Skip to main content

Understanding the commonalities and differences in genomic organizations across closely related bacteria from an energy perspective

Abstract

The availability of a large number of sequenced bacterial genomes facilitates in-depth studies about why genes (operons) in a bacterial genome are globally organized the way they are. We have previously discovered that (the relative) transcription- activation frequencies among different biological pathways encoded in a genome have a dominating role in the global arrangement of operons. One complicating factor in such a study is that some operons may be involved in multiple pathways with different activation frequencies. A quantitative model has been developed that captures this information, which tends to be minimized by the current global arrangement of operons in a bacterial (and archaeal) genome compared to possible alternative arrangements. A study is carried out here using this model on a collection of 52 closely related E. coli genomes, which revealed interesting new insights about how bacterial genomes evolve to optimally adapt to their environments through adjusting the (relative) genomic locations of the encoding operons of biological pathways once their utilization and hence transcription activation frequencies change, to maintain the above energy-efficiency property. More specifically we observed that it is the frequencies of the transcription activation of pathways relative to those of the other encoded pathways in an organism as well as the variation in the activation frequencies of a specific pathway across the related genomes that play a key role in the observed commonalities and differences in the genomic organizations of genes (and operons) encoding specific pathways across different genomes.

References

  1. 1

    Breed RS, Conn HJ. The Status of the Generic Term Bacterium Ehrenberg 1828. J Bacteriol, 1936, 31: 517–518

    PubMed  CAS  PubMed Central  Google Scholar 

  2. 2

    Jacob F, Perrin D, Sanchez C, Monod J. Operon: a group of genes with the expression coordinated by an operator. C R Hebd Seances Acad Sci, 1960, 250: 1727–1729

    PubMed  CAS  Google Scholar 

  3. 3

    Manson McGuire A, Church GM. Predicting regulons and their cis-regulatory motifs by comparative genomics. Nucleic Acids Res, 2000, 28: 4523–4530

    PubMed  CAS  Article  Google Scholar 

  4. 4

    Stock AM, Robinson VL, Goudreau PN. Two-component signal transduction. Ann Rev Biochem, 2000, 69: 183–215

    PubMed  CAS  Article  Google Scholar 

  5. 5

    Mao X, Ma Q, Zhou C, Chen X, Zhang H, Yang J, Mao F, Lai W, Xu Y. DOOR 2.0: presenting operons and their functions through dynamic and integrated views. Nucleic Acids Res, 2014, 42: D654–659

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  6. 6

    Salgado H, Peralta-Gil M, Gama-Castro S, Santos-Zavaleta A, Muniz-Rascado L, Garcia-Sotelo JS, Weiss V, Solano-Lira H, Martinez-Flores I, Medina-Rivera A, Salgado-Osorio G, Alquicira-Hernandez S, Alquicira-Hernandez K, Lopez-Fuentes A, Porron-Sotelo L, Huerta AM, Bonavides-Martinez C, Balderas-Martinez YI, Pannier L, Olvera M, Labastida A, Jimenez-Jacinto V, Vega-Alvarado L, Del Moral-Chavez V, Hernandez-Alvarez A, Morett E, Collado-Vides J. RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more. Nucleic Acids Res, 2013, 41: D203–213

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  7. 7

    Kanehisa M, Goto S, Sato Y, Kawashima M, Furumichi M, Tanabe M. Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res, 2014, 42: D199–205

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  8. 8

    Medini D, Donati C, Tettelin H, Masignani V, Rappuoli R. The microbial pan-genome. Curr Opin Genet Dev, 2005, 15: 589–594

    PubMed  CAS  Article  Google Scholar 

  9. 9

    Dillon SC, Dorman CJ. Bacterial nucleoid-associated proteins, nucleoid structure and gene expression. Nat Rev Microbiol, 2010, 8: 185–195

    PubMed  CAS  Article  Google Scholar 

  10. 10

    Benza VG, Bassetti B, Dorfman KD, Scolari VF, Bromek K, Cicuta P, Lagomarsino MC. Physical descriptions of the bacterial nucleoid at large scales, and their biological implications. Rep Prog Phys Phys Soc, 2012, 75: 076602

