Skip to main content

Genome-Wide Essential Gene Identification in Pathogens

  • Chapter
  • First Online:
Current trends in Bioinformatics: An Insight
  • 1259 Accesses

Abstract

Genome-wide, a gene can be designated as indispensable for the survival of a cell or an organism, and its interruption can lead to the malfunctioning or death of the organism. Due to its essentiality for survival, these could be proposed as novel and promising candidates for broad-spectrum drug targets, if these are conserved across a genus. Identification of essential gene has been done in many organisms, and interestingly, most of them were pathogenic in nature. The genome-scale elucidation of essential genes plays an important role in development and complete genome availability. At large scale, gene-inactivation technologies such as targeted gene inactivation, genetic footprinting, and transposon-based mutagenesis are controlled by essential genes. In silico, numerous strategies and tools also have been developed, such as subtractive genomics, essentiality base mapping, and target identification using phylogenetic profiling. Bioinformatic approaches can also be used to analyze experimentally generated data. This chapter is referred to provide an overview of some of these methodologies which are often used to identify essential genes and their functions and discuss advantage and drawbacks of the methods.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Akerley BJ et al (1998) Systematic identification of essential genes by in vitro mariner mutagenesis. Proc Natl Acad Sci 95:8927–8932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bardarov S et al (2002) Specialized transduction: an efficient method for generating marked and unmarked targeted gene disruptions in Mycobacterium tuberculosis, M. bovis BCG and M. smegmatis. Microbiology 148:3007–3017

    Article  CAS  PubMed  Google Scholar 

  • Barrett AD, Stanberry LR (2009) Vaccines for biodefense and emerging and neglected diseases. Academic, Amsterdam

    Google Scholar 

  • Basu MK et al (2011) ProPhylo: partial phylogenetic profiling to guide protein family construction and assignment of biological process. BMC Bioinformatics 12:1

    Article  Google Scholar 

  • Cooper I, Duffield M (2011) The in silico prediction of bacterial essential genes. In: Méndez-Vilas A (ed) Science against microbial pathogens: communicating current research and technological advances. FORMATEX Microbiology Series N° 3, vol 1. Formatex Research Center, Badajoz

    Google Scholar 

  • Date SV, Marcotte EM (2003) Discovery of uncharacterized cellular systems by genome-wide analysis of functional linkages. Nat Biotechnol 21:1055–1062

    Article  CAS  PubMed  Google Scholar 

  • Deng J et al (2010) Investigating the predictability of essential genes across distantly related organisms using an integrative approach. Nucleic Acids Res 39(3):795–807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Devine SE, Boeke JD (1994) Efficient integration of artificial transposons into plasmid targets in vitro: a useful tool for DNA mapping, sequencing and genetic analysis. Nucleic Acids Res 22:3765–3772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fleischmann RD et al (1995) Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269:496–512

    Article  CAS  PubMed  Google Scholar 

  • Forsyth R et al (2002) A genome-wide strategy for the identification of essential genes in Staphylococcus aureus. Mol Microbiol 43:1387–1400

    Article  CAS  PubMed  Google Scholar 

  • Freilich S et al (2009) Stratification of co-evolving genomic groups using ranked phylogenetic profiles. BMC Bioinformatics 10:1

    Article  CAS  Google Scholar 

  • Frøkjær-Jensen C et al (2010) Targeted gene deletions in C. elegans using transposon excision. Nat Methods 7:451–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gaasterland T, Ragan MA (1998) Microbial genescapes: phyletic and functional patterns of ORF distribution among prokaryotes. Microb Comp Genomics 3:199–217

    Article  CAS  PubMed  Google Scholar 

  • Gautam B et al (2012) Metabolic pathway analysis and molecular docking analysis for identification of putative drug targets in Toxoplasma gondii: novel approach. Bioinformationtics 8:134–141

