Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39

The genome sequences of Chlamydia trachomatis mouse pneumonitis (MoPn) stra in 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 sequen ced C.trachomatis serovar D. Differences between C.trachomatis strains were focused on an similar to 50 kb 'plasticity zone' near the termination orig ins. In this region MoPn contained three copies of a novel gene encoding a >3000 amino acid toxin homologous to a predicted toxin from Escherichia col i 0157:H7 but had apparently lost the tryptophan biosyntheis genes found in serovar D in this region. The C.pneumoniae AR39 chromosome was >99.9% iden tical to the previously sequenced C.pneumoniae CWL029 genome, however, comp arative analysis identified an invertible DNA segment upstream of the uridi ne kinase gene which was in different orientations in the two genomes. AR39 also contained a novel 4524 nt circular single-stranded (ss)DNA bacterioph age, the first time a virus has been reported infecting C.pneumoniae. Altho ugh the chlamydial genomes were highly conserved, there were intriguing dif ferences in key nucleotide salvage pathways: C.pneumoniae has a uridine kin ase gene for dUTP production, MoPn has a uracil phosphororibosyl transferas e, while C.trachomatis serovar D contains neither gene. Chromosomal compari son revealed that there had been multiple large inversion events since the species divergence of C.trachomatis and C.pneumoniae, apparently oriented a round the axis of the origin of replication and the termination region. The striking synteny of the Chlamydia genomes and prevalence of tandemly dupli cated genes are evidence of minimal chromosome rearrangement and foreign ge ne uptake, presumably owing to the ecological isolation of the obligate int racellular parasites. In the absence of genetic analysis, comparative genom ics will continue to provide insight into the virulence mechanisms of these important human pathogens.