Gene Essentiality Analysis Based on DEG 10, an Updated Database of Essential Genes

  • Feng Gao
  • Hao Luo
  • Chun-Ting Zhang
  • Ren ZhangEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1279)


The database of essential genes (DEG, available at, constructed in 2003, has been timely updated to harbor essential-gene records of bacteria, archaea, and eukaryotes. DEG 10, the current release, includes not only essential protein-coding genes determined by genome-wide gene essentiality screens but also essential noncoding RNAs, promoters, regulatory sequences, and replication origins. Therefore, DEG 10 includes essential genomic elements under different conditions in three domains of life, with customizable BLAST tools. Based on the analysis of DEG 10, we show that the percentage of essential genes in bacterial genomes exhibits an exponential decay with increasing genome sizes. The functions, ATP binding (GO:0005524), GTP binding (GO:0005525), and DNA-directed RNA polymerase activity (GO:0003899), are likely required for organisms across life domains.

Key words

DEG Gene ontology GO terms Essential gene Enrichment analysis 



The present work was supported in part by a startup fund from Wayne State University to R.Z., the National Natural Science Foundation of China (Grant Nos. 31171238 and 30800642 to F.G. and 90408028 to C.T.Z.), and Program for New Century Excellent Talents in University (No. NCET-12-0396) to F.G.


