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compbio-2017 / Discussion

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[mock] PopGen #13

Open shouldsee opened 6 years ago

shouldsee commented 6 years ago

Questions

Natural selection

  1. Contrast the definitions of Melthusian fitness and Darwinian fitness. Compare their solutions under a simple selection pressure if you can. answer
  2. Note that simple selection model consider a single loci with two candidate alleles. This is likely to be too simple in real life. State the assumptions behind this model and list common modifications accordingly.
  3. How would you construct a model to explain overdominance of heterzygote?
  4. What's the role of neutral mutation in selection? How is this related to epistasis? Do you think that effect of mutation is dependent/independent on its genetic background? Why?
  5. Allele fraction is often used in describing temporal dynamics of evolution, which means one lost information about absolute population size. Does this mean population size is not important at all?
  6. What is a Hardy-Weinberg equilibrium?

Fixation of new alleles in a diploid population:

  1. Consider the simple case where a single-locus is concerned with two alleles "a" and "A". Derive the probability for a rare mutation that produces an "A" in a all-"a" population to take up 1% of population, as well as its probability of fixation. (Actual)

Other models

  1. What is genetic drift, and how is allele fixation different with and without drift? How would you estimate the drift given a SNP dataset (aka calculating effective population size, tip: recall how drift is represented in the Wright-Fisher model)?
  2. What is epistasis? Is it better to assume additive fitness across loci or epstasis? State the biological motivation of your assumption. Contrast epistasis and recombination as two models for explaining loci-loci interaction. (e.g. why is it impossible to reflect recombination on the fitness landscape?)
  3. Apply both to predict the temporal evolution of influenza, given its particular genomic organization and means of inheritance. Comment on how evolution of influenza relates to its pathogenecity and how hypotheses can be tested using high-throughput sequencing. Evaluate the importance of different noise sources and why it is better to use long reads (e.g. Sanger sequencing) if available. (bonus: Name how novel genotypes can arise in influenza?)
  4. Out of the selection, mutation and drift, what is the fastest process and the slowest? If your answer depends on other parameters, name those with a direct effect on time-scales.
  5. How is mutation and copy-number/ploidy commonly modelled (in cancer for example)?
  6. How is genomic recombination/linkage disequilibrium commonly modelled in a diploid system?

Inference:

  1. What model would you use for inferring the selection strength given allele/haplotype/genotype counts over time?
  2. Why could direct measurement of evolution be hard in practice? How is such difficulty addressed in real research? What are the Pros and Cons of different model systems? answer

Overall

  1. How can you correlate phenotypic variation to genotypic variation? Give an example and make a quantitative/qualitative argument.
  2. Is the evolution happening on the protein level, mRNA level or DNA level? Give examples accordingly.answer

Answers

can be found in comments below, or this folder Mock-2017

shouldsee commented 6 years ago

Is the evolution happening on the protein level, mRNA level or DNA level? Give examples accordingly.

A: Since enzymes/proteins are the major workhorses of biological processes, they are of direct functional importance, as supported by the observation of enriched synonymous mutations in CDS(coding sequence) under a selection pressure. However, in system like influenza viruses and bacteria, it is beneficial to have a smaller genome both for efficient replication and for lower mutation load, where DNA is directed selected for.

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shouldsee commented 6 years ago

Real model

Real life models for evolution:

Pros/Cons:

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