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Evolutionary conservation of essential and highly expressed genes in Pseudomonas aeruginosa.

Dötsch A, Klawonn F, Jarek M, Scharfe M, Blöcker H, Häussler S - BMC Genomics (2010)

Bottom Line: Pooled sequencing of 36 clinical Pseudomonas aeruginosa isolates revealed that essential and highly expressed proteins evolve at lower rates, whereas extracellular proteins evolve at higher rates.Among the conserved nonessential genes we found several that are involved in regulation, motility and virulence, indicating that they represent factors of evolutionary importance for the lifestyle of a successful environmental bacterium and opportunistic pathogen.The detailed analysis of a comprehensive set of P. aeruginosa genomes in this study clearly disclosed detailed information of the genomic makeup and revealed a large set of highly conserved genes that play an important role for the lifestyle of this microorganism.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chronic Pseudomonas Infections Research Group, Helmholtz-Center for Infection Research, Braunschweig, Germany.

ABSTRACT

Background: The constant increase in development and spread of bacterial resistance to antibiotics poses a serious threat to human health. New sequencing technologies are now on the horizon that will yield massive increases in our capacity for DNA sequencing and will revolutionize the drug discovery process. Since essential genes are promising novel antibiotic targets, the prediction of gene essentiality based on genomic information has become a major focus.

Results: In this study we demonstrate that pooled sequencing is applicable for the analysis of sequence variations of strain collections with more than 10 individual isolates. Pooled sequencing of 36 clinical Pseudomonas aeruginosa isolates revealed that essential and highly expressed proteins evolve at lower rates, whereas extracellular proteins evolve at higher rates. We furthermore refined the list of experimentally essential P. aeruginosa genes, and identified 980 genes that show no sequence variation at all. Among the conserved nonessential genes we found several that are involved in regulation, motility and virulence, indicating that they represent factors of evolutionary importance for the lifestyle of a successful environmental bacterium and opportunistic pathogen.

Conclusion: The detailed analysis of a comprehensive set of P. aeruginosa genomes in this study clearly disclosed detailed information of the genomic makeup and revealed a large set of highly conserved genes that play an important role for the lifestyle of this microorganism. Sequencing strain collections enables for a detailed and extensive identification of sequence variations as potential bacterial adaptation processes, e.g., during the development of antibiotic resistance in the clinical setting and thus may be the basis to uncover putative targets for novel treatment strategies.

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Gene expression correlates with substitution rate and gene essentiality. A) Nonsynonymous substitution rate dN (coding sequences averaged for all 36 strains) versus the expression level. Color indicates the density of data points ranging from blue (single data point) to deep red. B) Boxplots of gene expression levels grouped by gene essentiality as annotated in the Database of Essential Genes [29]. Boxplots indicate 0.25 and 0.75 quantiles and the median (red line) with notches giving an estimate for the variance of the median. The green dashed line indicates the median dN for all genes.
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Figure 4: Gene expression correlates with substitution rate and gene essentiality. A) Nonsynonymous substitution rate dN (coding sequences averaged for all 36 strains) versus the expression level. Color indicates the density of data points ranging from blue (single data point) to deep red. B) Boxplots of gene expression levels grouped by gene essentiality as annotated in the Database of Essential Genes [29]. Boxplots indicate 0.25 and 0.75 quantiles and the median (red line) with notches giving an estimate for the variance of the median. The green dashed line indicates the median dN for all genes.

Mentions: In addition to gene essentiality, a high gene expression rate has previously been shown to correlate with low sequence variation [18], and it was proposed that the underlying driving force for the slower evolution of essential genes is that most of the highly expressed genes are also generally indispensable. To test this for P. aeruginosa, we compared the gene expression data of P. aeruginosa (averaged from 232 microarrays as described above) with the rate of nonsynonymous substitutions, dN (Figure 4A). Applying robust regression to predict dN from gene expression clearly demonstrated a negative correlation (not shown), which means that highly expressed genes are indeed more conserved in P. aeruginosa.


