Analyzing Natural Selection Name Weizheng Hu Name Name 1. The data graphed to the right are from virus particles that were isolated from a patient at different times after AZT therapy began. The virus particles were then exposed to 0.1 μM AZT. The researchers who did the study claim that it supports the hypothesis that the HIV population in this patient evolved resistance to AZT. Do you agree? Defend your answer. Survival of HIV particles (0.1 μM AZT) Infection with the human immunodeficiency virus (HIV) causes the fatal disease called AIDS. The first drug that was effective against HIV was AZT. When AZT was first administered to HIV-infected patients, virus populations High patients died of dropped dramatically. But with time, HIV populations in the treated patients rebounded and the AIDS. (Note: inside an infected person, individual HIV particles live for about a day, on average.) Med. Low 1 11 16 Months of therapy Yes, I agree. It appears that the data from the graph shows a rebound in HIV populations in the treated patient over time after initial suppression due to AZT therapy. If the virus populations rebounded and continued to grow despite exposure to AZT, it could indicate that the HIV population in the patient evolved resistance to the drug.The data are consistent with the hypothesis that natural selection favored virus particles that can survive in the presence of AZT. 2. AZT and other antiviral drugs work by binding to molecules that help HIV produce offspring inside a host cell. The binding is very specific— if the shape or composition of the target molecule changes, the drug may not work. AZT binds at a specific location on a molecule called reverse transcriptase. HIV has a gene that contains the information for making reverse transcriptase. But the genetic information varies among HIV particles. As a result, the structure and composition of reverse transcriptase varies among HIV particles. Based on this information, is there heritable variation in the “resistance to AZT” trait? Explain why or why not. Yes, there is heritable variation in the "resistance to AZT" trait within the HIV population. The genetic information for making reverse transcriptase is diversity can lead to variations in the structure and composition of reverse transcriptase among different HIV particles.If some HIV particles carry genetic mutations that alter the structure of reverse transcriptase in a way that prevents or reduces the binding of AZT, those particles may be less susceptible to the drug's effects. These resistant variants could then be passed on to future generations of HIV particles through replication and transmission. Because the genetic information for making reverse transcriptase is passed on to offspring, the trait is heritable. 3. Using the information in question 2 and the data in the graph, is it reasonable to infer that there is differential reproductive success among HIV with respect to the “resistance to AZT” trait? Explain why or why not. Based on the information provided in question 2 and the graphical data, it can be inferred that the reproductive success of HIV is correlated with the trait of resistance to AZT. The rebound of HIV after treatment with AZT reflects the fact that some HIV variants are resistant to AZT. If these resistant variants are able to successfully reproduce in the presence of AZT, then they may have some advantage in terms of resistance traits. 1 Second, the resistance trait has some heritability in inheritance. It is then possible that this resistance trait could be passed on to offspring in the HIV population, thus affecting the reproductive success of the population as a whole. 4. Did forms of reverse transcriptase that were resistant to AZT exist in the HIV population before the patient began receiving AZT? Explain why or why not. Yes,some AZT-resistant retrotransposons may be present in the HIV population prior to AZT treatment, but their presence may be relatively low.The selective pressure generated by AZT treatment may favor the expansion of these resistant forms, leading to the evolution of AZT resistance in the population. 5. When AZT is administered to a particular patient, does each individual HIV particle inside that patient change to become more resistant to the drug, so that eventually the HIV population would consist of drug-resistant forms? Defend your answer. When AZT is administered to a particular patient, not every HIV particle in the patient's body will change and become more resistant; resistant individuals will simply survive better and leave more offspring than those with less or no resistance to AZT; this is natural selection in the evolution of the virus, where favorable traits become more prevalent over generations, leading to the emergence of AZT resistance over time. pushback leads to the emergence of AZT drug resistance. 1 6. Physicians now have many drugs that they can prescribe for HIV-infected individuals, in addition to AZT. So if HIV populations begin rebounding in a patient who is receiving AZT, the patient stops taking AZT and switches to different drugs. When the environment inside the patient changes in this way, HIV populations again drop dramatically. Explain why. When a patient stops taking AZT and is switched to a different drug, the environment in the patient's body changes. The new drug has a different mechanism of action against HIV. At this point, the selective pressure on the viral population changes, and this change creates a situation in which drug-resistant variants that previously dominated under AZT treatment, though having multiplied, are now at a disadvantage to the new drugs, leading to a decline in the overall viral population. 7. When a patient stops taking AZT and switches to new drugs, predict whether AZT-resistant forms become more common, less common, or remain at the same frequency, in that patient. Explain your logic. The number of azt-resistant pathogens should be greatly reduced, AZT-resistant forms become less common. HIV variants that were previously azt-resistant may become less competitive in the presence of new drugs compared with other non- or less resistant variants. Other variants may now have the opportunity to replicate more successfully, leading to a decline in the number of azt-resistant phenotypes. 8. Suppose the patient stopped taking AZT after several months and switched to a new drug called a protease inhibitor (PI). On the axes below, use a solid line to predict how the frequency of AZT-resistant forms will change over time. Use a dashed line to predict how the frequency of PI-resistant forms will change over time, and a dotted line to predict the frequency of HIV particles that are resistant to both drugs. 2 ********* Please turn the completed exercise in. (and make sure that your names are legible!) ********* If you finish early, consider the following: Some humans have genes that either a) reduce the likelihood of HIV infection or b) delay the onset of AIDS if an infection does occur. • In human populations where HIV infection is common, are the frequencies of these “resistance genes” increasing, decreasing, or staying about the same? Explain your reasoning. In populations with prevalent HIV infection, the frequency of these genes may increase due to selective pressure for antiretroviral therapy, while the frequency of drug resistance genes may be influenced by a variety of factors. • In human populations where HIV infection is rare, are the frequencies of these resistance genes increasing, decreasing, or staying about the same? Explain your reasoning. The frequency of resistance genes will remain low. In the absence of HIV, there is no advantage to being resistant. 2