What’s true for E. coli is true of an elephant

The quote by Jacque Monod in the title celebrates our recent publication of an article suggesting that our previous results in Escherichia coli hold true for most other prokaryotes:

  • del Grande, M., & Moreno-Hagelsieb, G. (2014). The loose evolutionary relationships between transcription factors and other gene products across prokaryotes. BMC Research Notes, 7, 928. doi:10.1186/1756-0500-7-928

This article expands on the part about transcriptions factors presented in our previous study comparing the conservation of different kinds of functional associations:

  • Moreno-Hagelsieb, G., & Jokic, P. (2012). The evolutionary dynamics of functional modules and the extraordinary plasticity of regulons: the Escherichia coli perspective. Nucleic Acids Research, 40(15), 7104–7112. doi:10.1093/nar/gks443

The earlier article dealt with several experimentally-confirmed functional interactions determined in Escherichia coli: genes in operons, genes whose products physically interact, genes regulated by the same transcription factor (regulons), and genes coding for transcription factors and their regulated genes. In that study we found that the associations involving transcription factors tend to be much less conserved than any of the other associations studied. Our work is not the first to suggest this lack of conservation, but is the first to compare conservation across different kinds of associations, and thus show that those mediated by transcriptional regulation are the least conserved.

The most recent article was an expansion of the association between genes coding for transcription factors and other genes. The idea being to extend the study towards as many other prokaryotes as possible. But how could we determine conservation between genes coding for transcription factors and other genes without experimentally-determined interactions? We knew that at least some transcription factors could be predicted from their possessing a DNA binding domain. But what about their associations? Our prior experience has been that target genes are hard to predict even when there’s information on some characterized binding sites (sites that we like calling operators for tradition’s sake). So what to do if we have only the transcription factors? Well, to answer that we should first explain how we measured relative evolutionary conservation.

To measure evolutionary conservation we used a measure of co-occurrence called mutual information. For any two genes, the higher the mutual information, the less the observed co-occurrence looks random. Since we obtained mutual information scores for all gene pairs in the genomes we analyzed, we decided that instead of something as hard as predicting operators, and matching them to predicted transcription factors, we could use top scoring gene pairs as representatives of the most conserved interaction between our predicted transcription factors and anything else. This allowed us to compare the most conserved interactions involving transcription factors against the conservation of other interactions. Our findings suggest that interactions involving transcription factors evolve quickly in most-if-not-all of the genomes analyzed.

Please read the articles for more details and information.

-Gabo

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