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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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Protein evolution in essential and dispensable genes. Boxplots of nonsynonymous substitution rates dN of coding sequences averaged for all 36 strains. Data were grouped by gene essentiality as annotated in the Database of Essential Genes [13]. 87 genes showing a very low read depth (≤ 25% of the average read depth) were neglected in this analysis. 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. Values with dN above 20 × 10-3 are not shown.
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Figure 2: Protein evolution in essential and dispensable genes. Boxplots of nonsynonymous substitution rates dN of coding sequences averaged for all 36 strains. Data were grouped by gene essentiality as annotated in the Database of Essential Genes [13]. 87 genes showing a very low read depth (≤ 25% of the average read depth) were neglected in this analysis. 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. Values with dN above 20 × 10-3 are not shown.

Mentions: It has previously been shown that essential genes are more evolutionarily conserved than nonessential genes [17], and indeed determination of non-synonymous and synonymous substitution rates dN and dS for the 36 clinical P. aeruginosa strains confirmed this expected correlation of sequence variation and essentiality (Figure 2). If genes are grouped by their functional classification, the variation is lowest for genes involved in 'transcription, RNA processing, degradation', 'translation, post-translational modification, degradation' and 'cell division', which are enriched for essential genes (Figure 3).


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)

Protein evolution in essential and dispensable genes. Boxplots of nonsynonymous substitution rates dN of coding sequences averaged for all 36 strains. Data were grouped by gene essentiality as annotated in the Database of Essential Genes [13]. 87 genes showing a very low read depth (≤ 25% of the average read depth) were neglected in this analysis. 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. Values with dN above 20 × 10-3 are not shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Protein evolution in essential and dispensable genes. Boxplots of nonsynonymous substitution rates dN of coding sequences averaged for all 36 strains. Data were grouped by gene essentiality as annotated in the Database of Essential Genes [13]. 87 genes showing a very low read depth (≤ 25% of the average read depth) were neglected in this analysis. 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. Values with dN above 20 × 10-3 are not shown.
Mentions: It has previously been shown that essential genes are more evolutionarily conserved than nonessential genes [17], and indeed determination of non-synonymous and synonymous substitution rates dN and dS for the 36 clinical P. aeruginosa strains confirmed this expected correlation of sequence variation and essentiality (Figure 2). If genes are grouped by their functional classification, the variation is lowest for genes involved in 'transcription, RNA processing, degradation', 'translation, post-translational modification, degradation' and 'cell division', which are enriched for essential genes (Figure 3).

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