    Article  Google Scholar 

  • Gil R et al (2004) Determination of the core of a minimal bacterial gene set. Microbiol Mol Biol Rev 68:518–537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grünblatt E et al (2014) Imaging genetics in obsessive-compulsive disorder: linking genetic variations to alterations in neuroimaging. Prog Neurobiol 121:114–124

    Article  CAS  PubMed  Google Scholar 

  • Hayes F (2003) Transposon-based strategies for microbial functional genomics and proteomics. Annu Rev Genet 37:3–29

    Article  CAS  PubMed  Google Scholar 

  • Holman AG et al (2009) Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayi. BMC Microbiol 9:1

    Article  CAS  Google Scholar 

  • Hosen MI et al (2014) Application of a subtractive genomics approach for in silico identification and characterization of novel drug targets in Mycobacterium tuberculosis F11. Interdiscip Sci Comput Life Sci 6:48–56

    Article  CAS  Google Scholar 

  • Huynen MA, Bork P (1998) Measuring genome evolution. Proc Natl Acad Sci 95:5849–5856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishikawa M, Hori K (2013) A new simple method for introducing an unmarked mutation into a large gene of non-competent Gram-negative bacteria by FLP/FRT recombination. BMC Microbiol 13:86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ivics Z et al (2009) Transposon-mediated genome manipulation in vertebrates. Nat Methods 6:415–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jimenez-Ruiz E et al (2014) Advantages and disadvantages of conditional systems for characterization of essential genes in Toxoplasma gondii. Parasitology 141:1390–1398

    Article  CAS  PubMed  Google Scholar 

  • Jordan IK et al (2002) Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. Genome Res 12:962–968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joshi PB et al (2002) Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor. Mol Biochem Parasitol 120:33–40

    Article  CAS  PubMed  Google Scholar 

  • Jothi R et al (2007) Discovering functional linkages and uncharacterized cellular pathways using phylogenetic profile comparisons: a comprehensive assessment. BMC Bioinformatics 8:1

    Article  CAS  Google Scholar 

  • Judson N, Mekalanos JJ (2000) Transposon-based approaches to identify essential bacterial genes. Trends Microbiol 8:521–526

    Article  CAS  PubMed  Google Scholar 

  • Juhas M et al (2012) High confidence prediction of essential genes in Burkholderia cenocepacia. PLoS One 7:e40064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang DC, Fisher PB (2005) Complete open reading frame (C-ORF) technology: simple and efficient technique for cloning full-length protein-coding sequences. Gene 353:1–7

    Article  CAS  PubMed  Google Scholar 

  • Kensche PR et al (2008) Practical and theoretical advances in predicting the function of a protein by its phylogenetic distribution. J R Soc Interface 5:151–170

    Article  CAS  PubMed  Google Scholar 

  • Kleckner N (1981) Transposable elements in prokaryotes. Annu Rev Genet 15:341–404

    Article  CAS  PubMed  Google Scholar 

  • Koonin EV (2000) How many genes can make a cell: the minimal-gene-Set concept 1. Annu Rev Genomics Hum Genet 1:99–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langille MG et al (2013) Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 31:814–821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lehoux DE et al (2001) Discovering essential and infection-related genes. Curr Opin Microbiol 4:515–519

    Article  CAS  PubMed  Google Scholar 

  • Lin Y, Zhang RR (2011) Putative essential and core-essential genes in Mycoplasma genomes. Sci Rep 1

    Google Scholar 

  • Luisi PL et al (2002) The notion of a DNA minimal cell: a general discourse and some guidelines for an experimental approach. Helv Chim Acta 85:1759–1777

    Article  CAS  Google Scholar 

  • Luo H et al (2013) DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements. Nucleic Acids Res 42(Database issue):D574–D580

    PubMed  PubMed Central  Google Scholar 

  • Mikkelsen TS et al (2005) Improving genome annotations using phylogenetic profile anomaly detection. Bioinformatics 21:464–470

    Article  CAS  PubMed  Google Scholar 

  • O’sullivan GJ et al (2006) Potential and limitations of genetic manipulation in animals. Drug Discov Today Technol 3:173–180

