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Seminar in Evolutionary Ecology of Infectious Diseases 2015 Questions November 17: • How could dry treatment have shifted the sign off epistasis (e.g. to more positive values?) ? • Could you design and experiment these tests, with unlimited molecular tools, directly for the sign off epistasis ? • Could an extremely fit asexual strain still outcompete a sexual line with positive epistasis ? • Why is drift related with recombination ? • How does the Hamming distance work ? • How is fitness defined in HIV-­‐1 ? • Has positive epistasis been shown to prevail among mutation in most regions of the HIV genome ? • Did some studies find evidence for predominance of positive epistasis in eukaryotes ? • Which could be the implications for drug therapy ? • What is the difference between “normal” mutations, detrimental mutations and beneficial mutations ? • How does the reverse transcription happen ? • How did the randomisation of the data prove the p-­‐value ? What is the methodology behind it ? • I did not quite understand how you evaluated viral fitness. Does fitness change a lot if the test was conducted in a drug-­‐free environment ? • Positive epistasis means that mutations are causing a fitter phenotype; do they generate greater improvement than expected ? • Why does “recombination impairs rather then facilitates the evolution of drug resistance in HIV” ? • What could the implications for drug therapy be ? • What is epistasis (I still don’t understand it) ? • Have there been more studies finding positive epistasis ? • How did they make sure all viruses were heterozygous ? • Why didn’t they take samples of untreated patients ? • Fitness measure: production of infections progeny viruses š is this really an adequate fitness indicator ? • What other benefits (than increasing recombination) could sexual reproduction have ? • What other factor than sexual reproduction and recombination can increase genetic variation ? • What data are needed for testing the two classes of theories proposed in the paper ? • What are a negative and a positive epistasis ? • Could you explain the theory of the evolution of sexual recombination based on negative epistasis ? I don’t understand why negative epistasis is beneficial. • When does resp. can sexual reproduction not increase genetic variation (compared to clonal reproduction) ? • To me, it seems that the virus has just adapted to the host. How would a non-­‐sexual reproduction system look like ? •
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What does “multiplicatively of the effect” mean and how can it be explained biologically ? What is the Hamming distance ? What does the “mean epistasis” mean for the “phenotype” of the virus ? Why should greater genetic variation not be adaptive ? What is the difference between beneficial and detrimental mutations ? Do you have any hypothesis why retroviruses have (nevertheless) evolved the capacity to recombine ? What is epistasis ? To which organisms can the results of this study be transferred to? What is the main goal of the study ? Is this relevant for HIV treatment ? I don’t understand how the epistasis can be estimated with the mentioned formula. What dies it mean if the highest frequency of the mean epistasis is O ? Through what is epistasis actually controlled ? Why is the data set considered representative, if already selected by drug treatment ? Why retroviruses ? How does the mutation differ from asexual reproduction of other alleles ? How is fitness defined here ? Replication per cell ? Virulence per produced viral copy ? How was fitness actually measured (I didn’t understand the method) and how much does the virus’ fitness /reproduction depend on the host’s ability to shield against the virus ? “After this paper had been accepted, a related paper or epistasis in the vesicular stomatitis virus by Sanjua’n et al. (29)” I couldn’t find the paper. Does it support the findings of this paper ? How does this paper challenge hypothesis about evolution of recombination based on negative epistasis ? Why does recombination affect epistasis ? Is this always the case ? Could it be, that some genes (of HIV) are pleiotropic and therefore disturb the results of this paper ? Why is it that beneficial mutations need to interact antagonistically & detrimental mutations synergistically? Is it possible to use this results from HIV as well for other organisms ? “However, if there is measurement error in fitness, it can be shown that defining ab as the fittest genotype results in a bias toward positive epistasis. Similarly, defining AB as the least fit genotype results in a bias toward negative epistasis.” Why ? “However, in contrast to studies measuring epistasis in Escherichia coli, yeast, or Caenorhabditis elegans (10, 13, 15), we have measured epistasis in an organism in which recombination occurs frequently. Therefore, it may in fact be more appropriate to extrapolate from retroviruses than from organisms that are effectively asexual.” What is the advantage of using retroviruses for this instead of these other organisms if they are asexual ? As far as I understand it, viruses are asexual too (?) I don’t get the point. The sentence before says that it needs to be shown whether the pattern of epistasis found in HIV-­‐1 is representative of that in other organisms (in particular of hat in eukaryotes). But why do they want to do this with HIV-­‐1 or other retroviruses for eukaryotes ? Wouldn’t it be better to use eukaryotes for this type of experiment ?