    Article  Google Scholar 

  11. 11

    Ma Q, Yin Y, Schell MA, Zhang H, Li G, Xu Y. Computational analyses of transcriptomic data reveal the dynamic organization of the Escherichia coli chromosome under different conditions. Nucleic Acids Res, 2013, 41: 5594–5603

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  12. 12

    Ma Q, Xu Y. Global Genomic arrangement of bacterial genes is closely tied with the total transcriptional efficiency. Genom Proteom Bioinform, 2013, 11: 66–71

    Article  Google Scholar 

  13. 13

    Blattner FR, Plunkett G, 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y. The complete genome sequence of Escherichia coli K-12. Science, 1997, 277: 1453–1462

    PubMed  CAS  Article  Google Scholar 

  14. 14

    Hayashi T, Makino K, Ohnishi M, Kurokawa K, Ishii K, Yokoyama K, Han CG, Ohtsubo E, Nakayama K, Murata T, Tanaka M, Tobe T, Iida T, Takami H, Honda T, Sasakawa C, Ogasawara N, Yasunaga T, Kuhara S, Shiba T, Hattori M, Shinagawa H. Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res, 2001, 8: 11–22

    PubMed  CAS  Article  Google Scholar 

  15. 15

    Welch RA, Burland V, Plunkett G, 3rd, Redford P, Roesch P, Rasko D, Buckles EL, Liou SR, Boutin A, Hackett J, Stroud D, Mayhew GF, Rose DJ, Zhou S, Schwartz DC, Perna NT, Mobley HL, Donnenberg MS, Blattner FR. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci USA, 2002, 99: 17020–17024

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  16. 16

    Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, 3rd, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL. Escherichia coli K-12: a cooperatively developed annotation snapshot-2005. Nucleic Acids Res, 2006, 34: 1–9

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  17. 17

    Chen SL, Hung CS, Xu J, Reigstad CS, Magrini V, Sabo A, Blasiar D, Bieri T, Meyer RR, Ozersky P, Armstrong JR, Fulton RS, Latreille JP, Spieth J, Hooton TM, Mardis ER, Hultgren SJ, Gordon JI. Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach. Proc Natl Acad Sci USA, 2006, 103: 5977–5982

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  18. 18

    Johnson TJ, Wannemeuhler YM, Scaccianoce JA, Johnson SJ, Nolan LK. Complete DNA sequence, comparative genomics, and prevalence of an IncHI2 plasmid occurring among extraintestinal pathogenic Escherichia coli isolates. Antimicrob Agents Chemother, 2006, 50: 3929–3933

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  19. 19

    Rasko DA, Rosovitz MJ, Myers GS, Mongodin EF, Fricke WF, Gajer P, Crabtree J, Sebaihia M, Thomson NR, Chaudhuri R, Henderson IR, Sperandio V, Ravel J. The pangenome structure of Escherichia coli: comparative genomic analysis of E. coli commensal and pathogenic isolates. J Bacteriol, 2008, 190: 6881–6893

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  20. 20

    Durfee T, Nelson R, Baldwin S, Plunkett G, 3rd, Burland V, Mau B, Petrosino JF, Qin X, Muzny DM, Ayele M, Gibbs RA, Csorgo B, Posfai G, Weinstock GM, Blattner FR. The complete genome sequence of Escherichia coli DH10B: insights into the biology of a laboratory workhorse. J Bacteriol, 2008, 190: 2597–2606

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  21. 21

    Fricke WF, Wright MS, Lindell AH, Harkins DM, Baker-Austin C, Ravel J, Stepanauskas R. Insights into the environmental resistance gene pool from the genome sequence of the multidrug-resistant environmental isolate Escherichia coli SMS-3-5. J Bacteriol, 2008, 190: 6779–6794

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  22. 22

    Eppinger M, Mammel MK, Leclerc JE, Ravel J, Cebula TA. Genomic anatomy of Escherichia coli O157:H7 outbreaks. Proc Natl Acad Sci USA, 2011, 108: 20142–20147

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  23. 23

    Oshima K, Toh H, Ogura Y, Sasamoto H, Morita H, Park SH, Ooka T, Iyoda S, Taylor TD, Hayashi T, Itoh K, Hattori M. Complete genome sequence and comparative analysis of the wild-type commensal Escherichia coli strain SE11 isolated from a healthy adult. DNA Res, 2008, 15: 375–386

