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References of genome data Comparative genomic analysis was performed, using 23 complete prokaryotic genomes : Haemophilus influenzae1 (NC_000907), Mycoplasma genitalium2 (NC_000908), Methanococcus jannaschii3 (NC_000909), Synechocystis sp.4 (NC_000911), Mycoplasma pneumoniae5 (NC_000912), Helicobacter pylori 266956 (NC_000915), Helicobacter pylori J997 (NC_000921), Escherichia coli8 (NC_000913), Methanobacterium thermoautotrophicum9 (NC_000916), Bacillus subtilis10 (NC_000964), Archaeoglobus fulgidus11 (NC_000917), Borrelia burgdorferi12 (NC_001318), Aquifex aeolicus13 (NC_000918), Pyrococcus horikoshii 14 (NC_000961), Pyrococcus abyssi (NC_000868), Mycobacterium tuberculosis15 (NC_000962), Treponema pallidum 16 (NC_000919), Chlamydia trachomatis17 (NC_000117), Rickettsia prowazekii18 (NC_000963), Chlamydia pneumoniae19 (NC_000922), Aeropyrum pernix 20 (NC_000854), Thermotoga maritina 21 (NC_000853), and Buchnera sp. APS. These sequence data, except Buchnera genome, were obtained from Entrez Genomes at NCBI website (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome). 1. Fleischmann, R. D. et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269, 496-512 (1995). 2. Fraser, C. M. et al. The minimal gene complement of Mycoplasma genitalium. Science 270, 397-403 (1995). 3. Bult, C. J. et al. Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Science 273, 1058-1073 (1996). 4. Kaneko, T. et al. Sequence analysis of the genome of the unicellular cyanobacterium Synechocystis sp. strain PCC6803. II. Sequence determination of the entire genome and assignment of potential protein-coding regions. DNA Res 3, 109-136 (1996). 5. Himmelreich, R. et al. Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae. Nucleic Acids Res. 24, 4420-4449 (1996). 6. Tomb, J. F. et al. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388, 539-547 (1997). 7. Alm, R. A. et al. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397, 176-180 (1999). 8. Blattner, F. R. et al. The complete genome sequence of Escherichia coli K-12. Science 277, 1453-1474 (1997). 9. Smith, D. R. et al. Complete genome sequence of Methanobacterium thermoautotrophicum deltaH: functional analysis and comparative genomics. J Bacteriol 179, 7135-7155 (1997). 10. Kunst, F. et al. The complete genome sequence of the gram-positive bacterium Bacillus subtilis. Nature 390, 249-256 (1997). 11. Klenk, H. P. et al. The complete genome sequence of the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus. Nature 390, 364-370 (1997). 12. Fraser, C. M. et al. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390, 580-586 (1997). 13. Deckert, G. et al. The complete genome of the hyperthermophilic bacterium Aquifex aeolicus. Nature 392, 353-358 (1998). 14. Kawarabayasi, Y. et al. Complete sequence and gene organization of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3 (supplement). DNA Res 5, 147-155 (1998). 15. Cole, S. T. et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537-544 (1998). 16. Fraser, C. M. et al. Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281, 375-388 (1998). 17. Stephens, R. S. et al. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282, 754-759 (1998). 18. Andersson, S. G. et al. The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396, 133-140 (1998). 19. Kalman, S. et al. Comparative genomes of Chlamydia pneumoniae and C. trachomatis. Nat. Genet. 21, 385-389 (1999). 20. Kawarabayasi, Y. et al. Complete genome sequence of an aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1. DNA Res 6, 83-101, 145-152 (1999). 21. Nelson, K. E. et al. Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima. Nature 399, 323-329 (1999).