Abstract

Availability of genome-wide gene expression datasets provides the opportunity to study gene expression across different organisms under a plethora of experimental conditions. In our previous work, we developed an algorithm called COMODO (COnserved MODules across Organisms) that identifies conserved expression modules between two species. In the present study, we expanded COMODO to detect the co-expression conservation across three organisms by adapting the statistics behind it. We applied COMODO to study expression conservation/divergence between Escherichia coli, Salmonella enterica, and Bacillus subtilis. We observed that some parts of the regulatory interaction networks were conserved between E. coli and S. enterica especially in the regulon of local regulators. However, such conservation was not observed between the regulatory interaction networks of B. subtilis and the two other species. We found co-expression conservation on a number of genes involved in quorum sensing, but almost no conservation for genes involved in pathogenicity across E. coli and S. enterica which could partially explain their different lifestyles. We concluded that despite their different lifestyles, no significant rewiring have occurred at the level of local regulons involved for instance, and notable conservation can be detected in signaling pathways and stress sensing in the phylogenetically close species S. enterica and E. coli. Moreover, conservation of local regulons seems to depend on the evolutionary time of divergence across species disappearing at larger distances as shown by the comparison with B. subtilis. Global regulons follow a different trend and show major rewiring even at the limited evolutionary distance that separates E. coli and S. enterica.

Highlights

  • One of the key issues in system biology is to identify functional orthologous genes

  • Applying COMODO to expression compendia of E. coli and S. enterica resulted in the identification of 211 conserved module pairs that were linked through a statistically significant set of homologous genes (Table S1)

  • Applying COMODO to infer modules that were conserved between E. coli, B. subtilis, and S. enterica resulted in 110 conserved module triplets linked through a statistically significant set of homologous genes (Table S2).Table 1 and Table 2 give an overview of the functional categories in which genes in the conserved co-expressed module across the three organisms are involved

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Summary

Introduction

One of the key issues in system biology is to identify functional orthologous genes. These are genes that share sequence ancestry, and are expected to perform the same function in different organisms. COMODO is initialized with finding co-expressed seeds or seed modules obtained from each of the species. These seeds are gradually expanded in each of the species until a pair of modules is obtained for which the number of shared homologs is statistically optimal relative to the size of the linked modules. The retrieved pairs can cover a large range of co-expression levels (e.g. operon or regulon level conservation) and module sizes

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