INTRODUCTION TO EVOLUTION: THE EVOLUTION OF HIV.

Questions: Answer the following questions based on Chapter 1 of Freeman and Herron (2003).

1. What do the authors mean when they say (section 1.3) that "one of the keys to becoming an evolutionary biologist is to learn selection thinking"? 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 (at least at first) harming human cells? How does the ability of AZT to halt the decline of CD4 cells change in an individual over time? 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 over several years of treatment with AZT? How does this 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 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. What does it mean when the authors say that the evolution of HIV within an individual host is “short-sighted”? What do the authors mean when they say there appears to be a correlation between lethality and transmission? How does this affect the evolution of the virus?

7. Now think about what has to happen for the virus to be transferred from one host to another? Consider two different strains of HIV: strain 1 is highly virulent (replicates rapidly in the host, causes high viral loads and host death relatively quickly); strain 2 is less virulent and an individual host may live many years. Which would be more likely to be transmitted from a host to uninfected person in a single encounter? Now imagine two human populations: in population 1, the number of unprotected encounters in a given period of time (say one year) between individuals is high (NOTE: this could be due to unprotected blood supplies, high promiscuity, or low use of condoms, etc.). In the second population, the encounter rate for a host is low, so the number of opportunities for transfer in a given time period is small. Which viral strain will be most successful in each of these populations? What does this indicate about how HIV education programs could affect the evolution of the virus?

8. Most of the chapter focuses on the evolution of the virus. Section 1.4 discusses how the human population may respond evolutionarily to the HIV virus. Is there evidence that there is genetic variation among humans for resistance to HIV infection? What is the basis of this variation? If the HIV virus continues to spread, what should happen in the human population?

9. Figure 1.12 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 other’s 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)?

10. What does the pattern 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?