Evolutionary conservation of essential and highly expressed genes in Pseudomonas aeruginosa.

Dötsch A, Klawonn F, Jarek M, Scharfe M, Blöcker H, Häussler S - BMC Genomics (2010)

Gene expression correlates with substitution rate and gene essentiality. A) Nonsynonymous substitution rate dN (coding sequences averaged for all 36 strains) versus the expression level. Color indicates the density of data points ranging from blue (single data point) to deep red. B) Boxplots of gene expression levels grouped by gene essentiality as annotated in the Database of Essential Genes [29]. Boxplots indicate 0.25 and 0.75 quantiles and the median (red line) with notches giving an estimate for the variance of the median. The green dashed line indicates the median dN for all genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2864246&req=5

Figure 4: Gene expression correlates with substitution rate and gene essentiality. A) Nonsynonymous substitution rate dN (coding sequences averaged for all 36 strains) versus the expression level. Color indicates the density of data points ranging from blue (single data point) to deep red. B) Boxplots of gene expression levels grouped by gene essentiality as annotated in the Database of Essential Genes [29]. Boxplots indicate 0.25 and 0.75 quantiles and the median (red line) with notches giving an estimate for the variance of the median. The green dashed line indicates the median dN for all genes.
Mentions: In addition to gene essentiality, a high gene expression rate has previously been shown to correlate with low sequence variation [18], and it was proposed that the underlying driving force for the slower evolution of essential genes is that most of the highly expressed genes are also generally indispensable. To test this for P. aeruginosa, we compared the gene expression data of P. aeruginosa (averaged from 232 microarrays as described above) with the rate of nonsynonymous substitutions, dN (Figure 4A). Applying robust regression to predict dN from gene expression clearly demonstrated a negative correlation (not shown), which means that highly expressed genes are indeed more conserved in P. aeruginosa.

Bottom Line: Pooled sequencing of 36 clinical Pseudomonas aeruginosa isolates revealed that essential and highly expressed proteins evolve at lower rates, whereas extracellular proteins evolve at higher rates.Among the conserved nonessential genes we found several that are involved in regulation, motility and virulence, indicating that they represent factors of evolutionary importance for the lifestyle of a successful environmental bacterium and opportunistic pathogen.The detailed analysis of a comprehensive set of P. aeruginosa genomes in this study clearly disclosed detailed information of the genomic makeup and revealed a large set of highly conserved genes that play an important role for the lifestyle of this microorganism.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chronic Pseudomonas Infections Research Group, Helmholtz-Center for Infection Research, Braunschweig, Germany.

ABSTRACT

Background: The constant increase in development and spread of bacterial resistance to antibiotics poses a serious threat to human health. New sequencing technologies are now on the horizon that will yield massive increases in our capacity for DNA sequencing and will revolutionize the drug discovery process. Since essential genes are promising novel antibiotic targets, the prediction of gene essentiality based on genomic information has become a major focus.

Results: In this study we demonstrate that pooled sequencing is applicable for the analysis of sequence variations of strain collections with more than 10 individual isolates. Pooled sequencing of 36 clinical Pseudomonas aeruginosa isolates revealed that essential and highly expressed proteins evolve at lower rates, whereas extracellular proteins evolve at higher rates. We furthermore refined the list of experimentally essential P. aeruginosa genes, and identified 980 genes that show no sequence variation at all. Among the conserved nonessential genes we found several that are involved in regulation, motility and virulence, indicating that they represent factors of evolutionary importance for the lifestyle of a successful environmental bacterium and opportunistic pathogen.

Conclusion: The detailed analysis of a comprehensive set of P. aeruginosa genomes in this study clearly disclosed detailed information of the genomic makeup and revealed a large set of highly conserved genes that play an important role for the lifestyle of this microorganism. Sequencing strain collections enables for a detailed and extensive identification of sequence variations as potential bacterial adaptation processes, e.g., during the development of antibiotic resistance in the clinical setting and thus may be the basis to uncover putative targets for novel treatment strategies.

Show MeSH
Related in: MedlinePlus