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  24. 24

    Iguchi A, Thomson NR, Ogura Y, Saunders D, Ooka T, Henderson IR, Harris D, Asadulghani M, Kurokawa K, Dean P, Kenny B, Quail MA, Thurston S, Dougan G, Hayashi T, Parkhill J, Frankel G. Complete genome sequence and comparative genome analysis of enteropathogenic Escherichia coli O127:H6 strain E2348/69. J Bacteriol, 2009, 191: 347–354

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  25. 25

    Touchon M, Hoede C, Tenaillon O, Barbe V, Baeriswyl S, Bidet P, Bingen E, Bonacorsi S, Bouchier C, Bouvet O, Calteau A, Chiapello H, Clermont O, Cruveiller S, Danchin A, Diard M, Dossat C, Karoui ME, Frapy E, Garry L, Ghigo JM, Gilles AM, Johnson J, Le Bouguenec C, Lescat M, Mangenot S, Martinez-Jehanne V, Matic I, Nassif X, Oztas S, Petit MA, Pichon C, Rouy Z, Ruf CS, Schneider D, Tourret J, Vacherie B, Vallenet D, Medigue C, Rocha EP, Denamur E. Organised genome dynamics in the Escherichia coli species results in highly diverse adaptive paths. PLoS Genet, 2009, 5: e1000344

    PubMed  PubMed Central  Article  Google Scholar 

  26. 26

    Ferenci T, Zhou Z, Betteridge T, Ren Y, Liu Y, Feng L, Reeves PR, Wang L. Genomic sequencing reveals regulatory mutations and recombinational events in the widely used MC4100 lineage of Escherichia coli K-12. J Bacteriol, 2009, 191: 4025–4029

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  27. 27

    Jeong H, Barbe V, Lee CH, Vallenet D, Yu DS, Choi SH, Couloux A, Lee SW, Yoon SH, Cattolico L, Hur CG, Park HS, Segurens B, Kim SC, Oh TK, Lenski RE, Studier FW, Daegelen P, Kim JF. Genome sequences of Escherichia coli B strains REL606 and BL21(DE3). J Mol Biol, 2009, 394: 644–652

    PubMed  CAS  Article  Google Scholar 

  28. 28

    Kulasekara BR, Jacobs M, Zhou Y, Wu Z, Sims E, Saenphimmachak C, Rohmer L, Ritchie JM, Radey M, McKevitt M, Freeman TL, Hayden H, Haugen E, Gillett W, Fong C, Chang J, Beskhlebnaya V, Waldor MK, Samadpour M, Whittam TS, Kaul R, Brittnacher M, Miller SI. Analysis of the genome of the Escherichia coli O 157:H7 2006 spinach-associated outbreak isolate indicates candidate genes that may enhance virulence. Infect Immun, 2009, 77: 3713–3721

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  29. 29

    Ogura Y, Ooka T, Iguchi A, Toh H, Asadulghani M, Oshima K, Kodama T, Abe H, Nakayama K, Kurokawa K, Tobe T, Hattori M, Hayashi T. Comparative genomics reveal the mechanism of the parallel evolution of O157 and non-O157 enterohemorrhagic Escherichia coli. Proc Natl Acad Sci USA, 2009, 106: 17939–17944

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  30. 30

    Toh H, Oshima K, Toyoda A, Ogura Y, Ooka T, Sasamoto H, Park SH, Iyoda S, Kurokawa K, Morita H, Itoh K, Taylor TD, Hayashi T, Hattori M. Complete genome sequence of the wild-type commensal Escherichia coli strain SE15, belonging to phylogenetic group B2. J Bacteriol, 2010, 192: 1165–1166

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  31. 31

    Zhou Z, Li X, Liu B, Beutin L, Xu J, Ren Y, Feng L, Lan R, Reeves PR, Wang L. Derivation of Escherichia coli O157:H7 from its O55:H7 precursor. PLoS One, 2010, 5: e8700

    PubMed  PubMed Central  Article  Google Scholar 

  32. 32

    Turner PC, Yomano LP, Jarboe LR, York SW, Baggett CL, Moritz BE, Zentz EB, Shanmugam KT, Ingram LO. Optical mapping and sequencing of the Escherichia coli KO11 genome reveal extensive chromosomal rearrangements, and multiple tandem copies of the Zymomonas mobilis pdc and adhB genes. J Ind Microbiol Biotechnol, 2012, 39: 629–639