  1. 1.
    Juhas M, Eberl L, Church GM (2012) Essential genes as antimicrobial targets and cornerstones of synthetic biology. Trends Biotechnol 30:601–607PubMedCrossRefGoogle Scholar
  2. 2.
    Henkel J, Maurer SM (2009) Parts, property and sharing. Nat Biotechnol 27:1095–1098PubMedCrossRefGoogle Scholar
  3. 3.
    de S Cameron NM, Caplan A (2009) Our synthetic future. Nat Biotechnol 27:1103–1105PubMedCrossRefGoogle Scholar
  4. 4.
    May M (2009) Engineering a new business. Nat Biotechnol 27:1112–1120PubMedCrossRefGoogle Scholar
  5. 5.
    Pennisi E (2010) Synthetic genome brings new life to bacterium. Science 328:958–959PubMedCrossRefGoogle Scholar
  6. 6.
    Koonin EV (2000) How many genes can make a cell: the minimal-gene-set concept. Annu Rev Genomics Hum Genet 1:99–116PubMedCrossRefGoogle Scholar
  7. 7.
    Zhang R, Ou HY, Zhang CT (2004) DEG: a database of essential genes. Nucleic Acids Res 32:D271–D272PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Luo H, Lin Y, Gao F, Zhang C-T, Zhang R (2014) DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements. Nucleic Acids Res 42:D574–D580PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Mushegian AR, Koonin EV (1996) A minimal gene set for cellular life derived by comparison of complete bacterial genomes. Proc Natl Acad Sci U S A 93:10268–10273PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Kobayashi K, Ehrlich SD, Albertini A, Amati G, Andersen KK, Arnaud M et al (2003) Essential Bacillus subtilis genes. Proc Natl Acad Sci U S A 100:4678–4683PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Rocha EP, Danchin A (2003) Essentiality, not expressiveness, drives gene-strand bias in bacteria. Nat Genet 34:377–378PubMedCrossRefGoogle Scholar
  12. 12.
    Jordan IK, Rogozin IB, Wolf YI, Koonin EV (2002) Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. Genome Res 12:962–968PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Gustafson AM, Snitkin ES, Parker SC, Delisi C, Kasif S (2006) Towards the identification of essential genes using targeted genome sequencing and comparative analysis. BMC Genomics 7:265PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Gao F, Zhang RR (2011) Enzymes are enriched in bacterial essential genes. PLoS One 6:e21683PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Lin Y, Gao F, Zhang CT (2010) Functionality of essential genes drives gene strand-bias in bacterial genomes. Biochem Biophys Res Commun 396:472–476PubMedCrossRefGoogle Scholar
  16. 16.
    Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM et al (2000) Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat Genet 25:25–29PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Jensen LJ, Gupta R, Staerfeldt HH, Brunak S (2003) Prediction of human protein function according to gene ontology categories. Bioinformatics 19:635–642PubMedCrossRefGoogle Scholar
  18. 18.
    Chou KC, Cai YD (2003) A new hybrid approach to predict subcellular localization of proteins by incorporating gene ontology. Biochem Biophys Res Commun 311:743–747PubMedCrossRefGoogle Scholar
  19. 19.
    Wu X, Zhu L, Guo J, Zhang DY, Lin K (2006) Prediction of yeast protein-protein interaction network: insights from the gene ontology and annotations. Nucleic Acids Res 34:2137–2150PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Dimmer EC, Huntley RP, Alam-Faruque Y, Sawford T, O’donovan C, Martin MJ et al (2012) The UniProt-GO annotation database in 2011. Nucleic Acids Res 40:D565–D570PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57CrossRefGoogle Scholar
  22. 22.
    Hulsen T, De Vlieg J, Alkema W (2008) BioVenn—a web application for the comparison and visualization of biological lists using area-proportional Venn diagrams. BMC Genomics 9:488PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Griffin JE, Gawronski JD, Dejesus MA, Ioerger TR, Akerley BJ, Sassetti CM (2011) High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. PLoS Pathog 7:e1002251PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Zhang YJ, Ioerger TR, Huttenhower C, Long JE, Sassetti CM, Sacchettini JC et al (2012) Global assessment of genomic regions required for growth in Mycobacterium tuberculosis. PLoS Pathog 8:e1002946PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Sassetti CM, Boyd DH, Rubin EJ (2003) Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48:77–84PubMedCrossRefGoogle Scholar
  26. 26.
    Goodman AL, Mcnulty NP, Zhao Y, Leip D, Mitra RD, Lozupone CA et al (2009) Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe 6:279–289PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Klein BA, Tenorio EL, Lazinski DW, Camilli A, Duncan MJ, Hu LT (2012) Identification of essential genes of the periodontal pathogen Porphyromonas gingivalis. BMC Genomics 13:578PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Commichau FM, Pietack N, Stulke J (2013) Essential genes in Bacillus subtilis: a re-evaluation after ten years. Mol Biosyst 9:1068–1075PubMedCrossRefGoogle Scholar
  29. 29.
    Chaudhuri RR, Allen AG, Owen PJ, Shalom G, Stone K, Harrison M et al (2009) Comprehensive identification of essential Staphylococcus aureus genes using Transposon-Mediated Differential Hybridisation (TMDH). BMC Genomics 10:291PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Xu P, Ge X, Chen L, Wang X, Dou Y, Xu JZ et al (2011) Genome-wide essential gene identification in Streptococcus sanguinis. Sci Rep 1:125PubMedCentralPubMedGoogle Scholar
  31. 31.