    Article  PubMed  Google Scholar 

  • Pellegrini M (2012) Using phylogenetic profiles to predict functional relationships. Bacterial Mol Netw Methods Protoc 804:167–177

    Google Scholar 

  • Plaimas K et al (2010) Identifying essential genes in bacterial metabolic networks with machine learning methods. BMC Syst Biol 4:1

    Article  CAS  Google Scholar 

  • Psomopoulos FE et al (2013) Detection of genomic idiosyncrasies using fuzzy phylogenetic profiles. PLoS One 8:e52854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ranea JA et al (2007) Predicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes. PLoS Comput Biol 3:e237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rusmini R et al (2014) A shotgun antisense approach to the identification of novel essential genes in Pseudomonas aeruginosa. BMC Microbiol 14:1

    Article  CAS  Google Scholar 

  • Sakharkar KR et al (2004) A novel genomics approach for the identification of drug targets in pathogens, with special reference to Pseudomonas aeruginosa. In Silico Biol 4:355–360

    PubMed  CAS  Google Scholar 

  • Salama NR et al (2004) Global transposon mutagenesis and essential gene analysis of Helicobacter pylori. J Bacteriol 186:7926–7935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarangi AN et al (2009) Subtractive genomics approach for in silico identification and characterization of novel drug targets in Neisseria meningitidis serogroup B. J Comput Sci Syst Biol 2:255–258

    CAS  Google Scholar 

  • Sassetti CM et al (2003) Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48:77–84

    Article  CAS  PubMed  Google Scholar 

  • Schmidt M, Oliver D (1989) SecA protein autogenously represses its own translation during normal protein secretion in Escherichia coli. J Bacteriol 171:643–649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh IR et al (1997) High-resolution functional mapping of a cloned gene by genetic footprinting. Proc Natl Acad Sci 94:1304–1309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith V et al (1995) Genetic footprinting: a genomic strategy for determining a gene’s function given its sequence. Proc Natl Acad Sci 92:6479–6483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Snitkin ES et al (2006) Comparative assessment of performance and genome dependence among phylogenetic profiling methods. BMC Bioinformatics 7:420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song JH, Ko KS (2008) Detection of essential genes in Streptococcus pneumoniae using bioinformatics and allelic replacement mutagenesis. Microb Gene Essentiality Protoc Bioinformatics 416:401–408

    Article  CAS  Google Scholar 

  • Tatusov RL et al (1997) A genomic perspective on protein families. Science 278:631–637

    Article  CAS  PubMed  Google Scholar 

  • Touchon M et al (2009) Organised genome dynamics in the Escherichia coli species results in highly diverse adaptive paths. PLoS Genet 5:e1000344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong SM, Mekalanos JJ (2000) Genetic footprinting with mariner-based transposition in Pseudomonas aeruginosa. Proc Natl Acad Sci 97:10191–10196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong J et al (2006) Genome wide prediction of protein function via a generic knowledge discovery approach based on evidence integration. BMC Bioinformatics 7:268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu P et al (2011) Genome-wide essential gene identification in Streptococcus sanguinis. Sci Rep 1:125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yaveroglu ON, Can T (2009) Predicting protein-protein interactions from protein sequences using phylogenetic profiles. Int J Comput Electr Autom Control Inf Eng 3:1971–1977

    Google Scholar 

  • Zhang Z, Ren Q (2015) Why are essential genes essential? – the essentiality of Saccharomyces genes. Microbial Cell 2:280–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

The authors are grateful to the Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad, for providing the facilities and support to complete the present research work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Budhayash Gautam .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gautam, B., Goswami, K., Singh, S., Wadhwa, G. (2018). Genome-Wide Essential Gene Identification in Pathogens. In: Wadhwa, G., Shanmughavel, P., Singh, A., Bellare, J. (eds) Current trends in Bioinformatics: An Insight. Springer, Singapore. https://doi.org/10.1007/978-981-10-7483-7_13

Download citation

Publish with us

Policies and ethics