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The chlamydial genome.

Sequences for the whole genome of a considerable number of the family Chlamydiaceae have become available since 1998, including partial or complete genome sequences for C. trachomatis serotypes B, D and L2 and C. muridarum (formerly the mouse pneumonitis agent). Among the genus Chlamydophila, almost identical genome sequences have been published for C. pneumoniae strains J139 and CUL039. Genome sequences for C. caviae (the former guinea pig inclusion conjunctivitis agent) and for C. abortus have also been published and C. felis has also reportedly been sequenced in Japan. In the Parachlamydiaceae, there is an ongoing Parachlamydia genome sequencing project, preliminary reports of which are given in the CBRS Memphis meeting report. Reports of the results of chlamydial sequencing, and extensive comparisons of chlamydial genomes with themselves [Stephens et al., 1998; Kalman et al., 1999; Read et al., 2000; Makarova et al., 2000; Shirai et al., 2000] and with R. prowazekii [Zomorodipour & Andersson, 1999] have been published in paper and web format. [See also: chlamydial evolution & genomic sequences;  chlamydial genome web links].  

Chlamydiae have a small genome for bacteria [See: chlamydial evolution & genome degradation] just slightly larger than Mycoplasma, (which has the smallest bacterial genome) and about a quarter of the size of the genome of common free-living bacteria such as Bacillus subtilis or Escherichia coli. Within the Chlamydiaceae, the genome of C. pneumoniae is slightly larger than that of C. trachomatis at 1,230,230 base pair (bp) chromosome as opposed to 1,042,519 bp [For comparisons see links given with the Kalman et al., 1999 paper below]. However, C. trachomatis has a 7,493 bp cryptic plasmid (a piece of extra-chromosomal DNA) lacking in the strains of C. pneumoniae so far sequenced. Not to be outdone, Chlamydophila species have phages [bacteriophage ] which Chlamydia species so far lack. 

In C. trachomatis the genome codes for approximately 875 proteins, not all of which are necessarily expressed. Genomic sequencing indicates approximately 70 proteins are exclusive to C. trachomatis but not C. pneumoniae. Conversely, some 200 proteins are unique to  C. pneumoniae but not C. trachomatis [Kalman et al., 1999].

In the case of C. pneumoniae, comparison of the sequences of a Japanese isolate of C. pneumoniae,  strain J138 with that of US isolate CWL 029 showed a nucleotide sequence identity for predicted outer membrane proteins varying between  89.6%-100% (deduced amino acid sequence identity, 71.1%-100%). The overall genomic organization and location of genes was identical in both strains. It was postulated that a few unique sequences of the outer membrane proteins might be sufficient to cause strain specific differences in the biology of C. pneumoniae [Shirai et al., 2000].

Before genomic sequencing, chlamydiae were a "black box", whose genes were largely unknown. The most tangible benefit of chlamydial genomic sequencing has been that we now have a pretty good idea of chlamydial metabolic and synthetic capabilities [Kalman et al., 1999; McClarty 1999]. However no whole genomic sequence data are yet available for Chlamydiales outside the  Chlamydiaceae. Consequently, genomic sequencing has, not yet added much to our understanding of the interrelationships among the Order Chlamydiales or the evolution of these organisms. Generally, the emerging picture is one of a relatively stable genome with few gene rearrangements or differentially expanded gene families. Nevertheless, comparison of the C. pneumoniae and C. trachomatis genomes indicates a region near the putative origin of replication of the chlamydial chromosome, where there is higher genetic diversity than elsewhere [Kalman et al., 1999]. This region includes genes controlling chlamydial tryptophan synthesis and utilisation, which has been implicated in interferon gamma -mediated delayed chlamydial development and persistent infection. In human genital tract C. trachomatis strains and in Ch. muridae this region also includes gene homologues of cytotoxins found in enterohaemorrhagic E. coli O157 and Clostridia respectively [Belland et al., 2001]. Genomic stability may have been increased by the apparent rarity of recombination (genetic exchange) events or of gene duplications in chlamydiae.

The restricted evolutionary path of this group of obligate intracellular micro-organisms, must be unravelled through comprehensive comparative analysis of whole genomic sequences across all families of the Order Chlamydiales. In this respect it is particularly interesting to note that Simkania is so far the only member of the Chlamydiales, or indeed any other bacterium, to have a group 1 intron [Everett et al., 1999], a characteristic pattern of nucleotide bases that is found in amoebae and other higher organisms. Genomic sequencing is relatively easy in chlamydiae because of the small genome and is particularly important given the absence of other tools with which to explore chlamydial gene function. There have already been a number of considerable surprises arising from chlamydial genomic sequencing [see next section]. Expanded comparative whole genomic sequencing should be rewarding in helping to unravel the probable process of chlamydial evolution [see: genome sequencing and evolution].

[MEW] May 2003

NEXT: Surprises from chlamydial genomic sequencing.

Genome web links

References

Belland, R. J., Scidmore, M. A., Crane, D. D., Hogan, D. M., Whitmire, W., McClarty, G. & Caldwell, H. D. (2001). Chlamydia trachomatis cytotoxicity associated with complete and partial cytotoxicity genes. Proceedings of the National Academy of Sciences of the U. S. A. 98, 13984 - 13989. Full article [Acrobat]

Everett K. D. E., Kahane S, Bush R. M.  Friedman, M. G. (1999). An unspliced group I intron in 23S rRNA links Chlamydiales, chloroplasts, and mitochondria. Journal of Bacteriology 181, 4734 - 4740.  Full article

Kalman, S., Mitchell, W., Marathe, R., et al., (1999). Comparative genomes of Chlamydia pneumoniae and C. trachomatis. Nature Genetics 21, 385-389. Full article [Acrobat] Chromosome map C. pneumoniae [Acrobat] Functional assignments table of genes in C. pneumoniae and C. trachomatis  [Acrobat]

Makarova, K. S., Aravind, L. & Koonin, E. V. (2000). A novel superfamily of predicted cysteine proteases from eukaryotes, viruses and Chlamydia pneumoniae. Trends in Biochemical Science 25, 50 - 52

McClarty, G. (1999). Chlamydial metabolism as inferred from the complete genome sequence. Pp 69 - 100 In: (Stephens, R. S. editor) Chlamydia Intracellular Biology, Pathogenesis and Immunity. ASM Press, Washington. ISBN 1-55581-155-8  [Excellent review in an outstanding book

Shirai, M., et al., (2000). Comparison of whole genome sequences of Chlamydia pneumoniae J138 from Japan and CWL029 from USA. Nucleic Acids Res. 28, 2311 - 2314. Full article [Acrobat]

Stephens, R. S. (1999). Genomic autobiographies of chlamydiae. Chapter 2, pp 9 – 27 In: Chlamydia Intracellular Biology, Pathogenesis and Immunity (Stephens, R. S. editor). ASM Press, Washington. ISBN 1-55581-155-8.

Stephens, R. S., Kalman, S., Lammel, C. et al., (1998). Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282, 754 - 759. + [The first genomic sequence, and high quality]

Read, T. D., Brunham, R. C., Shen, C., et al., (2000). Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39. Nucleic Acids Res. 28, 1397 - 1406.Full article [Acrobat]  

Zomorodipour, A, and Andersson, S. G. E. (1999). Obligate intracellular parasites: Rickettsia prowazekii and Chlamydia trachomatis. FEBS Letters 452, 11 - 15.

NEXT: Surprises from chlamydial genomic sequencing.

 


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