Abstract.
An approach for genome comparison, combining function classification of gene products and sequence comparison, is presented. The genomes of Haemophilus influenzae and Escherichia coli are analyzed, and all genes are classified into nine major functional classes, corresponding to important cellular processes. To study gene order relationships and genome organization in the two bacteria, we performed statistics on neighboring pairs of genes. To estimate the significance of the observations, a statistical model based on binomial distributions has been developed. Significant patterns of gene order are observed within, as well as between, the two bacterial genomes: Functionally related genes tend to be neighbors more often than do unrelated genes. Some of these groups represent well-known operons, but additional gene clusters are identified. These clusters correspond to genomic elements that have been conserved during bacterial evolution. In addition to nearest-neighbor relationships, the method is also useful to study the relative direction of transcription in genomes, which is also highly conserved between homologous gene pairs. This new approach combines the high-level description of molecular function with pair statistics that express genome organization. It is expected to complement traditional methods of sequence analysis in the study of genomic structure, function, and evolution.
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References
Adams MD, Kerlavage AR, Fields C, Venter JC (1993) 3,400 new expressed sequence tags identify diversity of transcripts in human brain. Nat Genet 4:256–267
Ahn S, Tanksley SD (1993) Comparative linkage maps of the rice and maize genomes. Proc Natl Acad Sci USA 90:7980–7984
Bairoch A, Boeckmann B (1991) The SWISS-PROT protein sequence data bank. Nucleic Acids Res 19:2247–2250
Bork P, Ouzounis C, Casari G, Schneider R, Sander C, Dolan M, Gilbert W, Gillevet PM (1995) Exploring the Mycoplasma capricolum genome: a minimal cell reveals its physiology. Mol Microbiol 16:955–967
Boudreau E, Otis C, Turmel M (1994) Conserved gene clusters in the highly rearranged chloroplast genomes of Chlamydomonas moewusii and Chlamydomonas reinhardtii. Plant Mol Biol 24:585–602
Casari G, Andrade A, Bork P, Boyle J, Daruvar A, Ouzounis C, Schneider R, Tamames J, Valencia A, Sander C (1995) Challenging times for bioinformatics. Nature 376:647–648
Casari G, Ouzounis C, Valencia A, Sander C (1996) GeneQuiz II: automatic function assignment for genome sequence analysis. In: Hunter L, Klein TE (eds) First annual Pacific symposium on biocomputing. World Scientific, Hawaii, pp 707–709
Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb J-F, Dougherty BA, Merrick JM, McKenney K, Sutton G, FitzHugh W, Fields C, Gocayne JD, Scott J, Shirley R, Liu L-I, Glodek A, Kelley JM, Weidman JF, Phillips CA, Spriggs T, Hedblom E, Cotton MD, Utterback TR, Hanna MC, Nguyen DT, Saudek DM, Brandon RC, Fine LD, Fritchman JL, Fuhrmann JL, Geoghagen NSM, Gnehm CL, McDonald LA, Small KV, Fraser CM, Smith O, Venter JC (1995) Whole-genome random sequencing an assembly of Haemophilus influenzae Rd. Science 269:496–512
Fraser FC, Gocayne JD, White O, Adams MD, Clayton RA, Fleischmann RD, Bult CJ, Kerlavage AR, Sutton G, Kelley JM, Fritchman JL, Weidman JF, Small KV, Sandusky M, Fuhrmann J, Nguyen D, Utterback TR, Saudek DM, Phillips CA, Merrick JM, Tomb J-F, Dougherty BA, Bott KF, Hu P-C, Lucier TS, Peterson SN, Smith HO, Hutchison CAI, Venter JC (1995) The minimal gene complement of Mycoplasma genitalium. Science 270:397–403
