Growth rate-coordinated transcriptome reorganization in bacteria

Abstract

Background: Cell growth rate reflects an organism's physiological state and largely relies on the ability of gene expression to respond to the environment. The relationship between cellular growth rate and gene expression remains unknown.

Results: Growth rate-coordinated changes in gene expression were discovered by analyzing exponentially growing Escherichia coli cells cultured under multiple defined environments, in which osmotic pressure, temperature and starvation status were varied. Gene expression analyses showed that all 3,740 genes in the genome could be simply divided into three clusters (C1, C2 and C3), which were accompanied by a generic trend in the growth rate that was coordinated with transcriptional changes. The direction of transcriptional change in C1 indicated environmental specificity, whereas those in C2 and C3 were correlated negatively and positively with growth rates, respectively. The three clusters exhibited differentiated gene functions and gene regulation task division.

Conclusions: We identified three gene clusters, exhibiting differential gene functions and distinct directions in their correlations with growth rates. Reverses in the direction of the growth rate correlated transcriptional changes and the distinguished duties of the three clusters indicated how transcriptome homeostasis is maintained to balance the total expression cost for sustaining life in new habitats.

Figure 1

Growth rates under various conditions. Grey, blue, red, and violet represent growth under regular, osmotic pressure (osmo), high temperature (heat) and starvation (strv) environments, respectively. Differences in color saturation represent different growth rates.

Figure 2

Similarities in transcriptional changes. The GSEA results are shown as heat maps. Two types of annotations were used to enrich the gene categories (A) and the transcriptional networks (TFs, B). The statistical significance (FDR q-value) of the transcriptional changes in the TF and gene categories is represented by the gradation from dark brown to yellow or blue on a logarithmic scale. Vivid colors represent high significance in the directions of either upregulated (yellow) or downregulated (blue) genes. The environments responsible for the transcriptome are indicated as follows: regular, osmotic pressure (osmo), temperature (heat), and starvation (strv). The numbers following the environmental abbreviations represent differences in growth rates, as indicated in Figure 1 with higher numbers equivalent to slower growth.

Figure 3

Genes having similar transcriptional change dynamics. A. Gene clusters. The three gene clusters determined by K-means clustering are shown in yellow (C1), blue (C2), and green (C3). The number of genes in each cluster is indicated. The essential genes comprising the three clusters are shown in dark green. An asterisk indicates the statistical significance (p < 0.01) of the biased number of essential genes within cluster C3, as evaluated using binomial tests. B. The three-dimensional space formed by the three clusters. Clusters C1, C2, and C3 are represented by the axes z, x, and y, respectively. The lines representing zero on the three axes are indicated using dashed lines. Gene expression under regular conditions is marked in black and located at the zero points of all three axes. Gene expression under the three studied environmental types having varied growth rates are indicated separately. The use of color hue and saturation are as described in Figure 1: osmotic pressure (blue), temperature (red), and starvation (violet).

Figure 4

Differentiated gene functions and regulations. Gene functions are designated using MultiFun, gene categories, and GO terms. The gene regulations are based on transcriptional networks (TFs). All annotations were made according to public data banks as described in the main text. C1 (yellow), C2 (blue) and C3 (green) represent the three gene clusters determined in Figure 3, and color bars indicate the statistical significance in log-scaled p values obtained using binomial tests with Bonferroni corrections.

Figure 5

Correlations between changes in gene expression and growth rates. The three gene clusters (C1–3) determined by K-means clustering (K = 3) are shown in relation to growth rates. The mean values of the normalized transcriptional changes for all genes within the cluster are plotted against growth rates. The standard deviations represent the variation among genes within the same cluster. Black circles represent the expression levels measured under regular conditions. Differences in color saturation represent differences in growth rate. The use of color hue and saturation are as described in Figure 1: osmotic pressure (blue), temperature (red), and starvation (violet).

Figure 6

Growth coordinated with transcriptome reorganization. Exponentially growing cells comprise the three gene clusters (A) as follows: one cluster comprises environment-specific genes (orange), and two clusters comprise environment-nonspecific genes (navy). Clusters C1, C2, and C3 are noted in Figure 3. Balanced changes in gene expression among the three clusters are illustrated in coordination with growth rates (B).