Essential Genes

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EGGS: Essential Genes on Genomic Scale

Data Curation

NMPDR curators have collated genome-scale essentiality datasets from published studies involving 10 bacterial species, including the priority pathogens Staphylococcus aureus, Streptococcus pneumoniae, Mycobacterium tuberculosis, Salmonella enterica, and Escherichia coli. The results of each of the studies cited below have been mapped onto only one genome. Projecting essentiality from one strain to another is problematic, so we have attributed essentiality only to genes in the complete genome that was both available in 2006 when these studies were reviewed, and that is most similar to the strain used for the in vivo experiment. While there are 16 studies cited, there is one strain (genome) annotated for each of 10 different organisms studied.

Establishing essentiality

The notion of essential for life is entirely dependent on the specific lifestyle and organism studied, that is, the environmental and genetic conditions surveyed. The methodology used to generate each dataset influences gene essentiality assessments as well. Bacterial genes may be inactivated with antisense RNAs or by deletion or insertional disruption, either randomly or in a specifically targeted manner. The important distinction between the techniques is whether the growth of each mutant occurs clonally or in a mixed population. Although in both strategies gene "essentiality" is deduced from the inability of a mutant cell to undergo a certain number of divisions, the passing threshold is much more stringent in mixed populations than in clonal studies. Thus, a mutant with substantially decreased fitness would be quickly selected against under the conditions of competitive outgrowth in planktonic culture, while it might still be capable of forming an isolated colony.

Analysis

Comparative analysis of these data across multiple organisms in a rich genomic, biochemical, and phylogenetic contexts provided by the collection of annotated Subsystems greatly facilitates their interpretation and practical applications, such as understanding of cellular networks, gene and pathway discovery, identification of novel drug targets, and strain engineering. These data may also be viewed and explored in the SEED. A comparative analysis of these essential genes in the context of functional subsystems has recently been published by our annotators, and here we make available the icon supplemental data tables discussed in the paper. Another resource is the Database of Essential Genes.

Data

Data Curation Experimental Conditions Essentiality Assessment
Genome Attribute Key Mutagenesis Outgrowth ORFs tested N E U Ref
S. aureus N315 158879.1 SA_essential_Ji random RNAi clonal on undefined rich agar TSA, aerobic 2648 n/a 146 n/a 1
S. aureus N315 158879.1 SA_essential_Forsyth random RNAi clonal on undefined rich agar LB+0.2% glucose, 37C, aerobic 2648 n/a 658* n/a 2
S. aureus N315 158879.1 SA_essential_Ko targeted deletion clonal on undefined rich agar TSA+2% sheep blood, 37C, microaerobic in 5% CO2 481 359* 123 216 3
S. pneumoniae R6 171101.1 SP_essential_Thanassi targeted insertion clonal on undefined rich agar Todd-Hewitt, 37C, microaerobic growth in 5% CO2 347 234 113 n/a 4
S. pneumoniae R6 171101.1 SP_essential_Song targeted deletion clonal on undefined rich agar Todd-Hewitt, 37C, microaerobic growth in 5% CO2 693 560 133   5
H. pylori 26695 85962.1 HP_candidate_essential_Salama random insertion population in undefined rich broth HB, 37C, microaerobic in 10% CO2 1760 1178 344 54 6
M. genitalium 243273.1 MG_essential_Hutchison_2006 random insertion clonal on undefined rich agar SP4, 37C, microaerobic in 5% CO2 482 100 382 0 7
M. tuberculosis H37 Rv 83332.1 MT_contribute_to_fitness_Rubin random insertion population in defined rich broth OADC 3989 2567 614 808 8
H. influenzae KW20 Rd 71421.1 HI_contribute_to_fitness_Akerley random insertion population in undefined rich broth BHI, 37C, aerobic 1657 602 670 385 9
P. aeruginosa PAO1 208964.1 PA_candidate_essential_Jacobs random insertion clonal on undefined rich agar LB, room temp, aerobic 5570 4783 787 0 10
P. aeruginosa PAO1 208964.1 PA_essential_PA14_PAO1_Liberati random insertion clonal on undefined rich agar LB, aerobic 5688 4,469 335 884 11
B. subtilis 168 224308.1 BS_essential_Kobayashi targeted insertion clonal on undefined rich agar LB, 37C, aerobic 4105 3830 271 4 12
S. typhimurium LT2 99287.1 ST_essential_Knuth random insertion clonal on undefined rich agar LB, 30C, aerobic 4425 n/a 257 n/a 13
E. coli K-12 83333.1 EC_contribute_to_fitness random insertion population in undefined rich broth LB, 37C, aerobic 4308 3126 620 562 14
E. coli K-12 83333.1 EC_essential_Keio targeted deletion clonal on undefined rich agar LB, 37C, aerobic 4390 3985 303 102 15
E. coli K-12 83333.1 EC_essential_Blattner targeted insertion clonal on undefined rich agar LB, 37C, aerobic 4308 2001 n/a 2201 16

Mutagenesis and outgrowth conditions used in the studies are listed in brief. For complete details, see the published experiments. Results are recorded in NMPDR as attributes in key-value pairs. The attribute keys are listed. Values are N onessential, E ssential, or U ndetermined (or unreported). *Only partial data reported.

