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Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39
T D Read1, R C Brunham, C Shen
1The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA.
Abstract:
The genome sequences of Chlamydia trachomatis mouse pneumonitis (MoPn) strain Nigg (1 069 412 nt) and Chlamydia pneumoniae strain AR39 (1 229 853 nt) were determined using a random shotgun strategy. The MoPn genome exhibited a general conservation of gene order and content with the previously sequenced C.trachomatis serovar D. Differences between C.trachomatis strains were focused on an approximately 50 kb 'plasticity zone' near the termination origins. In this region MoPn contained three copies of a novel gene encoding a >3000 amino acid toxin homologous to a predicted toxin from Escherichia coli O157:H7 but had apparently lost the tryptophan biosyntheis genes found in serovar D in this region. The C. pneumoniae AR39 chromosome was >99.9% identical to the previously sequenced C.pneumoniae CWL029 genome, however, comparative analysis identified an invertible DNA segment upstream of the uridine kinase gene which was in different orientations in the two genomes. AR39 also contained a novel 4524 nt circular single-stranded (ss)DNA bacteriophage, the first time a virus has been reported infecting C. pneumoniae. Although the chlamydial genomes were highly conserved, there were intriguing differences in key nucleotide salvage pathways: C.pneumoniae has a uridine kinase gene for dUTP production, MoPn has a uracil phosphororibosyl transferase, while C.trachomatis serovar D contains neither gene. Chromosomal comparison revealed that there had been multiple large inversion events since the species divergence of C.trachomatis and C.pneumoniae, apparently oriented around the axis of the origin of replication and the termination region. The striking synteny of the Chlamydia genomes and prevalence of tandemly duplicated genes are evidence of minimal chromosome rearrangement and foreign gene uptake, presumably owing to the ecological isolation of the obligate intracellular parasites. In the absence of genetic analysis, comparative genomics will continue to provide insight into the virulence mechanisms of these important human pathogens.
Insights
Comparative genomics reveals significant differences in Chlamydia trachomatis and Chlamydia pneumoniae genomes, particularly in nucleotide salvage pathways and a novel bacteriophage in C. pneumoniae. These findings offer insights into pathogen virulence.
Area of Science:
- Microbiology
- Genomics
- Comparative Genomics
Background:
- Chlamydia trachomatis and Chlamydia pneumoniae are significant human pathogens.
- Previous genomic sequencing provided a foundation for comparative analysis.
- Understanding genomic variations is crucial for identifying virulence factors.
Purpose of the Study:
- To determine and compare the genome sequences of Chlamydia trachomatis mouse pneumonitis (MoPn) strain Nigg and Chlamydia pneumoniae strain AR39.
- To identify genomic differences and similarities between C. trachomatis strains and between C. pneumoniae strains.
- To investigate variations in nucleotide salvage pathways and identify novel genetic elements.
Main Methods:
- Whole-genome sequencing using a random shotgun strategy.
- Comparative genomic analysis of C. trachomatis MoPn, C. trachomatis serovar D, and two C. pneumoniae strains (AR39 and CWL029).
- Identification and characterization of unique genetic elements, including a novel bacteriophage.
Main Results:
- MoPn genome shows conserved gene order with C. trachomatis serovar D, with variations in a 'plasticity zone' including a novel toxin gene and absence of tryptophan biosynthesis genes.
- C. pneumoniae AR39 genome is highly similar to CWL029 but contains an invertible DNA segment and a novel ssDNA bacteriophage.
- Significant differences were observed in nucleotide salvage pathways (uridine kinase, uracil phosphororibosyl transferase) between the studied Chlamydia species.
- Chromosomal analysis revealed large inversion events and high synteny, suggesting minimal rearrangement and foreign gene uptake.
Conclusions:
- Comparative genomics highlights key differences in Chlamydia genomes, particularly in metabolic pathways and the presence of novel genetic elements like bacteriophages.
- The high synteny and conserved gene order suggest limited horizontal gene transfer in these obligate intracellular parasites.
- Genomic insights are essential for understanding Chlamydia virulence mechanisms in the absence of extensive genetic analysis.