Questions:  Answer the following questions based on the information Freeman and Herron (2001) Chapter 1

1. What do the textbook authors (Freeman and Heron 2001) mean when they say (at the start of section 1.3) that "one of the keys to becoming an evolutionary biologist is to learn to think like an organism"?  Note that you will need to learn to think this way for this course!
2. Why does AZT work against retroviruses such as HIV without (except in a few cases) harming human cells? How does the ability of AZT to halt the decline of CD4 cells change in an individual over time (is it most effective at the start of treatment or later in treatment? Does it become more or less effective?) NOTE: be sure as you answer this question that you can also explain what HIV is, what AZT is, what a retrovirus is, and what CD4 cells are.
3. How does the sequence of the gene for reverse transcriptase in HIV virions compare within a single individual person from the time that person is first treated with AZT over several years of treatment with AZT?  How does this change affect the ability of AZT to halt HIV infection?
4. What causes the variation in the gene coding for reverse transcriptase among the HIV virions within a single individual person infected with HIV?  Are all forms of the enzyme reverse transcriptase that are coded for by these different forms of the gene equally susceptible to treatment with AZT? Do all different forms of the enzyme reverse transcriptase that are coded by these different forms of the gene function equally well in the absence of AZT?
5. Describe the steps through which AZT resistant forms of HIV evolve within an individual person who is infected with HIV and is receiving AZT treatment.  Would AZT resistance also develop in an individual who was infected with HIV but was not receiving AZT treatment? Why/ why not?
6. According to the hypothesis proposed by Paul Ewald (described in your textbook), how should the transmission rate of HIV affect the evolution of the level of virulence (high virulence or low virulence) of HIV?  Explain why.  Use the concepts of trade-offs, and cost-benefit analysis, in your explanation.
7. Ewald's hypothesis about the evolution of the level of virulence of HIV makes predictions that may be tested in the future as a result of two "natural experiments" -- that is, two situations that have occurred naturally that will allow people to evaluate the prediction.  What are these two situations and why will they allow Ewald's hypothesis to be tested?
8. Figure 1.6 on p. 16 of your text shows a phylogeny of some retroviruses.  What is a phylogeny?  What does this diagram represent?  According to this diagram, are the immunodeficiency viruses of humans (HIV-1 and HIV-2) each otherís closest relatives or are different strains of HIV more related to immunodeficiency viruses of other primates (chimpanzees, macaques, monkeys such as sooty mangabeys and green monkeys)?
9. What does the patter of phylogenetic relationship among immunodeficiency viruses of humans and other primates indicate about the origin of HIV in humans?  To answer this, consider the relationships between HIV and the SIVs that are shown in Figure 1.6.  What would you predict the relationships to be like if HIV had been present in humans when humans speciated from chimpanzees (our closest living relatives)?  What would you predict the relationships to be like if HIV had originated once, when the virus moved from another primate into humans?  What would you predict the relationships to be like if HIV had originated many times in humans from transfers to humans from other primates?  Which of these patterns is observed?  What is the likely explanation, as proposed by Gao, for how this came about, based on the ways human interact with the other primates that have various forms of SIV?