Final Assignment in the Course Regulatory Genomics 2012
Part A: Select 2 of the following papers and in each of the selected papers select and answer all
but one of questions.
1. Read the paper: “Environmental perturbations lift the degeneracy of the genetic code to
regulate protein levels in bacteria” (Subramaniam et al, PNAS 2012)
http://www.pnas.org/content/early/2012/12/28/1211077110.long
Limit your answer to 50 words per question unless otherwise noted.
1. State the most important take-home message of the paper.
2. Give 2 points of criticisms on the approach, findings, or conclusions.
3. How does “lifting the degeneracy of the genetic code” enable cells to control protein
levels?
4. How could cells cope, on a physiological time scale, with the change in supply-todemand of tRNAs? How could they cope with such a change on an evolutionary time
scale (i.e. by genetic changes)?
5. Design an experiment to assess the functional significance of the ability of cells to “lift
the degeneracy of the code”.
2. Read the paper: “A Role for Codon Order in Translation Dynamics” (Cannarozzi et al, Cell
2010)
http://www.sciencedirect.com/science/article/pii/S0092867410001893#
Limit your answer to 50 words per question unless otherwise noted.
1. State the most important take-home message of the paper.
2. Give 2 points of criticisms on the approach, findings, or conclusions.
3. Does the paper consider “codon corelation” a direct result from selection or an indirect
consequence of another source? How did the authors discreminate between the two
options?
4. Does codon correlation result from codon bias? How did the author check that?
1
5. Figure 5 considers the relative rates of tRNA diffusion and translation (codons/second).
Explain the question that the figure deals with. Obtain data (probably outside the
current paper) that compare the rates of tRNA diffusion and ribosome traslation and
conclude if a mechanism has to exist that would sequester the tRNA in the vicinity of the
ribosome for tRNA recycling to work (75 words).
6. Considering the following table of the genetic code, the tRNA genes and their wobble
interactions:
In the table the genetic code is shown along with the identity of the anti-codon for each
codon. tRNAs are shown with their base modifications (for example, the anti-codon GAA
appears as GmAA to indicate a methylation on the G nucleotide). The copy number of
genes encoding each tRNA is shown, and no value means zero copy for that
corresponding tRNA. The green arrows show which wobble-based interactions allow to
decode codons for which a cognate tRNA is not present in the genome, for example the
tRNA with the GmAA anti-codon can decode the codon UUU in addition to its cognate
codon UUC. Consider two codons for the same amino acid, C1 and C2. The paper shows
that codons tend to be repeated twice when the corresponding amino acid occurs twice
in proximity. For which codon pair C1,C2 (give a couple of actual examples for such a
2
codon pairs) would you expected C1 to be followed not only by C1, but also by C2 (or C2
to be also followed by C1). In which codons (give a couple of examples) would you
expect that C1 will mainly be followed by C1, and C2 by C2? Explain.
3. Read the paper: “Genome-wide structure and organization of eukaryotic pre-initiation
complexes” (Ho Sung Rhee & B. Franklin Pugh, Science 2012)
http://www.nature.com/nature/journal/v483/n7389/full/nature10799.html
Limit your answer to 50 words per question unless otherwise noted.
1. State the most important take-home message of the paper.
2. Give 2 points of criticisms on the approach, findings, or conclusions.
3. What is the prevalence of the TATA sequence in the yeast promoters?
4. What is the difference in the PICs organizations between TATA-containing and TATA-like
promoters? Which of these two classes of genes is expected to be with a higher
plasticity? Design an experiment to shows such potential effect of TATA elements on
plasticity. (100 words)
5. Why are ‘dubious’ genes suggested not to be transcribed?
6. How does the organization of adjacent genes influence PICs? What is the situation for
the closest inverted genes? What are the regulatory implications? (75 words)
7. What are the differences between PICs of mRNAs and ncRNAs? Where do ncRNA PICs
tend to be localized in respect to mRNA PICs?
3
Part B: Answer a single question out of the following 5. Limit your answer to 1 page written in
Calibri size 12 and 1.5 line spacing.
1. Design an enzymatic machinery that can be built in cells that will convert proteins to
DNA.
2. Generalize the formula for hyper-geometric distribution to the case of n overlapping
sets. Apply the case of n=3 to look for sets of 3 transcription factors in the yeast
(http://longitude.weizmann.ac.il/TFLocation/Data.html use the “union matrix.xls”)transcrption
network that co-occur in a significantly high number of target genes .
3. A foreign transcript with a known sequence is expressed in a cell. Design a synthetic
circuit that will be expressed in the cell that will turn the cell green if the transcript has
an expression profile with a cell cycle periodicity and red if it has twice that periodicity.
4. Select an organism of your choice and an environmental growth condition and introduce
as many mutations or modifications into the genome that will improve the fitness of the
original organism in that environment.
5. Under stressful conditions an organism increases the rate at which its chromosome missegregate thus generating aneuploidic cells. Is this an adaptive trait, or a result of the
segregation machinery working with lower fidelity? Design an experiment that will
provide an answer to the question.
Please send your final work to: [email protected]
In the subject write: Final Work for Regolatory Genomics Course by YOUR NAME
Deadline is: 15.3.13
4