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Paper Review Number One:

Human gut microbiome adopts an alternative state following small bowel transplantation

Hartman et al., 2009

Analysis of Figures

Conclusion and References

Conclusions / Opinion:

Overall I thought the researchers’ ideas behind globally assessing phenotypic variation, also known as noise, through promoter behavior was novel.  It shows that a complicated topic such as noise can be studied on a global scale simply by directive selection for high and low expression levels of a reporter gene.  The method created by the authors is clearly described and the supporting facts and figures convince me that this particular method does establish specific promoters that have high phenotypic noise levels, most likely controlled by a varying rate of transcription and translation.  I enjoyed the beginning of the paper and thought that the figures generated to show that the method created was accurate were very clear. 

On the other hand, the end of the paper focused on the link between the promoters with high noise levels and the genes downstream of these promoters, which were mostly flagellar genes.  I thought that more time should have been spent discussing the possible biological role of noise in relation to these flagellar genes.  The authors touch briefly on how the ability of these particular flagellar genes to change expression abruptly may be advantageous in terms of pathogen interaction.  Since the authors note the importance of investigating the possible biological role of noise and how discovering new promoters and genes under high noise levels may lead to more knowledge of the importance of noise, they should have explored the biological consequences and benefits on increased noise more. 

The authors also note that the selection of populations was random and therefore some promoters that may be relatively noisier than the promoters studied in this paper may have been missed.  In order to study on a true global scale the authors would have to exhaust the promoter library, which they did not do in this experiment.  I did think it was interesting that the authors noted the difference between selecting for a high GFP expressing clone first rather than a low one.  It would be interesting to see which promoters turned out to show high noise levels but with a lower average expression rather than a higher average expression, which is what was studied in this paper.  I also enjoyed the movies they included and thought that they were a great visualization.  I would suggest a more robust study of the promoter library and acknowledge that the applications of such a study do not apply to organisms that cannot uptake a plasmid. Overall, I though Freed et al.’s paper was well organized and thought out.  They asked interesting questions and certainly contributed to the scientific field with their new method.




Freed, et al. (2008) A simple screen to identify promoters conferring high levels of  phenotypic noise. PLoS Genet 4(12): e1000307.


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