Genome-scale co-expression network comparison across escherichia coli and salmonella enterica serovar typhimurium reveals significant conservation at the regulon level of local regulators despite their dissimilar lifestyles

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

Overview of evolutionary conserved regulators across <i>E. coli</i> and <i>S. enterica</i>.

<p>Conserved regulators only between <i>E. coli</i> and <i>S. enterica</i> and their corresponding number of the modules which are enriched as the targets of these regulators. The same module numbers are used as in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102871#pone.0102871.s001" target="_blank">Table S1</a></b>. <b>Targets' co-expression conservation</b>: refers to whether the known targets of the corresponding regulator showed co-expression conservation across the studies species (i.e. they were detected on the core part of the co-expressed module). <b>Regulator co-expression conservation</b>: refers to whether the corresponding regulator itself showed co-.expression conservation across the studied species.</p

Expression behavior of genes in co-expressed modules 166 (Panel A) and 193 (Panel B) of Table S1 in <i>S. enterica</i>.

<p>Genes in black are the genes which are found as the co-expressed modules by COMODO. While genes in red (csgD and rpoE) are the ones which are not found in the co-expressed modules, but their ortholgous pair are co-expressed with the <i>E. coli</i> counterpart modules. We expect that genes in red (csgD and rpoE) should also be part of their modules as they are in the same operon with some genes of their modules. Shaded areas correspond to conditions not shared for the genes which were not detected as co-expressed in <i>S. enterica</i> (red genes). The fact that these conditions are much smaller in number than the conditions genes in red (csgD and rpoE) show co-expression with the rest of the modules genes increases the probability that these genes are actually in those modules.</p

Schematic representation of COMODO output for the first detected module across <i>E. coli</i>, <i>B. subtilis</i>, and <i>S. enterica</i>.

<p>Modules in conserved co-expressed triplets are composed of homologous triplets between three organisms (core part). In addition, homologous pairs can be detected which are conserved only between two organisms, that share a mutual co-expression in each of the species. Furthermore, additional genes can also be detected for which the co-expression with the homologous linker genes was found to be species-specific.</p

Phylogenetic tree of STM0347 and CsgD.

<p>Both proteins were used as queries for BLAST searches to retrieve their closest relatives. Collected sequences were aligned using CLUSTALW <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102871#pone.0102871-Andrews1" target="_blank">[31]</a> and the resulting alignment file used as input for the program ‘neighbor’ of the PHYLIP tree <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102871#pone.0102871-Lai1" target="_blank">[30]</a> to derive the tree. A total of 100 bootstrap replicates were generated (numbers on the branches). STM0347 and CsgD (<i>Salmonella enterica</i>) are far apart on the tree suggesting they have evolved from each other long time ago and might be involved in different functions.</p

Overview of evolutionary conserved regulators across three organisms.

<p>Conserved regulators between <i>E. coli</i>, <i>B. subtilis</i>, and <i>S. enterica</i> and the corresponding number of the modules which are enriched as the targets of these regulators. The same module numbers are used as in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102871#pone.0102871.s002" target="_blank">Table S2</a></b>. <b>Targets' co-expression conservation</b>: refers to whether the known targets of the corresponding regulator showed co-expression conservation across the studies species (i.e. they were detected on the core part of the co-expressed module). <b>Regulator co-expression conservation</b>: refers to whether the corresponding regulator itself showed co-.expression conservation across the studied species. The non-orthologous regulators between <i>E. coli</i> and <i>B. subtilis</i> predicted as being functional counterparts i.e. they are responsible for co-expression conserved target genes are highlighted by bold characters.</p

Overview of evolutionary co-expressed conserved modules across <i>E. coli</i> and <i>S. enterica</i>.

<p>The most enriched GO term from the biological process subtree amongst the genes in each module is shown (left column). The numbers of co-expressed modules showing enrichment in the same term are grouped (right column). Conserved co-expressed modules across <i>E. coli</i> and <i>S. enterica</i> are their corresponding module numbers as in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102871#pone.0102871.s001" target="_blank">Table S1</a></b>. The module numbers related to large evolutionary conserved co-expressed module, which contain at least 16 genes in their core part, are highlighted by bold characters.</p

Overview of evolutionary co-expressed conserved modules across three organisms.

<p>The most enriched GO term from the biological process subtree amongst the genes in each module is shown (left column). The numbers of co-expressed modules showing enrichment in the same term are grouped (right column). Conserved co-expressed modules across <i>E. coli</i>, <i>B. subtilis</i>, and <i>S. enterica</i> are their corresponding module numbers as in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102871#pone.0102871.s002" target="_blank">Table S2</a></b>. The module numbers related to large evolutionary conserved co-expressed module, which contain at least 16 genes in their core part, are highlighted by bold characters.</p