Published Experiments

1. Ji YD, Zhang B, Van Horn SF, Warren P, Woodnutt G, Burnham MKR, Rosenberg M. 2001 Identification of critical staphylococcal genes using conditional phenotypes generated by antisense RNA. Science 293: 2266-2269. PubMedID 11567142

2. Forsyth RA, Haselbeck RJ, Ohlsen KL, Yamamoto RT, Xu H, Trawick JD, Wall D, Wang LS, Brown-Driver V, Froelich JM, et al. 2002 A genome-wide strategy for the identification of essential genes in Staphylococcus aureus. Molecular Microbiology 43: 1387-1400. PubMedID 11952893

3. Ko KS, Lee JY, Song JH, Baek JY, Oh WS, Chun J, Yoon HS. 2006 Screening of essential genes in Staphylococcus aureus N315 using comparative genomics and allelic replacement mutagenesis. J. Microbiol. Biotechnol. 16(4): 623%u2013632. journal ToC

4. Thanassi JA, Hartman-Neumann SL, Dougherty TJ, Dougherty BA, J. PM. 2002 Identification of 113 conserved essential genes using a high-throughput gene disruption system in Streptococcus pneumoniae. Nucleic Acids Research 30: 3152-3162. PubMedID 12136097

5. Song JH, Ko KS, Lee JY, Baek JY, Oh WS, Yoon HS, Jeong JY, Chun J. 2005 Identification of essential genes in Streptococcus pneumoniae by allelic replacement mutagenesis. Mol Cells 19 365-374. PubMedID 15995353

6. Salama NR, Shepherd B, Falkow S. 2004 Global transposon mutagenesis and essential gene analysis of Helicobacter pylori. J Bacteriol 186: 7926-7935. PubMedID 15547264

7. Glass JI, Assad-Garcia N, Alperovich N, Yooseph S, Lewis MR, Maruf M, Hutchison CA, 3rd, Smith HO, Venter JC. 2006 Essential genes of a minimal bacterium. Proc Natl Acad Sci USA 103: 425-430. PubMedID 16407165

8. Sassetti CM, Boyd DH, Rubin EJ 2003 Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48: 77-84. PubMedID 12657046

9. 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 USA 99: 966-971. PubMedID 11805338

10. Jacobs MA, Alwood A, Thaipisuttikul I, Spencer D, Haugen E, Ernst S, Will O, Kaul R, Raymond C, Levy R, et al. 2003 Comprehensive transposon mutant library of Pseudomonas aeruginosa. Proc Natl Acad Sci USA 100: 14339-14344. PubMedID 14617778

11. Liberati NT, Urbach JM, Miyata S, Lee DG, Drenkard E, Wu G, Villanueva J, Wei T, Ausubel FM 2006 An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants. Proc Natl Acad Sci USA 103 :2833-2838. PubMedID 16477005

12. Kobayashi K, Ehrlich SD, Albertini A, Amati G, Andersen KK, Arnaud M, Asai K, Ashikaga S, Aymerich S, Bessieres P, et al. 2003 Essential Bacillus subtilis genes. Proc Natl Acad Sci USA 100: 4678-4683. PubMedID 12682299

13. Knuth K, Niesalla H, Hueck CJ, Fuchs TM 2004 Large-scale identification of essential Salmonella genes by trapping lethal insertions. Mol Microbiol 51: 1729-1744. PubMedID 15009898

14. Gerdes S, Scholle M, Campbell J, Balazsi G, Ravasz E, Daugherty M, Somera AL, Kyrpides N, Anderson I, Gelfand MS, et al. 2003 Experimental determination and system-level analysis of essential genes in E. coli MG1655. J Bacteriol 185: 5673-5684. PubMedID 13129938

15. Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H. 2006 Construction of Escherichia coli K-12 in-frame, single-gene knock-out mutants: the Keio collection. Mol Systems Biol doi:10.1038/msb4100050. PubMedID 16738554

16. Kang Y, Durfee T, Glasner JD, Qiu Y, Frisch D, Winterberg KM, Blattner FR. 2004 Systematic mutagenesis of the Escherichia coli genome. J Bacteriol. 186: 8548. PubMedID 15262929

Topic revision: r31 - 20 Mar 2009 - 21:48:42 - TWiki Guest
 
Notice to NMPDR Users - The NMPDR BRC contract has ended and bacterial data from NMPDR has been transferred to PATRIC (http://www.patricbrc.org), a new consolidated BRC for all NIAID category A-C priority pathogenic bacteria. NMPDR was a collaboration among researchers from the Computation Institute of the University of Chicago, the Fellowship for Interpretation of Genomes (FIG), Argonne National Laboratory, and the National Center for Supercomputing Applications (NCSA) at the University of Illinois. NMPDR is funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract HHSN266200400042C. Banner images are copyright © Dennis Kunkel.