    PubMed  CAS  Article  Google Scholar 

  33. 33

    Moriel DG, Bertoldi I, Spagnuolo A, Marchi S, Rosini R, Nesta B, Pastorello I, Corea VA, Torricelli G, Cartocci E, Savino S, Scarselli M, Dobrindt U, Hacker J, Tettelin H, Tallon LJ, Sullivan S, Wieler LH, Ewers C, Pickard D, Dougan G, Fontana MR, Rappuoli R, Pizza M, Serino L. Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli. Proc Natl Acad Sci USA, 2010, 107: 9072–9077

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  34. 34

    Zdziarski J, Brzuszkiewicz E, Wullt B, Liesegang H, Biran D, Voigt B, Gronberg-Hernandez J, Ragnarsdottir B, Hecker M, Ron EZ, Daniel R, Gottschalk G, Hacker J, Svanborg C, Dobrindt U. Host imprints on bacterial genomes-rapid, divergent evolution in individual patients. PLoS Pathog, 2010, 6: e1001078

    PubMed  PubMed Central  Article  Google Scholar 

  35. 35

    Krause DO, Little AC, Dowd SE, Bernstein CN. Complete genome sequence of adherent invasive Escherichia coli UM146 isolated from Ileal Crohn’s disease biopsy tissue. J Bacteriol, 2011, 193: 583

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  36. 36

    Crossman LC, Chaudhuri RR, Beatson SA, Wells TJ, Desvaux M, Cunningham AF, Petty NK, Mahon V, Brinkley C, Hobman JL, Savarino SJ, Turner SM, Pallen MJ, Penn CW, Parkhill J, Turner AK, Johnson TJ, Thomson NR, Smith SG, Henderson IR. A commensal gone bad: complete genome sequence of the prototypical enterotoxigenic Escherichia coli strain H10407. J Bacteriol, 2010, 192: 5822–5831

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  37. 37

    Nash JH, Villegas A, Kropinski AM, Aguilar-Valenzuela R, Konczy P, Mascarenhas M, Ziebell K, Torres AG, Karmali MA, Coombes BK. Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes. BMC Genomics, 2010, 11: 667

    PubMed  PubMed Central  Article  Google Scholar 

  38. 38

    Suzuki S, Ono N, Furusawa C, Ying BW, Yomo T. Comparison of sequence reads obtained from three next-generation sequencing platforms. PLoS One, 2011, 6: e19534

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  39. 39

    Fernandez-Alarcon C, Singer RS, Johnson TJ. Comparative genomics of multidrug resistance-encoding IncA/C plasmids from commensal and pathogenic Escherichia coli from multiple animal sources. PLoS One, 2011, 6: e23415

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  40. 40

    Avasthi TS, Kumar N, Baddam R, Hussain A, Nandanwar N, Jadhav S, Ahmed N. Genome of multidrug-resistant uropathogenic Escherichia coli strain NA114 from India. J Bacteriol, 2011, 193: 4272–4273

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  41. 41

    Lu S, Zhang X, Zhu Y, Kim KS, Yang J, Jin Q. Complete genome sequence of the neonatal-meningitis-associated Escherichia coli strain CE10. J Bacteriol, 2011, 193: 7005

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  42. 42

    Reeves PR, Liu B, Zhou Z, Li D, Guo D, Ren Y, Clabots C, Lan R, Johnson JR, Wang L. Rates of mutation and host transmission for an Escherichia coli clone over 3 years. PLoS One, 2011, 6: e26907

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  43. 43

    Kyle JL, Cummings CA, Parker CT, Quinones B, Vatta P, Newton E, Huynh S, Swimley M, Degoricija L, Barker M, Fontanoz S, Nguyen K, Patel R, Fang R, Tebbs R, Petrauskene O, Furtado M, Mandrell RE. Escherichia coli serotype O55:H7 diversity supports parallel acquisition of bacteriophage at Shiga toxin phage insertion sites during evolution of the O157:H7 lineage. J Bacteriol, 2012, 194: 1885–1896