Gompels UA, Nicholas J, Lawrence G, Jones M, Thomson BJ, Martin ME, Efstathiou S, Craxton M, Macaulay HA (1995) The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution. Virology 209:29–51
Irving NG, Cabin DE, Swanson DA, Reeves RH (1994) Gene order is conserved within the human chromosome 21 linkage group on mouse chromosome 10. Genomics 21:144–149
Johansson M, Ellegren H, Andersson L (1995) Comparative mapping reveals extensive linkage conservation but with gene order rearrangements-between the pig and the human genomes. Genomics 25:682–690
Karlin S, Ladunga I (1994) Comparisons of eukaryotic genomic sequences. Proc Natl Acad Sci USA 91:12832–12836
Keeling PJ, Charlebois RL, Doolittle WF (1994) Archaebacterial genomes: eubacterial form and eukaryotic content. Curr Opin Genet Dev 4:816–822
Kingsmore SF, Watson ML, Howard TA, Seldin MF (1989) A 6000 Kb segment of chromosome 1 is conserved in human and mouse. EMBO J 8:4073–4080
Kunisawa T (1995) Identification and chromosomal distribution of DNA sequence segments conserved since divergence of Escherichia coli and Bacillus subtilis. J Mol Evol 40:585–593
Liu SL, Sanderson KE (1995) Rearrangements in the genome of the bacterium Salmonella typhi. Proc Natl Acad Sci USA 92:1018–1022
Lopez-Garcia P, St Jean A, Amils R, Charlebois RL (1995) Genomic stability in the archaeae Haloferax volcanii and Haloferax mediterraneii. J Bacteriol 177:1405–1408
Lundin LG (1979) Evolutionary conservation of large chromosomal segments reflected in mammalian gene maps. Clin Genet 16:72–81
O’Brien SJ, Seuanez HN, Womack JE (1988) Mammalian genome organization: an evolutionary view. Annu Rev Genet 22:323–351
Ouzounis C, Valencia A, Tamames J, Bork P, Sander C (1995) The functional composition of living machines as a design principle for artificial organisms. In: Morán F, Moreno A, Merelo JJ, Chacón P (eds) European conference on artificial life 1995 (ECAL95). Springer-Verlag, Granada, Spain, pp 843–851
Ouzounis C, Casari G, Valencia A, Sander C (1996) Novelties from the complete genome of Mycoplasma genitalium. Mol Microbiol 20: 897–899
Riley M (1993) Functions of the gene products of Escherichia coli. Microbiol Rev 57:862–952
Rogatko A, Zacks S (1989) Statistical inference in the gene order problem: theoretical aspects. Prog Clin Biol Res 329:63–68
Rudd KE (1993) Maps, genes, sequences, and computers: an Escherichia coli case study. ASM News 59:335–341
Sankoff D, Goldstein M (1989) Probabilistic models of genome shuffling. Bull Math Biol 51:117–124
Sankoff D, Leduc G, Antoine N, Paquin B, Lang BF, Cedergren R (1992) Gene order comparisons for phylogenetic inference: evolution of the mitochondrial genome. Proc Natl Acad Sci USA 89: 6575–6579
Shapiro JA (1982) Changes in gene order and gene expression. Natl Cancer Inst Monogr 60:87–110
Tamames J, Ouzounis C, Sander C, Valencia A (1996) Genomes with distinct functional composition. FEBS Lett 389:96-101 Zakharov IA, Nikiforov VS, Stepaniuk EV (1992) Homology and evolution of gene orders: combinatorial measure of synteny group similarity and simulation of the evolution process. Genetika 28:77–81
Zorio DAR, Cheng NN, Blumenthal T, Spieth J (1994) Operons as a common form of chromosomal organization in C. elegans. Nature 372:270–273
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Received: 6 June 1996 / Accepted: 9 July 1996
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Tamames, J., Casari, G., Ouzounis, C. et al. Conserved Clusters of Functionally Related Genes in Two Bacterial Genomes. J Mol Evol 44, 66–73 (1997). https://doi.org/10.1007/PL00006122
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DOI: https://doi.org/10.1007/PL00006122