    De Berardinis V, Vallenet D, Castelli V, Besnard M, Pinet A, Cruaud C et al (2008) A complete collection of single-gene deletion mutants of Acinetobacter baylyi ADP1. Mol Syst Biol 4:174PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Baugh L, Gallagher LA, Patrapuvich R, Clifton MC, Gardberg AS, Edwards TE et al (2013) Combining functional and structural genomics to sample the essential Burkholderia structome. PLoS One 8:e53851PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Metris A, Reuter M, Gaskin DJ, Baranyi J, Van Vliet AH (2011) In vivo and in silico determination of essential genes of Campylobacter jejuni. BMC Genomics 12:535PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Christen B, Abeliuk E, Collier JM, Kalogeraki VS, Passarelli B, Coller JA et al (2011) The essential genome of a bacterium. Mol Syst Biol 7:528PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD et al (2003) Experimental determination and system level analysis of essential genes in Escherichia coli MG1655. J Bacteriol 185:5673–5684PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M et al (2006) Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol 2:2006 0008PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Gallagher LA, Ramage E, Jacobs MA, Kaul R, Brittnacher M, Manoil C (2007) A comprehensive transposon mutant library of Francisella novicida, a bioweapon surrogate. Proc Natl Acad Sci U S A 104:1009–1014PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Akerley BJ, Rubin EJ, Novick VL, Amaya K, Judson N, Mekalanos JJ (2002) A genome-scale analysis for identification of genes required for growth or survival of Haemophilus influenzae. Proc Natl Acad Sci U S A 99:966–971PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Salama NR, Shepherd B, Falkow S (2004) Global transposon mutagenesis and essential gene analysis of Helicobacter pylori. J Bacteriol 186:7926–7935PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Liberati NT, Urbach JM, Miyata S, Lee DG, Drenkard E, Wu G et al (2006) An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants. Proc Natl Acad Sci U S A 103:2833–2838PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Gallagher LA, Shendure J, Manoil C (2011) Genome-scale identification of resistance functions in Pseudomonas aeruginosa using Tn-seq. MBio 2:e00315–e00310PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Barquist L, Langridge GC, Turner DJ, Phan MD, Turner AK, Bateman A et al (2013) A comparison of dense transposon insertion libraries in the Salmonella serovars Typhi and Typhimurium. Nucleic Acids Res 41:4549–4564PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Langridge GC, Phan MD, Turner DJ, Perkins TT, Parts L, Haase J et al (2009) Simultaneous assay of every Salmonella Typhi gene using one million transposon mutants. Genome Res 19:2308–2316PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Khatiwara A, Jiang T, Sung SS, Dawoud T, Kim JN, Bhattacharya D et al (2012) Genome scanning for conditionally essential genes in Salmonella enterica Serotype Typhimurium. Appl Environ Microbiol 78:3098–3107PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Knuth K, Niesalla H, Hueck CJ, Fuchs TM (2004) Large-scale identification of essential Salmonella genes by trapping lethal insertions. Mol Microbiol 51:1729–1744PubMedCrossRefGoogle Scholar
  46. 46.
    Deutschbauer A, Price MN, Wetmore KM, Shao W, Baumohl JK, Xu Z et al (2011) Evidence-based annotation of gene function in Shewanella oneidensis MR-1 using genome-wide fitness profiling across 121 conditions. PLoS Genet 7:e1002385PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Roggo C, Coronado E, Moreno-Forero SK, Harshman K, Weber J, Van Der Meer JR (2013) Genome-wide transposon insertion scanning of environmental survival functions in the polycyclic aromatic hydrocarbon degrading bacterium Sphingomonas wittichii RW1. Environ Microbiol 15(10):2681–2695PubMedGoogle Scholar
  48. 48.
    Cameron DE, Urbach JM, Mekalanos JJ (2008) A defined transposon mutant library and its use in identifying motility genes in Vibrio cholerae. Proc Natl Acad Sci U S A 105:8736–8741PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Glass JI, Assad-Garcia N, Alperovich N, Yooseph S, Lewis MR, Maruf M et al (2006) Essential genes of a minimal bacterium. Proc Natl Acad Sci U S A 103:425–430PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Hutchison CA, Peterson SN, Gill SR, Cline RT, White O, Fraser CM et al (1999) Global transposon mutagenesis and a minimal Mycoplasma genome. Science 286:2165–2169PubMedCrossRefGoogle Scholar
  51. 51.
    French CT, Lao P, Loraine AE, Matthews BT, Yu H, Dybvig K (2008) Large-scale transposon mutagenesis of Mycoplasma pulmonis. Mol Microbiol 69:67–76PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Sarmiento F, Mrazek J, Whitman WB (2013) Genome-scale analysis of gene function in the hydrogenotrophic methanogenic archaeon Methanococcus maripaludis. Proc Natl Acad Sci U S A 110:4726–4731PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Giaever G, Chu AM, Ni L, Connelly C, Riles L, Veronneau S et al (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418:387–391PubMedCrossRefGoogle Scholar
  54. 54.
    Kim D-U, Hayles J, Kim D, Wood V, Park H-O, Won M et al (2010) Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe. Nat Biotechnol 28:617–623PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Smith V, Botstein D, Brown PO (1995) Genetic footprinting: a genomic strategy for determining a gene’s function given its sequence. Proc Natl Acad Sci U S A 92:6479–6483PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of PhysicsTianjin UniversityTianjinChina
  2. 2.Center for Molecular Medicine and Genetics, School of MedicineWayne State UniversityDetroitUSA

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