species, eye development is abnormal in Pax6 mutants.

Hold a brief class discussion to go over the answers that students gave to the questions on Master 1.3.

Simply allow a few students to express their ideas. Do not go through the correct answers at this point. Students will revise their answers later.

Content Standard A: Formulate and revise scientific explanations and models using logic and evidence.
Content Standard A: Recognize and analyze alternative explanations and models.

Answer key for questions on Master 1.3, Learning about Human Health from Other Organisms

Part 1

1. What do you notice about the amino acid sequences in the different species?
   
   In all four species, the amino acid sequences are very similar. In fact, for this part of the protein, the sequences are identical in zebrafish, mice, and humans. The fruit fly sequence differs by six amino acids.
2. What can you infer about the Pax6 gene from the protein sequences from these four species?
   
   Because the protein sequences are so similar, students should expect the gene sequences also to be very similar in these organisms. (If students have trouble making this connection, remind them that the DNA sequence codes for the protein sequence.)

Part 2

3. On the basis of the pictures, do you think the function of the Pax6 gene is similar in all four species? Explain your reasoning.
   
   In each of the different species, individuals with mutations in the Pax6 gene have abnormalities in the eye structure. This suggests that Pax6 plays a role in the formation of the eye in each species.

Part 3

4. What do these experiments suggest about the function of the Pax6 gene? Explain your thinking.
   
   These experiments suggest that the Pax6 gene is similar enough in all these species that the gene can still function in a different species.

Continue the discussion by asking students, “Do the Pax6 experiments support the idea that medical scientists can learn about gene function in humans by studying different organisms?”

Yes, these experiments do support the idea that medical scientists can learn about human health by studying other organisms. The Pax6 gene is a good example because

• it is conserved across a wide variety of organisms;
• when mutated, it causes abnormalities in eye development in all species; and
• the gene can be expressed in other organisms and produce the same feature that it normally would.

This leads scientists to the conclusion that the mechanisms that regulate this gene are probably very similar in a wide variety of organisms, including humans.

After students express their ideas, inform them that species commonly used in scientific research are called “model species” or “model organisms.” Briefly discuss why model organisms might be valuable for scientific research. Prompt the discussion by asking, “Why would scientists want to study a gene and its function in a mouse, a fruit fly, a zebrafish, or even a bacterium when they already know the gene is present in humans?”

It can be difficult to study some issues in humans. Not only are the generation times very long, but some investigations would be unethical to do in humans. For example, it would never be appropriate to induce mutations intentionally in humans because the potential consequences of this manipulation are unknown.

The organisms that students considered in the Pax6 example are very common model species, but many others exist. Which species a scientist uses for a model depends on the question being investigated. For example, scientists’ extensive knowledge of the fruit fly’s genetic makeup and its relatively short generation time are advantages. For some questions, a scientist would want to study a mammalian system, making the mouse a good choice.

This discussion does not need to be long, but use it as an opportunity to help students understand why medical researchers rely on model organisms to learn about human health issues.

Tell students that understanding evolution helps us explain why model species are useful for understanding human disease. Introduce students to evolutionary trees by explaining that these diagrams show relationships among species. Hand out one copy of Master 1.5, An Evolutionary Tree, to each student. Ask the students to use the evolutionary tree to answer the questions on the handout.

Again, you may need to reassure students that these questions are not part of a test. Instead, the questions are designed so that they can express their initial ideas about how to interpret an evolutionary tree diagram. They will revisit their answers to these questions in Steps 11 and 12. Give students about five minutes to complete this task.

This is a chance to look for prominent misconceptions that students may have (which will inform your teaching for Step 11; see Section 4.0 in the Information chapter). Do not go over the correct answers with students at this point in the learning cycle; the correct answers are included with Step 12. The information below points out some common responses, problems, and misconceptions that students may have when interpreting trees:

1. What part of the evolutionary tree diagram represents the common ancestor of humans, mice, and zebrafish (but not fruit flies)? Why did you identify this part of the diagram?
   
   Students’ responses to this will indicate their current understandings of how a common ancestor is represented on an evolutionary tree. Students may not, at this point, understand that the line leading up to the splitting point labeled “2” represents a lineage that is the common ancestor of humans, mice, and zebrafish.
2. Does the evolutionary tree suggest that the mouse is more closely related to the zebrafish or the fruit fly?
   
   The common incorrect response is that the mouse is more closely related to the fruit fly than to the zebrafish because the two organisms are next to each other on the evolutionary tree. This does not take into account that the mouse and the zebrafish share a more recent common ancestor than do the mouse and the fruit fly. This response may indicate that students do not understand what the splitting points signify or how time is represented on the evolutionary tree.
3. Is the fruit fly the ancestor of all the other species on the evolutionary tree? Explain your answer.
   
   No. Many students assume that the species on the left part of the diagram or the species that branched off from the other species in the most distant past is the ancestor of the other species on the tree. Again, this may indicate a lack of understanding of the splitting points or of the representation of time on the evolutionary tree.
4. What does the vertical line beneath Point 1 represent?
   
   The vertical line beneath Point 1 represents the root of this evolutionary tree. This line is the lineage that leads to the most recent common ancestor of the four species shown on the tree.