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  44. 44

    Liu B, Hu B, Zhou Z, Guo D, Guo X, Ding P, Feng L, Wang L. A novel non-homologous recombination-mediated mechanism for Escherichia coli unilateral flagellar phase variation. Nucleic Acids Res, 2012, 40: 4530–4538

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  45. 45

    Ahmed SA, Awosika J, Baldwin C, Bishop-Lilly KA, Biswas B, Broomall S, Chain PS, Chertkov O, Chokoshvili O, Coyne S, Davenport K, Detter JC, Dorman W, Erkkila TH, Folster JP, Frey KG, George M, Gleasner C, Henry M, Hill KK, Hubbard K, Insalaco J, Johnson S, Kitzmiller A, Krepps M, Lo CC, Luu T, McNew LA, Minogue T, Munk CA, Osborne B, Patel M, Reitenga KG, Rosenzweig CN, Shea A, Shen X, Strockbine N, Tarr C, Teshima H, van Gieson E, Verratti K, Wolcott M, Xie G, Sozhamannan S, Gibbons HS, Threat Characterization C. Genomic comparison of Escherichia coli O104:H4 isolates from 2009 and 2011 reveals plasmid, and prophage heterogeneity, including shiga toxin encoding phage stx2. PLoS One, 2012, 7: e48228

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  46. 46

    Barrett T, Edgar R. Reannotation of array probes at NCBI’s GEO database. Nat Methods, 2008, 5: 117

    PubMed  CAS  Article  Google Scholar 

  47. 47

    Faith JJ, Driscoll ME, Fusaro VA, Cosgrove EJ, Hayete B, Juhn FS, Schneider SJ, Gardner TS. Many Microbe Microarrays Database: uniformly normalized Affymetrix compendia with structured experimental metadata. Nucleic Acids Res, 2008, 36: D866–870

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  48. 48

    Lemuth K, Hardiman T, Winter S, Pfeiffer D, Keller MA, Lange S, Reuss M, Schmid RD, Siemann-Herzberg M. Global transcription and metabolic flux analysis of Escherichia coli in glucose-limited fed-batch cultivations. Appl Environ Microbiol, 2008, 74: 7002–7015

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  49. 49

    Abe H, Miyahara A, Oshima T, Tashiro K, Ogura Y, Kuhara S, Ogasawara N, Hayashi T, Tobe T. Global regulation by horizontally transferred regulators establishes the pathogenicity of Escherichia coli. DNA Res, 2008, 15: 25–38

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  50. 50

    Sahl JW, Rasko DA. Analysis of global transcriptional profiles of enterotoxigenic Escherichia coli isolate E24377A. Infect Immun, 2012, 80: 1232–1242

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  51. 51

    Eashwar Rajaraman MAE. Transcriptional analysis and adaptive evolution of Escherichia coli growing on acetate. Dissertation for Doctoral Degree. Athens: University of Georgia, 2012

    Google Scholar 

  52. 52

    Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol, 2004, 5: R80

    PubMed  PubMed Central  Article  Google Scholar 

  53. 53

    Li G, Ma Q, Mao X, Yin Y, Zhu X, Xu Y. Integration of sequence- similarity and functional association information can overcome intrinsic problems in orthology mapping across bacterial genomes. Nucleic Acids Res, 2011, 39: e150

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  54. 54

    Enright AJ, Van Dongen S, Ouzounis CA. An efficient algorithm for large-scale detection of protein families. Nucleic Acids Res, 2002, 30: 1575–1584

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  55. 55

    Yin Y, Zhang H, Olman V, Xu Y. Genomic arrangement of bacterial operons is constrained by biological pathways encoded in the genome. Proc Natl Acad Sci USA, 2010, 107: 6310–6315

    PubMed  CAS  PubMed Central  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Ying Xu.

Additional information

Contributed equally to this work

This article is published with open access at link.springer.com

Electronic supplementary material

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ma, Q., Chen, X., Liu, C. et al. Understanding the commonalities and differences in genomic organizations across closely related bacteria from an energy perspective. Sci. China Life Sci. 57, 1121–1130 (2014). https://doi.org/10.1007/s11427-014-4734-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-014-4734-y

Keywords

  • genomic organization
  • transcription activation frequency
  • pathway modeling
  • comparative genomics analysis