Project Master 1.5. This evolutionary tree shows the relationships among the four species in the Pax6 case. Go over the following information with students. Ask them to record notes on their handouts.

The information in bold below is essential for students to understand. The information in parentheses is additional information for you to use if questions arise.

Content Standard C: The millions of different species of plants, animals, and microorganisms that live on earth today are related by descent from common ancestors.

The evolutionary tree in Master 1.5 shows the relationships among four different species.

• The vertical lines represent separate lineages. A lineage is the line of species and populations for a group of organisms over time. The group may contain a single species, a single population, or a group of species. (A common misconception is that the vertical branches, or lineages, on the tree indicate that no change occurred over time (that is, that the lines are simply connections between one ancestor species and the present-day species). In actuality, change occurs throughout time. There were certainly other organisms that went extinct on the lineage between the common ancestor and the zebrafish, for example.)
• The vertical line below Point 1 represents the root of the tree, or the lineage leading to the common ancestor shown on this tree.
• The splitting points show where one lineage splits into two new lineages. The organism at the splitting point is the common ancestor for the two new lineages.
• Point 1 is the most recent common ancestor of all the organisms on the tree.
• Point 2 is the most recent common ancestor of zebrafish, humans, and mice. (This ancestor can be described as “fishlike,” but it was not the same as today’s fish.)
• Point 3 is the most recent common ancestor of humans and mice.
• Time is represented on the vertical axis of the diagram. The present time is at the top. More-distant historical times are toward the bottom.
• To answer the question, Who is more closely related to whom? compare the most recent point where the different organisms share a common ancestor. An organism is more closely related to the organisms with which it shares more recent common ancestors. If students understand this, they should understand that the sequence of organisms from left to right on the diagram is not informative. It may help to describe the evolutionary tree as a mobile that can be picked up by the root and twirled without changing any of the relationships among the species.

Ask students to work with a partner to use the information they just learned to revise their answers to the questions on Master 1.5. Ask students to use a different-colored pen or pencil to make their revisions. Encourage students to simply put a single line through any text they wish to delete instead of erasing or scribbling it out.

Individual students should describe why they answered the questions as they did and should change their answers based on what they learned in Step 10. Using a different color for revisions makes it easier for students to see when they changed their minds. This reinforces the importance of students monitoring their own understandings.

Conduct a class discussion to review students’ revised answers to the questions on Master 1.5. Ask students to explain their answers and compare them with their initial ideas.

Answer key for questions on Master 1.5, An Evolutionary Tree

1. What part of the evolutionary tree diagram represents the common ancestor of humans, mice, and zebrafish (but not fruit flies)? Why did you identify this part of the diagram?
   
   The common ancestor for humans, mice, and zebrafish is at Point 2 on the evolutionary tree. Point 3 represents the common ancestor for mice and humans, and Point 1 is the common ancestor for all four species.
2. Does the evolutionary tree suggest that the mouse is more closely related to the zebrafish or the fruit fly?
   
   The mouse is more closely related to the zebrafish than the fruit fly. To answer this question, students need to find the most recent common ancestor of the mouse and the zebrafish and then of the mouse and the fruit fly. Once they identify the most recent common ancestor, they can mark the time frame for the existence of that common ancestor on the timeline. In this case, the most recent common ancestor for the mouse and the zebrafish occurred more recently than did the most recent common ancestor for the mouse and the fruit fly.
3. Is the fruit fly the ancestor of all the other species on the evolutionary tree? Explain your answer.
   
   No. The fruit fly is a modern, living species. Fruit flies share a common ancestor with all the other species on the diagram.
4. What does the vertical line beneath Point 1 represent?
   
   The vertical line beneath Point 1 represents the root of this evolutionary tree. It is the lineage that represents the common ancestor of the four species shown on the tree.

Conclude the activity by asking students to consider the following questions:

• Do you think that the common ancestor of fruit flies, zebrafish, mice, and humans had a gene similar to Pax6? Explain your answer.
  If students understand that the Pax6 gene is very similar in these four species and that the four species all share a common ancestor, then students should respond that Pax6 was present in the common ancestor. Students should cite the highly similar amino acid sequences for the Pax6 protein in the four species and the evolutionary tree as evidence.
• How does shared ancestry explain why scientists can use model organisms to learn about human health?
  Common (shared) ancestry allows scientists to study genes in model organisms that are similar to those in humans and make inferences to how the gene and its products function in humans. This allows scientists to conduct studies that may not be feasible in humans. If a gene had a different function in a different species or if there were a large number of significant changes in the gene in a given species, then that species might not be a good candidate as a model organism for that particular trait. Pax6 is a very strong example of the conservation of both gene sequence and gene function; not only is the sequence highly conserved in a wide variety of species, but it has a similar function in all of these species. Therefore, learning how it functions in a model organism (descended from the same common ancestor as humans) can provide valuable information for scientists about how it functions in humans.

Before discussing the answers to the questions in Step 13, you may want to ask students to write their answers first. You can then collect their responses to assess their understandings of common ancestry and its relationship to the value of model organisms. Students will revise their answers to these questions later in the supplement.